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The mitochondrial electron transport chain (mETC) and F 1 F o -ATP synthase are of central importance for energy and metabolism in eukaryotic cells. The Apicomplexa, important pathogens of humans causing diseases such as toxoplasmosis and malaria, depend on their mETC in every known stage of their complicated life cycles. Here, using a complexome profiling proteomic approach, we have characterised the Toxoplasma mETC complexes and F 1 F o -ATP synthase. We identified and assigned 60 proteins to complexes II, IV and F 1 F o -ATP synthase of Toxoplasma , of which 16 have not been identified previously. Notably, our complexome profile elucidates the composition of the Toxoplasma complex III, the target of clinically used drugs such as atovaquone. We identified two new homologous subunits and two new parasite-specific subunits, one of which is broadly conserved in myzozoans. We demonstrate all four proteins are essential for complex III stability and parasite growth, and show their depletion leads to decreased mitochondrial potential, supporting their assignment as complex III subunits. Our study highlights the divergent subunit composition of the apicomplexan mETC and F 1 F o -ATP synthase complexes and sets the stage for future structural and drug discovery studies.

A central current debate in community ecology concerns the relative importance of deterministic versus stochastic processes underlying community structure. However, the concept of stochasticity presents several profound philosophical, theoretical and empirical challenges, which we address here. The philosophical argument that nothing in nature is truly stochastic can be met with the following operational concept of neutral stochasticity in community ecology: change in the composition of a community (i.e. community dynamics) is neutrally stochastic to the degree that individual demographic events – birth, death, immigration, emigration – which cause such changes occur at random with respect to species identities. Empirical methods for identifying the stochastic component of community dynamics or structure include null models and multivariate statistics on observational species-by-site data (with or without environmental or trait data), and experimental manipulations of 'stochastic' species colonization order or relative densities and frequencies of competing species. We identify the fundamental limitations of each method with respect to its ability to allow inferences about stochastic community processes. Critical future needs include greater precision in articulating the link between results and ecological inferences, a comprehensive theoretical assessment of the interpretation of statistical analyses of observational data, and experiments focusing on community size and on natural variation in species colonization order.

Background The objective of this systematic review was to examine for the first time the associations between sleep duration and a broad range of health indicators in children aged 0 to 4 years. Methods Electronic databases were searched with no limits on date or study design. Included studies (published in English or French) were peer-reviewed and met the a priori determined population (apparently healthy children aged 1 month to 4.99 years), intervention/exposure/comparator (various sleep durations), and outcome criteria (adiposity, emotional regulation, cognitive development, motor development, growth, cardiometabolic health, sedentary behaviour, physical activity, quality of life/well-being, and risks/injuries). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Due to high levels of heterogeneity across studies, narrative syntheses were employed. Results A total of 69 articles/studies (62 unique samples) met inclusion criteria. Data across studies included 148,524 unique participants from 23 countries. The study designs were randomized trials ( n  = 3), non-randomized interventions ( n  = 1), longitudinal studies ( n  = 16), cross-sectional studies ( n  = 42), or longitudinal studies that also reported cross-sectional analyses ( n  = 7). Sleep duration was assessed by parental report in 70% of studies ( n  = 48) and was measured objectively (or both objectively and subjectively) in 30% of studies ( n  = 21). Overall, shorter sleep duration was associated with higher adiposity (20/31 studies), poorer emotional regulation (13/25 studies), impaired growth (2/2 studies), more screen time (5/5 studies), and higher risk of injuries (2/3 studies). The evidence related to cognitive development, motor development, physical activity, and quality of life/well-being was less clear, with no indicator showing consistent associations. No studies examined the association between sleep duration and cardiometabolic biomarkers in children aged 0 to 4 years. The quality of evidence ranged from “very low” to “high” across study designs and health indicators. Conclusions Despite important limitations in the available evidence, longer sleep duration was generally associated with better body composition, emotional regulation, and growth in children aged 0 to 4 years. Shorter sleep duration was also associated with longer screen time use and more injuries. Better-quality studies with stronger research designs that can provide information on dose-response relationships are needed to inform contemporary sleep duration recommendations.

The mitochondrial electron transport chain (mETC) is a series of membrane embedded enzymatic complexes critical for energy conversion and mitochondrial metabolism. In commonly studied eukaryotes, including humans and animals, complex II, also known as succinate dehydrogenase (SDH), is an essential four-subunit enzyme that acts as an entry point to the mETC, by harvesting electrons from the TCA cycle. Apicomplexa are pathogenic parasites with significant impact on human and animal health. The phylum includes Toxoplasma gondii which can cause fatal infections in immunocompromised people. Most apicomplexans, including Toxoplasma , rely on their mETC for survival, yet SDH remains largely understudied. Previous studies pointed to a divergent apicomplexan SDH with nine subunits proposed for the Toxoplasma complex, compared to four in humans. While two of the nine are homologs of the well-studied SDHA and B, the other seven have no homologs in SDHs of other systems. Moreover, SDHC and D, that anchor SDH to the membrane and participate in substrate bindings, have no homologs in Apicomplexa. Here, we validated five of the seven proposed subunits as bona fide SDH components and demonstrated their importance for SDH assembly and activity. We further find that all five subunits are important for parasite growth, and that disruption of SDH impairs mitochondrial respiration and results in spontaneous initiation of differentiation into bradyzoites. Finally, we provide evidence that the five subunits are membrane bound, consistent with their potential role in membrane anchoring, and we demonstrate that a DY motif in one of them, SDH10, is essential for complex formation and function. Our study confirms the divergent composition of Toxoplasma SDH compared to human, and starts exploring the role of the lineage-specific subunits in SDH function, paving the way for future mechanistic studies.

Affective touch is a crucial element of early human development, social bonding, and emotional support. Technically and socially difficult to study, it has received little research attention. Our approach employs animal models instantiated by the Haptic Creature, a touch-centric social robot. In this paper, we examine how humans communicate emotional state through touch to the Haptic Creature and their expectations of its reactions. A user study is presented where participants selected and performed gestures they would likely use when conveying nine different emotions to the Haptic Creature. We report a touch dictionary compiled for our research; the gestures participants chose from it; and video analysis of their enactment. Our principal findings regard patterns of gesture use for emotional expression; physical properties of the likely gestures; expectations for the Haptic Creature’s response to mirror the emotion communicated; and analysis of the human’s higher intent in communication. From the latter finding, we present five tentative categories of “intent” that overlap emotion states: protective , comforting , restful , affectionate , and playful . These results can help inform the future design of social robots by illuminating details of one direction in affective touch interactions.

Neural synchronization is a mechanism whereby functionally specific brain regions establish transient networks for perception, cognition, and action. Direct addition of weak noise (fast random fluctuations) to various neural systems enhances synchronization through the mechanism of stochastic resonance (SR). Moreover, SR also occurs in human perception, cognition, and action. Perception, cognition, and action are closely correlated with, and may depend upon, synchronized oscillations within specialized brain networks. We tested the hypothesis that SR-mediated neural synchronization occurs within and between functionally relevant brain areas and thus could be responsible for behavioral SR. We measured the 40-Hz transient response of the human auditory cortex to brief pure tones. This response arises when the ongoing, random-phase, 40-Hz activity of a group of tuned neurons in the auditory cortex becomes synchronized in response to the onset of an above-threshold sound at its \"preferred\" frequency. We presented a stream of near-threshold standard sounds in various levels of added broadband noise and measured subjects' 40-Hz response to the standards in a deviant-detection paradigm using high-density EEG. We used independent component analysis and dipole fitting to locate neural sources of the 40-Hz response in bilateral auditory cortex, left posterior cingulate cortex and left superior frontal gyrus. We found that added noise enhanced the 40-Hz response in all these areas. Moreover, added noise also increased the synchronization between these regions in alpha and gamma frequency bands both during and after the 40-Hz response. Our results demonstrate neural SR in several functionally specific brain regions, including areas not traditionally thought to contribute to the auditory 40-Hz transient response. In addition, we demonstrated SR in the synchronization between these brain regions. Thus, both intra- and inter-regional synchronization of neural activity are facilitated by the addition of moderate amounts of random noise. Because the noise levels in the brain fluctuate with arousal system activity, particularly across sleep-wake cycles, optimal neural noise levels, and thus SR, could be involved in optimizing the formation of task-relevant brain networks at several scales under normal conditions.

During seed germination, iron (Fe) stored in vacuoles is exported by the redundant NRAMP3 and NRAMP4 transporter proteins. A double nramp3 nramp4 mutant is unable to mobilize Fe stores and does not develop in the absence of external Fe. We used RNA sequencing to compare gene expression in nramp3 nramp4 and wild type during germination and early seedling development. Even though sufficient Fe was supplied, the Fe-responsive transcription factors bHLH38, 39, 100, and 101 and their downstream targets FRO2 and IRT1 mediating Fe uptake were strongly upregulated in the nramp3 nramp4 mutant. Activation of the Fe deficiency response was confirmed by increased ferric chelate reductase activity in the mutant. At early stages, genes important for chloroplast redox control (FSD1 and SAPX), Fe homeostasis (FER1 and SUFB), and chlorophyll metabolism (HEMA1 and NYC1) were downregulated, indicating limited Fe availability in plastids. In contrast, expression of FRO3, encoding a ferric reductase involved in Fe import into the mitochondria, was maintained, and Fe-dependent enzymes in the mitochondria were unaffected in nramp3 nramp4. Together, these data show that a failure to mobilize Fe stores during germination triggered Fe deficiency responses and strongly affected plastids, but not mitochondria.

Background People who are homeless experience an increased prevalence of traumatic events, including childhood trauma, trauma related to being homeless, and structural trauma. It is important to consider trauma in the delivery of health services for this population. Using a trauma-informed care approach is one way to ensure that a service or program takes into consideration the effects of trauma. The aims of this study are to describe how best to design a service to engage people experiencing homelessness in a trauma-focused therapy as well as detail what trauma-informed care would look like in this setting. Methods We conducted a series of qualitative interviews about how to design a trauma-informed trauma therapy for people experiencing homelessness and their perspectives on different principles of trauma-informed care. Thematic analysis was used to identify, analyze and report themes identified in the data. Results We conducted 12 in-depth interviews (8 women, 4 men) with people who were currently peer support workers with lived experience of trauma and homelessness. We identified themes to design a trauma-informed service including low-barrier access, communication strategies, meeting people’s needs, and how to engage and retain people in the service. We also identified themes related to how people with lived experience understand the principles of trauma informed care. Discussion The findings from this study provide insight and practical recommendations for designing and implementing a trauma-informed therapy tailored for people experiencing homelessness. The findings here shed light on the lived experience perspective of trauma-informed care principles, adding nuance to our understanding of what it means to be trauma-informed.

To describe longitudinal trends in long-term non-invasive ventilation (NIV) use in children including changes in clinical characteristics, NIV technology, and outcomes. This was a multicenter retrospective cohort of all children started on long-term NIV from 2005 to 2014. All children 0 to 18 years who used NIV continuously for at least 3 months were included. Measures and main outcomes were: 1) Number of children starting NIV; 2) primary medical condition; 3) medical complexity defined by number of comorbidities, surgeries and additional technologies; 4) severity of sleep disordered breathing measured by diagnostic polysomnography; 5) NIV technology and use; 6) reasons for NIV discontinuation including mortality. Data were divided into equal time periods for analysis. A total of 622 children were included in the study. Median age at NIV initiation was 7.8 years (range 0-18 years). NIV incidence and prevalence increased five and three-fold over the 10-year period. More children with neurological and cardio-respiratory conditions started NIV over time, from 13% (95%CI, 8%-20%) and 6% (95%CI, 3%-10%) respectively in 2005-2008 to 23% (95%CI, 18%-28%) and 9% (95%CI, 6%-14%, p = 0.008) in 2011-2014. Medical complexity and severity of the sleep-disordered breathing did not change over time. Overall, survival was 95%; mortality rates, however, rose from 3.4 cases (95% CI, 0.5-24.3) to 142.1 (95% CI 80.7-250.3, p<0.001) per 1000 children-years between 2005-2008 and 2011-2014. Mortality rates differed by diagnostic category, with higher rates in children with neurological and cardio-respiratory conditions. As demonstrated in other centers, there was a significant increase in NIV prevalence and incidence rate. There was no increase in medical complexity or severity of the breathing abnormalities of children receiving long-term NIV over time. The mortality rate increased over time, maybe attributable to increased use of NIV for children with neurological and cardio-respiratory conditions.

Aims/hypothesis Short-term dietary studies suggest that high-protein diets can enhance weight loss and improve glycaemic control in people with type 2 diabetes. However, the long-term effects of such diets are unknown. The aim of this study was to determine whether high-protein diets are superior to high-carbohydrate diets for improving glycaemic control in individuals with type 2 diabetes. Methods Overweight/obese individuals (BMI 27-40 kg/m²) with type 2 diabetes (HbA₁c 6.5-10%) were recruited for a 12 month, parallel design, dietary intervention trial conducted at a diabetes specialist clinic (Melbourne, VIC, Australia). Of the 108 initially randomised, 99 received advice to follow low-fat (30% total energy) diets that were either high in protein (30% total energy, n = 53) or high in carbohydrate (55% total energy, n = 46). Dietary assignment was done by a third party using computer-generated random numbers. The primary endpoint was change in HbA₁c. Secondary endpoints included changes in weight, lipids, blood pressure, renal function and calcium loss. Study endpoints were assessed blinded to the diet group, but the statistical analysis was performed unblinded. This study used an intention-to-treat model for all participants who received dietary advice. Follow-up visits were encouraged regardless of dietary adherence and last measurements were carried forward for study non-completers. Results Ninety-nine individuals were included in the analysis (53 in high protein group, 46 in high carbohydrate group). HbA₁c decreased in both groups over time, with no significant difference between groups (mean difference of the change at 12 months; 0.04 [95% CI −0.37, 0.46]; p = 0.44). Both groups also demonstrated decreases over time in weight, serum triacylglycerol and total cholesterol, and increases in HDL-cholesterol. No differences in blood pressure, renal function or calcium loss were seen. Conclusions/interpretation These results suggest that there is no superior long-term metabolic benefit of a high-protein diet over a high-carbohydrate in the management of type 2 diabetes. Trial registration ACTRN12605000063617 (www.anzctr.org.au). Funding This study was funded by a nutritional research grant from Meat and Livestock Australia (MLA). J.E. Shaw is supported by NHMRC Fellowship 586623.