Global Catholicism in Seventeenth-Century Prague

The histories of early modern religion and trade have both benefited from the global turn in recent years. This article brings the two fields together through the study of religious objects in Prague in the seventeenth century and shows ways in which religion and religious practice were entangled with new commercial and artistic ventures that crossed regional and international borders. Amongst the possessions of seventeenth-century Prague burghers were religious objects that had come from exotic lands, such as a ‘coconut’ rosary and a ruby and diamond ‘pelican in her piety’ jewel. These objects were made in multiple locations and traded to satisfy a new demand for items that could aid and display devotion, as well as act as markers of wealth and confessional identity. Through this study of religious objects, Central Europe is revealed to be an important locale to the global history of the early modern period

A Loss‐of‐Function Variant in the Human Histidyl‐t RNA Synthetase ( HARS ) Gene is Neurotoxic In Vivo

Aminoacyl‐t RNA synthetases ( ARS s) are ubiquitously expressed enzymes responsible for ligating amino acids to cognate t RNA molecules. Mutations in four genes encoding an ARS have been implicated in inherited peripheral neuropathy with an axonal pathology, suggesting that all ARS genes are relevant candidates for disease in patients with related phenotypes. Here, we present results from a mutation screen of the histidyl‐t RNA synthetase ( HARS ) gene in a large cohort of patients with peripheral neuropathy. These efforts revealed a rare missense variant (c.410G>A/p.Arg137Gln) that resides at a highly conserved amino acid, represents a loss‐of‐function allele when evaluated in yeast complementation assays, and is toxic to neurons when expressed in a worm model. In addition to the patient with peripheral neuropathy, p.Arg137Gln HARS was detected in three individuals by genome‐wide exome sequencing. These findings suggest that HARS is the fifth ARS locus associated with axonal peripheral neuropathy. Implications for identifying ARS alleles in human populations and assessing them for a role in neurodegenerative phenotypes are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95567/1/humu22210.pd

Direct Observation of ATP-Induced Conformational Changes in Single P2X4 Receptors

The ATP-gated P2X4 receptor is a cation channel, which is important in various pathophysiological events. The architecture of the P2X4 receptor in the activated state and how to change its structure in response to ATP binding are not fully understood. Here, we analyze the architecture and ATP-induced structural changes in P2X4 receptors using fast-scanning atomic force microscopy (AFM). AFM images of the membrane-dissociated and membrane-inserted forms of P2X4 receptors and a functional analysis revealed that P2X4 receptors have an upward orientation on mica but lean to one side. Time-lapse imaging of the ATP-induced structural changes in P2X4 receptors revealed two different forms of activated structures under 0 Ca2+ conditions, namely a trimer structure and a pore dilation-like tripartite structure. A dye uptake measurement demonstrated that ATP-activated P2X4 receptors display pore dilation in the absence of Ca2+. With Ca2+, the P2X4 receptors exhibited only a disengaged trimer and no dye uptake was observed. Thus our data provide a new insight into ATP-induced structural changes in P2X4 receptors that correlate with pore dynamics

Mapping Hidden Potential Identity Elements by Computing the Average Discriminating Power of Individual tRNA Positions

The recently published discrete mathematical method, extended consensus partition (ECP), identifies nucleotide types at each position that are strictly absent from a given sequence set, while occur in other sets. These are defined as discriminating elements (DEs). In this study using the ECP approach, we mapped potential hidden identity elements that discriminate the 20 different tRNA identities. We filtered the tDNA data set for the obligatory presence of well-established tRNA features, and then separately for each identity set, the presence of already experimentally identified strictly present identity elements. The analysis was performed on the three kingdoms of life. We determined the number of DE, e.g. the number of sets discriminated by the given position, for each tRNA position of each tRNA identity set. Then, from the positional DE numbers obtained from the 380 pairwise comparisons of the 20 identity sets, we calculated the average excluding value (AEV) for each tRNA position. The AEV provides a measure on the overall discriminating power of each position. Using a statistical analysis, we show that positional AEVs correlate with the number of already identified identity elements. Positions having high AEV but lacking published identity elements predict hitherto undiscovered tRNA identity elements