The influence of molecular structure on odor qualities and odor detection thresholds of volatile alkylated phenols

The relationship between chemical structure and odor characteristics of aroma compounds is interesting in terms of establishing a fundamental understanding and, in the long term, a perspective for the prediction of odor qualities and intensities of unknown compounds; on the other hand, such studies provide a useful tool to analytically elucidate compounds that are exceptionally potent odor contributors to a specific smell. In this respect, a broad knowledge of compounds with regard to their odor threshold and smell specificities compiled in a comprehensive odor library would drastically simplify the chemoanalytical process in identifying aromas and smells. Whereas numerous odor-active substance classes have been investigated intensively, such relationships and fundamental data have hitherto not been established for volatile phenols. In this study, a homologous series and isomers of 30 volatile phenols, including monoalkylated phenols and di- and trimethylphenols, were evaluated by determining their aroma attributes and their odor detection thresholds in air. The investigation demonstrates that the odor qualities, among them leather-like, horse stable-like, and medicinal, as well as the respective threshold values clearly depend on the arrangement of the alkyl substituents at the phenol ring. In particular, phenols with monoalkyl groups in the meta-position were found with very low odor detection thresholds of <1 ng/L air. A comparison of some selected phenols and their corresponding toluenes, which were found to be almost odorless, showed in addition that the phenolic hydroxyl group is obviously an important factor for the odor characteristic of this substance class.     

Oxidation of 3,4-dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho-quinone

The oxidation and toxicity of dopamine is believed to contribute to the selective neurodegeneration associated with Parkinson disease. The formation of reactive radicals and quinones greatly contributes to dopaminergic toxicity through a variety of mechanisms. The physiological metabolism of dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL) via monoamine oxidase significantly increases its toxicity. To more adequately explain this enhanced toxicity, we hypothesized that DOPAL is capable of forming radical and quinone species upon oxidation. Here, two unique oxidation products of DOPAL are identified. Several different oxidation methods gave rise to a transient DOPAL semiquinone radical, which was characterized by electron paramagnetic resonance spectroscopy. NMR identified the second oxidation product of DOPAL as the ortho-quinone. Also, carbonyl hydration of DOPAL in aqueous media was evident via NMR. Interestingly, the DOPAL quinone exists exclusively in the hydrated form. Furthermore, the enzymatic and chemical oxidation of DOPAL greatly enhance protein cross-linking, whereas auto-oxidation results in the production of superoxide. Also, DOPAL was shown to be susceptible to oxidation by cyclooxygenase-2 (COX-2). The involvement of this physiologically relevant enzyme in both oxidative stress and Parkinson disease underscores the potential importance of DOPAL in the pathogenesis of this condition.     

The importance of water-level fluctuation for the conservation of shallow water benthic macroinvertebrates: an example in the Andean zone of Chile

Many researchers have shown the importance of water chemistry and benthic habitat characteristics for the conservation of the freshwater macroinvertebrate biodiversity. However, few authors have examined the physical effect of extreme water-level fluctuations in lakes. The present study set out to determine, through a comparative study between a regulated lake (Laja Lake, LL) and an unregulated lake (Icalma Lake, IL) of the Andean zone of southern Chile, how man-made disturbances of the natural hydrological regime affect the structure of the benthic macroinvertebrate community. The results showed LL had very low values for species richness, density and biomass in comparison with IL, and the community was composed mainly of few individuals belonging to opportunistic taxa such as Chironomidae and Naididae. We suggest that the low values in the regulated lake are potentially explained by littoral zone factors driven by the water-level fluctuations such as: desiccation, freezing of the biota, removal of organic particles from the sediment and absence of aquatic macrophytes.     

In vivo glenohumeral translation under anterior loading in an open-MRI set-up

The evaluation of the glenohumeral joint laxity requires the estimate of displacements of the humeral head centre (HHC) with respect to the glenoid. To the authors? knowledge, several studies have been conducted to estimate HHC translations in vivo but data under anterior loading conditions has not been collected yet. Aim of this study was to develop a non-invasive experimental methodology based on magnetic resonance (MR) imaging for the in vivo evaluation of the HHC translations due to an anteriorly directed force. Fourteen asymptomatic shoulders were acquired using a horizontal open MR scanner with the subjects in the supine position both at 15° and 90° of arm abduction with and without an anterior force of 20 N applied at the HHC level. When no load was applied, from 15° to 90° of arm abduction, the HHC moved, anteriorly (1.5±1.3 mm) and superiorly (1.8±1.3 mm) while smaller displacements were observed medio-laterally (0.4±0.7 mm). Under the application of the anterior force the 3D displacement of the HHC with respect to the glenoid was 1.6±1.2 mm and 1.3 ±0.7 mm, respectively at 15° and 90° of arm abduction. The level of precision associated to the GHJ translation was less than 0.33 mm along all directions i.e. one order of magnitude smaller than the relevant translations. In conclusion, the MRI-based methodology allowed for the analysis of HHC displacements under conditions of anterior loads within an acceptable level of reliability.     

Hippo Signaling Mediates Proliferation,Invasiveness, and Metastatic Potential of Clear Cell Renal Cell Carcinoma

Recent work has identified dysfunctional Hippo signaling to be involved in maintenance and progression of various human cancers, although data on clear cell renal cell carcinoma (ccRCC) have been limited. Here, we provide evidence implicating aberrant Hippo signaling in ccRCC proliferation, invasiveness, and metastatic potential. Nuclear overexpression of the Hippo target Yes-associated protein (YAP) was found in a subset of patients with ccRCC. Immunostaining was particularly prominent at the tumor margins and highlighted neoplastic cells invading the tumor-adjacent stroma. Short hairpin RNA-mediated knockdown of YAP significantly inhibited proliferation, migration, and anchorage-independent growth of ccRCC cells in soft agar and led to significantly reduced murine xenograft growth. Microarray analysis of YAP knockdown versus mock-transduced ccRCC cells revealed down-regulation of endothelin 1, endothelin 2, cysteine-rich, angiogenic inducer, 61 (CYR61), and c-Myc in ccRCC cells as well as up-regulation of the cell adhesion molecule cadherin 6. Signaling pathway impact analysis revealed activation of the p53 signaling and cell cycle pathways as well as inhibition of mitogen-activated protein kinase signaling on YAP down-regulation. Our data suggest CYR61 and c-Myc as well as signaling through the endothelin axis as bona fide downstream effectors of YAP and establish aberrant Hippo signaling as a potential therapeutic target in ccRCC.