Functionalized galactoglucomannan‐based hydrogels for the removal of metal cations from aqueous solutions

New types of hydrogels derived from O‐acetyl galactoglucomannan (AcGGM) hemicellulose have been synthesized and characterized. The objective of this work was to analyze the sorption capacity (S) of three types of hydrogels containing AcGGM derivatives incorporated into the carboxylic groups of the polymer chain in the AA hydrogel, sulfonic groups in the APA hydrogel, and amide groups in the acrylamide (Aam) hydrogel. These hydrogels are capable of interacting and removing ions such as cadmium [Cd(II)], copper [Cu(II)], lead [Pb(II)], nickel [Ni(II)], and zinc [Zn(II)]. The results show that AA and Aam hydrogels had a lower sorption capacity of ions compared to the APA hydrogel, which had a high sorption capacity. The maximal sorption capacity was determined by the successive enrichment method, obtaining Pb(II) amount of 48.3 mg/g of AA hydrogel, 65.8 mg/g of APA hydrogel, and 40.8 mg/g of Aam hydrogel. Hence, Pb(II) ions are greatly retained by the three hydrogels. These results are promising for the development of new materials with potential applications in metal ion removal. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44093.     

An Efficient New Pyrimidine Synthesis – a pathway to octupoles

The condensation of N,N,N′-tris(trimethylsilyl)-amidines ( 6 , 11 , 22 ) with vinamidinium salts ( 1 , 7 ) in the presence of potassium fluoride is the method of choice for the synthesis of pyrimidines ( 8 , 12 , 20 , 23 ). Octupoles comprising 1,3,5-benzene ( 8 ) and triphenylamine ( 12 , 20 ) derivatives can be prepared in high yields.     

Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells

The cAMP-dependent aquaporin-2 (AQP2) redistribution from intracellular vesicles into the plasma membrane of renal collecting duct principal cells induces water reabsorption and fine-tunes body water homeostasis. However, the mechanisms controlling the localization of AQP2 are not understood in detail. Using immortalized mouse medullary collecting duct (MCD4) and primary rat inner medullary collecting duct (IMCD) cells as model systems, we here discovered a key regulatory role of Aurora kinase A (AURKA) in the control of AQP2. The AURKA-selective inhibitor Aurora-A inhibitor I and novel derivatives as well as a structurally different inhibitor, Alisertib, prevented the cAMP-induced redistribution of AQP2. Aurora-A inhibitor I led to a depolymerization of actin stress fibers, which serve as tracks for the translocation of AQP2-bearing vesicles to the plasma membrane. The phosphorylation of cofilin-1 (CFL1) inactivates the actin-depolymerizing function of CFL1. Aurora-A inhibitor I decreased the CFL1 phosphorylation, accounting for the removal of the actin stress fibers and the inhibition of the redistribution of AQP2. Surprisingly, Alisertib caused an increase in actin stress fibers and did not affect CFL1 phosphorylation, indicating that AURKA exerts its control over AQP2 through different mechanisms. An involvement of AURKA and CFL1 in the control of the localization of AQP2 was hitherto unknown.     

SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?

Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.     

Konduktometrische und spektroskopische Untersuchungen der Wechselwirkung von Lewis-Säuren mit Halogenkomplexen

Conductometric and Spectroscopic Investigations of the Interaction of Lewis Acids with Halide Complexes The interaction of counter ions with Lewis acids has been investigated using mode systems of the type (C₆H₅)₃C^⊕ MX_n+1^⊖ (M = Sb, As, B, Fe; X = Cl, F) by means of conductometrical and UV-spectroscopic methods. The changes of conductivity were strongly dependent on the nature and concentration of the Lewis acid. The results point to 1:1-complexes between Lewis acids and counter ions. The behaviour was found to be complicated by dissoziation resp. assoziation processes. Ligand exchange reactions between Lewis acid and counter ion have also been found.     

Atopic Dermatitis: The Fate of the Fat

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease in which dry and itchy skin may develop into skin lesions. AD has a strong genetic component, as children from parents with AD have a two-fold increased chance of developing the disease. Genetic risk loci and epigenetic modifications reported in AD mainly locate to genes involved in the immune response and epidermal barrier function. However, AD pathogenesis cannot be fully explained by (epi)genetic factors since environmental triggers such as stress, pollution, microbiota, climate, and allergens also play a crucial role. Alterations of the epidermal barrier in AD, observed at all stages of the disease and which precede the development of overt skin inflammation, manifest as: dry skin; epidermal ultrastructural abnormalities, notably anomalies of the lamellar body cargo system; and abnormal epidermal lipid composition, including shorter fatty acid moieties in several lipid classes, such as ceramides and free fatty acids. Thus, a compelling question is whether AD is primarily a lipid disorder evolving into a chronic inflammatory disease due to genetic susceptibility loci in immunogenic genes. In this review, we focus on lipid abnormalities observed in the epidermis and blood of AD patients and evaluate their primary role in eliciting an inflammatory response.     

Novel Design of Neuropeptide-Based Drugs with β-Sheet Breaking Potential in Amyloid-Beta Cascade: Molecular and Structural Deciphers

Our work discusses the investigation of 75 peptide-based drugs with the potential ability to break the β-sheet structures of amyloid-beta peptides from senile plaques. Hence, this study offers a unique insight into the design of neuropeptide-based drugs with β-sheet breaker potential in the amyloid-beta cascade for Alzheimer’s disease (AD). We started with five peptides (¹⁵QKLVFF²⁰, ¹⁶KLVFF²⁰, ¹⁷LVFF²⁰, ¹⁶KLVF¹⁹ and ¹⁵QKLV¹⁸), to which 14 different organic acids were attached at the N-terminal. It was necessary to evaluate the physiochemical features of these sequences due to the biological correlation with our proposal. Hence, the preliminary analysis of different pharmacological features provided the necessary data to select the peptides with the best biocompatibility for administration purposes. Our approaches demonstrated that the peptides ¹⁷LVFF²⁰, NA-¹⁷LVFF²⁰, ¹⁶KLVF¹⁹ and NA-¹⁶KLVF¹⁹ (NA-nicotinic acid) have the ability to interfere with fibril formation and hence improve the neuro and cognitive functions. Moreover, the peptide conjugate NA-¹⁶KLVF¹⁹ possesses attractive pharmacological properties, demonstrated by in silico and in vitro studies. Tandem mass spectrometry showed no fragmentation for the spectra of ¹⁶KLVF¹⁹. Such important results suggest that under the action of protease, the peptide cleavage does not occur at all. Additionally, circular dichroism confirmed docking simulations and showed that NA-¹⁶KLVF¹⁹ may improve the β-sheet breaker mechanism, and thus the entanglement process of amyloid-beta peptides can be more effective.