Rapid Synthesis and Antiproliferative Properties of Polyazamacrocycle-Based Bi- and Tetra-Gold(I) Phosphine Dithiocarbamate Complexes

A family of bi- and tetrametallic gold(I) phosphine dithiocarbamate complexes were synthesized, starting from cyclam and dimethylcyclam polyazamacrocycles, respectively, along with their monometallic gold(I) chloridophosphine precursors. Their antiproliferative properties were evaluated on two cancer cell lines (A549 and NSCLC-N6-L16). Most of the mono- and bimetallic complexes displayed strong activities and, in particular, one bimetallic derivative showed antiproliferative properties in the low micromolar range. Insights into the structure–activity relationships are given, along with determination of the thioredoxin reductase inhibition potential, two-photon imaging of the fluorescent derivatives, and evaluation of gold uptake.     

Photography in Australia: A select bibliography

Abstract

Olana, the extraordinary private home of American painter Frederic Church, perches high above the Hudson River, with commanding views of the Catskill Mountains and the verdant countryside, approximately 120 miles north of New York City (figure 1). Frederic Edwin Church (1826–1900), the internationally recognized painter of exotic locales and the North American landscape, lived much of his adult life at Olana, and it was here he retreated when arthritis curtailed his passion for world travel. Designed by architect Calvert Vaux in a Persian style, but in large measure created by Church, the house is architecturally eclectic, an exuberant physical manifestation of the artist's interests, beliefS and travels. Olana is also home to Church's personal collections offine art, books and photographs. Church assembled at Olana an art collection of fifty pieces (including old master paintings, art by his friends and contemporaries, as well as work of his own), a library of 1900 volumes (mainly travel, geography, science and religion), and a collection of approximately 5700 photographs. Although not a photographer himself, Church was an active collector of photographs throughout his life. This photograph collection, wellpreserved but only recently catalogued, and exhibited for the first time at the Dahesh Museum of Art, New York, is of compelling interest to historians of art and photography alike.     

Application of organosilane coatings for improved anti-adhesive properties enabling facilitated demolding in polymer processing

Easy and residue-free demolding is an everlasting topic in the plastics processing industry. Typically, facile ejection of the produced parts from the mold is provided by separation agents (silicon sprays, surface coatings). In this work, a perfluoroalkyl-based organosilane coating is applied to exchangeable substrates of an injection mold. Besides the simple application, the coating can also be restored easily in a procedure based on flame treatment. Coating and recoating are proven by contact angle measurements with water, while the anti-adhesive effect and the related relief during demolding are evaluated using a special measuring device in an instrumented two-plate injection mold. The results reveal that the organosilane layer reduces the demolding forces and the resulting static friction coefficient by 50%. Furthermore, multiple recoating significantly improves the durability of the anti-adhesive coating. Based on these findings, the easily applicable and renewable organosilane coating represents a suitable alternative to conventional release coatings.     

Intervertebral Disc Regeneration Injection of a Cell-Loaded Collagen Hydrogel in a Sheep Model

Degenerated intervertebral discs (IVDs) were treated with autologous adipose-derived stem cells (ASC) loaded into an injectable collagen scaffold in a sheep model to investigate the implant’s therapeutic potential regarding the progression of degeneration of previously damaged discs. In this study, 18 merino sheep were subjected to a 3-step minimally invasive injury and treatment model, which consisted of surgically induced disc degeneration, treatment of IVDs with an ASC-loaded collagen hydrogel 6 weeks post-operatively, and assessment of the implant’s influence on degenerative tissue changes after 6 and 12 months of grazing. Autologous ASCs were extracted from subcutaneous adipose tissue and cultivated in vitro. At the end of the experiment, disc heights were determined by µ-CT measurements and morphological tissue changes were histologically examined.Histological investigations show that, after treatment with the ASC-loaded collagen hydrogel implant, degeneration-specific features were observed less frequently. Quantitative studies of the degree of degeneration did not demonstrate a significant influence on potential tissue regeneration with treatment. Regarding disc height analysis, at both 6 and 12 months after treatment with the ASC-loaded collagen hydrogel implant a stabilization of the disc height can be seen. A complete restoration of the intervertebral disc heights however could not be achieved.The reported injection procedure describes in a preclinical model a translational therapeutic approach for degenerative disc diseases based on adipose-derived stem cells in a collagen hydrogel scaffold. Further investigations are planned with the use of a different injectable scaffold material using the same test model.     

Presentation of a mixed reality software with a HoloLens headset for a nutrition workshop

Multimedia Tools and Applications - Microsoft has recently released a mixed reality headset called HoloLens. This semi-transparent visor headset allows the user who wears it to view the projection...     

Integrative Analysis of Metabolomic,Proteomic and Genomic Data to Reveal Functional Pathways and Candidate Genes for Drip Loss in Pigs

The aim of this study was to integrate multi omics data to characterize underlying functional pathways and candidate genes for drip loss in pigs. The consideration of different omics levels allows elucidating the black box of phenotype expression. Metabolite and protein profiling was applied in Musculus longissimus dorsi samples of 97 Duroc × Pietrain pigs. In total, 126 and 35 annotated metabolites and proteins were quantified, respectively. In addition, all animals were genotyped with the porcine 60 k Illumina beadchip. An enrichment analysis resulted in 10 pathways, amongst others, sphingolipid metabolism and glycolysis/gluconeogenesis, with significant influence on drip loss. Drip loss and 22 metabolic components were analyzed as intermediate phenotypes within a genome-wide association study (GWAS). We detected significantly associated genetic markers and candidate genes for drip loss and for most of the metabolic components. On chromosome 18, a region with promising candidate genes was identified based on SNPs associated with drip loss, the protein “phosphoglycerate mutase 2” and the metabolite glycine. We hypothesize that association studies based on intermediate phenotypes are able to provide comprehensive insights in the genetic variation of genes directly involved in the metabolism of performance traits. In this way, the analyses contribute to identify reliable candidate genes.     

Translational Read-Through Therapy of RPGR Nonsense Mutations

X-chromosomal retinitis pigmentosa (RP) frequently is caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. We evaluated the potential of PTC124 (Ataluren, Translama^TM) treatment to promote ribosomal read-through of premature termination codons (PTC) in RPGR. Expression constructs in HEK293T cells showed that the efficacy of read-through reagents is higher for UGA than UAA PTCs. We identified the novel hemizygous nonsense mutation c.1154T > A, p.Leu385* ({"type":"entrez-nucleotide","attrs":{"text":"NM_000328.3","term_id":"1677500221"}}NM_000328.3) causing a UAA PTC in RPGR and generated patient-derived fibroblasts. Immunocytochemistry of serum-starved control fibroblasts showed the RPGR protein in a dot-like expression pattern along the primary cilium. In contrast, RPGR was no longer detectable at the primary cilium in patient-derived cells. Applying PTC124 restored RPGR at the cilium in approximately 8% of patient-derived cells. RT-PCR and Western blot assays verified the pathogenic mechanisms underlying the nonsense variant. Immunofluorescence stainings confirmed the successful PTC124 treatment. Our results showed for the first time that PTC124 induces read-through of PTCs in RPGR and restores the localization of the RPGR protein at the primary cilium in patient-derived cells. These results may provide a promising new treatment option for patients suffering from nonsense mutations in RPGR or other genetic diseases.