New Acyclic Cytotoxic Jasplakinolide Derivative from the Marine Sponge .

A new acylic jasplakinolide congener (), another acyclic derivative requiring revision (), together with two jasplakinolide derivatives including the parent compound jasplakinolide () were isolated from the Indonesian marine sponge . The chemical structures of the new and known compounds were unambiguously elucidated based on HRESIMS and exhaustive 1D and 2D NMR spectral analysis as well as a comparison of their NMR data with those of jasplakinolide (). The isolated jasplakinolides inhibited the growth of mouse lymphoma (L5178Y) cells in vitro with IC values in the low micromolar to nanomolar range.

Systematic characterization of position one variants within the lantibiotic nisin.

Lantibiotics are a growing class of natural compounds, which possess antimicrobial activity against a broad range of Gram-positive bacteria. Their high potency against human pathogenic strains such as MRSA and VRE makes them excellent candidates as substitutes for classic antibiotics in times of increasing multidrug resistance of bacterial strains. New lantibiotics are detected in genomes and can be heterologously expressed.

Powder bed 3D-printing of highly loaded drug delivery devices with hydroxypropyl cellulose as solid binder.

3D-printing is a promising tool to pave the way to the widespread adaption of individualized medicine. Several printing techniques have been investigated and introduced to pharmaceutical research. Until now, only one 3D-printed medicine is approved on the US market.

Monodisperse Sequence-Controlled α-l-Fucosylated Glycooligomers and Their Multivalent Inhibitory Effects on LecB.

The opportunistic bacterium Pseudomonas aeruginosa, often exhibiting multiresistance against conventional antibiotics, expresses the lectin LecB that is suspected to be an important factor during biofilm formation via interactions with cell-surface presented carbohydrate ligands such as the blood group antigens. Therefore, carbohydrate-based ligands interfering with LecB binding have the potential to lead to new anti-biofilm and anti-adhesion therapies. This study explores in vitro binding potencies of glycomimetic ligands containing up to six α-l-fucose ligands on a monodisperse, sequence-controlled oligoamide scaffold interacting with LecB.

How relevant is ribbon homogeneity in roll compaction/dry granulation and can it be influenced?

A homogeneous distribution of solid fraction in ribbons is generally assumed to be beneficial during roll compaction/dry granulation. Numerous attempts have been made to increase this homogeneity by modification of the machine, i.e.

Evidence for Stabilizing Selection Driving Mutational Turnover of Short Motifs in the Eukaryotic Complementary Sex Determiner (Csd) Protein.

Short linear motifs (SLiMs) can play pivotal functional roles in proteins, such as targeting proteins to specific subcellular localizations, modulating the efficiency of translation and tagging proteins for degradation. Until recently we had little knowledge about SLiM evolution. Only a few amino acids in these motifs are functionally important, making them likely to evolve and suggesting that they can play key roles in protein evolution.

Lead Compounds from Mangrove-Associated Microorganisms.

The mangrove ecosystem is considered as an attractive biodiversity hotspot that is intensively studied in the hope of discovering new useful chemical scaffolds, including those with potential medicinal application. In the past two decades, mangrove-derived microorganisms, along with mangrove plants, proved to be rich sources of bioactive secondary metabolites as exemplified by the constant rise in the number of publications, which suggests the great potential of this important ecological niche. The present review summarizes selected examples of bioactive compounds either from mangrove endophytes or from soil-derived mangrove fungi and bacteria, covering the literature from 2014 to March 2018.

Sidestep-induced neuromuscular miswiring causes severe locomotion defects in larvae.

Mutations in motor axon guidance molecules cause aberrant projection patterns of motor nerves. As most studies in have analysed these molecules in fixed embryos, the consequences for larval locomotion are entirely unexplored Here, we took advantage of ()-mutant larvae that display severe locomotion defects because of irreparable innervation errors. Mutations in affected all motor nerve branches and all body wall regions.

Synthesis of highly controlled carbohydrate-polymer based hybrid structures by combining heparin fragments and sialic acid derivatives, and solid phase polymer synthesis.

Heparin is a polymeric carbohydrate with a variety of biomedical applications that is particularly challenging from a synthetic point of view. Here, we present the synthesis of carbohydrate-polymer based hybrid structures by combining defined heparin fragments with monodisperse, sequence-controlled glycooligo(amidoamines) suitable as glycan mimetic model compounds of heparin as demonstrated by STD-NMR binding studies with viral capsids.

CFA-14 - a perfluorinated metal-organic framework with linear 1-D Co-chains showing temperature dependent spin-chain magnetic ordering.

The synthesis and crystal structure of the perfluorinated metal-organic framework (MOF) CFA-14 (Coordination Framework Augsburg University-14), CoII2(tfpb)(OH)2 (H2-tfpb = 1,4-bis(3,5-bis(trifluoromethyl)-1H-pyrazole-4-yl)benzene) are described. The cobalt-containing MOF crystallizes in the tetragonal crystal system within the space group I41/acd (no. 142) and the unit cell parameters are as follows: a = 20.

Adenosine enhances cisplatin sensitivity in human ovarian cancer cells.

Ovarian cancer is the deadliest gynecologic cancer due to lack of early effective diagnosis and development of resistance to platinum-based chemotherapy. Several studies reported that adenosine concentrations are higher in tumor microenvironment than in non-tumor tissue. This finding inspired us to study the role of adenosine in ovarian cancer cells and to investigate if adenosine pathways offer new treatment options urgently needed to prevent or overcome chemoresistance.

Polypharmacology by Design: A Medicinal Chemist's Perspective on Multitargeting Compounds.

Multitargeting compounds comprising activity on more than a single biological target have gained remarkable relevance in drug discovery owing to the complexity of multifactorial diseases such as cancer, inflammation, or the metabolic syndrome. Polypharmacological drug profiles can produce additive or synergistic effects while reducing side effects and significantly contribute to the high therapeutic success of indispensable drugs such as aspirin. While their identification has long been the result of serendipity, medicinal chemistry now tends to design polypharmacology.

Laser based thermo-conductometry as an approach to determine ribbon solid fraction off-line and in-line.

Ribbon solid fraction is one of the most important quality attributes during roll compaction/dry granulation. Accurate and precise determination is challenging and no in-line measurement tool has been generally accepted, yet. In this study, a new analytical tool with potential off-line as well as in-line applicability is described.

Cotransporter-mediated water transport underlying cerebrospinal fluid formation.

Cerebrospinal fluid (CSF) production occurs at a rate of 500 ml per day in the adult human. Conventional osmotic forces do not suffice to support such production rate and the molecular mechanisms underlying this fluid production remain elusive. Using ex vivo choroid plexus live imaging and isotope flux in combination with in vivo CSF production determination in mice, we identify a key component in the CSF production machinery.

Continuous inkjet printing of enalapril maleate onto orodispersible film formulations.

Piezoelectric inkjet printing onto orodispersible films (ODFs) was proven to be a successful technique applying flexible doses of active pharmaceutical ingredients (APIs) onto edible substrates. The reported API printing and ODF production was conducted in a non-continuous production approach. Within this study, drug-free and hydrochlorothiazide (HCT) containing ODFs should be imprinted in-line with enalapril maleate (EM) ink during continuous ODF production.

Pallidal deep brain stimulation in juvenile Huntington's disease: local field potential oscillations and clinical data.

Background: Recently, therapeutic attempts to control motor choreatic hyperkinesia of Huntington's disease (HD) by means of pallidal deep brain stimulation (Gp-DBS) were successful. With respect to the clinical effects of Gp-DBS in juvenile hypokinetic-rigid HD (jHD; Westphal variant), only one single-case has been reported up to date. Oscillatory patterns of the Gp in jHD are not known.

The histamine H4 receptor modulates the differentiation process of human monocyte-derived M1 macrophages and the release of CCL4/MIP-1β from fully differentiated M1 macrophages.

Objective: Histamine is an important mediator of biological functions and present in high amounts in inflammatory skin lesions which are characterised by a marked infiltration of myeloid derived cell populations. The aim of the study was to investigate the expression and function of histamine receptors, with a focus on the histamine H4 receptor (H4R) in detail during the differentiation process from monocytes to macrophages and on fully differentiated M1 macrophages.

Methods: Quantitative PCR, ELISA technique, and flow cytometry were applied to analyze expression levels of histamine receptors, of CXCL10, CCL4, CCL3, or IL-23 and of the macrophage differentiation marker CD68, respectively.

Continuous manufacturing and analytical characterization of fixed-dose, multilayer orodispersible films.

Various drug therapies require more than one active pharmaceutical ingredient (API) for an effective treatment. There are many advantages, e.g.

Age differences in the association between stressful work and sickness absence among full-time employed workers: evidence from the German socio-economic panel.

Purpose: We aim to extend current knowledge on associations between stressful work and sickness absence, first, by studying associations between ERI and sickness absence among full-time employees from various occupations, and second, by investigating if associations vary by age.

Methods: We use data from four waves of the German socio-economic panel (GSOEP), collected among men and women between 2006 and 2012, with 9418 observations. Stressful work is measured with a short form of the ERI questionnaire.

Flexible and precise dosing of enalapril maleate for all paediatric age groups utilizing orodispersible minitablets.

Enalapril is an off-patent angiotensin-converting enzyme inhibitor for which no paediatric age-appropriate formulation is commercially available in Europe, and enalapril maleate (EM) orodispersible minitablets (ODMTs) have previously been formulated within the LENA (labelling enalapril from neonates to adolescents) project. In this study, a dilution method has been developed by dispersing the lowest dose strength ODMTs to enable flexible and precise EM dosing during the dose titration phase of the therapy. Furthermore, the physicochemical stability of the ODMTs has been investigated in child-friendly beverages and the administration of ODMTs via nasogastric tubes (NGT) of different sizes and materials has been evaluated.

Gene expression and activity of digestive enzymes of Daphnia pulex in response to food quality differences.

Food quality is an important factor influencing organisms' well-being. In freshwater ecosystems, food quality has been studied extensively for the keystone herbivore genus Daphnia, as they form the critical trophic link between primary producers and higher order consumers such as fish. For Daphnia, the edible fraction of phytoplankton in lakes (consisting mostly of unicellular algae and cyanobacteria) is extraordinarily diverse.

Spheronization of solid lipid extrudates: Elucidation of spheroid formation mechanism.

To explain the rounding mechanism of extrudates by spheronization method, two main concepts are found in literature: one proposed by Rowe (1985) and one proposed by Baert et al. (1993). These concepts are based on wet extrusion-spheronization method using microcrystalline cellulose as mains excipient.

Jasmonic and salicylic acid response in the fern Azolla filiculoides and its cyanobiont.

Plants sense and respond to microbes utilizing a multilayered signalling cascade. In seed plants, the phytohormones jasmonic and salicylic acid (JA and SA) are key denominators of how plants respond to certain microbes. Their interplay is especially well-known for tipping the scales in plants' strategies of dealing with phytopathogens.

Roll Compaction/Dry Granulation of Dibasic Calcium Phosphate Anhydrous-Does the Morphology of the Raw Material Influence the Tabletability of Dry Granules?

The influence of raw material particle morphology on the tabletabilty of dry granules was investigated. Therefore, dibasic calcium phosphate anhydrous was used as a model material. One milled grade, 2 agglomerated grades with different porosities, and a functionalized structure, that is, an agglomerate formed by very small primary particles, were included.

Orodispersible films: Product transfer from lab-scale to continuous manufacturing.

Orodispersible films have been described as new beneficial dosage forms for special patient populations. Due to various production settings, different requirements on film formulations are required for non- continuous and continuous manufacturing. In this study, a continuous coating machine was qualified in regards of the process conditions for film compositions and their effects on the formed films.