Phylogenomic insights into the first multicellular streptophyte.

Streptophytes are best known as the clade containing the teeming diversity of embryophytes (land plants). Next to embryophytes are however a range of freshwater and terrestrial algae that bear important information on the emergence of key traits of land plants. Among these, the Klebsormidiophyceae stand out.

Application of advanced high resolution mass spectrometric techniques for the analysis of losartan potassium regarding known and unknown impurities.

Recalls of medicinal products can cause supply bottlenecks. This is often due to the findings of unexpected impurities that pose a health risk to patients. A recent example is losartan potassium which was contaminated with azido-impurities.

The quality of drugs and drug products - Always guaranteed?

To ensure the efficacy, safety, and quality of drugs, several national and international guidelines and regulatory requirements exist. The most important international regulatory framework for quality is the collection of the guidelines ICH Q1-Q14 (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use), which form the basis for the development and approval of medicinal products. Additionally, international and national pharmacopoeias and national regulatory authorities like Food and Drug Administration (FDA) and European Directory for the Quality of Medicines and HealthCare (EDQM) have to be considered during the lifecycle of a drug.

Environmental gradients reveal stress hubs pre-dating plant terrestrialization.

Plant terrestrialization brought forth the land plants (embryophytes). Embryophytes account for most of the biomass on land and evolved from streptophyte algae in a singular event. Recent advances have unravelled the first full genomes of the closest algal relatives of land plants; among the first such species was Mesotaenium endlicherianum.

Structure-based Design of Novel Hepatitis B Virus Capsid Assembly Modulators.

Small-molecule capsid assembly modulators (CAMs) have been recently recognized as promising antiviral agents for curing chronic hepatitis B virus (HBV) infection. A target-based in silico screening study is described, aimed towards the discovery of novel HBV CAMs. Initial optimization of four weakly active screening hits was performed via focused library synthesis.

Mechanochemical Oxidative Degradation of Thienopyridine Containing Drugs: Toward a Simple Tool for the Prediction of Drug Stability.

The long-term stability of an active-pharmaceutical ingredient and its drug products plays an important role in the licensing process of new pharmaceuticals and for the application of the drug at the patient. It is, however, difficult to predict degradation profiles at early stages of the development of new drugs, making the entire process very time-consuming and costly. Forced mechanochemical degradation under controlled conditions can be used to realistically model long-term degradation processes naturally occurring in drug products, avoiding the use of solvents, thus excluding irrelevant solution-based degradation pathways.

Chromosome-level genomes of multicellular algal sisters to land plants illuminate signaling network evolution.

The filamentous and unicellular algae of the class Zygnematophyceae are the closest algal relatives of land plants. Inferring the properties of the last common ancestor shared by these algae and land plants allows us to identify decisive traits that enabled the conquest of land by plants. We sequenced four genomes of filamentous Zygnematophyceae (three strains of and one strain of ) and generated chromosome-scale assemblies for all strains of the emerging model system .

Discovery, Chemistry, and Preclinical Development of Pritelivir, a Novel Treatment Option for Acyclovir-Resistant Herpes Simplex Virus Infections.

When the nucleoside analogue acyclovir was introduced in the early 1980s, it presented a game-changing treatment modality for herpes simplex virus infections. Since then, work has been ongoing to improve the weaknesses that have now been identified: a narrow time window for therapeutic success, resistance in immunocompromised patients, little influence on frequency of recurrences, relatively fast elimination, and poor bioavailability. The present Drug Annotation focuses on the helicase-primase inhibitor pritelivir currently in development for the treatment of acyclovir-resistant HSV infections and describes how a change of the molecular target (from viral DNA polymerase to the HSV helicase-primase complex) afforded improvement of the shortcomings of nucleoside analogs.

A phylogenomically informed five-order system for the closest relatives of land plants.

The evolution of streptophytes had a profound impact on life on Earth. They brought forth those photosynthetic eukaryotes that today dominate the macroscopic flora: the land plants (Embryophyta). There is convincing evidence that the unicellular/filamentous Zygnematophyceae-and not the morphologically more elaborate Coleochaetophyceae or Charophyceae-are the closest algal relatives of land plants.

Developmental Plasticity of the Amphibious Liverwort .

The colonization of land by ancestors of embryophyte plants was one of the most significant evolutionary events in the history of life on earth. The lack of a buffering aquatic environment necessitated adaptations for coping with novel abiotic challenges, particularly high light intensities and desiccation as well as the formation of novel anchoring structures. Bryophytes mark the transition from freshwater to terrestrial habitats and form adaptive features such as rhizoids for soil contact and water uptake, devices for gas exchange along with protective and repellent surface layers.

An automated microfluidic platform for the screening and characterization of novel hepatitis B virus capsid assembly modulators.

To date, hepatitis B virus (HBV) capsid assembly modulators (CAMs), which target the viral core protein and induce the formation of non-functional viral capsids, have been identified and characterized in microtiter plate-based biochemical or cell-based assays. In this work, we developed an automated microfluidic screening assay, which uses convection-dominated Taylor-Aris dispersion to generate high-resolution dose-response curves, enabling the measurements of compound EC values at very short incubation times. The measurement of early kinetics down to 7.

Split-HaloTag imaging assay for sophisticated microscopy of protein-protein interactions .

An ever-increasing number of intracellular multi-protein networks have been identified in plant cells. Split-GFP-based protein-protein interaction assays combine the advantages of interaction studies in a native environment with additional visualization of protein complex localization. Because of their simple protocols, they have become some of the most frequently used methods.

Ball milling - a new concept for predicting degradation profiles in active pharmaceutical ingredients.

A method for forced oxidative mechanochemical degradation of active pharmaceutical ingredients (APIs) using clopidogrel hydrogensulfate as a model compound is presented. Considerable and selective formation of degradants occurs already after very short reaction times of less than 15 minutes and the nature of the products is strongly dependent on the used oxidant.

Locality, time and heterozygosity affect chytrid infection in yellow-bellied toads.

The chytrid fungus Batrachochytrium dendrobatidis (Bd) infects numerous amphibian species worldwide and is suggested to drive population declines and extinction events. We report a study of Bd infection at the northernmost distribution of the European yellow-bellied toad Bombina variegata. A total of 577 individuals from ponds in 16 study sites were sampled for DNA and Bd throughout the breeding season.

Into another dimension: how streptophyte algae gained morphological complexity.

Land plants with elaborated three-dimensional (3D) body plans have evolved from streptophyte algae. The streptophyte algae are known to exhibit varying degrees of morphological complexity, ranging from single-celled flagellates to branched macrophytic forms exhibiting tissue-like organization. In this review, I discuss mechanisms by which, during evolution, filamentous algae may have gained 2D and eventually 3D body plans.

Update on plant cytokinesis: rule and divide.

Many decisions made during plant development depend on the placement of the cytokinetic wall. Cytokinesis involves the biogenesis of the cell plate that progresses centrifugally and until the fusion of the cell plate with the parental cell wall. The phragmoplast facilitates the growth of the cell plate and directs it's insertion at the cell cortex by a mechanism known as phragmoplast guidance.

Handedness in plant cell expansion: a mutant perspective on helical growth.

Many plant mutants are known that exhibit some degree of helical growth. This 'twisted' phenotype has arisen frequently in mutant screens of model organisms, but it is also found in cultivars of ornamental plants, including trees. The phenomenon, in many cases, is based on defects in cell expansion symmetry.

[Exercise Testing in Respiratory Medicine - DGP Recommendations].

This document replaces the DGP recommendations published in 1998 and 2013. Based on recent studies and a consensus conference, the indications, choice and performance of the adequate exercise testing method and its necessary technical and staffing setting are discussed. Detailed recommendations are provided: for blood gas analysis and right heart catheterization during exercise, walk tests, spiroergometry, and stress echocardiography.

Diffusion ordered NMR spectroscopy measurements as screening method of potential reactions of API and excipients in drug formulations.

In the development of new pharmaceutical formulations it is important to consider the possible interactions between the active pharmaceutical ingredient (API) and excipients which is a well-known problem. The objective of the work presented here was to investigate such reactions by means of diffusion ordered NMR spectroscopy (DOSY). The known reaction of 5-aminosalicylic acid (5-ASA) and the excipient citric acid was studied.