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    Parents’ Retrospectively Recalled Structured Feeding Practices Are Associated With Lower Current Disordered Eating and Mental Health Concerns in Their Young Adult Children: Findings in Parent-Child Dyads

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    Parental feeding practices are linked to child disordered eating. Less research has examined these associations in young adult children, particularly college-aged, and studies examining relationships between parent feeding practices and mental health concerns are also limited. Examining these relationships in college students is important because higher education represents a period of marked development and maintenance of maladaptive eating behaviors and mental health concerns. A cross-sectional study with the inclusion of 64 parent-child (i.e., young adult) dyads examined relationships between retrospective parental feeding practices and current disordered eating and mental health concerns in their young adult children. Higher retrospective parental structured feeding practices were associated with lower young adult current disordered eating and mental health concerns. Collegiate health-promotion programs may consider college students’ early food environments, particularly structured food environments, as factors that may be associated with adaptive eating behaviors and better mental health outcomes

    Diurnal Cortisol Change Moderates the Associations Between Bedtime Parenting Sensitivity and Young Children’s Executive Functioning and Emotion Regulation

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    The present study examined children’s diurnal cortisol as a moderator of the association between parenting sensitivity at bedtime and young children’s executive functioning and emotion regulation. Fifty-one children (Mage = 4.47 years) and their families participated. Parenting sensitivity was assessed from video recordings of child bedtime. Average child morning and evening cortisol levels were measured from saliva across 3 days. A greater decline in cortisol from morning to evening reflected healthy diurnal patterning. Children’s executive functioning was measured objectively, and parents reported on children’s emotion regulation. Regression analyses showed that lower parenting sensitivity at bedtime was associated with lower executive functioning and more labile and less adaptive emotion regulation only for children who showed less cortisol decline from morning to evening, suggesting that adaptive cortisol patterning may be protective in the context of low parenting sensitivity. The findings identify children at greatest risk and inform interventions targeting children’s developmental outcomes

    Widespread X Chromosome Repeats Play A Central Role In Drosophila Melanogaster X Chromosome Recognition

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    Organisms with differentiated sex chromosomes must accommodate unequal gene dosage in males and females. Male fruit flies increase X-linked gene expression to compensate for hemizygosity of the single X chromosome. Full compensation requires localization of the Male-Specific Lethal (MSL) complex to active genes on the male X, where it modulates chromatin to elevate expression. The mechanisms that identify X chromatin are poorly understood. The euchromatic X is enriched for AT-rich, ~359 bp satellites termed the 1.688X repeats. Autosomal insertions of 1.688X DNA enable MSL recruitment to nearby genes. Ectopic expression of dsRNA from one of these repeats produces siRNA and partially restores X-localization of MSLs in males with defective X recognition. Surprisingly, expression of double stranded RNA from three other 1.688X repeats failed to rescue males. We reconstructed dsRNA-expressing transgenes with sequence from two of these repeats and identified phasing of repeat DNA, rather than sequence or orientation, as the factor that determines rescue of males with defective X recognition. Small RNA sequencing revealed that siRNA was produced in flies with transgene that rescues, but not in those carrying a transgene with identical sequence and different phasing. We demonstrate that closely related repeats in pericentromeric X heterochromatin promote X-recognition through a maternal effect, potentially mediated by small RNA, suggesting that the sources of siRNAs that promote X recognition are highly redundant. We propose that enrichment of satellite repeats on Drosophilid X chromosomes facilitates the rapid evolution of differentiated sex chromosomes by marking the X for compensation

    Plasma Neurofilament Light As A Biomarker Of Neurodegeneration And Memory Function In Older Adults

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    Plasma neurofilament light (NfL) is a promising biomarker for monitoring and predicting cognitive function and neurodegeneration in Alzheimer’s disease (AD). However, the field still needs a better understanding of what plasma NfL reflects about neurodegenerative and cognitive changes occurring in AD, especially in the early stages of Alzheimer’s disease, for the optimized use of plasma NfL as a biomarker for AD for clinical and research purposes. Therefore, here I investigated how NfL is associated with memory function, the functional connectivity of the default mode network, and the microstructural properties of white matter and gray matter regions vulnerable to Alzheimer’s pathologies in older adults with normal cognition to mildly declined cognition likely due to Alzheimer’s disease. Furthermore, I examined how the association between NfL and white matter and gray matter microstructural characteristics differ depending on memory performance. I found that higher plasma NfL was associated with lower neurite density in white matter regions in anterior temporal, parietal, and superior frontal regions and lower fiber orientation dispersion in white matter regions with abundant crossing fibers in older adults with and without cognitive decline. Higher plasma NfL was also associated with lower neurite density in the entorhinal cortex in older adults with lower memory function, but not in those with higher memory function. However, plasma NfL was not associated with the functional connectivity within the posterior midline DMN subnetwork, as well as the functional connectivity between the posterior midline DMN and other DMN subregions. The findings of these studies provide knowledge that enhances the understanding of plasma NfL as a marker tracking the severity of cognitive decline and neurodegenerative changes in the early stages of AD, illuminating the differential sensitivity of plasma NfL to different aspects of neurodegenerative changes. These findings would contribute to future research to develop accurate disease prediction models using biomarkers including plasma NfL, as well as to future investigations to clarify the mechanisms of neurodegeneration and cognitive decline in AD using NfL

    Rhodium-Catalyzed Asymmetric Transformations Of Morita-Baylis-Hillman Trichloroacetimidates

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    Asymmetric transformations of Morita-Baylis-Hillman (MBH) adducts have proven useful in the construction of frameworks of various classes of biologically active compounds which have such as amino acids, lactams, peptides, carbocycles, cinnamic acids, alkaloids, and other natural products. The polyfunctionality of MBH compounds renders them attractive synthetic blocks in organic chemistry. In this dissertation, the versatility of MBH adducts was exploited for the synthesis of different classes of chiral synthetic motifs. While there are many methods for the asymmetric synthesis of monosubstituted allylic fluorides, construction of enantioenriched 1,2-disubstituted allylic fluorides has not been reported. To address this gap, an enantioselective synthesis of 1,2-disubstituted allylic fluorides using chiral diene-ligated rhodium catalyst, Et3N•3HF as a source of fluoride, and Morita Baylis Hillman (MBH) trichloroacetimidates is reported herein. Kinetic studies show that one enantiomer of racemic MBH substrate reacts faster than the other. Computational studies reveal that both syn and anti -allyl complexes are formed upon ionization of allylic substrate, and the syn complexes are slightly energetically favorable. This is in contrast to our previous observation for formation of monosubstituted -allyl intermediates, in which the syn -allyl conformation is strongly preferred. In addition, the presence of an electron-withdrawing group at C2 position of racemic MBH substrate renders 1,2-disubstituted -allyl intermediate formation endergonic and reversible. To compare, formation of monosubstituted -allyl intermediates was exergonic and irreversible. DFT calculations and kinetic studies support a dynamic kinetic asymmetric transformation process wherein the rate of isomerization of the 1,2-disubstituted pi-allylrhodium complexes is faster than that of fluoride addition onto the more reactive intermediate. Also, chiral b-amino nitriles represent a fundamentally important class of versatile synthetic intermediates. They are also ubiquitous motifs in natural products, pharmaceuticals, and fine chemicals, however there are limitations in the asymmetric aminocyanation protocols reported for the synthesis of aminonitriles. A two-step approach starting from MBH trichloroacetimidates was envisioned as alternative access to chiral aminonitriles. Herein, the construction of functionalized -amino nitriles containing two adjacent stereocenters, in a congruent manner and with very high diastereocontrol has been completed. This strategy provides direct access to functionalized -tertiary amino nitrile products through an amination-arylation sequence involving readily available starting materials. This protocol displays exceptionally robust scope for various MBH Michael acceptors and cyclic secondary amines. In summary, this work has shown that MBH trichloroacetimidates are powerful synthetic intermediates that can provide access to otherwise challenging classes of valuable organic motifs via asymmetric transformations

    The Effects Of Alcohol On Crash Avoidance Reaction Time In A Driving Simulator Task In Humans

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    AIM 1: Alcohol-impaired driving continues to be a significant cause of car crash injuries and deaths. The blood alcohol concentration (BAC) cut-off level for drunk driving is 0.08% in Michigan, and is estimated that lowering this cut-off to 0.05%would save 500–800 lives every year in the US alone. We used a portable virtual reality (VR)-based driving simulator to demonstrate the effects of alcohol at BAC concentrations 0.02-0.08%, grouped into 0.01% increments, on driving performance, specifically Crash Avoidance Reaction Time (CART), i.e., the time (in msec) required to initiate a steering avoidance response. We found that BAC concentrations as low as 0.031-0.04% significantly increased CART. These data are consistent with the hypothesis that the BAC cut-off for drunk driving should be lowered to 0.05%, or even lower. AIM 2: Safe driving requires that a driver remain attentive and focused on the driving task. Ethanol impairs a person’s ability to ‘pay attention’, so it is possible that driving impairment from alcohol results from a loss of attention to the driving task. Therefore, on approximately half of the crash avoidance trials, a Warning Bell was used to increase the drivers’ attention. Treatment with 4 and 5 drinks generated BACs in the target range and significantly increased CART compared to placebo. Presentation of Warning Bell significantly reduced the effects of alcohol to increase CART relative to vehicle treatment. These data are consistent with the hypothesis that the effects of alcohol at BAC levels at or below 0.08% result at least in part from changes in attention to the driving task. AIM 3: It was predicted that the subjects who reported alcohol tolerance would show smaller impairments in driving for a given BAC when compared to subjects with a history of no or more limited exposure. To examine this effect, we used subject self-reported drinking history (NIAAA scale). Unfortunately, we were unable to recruit a sufficient number of ‘binge drinkers’ to serve as participants in our study, and the sample size was therefore inadequate to draw any meaningful conclusions regarding this question

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