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\"Inspired by the story of John Walker Lindh, the \"American Taliban,\" Whiting Award winner John Wray explores the circumstances that could impel a young American to exchange identity, home, and to become an Islamist militant\"-- Provided by publisher.
Book
Kenneth C. Holmes (1934–2021)
Obituary for Kenneth C. Holmes Obituary for Kenneth C. Holmes
Journal Article
Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder
Background
Autism spectrum disorders (ASDs) are complex, pervasive, and heterogeneous neurodevelopmental conditions with varying trajectories, significant male bias and largely unknown etiology. However, an understanding of the biological mechanisms driving pathophysiology is evolving. Immune system aberrations, as identified through cytokine profiles, are believed to have a role in ASD. Altered cytokine levels may facilitate identification of ASD subtypes as well as provide biological markers of response to effective treatments. Research exploring the relationship between cytokine profiles and ASD symptoms is, however, in its infancy. The objective of this study was to explore relationships between cytokine levels and the severity of ASD and other clinical traits.
Methods
Multiplex assay techniques were used to measure levels of 27 cytokines in plasma samples from a cohort of 144 children diagnosed with ASD.
Results
Overall, results showed a significant negative association between platelet-derived growth factor (PDGF)-BB, and the severity of ASD symptoms. Furthermore, a significant interaction with sex suggested a different immune profile for females compared to males. ASD symptom severity was negatively associated with levels of 4 cytokines, IL-1β, IL-8, MIP-1β, and VEGF, in females, but not in males.
Conclusions
Results of the present study suggest that an altered cytokine response or profile is associated with the severity of ASD-related symptoms, with sex a potential modifier of this relationship. Further research in larger populations which recognizes the importance of sex comparisons and longitudinal assessments are now required to extend and further describe the role of the immune system in ASD.
Journal Article
Crystal Structures of Human Cardiac β-myosin II S2-Δ Provide Insight into the Functional Role of the S2 Subfragment
Myosin II is the major component of the muscle thick filament. It consists of two N-terminal S1 subfragments (\"heads\") connected to a long dimeric coiled-coil rod. The rod is in itself twofold symmetric, but in the filament, the two heads point away from the filament surface and are therefore not equivalent. This breaking of symmetry requires the initial section of the rod, subfragment 2 (S2), to be relatively flexible. S2 is an important functional element, involved in various mechanisms by which the activity of smooth and striated muscle is regulated. We have determined crystal structures of the 126 N-terminal residues of 52 from human cardiac β-myosin II (S2-Δ), of both WT and the disease-associated E924K mutant. S2-Δ is a straight parallel dimeric coiled coil, but the N terminus of one chain is disordered in WT-52-Δ due to crystal contacts, indicative of unstable local structure. Bulky noncanonical side chains pack into a/d positions of S2-Δ's N terminus, leading to defined local asymmetry and axial stagger, which could induce nonequivalence of the S1 subfragments. Additionally, 52 possesses a conserved charge distribution with three prominent rings of negative potential within S2-Δ, the first of which may provide a binding interface for the \"blocked head\" of smooth muscle myosin in the OFF state. The observation that many disease-associated mutations affect the second negatively charged ring further suggests that charge interactions play an important role in regulation of cardiac muscle activity through myosin-binding protein C.
Journal Article
Early Moves: a protocol for a population-based prospective cohort study to establish general movements as an early biomarker of cognitive impairment in infants
IntroductionThe current diagnostic pathways for cognitive impairment rarely identify babies at risk before 2 years of age. Very early detection and timely targeted intervention has potential to improve outcomes for these children and support them to reach their full life potential. Early Moves aims to identify early biomarkers, including general movements (GMs), for babies at risk of cognitive impairment, allowing early intervention within critical developmental windows to enable these children to have the best possible start to life.Method and analysisEarly Moves is a double-masked prospective cohort study that will recruit 3000 term and preterm babies from a secondary care setting. Early Moves will determine the diagnostic value of abnormal GMs (at writhing and fidgety age) for mild, moderate and severe cognitive delay at 2 years measured by the Bayley-4. Parents will use the Baby Moves smartphone application to video their babies’ GMs. Trained GMs assessors will be masked to any risk factors and assessors of the primary outcome will be masked to the GMs result. Automated scoring of GMs will be developed through applying machine-based learning to the data and the predictive value for an abnormal GM will be investigated. Screening algorithms for identification of children at risk of cognitive impairment, using the GM assessment (GMA), and routinely collected social and environmental profile data will be developed to allow more accurate prediction of cognitive outcome at 2 years. A cost evaluation for GMA implementation in preparation for national implementation will be undertaken including exploring the relationship between cognitive status and healthcare utilisation, medical costs, health-related quality of life and caregiver burden.Ethics and disseminationEthics approval has been granted by the Medical Research Ethics Committee of Joondalup Health Services and the Health Service Human Research Ethics Committee (1902) of Curtin University (HRE2019-0739).Trial registration numberACTRN12619001422112.
Journal Article
Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial
To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3–8 years. Outcome measurement tools included monthly Global Behaviour Rating Scales, Additional Rating Scales of other symptoms by parents and therapists, and monthly completion of the Rescorla Language Development Survey. Compared with placebo, treatment with enzyme was not associated with clinically significant improvement in behaviour, food variety, gastrointestinal symptoms, sleep quality, engagement with therapist, or the Language Development Survey Vocabulary or Sentence Complexity Scores. A small statistically significant improvement on enzyme therapy was seen for the food variety scores. No clinically significant effect improvement of autism symptoms with enzyme use was shown with this trial, however, possible effects on improvement in food variety warrants further detailed investigation.
Journal Article
A “Bottom-Up” Approach to Aetiological Research in Autism Spectrum Disorders
Autism spectrum disorders (ASD) are currently diagnosed in the presence of impairments in social interaction and communication, and a restricted range of activities and interests. However, there is considerable variability in the behaviors of different individuals with an ASD diagnosis. The heterogeneity spans the entire range of IQ and language abilities, as well as other behavioral, communicative, and social functions. While any psychiatric condition is likely to incorporate a degree of heterogeneity, the variability in the nature and severity of behaviors observed in ASD is thought to exceed that of other disorders. The current paper aims to provide a model for future research into ASD subgroups. In doing so, we examined whether two proposed risk factors - low birth weight (LBW), and in utero exposure to selective serotonin reuptake inhibitors (SSRIs) - are associated with greater behavioral homogeneity. Using data from the Western Australian Autism Biological Registry, this study found that LBW and maternal SSRI use during pregnancy were associated with greater sleep disturbances and a greater number of gastrointestinal complaints in children with ASD, respectively. The findings from this \"proof of principle\" paper provide support for this \"bottom-up\" approach as a feasible method for creating homogenous groups.
Journal Article
The serine acetyltransferase gene family in Arabidopsis thaliana and the regulation of its expression by cadmium
Expression of the serine acetyltransferase (SAT) gene family from Arabidopsis thaliana was investigated in response to treatment with the heavy metal cadmium (Cd). A fourth member of the SAT gene family, Sat-106, was also cloned and the complete SAT gene family from A. thaliana is discussed. Northern analysis of the gene family revealed tissue-specific expression patterns for each isogene. A. thaliana plants grown under 50 microM CdCl2 for a 24 h time course were also used for northern analysis. Expression of all SAT genes was increased to some extent by Cd treatment. Sat-5 expression showed particularly high levels of induction in the leaves of treated plants and was chosen for study by in situ hybridisation. Sat-5 expression was induced in the root and stem cortex and the leaf lamella and trichomes in response to heavy metal stress. SAT and its product O-acetylserine have previously been shown to be implicated in the control of sulphate reduction and cysteine biosynthesis in plants. These results suggest that specific SAT isoforms have a role in increasing cysteine production under conditions of heavy-metal stress when increased biosynthesis of glutathione and phytochelatins is required for detoxification purposes.
Journal Article
