244 research outputs found
Formation of the Acyl Chain within the Alkamides
poster abstractEchinacea, a coneflower species that is native to North America, are the most consumed medicinal plants
in the United States and Europe. Their medicinal usage focuses on the treatment and prevention of colds,
influenza, and other upper respiratory tract infections. In part, the traditional medicinal uses of Echinacea
are attributed to their alkamide content. Structurally alkamides consist of an amine moiety acylated with
a variety of fatty acids. To better describe the biosynthetic process leading to the formation of acyl chains
within alkamides of Echinacea purpurea, stable isotope labeling experiments with analysis via LC/MS
and NMR was undertaken. As previously reported from our lab, the acyl chains of alkamides are
synthesized from fatty acid synthesis via HSQC NMR analysis of a tetraenoic isobutyl amide alkamide.
As part of our continuing efforts to probe the acyl chain biosynthesis within E. purpurea, we herein report
the HSQC NMR analysis of a proposed dienoic isobutyl amide alkamide that was labeled with a 70/30
[U-12C6]/[U-13C6]glucose mixture. The magnitude of 13C-13C one-bond coupling observed by NMR will
allow for incorporation patterns to be determined and will help to elucidate the structure and biogenesis of
this dienoic isobutyl amide alkamide
Comparative studies on the structure of an upland African stream ecosystem
Upland stream systems have been extensively investigated in Europe, North America and Australasia and many of the central ideas concerning their function are based on these systems. One central paradigm, the river continuum concept is ultimately derived from those North American streams whose catchments remain forested with native vegetation. Streams of the tropics may or may not fit the model. They have been little studied. The Amani Nature Reserve in the East Usambara Mountains of north-eastern Tanzania offers an opportunity to bring these naturally forested systems to the attention of the ecological community. This article describes a comparison made between two lengths of the River Dodwe in this area. The work was carried out by a group of postgraduate students from eighteen European and African countries with advice from five staff members, as part of a course organised by the Tropical Biology Association. Rigorous efforts were made to standardise techniques, in a situation where equipment and laboratory facilities were very basic, through a management structure and deliberate allocation of work to specialists in each area.The article offers a summary of invertebrate communities found in the stream and its biomass. Crabs seem to be the key organism in both sections of the streams
Educação superior no PNE (2014-2024): apontamentos sobre as relações público-privadas
Combination therapy in a xenograft model of glioblastoma: enhancement of the antitumor activity of temozolomide by an MDM2 antagonist
OBJECTIVE Improvement in treatment outcome for patients with glioblastoma multiforme (GBM) requires a multifaceted approach due to dysregulation of numerous signaling pathways. The murine double minute 2 (MDM2) protein may fulfill this requirement because it is involved in the regulation of growth, survival, and invasion. The objective of this study was to investigate the impact of modulating MDM2 function in combination with front-line temozolomide (TMZ) therapy in GBM. METHODS The combination of TMZ with the MDM2 protein-protein interaction inhibitor nutlin3a was evaluated for effects on cell growth, p53 pathway activation, expression of DNA repair proteins, and invasive properties. In vivo efficacy was assessed in xenograft models of human GBM. RESULTS In combination, TMZ/nutlin3a was additive to synergistic in decreasing growth of wild-type p53 GBM cells. Pharmacodynamic studies demonstrated that inhibition of cell growth following exposure to TMZ/nutlin3a correlated with: 1) activation of the p53 pathway, 2) downregulation of DNA repair proteins, 3) persistence of DNA damage, and 4) decreased invasion. Pharmacokinetic studies indicated that nutlin3a was detected in human intracranial tumor xenografts. To assess therapeutic potential, efficacy studies were conducted in a xenograft model of intracranial GBM by using GBM cells derived from a recurrent wild-type p53 GBM that is highly TMZ resistant (GBM10). Three 5-day cycles of TMZ/nutlin3a resulted in a significant increase in the survival of mice with GBM10 intracranial tumors compared with single-agent therapy. CONCLUSIONS Modulation of MDM2/p53-associated signaling pathways is a novel approach for decreasing TMZ resistance in GBM. To the authors' knowledge, this is the first study in a humanized intracranial patient-derived xenograft model to demonstrate the efficacy of combining front-line TMZ therapy and an inhibitor of MDM2 protein-protein interactions
Investigation of origin of attached Cu-Ag droplets to solid particles during high-temperature Slag/Copper/Spinel interactions
Potentiation of Carboplatin-Mediated DNA Damage by the Mdm2 Modulator Nutlin-3a in a Humanized Orthotopic Breast-to-Lung Metastatic Model
Triple-negative breast cancers (TNBC) are typically resistant to treatment, and strategies that build upon frontline therapy are needed. Targeting the murine double minute 2 (Mdm2) protein is an attractive approach, as Mdm2 levels are elevated in many therapy-refractive breast cancers. The Mdm2 protein-protein interaction inhibitor Nutlin-3a blocks the binding of Mdm2 to key signaling molecules such as p53 and p73α and can result in activation of cell death signaling pathways. In the present study, the therapeutic potential of carboplatin and Nutlin-3a to treat TNBC was investigated, as carboplatin is under evaluation in clinical trials for TNBC. In mutant p53 TMD231 TNBC cells, carboplatin and Nutlin-3a led to increased Mdm2 and was strongly synergistic in promoting cell death in vitro. Furthermore, sensitivity of TNBC cells to combination treatment was dependent on p73α. Following combination treatment, γH2AX increased and Mdm2 localized to a larger degree to chromatin compared with single-agent treatment, consistent with previous observations that Mdm2 binds to the Mre11/Rad50/Nbs1 complex associated with DNA and inhibits the DNA damage response. In vivo efficacy studies were conducted in the TMD231 orthotopic mammary fat pad model in NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice. Using an intermittent dosing schedule of combined carboplatin and Nutlin-3a, there was a significant reduction in primary tumor growth and lung metastases compared with vehicle and single-agent treatments. In addition, there was minimal toxicity to the bone marrow and normal tissues. These studies demonstrate that Mdm2 holds promise as a therapeutic target in combination with conventional therapy and may lead to new clinical therapies for TNBC
DEVELOPING NEW APPROACHES TO GLOBAL STOCK STATUS ASSESSMENT AND FISHERY PRODUCTION POTENTIAL OF THE SEAS
Stock status is a key parameter for evaluating the sustainability of fishery resources and developing
corresponding management plans. However, the majority of stocks are not assessed, often as a result of
insufficient data and a lack of resources needed to execute formal stock assessments. The working
group involved in this publication focused on two approaches to estimating fisheries status: one based
on single-stock status, and the other based on ecosystem production.JRC.G.4-Maritime affair
Population pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery
Biofilm Derived Oxylipin Mediated Autoimmune Response in Breast Implant Subjects
Over 10 million women worldwide have breast implants for breast cancer/prophylactic reconstruction or cosmetic augmentation. In recent years, a number of patients have described a constellation of symptoms that are believed to be related to their breast implants. This constellation of symptoms has been named Breast Implant Illness (BII). The symptoms described include chronic fatigue, joint pain, muscle pain and a host of other manifestations often associated with autoimmune illnesses. In this work, we report that bacterial biofilm is associated with BII. We postulate that the pathogenesis of BII is mediated via a host-pathogen interaction whereby the biofilm bacteria Staphylococcus epidermidis interacts with breast lipids to form the oxylipin 10-HOME. The oxylipin 10-HOME was found to activate CD4+ T cells to Th1 subtype. An increased abundance of CD4+Th1 was observed in the breast tissue of BII subjects. The identification of a mechanism of immune activation associated with BII via a biofilm enabled pathway provides insight into the pathogenesis for implant-associated autoimmune symptoms
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