Spontaneous Quaternary and Tertiary T-R Transitions of Human Hemoglobin in Molecular Dynamics Simulation

We present molecular dynamics simulations of unliganded human hemoglobin (Hb) A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(β)146, and they sum up to a total length of 5.6µs. We observe spontaneous and reproducible T→R quaternary transitions of the Hb tetramer and tertiary transitions of the α and β subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the α and β subunits. Using the mutual information as correlation measure, we find that the β subunits are substantially more strongly linked to the quaternary transition than the α subunits. In addition, the tertiary populations of the α and β subunits differ substantially, with the β subunits showing a tendency towards R, and the α subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb

Management of Pelvic Trauma: Neurological damage, urinary tract disruption and pelvic fractures

Practical relevance: Cats commonly present with pelvic trauma following road traffic accidents (RTAs). A logical step-wise approach to diagnostics and subsequent management can significantly improve the prognosis in the majority of cases. This article provides a practical guide to assist decision-making and optimise management of these cats. Clinical challenges: Affected cats may have sustained trauma to several body systems and, hence, their management can be complex, requiring good clinical, diagnostic and surgical skills (often both soft tissue and orthopaedic!). Patient group: Any cat allowed access to the outdoors is potentially at risk of being involved in an RTA and sustaining pelvic trauma. Young male cats are most commonly affected. Evidence base: Many original articles and textbook chapters have been published on aspects of pelvic trauma. However, to the authors’ knowledge, this is the first comprehensive overview of the assessment and management of the feline pelvic trauma case. The review begins by discussing initial triage and neurological examination, and then focuses, in turn, on assessment and management of the ‘tail pull’ injury, the diagnosis and management of urinary tract rupture, and the approach to managing specific pelvic fractures