Synthesis and properties of macroporous thin films : towards multifunctional photonic crystals

Imperial Users onl

Impaired burrowing is the most prominent behavioral deficit of aging htau mice

htau mice are deficient of murine tau but express all six human tau isoforms, leading to gradual tau misprocessing and aggregation in brain areas relevant to Alzheimer's disease. Whilst histopathological changes in htau mice have been researched in the past, we focused here on functional consequences of human tau accumulation. htau mice and their background controls - murine tau knock-out (mtau-/-) and C57Bl/6J mice - underwent a comprehensive trial battery to investigate species-specific behaviour, locomotor activity, emotional responses, exploratory traits, spatial and recognition memory as well as acquisition, retention and extinction of contextual fear at two-, four-, six-, nine- and twelve-months-of-age. In htau mice, tau pathology was already present at two-months-of-age, whereas deficits in food burrowing and spatial working memory were first noted at four-months-of-age. At later stages the presence of human tau on a murine tau knockout background appeared to guard cognitive performance; as mtau-/- but not htau mice differed from C57Bl/6J mice in the food burrowing, spontaneous alternation and object discrimination tasks. Aging mtau-/- mice also exhibited increased body mass and locomotor activity. This data highlights that reduced food burrowing performance was the most robust aspect of the htau phenotype with ageing. htau and mtau-/-deficits in food burrowing pointed at the necessity of intact tau systems for daily life activities. Whilst some htau and mtau-/- deficits overlap, age differences between the two genotypes may reflect distinct functional effects and compared to C57Bl/6J mice, the htau phenotype appeared stronger than the mtau-/- phenotype at young ages but milder with ageing

A Novel HDL-Mimetic Peptide HM-10/10 Protects RPE and Photoreceptors in Murine Models of Retinal Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO3), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration

A state of delirium: deciphering the effect of inflammation on tau pathology in Alzheimer's disease

Alzheimer's disease (AD), the predominant form of dementia, is highly correlated with the abnormal hyperphosphorylation and aggregation of tau. Immune responses are key drivers of AD and how they contribute to tau pathology in human disease remains largely unknown. This review summarises current knowledge on the association between inflammatory processes and tau pathology. While, preclinical evidence suggests that inflammation can indeed induce tau hyperphosphorylation at both pre- and post-tangles epitopes, a better understanding of whether this develops into advanced pathological features such as neurofibrillary tangles is needed. Microglial cells, the immune phagocytes in the central nervous system, appear to play a key role in regulating tau pathology, but the underlying mechanisms are not fully understood. Their activation can be detrimental via the secretion of pro-inflammatory mediators, particularly interleukin-1β, but also potentially beneficial through phagocytosis of extracellular toxic tau oligomers. Nevertheless, anti-inflammatory treatments in animal models were found protective, but whether or not they affect microglial phagocytosis of tau species is unknown. However, one major challenge to our understanding of the role of inflammation in the progression of tau pathology is the preclinical models used to address this question. They mostly rely on the use of septic doses of lipopolysaccharide that do not reflect the inflammatory conditions experienced AD patients, questioning whether the impact of inflammation on tau pathology in these models is dose-dependent and relevant to the human disease. The use of more translational models of inflammation corroborated with verification in clinical investigations are necessary to progress our understanding of the interplay between inflammation and tau pathology

Increasing Tau 4R Tau Levels Exacerbates Hippocampal Tau Hyperphosphorylation in the hTau Model of Tauopathy but Also Tau Dephosphorylation Following Acute Systemic Inflammation

Copyright © 2020 Barron, Gartlon, Dawson, Atkinson and Pardon. Inflammation is considered a mechanistic driver of Alzheimer's disease, thought to increase tau phosphorylation, the first step to the formation of neurofibrillary tangles (NFTs). To further understand how inflammation impacts the development of tau pathology, we used (hTau) mice, which express all six, non-mutated, human tau isoforms, but with an altered ratio of tau isoforms favoring 3R tau due to the concomitant loss of murine tau (mTau) that is predominantly 4R. Such an imbalance pattern has been related to susceptibility to NFTs formation, but whether or not this also affects susceptibility to systemic inflammation and related changes in tau phosphorylation is not known. To reduce the predominance of 3R tau by increasing 4R tau availability, we bred hTau mice on a heterozygous mTau background and compared the impact of systemic inflammation induced by lipopolysaccharide (LPS) in hTau mice hetero- or homozygous mTau knockout. Three-month-old male wild-type (Wt), mTau+/-, mTau-/-, hTau/mTau+/-, and hTau/mTau-/- mice were administered 100, 250, or 330 μg/kg of LPS or its vehicle phosphate buffer saline (PBS) [intravenously (i.v.), n = 8-9/group]. Sickness behavior, reflected by behavioral suppression in the spontaneous alternation task, hippocampal tau phosphorylation, measured by western immunoblotting, and circulating cytokine levels were quantified 4 h after LPS administration. The persistence of the LPS effects (250 μg/kg) on these measures, and food burrowing behavior, was assessed at 24 h post-inoculation in Wt, mTau+/-, and hTau/mTau+/- mice (n = 9-10/group). In the absence of immune stimulation, increasing 4R tau levels in hTau/mTau+/- exacerbated pS202 and pS396/404 tau phosphorylation, without altering total tau levels or worsening early behavioral perturbations characteristic of hTau/mTau-/- mice. We also show for the first time that modulating 4R tau levels in hTau mice affects the response to systemic inflammation. Behavior was suppressed in all genotypes 4 h following LPS administration, but hTau/mTau+/- exhibited more severe sickness behavior at the 100 μg/kg dose and a milder behavioral and cytokine response than hTau/mTau-/- mice at the 330 μg/kg dose. All LPS doses decreased tau phosphorylation at both epitopes in hTau/mTau+/- mice, but pS202 levels were selectively reduced at the 100 μg/kg dose in hTau/mTau-/- mice. Behavioral suppression and decreased tau phosphorylation persisted at 24 h following LPS administration in hTau/mTau+/- mice

The influence of cultural-linguistic background on family and SLP perceptions of pragmatic communication skills following right-hemisphere stroke

Pragmatic communication abilities are frequently impaired in persons who have had a right-hemisphere stroke. Speech-language pathologists (SLPs) often supplement their own pragmatic communication assessment ratings with ratings from the patients’ family members. These ratings, by both SLPs and family members, are likely to be biased by their respective cultural-linguistic backgrounds. The pragmatic communication ratings of Caucasian SLPs were compared with Caucasian and African-American families’ ratings for patients following right-hemisphere stroke. SLPs’ ratings agreed more closely with Caucasian families, but not to a degree that reached statistical significance. The nature of this agreement regarding specific pragmatic communication behaviors, as well as clinical implications, are discussed

Older UK sheltered housing tenants’ perceptions of wellbeing and their usage of hospital services

The aim of this study was to examine sheltered housing tenants’ views of health and wellbeing, the strategies they adopted to support their wellbeing and their use of health and social care services through a Health Needs Assessment. Sheltered housing in the UK is a form of service-integrated housing for people, predominantly over 60. The study used a parallel, three-strand mixed method approach to encompass the tenants’ perceptions of health and wellbeing (n=96 participants), analysis of the service’s health and wellbeing database and analysis of emergency and elective hospital admissions (n= 978 tenant data sets for the period January to December 2012). Tenants’ perceptions of wellbeing were seen to reinforce much of the previous work on the subject with strategies required to sustain social, community, physical, economic, environmental, leisure, emotional and spiritual dimensions. Of the tenants’ self-reported chronic conditions, arthritis, heart conditions and breathing problems were identified as their most common health concerns. Hospital admission data indicated that 43% of the tenant population was admitted to hospital (886 admissions) with 53% emergency and 47% elective admissions. The potential cost of emergency as opposed to elective admissions was substantial. The mean length of stay for emergency admissions was 8.2 days (median 3.0 days). While elective hospital admission had a mean length of stay of 1.0 day (median 0.0 days). These results suggest the need for multi-professional health, social care and housing services interventions to facilitate sheltered housing tenants’ aspirations and support their strategies to live well and independently in their own homes. Equally there is a need to increase tenants’ awareness of health conditions and their management; the importance of services which offer facilitation, resources and support and the key role played by prevention and reablement

Examining the association between elementary students lexcio-syntactic writingfeatures and cognitive-motivational profiles using Natural Language Processing

Natural language processing (NLP) provides an innovative avenue to understand and explore human language content,yet minimal research has utilized it to classify students literacy, cognition, or motivation. This study investigated theassociation between grade 4-6 students (n = 143) writing and their cognitive-motivational profiles (CMPs) based on theirself-regulated learning, locus of control, writing self-efficacy, and goal-orientation. LPA (Mplus 7.4) results indicated atwo-class CMP solution with predominantly positive or negative CMPs. Using NLP, 404 lexico-syntactic writing featureswere extracted from students writing. Random forest with 10-fold cross-validation was implemented in Weka 3.8 (withSMOTE to equate class instances) to accurately (93%) classify students CMPs (class 1 True Positive Rate (TPR) = .942;class 2 TPR = .925) based on the NLP-processed lexico-syntactic writing features. These results highlight the potentialfor machine learning to analyze students writing and accurately classify learner profiles to provide formative feedback andcustomized interventions