Catheter-ocking device-assisted external ventricular drain placement: a new surgical technique preventing intracranial drain displacement-technical note with preliminary single-center results

Background: External ventricular drain (EVD) placement is frequently performed in neurosurgical patients to divert cerebrospinal fluid (CSF) and monitor intracranial pressure. The traditional practice is the tunneled EVD technique performed in the operating room. EVD insertion through a bolt in intensive care units has also been reported. We describe here the usage of a novel technique, the catheter-locking device-assisted EVD placement, reporting our preliminary, observational single-center results. Methods: From January to October 2021, 15 patients underwent a catheter-locking device-assisted EVD placement at our institute. For each of these patients, the following data were evaluated: (1) demographics, (2) etiology, (3) clinical presentation, (4) EVD complications, and (5) final clinical outcomes. Results: Median age of our population was 64 years, with a female/male ratio of 2:1. Average Glasgow Coma Scale score on admission was 8. Each patient maintained the drainage for an average time of 14 days. None of the patients suffered from postoperative intracerebral hemorrhage, CSF leakage, catheter migration, or discontinuation of the drainage system; none developed signs of infection. Nine patients required a permanent CSF diversion system. Outcome was good in 14 patients. One patient died for the underlying disease. Conclusions: The catheter-locking device-assisted EVD placement appears to be a safe and accurate alternative to both the standard tunneled and the bolt-assisted EVD insertion techniques. The use of this procedure may significantly reduce the incidence of the commonest EVD complications, though further investigation is required

The progenitor of SN 2023ixf from hydrodynamical modelling

Context: Supernova (SN) 2023ixf is among the most nearby Type II SNe in the last decades. As such, there is a wealth of observational data of both the event itself and of the associated object identified in pre-explosion images. This allows to perform a variety of studies that aim at determining the SN properties and the nature of the putative progenitor star. Modelling of the light curve is a powerful method to derive physical properties independently of direct progenitor analyses. Aims: To investigate the physical nature of SN 2023ixf based on hydrodynamical modelling of its bolometric light curve and expansion velocities during the complete photospheric phase. Methods: A grid of one dimensional explosions was calculated for evolved stars of different masses. We derived properties of SN 2023ixf and its progenitor by comparing our models with the observations. Results: The observations are well reproduced by the explosion of a star with zero age main sequence mass of f $M_\mathrm{ZAMS} = 12 M_\odot$ , an explosion energy of $1.2 \times 10^{51}$ erg, and a nickel production of 0.05M . This indicates that SN 2023ixf was a normal event. Our modelling suggests a limit of $M_\mathrm{ZAMS} < 15 M_\odot$ and therefore favours the low mass range among the results from pre-explosion observations.Comment: Accepted - A&A Lette

Comparison of the Structures and Mechanisms of the Pistol and Hammerhead Ribozymes

Comparison of the secondary and three-dimensional structures of the hammerhead and pistol ribozymes reveals many close similarities, so in this work we have asked if they are mechanistically identical. We have determined a new crystal structure of the pistol ribozyme and have shown that G40 acts as general base in the cleavage reaction. The conformation in the active site ensures an in-line attack of the O2′ nucleophile, and the conformation at the scissile phosphate and the position of the general base are closely similar to those in the hammerhead ribozyme. However, the two ribozymes differ in the nature of the general acid. 2′-Amino substitution experiments indicate that the general acid of the hammerhead ribozyme is the O2′ of G8, while that of the pistol ribozyme is a hydrated metal ion. The two ribozymes are related but mechanistically distinct

Comparison of the Structures and Mechanisms of the Pistol and Hammerhead Ribozymes

Comparison of the secondary and three-dimensional structures of the hammerhead and pistol ribozymes reveals many close similarities, so in this work we have asked if they are mechanistically identical. We have determined a new crystal structure of the pistol ribozyme and have shown that G40 acts as general base in the cleavage reaction. The conformation in the active site ensures an in-line attack of the O2′ nucleophile, and the conformation at the scissile phosphate and the position of the general base are closely similar to those in the hammerhead ribozyme. However, the two ribozymes differ in the nature of the general acid. 2′-Amino substitution experiments indicate that the general acid of the hammerhead ribozyme is the O2′ of G8, while that of the pistol ribozyme is a hydrated metal ion. The two ribozymes are related but mechanistically distinct

General Acid–Base Catalysis Mediated by Nucleobases in the Hairpin Ribozyme

The catalytic mechanism by which the hairpin ribozyme accelerates cleavage or ligation of the phosphodiester backbone of RNA has been incompletely understood. There is experimental evidence for an important role for an adenine (A38) and a guanine (G8), and it has been proposed that these act in general acid-base catalysis. In this work we show that a large reduction in cleavage rate on substitution of A38 by purine (A38P) can be reversed by replacement of the 5′-oxygen atom at the scissile phosphate by sulfur (5′-PS), which is a much better leaving group. This is consistent with A38 acting as the general acid in the unmodified ribozyme. The rate of cleavage of the 5′-PS substrate by the A38P ribozyme increases with pH log-linearly, indicative of a requirement for a deprotonated base with a relatively high pK(a). On substitution of G8 by diaminopurine, the 5′-PS substrate cleavage rate at first increases with pH and then remains at a plateau, exhibiting an apparent pK(a) consistent with this nucleotide acting in general base catalysis. Alternative explanations for the pH dependence of hairpin ribozyme reactivity are discussed, from which we conclude that general acid-base catalysis by A38 and G8 is the simplest and most probable explanation consistent with all the experimental data

Hachimoji DNA and RNA: A genetic system with eight building blocks

Reported here are DNA and RNA-like systems built from eight (hachi-) nucleotide letters (-moji) that form four orthogonal pairs. This synthetic genetic biopolymer meets the structural requirements needed to support Darwinism, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to double the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos

New Strategies for Exploring RNA's 2′-OH Expose the Importance of Solvent during Group II Intron Catalysis

AbstractThe 2′-hydroxyl group contributes inextricably to the functional behavior of many RNA molecules, fulfilling numerous essential chemical roles. To assess how hydroxyl groups impart functional behavior to RNA, we developed a series of experimental strategies using an array of nucleoside analogs. These strategies provide the means to investigate whether a hydroxyl group influences function directly (via hydrogen bonding or metal ion coordination), indirectly (via space-filling capacity, inductive effects, and sugar conformation), or through interactions with solvent. The nucleoside analogs span a broad range of chemical diversity, such that quantitative structure activity relationships (QSAR) now become possible in the exploration of RNA biology. We employed these strategies to investigate the spliced exons reopening (SER) reaction of the group II intron. Our results suggest that the cleavage site 2′-hydroxyl may mediate an interaction with a water molecule