Thermodynamic analysis of enzyme enantioselectivity: a statistical approach by means of new differential HybridMIF descriptors

The study of relationships between substrate structure and enzyme stereoselectivity was approached by means of a new molecular descriptor: the \u201cdifferential Hybrid Molecular Interaction Field\u201d (dH-MIF). The descriptor was conceived with the purpose of combining enthalpic and entropic information related to enzyme\u2013enantiomer interactions. The dH-MIFs were developed based on experimental data previously published by the group of Karl Hult on the enantioselectivity of the W104A mutant of lipase B from Candida antarctica, which is endowed with an enlarged stereoselectivity pocket. Because of the increased conformational freedom of substrates, the entropic contribution to enantiodiscrimination is particularly relevant in kinetic resolution of alcohols catalyzed by this enzyme. By combining molecular dynamic simulations and GRID analysis the new dH-MIF descriptors proved to be able to extract both enthalpic and entropic information from models of the tetrahedral intermediates of enantiomers

Median nerve small- and large-fiber damage in carpal tunnel syndrome: a quantitative sensory testing study.

We explored the contribution of median nerve small (Adelta, C)-and large (Abeta)-fiber damage to the severity and topographic distribution of sensory symptoms in carpal tunnel syndrome (CTS) and the timing of fiber damage across CTS stages. We recruited 106 CTS patients. After selection, 49 patients were included. They underwent electrodiagnostic and quantitative sensory testing (QST) study and were asked on the severity of Boston Carpal Tunnel Questionnaire (BCTQ) Symptoms Severity Scale, daytime pain (DP), night pain and paresthesia, on the distribution of hand symptoms, and the presence of proximal symptoms. BCTQ Symptoms Severity Scale and DP severity was significantly correlated with Adelta-fiber damage. Small-fiber QST measures were impaired in electrodiagnostic-negative CTS patients and did not change across CTS neurographic stages. QST findings were not correlated to the topographical distribution of symptoms. Adelta-fiber damage contributes to CTS symptoms and in particular to DP. Night pain and paresthesia might be ascribed to ectopic fiber discharges secondary to median nerve enhanced mechanosensitivity. Small-fiber damage takes place earlier than large fiber. Median nerve fiber involvement does not directly contribute to extraterritorial symptoms spread. Our data may help understanding CTS pathophysiology and explain the well-known discrepancy between CTS symptoms and electrodiagnostic findings. PERSPECTIVE: We explored the involvement of median nerve small and large fibers in carpal tunnel syndrome (CTS). We found a significant correlation between Adelta-fiber function and CTS symptoms. Small-fiber involvement took place in milder disease stages. These findings could help reconcile the discrepancy between CTS symptoms and electrodiagnostic data

Acute hemichorea-hemiballism ipsilateral to ischemic stroke involving middle cerebral artery territory

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BioGPS descriptors for rational engineering of enzyme promiscuity and structure-based bioinformatic analysis

A new bioinformatic methodology was developed founded on the Unsupervised Pattern Cognition Analysis of GRID-based BioGPS descriptors (Global Positioning System in Biological Space). The procedure relies entirely on three-dimensional structure analysis of enzymes and does not stem from sequence or structure alignment. The BioGPS descriptors account for chemical, geometrical and physical-chemical features of enzymes and are able to describe comprehensively the active site of enzymes in terms of \u2018\u2018pre-organized environment\u2019\u2019 able to stabilize the transition state of a given reaction. The efficiency of this new bioinformatic strategy was demonstrated by the consistent clustering of four different Ser hydrolases classes, which are characterized by the same active site organization but able to catalyze different reactions. The method was validated by considering, as a case study, the engineering of amidase activity into the scaffold of a lipase. The BioGPS tool predicted correctly the properties of lipase variants, as demonstrated by the projection of mutants inside the BioGPS \u2018\u2018roadmap\u2019\u2019

EXTRATERRITORIAL SPREAD OF NEUROPATHIC PAIN SYMPTOMS IS FREQUENT IN PATIENTS WITH ULNAR NEUROPATHY AT THE ELBOW

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