Effects of contextual socioeconomic stressors on adolescents: mediation and moderation by marital and parent-child relationships

This study presents different methods of longitudinal data analysis used to model continuity and change in family research. Innovative modeling techniques such as auto-regressive models, cross-lagged models, latent growth curves, interlocking growth trajectories, latent class growth analysis, and general mixture modeling are used to model the mechanisms in the family stress model. According to the family stress paradigm, negative stressors such as economic stress, work-related stress, and negative life events lead to poor mental health in parents, negatively impact the marital relationship, and undermine effective parenting. In turn, poor parental mental health, marital distress, and ineffective parenting are expected to have a cumulative negative impact on adolescent well-being. The purpose of this study is to explore the mechanisms through which contextual socioeconomic stressors may negatively impact parental and adolescent mental health and undermine effective parenting skills among single-parent mothers. It was expected that the negative effects of these distal stressors on children are mediated through their parents. In addition, this study investigates the possible role of spousal support from the single-mothers\u27 former spouse as moderator of these contextual stressors. Specifically, it was expected that a positive relationship with the former spouse will significantly buffer the effects of these negative stressors on parenting and on the mental health of the single mothers and their adolescent children. The implications of such findings would be that the benefits of positive spousal support may not be limited to married couples. Rather, divorced parents may also benefit from receiving support from their former spouses, particularly in the form of supportive parenting. Hence, the long-term outlook on the well-being and parenting effectiveness of divorced single-parents does not necessarily have to be as bleak as many make it out to be

PPARG SIGNALING IN THE NUCLEUS ACCUMBENS REGULATES MESOLIMBIC DOPAMINE ACTIVITY

Background: The mesolimbic dopamine system consists of dopamine neuron projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). The NAc regulates VTA dopamine release through inhibitory GABA projections to the VTA. Hyperactive mesolimbic dopamine signaling is implicated in anxiety. Cannabidiol, a compound found in cannabis, demonstrates promising therapeutic potential for anxiety through the regulation of the mesolimbic dopamine system. Previous studies have revealed that cannabidiol infusions into the NAc decreases mesolimbic dopamine activity - potentially through the inhibitory GABA signaling to the VTA. However, the receptor mechanism in the NAc through which CBD produces its effects is unknown. Peroxisome proliferator-activated receptor gamma (PPARG) is a nuclear transcription factor that binds to CBD and colocalizes with GABA neurons. Recent evidence suggests that PPARG activation can decrease mesolimbic dopamine activity through inhibitory GABA signaling. Considering that the NAc expresses high levels of PPARG, intra-NAc CBD may regulate mesolimbic dopamine activity through PPARG activation. Hypothesis: PPARG activation in the NAc regulates mesolimbic dopamine transmission through the modulation of the GABAergic inhibition of the VTA. Methods: In-vivo electrophysiology was used to investigate the effects of intra-NAc PPARG activation on mesolimbic dopamine activity. The anxiolytic effects of intra-NAc PPARG activation was measured using the light-dark box and elevated plus maze behavioural tests. Results: We report that PPARG activation in the NAc significantly decreases mesolimbic dopamine activity whereas PPARG antagonists block this effect. Additionally, we reveal that intra-NAc PPARG activation produces anxiolytic effects as measured in the light-dark box and elevated plus maze behavioural tests

Asking the readers: audience research into alternative journalism

Alternative forms of journalism are said to challenge the passive role of audience members as receivers and to foster active citizenship among alternative journalists and audiences. Yet the scholarly literature on alternative journalism contains more assertions about than evidence from the audience. Downing has described the audience for alternative media as “the virtually unknown”, prompting him to urge journalism scholars to undertake more audience research to help increase our understanding of this allegedly active and civic-minded public. This exploratory study of the people who regularly read a contemporary example of alternative journalism—an investigative local blog covering one UK city—is intended to contribute towards filling the gap identified by Downing. Audience views are explored by means of questionnaires and focus groups, providing some evidence that individuals are attracted to alternative journalism by their dissatisfaction with mainstream media; that they see alternative media as helping them make sense of the world; and that, to an extent, engaging with such media is both a prompt to, and a reflection of, readers’ democratic engagement as citizens. Recognising the limitations of this small study, the article concludes by reiterating Downing's call for further research

New Plasma Separation Glucose Oxidase-based Glucometer in Monitoring of Blood With Different PO2 Levels

BackgroundThe PalmLab glucometer is a newly designed plasma separation glucose oxidase (GO)-based glucometer. Past studies have shown that the accuracy of GO-based glucometers is compromised when measurements are taken in patients with high PO2 levels. We performed a two-arm study comparing the fitness of the PalmLab blood glucometer with that of a standard glucose analyzer in monitoring blood glucose levels in pediatric patients, especially when arterial partial pressure of oxygen (PO2) was high.MethodsIn the first arm of the study, arterial blood samples from pediatric patients were measured by the PalmLab blood glucometer and the YSI 2302 Plus Glucose/Lactate analyzer. In the second arm of the study, venous blood samples from adult volunteers were spiked with glucose water to prepare three different levels of glucose (65, 150, and 300mg/dL) and then oxygenated to six levels of PO2 (range, 40–400mmHg). The biases of the PalmLab glucometer were calculated.ResultsA total of 162 samples were collected in the first arm of the study. Results of linear regression showed that the coefficient of determination (R2) between PalmLab glucometer and standard glucose analyzer was 0.9864. Error grid analysis revealed that all the results were within Zone A (clinically accurate estimate zone). The biases between the two systems were low at different PO2 levels. In the second arm of the study, the results were also unaffected by changes in PO2.ConclusionThe PalmLab glucometer provides accurate results in samples with high PO2 and is suitable for measuring arterial glucose levels in pediatric patients

Superresolution Pattern Recognition Reveals the Architectural Map of the Ciliary Transition Zone

The transition zone (TZ) of primary cilia serves as a diffusion barrier to regulate ciliogenesis and receptor localization for key signaling events such as sonic hedgehog signaling. Its gating mechanism is poorly understood due to the tiny volume accommodating a large number of ciliopathy-associated molecules. Here we performed stimulated emission depletion (STED) imaging of collective samples and recreated superresolved relative localizations of eight representative species of ciliary proteins using position averages and overlapped with representative electron microscopy (EM) images, defining an architectural foundation at the ciliary base. Upon this framework, transmembrane proteins TMEM67 and TCTN2 were accumulated at the same axial level as MKS1 and RPGRIP1L, suggesting that their regulation roles for tissue-specific ciliogenesis occur at a specific level of the TZ. CEP290 is surprisingly localized at a different axial level bridging the basal body (BB) and other TZ proteins. Upon this molecular architecture, two reservoirs of intraflagellar transport (IFT) particles, correlating with phases of ciliary growth, are present: one colocalized with the transition fibers (TFs) while the other situated beyond the distal edge of the TZ. Together, our results reveal an unprecedented structural framework of the TZ, facilitating our understanding in molecular screening and assembly at the ciliary base

TTBK2: A Tau Protein Kinase beyond Tau Phosphorylation

Tau tubulin kinase 2 (TTBK2) is a kinase known to phosphorylate tau and tubulin. It has recently drawn much attention due to its involvement in multiple important cellular processes. Here, we review the current understanding of TTBK2, including its sequence, structure, binding sites, phosphorylation substrates, and cellular processes involved. TTBK2 possesses a casein kinase 1 (CK1) kinase domain followed by a ∼900 amino acid segment, potentially responsible for its localization and substrate recruitment. It is known to bind to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein. In addition to autophosphorylation, known phosphorylation substrates of TTBK2 include tau, tubulin, CEP164, CEP97, and TDP-43, a neurodegeneration-associated protein. Mutations of TTBK2 are associated with spinocerebellar ataxia type 11. In addition, TTBK2 is essential for regulating the growth of axonemal microtubules in ciliogenesis. It also plays roles in resistance of cancer target therapies and in regulating glucose and GABA transport. Reported sites of TTBK2 localization include the centriole/basal body, the midbody, and possibly the mitotic spindles. Together, TTBK2 is a multifunctional kinase involved in important cellular processes and demands augmented efforts in investigating its functions

A specific group of genes respond to cold dehydration stress in cut Alstroemeria flowers whereas ambient dehydration stress accelerates developmental senescence expression patterns

Petal development and senescence entails a normally irreversible process. It starts with petal expansion and pigment production, and ends with nutrient remobilization and ultimately cell death. In many species this is accompanied by petal abscission. Post-harvest stress is an important factor in limiting petal longevity in cut flowers and accelerates some of the processes of senescence such as petal wilting and abscission. However, some of the effects of moderate stress in young flowers are reversible with appropriate treatments. Transcriptomic studies have shown that distinct gene sets are expressed during petal development and senescence. Despite this, the overlap in gene expression between developmental and stress-induced senescence in petals has not been fully investigated in any species. Here a custom-made cDNA microarray from Alstroemeria petals was used to investigate the overlap in gene expression between developmental changes (bud to first sign of senescence) and typical post-harvest stress treatments. Young flowers were stressed by cold or ambient temperatures without water followed by a recovery and rehydration period. Stressed flowers were still at the bud stage after stress treatments. Microarray analysis showed that ambient dehydration stress accelerates many of the changes in gene expression patterns that would normally occur during developmental senescence. However, a higher proportion of gene expression changes in response to cold stress were specific to this stimulus and not senescence related. The expression of 21 transcription factors was characterized, showing that overlapping sets of regulatory genes are activated during developmental senescence and by different stresses

Prenatal THC Exposure Induces Sex-Dependent Neuropsychiatric Endophenotypes in Offspring and Long-Term Disruptions in Fatty-Acid Signaling Pathways Directly in the Mesolimbic Circuitry

Despite increased prevalence of maternal cannabis use, little is understood regarding potential long-term effects of prenatal cannabis exposure (PCE) on neurodevelopmental outcomes. While neurodevelopmental cannabis exposure increases the risk of developing affective/mood disorders in adulthood, the precise neuro-pathophysiological mechanisms in male and female offspring are largely unknown. Given the interconnectivity of the endocannabinoid (ECb) system and the brain’s fatty acid pathways, we hypothesized that prenatal exposure to ∆9-tetrahydrocannabinol (THC) may dysregulate fetal neurodevelopment through alterations of fatty-acid dependent synaptic and neuronal function in the mesolimbic system. To investigate this, pregnant Wistar rats were exposed to vehicle or THC (3 mg/kg) from gestational day (GD)7 until GD22. Anxiety-like, depres-sive-like, and reward-seeking behavior, electrophysiology, and molecular assays were performed on adult male/female offspring. Imaging of fatty acids using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) was performed at prepubescence and adulthood. We report that PCE induces be-havioral, neuronal, and molecular alterations in the mesolimbic system in male and female offspring, resem-bling neuropsychiatric endophenotypes. Additionally, PCE resulted in profound dysregulation of critical fatty acid pathways in the developing brain lipidome. Female progeny exhibited significant alterations to fatty acid levels at prepubescence but recovered from these deficits by early adulthood. In contrast, males exhibited persistent fatty acid deficits into adulthood. Moreover, both sexes maintained enduring abnormalities in gluta-matergic/GABAergic function in the nucleus accumbens (NAc). These findings identify several novel long-term risks of maternal cannabis use and demonstrate for the first time, sex-related effects of maternal cannabinoid exposure directly in the developing neural lipidome