Bilirubin Oxidation End Products (BOXes) Induce Neuronal Oxidative Stress Involving the Nrf2 Pathway.

Delayed ischemic neurological deficit (DIND) is a severe complication after subarachnoid hemorrhage (SAH). Previous studies have suggested that bilirubin oxidation end products (BOXes) are probably associated with the DIND after SAH, but there is a lack of direct evidence yet even on cellular levels. In the present study, we aim to explore the potential role of BOXes and the involved mechanisms in neuronal function.

ADP-ribosyltransferases, an update on function and nomenclature.

ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- and extracellular signaling, chromatin and transcriptional regulation, protein biosynthesis, and cell death. ADP-ribosylation is catalyzed by ADP-ribosyltransferases (ARTs), which transfer ADP-ribose from NAD onto substrates. The modification, which occurs as mono- or poly-ADP-ribosylation, is reversible due to the action of different ADP-ribosylhydrolases.

Comparative effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG HP) in assisted reproductive technology (ART) treatments: a non-interventional study in Germany.

Background: This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP), during assisted reproductive technology (ART) treatments in Germany.

Methods: Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC).

Comparative Study between Exogenously Applied Plant Growth Hormones versus Metabolites of Microbial Endophytes as Plant Growth-Promoting for L.

Microbial endophytes organize symbiotic relationships with the host plant, and their excretions contain diverse plant beneficial matter such as phytohormones and bioactive compounds. In the present investigation, six bacterial and four fungal strains were isolated from the common bean ( L.) root plant, identified using molecular techniques, and their growth-promoting properties were reviewed.

Bremerella alba sp. nov., a novel planctomycete isolated from the surface of the macroalga Fucus spiralis.

A bacterial strain, designated FF15, was isolated from the thallus surface of the macroalga Fucus spiralis sampled on a rocky beach in Porto, Portugal. Based on the 16S rRNA gene sequence, strain FF15 was affiliated to the phylum Planctomycetes. This strain forms white colonies on modified M13 medium and the cells are pear-shaped, can form rosettes, divide by polar budding and are motile.

Chemoenzymatic Synthesis of 5-Methylpsilocybin: A Tryptamine with Potential Psychedelic Activity.

A novel analogue of psilocybin was produced by hybrid chemoenzymatic synthesis in sufficient quantity to enable bioassay. Utilizing purified 4-hydroxytryptamine kinase from , chemically synthesized 5-methylpsilocin () was enzymatically phosphorylated to provide 5-methylpsilocybin (). The zwitterionic product was isolated from the enzymatic step with high purity utilizing a solvent-antisolvent precipitation approach.

Chronic ethanol consumption does not reduce true bone density in male Wistar rats.

Osteoporosis is characterized by reduced bone mineral density (BMD) and increased bone fragility, which may be modified by lifestyle behaviors. In observational studies, chronic moderate ethanol consumption is associated with higher BMD, but results are inconsistent and underlying mechanisms are unknown. To understand the influence of chronic ethanol consumption on true bone density (Archimedes principal), bone mechanical properties (Young's Modulus of bend), and osteogenic gene expression, 12-month-old male Wistar rats were randomly assigned to a control group or ethanol intervention (20% ethanol in drinking water on alternate days) group for 13 weeks and tibiae and femurs were collected.

Pathways linking biodiversity to human health: A conceptual framework.

Biodiversity is a cornerstone of human health and well-being. However, while evidence of the contributions of nature to human health is rapidly building, research into how biodiversity relates to human health remains limited in important respects. In particular, a better mechanistic understanding of the range of pathways through which biodiversity can influence human health is needed.

Evidence for multi-copy Mega-NUMTs in the human genome.

The maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals.

Targeting Chromatin Complexes in Myeloid Malignancies and Beyond: From Basic Mechanisms to Clinical Innovation.

The aberrant function of chromatin regulatory networks (epigenetics) is a hallmark of cancer promoting oncogenic gene expression. A growing body of evidence suggests that the disruption of specific chromatin-associated protein complexes has therapeutic potential in malignant conditions, particularly those that are driven by aberrant chromatin modifiers. Of note, a number of enzymatic inhibitors that block the catalytic function of histone modifying enzymes have been established and entered clinical trials.

Retinoic Acid and Its Derivatives in Skin.

The retinoids are a group of compounds including vitamin A and its active metabolite all-trans-retinoic acid (ATRA). Retinoids regulate a variety of physiological functions in multiple organ systems, are essential for normal immune competence, and are involved in the regulation of cell growth and differentiation. Vitamin A derivatives have held promise in cancer treatment and ATRA is used in differentiation therapy of acute promyelocytic leukemia (APL).

Overcoming the hydrophilicity of bacterial nanocellulose: Incorporation of the lipophilic coenzyme Q10 using lipid nanocarriers for dermal applications.

Although used in a wide range of medical and pharmaceutical applications, the potential of the natural biopolymer bacterial nanocellulose (BNC) as drug delivery system is by far not fully exploited. Particularly, the incorporation of lipophilic drugs is still considered as an unsolved task. In the present study, the homogeneous incorporation of the lipophilic coenzyme Q10 (CoQ10) into BNC was accomplished by several post-synthesis techniques utilizing different nanoemulsions and liposomes.

12-Oxo-10-glutathionyl-5,8,14-eicosatrienoic acid (TOG), a novel glutathione-containing eicosanoid generated via the 12-lipoxygenase pathway in human platelets.

Biologically active glutathione (GSH) conjugates of oxygenated fatty acids comprise a group of pro- and anti-inflammatory lipid mediators. While arachidonic acid (AA)-derived conjugates, as the cysteinyl leukotrienes (cys-LTs) and eoxins (EXs) have pro-inflammatory properties, conjugates in tissue regeneration (CTRs) biosynthesized from docosahexaenoic acid (DHA) exhibit pro-resolving activity. Human platelets express abundant amounts of platelet-type 12-lipoxygenase (pt12-LOX) and leukotriene C synthase (LTCS).

Comparative Genome Analysis of 33 Strains Reveals Characteristic Features of and Closely Related Species.

To identify genome-based features characteristic of the avian and human pathogen and related chlamydiae, we analyzed whole-genome sequences of 33 strains belonging to 12 species. Using a novel genome analysis tool termed Roary ILP Bacterial Annotation Pipeline (RIBAP), this panel of strains was shown to share a large core genome comprising 784 genes and representing approximately 80% of individual genomes. Analyzing the most variable genomic sites, we identified a set of features of that in its entirety is characteristic of this species: (i) a relatively short plasticity zone of less than 30,000 nt without a tryptophan operon (also in ), (ii) a characteristic set of of Inc proteins comprising IncA, B, C, V, X, Y (with homologs in and as closest relatives), (iii) a 502-aa SinC protein, the largest among spp.

Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer's Disease.

Background: Hyperhomocysteinemia is considered a possible contributor to the complex pathology of Alzheimer's disease (AD). For years, researchers in this field have discussed the apparent detrimental effects of the endogenous amino acid homocysteine in the brain. In this study, the roles of hyperhomocysteinemia driven by vitamin B deficiency, as well as potentially beneficial dietary interventions, were investigated in the novel knock-in mouse model for AD, simulating an early stage of the disease.

Cyanide Bridged Platinum-Iron Complexes as Cisplatin Prodrug Systems: Design and Computational Study.

The potential role of cyanide-bridged platinum-iron complexes as an anti-cancer Pt(IV) prodrug is studied. We present design principles of a dual-function prodrug that can upon reduction dissociate and release concurrently six cisplatin units and a ferricyanide anion per prodrug unit. The prodrug molecule is a unique complex of hepta metal centers consisting of a ferricyanide core with six Pt(IV) centers each bonded to the Fe(III) core through a cyano ligand.

Enantioseparation of alanyl-phenylalanine analogs by capillary electrophoresis using negatively charged cyclodextrins as chiral selectors.

The separation of the ll- and dd-enantiomers of the dipeptides Ala-Phe, Ala-phenylglycine (Phg), Ala-homoPhe, Ala-β-Phe, Gly-Phe and β-Ala-Phe was studied by capillary electrophoresis in the presence of negatively charged α-, β- and γ-cyclodextrin (CD) derivatives. Analysis was performed under standardized conditions in fused-silica capillaries at pH 2.5, 3.

Effect of Hydrophilic Monomer Distribution on Self-Assembly of a pH-Responsive Copolymer: Spheres, Worms and Vesicles from a Single Copolymer Composition.

A series of copolymers containing 50 mol % acrylic acid (AA) and 50 mol % butyl acrylate (BA) but with differing composition profiles ranging from an AA-BA diblock copolymer to a linear gradient poly(AA-grad-BA) copolymer were synthesized and their pH-responsive self-assembly behavior was investigated. While assemblies of the AA-BA diblock copolymer were kinetically frozen, the gradient-like compositions underwent reversible changes in size and morphology in response to changes in pH. In particular, a diblock copolymer consisting of two random copolymer segments of equal length (16 mol % and 84 mol % AA content, respectively) formed spherical micelles at pH >5, a mix of spherical and wormlike micelles at pH 5 and vesicles at pH 4.

Synthetic Analogues of Aminoadamantane as Influenza Viral Inhibitors-In Vitro, In Silico and QSAR Studies.

A series of nineteen amino acid analogues of amantadine (Amt) and rimantadine (Rim) were synthesized and their antiviral activity was evaluated against influenza virus A (H3N2). Among these analogues, the conjugation of rimantadine with glycine illustrated high antiviral activity combined with low cytotoxicity. Moreover, this compound presented a profoundly high stability after in vitro incubation in human plasma for 24 h.

Polymer-Based Batteries-Flexible and Thin Energy Storage Systems.

Batteries have become an integral part of everyday life-from small coin cells to batteries for mobile phones, as well as batteries for electric vehicles and an increasing number of stationary energy storage applications. There is a large variety of standardized battery sizes (e.g.

Unusual complexation behavior between daclatasvir and γ-Cyclodextrin. A multiplatform study.

During a screening of cyclodextrins (CDs) as chiral selectors for the separation of daclatasvir (DCV) and its enantiomer by capillary electrophoresis (CE), an unusual phenomenon for CDs was observed, that is two peaks with a plateau in between using γ-CD as chiral selector. The same result was encountered when enantiopure DCV was injected or when analyzing a sample containing enantiopure DCV and γ-CD in a CD-free background electrolyte. Peak coalescence was observed at 45°C and at a pH above 3.