Is neighborhood poverty harmful to every child? Neighborhood poverty, family poverty, and behavioral problems among young children

This longitudinal study investigates the association between neighborhood poverty and behavioral problems among young children. This study also examines whether social environments mediate the relationship between neighborhood poverty and behavioral problems. We used data from the third and fourth waves of the Fragile Families and Child Wellbeing study to assess behavioral problems separately for children who experienced no family poverty, moved out of family poverty, moved into family poverty, and experienced long‐term family poverty. Regression models assessed the effect of neighborhood poverty on behavioral problem outcomes among children aged 5 years, after controlling for sociodemographic characteristics and earlier behavioral problems. Results showed an association between neighborhood poverty and lower social cohesion and safety, which lead to greater externalizing problems among children with long‐term family poverty living in high‐poverty neighborhoods compared with those in low‐poverty neighborhoods. Policies and community resources need to be allocated to improve neighborhood social environments, particularly for poor children in high‐poverty neighborhoods.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148233/1/jcop22140.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148233/2/jcop22140_am.pd

LIGAND ARCHITECTURE EFFECTS UPON PRIMARY COPPER-DIOXYGEN ADDUCT CHEMISTRY

The investigation into the chemical/physical properties of synthetic copper complexes provide fundamental insights into the understanding of the enzyme chemistry overviewed in this dissertation. In Chapter 1, copper monooxygenases and oxidases involved in C–H/O–H bond oxidation are introduced, along with biological functions, coordination environment of their metal active sites and their proposed mechanisms. Recent investigations of various synthetic oxygen-derived copper intermediates, including their characteristics and reactivity, are described. Possible reaction mechanisms are also highlighted by comparison to aqueous O2-reduction chemistry. In Chapter 2, with the goal of understanding the mechanism of phenol oxidation by mononuclear cupric superoxo species, kinetic studies were performed with the reaction of a new copper(II) superoxo complex [(DMM-tmpa)CuII(O2•¬–)]+ and a series of para-substituted-2,6-di-tert-butylphenols (p-X-DTBP’s) affording 2,6-di-tert-butyl-1,4-benzoquinones (DTBQ’s). Significant deuterium kinetic isotope effects (KIE's) and a positive correlation of second-order-rate constants (k2’s) compared to rate constants for p-X-DTBP’s plus cumylperoxyl radical reactions indicate a mechanism involves rate-limiting hydrogen atom transfer (HAT). Product analyses, 18O-labeling experiments, and separate reactivity employing the 2,4,6-tri-tert-butylphenoxyl radical provide further mechanistic insights. Chapter 3 reports the first example of sulfur-ligated mononuclear superoxo species which mimics the putative CuII(O2•–) active species of the peptidylglycine-α-hydroxylating monooxygenase, PHM. This complex exhibits enhanced reactivity towards both O-H and C-H substrates in comparison to close analogues [(L)CuII(O2•–)]+, where L contains only nitrogen donor atoms. Cu-S(thioether) ligation with its weaker donor ability (relative to an N-donor) are demonstrated by comparisons to the chemistry of analogue compounds. Chapter 4 provides the coordination chemistry and reactivity study of primary CuI/O2 species featuring an intramolecular hydrogen bonding substituent, (XBA)CuII(O2●–) (XS). The stability of XS compounds are ascribed to internal H-bond, from the secondary coordination sphere, to the proximal superoxide ‘O’ atom. Direct evidence for hydrogen atom transfer from phenol substrates by XS complexes was obtained, and enhanced reactivity of copper(II) superoxo complexes possessing electron-withdrawing groups (i.e., X) compared with other CuII(O2●–) analogues was observed. This behavior is discussed and correlated to the H-bonding ability of the XBA ligands and the copper ion centered redox behavior for varying XS complexes. In Chapter 5, we describe an overview of the copper proteins with respect to their preference for tautomeric histidine binding sites (δNHis vs εNHis) and a unique histidine-chelated ligand environment. Newly designed copper-histidine complexes are introduced, which possess ligands mimicking the copper center of certain enzymes. Dioxygen-derived copper species are determined to be (trans-peroxo)CuII2 and (bis-μ-oxo)CuIII2 complexes based on spectroscopic studies

Reciprocal knock-in mice to investigate the functional redundancy of lamin B1 and lamin B2.

Lamins B1 and B2 (B-type lamins) have very similar sequences and are expressed ubiquitously. In addition, both Lmnb1- and Lmnb2-deficient mice die soon after birth with neuronal layering abnormalities in the cerebral cortex, a consequence of defective neuronal migration. The similarities in amino acid sequences, expression patterns, and knockout phenotypes raise the question of whether the two proteins have redundant functions. To investigate this topic, we generated "reciprocal knock-in mice"-mice that make lamin B2 from the Lmnb1 locus (Lmnb1(B2/B2)) and mice that make lamin B1 from the Lmnb2 locus (Lmnb2(B1/B1)). Lmnb1(B2/B2) mice produced increased amounts of lamin B2 but no lamin B1; they died soon after birth with neuronal layering abnormalities in the cerebral cortex. However, the defects in Lmnb1(B2/B2) mice were less severe than those in Lmnb1-knockout mice, indicating that increased amounts of lamin B2 partially ameliorate the abnormalities associated with lamin B1 deficiency. Similarly, increased amounts of lamin B1 in Lmnb2(B1/B1) mice did not prevent the neurodevelopmental defects elicited by lamin B2 deficiency. We conclude that lamins B1 and B2 have unique roles in the developing brain and that increased production of one B-type lamin does not fully complement loss of the other

The Effects of Celebrity-Brand Congruence and Publicity on Consumer Attitudes, Buying Intention, and Loyalty

Celebrities have been used for decades as a marketing tool to endorse brands or products. However, once a direct link has been formed from a celebrity to a brand, the negative information about the celebrity may reflect back on to the endorsed brand. Applying the balance theory, the purpose of this study was to investigate the effects of celebrity-brand congruence and publicity on consumers\u27 attitudes toward the celebrity and brand as well as their buying intention and loyalty. A survey with 2(congruence vs. incongruence)×2(positive vs. negative publicity) experimental design was conducted and a total of 105 usable data from generation Y female consumers were collected. The study revealed that consumers tend to like and be loyal to the brand/product when there is a celebrity-brand congruence and positive publicity. Interestingly, the congruence was found to be more important influencer to motivate consumers to purchase a brand than publicity

Pubertal timing and breast density in young women: a prospective cohort study.

BACKGROUND:Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. METHODS:From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. RESULTS:The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). CONCLUSIONS:Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk

Magnesium Intake in Relation to Systemic Inflammation, Insulin Resistance, and the Incidence of Diabetes

OBJECTIVETo investigate the long-term associations of magnesium intake with incidence of diabetes, systemic inflammation, and insulin resistance among young American adults.RESEARCH DESIGN AND METHODSA total of 4,497 Americans, aged 18–30 years, who had no diabetes at baseline, were prospectively examined for incident diabetes based on quintiles of magnesium intake. We also investigated the associations between magnesium intake and inflammatory markers, i.e., high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and fibrinogen, and the homeostasis model assessment of insulin resistance (HOMA-IR).RESULTSDuring the 20-year follow-up, 330 incident cases of diabetes were identified. Magnesium intake was inversely associated with incidence of diabetes after adjustment for potential confounders. The multivariable-adjusted hazard ratio of diabetes for participants in the highest quintile of magnesium intake was 0.53 (95% CI, 0.32–0.86; Ptrend < 0.01) compared with those in the lowest quintile. Consistently, magnesium intake was significantly inversely associated with hs-CRP, IL-6, fibrinogen, and HOMA-IR, and serum magnesium levels were inversely correlated with hs-CRP and HOMA-IR.CONCLUSIONSMagnesium intake was inversely longitudinally associated with incidence of diabetes in young American adults. This inverse association may be explained, at least in part, by the inverse correlations of magnesium intake with systemic inflammation and insulin resistance

Coordination-Driven Monolayer-to-Bilayer Transition in 2D Metal-Organic Networks

We report on monolayer-to-bilayer transitions in 2D metal−organic networks (MONs) from amphiphiles supported at the water−air interface. Functionalized calix[4]arenes are assembled through the coordination of selected transition metal ions to yield monomolecular 2D crystalline layers. In the presence of Ni(II) ions, interfacial self-assembly and coordination yields stable monolayers. Cu(II) promotes 2D coordination of a monolayer which is then diffusively reorganizing, nucleates, and grows a progressive amount of second layer islands. Atomic force microscopic data of these layers after transfer onto solid substrates reveal crystalline packing geometries with submolecular resolution as they are varying in function of the building blocks and the kinetics of the assembly. We assign this monolayer-to- bilayer transition to a diffusive reorganization of the initial monolayers owing to chemical vacancies of the predominant coordination motif formed by Cu2+ ions. Our results introduce a new dimension into the controlled monolayer-to-multilayer architecturing of 2D metal− organic networks

In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma

Although dendritic cells (DCs) play an important role in sensitization to inhaled allergens, their function in ongoing T helper (Th)2 cell–mediated eosinophilic airway inflammation underlying bronchial asthma is currently unknown. Here, we show in an ovalbumin (OVA)-driven murine asthma model that airway DCs acquire a mature phenotype and interact with CD4+ T cells within sites of peribronchial and perivascular inflammation. To study whether DCs contributed to inflammation, we depleted DCs from the airways of CD11c-diphtheria toxin (DT) receptor transgenic mice during the OVA aerosol challenge. Airway administration of DT depleted CD11c+ DCs and alveolar macrophages and abolished the characteristic features of asthma, including eosinophilic inflammation, goblet cell hyperplasia, and bronchial hyperreactivity. In the absence of CD11c+ cells, endogenous or adoptively transferred CD4+ Th2 cells did not produce interleukin (IL)-4, IL-5, and IL-13 in response to OVA aerosol. In CD11c-depleted mice, eosinophilic inflammation and Th2 cytokine secretion were restored by adoptive transfer of CD11c+ DCs, but not alveolar macrophages. These findings identify lung DCs as key proinflammatory cells that are necessary and sufficient for Th2 cell stimulation during ongoing airway inflammation

Cerebellar volume and functional connectivity in neonates predicts social and emotional development in toddlers

Over the past decade, a growing body of research in adults has emphasized the role of the cerebellum in social and emotional cognition. This has been further supported by findings of delayed social and emotional development in toddlers with cerebellar injury during the fetal and newborn periods. However, the contributions of the cerebellum to social–emotional development in typically developing newborns are unclear. To bridge this gap in knowledge, we used multimodal MRI to investigate associations between cerebellar structure and function in 88 healthy neonates (mean ± sd of postmenstrual age, = 42.00 ± 1.91 weeks) and social–emotional development at 18-months assessed using the Infant-Toddler Social–Emotional Assessment (ITSEA) (mean age on ITSEA: 18.32 ± 1.19 months old). We found that cerebellar volume was not associated with ITSEA domain scores at 18 months. We further demonstrated cerebellar functional gradient (FGR) defined using principal component analysis (PCA) was associated with Externalizing domain (linear regression model, false-discovery-rate-adjusted p = 0.013). This cluster (FGR7) included the left dentate, right VI, left Vermis VIIIb, and right V lobules. Finally, we demonstrated that either structural or functional features of the cerebellum reliably predicted scores on the Externalizing and Internalizing domains (correlation between actual and predicted scores: for structural, Fisher’s z = 0.48 ± 0.01 for Internalizing, p = 0.01; for functional, Fisher’s z = 0.45 ± 0.01 for Externalizing, p = 0.02; with permutation test). Collectively, our findings suggest that the cerebellum plays an important role in social–emotional development during the critical early stages of life