Neuroanatomical Correlates of Recognizing Face Expressions in Mild Stages of Alzheimer’s Disease

Early Alzheimer’s disease can involve social disinvestment, possibly as a consequence of impairment of nonverbal communication skills. This study explores whether patients with Alzheimer’s disease at the mild cognitive impairment or mild dementia stage have impaired recognition of emotions in facial expressions, and describes neuroanatomical correlates of emotion processing impairment. As part of the ongoing PACO study (personality, Alzheimer’s disease and behaviour), 39 patients with Alzheimer’s disease at the mild cognitive impairment or mild dementia stage and 39 matched controls completed tests involving discrimination of four basic emotions—happiness, fear, anger, and disgust—on photographs of faces. In patients, automatic volumetry of 83 brain regions was performed on structural magnetic resonance images using MAPER (multi-atlas propagation with enhanced registration). From the literature, we identified for each of the four basic emotions one brain region thought to be primarily associated with the function of recognizing that emotion. We hypothesized that the volume of each of these regions would be correlated with subjects’ performance in recognizing the associated emotion. Patients showed deficits of basic emotion recognition, and these impairments were correlated with the volumes of the expected regions of interest. Unexpectedly, most of these correlations were negative: better emotional facial recognition was associated with lower brain volume. In particular, recognition of fear was negatively correlated with the volume of amygdala, disgust with pallidum, and happiness with fusiform gyrus. Recognition impairment in mild stages of Alzheimer’s disease for a given emotion was thus associated with less visible atrophy of functionally responsible brain structures within the patient group. Possible explanations for this counterintuitive result include neuroinflammation, regional β-amyloid deposition, or transient overcompensation during early stages of Alzheimer’s disease.     

Neuroanatomical Correlates of Theory of Mind Deficit in Parkinson’s Disease: A Multimodal Imaging Study

BackgroundParkinson’s disease (PD) patients show theory of mind (ToM) deficit since the early stages of the disease, and this deficit has been associated with working memory, executive functions and quality of life impairment. To date, neuroanatomical correlates of ToM have not been assessed with magnetic resonance imaging in PD. The main objective of this study was to assess cerebral correlates of ToM deficit in PD. The second objective was to explore the relationships between ToM, working memory and executive functions, and to analyse the neural correlates of ToM, controlling for both working memory and executive functions.MethodsThirty-seven PD patients (Hoehn and Yahr median = 2.0) and 15 healthy controls underwent a neuropsychological assessment and magnetic resonance images in a 3T-scanner were acquired. T1-weighted images were analysed with voxel-based morphometry, and white matter integrity and diffusivity measures were obtained from diffusion weighted images and analysed using tract-based spatial statistics.ResultsPD patients showed impairments in ToM, working memory and executive functions; grey matter loss and white matter reduction compared to healthy controls. Grey matter volume decrease in the precentral and postcentral gyrus, middle and inferior frontal gyrus correlated with ToM deficit in PD. White matter in the superior longitudinal fasciculus (adjacent to the parietal lobe) and white matter adjacent to the frontal lobe correlated with ToM impairment in PD. After controlling for executive functions, the relationship between ToM deficit and white matter remained significant for white matter areas adjacent to the precuneus and the parietal lobe.ConclusionsFindings reinforce the existence of ToM impairment from the early Hoehn and Yahr stages in PD, and the findings suggest associations with white matter and grey matter volume decrease. This study contributes to better understand ToM deficit and its neural correlates in PD, which is a basic skill for development of healthy social relationships.     

Altitudinally restricted communities of Schizophoran flies in Queensland’s Wet Tropics: vulnerability to climate change

The Australian Wet Tropics World Heritage Area (WTWHA) contains a number of highland vertebrates predicted to face extinction due to a warming climate, but little is known about risks to invertebrates, which are vital to ecosystem health. This study investigates the distribution and abundance patterns of the Dipteran sub-order Schizophora along an altitudinal transect in the Carbine Uplands of the WTWHA using Malaise traps. The season of peak abundance changed with altitude, with highland abundance peaking in October, and lowland abundance peaking in April. There was a high level of species turnover with altitude, and some evidence for distinct low-, mid-, and high-elevation assemblages, with the high-elevation assemblage containing the most restricted species. We would expect this high-elevation assemblage to be at risk of local extinction with 2–3° of warming, and the mid-elevation assemblage to be at risk with 4–5° warming. Future work should continue sampling to confirm patterns presented here and to monitor range shifts with climate change. A highland species—Helosciomyza ferruginea Hendel is suggested as a good indicator species for such monitoring.     

Breeding biology of Sabine’s gull (Xema sabini) in the Canadian high Arctic

The Sabine’s gull (Xema sabini) is a small seabird that breeds in select locations across the circumpolar Arctic, but there have been few studies on its breeding biology, particularly from the high Arctic. We studied nesting phenology, breeding effort, and breeding success of Sabine’s gulls over 5 years at a colony on a small island (Nasaruvaalik) in the Canadian high Arctic. Compared to studies in the low Arctic, nest initiation dates and adult body mass were more consistent across years, and reproductive success was typically higher at Nasaruvaalik Island. These differences may be related to the more predictable food sources available in the nearby polynya upon arrival from migration, as well as the lower predation pressure at our site.     

Children’s Experience of Posttraumatic Growth: Distinguishing General from Domain-Specific Correlates

Although the five domains of posttraumatic growth (new possibilities, relating to others, personal strength, spiritual change and appreciation of life) have been studied extensively in adults, little is known about these domains and their correlates in children. We aimed to examine whether demographic and/or social characteristics are related to children’s reports of overall posttraumatic growth and of growth in specific domains. In a general population study, children aged 8–12 years who had been exposed to adverse events (N = 1290) filled out questionnaires on their experiences, demographic characteristics (gender, age, time lag since event), stress reactions, peer support, religiosity and posttraumatic growth. All demographic and social characteristics were related to overall posttraumatic growth, except time lag. Associations varied across the five domains with the strongest effects being found for stress reactions and religiosity. A higher level of stress reactions was related to more growth in all domains (general effect), whereas religious children experienced more spiritual growth than non-religious children without differences on other domains (domain specific effect). Other effects were small, and some did not remain significant after Bonferroni corrections. These findings suggest the presence of both general and domain-specific correlates of child posttraumatic growth. Although effects were generally small, the current findings show the need to differentiate between the domains of posttraumatic growth in both further research and clinical practice. This will allow a better understanding of the mechanisms of posttraumatic growth in children as well as more tailored assessment and intervention.     

Parkin promotes proteasomal degradation of p62: implication of selective vulnerability of neuronal cells in the pathogenesis of Parkinson’s disease

Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson’s disease (PD), respectively, which manifested with the selective vulnerability of neuronal cells in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.     

Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

Sphingolipids are important in many brain functions but their role in Alzheimer’s disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β₄₂ concentration in CSF from cognitively normal but not impaired participants. In dementia, altered sphingolipid metabolism, decreased acid sphingomyelinase activity and its lost association with CSF amyloid β₄₂ concentration, underscores the potential of sphingolipids as disease biomarkers, and acid sphingomyelinase as a target for AD diagnosis and/or treatment.     

Enhanced Expression of Glia Maturation Factor Correlates with Glial Activation in the Brain of Triple Transgenic Alzheimer’s Disease Mice

We previously demonstrated that glia maturation factor (GMF), a brain specific protein, isolated, sequenced and cloned in our laboratory, induce expression of proinflammatory cytokines and chemokines in the central nervous system. We also reported that the up-regulation of GMF in astrocytes leads to the destruction of neurons suggesting a novel pathway of GMF-mediated cytotoxicity of brain cells, and implicated its involvement in the pathogenesis of inflammatory neurodegenerative diseases. In the present study, we examined the expressions of GMF in triple-transgenic Alzheimer’s disease (3xTg-AD) mice. Our results show a 13-fold up-regulation of GMF and 8–12-fold up-regulation of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, interferon gamma (IFN-γ), and chemokine (C–C motif) ligand 2 (CCL2) and C–X–C motif chemokine 10 (CXCL10/IP-10) mRNA as determined by quantitative real-time RT-PCR in the brain of 3xTg-AD mice as compared to non-transgenic (Non-Tg) mice. In conclusion, the increase in GMF and cytokine/chemokine expression was correlated with reactive glial fibrillary acidic protein positive astrocytes and ionized calcium binding adaptor molecule 1 (Iba-1)-positive microglia in 3xTg-AD mice.     

Increasing Specificity of Correlate Research: Exploring Correlates of Children’s Lunchtime and After-School Physical Activity

Background

The lunchtime and after-school contexts are critical windows in a school day for children to be physically active. While numerous studies have investigated correlates of children’s habitual physical activity, few have explored correlates of physical activity occurring at lunchtime and after-school from a social-ecological perspective. Exploring correlates that influence physical activity occurring in specific contexts can potentially improve the prediction and understanding of physical activity. Using a context-specific approach, this study investigated correlates of children’s lunchtime and after-school physical activity.

Methods

Cross-sectional data were collected from 423 South Australian children aged 10.0–13.9 years (200 boys; 223 girls) attending 10 different schools. Lunchtime and after-school physical activity was assessed using accelerometers. Correlates were assessed using purposely developed context-specific questionnaires. Correlated Component Regression analysis was conducted to derive correlates of context-specific physical activity and determine the variance explained by prediction equations.

Results

The model of boys’ lunchtime physical activity contained 6 correlates and explained 25% of the variance. For girls, the model explained 17% variance from 9 correlates. Enjoyment of walking during lunchtime was the strongest correlate for both boys and girls. Boys’ and girls’ after-school physical activity models explained 20% variance from 14 correlates and 7% variance from the single item correlate, “I do an organised sport or activity after-school because it gets you fit”, respectively.

Conclusions

Increasing specificity of correlate research has enabled the identification of unique features of, and a more in-depth interpretation of, lunchtime and after-school physical activity behaviour and is a potential strategy for advancing the physical activity correlate research field. The findings of this study could be used to inform and tailor gender-specific public health messages and interventions for promoting lunchtime and after-school physical activity in children.     

Role of RAGE in Alzheimer’s Disease

Receptor for advanced glycation end products (RAGE) is a receptor of the immunoglobulin super family that plays various important roles under physiological and pathological conditions. Compelling evidence suggests that RAGE acts as both an inflammatory intermediary and a critical inducer of oxidative stress, underlying RAGE-induced Alzheimer-like pathophysiological changes that drive the process of Alzheimer’s disease (AD). A critical role of RAGE in AD includes beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangles, failure of synaptic transmission, and neuronal degeneration. The steady-state level of Aβ depends on the balance between production and clearance. RAGE plays an important role in the Aβ clearance. RAGE acts as an important transporter via regulating influx of circulating Aβ into brain, whereas the efflux of brain-derived Aβ into the circulation via BBB is implemented by LRP1. RAGE could be an important contributor to Aβ generation via enhancing the activity of β- and/or γ-secretases and activating inflammatory response and oxidative stress. However, sRAGE–Aβ interactions could inhibit Aβ neurotoxicity and promote Aβ clearance from brain. Meanwhile, RAGE could be a promoting factor for the synaptic dysfunction and neuronal circuit dysfunction which are both the material structure of cognition, and the physiological and pathological basis of cognition. In addition, RAGE could be a trigger for the pathogenesis of Aβ and tau hyper-phosphorylation which both participate in the process of cognitive impairment. Preclinical and clinical studies have supported that RAGE inhibitors could be useful in the treatment of AD. Thus, an effective measure to inhibit RAGE may be a novel drug target in AD.     

Prevention of progression in Parkinson’s disease

Environmental influences affecting genetically susceptible individuals seem to contribute significantly to the development of Parkinson’s disease (PD). Xenobiotic exposure including transitional metal deposition into vulnerable CNS regions appears to interact with PD genes. Such exposure together with mitochondrial dysfunction evokes a destructive cascade of biochemical events, including oxidative stress and degeneration of the sensitive dopamine (DA) production system in the basal ganglia. Recent research indicates that the substantia nigra degeneration can be decelerated by treatment with iron binding compounds such as deferiprone. Interestingly compounds known to decrease PD risk including caffeine, niacin, nicotine and salbutamol also possess iron binding properties. Adequate function of antioxidative mechanisms in the vulnerable brain cells can be restored by acetylcysteine supplementation to normalize intracellular glutathione activity. Other preventive measures to reduce deterioration of dopaminergic neurons may involve life-style changes such as intake of natural antioxidants and physical exercise. Further research is recommended to identify therapeutic targets of the proposed interventions, in particular protection of the DA biosynthesis by oxygen radical scavengers and iron binding agents.     

Transport of ethanol in baker’s yeast

Ethanol is transported into various strains of baker's yeast by simple diffusion (no effect of inhibitors and a linear concentration dependence of the initial rate of uptake and final distribution in cells). It distributes itself in 96.6 +/- 16.2% of intracellular water.     

‘Tales of Symphonia’: extinction dynamics in response to past climate change in Madagascan rainforests

Madagascar''s rainforests are among the most biodiverse in the world. Understanding the population dynamics of important species within these forests in response to past climatic variability provides valuable insight into current and future species composition. Here, we use a population-level approach to analyse palaeoecological records over the last 5300 years to understand how populations of Symphonia cf. verrucosa became locally extinct in some rainforest fragments along the southeast coast of Madagascar in response to rapid climate change, yet persisted in others. Our results indicate that regional (climate) variability contributed to synchronous decline of S. cf. verrucosa populations in these forests. Superimposed on regional fluctuations were local processes that could have contributed or mitigated extinction. Specifically, in the forest with low soil nutrients, population model predictions indicated that there was coexistence between S. cf. verrucosa and Erica spp., but in the nutrient-rich forest, interspecific effects between Symphonia and Erica spp. may have pushed Symphonia to extinction at the peak of climatic change. We also demonstrate that Symphonia is a good indicator of a threshold event, exhibiting erratic fluctuations prior to and long after the critical climatic point has passed.     

Microbial degradation of microcystin in Florida’s freshwaters

Presence of microcystin (MC), a predominant freshwater algal toxin and a suspected liver carcinogen, in Florida’s freshwaters poses serious health threat to humans and aquatic species. Being recalcitrant to conventional physical and chemical water treatment methods, biological methods of MC removal is widely researched. Water samples collected from five sites of Lake Okeechobee (LO) frequently exposed to toxic Microcystis blooms were used as inoculum for enrichment with microcystin LR (MC-LR) supplied as sole C and N source. After 20 days incubation, MC levels were analyzed using high performance liquid chromatography (HPLC). A bacterial consortium consisting of two isolates DC7 and DC8 from the Indian Prairie Canal sample showed over 74% toxin degradation at the end of day 20. Optimal temperature requirement for biodegradation was identified and phosphorus levels did not affect the MC biodegradation. Based on 16S rRNA sequence similarity the isolate DC8 was found to have a match with Microbacterium sp. and the DC7 isolate with Rhizobium gallicum (AY972457).