Pore positioning: Current concepts in Pannexin channel trafficking

Pannexins (Panxs) are a multifaceted family of ion and metabolite channels that play key roles in a number of physiological and pathophysiological settings. These single membrane large-pore channels exhibit a variety of tissue, cell type, and subcellular distributions. The lifecycles of Panxs are complex, yet must be understood to accurately target these proteins for future therapeutic use. Here we review the basics of Panx function and localization, and then analyze the recent advances in knowledge regarding Panx trafficking. We examine several intrinsic features of Panxs including specific post-translational modifications, the divergent C-termini, and oligomerization, all of which contribute to Panx anterograde transport pathways. Further, we examine the potential influence of extrinsic factors, such as protein-protein interactions, on Panx trafficking. Finally, we highlight what is currently known with respect to Panx internalization and retrograde transport, and present new data illustrating Panx1 internalization following an activating stimulus.     

Conservation genomics of desert dwelling California voles (<Emphasis Type="Italic">Microtus californicus</Emphasis>) and implications for management of endangered Amargosa voles (<Emphasis Type="Italic">Microtus californicus scirpensis</Emphasis>)

Understanding population genetic structure and levels of genetic variation is critical for the conservation and management of imperiled populations, especially when reintroductions are planned. We used restriction-site associated DNA (RAD) sequencing to study the genetic diversity and evolutionary relationships of the endangered Amargosa vole and other closely related desert-dwelling California voles. Specifically, we sought to determine how Amargosa voles are related to other California voles, how genetic variation is partitioned among subpopulations in wild Amargosa voles, and how much genetic variation is captured within a captive insurance colony of Amargosa voles. Our multilocus nuclear dataset provides strong evidence that Amargosa voles are part of a northern clade of California voles. Amargosa voles have highly reduced genetic variation relative to other California voles, but do exhibit some sub-structure among sampled marshes. Captive Amargosa voles capture approximately half of the total genetic variation present in the wild Amargosa vole populations. We discuss the management implications of our findings in light of reintroductions planned for Amargosa voles. Our study highlights the utility of reduced representation genomic approaches, like RADseq, to resolve relationships among small populations that are difficult to study with traditional markers due to low genetic variation and few individuals left in the wild.     

Comparison of the protective effects of three phosphorothioate radioprotectors in the RIF-1 tumor

Three aminoalkyl phosphorothioates, WR-2721, WR-3689, and WR-77913, were compared as radioprotectors of RIF-1 tumors irradiated in vivo and assayed for cell survival in vitro. The protector doses were 50% of the acute drug LD50. The radiation dose modifying factors for the three drugs were nearly equal, ranging from 1.5 to 1.7 at surviving fractions of 0.1 and 0.05. Using biodistribution data obtained with 35S labeled drugs, the uptake in tumors was calculated as micromoles drug per gram of tumor. On this basis, tumor levels of WR-77913 were 4.5-fold those of WR-2721, and WR-3689 uptake was 2.7-fold greater than uptake of WR-2721. Thus, on a molar basis, WR-2721 appears to be the most effective protector, but all three phosphorothioates protect this tumor moderately well. In diffusible substance autoradiographs of 3H WR-3689 labeled tumors, label was generally distributed over cells with no evidence of preferential localization over nuclei.     

Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study

Background  

Adverse drug reactions (ADRs) are now recognized as an important cause of hospital admissions, with a proportion ranging from 0.9–7.9%. They also constitute a significant economic burden. We thus aimed at determining the prevalence and the economic burden of ADRs presenting to Medical Emergency Department (ED) of a tertiary referral center in India     

Assignment of the absolute configuration of zwitterionic and neutral macropodumines by means of TDDFT CD calculations

Macropodumines B and C (1, 2) are fused pentacyclic alkaloids previously isolated from the Chinese medicinal plant Daphniphyllum macropodum. Macropodumine B (1) possesses an amazing structural feature of a cyclopentadienyl carbanion, stabilized as a zwitterion by an internal iminium cation, which was confirmed by X-ray diffraction analysis. On the basis of the X-ray geometry, the absolute configuration of 1 was determined by employing the solid-state CD/TDDFT approach. The absolute configuration of 2 was instead determined by using TDDFT CD calculations on DFT-optimized geometries, in comparison with CD spectra recorded in solution.