Methods for the relative quantitation of human plasma lipidome using liquid chromatography coupled with mass spectrometry using minimal sample manipulation.

Extraction protocols and liquid chromatography coupled with mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS) methods for the measurement of four lipid categories, namely glycerophospholipids, glycerolipids, sphingolipids and sterol lipids in human plasma, are described here. Step-by-step instructions are provided for the liquid-liquid extraction methods, including solution preparation and the non-endogenous lipid internal standards used. All instrumental conditions, chromatography columns and solutions required for the LC-MS and LC-MS/MS methods are also provided in detail.

Cumulative effects of multiple stressors impact an endangered seagrass population and fish communities.

Coastal ecosystems are becoming increasingly threatened by human activities and there is growing appreciation that management must consider the impacts of multiple stressors. Cumulative effects assessments (CEAs) have become a popular tool for identifying the distribution and intensity of multiple human stressors in coastal ecosystems. Few studies, however, have demonstrated strong correlations between CEAs and change in ecosystem condition, questioning its management use. Here, we apply a CEA to the endangered seagrass Posidonia australis in Pittwater, NSW, Australia, using spatial data on known stressors to seagrass related to foreshore development, water quality, vessel traffic and fishing. We tested how well cumulative effects scores explained changes in P. australis extent measured between 2005 and 2019 using high-resolution aerial imagery. A negative correlation between P. australis and estimated cumulative effects scores was observed (R2 = 22 %), and we identified a threshold of cumulative effects above which losses of P. australis became more likely. Using baited remote underwater video, we surveyed fishes over P. australis and non-vegetated sediments to infer and quantify how impacts of cumulative effects to P. australis extent would flow on to fish assemblages. P. australis contained a distinct assemblage of fish, and on non-vegetated sediments the abundance of sparids, which are of importance to fisheries, increased with closer proximity to P. australis. Our results demonstrate the negative impact of multiple stressors on P. australis and the consequences for fish biodiversity and fisheries production across much of the estuary. Management actions aimed at reducing or limiting cumulative effects to low and moderate levels will help conserve P. australis and its associated fish biodiversity and productivity.

The unprecedented Pacific Northwest heatwave of June 2021.

In late June 2021 a heatwave of unprecedented magnitude impacted the Pacific Northwest region of Canada and the United States. Many locations broke all-time maximum temperature records by more than 5 °C, and the Canadian national temperature record was broken by 4.6 °C, with a new record temperature of 49.6 °C. Here, we provide a comprehensive summary of this event and its impacts. Upstream diabatic heating played a key role in the magnitude of this anomaly. Weather forecasts provided advanced notice of the event, while sub-seasonal forecasts showed an increased likelihood of a heat extreme with lead times of 10-20 days. The impacts of this event were catastrophic, including hundreds of attributable deaths across the Pacific Northwest, mass-mortalities of marine life, reduced crop and fruit yields, river flooding from rapid snow and glacier melt, and a substantial increase in wildfires-the latter contributing to landslides in the months following. These impacts provide examples we can learn from and a vivid depiction of how climate change can be so devastating.

Is adolescent internet use a risk factor for the development of depression symptoms or vice-versa?

BACKGROUND: The extent to which digital media use by adolescents contributes to poor mental health, or vice-versa, remains unclear. The purpose of the present study is to clarify the strength and direction of associations between adolescent internet use and the development of depression symptoms using a longitudinal modeling approach. We also examine whether associations differ for boys and girls. METHODS: Data are drawn from (N = 1547) participants followed for the Quebec longitudinal Study of Child Development (QLSCD 1998-2020). Youth self-reported internet use in terms of the average hours of use per week at the ages of 13, 15, and 17. Youth also self-reported depression symptoms at the same ages. RESULTS: After testing sex-invariance, random intercepts cross-lagged panel models stratified by sex, revealed that internet use by girls was associated with significant within-person (time-varying) change in depression symptoms. Girl's internet use at age 13 was associated with increased depression symptoms at age 15 (ß = 0.12) and internet use at age 15 increased depression at age 17 (ß = 0.10). For boys, internet use was not associated with significant time varying change in depression symptoms. CONCLUSIONS: The present findings support the hypothesis that internet use by adolescents can represent a significant risk factor for the development of depressive symptoms, particularly in girls.

Comprehensive lipidome of human plasma using minimal sample manipulation by liquid chromatography coupled with mass spectrometry.

RATIONALE: The present work shows comprehensive chromatographic methods and MS conditions that have been developed based on the chemical properties of each lipid subclass to detect low-abundance molecular species. This study shows that the developed methods can detect low- and/or very-low-abundant lipids like phosphatidic acid (PA) in the glycerophospholipid (GP) method; dihydroceramide (dhCer) and dihydrosphingosine/sphinganine (dhSPB) in the sphingolipid (SP) method; and lysophosphatidic acid (LPA), LPI, LPG and sphingosine-1-phosphate (SPBP) in the lysolipid method. METHODS: An optimised method for the extraction of lysolipids in plasma is used in addition to Folch extraction. Then, four chromatographic methods coupled with mass spectrometry using targeted and untargeted approaches are described here. Three of the methods use a tertiary pumping system to enable the inclusion of a gradient for analyte separation (pumps A and B) and an isocratic wash (pump C). This wash solution elutes interfering compounds that could cause background signal in the subsequent injections, reducing column lifetime. RESULTS: Semi-quantitative values for 37 lipid subclasses are reported for a plasma sample (NIST SRM 1950). Furthermore, the methods presented here enabled the identification of 338 different lipid molecular species for GPs (mono- and diacyl-phospholipds), SPs, sterols and glycerolipids. The methods have been validated, and the reproducibility is presented here. CONCLUSIONS: The comprehensive analysis of the lipidome addressed here of glycerolipids, GPs, sterols and SPs is in good agreement with previously reported results, in the NIST SRM 1950 sample, by other laboratories. Ten lipid subclasses LPS, LPI, alkyl-lysophosphatidic acid/alkenyl-lysophosphatidic acid, alkyl-lysophosphatidylethanolamine/alkenyl-lysophosphatidylethanolamine, dhCer (d18:0), SPB (d18:1), dhSPB (d18:0) and SPBP (d18:2) have been detected using this comprehensive method and are uniquely reported here.

Landmark-dependent Navigation Strategy Declines across the Human Life-Span: Evidence from Over 37,000 Participants.

Humans show a remarkable capacity to navigate various environments using different navigation strategies, and we know that strategy changes across the life span. However, this observation has been based on studies of small sample sizes. To this end, we used a mobile app-based video game (Sea Hero Quest) to test virtual navigation strategies and memory performance within a distinct radial arm maze level in over 37,000 participants. Players were presented with six pathways (three open and three closed) and were required to navigate to the three open pathways to collect a target. Next, all six pathways were made available and the player was required to visit the pathways that were previously unavailable. Both reference memory and working memory errors were calculated. Crucially, at the end of the level, the player was asked a multiple-choice question about how they found the targets (i.e., a counting-dependent strategy vs. a landmark-dependent strategy). As predicted from previous laboratory studies, we found the use of landmarks declined linearly with age. Those using landmark-based strategies also performed better on reference memory than those using a counting-based strategy. These results extend previous observations in the laboratory showing a decreased use of landmark-dependent strategies with age.

Associations Between Video Game Engagement and ADHD Symptoms in Early Adolescence.

OBJECTIVE: We aim to investigate the direction of causality of the association between adolescent video game playing and later development of ADHD symptoms using a population-based sample of Canadian Youth. METHOD: The present study is based on longitudinal cohort data (N = 1,467). Youth self-reported weekly hours of video game playing as well as ADHD symptoms at both 12 and 13 years of age. RESULTS: Cross-lagged panel model were estimated to examine how adolescent video game playing prospectively contributes to ADHD symptoms while simultaneously considering how adolescent ADHD symptoms may prospectively contribute to videogame playing. Analyses revealed a significant positive association between adolescent video games playing at age 12 and ADHD symptoms at age 13. Youth ADHD symptoms at age 12 did not predict video game use at age 13. CONCLUSION: Our results help clarify the direction of causality of the association between video game playing and ADHD symptoms and provide evidence that video game playing can represent a risk factor for the development of attention problems in early adolescence.

Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans.

To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane's phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-ß)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal.

The BDNF val66met polymorphism is associated with decreased use of landmarks and decreased fMRI activity in the hippocampus during virtual navigation.

People can navigate in a new environment using multiple strategies dependent on different memory systems. A series of studies have dissociated between hippocampus-dependent 'spatial' navigation and habit-based 'response' learning mediated by the caudate nucleus. The val66met polymorphism of the brain-derived neurotrophic factor (BDNF) gene leads to decreased secretion of BDNF in the brain, including the hippocampus. Here, we aim to investigate the role of the BDNF val66met polymorphism on virtual navigation behaviour and brain activity in healthy older adults. A total of 139 healthy older adult participants (mean age = 65.8 ± 4.4 years) were tested in this study. Blood samples were collected, and BDNF val66met genotyping was performed. Participants were divided into two genotype groups: val homozygotes and met carriers. Participants were tested on virtual dual-solution navigation tasks in which they could use either a hippocampus-dependent spatial strategy or a caudate nucleus-dependent response strategy to solve the task. A subset of the participants (n = 66) were then scanned in a 3T functional magnetic resonance imaging (fMRI) scanner while engaging in another dual-solution navigation task. BDNF val/val individuals and met carriers did not differ in learning performance. However, the two BDNF groups differed in learning strategy. BDNF val/val individuals relied more on landmarks to remember target locations (i.e., increased use of flexible spatial learning), while met carriers relied more on sequences and patterns to remember target locations (i.e., increased use of inflexible response learning). Additionally, BDNF val/val individuals had more fMRI activity in the hippocampus compared with BDNF met carriers during performance on the navigation task. This is the first study to show in older adults that BDNF met carriers use alternate learning strategies from val/val individuals and to identify differential brain activation of this behavioural difference between the two groups.

Object expectations alter information use during visual recognition.

Prior expectations influence how we perceive and recognize objects. However, how they do so remains unclear, especially in the case of real-world complex objects. Expectations of objects may affect which features are used to recognize them subsequently. In this study, we used reverse correlation to reveal with high precision how the use of information across time is modulated by real-world object expectations in a visual recognition task. We show that coarse information leads to accurate responses earlier when an object is expected, indicating that observers use diagnostic features earlier in this situation. We also demonstrate an increased variability in the use of coarse information depending on the expected object, indicating that observers adopt a more specialized recognition strategy when they expect a specific object. In summary, our results reveal potential mechanisms underlying the effect of expectations on the recognition of complex objects.

Differential stress response to psychological and physical stressors in children using spatial versus response-dependent navigation strategies.

Previous work from our lab has shown that basal cortisol levels are different between healthy young adults who spontaneously use caudate nucleus-dependent response strategies compared to young adults who use hippocampus-dependent spatial navigation strategies. Young adults who use caudate nucleus dependent strategies display lower basal cortisol levels compared to those who use hippocampus-dependent strategies. In the current study, we assessed navigation strategies in children using a virtual navigation task and measured cortisol at baseline as well as cortisol reactivity to both a psychological and to a physical stressor. Replicating what is observed in adults, we found that children who used caudate nucleus-dependent navigation strategies displayed lower cortisol levels at baseline compared to those who used hippocampus-dependent strategies. The psychological stressor, knowledge that a blood draw would be performed by a nurse, caused a significant increase in cortisol uniquely in response learners. The physical stressor, the actual blood draw, produced a significant increase in cortisol amongst spatial learners that was then comparable to levels observed in response learners. Lower baseline cortisol and higher cortisol psychological stress response observed amongst children who used response strategies may therefore reflect early biological changes during development which may have an impact later in life when considering risk for neuropsychiatric disorders.

Hook-shaped enterolith and secondary cachexia in a free-living grey nurse shark (Carcharias taurus, Rafinesque 1810).

The carcass of a critically endangered, juvenile female grey nurse shark (Carcharias taurus, Rafinesque 1810) was recovered from a south-eastern Australian beach and subjected to necropsy. The 1.98-m-long shark exhibited advanced cachexia with its total weight (19.0 kg) and liver weight (0.37 kg) reduced by 60% and 89%, respectively, compared with a healthy individual of the same length. Marked tissue decomposition was evident preventing histopathology and identification of a definitive cause of death. At necropsy, the abdominal organs were abnormally displaced and showed marked reductions in size compared with a healthy individual of the same size. Importantly, a hook-shaped enterolith (HSE), with a rough surface and cream in colour, was found within the spiral valve of the intestine and is to the authors' knowledge, the first description of such in any marine animal. X-ray diffractometry showed that the HSE comprised the minerals monohydrocalcite (Ca[CO3].H2O; ~70 wt%) and struvite (Mg [NH4 ] [PO4 ]. [H2 O]6 ; ~30 wt%). A CT scan showed concentric lamellate concretions around a 7/o offset J-hook that formed the nidus of the HSE. Nylon fishing line attached to the hook exited the HSE and was evident in the abdominal cavity through a perforation in the intestinal wall where the posterior intestinal artery merges. The most parsimonious reconstruction of events leading to enterolithiasis and secondary cachexia in this shark was the consumption of a hooked fish and subsequent hook migration causing perforations of the cardiac stomach wall followed by the thin, muscular wall of the apposed, sub-adjacent intestine.

Opposing effects of cortisol on learning and memory in children using spatial versus response-dependent navigation strategies.

Previous studies showed that healthy young adults who spontaneously use caudate nucleus-dependent strategies on a virtual navigation task, have significantly lower basal levels of cortisol compared with adults who use hippocampus-dependent spatial navigation strategies. In the current paper, we assessed the relation between basal cortisol levels and learning using a virtual navigation task in children. We show that basal cortisol level has a differential effect on learning and memory between children using spatial and response navigation strategies. Specifically, cortisol was found to be beneficial for learning performance in children using spatial strategies, such that higher levels of cortisol were associated with more efficient learning in a virtual maze. In contrast, cortisol had a deleterious effect on learning the virtual maze in children using response strategies, such that higher cortisol levels were associated with increased spatial working memory errors. Based on these results, individual differences in navigation strategy could help explain contradictory results in the literature showing that cortisol can have either a positive or negative association with learning and memory performance.

The effects of short-term musical training on the neural processing of speech-in-noise in older adults.

Experienced musicians outperform non-musicians in understanding speech-in-noise (SPIN). The benefits of lifelong musicianship endure into older age, where musicians experience smaller declines in their ability to understand speech in noisy environments. However, it is presently unknown whether commencing musical training in old age can also counteract age-related decline in speech perception, and whether such training induces changes in neural processing of speech. Here, we recruited older adult non-musicians and assigned them to receive a short course of piano or videogame training, or no training. Participants completed two sessions of functional Magnetic Resonance Imaging where they performed a SPIN task prior to and following training. While we found no direct benefit of musical training upon SPIN perception, an exploratory Region of Interest analysis revealed increased cortical responses to speech in left Middle Frontal and Supramarginal Gyri which correlated with changes in SPIN task performance in the group which received music training. These results suggest that short-term musical training in older adults may enhance neural encoding of speech, with the potential to reduce age-related decline in speech perception.

Musical training improves the ability to understand speech-in-noise in older adults.

It is well known that hearing abilities decline with age, and one of the most commonly reported hearing difficulties reported in older adults is a reduced ability to understand speech in noisy environments. Older adult musicians have an enhanced ability to understand speech in noise, and this has been associated with enhanced brain responses related to both speech processing and the deployment of attention; however, the causal impact of music lessons in older adults has not yet been demonstrated. To investigate whether a causal relationship exists between short-term musical training and performance on auditory tests in older adults and to determine if musical training can be used to improve hearing in older adult nonmusicians, we conducted a longitudinal training study with random assignment. A sample of older adults was randomly assigned to learn to play piano (Music), to learn to play a visuospatially demanding video game (Video), or to serve as a no-contact control (No-contact). After 6 months, the Music group improved their ability to understand a word presented in loud background noise, whereas the other 2 groups did not. This improvement was related to an increase in positive-going electrical brain activity at fronto-left electrodes 200-1000 ms after the presentation of a word in noise. Source analyses suggest that this activity was due to sources located in the left inferior frontal gyrus and other regions involved in the speech-motor system. These findings support the idea that musical training provides a causal benefit to hearing abilities. Importantly, these findings suggest that musical training could be used as a foundation to develop auditory rehabilitation programs for older adults.

Increased flanker task and forward digit span performance in caudate-nucleus-dependent response strategies.

One of two memory systems can be used to navigate in a new environment. Hippocampus-dependent spatial strategy consists of creating a cognitive map of an environment and caudate nucleus-dependent response strategy consists of memorizing a rigid sequence of turns. Spontaneous use of the response strategy is associated with greater activity and grey matter within the caudate nucleus while the spatial strategy is associated with greater activity and grey matter in the hippocampus. The caudate nucleus is involved in executive functions such as working memory, cognitive control and certain aspects of attention such as attentional disengaging. This study therefore aimed to investigate whether response learners would display better performance on tests of executive and attention functioning compared to spatial learners. Fifty participants completed the 4/8 virtual maze to assess navigational strategy, the forward and backward visual digit span and the Attention Network Test - Revised to assess both attention disengagement and cognitive control. Results revealed that response learners showed significantly higher working memory capacity, more efficient attention disengagement and better cognitive control. Results suggest that response learners, who putatively display more grey matter and activity in the caudate nucleus, are associated with better working memory span, cognitive control and attentional disengagement.

Caudate nucleus-dependent navigation strategies are associated with increased risk-taking and set-shifting behavior.

When people navigate, they use strategies dependent on one of two memory systems. The hippocampus-based spatial strategy consists of using multiple landmarks to create a cognitive map of the environment. In contrast, the caudate nucleus-based response strategy is based on the memorization of a series of turns. Importantly, response learners display more gray matter and functional activity in the caudate nucleus and less gray matter in the hippocampus. In parallel, the caudate nucleus is involved in decision-making by mediating attention toward rewards and in set-shifting by mediating preparatory actions. The present study, therefore, examined the link between navigational strategy use, that are associated with gray matter differences in the caudate nucleus and hippocampus, and decision-making and set-shifting performance. Fifty-three participants completed the 4 on 8 virtual maze, the Iowa Gambling Task (IGT), the Wisconsin Card Sorting Test-64 (WCST-64), and a task-switching test. The results revealed that people who use response strategies displayed increased risk-taking behavior in the IGT compared to the people using hippocampus-dependent spatial strategies. Response strategy was also associated with enhanced set-shifting performance in the WCST-64 and task-switching test. These results confirm that risk-taking and set-shifting behavior, that are differentially impacted by the caudate nucleus and hippocampus memory systems, can be predicted by navigational strategy.

Autistic traits in neurotypical individuals are associated with increased landmark use during navigation.

People adopt two distinct learning strategies during navigation. "Spatial learners" navigate by building a cognitive map using environmental landmarks, and display more grey matter in the hippocampus. Conversely, "response learners" memorize a series of rigid turns to navigate and display more grey matter in the caudate nucleus of the striatum. Evidence has linked these two structures with autism spectrum disorder (ASD) and autistic traits in non-clinical populations. Both people with ASD and neurotypical people with higher levels of autistic traits have been shown to display more grey matter in the hippocampus and less functional activity in the caudate nucleus. We therefore tested 56 healthy participants who completed the Autism Quotient (AQ) Scale and the 4-on-8 Virtual Maze (4/8 VM), which determines the reliance on landmarks during navigation. We found that people who relied on landmarks during navigation also displayed significantly higher scores on the AQ Scale. Because spatial strategies are associated with increased attention to environmental landmark use and are supported by the hippocampus, our results provide a potential behavioral mechanism linking higher autistic traits (e.g., increased attention to detail and increased sensory processes) to increased hippocampal grey matter.

Playing Super Mario increases oculomotor inhibition and frontal eye field grey matter in older adults.

Aging is associated with cognitive decline and decreased capacity to inhibit distracting information. Video game training holds promise to increase inhibitory mechanisms in older adults. In the current study, we tested the impact of 3D-platform video game training on performance in an antisaccade task and on related changes in grey matter within the frontal eye fields (FEFs) of older adults. An experimental group (VID group) engaged in 3D-platform video game training over a period of 6 months, while an active control group was trained on piano lessons (MUS group), and a no-contact control group did not participate in any intervention (CON group). Increased performance in oculomotor inhibition, as measured by the antisaccade task, and increased grey matter in the right FEF was observed uniquely in the VID group. These results demonstrate that 3D-platform video game training can improve inhibitory control known to decline with age.

Habitual action video game players display increased cortical thickness in the dorsal anterior cingulate cortex.

Action video game players (aVGPs) display increased performance in attention-based tasks and enhanced procedural motor learning. In parallel, the anterior cingulate cortex (ACC) is centrally implicated in specific types of reward-based learning and attentional control, the execution or inhibition of motor commands, and error detection. These processes are hypothesized to support aVGP in-game performance and enhanced learning though in-game feedback. We, therefore, tested the hypothesis that habitual aVGPs would display increased cortical thickness compared with nonvideo game players (nonVGPs). Results showed that the aVGP group (n=17) displayed significantly higher levels of cortical thickness specifically in the dorsal ACC compared with the nonVGP group (n=16). Results are discussed in the context of previous findings examining video game experience, attention/performance, and responses to affective components such as pain and fear.