A Multi-Center Study on Human Brain Glutathione Conformation using Magnetic Resonance Spectroscopy.

Molecular dynamics simulation and in vitro nuclear magnetic resonance (NMR) studies on glutathione (GSH) indicated existence of closed and extended conformations. The present work in a multi-center research setting reports in-depth analysis of GSH conformers in vivo using a common magnetic resonance spectroscopy (MRS) protocol and signal processing scheme. MEGA-PRESS pulse sequence was applied on healthy subjects using 3T Philips MRI scanner (India) and 3T GE MRI scanner (Norway) using the same experimental parameters (echo time, repetition time, and selective 180° refocusing ON-pulse at 4.40 ppm and 4.56 ppm). All MRS data were processed at one site National Brain Research Center (NBRC) using in-house MRS processing toolbox (KALPANA) for consistency. We have found that both the closed and extended GSH conformations are present in human brain and the relative proportion of individual conformer peak depends on the specific selection of refocusing ON-pulse position in MEGA-PRESS pulse sequence. It is important to emphasize that in vivo experiments with different refocusing and inversion pulse positions, echo time, and voxel size, clearly evidence the presence of both the GSH conformations. The GSH conformer peak positions for the closed GSH (Cys-Hß) peak at ∼2.80 ppm and extended GSH (Cys-Hß) peak at ∼2.95 ppm remain consistent irrespective of the selective refocusing OFF-pulse positions. This is the first in vivo study where both extended and closed GSH conformers are detected using the MEGA-PRESS sequence employing the parameters derived from the high resolution in vitro NMR studies on GSH.

Stimulus-dependent modulation of working memory for identity monitoring: A functional MRI study.

While the neural correlates of identity monitoring working memory (WM) have been well characterised in literature, the WM subsystems for different types of stimuli have not been established. The aim of our study was to examine the neural network subtending WM for identity monitoring of both verbal and visual stimuli. We used functional magnetic resonance imaging (fMRI) with words, objects, and faces as stimuli in an n-back WM task to delineate the similarities and differences in brain activation during presentation of verbal and visual stimuli. The results revealed a predominantly left lateralized core fronto-parieto-cerebellar identity WM network comprising bilateral insula, left inferior frontal gyrus, inferior parietal gyrus, and cerebellum that is common to all stimuli. In addition, our results showed stimulus-specific recruitment of brain regions, with exclusive activations in left inferior frontal gyrus and inferior temporal gyrus for identity WM for verbal stimuli, and left middle occipital gyrus and cerebellum for identity WM for visual stimuli. The present study reveals the existence of a central identity WM network for both verbal and visual information, along with activation of distinct verbal and visual representational regions that are sensitive to respective stimuli.

Concomitant nitrene and carbene insertion accompanying ring expansion: spectroscopic, X-ray, and computational studies.

Reinvestigation of the thermolysis of azido-meta-hemipinate (I) yielded, in addition to known II, unusual products III and IV. These products are formed via a rare intramolecular nitrene insertion into an adjacent methoxy C-H bond followed by an intermolecular reaction during a ring-expansion and a ring-extrusion reaction followed by a carbene insertion. The structures of the new compounds were confirmed using a battery of techniques, including HRMS (ESI-QTOF) and 2D NMR as well as X-ray crystallography for compound IV. Density functional theory methods were used to support the proposed mechanism of formation of the products.

Large-scale reorganization of the somatosensory cortex of adult macaque monkeys revealed by fMRI.

Somatosensory cortex of adult primates undergoes topographic reorganization following spinal cord or peripheral nerve injuries. Electrophysiological studies in monkeys show that after chronic lesions of dorsal columns of the spinal cord at cervical levels, there is an expansion of face representation into the deafferented hand region of area 3b of cortex. However, these techniques can sample only a limited portion of the brain. In order to help understand mechanisms of brain reorganization use of noninvasive tools in non-human primate experimental model is important. Use of blood oxygen level dependent-functional magnetic resonance imaging (BOLD-fMRI) to study brain reorganization in non-human primates has been extremely limited. Here, we show that in monkeys with long-term unilateral lesions of the dorsal columns at cervical levels, tactile stimulation of the chin showed BOLD activation in the deafferented hand region of contralesional area 3b in the post-central gyrus. In a monkey with a partial lesion of the dorsal columns, stimulations of both hand and chin activated the partially deafferented hand region. We also show that the somatotopic organization in the non-deafferented ipsilesional somatosensory cortex remained normal.

Determination of relaxation characteristics during preacute stage of lysophosphatidyl choline-induced demyelinating lesion in rat brain: an animal model of multiple sclerosis.

Relaxation time measurements were carried out during the preacute stage of lesion progression in an animal model of demyelination created in the internal capsule (ic) area of the rat brain using lysophosphatidyl choline (LPC). T1 and T2 were determined both before and after 36 h of lesion creation. Histology carried out on the rats after MR measurements showed focal demyelinating lesion and surrounding edema with prominent infiltration of inflammatory cells. Both T1 and T2 were statistically higher for the lesion compared to that determined before lesion creation. Percentage increase in T2 was found to be higher by approximately 45% compared to before lesion creation while T1 showed about 25% increase. Increase in T1 and T2 may be attributed to the early acute inflammatory response due to LPC. The beginning of the inflammatory response following LPC injection may also be a contributing factor. The study demonstrates that the quantitative estimate of MR relaxation provides useful information on the pathological events occurring during the early phase of the progression of demyelination.