A Step in Between: [Sn3Bi3]5− and Its Structural Relationship to [Sn3Bi5]3− and [Sn4Bi4]4−

Extraction of RbSnBi in liquid ammonia yielded the cluster anion [Sn3Bi5](3-), which could be crystallized in the compound [Rb@[2.2.2]crypt](3)[Sn3Bi5]8.87NH(3). This anion is found to be derived from the formerly reported [Sn4Bi4](4-) by the formal substitution of one tin atom by bismuth. In contrast, the extraction of RbSn2/Rb3Bi2 in liquid ammonia yielded the anion [Sn3Bi3](5-) in the compound Rb-6[Sn3Bi3][Sn-4](1/4)6.75NH(3). The structural correlation of the two novel clusters indicates that [Sn3Bi3](5-) might be an intermediate of the reaction pathway to [Sn3Bi5](3-) and [Sn4Bi4](4-). Each cluster is investigated by means of the electron localization function and further characterization was performed by using ESI-MS

cDNA and derived amino acid sequence of the hypusine containing protein from Dictyostelium discoideum

AbstractThe eukaryotic translation initiation factor eIF-4D is the only protein known to contain the unusual amino acid hypusine, a posttranslationally modified lysine. For the production of monoclonal antibodies the hypusine-containing protein (HP) was isolated from Dictyostelium discoideum. Using these monoclonal antibodies, a full-length cDNA clone was isolated from a λgt11 library. The D. discoideum HP consists of 169 amino acids and has a molecular mass of 18.3 kDa. It is encoded by a single gene. Tryptic and cyanogen bromide peptides were prepared from the purified protein and sequenced. The hypusine residue is located at amino acid position 65 of the HP. The corresponding mRNA of approx. 0.6 kb is present throughout the life cycle of D. discoideum

A Pharmacokinetic and Metabolism Study of the TRPC6 Inhibitor SH045 in Mice by LC-MS/MS

TRPC6, the sixth member of the family of canonical transient receptor potential (TRP) channels, contributes to a variety of physiological processes and human pathologies. This study extends the knowledge on the newly developed TRPC6 blocker SH045 with respect to its main target organs beyond the description of plasma kinetics. According to the plasma concentration-time course in mice, SH045 is measurable up to 24 h after administration of 20 mg/kg BW (i.v.) and up to 6 h orally. The short plasma half-life and rather low oral bioavailability are contrasted by its reported high potency. Dosage limits were not worked out, but absence of safety concerns for 20 mg/kg BW supports further dose exploration. The disposition of SH045 is described. In particular, a high extravascular distribution, most prominent in lung, and a considerable renal elimination of SH045 were observed. SH045 is a substrate of CYP3A4 and CYP2A6. Hydroxylated and glucuronidated metabolites were identified under optimized LC-MS/MS conditions. The results guide a reasonable selection of dose and application route of SH045 for target-directed preclinical studies in vivo with one of the rare high potent and subtype-selective TRPC6 inhibitors availabl

Synthesis of heteroatomic Zintl anions in liquid ammonia – the new highly charged [Sn4Bi4]4− and fully ordered [Sn2Bi2]2−

The new Zintl anion [Sn4Bi4]4−, synthesized by dissolving CsSnBi in liquid ammonia, forms a monocapped nortricyclane-like cage. Its electron localization function (ELF) analysis shows evidence for 3-centre bonding. The analogous reaction with KSnBi results in a crystallographically fully ordered tetrahedral [Sn2Bi2]2− ion

Posttransplantation malignancy in a patient presenting with weight loss and changed bowel habits: a case report

BACKROUND: Advancements in immunosuppressive therapy have significantly improved patient and graft survival following renal transplantation. This is paralleled by an increasing occurrence of posttransplantation malignancy. CASE PRESENTATION: We report on a patient who presented with a history reminding of colon cancer seven years after receiving a kidney transplant. Initial diagnostic imaging seemed to confirm this diagnosis showing a constricting colonic lesion. To our surprise, colonoscopy findings were unremarkable. Review of the imaging studies revealed that the tumor-like picture was caused by the renal graft impressing the intestine. The following search for malignancy in other locations resulted in the diagnosis of glioblastoma multiforme of which the patient died several weeks later. CONCLUSION: Follow-up of renal transplant patients must include screening tests directed at tumor detection. Imaging studies and other tests in this patient group should be interpreted by physicians who are familiar with transplant related peculiarities

Validation of an LC-MS/MS Method to Quantify the New TRPC6 Inhibitor SH045 (Larixyl N-methylcarbamate) and Its Application in an Exploratory Pharmacokinetic Study in Mice

TRPC6 (transient receptor potential cation channels; canonical subfamily C, member 6) is widespread localized in mammalian tissues like kidney and lung and associated with progressive proteinuria and pathophysiological pulmonary alterations, e.g., reperfusion edema or lung fibrosis. However, the understanding of TRPC6 channelopathies is still at the beginning stages. Recently, by chemical diversification of (+)-larixol originating from Larix decidua resin traditionally used for inhalation, its methylcarbamate congener, named SH045, was obtained and identified in functional assays as a highly potent, subtype-selective inhibitor of TRPC6. To pave the way for use of SH045 in animal disease models, this study aimed at developing a capable bioanalytical method and to provide exploratory pharmacokinetic data for this promising derivative. According to international guidelines, a robust and selective LC-MS/MS method based on MRM detection in positive ion mode was established and validated for quantification of SH045 in mice plasma, whereby linearity and accuracy were demonstrated for the range of 2–1600 ng/mL. Applying this method, the plasma concentration time course of SH045 following single intraperitoneal administration (20 mg/kg body weight) revealed a short half-life of 1.3 h. However, the pharmacological profile of SH045 is promising, as five hours after administration, plasma levels still remained sufficiently higher than published low nanomolar IC50 values. Summarizing, the LC-MS/MS method and exploratory pharmacokinetic data provide essential prerequisites for experimental pharmacological TRPC6 modulation and translational treatment of TRPC6 channelopathies

Isolation of planctomycetes from Aplysina sponges

There is mounting molecular evidence that bacteria belonging to the phylum Planctomycetes are abundant in marine sponges including members of the genus Aplysina. In an attempt to culture planctomycete bacteria from Aplysina sponges, 116 bacterial strains were isolated on selective oligotrophic media. Screening of the strain collection by fluorescence in situ hybridization with the planctomycete-specific probe Pla46 yielded 3 positive candidates. Nearly complete sequencing of the respective 16S rRNA genes revealed that the isolates were affiliated with 2 distinct clusters of the genus Pirellula: 1 isolate was obtained from a Mediterranean sponge, 1 from a Caribbean sponge and a third from Caribbean seawater. To our knowledge this is the first report of cultured Planctomycetes from marine sponges. The isolates grew slowly on oligotrophic media and failed to grow on nutrient-rich media. Pirellula sp. Strain 797 was pink-pigmented while the other 2 isolates, 16 and 81, were non-pigmented. Transmission electron microscopy revealed a pear- or droplet-shaped cell morphology that is characteristic of the genus Pirellula. The application of strain-specific oligonucleotide probes to sponge tissue cryosections showed that the isolates contribute only a minor fraction to the total microbial community that is associated with Aplysina spp. sponge

Characterization of coatings for straylight and photoluminescence suppression in the Raman Spectrometer for MMX (RAX)

The Martian Moons eXploration (MMX) mission led by JAXA to Mars moons Phobos and Deimos involves a small rover developed by DLR/CNES that will be operating on Phobos’ surface. Aboard it is the Raman Spectrometer for MMX (RAX), whose main scientific objectives address Phobos surface mineralogy, its heterogeneity and relation to the Mars mineralogy. Raman spectrometers require strong suppression of straylight, since this technique operates with few nano-Watt signals that should have significant contrast to all other sources of light inside the instrument. The mission requirements involving RAX call for a compact and sophisticated optical design, precluding space for straylight suppressive elements. To optimize straylight suppression in RAX, Raman scattering, Photoluminescence and reflection were characterized for candidate coatings representing different absorbing materials and fabrication technologies over spectral ranges between 530 nm and 680 nm. This was complimented by mechanical testing to aid selection of the coatings for parts inside the RAX flight model

Phenotypic and genotypic overlap between mosaic NF2 and schwannomatosis in patients with multiple non-intradermal schwannomas

Schwannomatosis and neurofibromatosis type 2 (NF2) are both characterized by the development of multiple schwannomas but represent different genetic entities. Whereas NF2 is caused by mutations of the NF2 gene, schwannomatosis is associated with germline mutations of SMARCB1 or LZTR1. Here, we studied 15 sporadic patients with multiple non-intradermal schwannomas, but lacking vestibular schwannomas and ophthalmological abnormalities, who fulfilled the clinical diagnostic criteria for schwannomatosis. None of them harboured germline NF2 or SMARCB1 mutations as determined by the analysis of blood samples but seven had germline LZTR1 variants predicted to be pathogenic. At least two independent schwannomas from each patient were subjected to NF2 mutation testing. In five of the 15 patients, identical somatic NF2 mutations were identified (33%). If only those patients without germline LZTR1 variants are considered (n = 8), three of them (37.5%) had mosaic NF2 as concluded from identical NF2 mutations identified in independent schwannomas from the same patient. These findings imply that a sizeable proportion of patients who fulfil the diagnostic criteria for schwannomatosis, are actually examples of mosaic NF2. Hence, the molecular characterization of tumours in patients with a clinical diagnosis of schwannomatosis is very important. Remarkably, two of the patients with germline LZTR1 variants also had identical NF2 mutations in independent schwannomas from each patient which renders differential diagnosis of LZTR1-associated schwannomatosis versus mosaic NF2 in these patients very difficult