Formation and structure of the ferryl [Fe=O] in-termediate in the non-haem iron halogenase SyrB2: classical and QM/MM modelling agree

To rationalise mechanistically the intriguing regio- and chemoselectivity patterns for different substrates of the non-haem iron/2-oxoglutarate dependent halogenase SyrB2, it is crucial to elucidate the structure of the pivotal [FeIV[double bond, length as m-dash]O] intermediate. We have approached the problem by a combination of classical and QM/MM modelling. We present complete atomistic models of SyrB2 in complex with its native substrate L-threonine as well as L-α-amino butyric acid and L-norvaline (all conjugated to the pantetheine tether), constructed by molecular docking and extensive MD simulations. We evaluate five isomers of the [Fe[double bond, length as m-dash]O] intermediate in these simulations, with a view to identifying likely structures based on a simple “reaction distance” measure. Starting from models of the resting state, we then use QM/MM calculations to investigate the formation of the [Fe[double bond, length as m-dash]O] species for all three substrates, identifying the intermediates along the O2 activation/decarboxylation pathway on the S = 1, 2, and 3 potential-energy surfaces. We find that, despite differences in the detailed course of the reaction, essentially all pathways produce the same [Fe[double bond, length as m-dash]O] structure, in which the oxido is directed away from the substrate

Editorial

The editorial frames a special issue that introduces Scandinavian cinema and media scholars to ecomedia studies and its potentials

Episodic encoding is more than the sum of its parts: An fMRI investigation of multifeatural contextual encoding

Episodic memories are characterized by their contextual richness, yet little is known about how the various features comprising an episode are brought together in memory. Here we employed fMRI and a multidimensional source memory procedure to investigate processes supporting the mnemonic binding of item and contextual information. Volunteers were scanned while encoding items for which the contextual features (color and location) varied independently, allowing activity elicited at the time of study to be segregated according to whether both, one, or neither feature was successfully retrieved on a later memory test. Activity uniquely associated with successful encoding of both features was identified in the intra-parietal sulcus, a region strongly implicated in the support of attentionally mediated perceptual binding. The findings suggest that the encoding of disparate features of an episode into a common memory representation requires that the features be conjoined in a common perceptual representation when the episode is initially experienced

The role of precuneus and left inferior frontal cortex during source memory episodic retrieval

The posterior medial parietal cortex and left prefrontal cortex (PFC) have both been implicated in the recollection of past episodes. In a previous study, we found the posterior precuneus and left lateral inferior frontal cortex to be activated during episodic source memory retrieval. This study further examines the role of posterior precuneal and left prefrontal activation during episodic source memory retrieval using a similar source memory paradigm but with longer latency between encoding and retrieval. Our results suggest that both the precuneus and the left inferior PFC are important for regeneration of rich episodic contextual associations and that the precuneus activates in tandem with the left inferior PFC during correct source retrieval. Further, results suggest that the left ventro-lateral frontal region/ frontal operculum is involved in searching for task-relevant information (BA 47) and subsequent monitoring or scrutiny (BA 44/45) while regions in the dorsal inferior frontal cortex are important for information selection (BA 45/46). (C) 2005 Elsevier Inc. All rights reserved.NIGMS NIH HHS [2 T32 GM 07266]info:eu-repo/semantics/publishedVersio

Arthroscopic Primary Bundle-Specific Posterior Cruciate Ligament Repair with Transosseous Fixation.

Posterior cruciate ligament (PCL) injuries are most commonly associated with multiligamentous knee injuries. Isolated rupture can be treated nonoperatively with bracing, but with concomitant surgical injuries or high-grade instability, operative intervention may be warranted. While historically PCL injuries were surgically managed with open primary repair, contemporary surgical options include arthroscopic primary repair and reconstruction. Appropriate patient selection is critical in avoiding residual laxity following primary repair, and innovations in advanced imaging and arthroscopic technology now allow for identification of suitable patients. In this technical vote, we describe a method for anatomic bundle-specific primary PCL repair with transosseous fixation. The appropriate patient for this procedure has a femoral-sided avulsion of 1 or both PCL bundles, presents with an acute or subacute injury, and has adequate tissue quality for bundle reapproximation to the footprint. This allows for minimally invasive, anatomic restoration of tension for each bundle

Cortical neuronal loss and hippocampal sclerosis are not detected by voxel-based morphometry in individual epilepsy surgery patients

Voxel-based morphometry (VBM) has detected differences between brains of groups of patients with epilepsy and controls, but the sensitivity for detecting subtle pathological changes in single subjects has not been established. The aim of the study was to test the sensitivity of VBM using statistical parametric mapping (SPM5) to detect hippocampal sclerosis (HS) and cortical neuronal loss in individual patients. T1-weighted volumetric 1.5 T MR images from 13 patients with HS and laminar cortical neuronal loss were segmented, normalised and smoothed using SPM5. Both modulated and non-modulated analyses were performed. Comparisons of one control subject against the rest (n ¼ 23) were first performed to ascertain the smoothing level with the lowest number of SPM changes in controls. Each patient was then compared against the whole control group. The lowest number of SPM changes in control subjects was found at a smoothing level of 10 mm full width half maximum for modulated and non-modulated data. In the patient group, no SPM abnormalities were found in the affected temporal lobe or hippocampus at this smoothing level. At lower smoothing levels there were numerous SPM findings in controls and patients. VBM did not detect any abnormalities associated with either laminar cortical neuronal loss or HS. This may be due to normalisation and smoothing of images and low statistical power in areas with larger interindividual differences. This suggests that the methodology may currently not be suitable to detect particular occult abnormalities possibly associated with seizure onset zone in individual epilepsy patients with unremarkable standard structural MRI

Retrieval Goal Modulates Memory for Context

fMRI was employed to assess whether the contents of recollection vary according to retrieval goal. At study, visually presented words were superimposed on urban or rural scenes or a gray background. The word–background pairs were presented in one of three spatial locations. During a scanned test phase, studied and unstudied words were presented. Two different source memory tasks were randomly interleaved. In the “background” task, the requirement was to judge whether the word had been presented against one of the two classes of scene, as opposed to the alternate class or the gray background. In the “location” task, discrimination was between words presented in one of the two lateral locations and words presented in either of the alternate locations. In both tasks, unstudied words required a separate response. In the background task, words studied against scenes elicited greater activity in parahippocampal and retrosplenial cortex than did words studied against the gray background, consistent with prior reports of scene reinstatement effects. Reinstatement effects were also evident in the location task. Relative to the background task, however, the effects were attenuated in parahippocampal cortex. In other regions, including medial prefrontal and posterior cingulate cortex, activity elicited in the location task by items associated with scenes was lower than that elicited by items presented on the gray background. The findings are interpreted as evidence that contextual retrieval is partially modulated by retrieval goal