Cromolyn/gelatin mixtures as aqueous alignment media and utilization of their mechanical stability for a layering technique.

In this study, aqueous blends of cromolyn and gelatin ("cromogels") are introduced as anisotropic media. The addition of gelatin enables an advantageous adjustability of the strength, the homogeneity, and the stability of the cromolyn alignment. The mechanical stability of these polymer-dispersed liquid crystals is further utilized by stacking layers of D2 O/cromolyn/gelatin with varying component ratio. The resulting distinct phases with correspondingly different degrees of alignment can be targeted by spatially resolved NMR techniques. As a case study, we investigated sucrose in a two-phase system with neat D2 O and analyte layered over the anisotropic medium. A recently presented spatially selective coupled-type HSQC experiment allows the determination of one-bond C-H splitting in both phases.

A Novel Bulky Heteroaromatic-Substituted Methanide Mimicking NacNac: Bis(4,6-tert-butylbenzoxazol-2-yl)methanide in s-Block Metal Coordination.

A novel bulky bis(4,6-tBu-benzoxazol-2-yl)methane ligand was synthesized in a straightforward three-step synthesis. The corresponding complexes [Li{(4,6-tBu-NCOC6 H2 )2 CH}THF], [K{η5 -(4,6-tBu-NCOC6 H2 )2 CH}]∞ , and [MgCl{(4,6-tBu-NCOC6 H2 )2 CH}(THF)2 ] were obtained upon metalation with alkaline or alkaline-earth-metal reagents. Reduction of [MgCl{(4,6-tBu-NCOC6 H2 )2 CH}(THF)2 ] with potassium metal or KC8 led to the formation of the homoleptic compound [Mg{(4,6-tBu-NCOC6 H2 )2 CH}2 ]. All compounds were fully characterized. Their solid-state structures as well as their behavior in solution, which was analyzed with the help of advanced NMR spectroscopic techniques, are discussed in detail.

Evaluation of RAG1 mutations in an adult with combined immunodeficiency and progressive multifocal leukoencephalopathy.

Here we describe novel mutations in recombination activation gene 1 (RAG1) in a compound heterozygous male patient with combined T and B cell immunodeficiency (CID). Clinical manifestations besides antibody deficiency included airway infections, granulomatosis and autoimmune features. He died at the age of 37 due to PML caused by JC virus infection. By targeted next-generation sequencing we detected post mortem in this patient three mutations in RAG1. One allele harbored two novel mutations (c.1123C>G, p.H375D and c.1430delC, p.F478Sfs*14), namely a missense variant and a frameshift deletion, of which the latter leads to a truncated RAG1 protein. The other allele revealed a previously described missense mutation (c.1420C>T, p.R474C, rs199474678). Functional analysis of the p.R474C variant in an in vitro V(D)J recombination assay exhibited reduced recombination activity compared to a wild-type control. Our findings suggest that mutations in RAG1, specifically the p.R474C variant, can be associated with relatively mild clinical symptoms or delayed occurrence of T cell and B cell deficiencies but may predispose to PML.

Gain-of-function STAT1 mutations are associated with intracranial aneurysms.

Chronic mucocutaneous candidiasis, characterized by persistent or recurrent fungal infections, represents the clinical hallmark in gain-of-function (GOF) signal transducer and activator of transcription 1 (STAT1) mutation carriers. Several cases of intracranial aneurysms have been reported in patients with GOF STAT1 mutation but the paucity of reported cases likely suggested this association still as serendipity. In order to endorse this association, we link the development of intracranial aneurysms with STAT1 GOF mutation by presenting the two different cases of a patient and her mother, and demonstrate upregulated phosphorylated STAT4 and IL-12 receptor ß1 upon stimulation in patient's blood cells. We also detected increased transforming growth factor (TGF)-ß type 2 receptor expression, particularly in CD14+ cells, and a slightly higher phosphorylation rate of SMAD3. In addition, the mother of the patient developed disseminated bacille Calmette-Guérin disease after vaccination, speculating that GOF STAT1 mutations may confer a predisposition to weakly virulent mycobacteria.