Left lateralized cerebral glucose metabolism declines in amyloid-β positive persons with mild cognitive impairment

Background: Previous publications indicate that Alzheimer\u27s Disease (AD) related cortical atrophy may develop in asymmetric patterns, with accentuation of the left hemisphere. Since fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the regional cerebral metabolic rate of glucose (rCMRgl) provide a sensitive and specific marker of neurodegenerative disease progression, we sought to investigate the longitudinal pattern of rCMRgl in amyloid-positive persons with mild cognitive impairment (MCI) and dementia, hypothesizing asymmetric declines of cerebral glucose metabolism. Methods: Using florbetapir PET and cerebrospinal fluid (CSF) measures to define amyloid-β (Aβ) positivity, 40 Aβ negative (Aβ-) cognitively unimpaired controls (CU; 76 ± 5y), 76 Aβ positive (Aβ+) persons with MCI (76 ± 7y) and 51 Aβ+persons with probable AD dementia (75 ± 7y) from the AD Neuroimaging Initiative (ADNI) were included in this study with baseline and 2-year follow-up FDG PET scans. The degree of lateralization of longitudinal rCMRgl declines in subjects with Aβ+MCI and AD in comparison with Aβ- CU were statistically quantified via bootstrapped lateralization indices [(LI); range−1 (right) to 1 (left)]. Results: Compared to Aβ- CU, Aβ+MCI patients showed marked left hemispheric lateralization (LI: 0.78). In contrast, modest right hemispheric lateralization (LI: −0.33) of rCMRgl declines was found in Aβ+persons with probable AD dementia. Additional comparisons of Aβ+groups (i.e. MCI and probable AD dementia) consequently indicated right hemispheric lateralization (LI: −0.79) of stronger rCMRgl declines in dementia stages of AD. For all comparisons, voxel-based analyses confirmed significant (pFWE\u3c0.05) declines of rCMRgl within AD-typical brain regions. Analyses of cognitive data yielded predominant decline of memory functions in both MCI and dementia stages of AD. Conclusions: These data indicate that in early stages, AD may be characterized by a more lateralized pattern of left hemispheric rCMRgl declines. However, metabolic differences between hemispheres appear to diminish with further progression of the disease

Left lateralized cerebral glucose metabolism declines in amyloid-β positive persons with mild cognitive impairment

Background: Previous publications indicate that Alzheimer\u27s Disease (AD) related cortical atrophy may develop in asymmetric patterns, with accentuation of the left hemisphere. Since fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the regional cerebral metabolic rate of glucose (rCMRgl) provide a sensitive and specific marker of neurodegenerative disease progression, we sought to investigate the longitudinal pattern of rCMRgl in amyloid-positive persons with mild cognitive impairment (MCI) and dementia, hypothesizing asymmetric declines of cerebral glucose metabolism. Methods: Using florbetapir PET and cerebrospinal fluid (CSF) measures to define amyloid-β (Aβ) positivity, 40 Aβ negative (Aβ-) cognitively unimpaired controls (CU; 76 ± 5y), 76 Aβ positive (Aβ+) persons with MCI (76 ± 7y) and 51 Aβ+persons with probable AD dementia (75 ± 7y) from the AD Neuroimaging Initiative (ADNI) were included in this study with baseline and 2-year follow-up FDG PET scans. The degree of lateralization of longitudinal rCMRgl declines in subjects with Aβ+MCI and AD in comparison with Aβ- CU were statistically quantified via bootstrapped lateralization indices [(LI); range−1 (right) to 1 (left)]. Results: Compared to Aβ- CU, Aβ+MCI patients showed marked left hemispheric lateralization (LI: 0.78). In contrast, modest right hemispheric lateralization (LI: −0.33) of rCMRgl declines was found in Aβ+persons with probable AD dementia. Additional comparisons of Aβ+groups (i.e. MCI and probable AD dementia) consequently indicated right hemispheric lateralization (LI: −0.79) of stronger rCMRgl declines in dementia stages of AD. For all comparisons, voxel-based analyses confirmed significant (pFWE\u3c0.05) declines of rCMRgl within AD-typical brain regions. Analyses of cognitive data yielded predominant decline of memory functions in both MCI and dementia stages of AD. Conclusions: These data indicate that in early stages, AD may be characterized by a more lateralized pattern of left hemispheric rCMRgl declines. However, metabolic differences between hemispheres appear to diminish with further progression of the disease

Inhibition of Diaphanous Formin Signaling In Vivo Impairs Cardiovascular Development and Alters Smooth Muscle Cell PhenotypeSignificance

We and others have previously shown that RhoA-dependent stimulation of myocardin related transcription factor (MRTF) nuclear localization promotes smooth muscle cell (SMC) marker gene expression. The goal of the present study was to provide direct in vivo evidence that actin polymerization by the diaphanous-related formins contributes to the regulation of SMC differentiation and/or phenotype

Home Range Use and Movement Patterns of Non-Native Feral Goats in a Tropical Island Montane Dry Landscape

Advances in wildlife telemetry and remote sensing technology facilitate studies of broad-scale movements of ungulates in relation to phenological shifts in vegetation. In tropical island dry landscapes, home range use and movements of non-native feral goats (Capra hircus) are largely unknown, yet this information is important to help guide the conservation and restoration of some of the world’s most critically endangered ecosystems. We hypothesized that feral goats would respond to resource pulses in vegetation by traveling to areas of recent green-up. To address this hypothesis, we fitted six male and seven female feral goats with Global Positioning System (GPS) collars equipped with an Argos satellite upload link to examine goat movements in relation to the plant phenology using the Normalized Difference Vegetation Index (NDVI). Movement patterns of 50% of males and 40% of females suggested conditional movement between non-overlapping home ranges throughout the year. A shift in NDVI values corresponded with movement between primary and secondary ranges of goats that exhibited long-distance movement, suggesting that vegetation phenology as captured by NDVI is a good indicator of the habitat and movement patterns of feral goats in tropical island dry landscapes. In the context of conservation and restoration of tropical island landscapes, the results of our study identify how non-native feral goats use resources across a broad landscape to sustain their populations and facilitate invasion of native plant communities

A Functional Henipavirus Envelope Glycoprotein Pseudotyped Lentivirus Assay System

<p>Abstract</p> <p>Background</p> <p>Hendra virus (HeV) and Nipah virus (NiV) are newly emerged zoonotic paramyxoviruses discovered during outbreaks in Queensland, Australia in 1994 and peninsular Malaysia in 1998/9 respectively and classified within the new <it>Henipavirus </it>genus. Both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals, and repeated outbreaks continue to occur. Extensive laboratory studies on the host cell infection stage of HeV and NiV and the roles of their envelope glycoproteins have been hampered by their highly pathogenic nature and restriction to biosafety level-4 (BSL-4) containment. To circumvent this problem, we have developed a henipavirus envelope glycoprotein pseudotyped lentivirus assay system using either a luciferase gene or green fluorescent protein (GFP) gene encoding human immunodeficiency virus type-1 (HIV-1) genome in conjunction with the HeV and NiV fusion (F) and attachment (G) glycoproteins.</p> <p>Results</p> <p>Functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells. The functional specificity of the assay was confirmed by the lack of reporter-gene signals when particles bearing either only the F or only G glycoprotein were prepared and assayed. Virus entry could be specifically blocked when infection was carried out in the presence of a fusion inhibiting C-terminal heptad (HR-2) peptide, a well-characterized, cross-reactive, neutralizing human mAb specific for the henipavirus G glycoprotein, and soluble ephrinB2 and B3 receptors. In addition, the utility of the assay was also demonstrated by an examination of the influence of the cytoplasmic tail of F in its fusion activity and incorporation into pseudotyped virus particles by generating and testing a panel of truncation mutants of NiV and HeV F.</p> <p>Conclusions</p> <p>Together, these results demonstrate that a specific henipavirus entry assay has been developed using NiV or HeV F and G glycoprotein pseudotyped reporter-gene encoding retrovirus particles. This assay can be conducted safely under BSL-2 conditions and will be a useful tool for measuring henipavirus entry and studying F and G glycoprotein function in the context of virus entry, as well as in assaying and characterizing neutralizing antibodies and virus entry inhibitors.</p

Central Effects of Botulinum Neurotoxin—Evidence from Human Studies

For more than three decades, Botulinum neurotoxin (BoNT) has been used to treat a variety of clinical conditions such as spastic or dystonic disorders by inducing a temporary paralysis of the injected muscle as the desired clinical effect. BoNT is known to primarily act at the neuromuscular junction resulting in a biochemical denervation of the treated muscle. However, recent evidence suggests that BoNT&rsquo;s pharmacological properties may not only be limited to local muscular denervation at the injection site but may also include additional central effects. In this review, we report and discuss the current evidence for BoNT&rsquo;s central effects based on clinical observations, neurophysiological investigations and neuroimaging studies in humans. Collectively, these data strongly point to indirect mechanisms via changes to sensory afferents that may be primarily responsible for the marked plastic effects of BoNT on the central nervous system. Importantly, BoNT-related central effects and consecutive modulation and/or reorganization of the brain may not solely be considered &ldquo;side-effects&rdquo; but rather an additional therapeutic impact responsible for a number of clinical observations that cannot be explained by merely peripheral actions