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Planetary praxis & pedagogy : transdisciplinary approaches to environmental sustainability
\"Good books make important points because their authors have something worthwhile to say. This book is more than a good book because its authors not only make important points but they do so in ways that exemplify the transdisciplinarity the authors write about. In eight interesting and insightful chapters the book connects pedagogy, marketing, development, immanence, race, resilience, technology, and the commons in ways that show the necessity and importance of transdisciplinary thinking. This is a book for those who seek deeper and more creative connections to a sustainable way of life, a way of life that opens up imaginative acts of hope.\"--John Novak, Professor in the Department of Graduate and Undergraduate Studies in Education at Brock University; his research interests include: Philosophy of education, Invitational theory and practice, Educational leadership, and Social-cultural contexts of education.
Book
A cellular hierarchy framework for understanding heterogeneity and predicting drug response in acute myeloid leukemia
The treatment landscape of acute myeloid leukemia (AML) is evolving, with promising therapies entering clinical translation, yet patient responses remain heterogeneous, and biomarkers for tailoring treatment are lacking. To understand how disease heterogeneity links with therapy response, we determined the leukemia cell hierarchy makeup from bulk transcriptomes of more than 1,000 patients through deconvolution using single-cell reference profiles of leukemia stem, progenitor and mature cell types. Leukemia hierarchy composition was associated with functional, genomic and clinical properties and converged into four overall classes, spanning Primitive, Mature, GMP and Intermediate. Critically, variation in hierarchy composition along the Primitive versus GMP or Primitive versus Mature axes were associated with response to chemotherapy or drug sensitivity profiles of targeted therapies, respectively. A seven-gene biomarker derived from the Primitive versus Mature axis was associated with response to 105 investigational drugs. Cellular hierarchy composition constitutes a novel framework for understanding disease biology and advancing precision medicine in AML.
A novel gene expression classifier of AML heterogeneity captures patient-specific variation in leukemia cell composition and predicts clinical responses to treatment.
Journal Article
Human-Specific Histone Methylation Signatures at Transcription Start Sites in Prefrontal Neurons
Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes, but little is known about the role of cis-regulatory changes affecting transcription start sites (TSS). Here, we mapped in human, chimpanzee, and macaque prefrontal cortex the genome-wide distribution of histone H3 trimethylated at lysine 4 (H3K4me3), an epigenetic mark sharply regulated at TSS, and identified 471 sequences with human-specific enrichment or depletion. Among these were 33 loci selectively methylated in neuronal but not non-neuronal chromatin from children and adults, including TSS at DPP10 (2q14.1), CNTN4 and CHL1 (3p26.3), and other neuropsychiatric susceptibility genes. Regulatory sequences at DPP10 and additional loci carried a strong footprint of hominid adaptation, including elevated nucleotide substitution rates and regulatory motifs absent in other primates (including archaic hominins), with evidence for selective pressures during more recent evolution and adaptive fixations in modern populations. Chromosome conformation capture at two neurodevelopmental disease loci, 2q14.1 and 16p11.2, revealed higher order chromatin structures resulting in physical contact of multiple human-specific H3K4me3 peaks spaced 0.5-1 Mb apart, in conjunction with a novel cis-bound antisense RNA linked to Polycomb repressor proteins and downregulated DPP10 expression. Therefore, coordinated epigenetic regulation via newly derived TSS chromatin could play an important role in the emergence of human-specific gene expression networks in brain that contribute to cognitive functions and neurological disease susceptibility in modern day humans.
Journal Article
Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury
Muscle regeneration depends on a robust albeit transient inflammatory response. Persistent inflammation is a feature of age-related regenerative deficits, yet the underlying mechanisms are poorly understood. Here, we find inflammatory-related CC-chemokine-receptor 2 (Ccr2) expression in non-hematopoietic myogenic progenitors (MPs) during regeneration. After injury, the expression of Ccr2 in MPs corresponds to the levels of its ligands, the chemokines Ccl2, 7, and 8. We find stimulation of Ccr2-activity inhibits MP fusion and contribution to myofibers. This occurs in association with increases in MAPKp38δ/γ signaling, MyoD phosphorylation, and repression of the terminal myogenic commitment factor Myogenin. High levels of Ccr2-chemokines are a feature of regenerating aged muscle. Correspondingly, deletion of
Ccr2
in MPs is necessary for proper fusion into regenerating aged muscle. Finally, opportune Ccr2 inhibition after injury enhances aged regeneration and functional recovery. These results demonstrate that inflammatory-induced activation of Ccr2 signaling in myogenic cells contributes to aged muscle regenerative decline.
Chronic inflammation is a feature of age-related regenerative decline in skeletal muscles, but how it directly affects resident muscle stem cell fate and function is unclear. Here, the authors show that Ccr2 signaling in muscle stem cell derived progenitors represses terminal myogenic differentiation, and that targeting Ccr2 on aged myogenic progenitors rejuvenates aged skeletal muscle healing and function.
Journal Article
Association of cancer caregiver stress and negative attribution style with depressive symptoms and cortisol: a cross-sectional study
Purpose
We examined the effect of informal cancer caregiver stress and negative attribution style (NAS) on depressive symptoms and salivary cortisol.
Method
The sample came from a hospital bone marrow unit and caregiver support organizations and included 60 informal cancer caregivers (51.7% partners) of individuals with cancer (provided care for a median of 27.5 h per week for 12 months) and 46 non-caregiver participants. In this cross-sectional study, participants completed questionnaires assessing NAS and depressive symptoms and provided saliva samples to measure cortisol.
Results
Linear regressions demonstrated that cancer caregiver stress (
p
= 0.001) and the cancer caregiver stress by NAS interaction (
p
= 0.017), but not NAS alone (
p
= 0.152), predicted depressive symptoms. Caregivers independent of their NAS and non-caregivers high in NAS reported high depression while non-caregivers low in NAS reported low depression. Neither cancer caregiver stress (
p
= 0.920) nor NAS alone (
p
= 0.114), but their interaction, predicted cortisol (
p
= 0.036). Higher NAS was associated with a higher cortisol in both groups while non-caregivers had
higher
cortisol than caregivers.
Conclusions
If the findings can be replicated, consideration of NAS in existing interventions to support informal cancer caregivers in managing chronic stress appears warranted.
Journal Article
Relationships among repetitive negative thinking types, change in employment, and mental health
Repetitive negative thinking (RNT) describes different, but related, maladaptive thought processes focused on stress or the emotional responses to stress. When activated by stress, RNT maintains and intensifies the emotional response leading to mental health problems. We examined whether four types of RNT (anger rumination, brooding, reflection, worry) are sub-constructs of one RNT or if they are related but distinct types of RNT. We also assessed their concurrent and longitudinal relationships with COVID-related changes in employment and three outcomes: aggression, depressive symptoms, and anxiety symptoms. Participants in our corss-sectional online study were 1,627 individuals (18–87 years, 80.1% White, 86.3% non-Hispanic, 70.8% women). Participants in our 3-wave longitudinal online study were 475 individuals (19–80 years, 92.2% White, 97.5% non-Hispanic, 82.3% women). Exploratory and Confirmatory Factor Analyses and Structural Equation Modeling demonstrated that the types of RNT are correlated but distinct. Brooding was positively associated with and mediated the effect of changes in employment on all three mental health problems. Worry was positively associated with and mediated the effect of changes in employment on depressive and anxiety symptoms but not aggression. Anger rumination was positively associated with and mediated the effect of changes in employment on aggression only. Reflection was unrelated to changes in employment and all three mental health problems. Clinicians should consider the transdiagnostic relevance of brooding with clients experiencing anger, anxiety, and/or depression.
Journal Article
Body weight affects ω-3 polyunsaturated fatty acid (PUFA) accumulation in youth following supplementation in post-hoc analyses of a randomized controlled trial
Guidelines for suggested intake of ω-3 polyunsaturated fatty acids (PUFAs) are limited in youth and rely primarily on age. However, body weight varies considerably within age classifications. The current analyses examined effects of body weight and body mass index (BMI) on fatty acid accumulation in 64 youth (7-14 years) with a diagnosed mood disorder in a double-blind randomized-controlled trial (2000mg ω-3 supplements or a control capsule) across 12 weeks. Weight and height were measured at the first study visit and EPA and DHA levels were determined using fasting blood samples obtained at both the first and end-of-study visits. In the ω-3 supplementation group, higher baseline body weight predicted less plasma accumulation of both EPA [B = -0.047, (95% CI = -0.077; -0.017), β = -0.54, p = 0.003] and DHA [B = -0.02, (95% CI = -0.034; -0.007), β = -0.52, p = 0.004]. Similarly, higher BMI percentile as well as BMI category (underweight, normal weight, overweight/obese) predicted less accumulation of EPA and DHA (ps≤0.01). Adherence to supplementation was negatively correlated with BMI percentile [B = -0.002 (95% CI = -0.004; 0.00), β = -0.44, p = 0.019], but did not meaningfully affect observed associations. As intended, the control supplement exerted no significant effect on plasma levels of relevant fatty acids regardless of youth body parameters. These data show strong linear relationships of both absolute body weight and BMI percentile with ω-3 PUFA accumulation in youth. A dose-response effect was observed across the BMI spectrum. Given increasing variability in weight within BMI percentile ranges as youth age, dosing based on absolute weight should be considered. Moreover, effects of weight should be incorporated into statistical models in studies examining clinical effects of ω-3 PUFAs in youth as well as adults, as weight-related differences in effects may contribute meaningfully to inconsistencies in the current literature.
WHO International Clinical Trial Registry Platform NCT01341925 and NCT01507753.
Journal Article
Repetitive negative thinking, meaning in life, and serum cytokine levels in pregnant women: varying associations by socioeconomic status
Elevated proinflammatory cytokines and decreased antiinflammatory cytokines are important in the context of perinatal health, and immune dysregulation has been found among perinatal women with low socioeconomic status (SES). Data examining psychological factors that may contribute to cytokines in pregnancy are lacking. Of importance, these associations may be most evident among women with low SES. This study examined the moderating role of SES on associations among presence of meaning in life and repetitive negative thinking with cytokine levels among 67 pregnant women. A cumulative SES index was calculated using income, education, perceived social class, and receipt of governmental support. Measures included the Perseverative Thinking Questionnaire, Meaning in Life Questionnaire, and serum interleukin (IL)-6 as well as IL-4. Using PROCESS, moderation analyses showed significant interactions between psychological factors and SES in predicting serum cytokines. In the context of high SES only, greater repetitive negative thinking was associated with higher levels of the proinflammatory cytokine IL-6 (p = 0.056) while greater meaning in life was associated with higher levels of the antiinflammatory cytokine IL-4 (p = 0.02). Findings from this study suggest that the benefits of these psychological factors on cytokine levels may be most readily observable among women with greater economic stability. Identifying psychological factors that positively contribute to biological functioning in women experiencing heightened economic distress will be crucial in addressing SES-related disparities in perinatal health.
Journal Article
Financial strain and birth weight: the mediating role of psychological distress
The effects of financial strain during pregnancy have received limited attention. In addition, data examining the pathways by which SES indicators contribute to birth weight are lacking. The objective of the current study was to examine the potential pathway of psychological distress in the relationship between financial strain and birth weight. Participants consisted of 138 pregnant women who completed measures assessing financial strain, depressive symptoms, pregnancy-specific distress, perceived stress, and general anxiety during pregnancy (mean gestational age = 18.5, SD = 7.2). Birth outcome data were obtained via medical record review. Simple and parallel mediation models were conducted using PROCESS. Simple mediation models showed that depressive symptoms (95% CI −24.65, −0.90) and pregnancy-specific distress (95% CI −37.31, −5.91), but not perceived stress (95% CI −31.17, 4.69) or anxiety (95% CI −25.84, 5.57), served as mediators in the relationship between financial strain and birth weight. When depressive symptoms and pregnancy-specific distress were included in the same mediation model, only pregnancy-specific distress remained significant. Financial strain was positively associated with all facets of psychological distress and negatively associated with birth weight during pregnancy. The current study demonstrated the mechanistic role of pregnancy-specific distress in the link between financial strain and birth weight in a racially diverse sample. Interventions targeting pregnancy-specific distress may mitigate the effects of financial strain on birth weight. Studies examining whether pregnancy-specific distress accounts for the relationship between other types of stressor exposures and birth weight would be informative.
Journal Article
Repetitive Negative Thinking, Depressive Symptoms, and Cortisol in Cancer Caregivers and Noncaregivers
OBJECTIVES: To examine the effect of informal cancer caregiving and repetitive negative thinking (RNT) on depressive symptoms and salivary cortisol levels. SAMPLE & SETTING: The sample was recruited from a hospital bone marrow unit and caregiver supportorganizations. It included 60 informal cancer caregivers (52% partners) of individuals with cancer who provided care for a median of 27.5 hours per week for 12 months, and 46 noncaregiver participants. METHODS & VARIABLES: In this cross-sectional study, participants completed questionnaires assessing RNT and depressive symptoms and provided saliva samples to measure cortisol levels. RESULTS: Cancer caregiving and RNT, butnotthe interaction, were associated with more depressive symptoms. RNT, but not cancer caregiving, was associated with salivary cortisol. A disordinal interaction effect suggests that cancer caregiving was associated with lower cortisol levels, and RNT in noncaregivers was associated with higher cortisol levels. IMPLICATIONS FOR NURSING: Given that RNT is related to depressive symptoms and cortisol, connecting cancer caregivers who experience RNT to resources and the development and evaluation of brief nurse-led interventions to reduce RNT in informal cancer caregivers seems warranted.
Journal Article