Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins.

Dinoflagelates and cyanobacteria produce saxitoxin (STX), a lethal bis-guanidinium neurotoxin causing paralytic shellfish poisoning. A number of metazoans have soluble STX-binding proteins that may prevent STX intoxication. However, their STX molecular recognition mechanisms remain unknown. Here, we present structures of saxiphilin (Sxph), a bullfrog high-affinity STX-binding protein, alone and bound to STX. The structures reveal a novel high-affinity STX-binding site built from a "proto-pocket" on a transferrin scaffold that also bears thyroglobulin domain protease inhibitor repeats. Comparison of Sxph and voltage-gated sodium channel STX-binding sites reveals a convergent toxin recognition strategy comprising a largely rigid binding site where acidic side chains and a cation-π interaction engage STX. These studies reveal molecular rules for STX recognition, outline how a toxin-binding site can be built on a naïve scaffold, and open a path to developing protein sensors for environmental STX monitoring and new biologics for STX intoxication mitigation

(S)-(−)-6-(4-Bromo­phen­yl)-2,3,5,6-tetra­hydro­thia­zolo[2,3-b]imidazolium hydrogen oxalate

The structure of the title compound, C11H12BrN2S+·C2HO4 − (common name 6-bromo­levamisole hydrogen oxalate), is stabilized mainly by hydrogen bonds. Hydrogen oxalate anions form parallel coplanar chains via O—H⋯O hydrogen bonds, while there are N—H⋯O hydrogen-bonding inter­actions between the 6-bromo­levamisole cations and oxalate anions. Both five-membered rings from the 6-bromo­levamisole mol­ecule have a twist conformation. The mol­ecule has an extended conformation, with the 4-bromo­phenyl substituent positioned equatorially with N—C—C—C and C—C—C—C torsion angles of 39.8 (3) and 100.4 (3)°, respectively

Redetermination of 2-[4-(2-hydroxy­ethyl)piperazin-1-ium-1-yl]ethanesul­fonate at 100 K

The crystal structure of the title compound (common name HEPES), C8H18N2O4S, has been redetermined at 100 K in order to properly elucidate the protonation state of the HEPES molecule. The piperazine ring has a chair conformation and one of the N atoms in the ring is protonated, which was not previously reported [Gao, Yin, Yang, & Xue (2004). Acta Cryst. E60, o1328–o1329]. The change of protonation state of the nitrogen atom significantly affects the intermolecular interactions in the HEPES crystal. The structure is stabilized by N—H⋯O and O—H⋯O hydrogen bonds and ionic inter­actions, as the title compound in solid state is a zwitterion. HEPES mol­ecules pack in layers that are held together by ionic and weak inter­actions, while a hydrogen-bonded network connects the layers

Indenture, Marshall County, MS, 20 May 1850

https://egrove.olemiss.edu/aldrichcorr_b/1265/thumbnail.jp

Indenture, Marshall County, MS, 10 December 1849

https://egrove.olemiss.edu/aldrichcorr_b/1263/thumbnail.jp

Oxygen persufflation as adjunct in liver preservation (OPAL): Study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Early graft dysfunction due to preservation/reperfusion injury represents a dramatic event after liver transplantation. Enhancement of donor organ criteria, in order to cope with the ever increasing donor shortage, further increases graft susceptibility to ischemic alterations.</p> <p>Major parts of post-preservation injury, however, occur at the time of warm reperfusion but not during ischemic storage; successful reperfusion of ischemic tissue in turn depends on an adequate redox and intracellular signal homeostasis. The latter has been shown experimentally to be favorably influenced by oxygen persufflation within short time spans. Thus viability of marginally preserved liver grafts could still be augmented by transient hypothermic reconditioning <b><it>even after </it></b>normal procurement and static cold storage. The present study is aimed to confirm the conceptual expectations, that hypothermic reconditioning by gaseous oxygen persufflation is a useful method to suppress injurious cellular activation cascades and to improve post-ischemic recovery of marginally preserved liver grafts.</p> <p>Methods/Design</p> <p>OPAL is a prospective single center randomized proof of concept study, including two parallel groups in a total of 116 liver transplant patients. The effect of an in hospital treatment of the isolated liver graft by 2 hours of oxygen persufflation immediately prior to transplantation will be assesses as compared to standard procedure (cold storage without further intervention). The primary endpoint is the peak transaminase serum level (AST) during the first three days after transplantation as a surrogate readout for parenchymal liver injury. Other outcomes comprise patient and graft survival, time of intensive care requirement, hepatic tissue perfusion 1h after revascularisation, early onset of graft dysfunction based on coagulation parameters, as well as the use of a refined scoring-system for initial graft function based on a multi-parameter (AST, ALT, Quick and bilirubin) score. Furthermore, the effect of OPAL on molecular pathways of autophagy and inflammatory cell activation will be evaluated. Final analysis will be based on all participants as randomized (intention to treat).</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN00167887">ISRCTN00167887</a></p