Differential transcriptional modulation of duplicated fatty acid-binding protein genes by dietary fatty acids in zebrafish (Danio rerio): evidence for subfunctionalization or neofunctionalization of duplicated genes

<p>Abstract</p> <p>Background</p> <p>In the Duplication-Degeneration-Complementation (DDC) model, subfunctionalization and neofunctionalization have been proposed as important processes driving the retention of duplicated genes in the genome. These processes are thought to occur by gain or loss of regulatory elements in the promoters of duplicated genes. We tested the DDC model by determining the transcriptional induction of fatty acid-binding proteins (Fabps) genes by dietary fatty acids (FAs) in zebrafish. We chose zebrafish for this study for two reasons: extensive bioinformatics resources are available for zebrafish at zfin.org and zebrafish contains many duplicated genes owing to a whole genome duplication event that occurred early in the ray-finned fish lineage approximately 230-400 million years ago. Adult zebrafish were fed diets containing either fish oil (12% lipid, rich in highly unsaturated fatty acid), sunflower oil (12% lipid, rich in linoleic acid), linseed oil (12% lipid, rich in linolenic acid), or low fat (4% lipid, low fat diet) for 10 weeks. FA profiles and the steady-state levels of <it>fabp </it>mRNA and heterogeneous nuclear RNA in intestine, liver, muscle and brain of zebrafish were determined.</p> <p>Result</p> <p>FA profiles assayed by gas chromatography differed in the intestine, brain, muscle and liver depending on diet. The steady-state level of mRNA for three sets of duplicated genes, <it>fabp1a/fabp1b.1/fabp1b.2</it>, <it>fabp7a/fabp7b</it>, and <it>fabp11a</it>/<it>fabp11b</it>, was determined by reverse transcription, quantitative polymerase chain reaction (RT-qPCR). In brain, the steady-state level of <it>fabp7b </it>mRNAs was induced in fish fed the linoleic acid-rich diet; in intestine, the transcript level of <it>fabp1b.1 </it>and <it>fabp7b </it>were elevated in fish fed the linolenic acid-rich diet; in liver, the level of <it>fabp7a </it>mRNAs was elevated in fish fed the low fat diet; and in muscle, the level of <it>fabp7a </it>and <it>fabp11a </it>mRNAs were elevated in fish fed the linolenic acid-rich or the low fat diets. In all cases, induction of the steady-state level of <it>fabp </it>mRNAs by dietary FAs correlated with induced levels of hnRNA for a given <it>fabp </it>gene. As such, up-regulation of the steady-state level of <it>fabp </it>mRNAs by FAs occurred at the level of initiation of transcription. None of the sister duplicates of these <it>fabp </it>genes exhibited an increase in their steady-state transcript levels in a specific tissue following feeding zebrafish any of the four experimental diets.</p> <p>Conclusion</p> <p>Differential induction of only one of the sister pair of duplicated <it>fabp </it>genes by FAs provides evidence to support the DDC model for retention of duplicated genes in the zebrafish genome by either subfunctionalization or neofunctionalization.</p

Sustained striatal ciliary neurotrophic factor expression negatively affects behavior and gene expression in normal and R6/1 mice

Huntington's disease (HD) is a neurodegenerative disorder caused by an elongation of CAG repeats in the HD gene, which encodes a mutant copy of huntingtin with an expanded polyglutatmine repeat. Individuals who are affected by the disease suffer from motor, cognitive, and emotional impairments. Levels of certain striatal-enriched mRNAs decrease in both HD patients and transgenic HD mice prior to the development of motor symptoms and neuronal cell death. Ciliary neurotrophic factor (CNTF) has been shown to protect neurons against chemically induced toxic insults in vitro and in vivo. To test the hypothesis that CNTF might protect neurons from the negative effects of the mutant huntingtin protein in vivo, CNTF was continuously expressed following transduction of the striatum by recombinant adeno-associated viral vectors (rAAV2). Wild-type and R6/1 HD transgenic (R6/1) mice that received bilateral or unilateral intrastriatal injections of rAAV2-CNTF experienced weight loss. The CNTF-treated R6/1 HD transgenic mice experienced motor impairments at an earlier age than expected compared with age-matched control R6/1 HD transgenic animals. CNTF also caused abnormal behavior in WT mice. In addition to behavioral impairments, in situ hybridization showed that, in both WT and R6/1 mice, CNTF expression caused a significant decrease in the levels of striatal-enriched transcripts. Overall, continuous expression of striatal CNTF at the dose mediated by the expression cassette used in this study was detrimental to HD and wild-type mice. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58641/1/21636_ftp.pd

Evidence that the fragmented ribosomal RNAs of Chlamydomonas mitochondria are associated with ribosomes

AbstractThe discontinuous and scrambled organization of the small subunit and large subunit rRNA coding regions in Chlamydomonas mitochondrial DNA has been well documented. Our goals were to demonstrate that the small transcripts produced by these coding regions in Chlamydomonas eugametos are assembled into mitochondrial ribosomes and to characterize the sedimentation properties of these ribosomes and their subunits in sucrose gradients. Putative mitochondrial ribosomes (60–66S) and their large (44–50S) and small (35–39S) subunits were identified by slot blot hybridization which sedimented independently of the chloroplast and cytosolic ribosomes. A crude mitochondrial pellet prepared from C. eugametos was enriched for mitochondrial small subunit and large subunit rRNA subfragments thereby providing independent confirmation of the mitochondrial association of these rRNA molecules

Development and Validation of the Combined Action Observation and Motor Imagery Ability Questionnaire

Combined use of action observation and motor imagery (AOMI) is an increasingly popular motor-simulation intervention, which involves observing movements on video while simultaneously imagining the feeling of movement execution. Measuring and reporting participant imagery-ability characteristics are essential in motor-simulation research, but no measure of AOMI ability currently exists. Accordingly, the AOMI Ability Questionnaire (AOMI-AQ) was developed to address this gap in the literature. In Study 1, two hundred eleven participants completed the AOMI-AQ and the kinesthetic imagery subscales of the Movement Imagery Questionnaire-3 and Vividness of Motor Imagery Questionnaire-2. Following exploratory factor analysis, an 8-item AOMI-AQ was found to correlate positively with existing motor-imagery measures. In Study 2, one hundred seventy-four participants completed the AOMI-AQ for a second time after a period of 7-10 days. Results indicate a good test-retest reliability for the AOMI-AQ. The new AOMI-AQ measure provides a valid and reliable tool for researchers and practitioners wishing to assess AOMI ability

Biased Type 1 Cannabinoid Receptor Signaling Influences Neuronal Viability in a Cell Culture Model of Huntington Disease

ABSTRACT Huntington disease (HD) is an inherited, autosomal dominant, neurodegenerative disorder with limited treatment options. Prior to motor symptom onset or neuronal cell loss in HD, levels of the type 1 cannabinoid receptor (CB 1 ) decrease in the basal ganglia. Decreasing CB 1 levels are strongly correlated with chorea and cognitive deficit. CB 1 agonists are functionally selective (biased) for divergent signaling pathways. In this study, six cannabinoids were tested for signaling bias in in vitro models of medium spiny projection neurons expressing wild-type (STHdh Q7/Q7 ) or mutant huntingtin protein (STHdh Q111/Q111 ). Signaling bias was assessed using the Black and Leff operational model. Relative activity [DlogR (t/K A )] and system bias (DDlogR) were calculated relative to the reference compound WIN55,212-2 for Ga i/o , Ga s , Ga q , Gbg, and b-arrestin1 signaling following treatment with 2-arachidonoylglycerol (2-AG), anandamide (AEA), CP55,940, D 9 -tetrahydrocannabinol (THC), cannabidiol (CBD), and THC1CBD (1:1), and compared between wild-type and HD cells. The E max of Ga i/o -dependent extracellular signal-regulated kinase (ERK) signaling was 50% lower in HD cells compared with wild-type cells. 2-AG and AEA displayed Ga i/o /Gbg bias and normalized CB 1 protein levels and improved cell viability, whereas CP55,940 and THC displayed b-arrestin1 bias and reduced CB 1 protein levels and cell viability in HD cells. CBD was not a CB 1 agonist but inhibited THC-dependent signaling (THC1CBD). Therefore, enhancing Ga i/o -biased endocannabinoid signaling may be therapeutically beneficial in HD. In contrast, cannabinoids that are b-arrestin-biased-such as THC found at high levels in modern varieties of marijuana-may be detrimental to CB 1 signaling, particularly in HD where CB 1 levels are already reduced

Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s)

ACKNOWLEDGMENTS The work was supported by National Institutes of Health grants DA027113 and EY024717 to G.A.T. and DA09158 to A.M. A portion of this work was submitted in 2011 by A. Kulkarni in partial fulfillment of M.S. degree requirements from Northeastern University, Boston, MA.Peer reviewedPublisher PD

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Developing autonomous learning in first year university students using perspectives from positive psychology

Autonomous learning is a commonly occurring learning outcome from university study, and it is argued that students require confidence in their own abilities to achieve this. Using approaches from positive psychology, this study aimed to develop confidence in first‐year university students to facilitate autonomous learning. Psychological character strengths were assessed in 214 students on day one at university. Two weeks later their top three strengths were given to them in study skills modules as part of a psycho‐educational intervention designed to increase their self‐efficacy and self‐esteem. The impact of the intervention was assessed against a control group of 40 students who had not received the intervention. The results suggested that students were more confident after the intervention, and that levels of autonomous learning increased significantly compared to the controls. Character strengths were found to be associated with self‐efficacy, self‐esteem and autonomous learning in ways that were theoretically meaningful

Assessing psychological health : the contribution of psychological strengths

Balanced assessment of mental health involves assessing wellbeing and strengths as well as psychopathology. The character strengths of curiosity, gratitude, hope, optimism and forgiveness, are assessed in 214 new undergraduates and their relationships to mental health, subjective wellbeing and self-esteem explored. Scoring the mental health scale for psychiatric caseness, case and non-case students did not differ in character strengths, positive affect or life satisfaction, supporting a dual-factor model. Hope pathways and gratitude predicted mental health. Gratitude, hope agency and exploratory curiosity predicted positive affect. Gratitude and hope agency predicted life satisfaction. Hope agency, hope pathways, exploratory curiosity and gratitude predicted self-esteem, with absorption curiosity a negative predictor. The benefits of assessing strengths are discussed and interventions designed to develop them. Keywords: character strengths; mental health; subjective wellbeing; dual-factor mental health model; self-estee