The Alzheimer's disease β-secretase enzyme, BACE1

The pathogenesis of Alzheimer's disease is highly complex. While several pathologies characterize this disease, amyloid plaques, composed of the β-amyloid peptide are hallmark neuropathological lesions in Alzheimer's disease brain. Indeed, a wealth of evidence suggests that β-amyloid is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. The BACE1 enzyme is essential for the generation of β-amyloid. BACE1 knockout mice do not produce β-amyloid and are free from Alzheimer's associated pathologies including neuronal loss and certain memory deficits. The fact that BACE1 initiates the formation of β-amyloid, and the observation that BACE1 levels are elevated in this disease provide direct and compelling reasons to develop therapies directed at BACE1 inhibition thus reducing β-amyloid and its associated toxicities. However, new data indicates that complete abolishment of BACE1 may be associated with specific behavioral and physiological alterations. Recently a number of non-APP BACE1 substrates have been identified. It is plausible that failure to process certain BACE1 substrates may underlie some of the reported abnormalities in the BACE1-deficient mice. Here we review BACE1 biology, covering aspects ranging from the initial identification and characterization of this enzyme to recent data detailing the apparent dysregulation of BACE1 in Alzheimer's disease. We pay special attention to the putative function of BACE1 during healthy conditions and discuss in detail the relationship that exists between key risk factors for AD, such as vascular disease (and downstream cellular consequences), and the pathogenic alterations in BACE1 that are observed in the diseased state

The longitudinal development of emotion regulation capacities in children at risk for externalizing disorders

The development of emotional regulation capacities in children at high versus low risk for externalizing disorder was examined in a longitudinal study investigating: a) whether disturbances in emotion regulation precede and predict the emergence of externalizing symptoms; and b) whether sensitive maternal behavior is a significant influence on the development of child emotion regulation. Families experiencing high (n=58) and low (n=63) levels of psychosocial adversity were recruited to the study during pregnancy. Direct observational assessments of child emotion regulation capacities and maternal sensitivity were completed in early infancy, at 12 and 18-months, and at 5-years. Key findings were as follows. First, high risk children showed poorer emotion regulation capacities than their low risk counterparts at every stage of assessment. Second, from 12-months onwards, emotion regulation capacities showed a degree of stability, and were associated with behavioral problems, both concurrently and prospectively. Third, maternal sensitivity was related to child emotion regulation capacities throughout development, with poorer emotion regulation in the high risk group being associated with lower maternal sensitivity. The results are consistent with a causal role for problems in the regulation of negative emotions in the etiology of externalizing psychopathology, and highlight insensitive parenting as a potentially key developmental influence

Oral complementary medicine and alternative practitioner use varies across chronic conditions and attitudes to risk

Objectives: To determine whether chronic conditions and patient factors, such as risk perception and decision-making preferences, are associated with complementary medicine and alternative practitioner use in a representative longitudinal population cohort. Participants and setting: Analysis of data from Stage 2 of the North West Adelaide Health Study of 3161 adults who attended a study clinic visit in 2004–2006. The main outcome measures were the medications brought by participants to the study clinic visit, chronic health conditions, attitudes to risk, levels of satisfaction with conventional medicine, and preferred decision-making style. Results: At least one oral complementary medicine was used by 27.9% of participants, and 7.3% were visiting alternative practitioners (naturopath, osteopath). Oral complementary medicine use was significantly associated with arthritis, osteoporosis, and mental health conditions, but not with other chronic conditions. Any pattern of complementary medicine use was generally significantly associated with female gender, age at least 45 years, patient-driven decision-making preferences(odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.08–1.77), and frequent general practitioner visits (.five per year; OR 3.62, 95% CI: 2.13–6.17). Alternative practitioner visitors were younger, with higher levels of education (diploma/trade [OR 1.88, 95% CI: 1.28–2.76], bachelor’s degree [OR 1.77, 95% CI: 1.11–2.82], income . $80,000 (OR 2.28, 95% CI: 1.26–4.11), female gender (OR 3.15, 95% CI: 2.19–4.52), joint pain not diagnosed as arthritis (OR 1.68, 95% CI: 1.17–2.41), moderate to severe depressive symptoms (OR 2.15, 95% CI: 1.04–4.46), and risk-taking behaviour (3.26, 1.80–5.92), or low-to-moderate risk aversion (OR 2.08, 95% CI: 1.26–4.11). Conclusion: Although there is widespread use of complementary medicines in the Australian community, there are differing patterns of use between those using oral complementary medicines and those using alternative practitioners.Robert J Adams, Sarah L Appleton, Antonia Cole, Tiffany K Gill, Anne W Taylor and Catherine L Hil

Posting selfies and body image in young adult women: The selfie paradox

This exploratory study was designed to investigate how young women make sense of their decision to post selfies, and perceived links between selfie posting and body image. Eighteen 19-22 year old British women were interviewed about their experiences of taking and posting selfies, and interviews were analysed using inductive thematic analysis. Women linked selfie posting to the ‘ideal’ body, identity management, and body exposure; objectifying their own and others’ selfies, and trying to portray an image that was as close to ‘ideal’ as possible. Women differentiated between their ‘unreal’, digitally manipulated online selfie identity and their ‘real’ identity outside Facebook and Instagram. Bodies were expected to be covered, and sexualised selfies were to be avoided. Results challenge conceptualisations of women as empowered and self-determined selfie posters; although women sought to control their image online, posting was constrained by postfeminist notions of what was considered socially appropriate to post

The Fold Illusion: The Origins and Implications of Ogives on Silicic Lavas

Folds on the surfaces of mafic lavas are among the most readily recognized geological structures and are used as first-order criteria for identifying ancient lavas on Earth and other planetary bodies. However, the presence of surface-folds on the surface of silicic lavas is contested in this study and we challenge the widely accepted interpretation that silicic lava surfaces contain folds using examples from the western United States and Sardinia, Italy. We interpret the ridges and troughs on their upper surfaces, typically referred to as ‘ogives’ or ‘pressure ridges’, as fracture-bound structures rather than folds. We report on the absence of large-scale, buckle-style folds and note instead the ubiquitous presence of multiple generations and scales of tensile fractures comparable to crevasses in glaciers and formed in ways similar to already recognized crease structures. We report viscosity data and results of stress analyses that preclude folding (ductile deformation in compression) of the upper surface of silicic lavas at timescales of emplacement (weeks to months). Therefore, analysis of fold geometry (wavelength, amplitude, etc.) is erroneous, and instead the signal produced reflects the strength and thickness of the brittle upper surface stretching over a ductile interior. The presence of ogives on the surfaces of lavas on other planetary bodies may help to elucidate their rheological properties and crustal thicknesses, but relating to their tensile strength, not viscosity

Gut Microbiome Diversity Is Associated with Sleep Physiology in Humans

The human gut microbiome can influence health through the brain-gut-microbiome axis. Growing evidence suggests that the gut microbiome can influence sleep quality. Previous studies that have examined sleep deprivation and the human gut microbiome have yielded conflicting results. A recent study found that sleep deprivation leads to changes in gut microbiome composition while a different study found that sleep deprivation does not lead to changes in gut microbiome. Accordingly, the relationship between sleep physiology and the gut microbiome remains unclear. To address this uncertainty, we used actigraphy to quantify sleep measures coupled with gut microbiome sampling to determine how the gut microbiome correlates with various measures of sleep physiology. We measured immune system biomarkers and carried out a neurobehavioral assessment as these variables might modify the relationship between sleep and gut microbiome composition. We found that total microbiome diversity was positively correlated with increased sleep efficiency and total sleep time, and was negatively correlated with wake after sleep onset. We found positive correlations between total microbiome diversity and interleukin-6, a cytokine previously noted for its effects on sleep. Analysis of microbiome composition revealed that within phyla richness of Bacteroidetes and Firmicutes were positively correlated with sleep efficiency, interleukin-6 concentrations and abstract thinking. Finally, we found that several taxa (Lachnospiraceae, Corynebacterium, and Blautia) were negatively correlated with sleep measures. Our findings initiate linkages between gut microbiome composition, sleep physiology, the immune system and cognition. They may lead to mechanisms to improve sleep through the manipulation of the gut microbiome

3D Printed PLA Scaffolds to Promote Healing of Large Bone Defects

One challenge modern medicine faces is the ability to repair large bone defects and stimulate healing. Small defects typically heal naturally, but large bone defects do not and current solutions are to replace the missing tissue with biologically inert materials such as titanium. This limits the amount of bone healing as the defect is not repaired but rather replaced. The focus of our research is to develop a method of using 3D printing to create biodegradable scaffolds which promote bone in-growth and replacement. To accomplish this we used poly lactic acid (PLA) filament and a desktop 3D printer. To promote bone healing and provide mechanical support our team investigated different design methodologies to provide a scaffold of customizable stiffness while allowing cell attachment and in-growth. Our team used CAD modeling to create unique architecture design systems which we analyzed for stiffness using Finite Element Analysis (FEA). We developed a unit cell method of scaffold construction that allowed for customized stiffness of irregular shapes. We 3D printed our designs using a desktop 3D printer and verified our stiffness through mechanical tension and compression testing. We investigated cell viability of the scaffolds by immersing test specimens in culturing media and fibroblast cells. Fibroblast cells are from the same lineage as osteoblast cells but are much faster growing, allowing for more efficient testing. Specimens were left in the media for one week then a total cell count was performed. Scaffold designs were then evaluated based on stiffness and cell viability. We have produced several different viable models with appropriate stiffness for human trabecular bone and good cellular adhesion

Needles in haystacks: using fast-response LA chambers and ICP-TOF-MS to identify asbestos fibres in malignant mesothelioma models

Malignant mesothelioma is an aggressive cancer associated with exposure to asbestos. Diagnosis of mesothelioma and other related lung diseases remains elusive due to difficulties surrounding identification and quantification of asbestos fibres in lung tissue. This article presents a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method to identify asbestos fibres in cellular models of mesothelioma. Use of a high-speed laser ablation system enabled rapid imaging of the samples with a lateral resolution of 3 μm, whilst use of a prototype time-of-flight ICP-MS provided pseudo-simultaneous detection of the elements between mass 23 (Na) and mass 238 (U). Three forms of asbestos fibre (actinolite, amosite and crocidolite) were distinguished from a non-asbestos control (wollastonite) based on their elemental profile, which demonstrated that LA-ICP-MS could be a viable technique for identification of asbestos fibres in clinical research samples

CFHT Legacy Ultraviolet Extension (CLUE): Witnessing Galaxy Transformations up to 7 Mpc from Rich Cluster Cores

Using the optical data from the Wide component of the CFHT Legacy Survey, and new ultraviolet data from GALEX, we study the colours and specific star formation rates (SSFR) of ~100 galaxy clusters at 0.16<z<0.36, over areas extending out to radii of r~7Mpc. We use a multicolour, statistical background subtraction method to study the galaxy population at this radius; thus our results pertain to those galaxies which constitute an excess over the average field density. We find that the average SSFR, and its distribution, of the star-forming galaxies (with SFR>0.7 M_sun/yr at z~0.2 and SFR>1.2 M_sun/yr at z~0.3) have no measurable dependence on the cluster-centric radius, and are consistent with the field values. However, the fraction of galaxies with SFR above these thresholds, and the fraction of optically blue galaxies, are lower for the overdense galaxy population in the cluster outskirts compared with the average field value, at all stellar masses M*>10^{9.8} M_sun and at all radii out to at least 7Mpc. Most interestingly, the fraction of blue galaxies that are forming stars at a rate below our UV detection limit is much higher in all radial bins around our cluster sample, compared with the general field value. This is most noticeable for massive galaxies M*>10^{10.7} M_sun; while almost all blue field galaxies of this mass have detectable star formation, this is true for less than 20% of the blue cluster galaxies, even at 7Mpc from the cluster centre. Our results support a scenario where galaxies are pre-processed in locally overdense regions, in a way that reduces their SFR below our UV detection limit, but not to zero.Comment: MNRAS accepte