Phylogeny and habitat adaptations within a monophyletic group of wetland moss genera (Amblystegiaceae)

Genus level phylogenetic patterns within a monophyletic group of wetland mosses consisting ofTomentypnum, Hamatocaulis, Scorpidium, Conardia, Calliergon, Warnstorfia, Straminergon, andLoeskypnum (Amblystegiaceae) are cladistically analysed, usingPalustriella and partlyCratoneuron as outgroups. The ingroup consists of two clades, one withTomentypnum, Hamatocaulis andScorpidium, the other with the other ingroup genera. The second clade gets completely resolved only with the inclusion of habitat data. The adaptation to relatively dry wetland habitats probably evolved in the ancestor ofStraminergon andLoeskypnum, the species ofCalliergon andWarnstorfia, which are more ancestral, growing in wetter habitats. The more primitive taxa of the ingroup, as well asPalustriella species, occur in relatively mineral-rich habitats and adaptations to poorer habitats occurred several times in the two clades.     

Life cycle inventory data

This article describes the work carried out by the Promoting Sound Practices (PSP) working group of SPOLD (Society for the Promotion of Lifecycle Development) on the development of a common format for reporting life cycle inventory data in a comparable and transparent way, and hence towards the eventual goal of a decentralised network of life cycle inventory databases. Establishing such a database network depends on the achievement of consensus amongst potential users, data owners and data generators. Accordingly, building consensus has been, and will continue to be given, a high priority in this work. As well as a summary of the consensus building activities, this article provides an outline of the developing format and an indication of the next steps planned, some of which are already underway.     

Waiving in vivo studies for monoclonal antibody biosimilar development: National and global challenges

Biosimilars are biological medicinal products that contain a version of the active substance of an already authorised original biological medicinal product (the innovator or reference product). The first approved biosimilar medicines were small proteins, and more recently biosimilar versions of innovator monoclonal antibody (mAb) drugs have entered development as patents on these more complex proteins expire. In September 2013, the first biosimilar mAb, infliximab, was authorised in Europe. In March 2015, the first biosimilar (Zarxio?, filgrastim-sndz, Sandoz) was approved by the US Food and Drug Administration; however, to date no mAb biosimilars have been approved in the US. There are currently major differences between how biosimilars are regulated in different parts of the world, leading to substantial variability in the amount of in vivo nonclinical toxicity testing required to support clinical development and marketing of biosimilars. There are approximately 30 national and international guidelines on biosimilar development and this number is growing. The European Union's guidance describes an approach that enables biosimilars to enter clinical trials based on robust in vitro data alone; in contrast, the World Health Organization's guidance is interpreted globally to mean in vivo toxicity studies are mandatory.

We reviewed our own experience working in the global regulatory environment, surveyed current practice, determined drivers for nonclinical in vivo studies with biosimilar mAbs and shared data on practice and study design for 25 marketed and as yet unmarketed biosimilar mAbs that have been in development in the past 5y. These data showed a variety of nonclinical in vivo approaches, and also demonstrated the practical challenges faced in obtaining regulatory approval for clinical trials based on in vitro data alone. The majority of reasons for carrying out nonclinical in vivo studies were not based on scientific rationale, and therefore the authors have made recommendations for a data-driven approach to the toxicological assessment of mAb biosimilars that minimises unnecessary use of animals and can be used across all regions of the world.     

Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study

ObjectiveTo study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring.DesignCross-sectional comparison of serum biomarkers.SettingUniversity Medical Center Utrecht.PatientsHyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6–8 years), and a paedriatic reference population (n = 30).ResultsThe cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R² = 0.219) and adiponectin (R² = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001), DPP-IV (P = 0.005), and adiponectin (P < 0.001). Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P < 0.001) concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing.ConclusionIn this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers (MMP-9, S100A8) were increased, suggesting that these children may exhibit increased chronic low-grade inflammation. Additional research is required to confirm results of the current exploratory investigation.     

A straightforward approach to isolate DNA sequences with potential linkage to the retinoblastoma locus

Summary From a human-Chinese hamster somatic cell hybrid a clone was derived containing chromosome 13 in duplicate as its only human material. This clone was used to construct a human chromosome 13-specific recombinant DNA-library. Overlapping Sau3AI DNA sequences (11.9–17.2 kb) from the cell hybrid were inserted into the lambda phage vector EMBL4. From eleven recombinants having a human insert thirteen putative unique DNA sequences were isolated and cloned into the plasmid vector pBR329. A human-mouse hybrid containing a human chromosome 13 with a deletion of 13q14 and lacking its undeleted homologue was constructed to be used in a selection procedure for DNA sequences belonging to band q14. Three probes originating from two different phages were assigned to 13q14 because they did not hybridise to DNA from this cell hybrid. One of these 13q14 probes detects a low frequency (2/44) Msp I restriction fragment length polymorphism. The probes are now being used for screening a cosmid library to find adjacent polymorphic sequences with a RFLP information content suitable for application in the diagnosis of hereditary retinoblastoma.Preliminary reports of these experiments were presented at the 8th International Workshop on Human Gene Mapping, Helsinki, August 4–10, 1985, and the 13th International Congress of Biochemistry, Amsterdam, August 25–30, 1985 (Scheffer et al. 1985a,b)     

The relationship between the in situ reduction level of the cytochrome c pool of Azorhizobium caulinodans growing in a chemostat with NH4+ or N2 as the N source and the total activity of cytochrome c oxidases

Abstract The in situ method for determination of reduction levels of cytochromes b and c pools during steady-state growth (Pronk et al., Anal. Biochem. 214, 149–155, 1993) was applied to chemostat cultures of the wild-type, a cytochrome aa₃ single mutant and a cytochrome aa₃/d double mutant of Azorhizobium caulinodans . For growth with NH₄⁺ as the N source, the results indicate that (i) the aa₃ mutant strains growing at a dissolved O₂ tension of 0.5% possess an active alternative cytochrome c oxidase, which is hardly present during fully aerobic growth, and assuming that (i) also pertains to the wild-type, (ii) the wild-type uses cytochrome aa₃ under fully aerobic conditions. For growth with N₂ as the N source, it was found that the aa₃ mutant strains growing at dissolved O₂ tensions ranging from 0.5 to 3.0% also contain an active alternative cytochrome c oxidase.     

The influence of light and air on the purification of polluted water

Summary A comparative study was made between the organic polluted water from the river Lieve (Ghent, Belgium), and the same water treated in the laboratory aquaria, with light and atmospheric air at a constant temperature.The treatment influenced the biological selfpurification, as well in its early start, as in its final qualitative and quantitative expression.There were significant changes in the chemical and biological composition of the treated Lieve-water, and some of the changes could be traced to differences in the treatment of the water.The biochemical oxygen demand and the KMnO₄-consumption test decreased fast and reached minimal values.On the other side pH values transparency, oxygen content, nitrite and nitrate nitrogen increased to maximal values.The evolution of the plankton organisms was followed up regularly and important changes occured as well in the quantitative as in the qualitative composition of the waters.The saprobic value of the initial Lieve-water and that of the waters in the aquaria was estimated.Important differences in the evolution of the saprobic values could be demonstrated.