Visible‐Light‐Induced Control over Reversible Single‐Chain Nanoparticle Folding

We introduce a class of single-chain nanoparticles (SCNPs) that respond to visible light (λ$_{max}$=415 nm) with complete unfolding from their compact structure into linear chain analogues. The initial folding is achieved by a simple esterification reaction of the polymer backbone constituted of acrylic acid and polyethylene glycol carrying monomer units, introducing bimane moieties, which allow for the photochemical unfolding, reversing the ester-bond formation. The compaction and the light driven unfolding proceed cleanly and are readily followed by size exclusion chromatography (SEC) and diffusion ordered NMR spectroscopy (DOSY), monitoring the change in the hydrodynamic radius (R$_H$). Importantly, the folding reaction and the light-induced unfolding are reversible, supported by the high conversion of the photo cleavage. As the unfolding reaction occurs in aqueous systems, the system holds promise for controlling the unfolding of SCNPs in biological environments

Fluorescent and Catalytically Active Single Chain Nanoparticles

Fluorescent and catalytically active single chain nanoparticle (SCNP) systems allow for the visualization and tracing of the catalyst's distribution in a reaction system. We herein report a synthetic strategy to such SCNPs, generated through a photoactivated reaction at visible light (λmax= 415 nm) irradiation. Notably, the compaction reaction generates a fluorescent entity via a pro-fluorescent precursor. A polymer backbone (Mn= 21,000 g mol-1and D = 1.3), carrying phosphine ligands for the coordination of catalytically active gold complexes and the photoreactive ortho-methylbenzaldehyde units and complementary alkyne moieties, was constructed based on nitroxide-mediated polymerization. The synthetic protocol entails an intermediate protection sequence for the catalyst-carrying phosphine unit to enable the installation of the cross-linking entities. The successful compaction of the SCNPs is demonstrated by a reduction in the chain's hydrodynamic volume via size exclusion chromatography and diffusion-ordered NMR spectroscopy.</p

Visible-Light-Induced Control over Reversible Single-Chain Nanoparticle Folding

We introduce a class of single-chain nanoparticles (SCNPs) that respond to visible light (λmax=415 nm) with complete unfolding from their compact structure into linear chain analogues. The initial folding is achieved by a simple esterification reaction of the polymer backbone constituted of acrylic acid and polyethylene glycol carrying monomer units, introducing bimane moieties, which allow for the photochemical unfolding, reversing the ester-bond formation. The compaction and the light driven unfolding proceed cleanly and are readily followed by size exclusion chromatography (SEC) and diffusion ordered NMR spectroscopy (DOSY), monitoring the change in the hydrodynamic radius (RH). Importantly, the folding reaction and the light-induced unfolding are reversible, supported by the high conversion of the photo cleavage. As the unfolding reaction occurs in aqueous systems, the system holds promise for controlling the unfolding of SCNPs in biological environments.</p

Trends in methadone-related deaths in Zurich

Methadone has a long and successful history in the treatment of opioid addiction. In recent years, it has become popular again—as potent and inexpensive analge- sic in patients with chronic pain. Since methadone has been used fatalities have been reported. In our study all methadone-associated deaths in Zurich from 1998 to 2007 were analysed. Most of the 146 detected deaths of the past 10 years occurred during substitution programmes or illicit intake of methadone while only three of them could be attributed to methadone used as an analgesic. Noticeable in our study was the high percentage of cases of combined drug intoxication (76%). The most frequent co-intoxicants were alcohol and cocaine. Mortalities attributed to metha- done intoxication alone were a rare finding and could only be detected in five cases of deceased who had received methadone maintenance treatment. The aim of our study is to assess the trends in the number and nature of methadone- related fatalities in Zurich during the last 19 years. For this purpose a previous study from Zurich (1989–1997) was included, whereby a very long observation period and large number of cases resulted

Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma

Extrachromosomal circularization of DNA is an important genomic feature in cancer. However, the structure, composition and genome-wide frequency of extrachromosomal circular DNA have not yet been profiled extensively. Here, we combine genomic and transcriptomic approaches to describe the landscape of extrachromosomal circular DNA in neuroblastoma, a tumor arising in childhood from primitive cells of the sympathetic nervous system. Our analysis identifies and characterizes a wide catalog of somatically acquired and undescribed extrachromosomal circular DNAs. Moreover, we find that extrachromosomal circular DNAs are an unanticipated major source of somatic rearrangements, contributing to oncogenic remodeling through chimeric circularization and reintegration of circular DNA into the linear genome. Cancer-causing lesions can emerge out of circle-derived rearrangements and are associated with adverse clinical outcome. It is highly probable that circle-derived rearrangements represent an ongoing mutagenic process. Thus, extrachromosomal circular DNAs represent a multihit mutagenic process, with important functional and clinical implications for the origins of genomic remodeling in cancer. Combined genomic and transcriptomic approaches identify the landscape of extrachromosomal circular DNA in neuroblastoma and reveal that extrachromosomal circular DNA is a major source of somatic rearrangements