Conserved transcriptional activity and ligand responsiveness of avian PPARs: Potential role in regulating lipid metabolism in mirgratory birds.

Migratory birds undergo metabolic remodeling in tissues, including increased lipid storage in white adipose and fatty acid uptake and oxidation in skeletal muscle, to optimize energy substrate availability and utilization in preparation for long-distance flight. Different tissues undergo gene expression changes in keeping with their specialized functions and driven by tissue specific transcriptional pathways. Peroxisome proliferator-activated receptors (PPARs) are lipid-activated nuclear receptors that regulate metabolic pathways involved in lipid and glucose utilization or storage in mammals. To examine whether PPARs might mediate fatty acid activation of metabolic gene programs that would be relevant during pre-migratory fattening, we used gray catbird as the focal species. PPAR isoforms cloned from catbird share high amino acid identity with mammalian homologs (% vs human): gcPPARα (88.1%), gcPPARδ (87.3%), gcPPARγ (91.2%). We tested whether gcPPARs activated fatty acid (FA) utilization genes using Lpl and Cpt1b gene promoter-luciferase reporters in mammalian cell lines. In C2C12 mouse myocytes gcPPARα was broadly activated by the saturated and unsaturated FAs tested; while gcPPARδ showed highest activation by the mono-unsaturated FA, 18:1 oleic acid (+80%). In CV-1 monkey kidney cells gcPPARγ responded to the poly-unsaturated fatty acid, 20:5 eicosapentaenoic acid (+60%). Moreover, in agreement with their structural conservation, gcPPARs were activated by isoform selective synthetic agonists similar to the respective mammalian isoform. Adenoviral mediated over-expression of PPARα in C2C12 myocytes induced expression of genes involved in fatty acid transport, including Cd36/Fat, as well as Cpt1b, which mediates a key rate limiting step of mitochondrial ß-oxidation. These gene expression changes correlated with increased lipid droplet accumulation in C2C12 myoblasts and differentiated myotubes and enhanced ß-oxidation in myotubes. Collectively, the data predict that the PPARs play a conserved role in gray catbirds to regulate lipid metabolism in target tissues that undergo metabolic remodeling throughout the annual migratory cycle.

Bidirectional Associations Between Teacher-Child Relationship Quality and Chinese American Immigrant Children's Behavior Problems.

The goal of the study was to test the bidirectional associations between teacher-child relationship quality and behavior problems in an elementary school age sample of Chinese American immigrant children. A socioeconomically diverse sample (N = 258) of first- and second-generation Chinese American children (M ages = 7.4 and 9.2 years at Wave 1 and Wave 2, respectively; 48% girls) was recruited from schools and communities and followed for 1 to 2 years. Two waves of data on dimensions of teacher-child relationship quality (i.e., warmth, closeness, and conflict) and children's externalizing and internalizing problems were collected through parents', teachers', and children's report. Path analyses were conducted to test the bidirectional associations between teacher-child relationship quality and behavior problems, controlling for prior levels, child demographic characteristics, and teacher ethnicity. Transactional associations between teacher-child relationship quality and children's behavior problems were found for externalizing problems. That is, teacher-rated externalizing problems negatively predicted child-rated closeness, and teacher-rated conflict positively predicted parent-rated externalizing problems. On the other hand, teacher-child relationship quality did not predict subsequent internalizing problems. However, parent-rated internalizing problems negatively predicted teacher-rated warmth, and teacher-rated internalizing problems negatively predicted teacher-rated conflict. Using a multiple informant approach and a diverse sample of Chinese American immigrant children, this study extends our knowledge of the reciprocal associations between teacher-child relationship quality and children's behavior problems. Based on the results of this study, the authors provide recommendations for educators and future research with this understudied population.

Neighborhood characteristics, parenting styles, and children's behavioral problems in Chinese American immigrant families.

Using data from a socioeconomically diverse sample of Chinese American children (n = 258, aged 6-9 years) in immigrant families, we examined the concurrent relations among neighborhood economic disadvantage and concentration of Asian residents, parenting styles, and Chinese American children's externalizing and internalizing problems. Neighborhood characteristics were measured with 2000 U.S. Census tract-level data, parents (mostly mothers) rated their own parenting styles, and parents and teachers rated children's behavioral problems. Path analysis was conducted to test two hypotheses: (a) parenting styles mediate the relations between neighborhood characteristics and children's behavioral problems, and (b) children's behavioral problems mediate the relations between neighborhood and parenting styles. We found that neighborhood Asian concentration was positively associated with authoritarian parenting, which in turn was associated with Chinese American children's higher externalizing and internalizing problems (by parents' reports). In addition, neighborhood economic disadvantage was positively related to children's externalizing problems (by parents' reports), which in turn predicted lower authoritative parenting. The current results suggest the need to consider multiple pathways in the relations among neighborhood, family, and child adjustment, and they have implications for the prevention and intervention of behavioral problems in Chinese American children.

Paediatric poisoning exposures in schools: reports to Australia's largest poisons centre.

OBJECTIVE: To describe poisoning exposures occurring at school in a large sample of Australian children. DESIGN: A population-based retrospective cohort study. SETTING: Cases reported to the New South Wales Poisons Information Centre (NSWPIC), Australia's largest poisons information centre, taking 50% of the nation's poisoning calls. PATIENTS: Poisoning exposures occurring in children and adolescents while at school were included, over a 4.5-year period (January 2014 to June 2018). MAIN OUTCOME MEASURES: Time trends in poisonings, demographics, exposure characteristics, substances involved, disposition. RESULTS: There were 1751 calls relating to exposures at school made to NSWPIC. Most calls concerned accidental exposures (60.8%, n=1064), followed by deliberate self-poisonings (self-harm, 12.3%, n=216). Over a quarter of cases were hospitalised (n=468), where the call originated from hospital or patients referred to hospital by NSWPIC. Disposition varied by exposure type, and hospitalisation was highest with deliberate self-poisonings (92.6%, n=200), recreational exposures (57.1%, n=12) and other intentional exposures (32.6%, n=45). The median age was 12 (IQR 8-15 years), and 54.7% were male (n=958). The most common pharmaceutical exposures were to paracetamol (n=100), methylphenidate (n=78) and ibuprofen (n=53), with the majority being deliberate self-poisonings. Copper sulfate was responsible for 55 science class cases, 45% of which were hospitalised. Cases may be increasing, with 81.3 (±8.2) calls per quarter, 2014-2016, and 129.3 (±24.3) calls per quarter, 2017-2018. CONCLUSIONS: Poisoning exposures occurring at school are common, with disposition and substances involved varying considerably by exposure reason. The relatively high number of referrals to hospital highlights the need for investigation into preventative measures.

Voltage-dependent anion-selective channel 1 (VDAC1)--a mitochondrial protein, rediscovered as a novel enzyme in the plasma membrane.

The eukaryotic porin or voltage-dependent anion-selective channel (VDAC1) is a pore-forming protein discovered twenty five years ago in the mitochondrial outer membrane. Its gene in eukaryotes is known, but its tertiary structure has never been solved. Structure predictions highlight the presence of several amphipathic beta-strands possibly organised in a beta-barrel. VDAC1 has recently been described as being a NADH:ferricyanide reductase in the plasma membrane. There it affects the regulation of cell growth and death. Physiological cell death (apoptosis) has become a major research focus of biomedical research. Regulation of the enzyme will have impacts on cancer and autoimmune diseases (insufficient apoptosis) as well as neurodegenerative diseases (excessive apoptosis). VDAC1 in the plasma membrane establishes a novel level of apoptosis regulation putatively via its redox activity.

Transplasma membrane electron transport: enzymes involved and biological function.

The notion of transmembrane electron transport is usually associated with mitochondria and chloroplasts. However, since the early 1970s, it has been known that this phenomenon also occurs at the level of the plasma membrane. Ever since, evidence has accumulated for the existence of a plethora of transplasma membrane electron transport enzymes. In this review, we discuss the various enzymes known, their molecular characteristics and their biological functions.

Correlation of cerebral blood flow and treatment effects of repetitive transcranial magnetic stimulation in depressed patients.

The aims of this study were to: (1) assess the effects of repetitive transcranial magnetic stimulation (rTMS) on brain activity in depressed patients as measured by single photon emission tomography (SPECT); (2) evaluate the predictive value of brain SPECT on the antidepressant efficacy of rTMS. Patients (n=17) received 1600 rTMS stimuli at a rate of 10 Hz, 5 days per week for 2 weeks to the left dorsolateral prefrontal cortex. Whole brain SPECT data were acquired using Tc99m-Bicisate. Regional cerebral blood flow (rCBF) was correlated with the % change in the 28-item Hamilton Depression Rating Scale Score (Delta-HDRS) and a semiquantitative region of interest (ROI) analysis was conducted. Prior to rTMS there was a significant left-right asymmetry favoring the right, whereas 2 weeks after the rTMS treatment this asymmetry was reversed. The rCBF in limbic structures was negatively correlated with the outcome and rCBF in several neocortical areas was positively correlated. Brain SPECT can provide information about mechanisms of action of rTMS and may have predictive value for the antidepressant efficacy of rTMS.

Characterization of VDAC1 as a plasma membrane NADH-oxidoreductase.

We have recently demonstrated that voltage dependent anion selective channel~1 (porin, isoform 1) can function as a transplasma membrane NADH:ferricyanide-reductase. However, both the specific redox characteristics and the mechanism of electron transport in this enzyme presently remain unclear. Here we demonstrate that the redox capability of porin 1 is specific for ferricyanide as this same enzyme cannot reduce DCIP or cytochrome c in vitro. Furthermore, NADH-dependent ferricyanide reduction associated with VDAC1 is not sensitive to the anion channel inhibitors DIDS and dextran sulfate. However, this activity can be inhibited by thiol chelators, suggesting that at least one of the two cysteine groups present in VDAC1 are critical for electron transfer. We propose a model on how electron transport may occur in VDAC1.

Parent-child cultural orientations and child adjustment in Chinese American immigrant families.

Direct and indirect/mediated relations of (a) children's and parents' cultural orientations and (b) parent-child gaps in cultural orientations to children's psychological adjustment were examined in a socioeconomically diverse sample of 258 Chinese American children (age = 6-9 years) from immigrant families. Parents reported on children's and their own Chinese and American orientations in language proficiency, media use, and social relationships. Parents and teachers rated children's externalizing and internalizing problems and social competence. Using structural equation modeling, we found evidence for both the effects of children's and parents' cultural orientations and the effects of parent-child gaps. Specifically, children's American orientations across domains were associated with their better adjustment (especially social competence). These associations were partly mediated by authoritative parenting. Parents' English and Chinese media use were both associated with higher authoritative parenting, which in turn was associated with children's better adjustment. Furthermore, greater gaps in parent-child Chinese proficiency were associated with children's poorer adjustment, and these relations were partly mediated by authoritative parenting. Together, the findings underscore the complex relations between immigrant families' dual orientations to the host and heritage cultures and children's psychological adjustment.

Cancer pain is not necessarily correlated with spinal overexpression of reactive glia markers.

Bone cancer pain is a common and disruptive symptom in cancer patients. In cancer pain animal models, massive reactive astrogliosis in the dorsal horn of the spinal cord has been reported. Because astrocytes may behave as driving partners for pathological pain, we investigated the temporal development of pain behavior and reactive astrogliosis in a rat bone cancer pain model induced by injecting MRMT-1 rat mammary gland carcinoma cells into the tibia. Along with the development of bone lesions, a gradual mechanical and thermal allodynia and hyperalgesia as well as a reduced use of the affected limb developed in bone cancer-bearing animals, but not in sham-treated animals. Dorsal horn Fos expression after nonpainful palpation of the injected limb was also increased in bone cancer-bearing animals. However, at any time during the evolution of tumor, there was no increase in glial fibrillary acidic protein (GFAP) immunoreactivity in the dorsal horn. Further analysis at 21days after injection of the tumor showed no increase in GFAP and interleukin (IL) 1ß transcripts, number of superficial dorsal horn S100ß protein immunoreactive astrocytes, or immunoreactivity for microglial markers (OX-42 and Iba-1). In contrast, all these parameters were increased in the dorsal horn of rats 2weeks after sciatic nerve ligation. This suggests that in some cases, bone cancer pain may not be correlated with spinal overexpression of reactive glia markers, whereas neuropathic pain is. Glia may thus play different roles in the development and maintenance of chronic pain in these 2 situations.

Teacher-child relationship quality and academic achievement of Chinese American children in immigrant families.

This study examined the cross-sectional relations between teacher-child relationship quality (TCRQ) and math and reading achievement in a socio-economically diverse sample of Chinese American first- and second-grade children in immigrant families (N=207). Teachers completed a questionnaire measuring TCRQ dimensions including closeness, conflict, and intimacy, and children completed a questionnaire measuring overall TCRQ. Standardized tests were used to assess children's math and reading skills. Analyses were conducted to (a) test the factor structure of measures assessing TCRQ among Chinese American children, (b) examine the associations between teacher- and child-rated TCRQ and children's academic achievement, controlling for demographic characteristics, and (c) examine the potential role of child gender as a moderator in the relations between TCRQ and achievement. Results indicated that teacher-rated TCRQ Warmth was positively associated with Chinese American children's reading achievement. Two child gender-by-TCRQ interactions were found: (a) teacher-rated TCRQ Conflict was negatively associated with girls' (but not boys') math achievement, and (b) child-rated Overall TCRQ was positively associated with boys' (but not girls') reading achievement. These findings highlight the valuable role of TCRQ in the academic success of school-aged children in immigrant families.

VDAC1 is a transplasma membrane NADH-ferricyanide reductase.

Porin isoform 1 or VDAC (voltage-dependent anion-selective channel) 1 is the predominant protein in the outer mitochondrial membrane. We demonstrated previously that a plasma membrane NADH-ferricyanide reductase activity becomes up-regulated upon mitochondrial perturbation, and therefore suggested that it functions as a cellular redox sensor. VDAC1 is known to be expressed in the plasma membrane; however, its function there remained a mystery. Here we show that VDAC1, when expressed in the plasma membrane, functions as a NADH-ferricyanide reductase. VDAC1 preparations purified from both plasma membrane and mitochondria fractions exhibit NADH-ferricyanide reductase activity, which can be immunoprecipitated with poly- and monoclonal antibodies directed against VDAC(1). Transfecting cells with pl-VDAC1-GFP, which carries an N-terminal signal peptide, directs VDAC1 to the plasma membrane, as shown by confocal microscopy and FACS analysis, and significantly increases the plasma membrane NADH-ferricyanide reductase activity of the transfected cells. This novel enzymatic activity of the well known VDAC1 molecule may provide an explanation for its role in the plasma membrane. Our data suggest that a major function of VDAC1 in the plasma membrane is that of a NADH(-ferricyanide) reductase that may be involved in the maintenance of cellular redox homeostasis.