High-throughput methods for miniaturization and automation of monoclonal antibody purification processes

In the last decade, high-throughput downstream process development techniques have entered the biopharmaceutical industry. As chromatography is the standard downstream purification method, several high-throughput chromatographic methods have been developed and applied including miniaturized chromatographic columns for utilization on liquid handling stations. These columns were used to setup a complete downstream process on a liquid handling station for the first time. In this article, a monoclonal antibody process was established in lab-scale and miniaturized afterwards. The scale-down methodology is presented and discussed. Liquid handling in miniaturized single and multicolumn processes was improved and applicability was demonstrated by volume balances. The challenges of absorption measurement are discussed and strategies were shown to improve volume balances and mass balances in 96-well microtiter plates. The feasibility of miniaturizing a complete downstream process was shown. In the future, analytical bottlenecks should be addressed to gain the full benefit from miniaturized complete process development.     

Semipreparative enantioseparation of Tröger base derivatives by HPLC

We describe the enantioseparation of functionalized derivatives of the Tr?ger base by HPLC on commercially available chiral stationary phases. Cellulose-derived Chiralcel OJ and brush-type Whelk O1 are demonstrated to be complementary to each other in their scope. On the basis of the results obtained, the separation of selected compounds was successfully transferred onto semipreparative columns. We believe that the availability of enantiopure functionalized derivatives of the Tr?ger base will stimulate the further use of this interesting molecular scaffold in molecular recognition, asymmetric catalysis, and related areas of research and technology.     

Remarkable nutritional diversity of basidiomycetes in the Corticiales, including a new foliicolous species of Marchandiomyces (anamorphic Basidiomycota, Corticiaceae) from Australia

Fungi in the basidiomycete order Corticiales are remarkably diverse nutritionally, including a variety of saprotrophs, plant and fungal pathogens, and lichen-forming fungi. Tracing the origin of this diversity depends on a clearer understanding of the phylogenetic relationships of fungi in the order. One of its core members is the genus Marchandiomyces, originally established for lichen pathogens that form orange or coral bulbils. We describe here a new species in the genus, M. marsonii sp. nov., which is unusual in its appearance, habit, and geographic provenance. It is foliicolous on leaves of Pandanus (screw pines, Pandanaceae) and produces flattened, coral bulbils resembling apothecia of the ascomycete genus Orbilia. It is also the first member of the genus to be collected from Australia. An isolate of the new fungus and several additional cultures of related plant pathogenic fungi were obtained and investigated phylogenetically using parsimony, likelihood, and Bayesian analyses of nuclear small and large subunit ribosomal sequences. Our phylogeny makes clear that Marchandiomyces species and their close relatives contribute significantly to the ecological diversity of the Corticiales and that this diversity is derived mainly from lignicolous ancestors.     

Cortisol and behavioral responses to enrichment in military working dogs

Our objective was to compare the effects of two schedules of enrichment exposure, a distributed (high frequency) and regular regime versus a mass (low frequency) and irregular regime, on the cortisol and behavioral responses of 14 kennelled military working dogs. The enrichment experiences were exercise coupled with human contact. Both groups of dogs were exposed to approximately the same total amount of enrichment per week for a total of 7 weeks. The distributed and regular regime (DRR) furnished enrichment for 20-min intervals three to four times a day every weekday; the mass and irregular regime (MIR) randomly furnished enrichment for 16 or 24 continuous hours 1 day out of 5. Our data show that: (1) cortisol concentrations of DRR dogs significantly decreased between the first and the last week of observations; this was not the case in MIR dogs; (2) at the 7th week DRR dogs had lower cortisol concentrations than did MIR dogs; (3) all dogs in each group exhibited stereotypies. Our results suggest that MIR dogs underwent a decline in welfare throughout the experiment, whereas DRR dogs appeared to undergo a period of acute stress at the beginning of their training that resolved over 7 weeks. This study suggests that the welfare of kennelled dogs, particularly military working dogs, is affected among other factors by schedules of exercise and contact with people.     

Gold from the sea: marine compounds as inhibitors of the hallmarks of cancer

Cancer is one of the most deadly diseases in the world. Although advances in the field of chemo-preventive and therapeutic medicine have been made regularly over the last ten years, the search for novel anticancer treatments continues. In this field, the marine environment, with its rich variety of organisms, is a largely untapped source of novel compounds with potent antitumor activity. Although many reviews of marine anticancer compounds have been published, we focus here on selected marine compounds that act on the six hallmarks of cancer presented namely self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replication, sustained angiogenesis and tissue invasion and metastasis.