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\"Members of Eli Baxter's generation are the last of the hunting and gathering societies living on Turtle Island. They are also among the last fluent speakers of the Anishinaabay language known as Anishinaabaymowin. Aki-wayn-zih is a story about the land and its spiritual relationship with the Anishinaabayg, from the beginning of their life on Miss-koh-tay-sih Minis (Turtle Island) to the present day. Baxter writes about Anishinaabay life before European contact, his childhood memories of trapping, hunting, and fishing with his family on traditional lands in Treaty 9 territory, and his personal experience surviving the residential school system. Examining how Anishinaabay Kih-kayn-daa-soh-win (knowledge) is an elemental concept embedded in the Anishinaabay language, Aki-wayn-zih explores history, science, math, education, philosophy, law, and spiritual teachings, outlining the cultural significance of language to Anishinaabay identity. Recounting traditional Ojibway legends in their original language, fables in which moral virtues double as survival techniques, and detailed guidelines for expertly trapping or ensnaring animals, Baxter reveals how the residential school system shaped him as an individual, transformed his family, and forever disrupted his reserve community and those like it. Through spiritual teachings, historical accounts, and autobiographical anecdotes, Aki-wayn-zih offers a new form of storytelling from the Anishinaabay point of view.\"-- Provided by publisher.

Andil Gosine’s participant-driven performance Cane Portraiture aestheticizes the social history of indentured labourers in the Caribbean. The work expands the field of relations surrounding the discourse of ‘coolitude’ – the dissemination of Indian labour during the 19th century – by redressing the ‘coolie odyssey’. By doing so, Gosine suggests that the pathos of displacement produced by the ‘coolie odyssey’ moves through generations of the Caribbean diaspora. In an attempt to define and reconcile this tension, Cane Portraiture attempts to locate a renewed sense of place and of ‘home’. For Gosine, then, the conceptualization of ‘home’ is approached as an embodiment of a person or site that is shared with others.

Complementing the genome with an understanding of the human exposome is an important challenge for contemporary science and technology. Tens of thousands of chemicals are used in commerce, yet cost for targeted environmental chemical analysis limits surveillance to a few hundred known hazards. To overcome limitations which prevent scaling to thousands of chemicals, we develop a single-step express liquid extraction and gas chromatography high-resolution mass spectrometry analysis to operationalize the human exposome. We show that the workflow supports quantification of environmental chemicals in human plasma (200 µL) and tissue (≤100 mg) samples. The method also provides high resolution, sensitivity and selectivity for exposome epidemiology of mass spectral features without a priori knowledge of chemical identity. The simplicity of the method can facilitate harmonization of environmental biomonitoring between laboratories and enable population level human exposome research with limited sample volume. Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, yet treatment remains “one size fits all,” despite phenotypic heterogeneity. We analyzed clinical and metabolomics data from 514 children (ages 5-18, 73% male) with biopsy-proven MASLD across three NASH Clinical Research Network studies. Unsupervised clustering of clinical data identified three distinct metabotypes: early-mild (49.4%, youngest, lowest lipids, liver enzymes, insulin resistance), cardiometabolic (36.8%, highest waist circumference, lipids, uric acid, SBP), and inflammatory-fibrotic (13.8%, highest liver enzymes, steatohepatitis, advanced fibrosis). Integrative network and pathway enrichment analyses revealed alterations in tryptophan metabolism within the inflammatory-fibrotic group, including elevated kynurenine pathway metabolites, which were significantly correlated with fibrosis stage. Branched-chain amino acid degradation, butanoate, and purine metabolism demonstrated greater enrichment in the cardiometabolic group. Here, we show that pediatric MASLD subtypes differ in clinical and metabolic features, providing a framework for targeted interventions, with validation needed in independent cohorts. Here the authors combine clinical and metabolomics data to identify distinct metabotypes of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD). The results provide information regarding heterogeneity of MASLD presentation, but require validation in independent cohorts.

•Indirect calorimetry provides limited information on macronutrient metabolism.•Metabolomics provides a global measure of whole-body metabolism.•A metabolome-wide association study was performed to characterize fasting metabolism.•The fasted plasma metabolome includes diverse pathways and metabolites.•Metabolomics may be useful in profiling fasting metabolism in clinical settings. High-resolution metabolomics enables global assessment of metabolites and molecular pathways underlying physiologic processes, including substrate utilization during the fasted state. The clinical index for substrate utilization, respiratory exchange ratio (RER), is measured via indirect calorimetry. The aim of this pilot study was to use metabolomics to identify metabolic pathways and plasma metabolites associated with substrate utilization in healthy, fasted adults. This cross-sectional study included 33 adults (mean age 27.7 ± 4.9 y, mean body mass index 24.8 ± 4 kg/m2). Participants underwent indirect calorimetry to determine resting RER after an overnight fast. Untargeted metabolomics was performed on fasted plasma samples using dual-column liquid chromatography and ultra-high-resolution mass spectrometry. Linear regression and pathway enrichment analyses identified pathways and metabolites associated with substrate utilization measured with indirect calorimetry. RER was significantly associated with 1389 metabolites enriched within 13 metabolic pathways (P < 0.05). Lipid-related findings included general pathways, such as fatty acid activation, and specific pathways, such as C21-steroid hormone biosynthesis and metabolism, butyrate metabolism, and carnitine shuttle. Amino acid pathways included those central to metabolism, such as glucogenic amino acids, and pathways needed to maintain reduction-oxidation reactions, such as methionine and cysteine metabolism. Galactose and pyrimidine metabolism were also associated with RER (all P < 0.05). The fasting plasma metabolome reflects the diverse macronutrient pathways involved in carbohydrate, amino acid, and lipid metabolism during the fasted state in healthy adults. Future studies should consider the utility of metabolomics to profile individual nutrient requirements and compare findings reported here to clinical populations.

Background Adiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females. Methods Thirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31 P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses. Results Mitochondrial metabolism was similar between sexes ( p  > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = − 0.73; p  = 0.002) and reduced muscle mitochondrial function (r = 0.58, p  = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = − 0.75, p  = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p  = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p  = 0.04). In all participants, insulin (r = 0.35; p  = 0.04) and HOMA-IR (r = 0.34; p  = 0.05) were associated with a higher τPCr. Conclusions These novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health.

Background The human exposome is composed of diverse metabolites and small chemical compounds originated from endogenous and exogenous sources, respectively. Genetic and environmental factors influence metabolite levels, while the extent of genetic contributions across metabolic pathways is not yet known. Untargeted profiling of human metabolome using high-resolution mass spectrometry (HRMS) combined with genome-wide genotyping allows comprehensive identification of genetically influenced metabolites. As such previous studies of adults discovered and replicated genotype–metabotype associations. However, these associations have not been characterized in children. Results We conducted the largest genome by metabolome-wide association study to date of children ( N  = 441) using 619,688 common genetic variants and 14,342 features measured by HRMS. Narrow-sense heritability ( h 2 ) estimates of plasma metabolite concentrations using genomic relatedness matrix restricted maximum likelihood (GREML) method showed a bimodal distribution with high h 2 (> 0.8) for 15.9% of features and low h 2 (< 0.2) for most of features (62.0%). The features with high h 2 were enriched for amino acid and nucleic acid metabolism, while carbohydrate and lipid concentrations showed low h 2 . For each feature, a metabolite quantitative trait loci (mQTL) analysis was performed to identify genetic variants that were potentially associated with plasma levels. Fifty-four associations among 29 features and 43 genetic variants were identified at a genome-wide significance threshold p  < 3.5 × 10 –12 (= 5 × 10 –8 /14,342 features). Previously reported associations such as UGT1A1 and bilirubin; PYROXD2 and methyl lysine; and ACADS and butyrylcarnitine were successfully replicated in our pediatric cohort. We found potential candidates for novel associations including CSMD1 and a monostearyl alcohol triglyceride ( m/z 781.7483, retention time (RT) 89.3 s); CALN1 and Tridecanol ( m/z 283.2741, RT 27.6). A gene-level enrichment analysis using MAGMA revealed highly interconnected modules for dADP biosynthesis, sterol synthesis, and long-chain fatty acid transport in the gene-feature network. Conclusion Comprehensive profiling of plasma metabolome across age groups combined with genome-wide genotyping revealed a wide range of genetic influence on diverse chemical species and metabolic pathways. The developmental trajectory of a biological system is shaped by gene–environment interaction especially in early life. Therefore, continuous efforts on generating metabolomics data in diverse human tissue types across age groups are required to understand gene–environment interaction toward healthy aging trajectories.

Prevalence of autism spectrum disorder (ASD) has been increasing in the United States in the past decades. The exact mechanisms remain enigmatic, and diagnosis of the disease still relies primarily on assessment of behavior. We first used a case–control design (75 idiopathic cases and 29 controls, enrolled at Boston Children’s Hospital from 2007-2012) to identify plasma biomarkers of ASD through a metabolome-wide association study approach. Then we leveraged a family-based design (31 families) to investigate the influence of shared genetic and environmental components on the autism-associated features. Using untargeted high-resolution mass spectrometry metabolomics platforms, we detected 19 184 features. Of these, 191 were associated with ASD (false discovery rate < 0.05). We putatively annotated 30 features that had an odds ratio (OR) between <0.01 and 5.84. An identified endogenous metabolite, O-phosphotyrosine, was associated with an extremely low autism odds (OR 0.17; 95% confidence interval 0.06-0.39). We also found that glutathione metabolism was associated with ASD (P = 0.048). Correlations of the significant features between proband and parents were low (median = 0.09). Of the 30 annotated features, the median correlations within families (proband–parents) were −0.15 and 0.24 for the endogenous and exogenous metabolites, respectively. We hypothesize that, without feature identification, family-based correlation analysis of autism-associated features can be an alternative way to assist the prioritization of potentially diagnostic features. A panel of ASD diagnostic metabolic markers with high specificity could be derived upon further studies.

(Breton's proposal appears less than a decade after the start of the First World War, during which he worked in a French mental health facility treating patients with \"shell shock,\" among other conditions). [...]the act of painting moves beyond its media and material to strengthen the bonds of community, fulfilling Sanchez's own promise to listen and share his teachings with younger generations. Though consensus varies, it can be defined as a gauge that shows the extent to which human beings have impacted Earth's ecosystems enough to cause grave and perhaps irreparable damage:4 We must leave something For the generations coming or Have we crossed a threshold that There is no repair for our violations? [...]Sanchez's paintings represent different conceptions of time and space, as