Upon the Symptomatic Treatment of Paralysis Agitans:

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A manual low-cost protein-crystallization plate jig for in situ diffraction in the home laboratory

A prototype jig to attach a protein crystallization plate to a standard X-ray goniometer has been designed and constructed. This allows a low-cost implementation of in situ diffraction using the available home-laboratory X-ray source

Aqua­(2,2′-diamino-4,4′-bi-1,3-thia­zole-κ2 N 3,N 3′)(thio­diacetato-κ3 O,S,O′)nickel(II) monohydrate

In the title compound, [Ni(C4H4O4S)(C6H6N4S2)(H2O)]·H2O, the NiII cation assumes a distorted octa­hedral coordination geometry formed by a diamino­bithia­zole (DABT) ligand, a thio­diacetate (TDA) dianion and a coordinated water mol­ecule. The tridentate TDA chelates to the Ni cation in a facial configuration, and both chelating rings display the envelope conformations. The two thia­zole rings of the DABT ligand are twisted with respect to each other, making a dihedral angle of 9.96 (9)°. Extensive O—H⋯O, N—H⋯O and weak C—H⋯O hydrogen bonding is present in the crystal structure

Tetra­aqua­(2,2′-diamino-4,4′-bi-1,3-thia­zole-κ2 N 3,N 3′)nickel(II) bis­(pyridine-2,6-dicarboxyl­ato-κ3 O 2,N,O 6)nickel(II) trihydrate

The crystal structure of the title compound, [Ni(C6H6N4S2)(H2O)4][Ni(C7H3NO4)2]·3H2O, consists of NiII complex cations, NiII complex anions and lattice water mol­ecules. The NiII ions in both the complex cation and anion assume a distorted octa­hedral coordination geometry. O—H⋯O, N—H⋯O and C—H⋯S hydrogen bonds occur in the crystal structure

Tris(4,4′-bi-1,3-thia­zole-κ2 N,N′)iron(II) tetra­bromidoferrate(III) bromide

In the [Fe(4,4′-bit)3]2+ (4,4′-bit is 4,4′-bi-1,3-thia­zole) cation of the title compound, [Fe(C6H4N2S2)3][FeBr4]Br, the FeII atom (3 symmetry) is six-coordinated in a distorted octa­hedral geometry by six N atoms from three 4,4′-bit ligands. In the [FeBr4]− anion, the FeIII atom (3 symmetry) is four-coordinated in a distorted tetra­hedral geometry. In the crystal, inter­molecular C—H⋯Br hydrogen bonds and Br⋯π inter­actions [Br⋯centroid distances = 3.562 (3) and 3.765 (2) Å] link the cations and anions, stabilizing the structure

Error-prone initiation factor 2 mutations reduce the fitness cost of antibiotic resistance

Mutations in the fmt gene (encoding formyl methionine transferase) that eliminate formylation of initiator tRNA (Met-tRNAi) confer resistance to the novel antibiotic class of peptide deformylase inhibitors (PDFIs) while concomitantly reducing bacterial fitness. Here we show in Salmonella typhimurium that novel mutations in initiation factor 2 (IF2) located outside the initiator tRNA binding domain can partly restore fitness of fmt mutants without loss of antibiotic resistance. Analysis of initiation of protein synthesis in vitro showed that with non-formylated Met-tRNAi IF2 mutants initiated much faster than wild-type IF2, whereas with formylated fMet-tRNAi the initiation rates were similar. Moreover, the increase in initiation rates with Met-tRNAi conferred by IF2 mutations in vitro correlated well with the increase in growth rate conferred by the same mutations in vivo, suggesting that the mutations in IF2 compensate formylation deficiency by increasing the rate of in vivo initiation with Met-tRNAi. IF2 mutants had also a high propensity for erroneous initiation with elongator tRNAs in vitro, which could account for their reduced fitness in vivo in a formylation-proficient strain. More generally, our results suggest that bacterial protein synthesis is mRNA-limited and that compensatory mutations in IF2 could increase the persistence of PDFI-resistant bacteria in clinical settings

Effects of Acute Ketamine Infusion on Visual Working Memory: Event-related Potentials

Background Working memory (WM) deficits are a core feature of schizophrenia. Electrophysiological studies suggest that impaired early visual processing may contribute to impaired WM in the visual domain. Abnormal N-methyl-D-aspartate (NMDA) receptor function has been implicated both in WM and in early visual processing deficits in schizophrenia. We investigated whether ketamine, a noncompetitive NMDA antagonist, would replicate in healthy volunteers the WM performance and early visual processing abnormalities we and others have reported in patients with schizophrenia. Methods Forty-four healthy volunteers were randomly assigned to receive intravenous ketamine or placebo. During infusion, the effects of ketamine were recorded using standardized psychiatric scales. Visual evoked potentials (P100 and P300 components) were recorded during performance of a delayed matching to sample task. Results Ketamine induced mild psychosis-like symptoms and impaired WM performance. It also significantly increased the P100 amplitude, while P300 amplitude decreased in a load-dependent manner. Amplitudes of P100 during retrieval correlated with cognitive performance only in the placebo group. Conclusions We confirmed previous studies showing that ketamine reproduces the impairment of WM performance and smaller P300 amplitudes observed in schizophrenia. However, ketamine increased visual P100 amplitude in contrast to our observation of reduced P100 amplitudes in established schizophrenia. The effects of ketamine on WM and P300 are likely to involve impaired NMDA function, as these receptors are implicated in changes of synaptic strength underlying associative learning and memory. Increased P100 amplitude may reflect the secondary disinhibition of cortical glutamate release that occurs after NMDA blockade

Family-based clusters of cognitive test performance in familial schizophrenia

BACKGROUND: Cognitive traits derived from neuropsychological test data are considered to be potential endophenotypes of schizophrenia. Previously, these traits have been found to form a valid basis for clustering samples of schizophrenia patients into homogeneous subgroups. We set out to identify such clusters, but apart from previous studies, we included both schizophrenia patients and family members into the cluster analysis. The aim of the study was to detect family clusters with similar cognitive test performance. METHODS: Test scores from 54 randomly selected families comprising at least two siblings with schizophrenia spectrum disorders, and at least two unaffected family members were included in a complete-linkage cluster analysis with interactive data visualization. RESULTS: A well-performing, an impaired, and an intermediate family cluster emerged from the analysis. While the neuropsychological test scores differed significantly between the clusters, only minor differences were observed in the clinical variables. CONCLUSIONS: The visually aided clustering algorithm was successful in identifying family clusters comprising both schizophrenia patients and their relatives. The present classification method may serve as a basis for selecting phenotypically more homogeneous groups of families in subsequent genetic analyses