Drug resistance of clinical varicella-zoster virus strains confirmed by recombinant thymidine kinase expression and by targeted resistance mutagenesis of a cloned wild-type isolate.

In this study, approaches were developed to examine the phenotypes of nonviable clinical varicella-zoster virus (VZV) strains with amino acid substitutions in the thymidine kinase (TK) (open reading frame 36 [ORF36]) and/or DNA polymerase (Pol) (ORF28) suspected to cause resistance to antivirals. Initially, recombinant TK proteins containing amino acid substitutions described as known or suspected causes of antiviral resistance were analyzed by measuring the TK activity by applying a modified commercial enzyme immunoassay. To examine the effects of these TK and Pol substitutions on the replication of recombinant virus strains, the method of en passant mutagenesis was used.

A click approach to novel D-ring-substituted 16α-triazolylestrone derivatives and characterization of their antiproliferative properties.

A simple and efficient synthesis of novel, D-ring substituted estrone derivatives containing a 16α-triazolyl moiety is described. Two epimeric azido alcohols (16α-azido-17α-hydroxy and 16α-azido-17β-hydroxy) of estra-1,3,5(10)-triene-3-methyl ether were prepared, followed by copper(I)-catalyzed azide-alkyne cycloaddition with various terminal alkynes. The steroidal triazoles were obtained in high yields and their activities against three human cancer cell lines (HeLa, MCF7 and A431) were screened.

Cellulose carbonates: a platform for promising biopolymer derivatives with multifunctional capabilities.

Cellulose carbonates as a platform compound open new possibilities for the design of advanced materials based on the most important renewable resource cellulose. In the present feature, the chemistry of cellulose carbonates is discussed considering own research results adequately. After a short overview about methods for activation of polysaccharides for a conversion with nucleophilic compounds in particular with amines, details about various methods for the synthesis of polysaccharide carbonates are discussed.

Flooding disturbances increase resource availability and productivity but reduce stability in diverse plant communities.

The natural world is increasingly defined by change. Within the next 100 years, rising atmospheric CO₂ concentrations will continue to increase the frequency and magnitude of extreme weather events. Simultaneously, human activities are reducing global biodiversity, with current extinction rates at ~1,000 × what they were before human domination of Earth's ecosystems.

Transcriptome analysis of cyclic AMP-dependent protein kinase A-regulated genes reveals the production of the novel natural compound fumipyrrole by Aspergillus fumigatus.

Aspergillus fumigatus is an opportunistic human pathogenic fungus causing life-threatening infections in immunocompromised patients. Adaptation to different habitats and also virulence of the fungus depends on signal perception and transduction by modules such as the cyclic AMP-dependent protein kinase A (PKA) pathway. Here, by transcriptome analysis, 632 differentially regulated genes of this important signaling cascade were identified, including 23 putative transcriptional regulators.

SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary.

Gonadotroph pituitary adenomas (GPAs) often present as invasive macroadenomas not amenable to complete surgical resection. Radiotherapy is the only post-operative option for patients with large invasive or recurrent lesions. No medical treatment is available for these patients.

Elevated serum 25(OH)-vitamin D levels are negatively correlated with molar-incisor hypomineralization.

To date, the precise etiology of molar-incisor hypomineralization (MIH) is uncertain. Vitamin D plays a key role in hard tissue formation. Therefore, this study aimed to analyze the relationship between serum 25-hydroxy-vitamin D (25(OH)D) status and dental health data obtained from 1,048 children in a 10-year follow-up of the Munich GINIplus and LISAplus birth cohorts.

Capillary electrophoresis separation of peptide diastereomers that contain methionine sulfoxide by dual cyclodextrin-crown ether systems.

A dual-selector system employing achiral crown ethers in combination with cyclodextrins has been developed for the separation of peptide diastereomers that contain methionine sulfoxide. The combinations of the crown ethers 15-crown-5, 18-crown-6, Kryptofix® 21 and Kryptofix® 22 and β-cyclodextrin, carboxymethyl-β-cyclodextrin, and sulfated β-cyclodextrin were screened at pH 2.5 and pH 8.

Increased arginase levels contribute to impaired perfusion after cardiopulmonary resuscitation.

Objectives: The postcardiac arrest syndrome occurs after global hypoxia leading to microcirculatory impairment. Nitric oxide (NO) is a key molecule regulating microvascular function. The enzyme arginase has been suggested to modulate microvascular function by regulating NO metabolism.

Amnesic shellfish poisoning biotoxin detection in seawater using pure or amino-functionalized Ag nanoparticles and SERS.

Domoic acid (DA) biotoxin responsible for the amnesic shellfish poisoning (ASP) has been unambiguously detected in seawater in a broad range of concentration, with both pure and amino-functionalized Ag nanoparticles employed for surface enhanced Raman scattering (SERS). To achieve this, a comprehensive SERS study on DA dissolved in distilled water has been conducted. SERS of DA dissolved in seawater in concentrations ranging from 3.

Modulation of amino acid metabolic signatures by supplemented isoenergetic diets differing in protein and cereal fiber content.

Context: Amino-acid (AA) metabolic signatures differ in insulin-resistant (IR) obese vs normal-weight subjects, improve after weight loss, and seem to predict the risk of type 2 diabetes. It is unknown whether weight-maintaining dietary measures aimed at influencing IR alter AA signatures of high-risk subjects.

Setting And Design: In the randomized controlled Protein, Fiber and Metabolic Syndrome (ProFiMet) trial we investigated effects of four isoenergetic, moderately fat-reduced diets varying in protein and cereal-fiber contents on complete AA metabolic signatures in 76 group-matched overweight or obese high-risk subjects.

The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial.

Introduction: Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress.

Experimental design-guided development of a stereospecific capillary electrophoresis assay for methionine sulfoxide reductase enzymes using a diastereomeric pentapeptide substrate.

A capillary electrophoresis method has been developed and validated to evaluate the stereospecific activity of recombinant human methionine sulfoxide reductase enzymes employing the C-terminally dinitrophenyl-labeled N-acetylated pentapeptide ac-KIFM(O)K-Dnp as substrate (M(O)=methionine sulfoxide). The separation of the ac-KIFM(O)K-Dnp diastereomers and the reduced peptide ac-KIFMK-Dnp was optimized using experimental design with regard to the buffer pH, buffer concentration, sulfated β-cyclodextrin and 15-crown-5 concentration as well as capillary temperature and separation voltage. A fractional factorial response IV design was employed for the identification of the significant factors and a five-level circumscribed central composite design for the final method optimization.

ASMase regulates autophagy and lysosomal membrane permeabilization and its inhibition prevents early stage non-alcoholic steatohepatitis.

Background & Aims: Acid sphingomyelinase (ASMase) is activated in non-alcoholic steatohepatitis (NASH). However, the contribution of ASMase to NASH is poorly understood and limited to hepatic steatosis and glucose metabolism. Here we examined the role of ASMase in high fat diet (HFD)-induced NASH.

An experimental cell-based model for studying the cell biology and molecular pharmacology of 5-lipoxygenase-activating protein in leukotriene biosynthesis.

Background: Subcellular distribution of 5-lipoxygenase (5-LO) to the perinuclear region and interaction with the 5-LO-activating protein (FLAP) are assumed as key steps in leukotriene biosynthesis and are prone to FLAP antagonists.

Methods: FLAP and/or 5-LO were stably expressed in HEK293 cells, 5-LO products were analyzed by HPLC, and 5-LO and FLAP subcellular localization was visualized by immunofluorescence microscopy.

Results: 5-LO and FLAP were stably expressed in HEK293 cells, and upon Ca(2+)-ionophore A23187 stimulation exogenous AA was efficiently transformed into the 5-LO products 5-hydro(pero)xyeicosatetraenoic acid (5-H(p)ETE) and the trans-isomers of LTB4.

Cyclodextrin-mediated enantioseparation of phenylalanine amide derivatives and amino alcohols by capillary electrophoresis-role of complexation constants and complex mobilities.

The separation of the enantiomers of phenylalanine amide and N-methyl derivatives as well as some amino alcohols was studied by CE in acidic BGEs using CDs as chiral selectors. The native CDs displayed only low chiral recognition ability at a concentration of 15 mg/mL in 20 mM sodium phosphate buffer, pH 2.5.

Overexpression of fatty acid synthase in human gliomas correlates with the WHO tumor grade and inhibition with Orlistat reduces cell viability and triggers apoptosis.

Fatty acid synthase (FASN), catalyzing the de novo synthesis of fatty acids, is known to be deregulated in several cancers. Inhibition of this enzyme reduces tumor cell proliferation. Unfortunately, adverse effects and chemical instability prevent the in vivo use of the best-known inhibitors, Cerulenin and C75.

Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity.

Objectives: Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model.

Methods: Cinnamon components (eugenol, cinnamaldehyde) were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis.

Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents.

Facing the multifactorial nature of Alzheimer's disease, twelve dibenzofuran/carbazole derivatives, which can be considered as the D-ring opened analogs of galantamine, have been designed and synthesized as multifunctional anti-Alzheimer agents. In vitro tests revealed that compounds 3 and 5, which bear a nitrate moiety in the molecule, showed a potent inhibition activity towards AChE and compound 3 showed a good Aβ42 aggregation inhibitory activity. Moreover, 3 and 5 could also release a relative low concentration of NO in vitro and they did not show toxicity to neuronal cells, while exerted a neuroprotective effect against the Aβ-induced toxicity.

Carboxyl-terminal multi-site phosphorylation regulates internalization and desensitization of the human sst2 somatostatin receptor.

The somatostatin receptor 2 (sst2) is the pharmacological target of somatostatin analogs that are widely used in the diagnosis and treatment of human neuroendocrine tumors. We have recently shown that the stable somatostatin analogs octreotide and pasireotide (SOM230) stimulate distinct patterns of sst2 receptor phosphorylation and internalization. Like somatostatin, octreotide promotes the phosphorylation of at least six carboxyl-terminal serine and threonine residues namely S341, S343, T353, T354, T356 and T359, which in turn leads to a robust receptor endocytosis.

Synthesis and characterization of poly(phenylacetylene)s with Ru(II) bis-terpyridine complexes in the side-chain.

An alkyne-functionalized ruthenium(II) bis-terpyridine complex is directly copolymerized with phenylacetylene by alkyne polymerization. The polymer is characterized by size-exclusion chromatography (SEC), (1) H NMR spectroscopy, cyclic voltammetry (CV) measurements, and thermal analysis. The photophysical properties of the polymer are studied by UV-vis absorption spectroscopy.

Protein-like fully reversible tetramerisation and super-association of an aminocellulose.

Unusual protein-like, partially reversible associative behaviour has recently been observed in solutions of the water soluble carbohydrates known as 6-deoxy-6-(ω-aminoalkyl)aminocelluloses, which produce controllable self-assembling films for enzyme immobilisation and other biotechnological applications. Now, for the first time, we have found a fully reversible self-association (tetramerisation) within this family of polysaccharides. Remarkably these carbohydrate tetramers are then seen to associate further in a regular way into supra-molecular complexes.

Stereospecific electrophoretically mediated microanalysis assay for methionine sulfoxide reductase enzymes.

An electrophoretically mediated microanalysis assay (EMMA) for the determination of the stereoselective reduction of L-methionine sulfoxide diastereomers by methionine sulfoxide reductase enzymes was developed using fluorenylmethyloxycarbonyl (Fmoc)-L-methionine sulfoxide as substrate. The separation of the diastereomers of Fmoc-L-methionine sulfoxide and the product Fmoc-L-methionine was achieved in a successive multiple ionic-polymer layer-coated capillary using a 50 mM Tris buffer, pH 8.0, containing 30 mM sodium dodecyl sulfate as background electrolyte and an applied voltage of 25 kV.

Fine-tuning somatostatin receptor signalling by agonist-selective phosphorylation and dephosphorylation: IUPHAR Review 5.

The biological actions of somatostatin are mediated by a family of five GPCRs, named sst1 to sst5 . Somatostatin receptors exhibit equally high-binding affinities to their natural ligand somatostatin-14 and largely overlapping distributions. The overexpression of somatostatin receptors in human tumours is the molecular basis for diagnostic and therapeutic application of the stable somatostatin analogues octreotide, lanreotide and pasireotide.

Oxidative stress markers and micronutrients in maternal and cord blood in relation to neonatal outcome.

Background/objectives: Oxidative stress and micronutrient deficiencies have been related to lower birth weight (BW), small for gestational age (SGA) offspring and preterm delivery.

Subjects/methods: The relation between neonatal outcome (BW, head circumference, SGA, preterm delivery) with markers of oxidative stress and micronutrients in maternal and cord blood was to be examined. Oxidative stress markers (protein carbonyls (PrCarb), 3-nitrotyrosine (3NT), malondialdehyde (MDA)), total protein concentration and lipid-soluble micronutrients (carotenoids, retinol, tocopherols) were measured in 200 newborns (11% preterms, 13% SGA) and 151 mothers.