X-ray absorption near-edge structure analysis of arsenic species for application to biological environmental samples

Arsenic is an element that is ubiquitous in the environment and is known to form compounds with toxic, even carcinogenic properties. Arsenic toxicity is a function of its chemical form (species). Identification of arsenic species is necessary to accurately determine the transformation and fate of arsenicals as well as the actual risk posed by arsenic contamination. We report X-ray absorption near-edge structure (XANES) measurements of 16 biologically important arsenic compounds. Solid and aqueous standards were studied for differences in XANES spectral features, white line positions, stability during exposure to the beam, and stability between two beam exposures separated by 48 h. Samples containing As(III) (11870.0-11871.7+/-0.5 eV) and As(V) (11872.6-11875.3+/-0.5 eV) were easily distinguished by white line energies and could be further subdivided into a total of seven groups. Valuable examples include As(III)-sulfur compounds (11870.0+/-0.5 eV), arsenobetaine and arsenocholine (11872.6+/-0.5 eV), and a dimethyl arsinyl riboside (11873.3+/-0.5 eV). A growing number of environmental and biological studies use X-ray absorption spectroscopy (XAS) results to complement their more traditional analyses. Results provided here are intended to help make XAS more accessible to new users interested in the study of arsenic in the environment.     

Untersuchungen des Trauben- und Weinaromas

The free aroma compounds of wines were isolated by liquid-liquid extraction with a mixture of trichlorofluoromethane/dichloromethane whereas the enrichment of glycosidically bound aroma components was carried out by adsorption on XAD and subsequent elution with various solvents. The glycosidic compounds were liberated enzymatically byβ-glucosidases. The extracts were analysed by gas chromatography. In 92 wines of the varieties Riesling, Weißburgunder, Silvaner and Ruländer of three vintages (1989, 1990, 1991), from different regions and wine producers 160 free aroma compounds were quantitatively determined. By use of statistical analysis the components were reduced to 23 significant aroma constituents. Analytical characterization of the investigated grape varieties was possible with these components. Terpene compounds, unsaturated C₆-alcohols and some components of the amino acid metabolism were especially typical for the varietal character. Using 18 glycosidically bound aroma substances it could be shown that these components can also contribute significantly to the characterization of grape varieties where monoterpenes and norisoprenoids play an important role. Computing at the same time free and glycosidically bound aroma components in discriminant analysis the characterization of neutral grape varieties (Silvaner, Ruländer, Weissburgunder) can be considerably improved.     

Small Leucine-Rich Proteoglycans (SLRPs) in the Retina

Retinal diseases such as age-related macular degeneration (AMD), retinopathy of prematurity (ROP), and diabetic retinopathy (DR) are the leading causes of visual impairment worldwide. There is a critical need to understand the structural and cellular components that play a vital role in the pathophysiology of retinal diseases. One potential component is the family of structural proteins called small leucine-rich proteoglycans (SLRPs). SLRPs are crucial in many fundamental biological processes involved in the maintenance of retinal homeostasis. They are present within the extracellular matrix (ECM) of connective and vascular tissues and contribute to tissue organization and modulation of cell growth. They play a vital role in cell–matrix interactions in many upstream signaling pathways involved in fibrillogenesis and angiogenesis. In this comprehensive review, we describe the expression patterns and function of SLRPs in the retina, including Biglycan and Decorin from class I; Fibromodulin, Lumican, and a Proline/arginine-rich end leucine-rich repeat protein (PRELP) from class II; Opticin and Osteoglycin/Mimecan from class III; and Chondroadherin (CHAD), Tsukushi and Nyctalopin from class IV.     

Expression and characterization of three important panallergens from hazelnut

Several hazelnut allergens with different clinical relevance and crossreactive properties have been identified and characterized so far. The aim of this study was to develop protocols for producing relatively large amounts of three recombinant hazelnut allergens Cor a 1.04, Cor a 2, and Cor a 8 in a folded and immunologically active form. The availability of well-characterized, pure recombinant allergens will improve diagnostic in vitro tests for food allergy, by allowing a highly sensitive component resolved diagnosis. Depending on the individual hazelnut allergen, protocols for heterologous production - either as fusion or nonfusion protein - were developed to obtain homogenous protein batches. The resulting proteins were purified by a two-step FPLC method and their IgE antibody reactivity was verified. Identity was verified by N-terminal sequencing and MALDI-TOF-MS analysis. Their secondary and tertiary structure was controlled by circular dichroism (CD)-spectroscopy and NMR analysis. Decisions on the strategies for expression and purification of allergens on a large scale were made on a case by case basis: Preparation of rCor a 1.04 and rCor a 2 as fusion proteins in E. coli from inclusion bodies resulted in approximately 10 mg pure protein per liter whereas rCor a 8 expression in yeast as nonfusion protein yielded 30 mg/L.     

Molecular Insights on the Role of (CTA+)(SiO−) Ion Pair into the Catalytic Activity of [CTA+]–Si–MCM-41

Topics in Catalysis - In this work, a theoretical study in conjunction with a spectroscopic analysis by FTIR were carried out in order to obtain molecular insights on the role of...     

Oral Selective Estrogen Receptor Degraders (SERDs) as a Novel Breast Cancer Therapy: Present and Future from a Clinical Perspective

Estrogen receptor-positive (ER+) is the most common subtype of breast cancer. Endocrine therapy is the fundamental treatment against this entity, by directly or indirectly modifying estrogen production. Recent advances in novel compounds, such as cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), or phosphoinositide 3-kinase (PI3K) inhibitors have improved progression-free survival and overall survival in these patients. However, some patients still develop endocrine resistance after or during endocrine treatment. Different underlying mechanisms have been identified as responsible for endocrine treatment resistance, where ESR1 gene mutations are one of the most studied, outstanding from others such as somatic alterations, microenvironment involvement and epigenetic changes. In this scenario, selective estrogen receptor degraders/downregulators (SERD) are one of the weapons currently in research and development against aromatase inhibitor- or tamoxifen-resistance. The first SERD to be developed and approved for ER+ breast cancer was fulvestrant, demonstrating also interesting activity in ESR1 mutated patients in the second line treatment setting. Recent investigational advances have allowed the development of new oral bioavailable SERDs. This review describes the evolution and ongoing studies in SERDs and new molecules against ER, with the hope that these novel drugs may improve our patients’ future landscape.     

Design,Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin

The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad-spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub-nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6/P5-P1 segments, which directly interact with furin. The cyclic derivatives together with two non-cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.