MRI Investigations of Metabolic and Structural Brain Changes in Alzheimer’s Disease and Vitamin D Deprivation

Alzheimer\u27s disease (AD) is a neurodegenerative disorder of the brain that presents as progressive impairment across several cognitive domains. The biological mechanisms underlying the development of AD remain unclear, with amyloid-beta plaques, neurofibrillary tangles, calcium dysregulation, and oxidative stress all contributing to neurodegeneration in AD. Vitamin D (VitD) deficiency, a common condition in the elderly, may modulate these mechanisms and complicate the AD process. Due to this complicated pathogenesis, the diagnosis of AD requires subjective clinical judgement, staging of AD is challenging, and it remains difficult to predict when and who will progress to AD. The purpose of this thesis was to study the metabolic and structural changes of specific brain regions as a consequence of AD alone and under conditions of AD and VitD deprivation. Identification of biological changes underlying the early symptoms of AD will help to identify and stage individuals prior to symptom onset. In one study, proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging (DTI), and neurospychological testing was used to measure the metabolic and microstructural processes associated with episodic memory impairment. Individuals with AD, mild cognitive impairment (MCI), and normal elderly controls (NEC) were studied. Left hippocampal glutamate and posterior cingulate N-acetyl aspartate concentrations were reduced in MCI and AD compared to NEC. Differences in DTI metrics indicated volume and white matter loss along the cingulum in AD compared to NEC. Metabolic and microstructural changes were also associated with episodic memory performance assessed using Craft Story 21 Recall and Benson Complex Figure Copy. The results of this study suggested that metabolite concentrations may provide insight into the underlying biological processes of AD and increase the confidence of a clinical diagnosis of MCI or AD. To improve glutamate measurement in future studies, the echo time (TE) for 1H-MRS measurement of glutamate at 7 T was optimized for signal strength and measurement precision in a second study. Time-domain simulations were performed and verified against in vivo and in vitro measurements. The results of this study indicated that TE = 105 ms was optimal for in vivo glutamate measurement at 7 T with the semi-LASER (localization by adiabatic selective refocusing) sequence as this echo time produced the greatest glutamate signal while also producing the lowest measurement coefficient of variation. Use of a long TE will also decrease power deposition and minimize macromolecule contributions to the spectrum. In a third study, the role of VitD deficiency in AD was comprehensively evaluated in the APPSwe/PS1ΔE9 mouse model of mild AD using 1H-MRS, high-resolution MRI, and spatial memory tasks. VitD deficiency did not change ventricle volume, an MRI marker of neuronal loss, but did result in changes in metabolite concentrations consistent with astrocytosis and gliosis. Overall, VitD deficient mice also performed better or improved on measures of spatial memory than mice on a nutritionally sufficient control diet. The results of this study suggested that VitD deficiency may improve memory by upregulating beneficial reactive astrocytosis in the prodromal stages of AD

Variation in the Response of Three Different Pinus Radiata Kraft Pulps to Xylanase Treatments

Two xylanase preparations (Pulpzyme HC and Xylanasc E) were assessed for their ability to enhance the refining properties of three different Pinus radiata kraft pulps. Both preparations selectively solubilized a significant proportion of the available xylan; however, xylanase E proved to be more aggressive, regardless of the pulp type. The selective removal of pulp xylan improved pulp beatability by increasing the apparent densities of the resultant handsheets over their corresponding controls. There were, however, variations in the response of the different pulp types, with an unbleached kappa 70 pulp showing the greatest improvement in sheet densification, as compared to an isothermal-cooked (kappa 33) and a fully bleached pulp. In general, xylanase treatments improved tear strength at a given density without significant loss in tensile strength and intrinsic fiber strength. These results suggest that xylanase treatments may be a means of enhancing the collapsibility/flexibility of certain kraft fibers while maintaining intrinsic strength

Investigation into some presumed maxims for residential design in Hong Kong

Thesis (M. Arch.)--Massachusetts Institute of Technology, Dept. of Architecture, 2008.Includes bibliographical references (p. 72).Formal expressions of architecture in a city are largely dictated by how the city is 'coded' ... re-coding - is capable of making fundamental changes in building forms that would proliferate across the entire city. Therefore, the City Coding Project consists of two primary components: * Through the study of how residential developments in Hong Kong are 'coded' the first part of this thesis seeks to understand the underlying logic of the city's zoning regulations, programming conventions, construction practices and building codes in order to earn one degree of freedom that would alter the city's form fundamentally. * Having that in mind, the second part of this thesis shows how, through creatively accepting, adding or tampering with the city's existing ge-nomes, new formal potentials within the domain of existing practices could be unleashed and manifested as a new architectural typology. These new formal potentials are particularly pertinent to residential design in Hong Kong be code-driven solutions to the problems of extreme density, mixed-use programming and cc tions is a - formally as well as programmatically - highly monotonous urban Iandscape.The ( a prototypical undertaking that demonstrates how one could wriggle free from - but not cor able constraints upon residential design. keywords: building codes, construction practices, mass production, mass customization, amenity programs.by Chit Kin Diclson Wong.M.Arch

\u3csup\u3e1\u3c/sup\u3eH MR spectroscopy of the motor cortex immediately following transcranial direct current stimulation at 7 Tesla

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that may modulate cortical excitability, metabolite concentration, and human behaviour. The supplementary motor area (SMA) has been largely ignored as a potential target for tDCS neurorehabilitation but is an important region in motor compensation after brain injury with strong efferent connections to the primary motor cortex (M1). The objective of this work was to measure tissue metabolite changes in the human motor cortex immediately following tDCS. We hypothesized that bihemispheric tDCS would change levels of metabolites involved in neuromodulation including N-acetylaspartate (NAA), glutamate (Glu), and creatine (tCr). In this single-blind, randomized, cross-over study, fifteen healthy adults aged 21–60 participated in two 7T MRI sessions, to identify changes in metabolite concentrations by magnetic resonance spectroscopy. Immediately after 20 minutes of tDCS, there were no significant changes in metabolite levels or metabolite ratios comparing tDCS to sham. However there was a trend toward increased NAA/tCr concentration (p = 0.08) in M1 under the stimulating cathode. There was a strong, positive correlation between the change in the absolute concentration of NAA and the change in the absolute concentration of tCr (p\u3c0.001) suggesting an effect of tDCS. Both NAA and creatine are important markers of neurometabolism. Our findings provide novel insight into the modulation of neural metabolites in the motor cortex immediately following application of bihemispheric tDCS

Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective Connectivity, and Computational Evidence in Schizophrenia

Background: Functional dysconnection in schizophrenia is underwritten by a pathophysiology of the glutamate neurotransmission that affects the excitation-inhibition balance in key nodes of the salience network. Physiologically, this manifests as aberrant effective connectivity in intrinsic connections involving inhibitory interneurons. In computational terms, this produces a pathology of evidence accumulation and ensuing inference in the brain. Finally, the pathophysiology and aberrant inference would partially account for the psychopathology of schizophrenia as measured in terms of symptoms and signs. We refer to this formulation as the 3-level hypothesis. Methods: We tested the hypothesis in core nodes of the salience network (the dorsal anterior cingulate cortex [dACC] and the anterior insula) of 20 patients with first-episode psychosis and 20 healthy control subjects. We established 3-way correlations between the magnetic resonance spectroscopy measures of glutamate, effective connectivity of resting-state functional magnetic resonance imaging, and correlations between measures of this connectivity and estimates of precision (inherent in evidence accumulation in the Stroop task) and psychopathology. Results: Glutamate concentration in the dACC was associated with higher and lower inhibitory connectivity in the dACC and in the anterior insula, respectively. Crucially, glutamate concentration correlated negatively with the inhibitory influence on the excitatory neuronal population in the dACC of subjects with first-episode psychosis. Furthermore, aberrant computational parameters of the Stroop task performance were associated with aberrant inhibitory connections. Finally, the strength of connections from the dACC to the anterior insula correlated negatively with severity of social withdrawal. Conclusions: These findings support a link between glutamate-mediated cortical disinhibition, effective-connectivity deficits, and computational performance in psychosis

Designer Gene Networks: Towards Fundamental Cellular Control

The engineered control of cellular function through the design of synthetic genetic networks is becoming plausible. Here we show how a naturally occurring network can be used as a parts list for artificial network design, and how model formulation leads to computational and analytical approaches relevant to nonlinear dynamics and statistical physics.Comment: 35 pages, 8 figure

Oligohydramnios compromises lung cells size and interferes with epithelial–endothelial development

Funded by National Institute of General Medical Sciences of the National Institutes of Health. Grant Number: P30GM114750 Department of Pediatrics Kilguss Research Core of Women & Infants Hospital of Rhode IslandPeer reviewedPostprin

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis

Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early CKD in mice. This revealed (C-C motif) ligands 6 and 9 (CCL6 and CCL9) as the most upregulated chemokines, with significantly higher levels of both chemokines in blood (CCL6: 3–4 fold; CCL9: 3–5 fold) as well as kidney as confirmed by Enzyme-linked Immunosorbent Assay (ELISA) in two additional CKD models. Chemokine treatment in a mouse model of early adenine-induced CKD almost completely abolished the CKD-induced infiltration of macrophages and myeloid cells in the kidney without impact on circulating leukocyte numbers. The other way around, especially CCL9-blockade aggravated monocyte and macrophage accumulation in kidney during CKD development, without impact on the ratio of M1-to-M2 macrophages. In parallel, CCL9-blockade raised serum creatinine and urea levels as readouts of kidney dysfunction. It also exacerbated CKD-induced expression of collagen (3.2-fold) and the pro-inflammatory chemokines CCL2 (1.8-fold) and CCL3 (2.1-fold) in kidney. Altogether, this study reveals for the first time that chemokines CCL6 and CCL9 are upregulated early in experimental CKD, with CCL9-blockade during CKD initiation enhancing kidney inflammation and fibrosis

Validation of the Chinese version of the CogState computerised cognitive assessment battery in Taiwanese patients with heart failure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116000/1/jocn12919.pd