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Glutamate receptor, metabotropic 7 (GRM7) gene variations and susceptibility to autism: A case-control study.
Glutamate receptor, metabotropic 7 (GRM7) gene variations and susceptibility to autism: A case-control study.
Autism Res. 2016 Jun 17;
Authors: Noroozi R, Taheri M, Movafagh A, Mirfakhraie R, Solgi G, Sayad A, Mazdeh M, Darvish H
Autism spectrum disorder (ASD) as a synaptopathy is revealed to be pertained to aberrant glutamatergic neurotransmission. Glutamate receptor, metabotropic 7 (GRM7), a receptor coding gene of this pathway, is a new candidate gene for autism. The aim of this study was to examine if there is a relationship between genetic variants rs779867 and rs6782011 of GRM7 with ASD. The present research was designed as a population-based, case-control study including 518 ASD patients versus 472 control individuals. The results showed that the frequency of rs779867 G/G genotype was significantly higher in ASD patients compared to healthy controls (P = 0.0001). Also, the G allele of this SNP was found to be significantly more frequent in the patients than control group (P = 0.0001). Haplotype analysis exhibited significant association of two estimated block of rs6782011/rs779867 in ASD patients versus control group. We found higher significant frequency of GT haplotype and lower frequencies of AT and AC haplotypes in the patients group compared to healthy controls (P = 0.001, P = 0.006, and P = 0.05, respectively). Our study indicated that the rs779867 polymorphism is associated with ASD; thus, results of this study provide supportive evidence of association of the GRM7 gene with ASD. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
PMID: 27312574 [PubMed - as supplied by publisher]
Biological Psychiatry and Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Adopt Neuroscience-Based Nomenclature.
Biological Psychiatry and Biological Psychiatry: Cognitive Neuroscience and Neuroimaging Adopt Neuroscience-Based Nomenclature.
Biol Psychiatry. 2016 Jul 1;80(1):2-3
Authors: Krystal JH, Abi-Dargham A, Barch DM, Bullmore ET, Carter CS, Geschwind DH, Harrison PJ, Nestler EJ, Stein MB
PMID: 27312230 [PubMed - in process]
Delayed diagnosis in a house of correction: Smith-Magenis syndrome due to a de novo nonsense RAI1 variant.
Delayed diagnosis in a house of correction: Smith-Magenis syndrome due to a de novo nonsense RAI1 variant.
Am J Med Genet A. 2016 Jun 17;
Authors: Yeetong P, Vilboux T, Ciccone C, Boulier K, Schnur RE, Gahl WA, Huizing M, Laje G, Smith AC
We report a 25-year-old female confirmed to have Smith-Magenis syndrome (SMS) due to a de novo RAI1 variant. Her past history is significant for developmental and intellectual delay, early and escalating maladaptive behaviors, and features consistent with significant sleep disturbance, the etiology of which was not confirmed for over two decades. The diagnosis of SMS was initially suspected in 1998 (at age 12 years), but that was 5 years before the initial report of RAI1 variants as causative of the SMS phenotype; cytogenetic fluorescence in situ hybridization studies failed to confirm an interstitial deletion of 17p11.2. Re-evaluation for suspected SMS was pursued with RAI1 sequencing analysis in response to urgent parental concerns of escalating behaviors and aggression with subsequent incarceration of the subject for assault of a health professional. Genetic analysis revealed a de novo RAI1 (NM_030665.3) nonsense variant, c.5536C>T; p.Q1846X. This case illustrates the importance of confirming the SMS diagnosis, which is associated with cognitive and functional impairment, as well as significant psychiatric co-morbidities and behavioral problems. The diagnosis was particularly relevant to the legal discussion and determination of her competence to stand trial. As other similar cases may exist, this report will help to increase awareness of the possibility of a very late diagnosis of SMS, with the need for re-evaluation of individuals suspected to have SMS who were initially evaluated prior to the identification of the RAI1 gene. © 2016 Wiley Periodicals, Inc.
PMID: 27311559 [PubMed - as supplied by publisher]
Social behavior in a genetic model of dopamine dysfunction at different neurodevelopmental time points.
Social behavior in a genetic model of dopamine dysfunction at different neurodevelopmental time points.
Genes Brain Behav. 2015 Sep;14(7):503-15
Authors: Kabitzke PA, Simpson EH, Kandel ER, Balsam PD
Impairments in social behavior characterize many neurodevelopmental psychiatric disorders. In fact, the temporal emergence and trajectory of these deficits can define the disorder, specify their treatment and signal their prognosis. The sophistication of mouse models with neurobiological endophenotypes of many aspects of psychiatric diseases has increased in recent years, with the necessity to evaluate social behavior in these models. We adapted an assay for the multimodal characterization of social behavior at different development time points (juvenile, adolescent and adult) in control mice in different social contexts (specifically, different sex pairings). Although social context did not affect social behavior in juvenile mice, it did have an effect on the quantity and type of social interaction as well as ultrasonic vocalizations in both adolescence and adulthood. We compared social development in control mice to a transgenic mouse model of the increase in postsynaptic striatal D2R activity observed in patients with schizophrenia (D2R-OE mice). Genotypic differences in social interactions emerged in adolescence and appeared to become more pronounced in adulthood. That vocalizations emitted from dyads with a D2R-OE subject were negatively correlated with active social behavior while vocalizations from control dyads were positively correlated with both active and passive social behavior also suggest social deficits. These data show that striatal dopamine dysfunction plays an important role in the development of social behavior and mouse models such as the one studied here provide an opportunity for screening potential therapeutics at different developmental time points.
PMID: 26176662 [PubMed - indexed for MEDLINE]
Overlap of autism spectrum disorder and glucose transporter 1 deficiency syndrome associated with a heterozygous deletion at the 1p34.2 region.
Overlap of autism spectrum disorder and glucose transporter 1 deficiency syndrome associated with a heterozygous deletion at the 1p34.2 region.
J Neurol Sci. 2015 Sep 15;356(1-2):212-4
Authors: Lee MS, Kim YJ, Kim EJ, Lee MJ
PMID: 26117362 [PubMed - indexed for MEDLINE]
Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy.
Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy.
J Child Neurol. 2015 Oct;30(11):1472-82
Authors: Banihani R, Smile S, Yoon G, Dupuis A, Mosleh M, Snider A, McAdam L
Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of < 70 was seen in 27%; learning disability in 44%, intellectual disability in 19%; attention-deficit/hyperactivity disorder in 32%; autism spectrum disorders in 15%; and anxiety in 27%. Mutations affecting Dp260 isoform and 5'untranslated region of Dp140 were observed in 60% with learning disability, 50% intellectual disability, 77% with autism spectrum disorders, and 94% with anxiety. No statistically significant correlation was noted between comorbidities and dystrophin isoforms; however, there is a trend of cumulative loss of dystrophin isoforms with declining full-scale IQ. Enhanced psychology testing to include both cognitive and neurobehavioral disorders is recommended for all individuals with Duchenne muscular dystrophy.
PMID: 25660133 [PubMed - indexed for MEDLINE]
The Altered Promoter Methylation Of Oxytocin Receptor Gene In Autism.
The Altered Promoter Methylation Of Oxytocin Receptor Gene In Autism.
J Neurogenet. 2016 Jun 16;:1-15
Authors: Elagoz Yuksel M, Yuceturk B, Karatas OF, Ozen M, Dogangun B
Autism spectrum disorders (ASDs) are one of the life long existing disorders. Abnormal methylation status of gene promoters of oxytonergic system has been implicated as among the etiologic factors of ASDs. We, therefore, investigated the methylation frequency of oxytocin receptor gene (OXTR) promoter from peripheral blood samples of children with autistic features. Our sample includes 66 children in total (22-94 months); 27 children with ASDs according to the DSM-IV-TR and the Childhood Autism Rating Scale and 39 children who don't have any autistic like symptoms as the healthy control group. We investigated the DNA methylation status of OXTR promoter by methylation specific enzymatic digestion of genomic DNA and polymerase chain reaction. A significant relationship has been found between ASDs and healthy controls for the reduction of methylation frequency of the regions MT1 and MT3 of OXTR. We could not find any association in the methylation frequency of MT2 and MT4 regions of OXTR. Although our findings indicate high frequency of OXTR promoter hypomethylation in ASDs, there is need for independent replication of the results in a bigger sample set. We expect that future studies with the inclusion of larger, more homogeneous samples will attempt to disentangle the causes of ASDs.
PMID: 27309964 [PubMed - as supplied by publisher]
Evaluation of polygenic risks for narcolepsy and essential hypersomnia.
Evaluation of polygenic risks for narcolepsy and essential hypersomnia.
J Hum Genet. 2016 Jun 16;
Authors: Yamasaki M, Miyagawa T, Toyoda H, Khor SS, Liu X, Kuwabara H, Kano Y, Shimada T, Sugiyama T, Nishida H, Sugaya N, Tochigi M, Otowa T, Okazaki Y, Kaiya H, Kawamura Y, Miyashita A, Kuwano R, Kasai K, Tanii H, Sasaki T, Honda Y, Honda M, Tokunaga K
In humans, narcolepsy is a sleep disorder that is characterized by sleepiness, cataplexy and rapid eye movement (REM) sleep abnormalities. Essential hypersomnia (EHS) is another type of sleep disorder that is characterized by excessive daytime sleepiness without cataplexy. A human leukocyte antigen (HLA) class II allele, HLA-DQB1*06:02, is a major genetic factor for narcolepsy. Almost all narcoleptic patients are carriers of this HLA allele, while 30-50% of EHS patients and 12% of all healthy individuals in Japan carry this allele. The pathogenesis of narcolepsy and EHS is thought to be partially shared. To evaluate the contribution of common single-nucleotide polymorphisms (SNPs) to narcolepsy onset and to assess the common genetic background of narcolepsy and EHS, we conducted a polygenic analysis that included 393 narcoleptic patients, 38 EHS patients with HLA-DQB1*06:02, 119 EHS patients without HLA-DQB1*06:02 and 1582 healthy individuals. We also included 376 individuals with panic disorder and 213 individuals with autism to confirm whether the results were biased. Polygenic risks in narcolepsy were estimated to explain 58.1% (PHLA-DQB1*06:02=2.30 × 10(-48), Pwhole genome without HLA-DQB1*06:02=6.73 × 10(-2)) including HLA-DQB1*06:02 effects and 1.3% (Pwhole genome without HLA-DQB1*06:02=2.43 × 10(-2)) excluding HLA-DQB1*06:02 effects. The results also indicated that small-effect SNPs contributed to the development of narcolepsy. Reported susceptibility SNPs for narcolepsy in the Japanese population, CPT1B (carnitine palmitoyltransferase 1B), TRA@ (T-cell receptor alpha) and P2RY11 (purinergic receptor P2Y, G-protein coupled, 11), were found to explain 0.8% of narcolepsy onset (Pwhole genome without HLA-DQB1*06:02=9.74 × 10(-2)). EHS patients with HLA-DQB1*06:02 were estimated to have higher shared genetic background to narcoleptic patients than EHS patients without HLA-DQB1*06:02 even when the effects of HLA-DQB1*06:02 were excluded (EHS with HLA-DQB1*06:02: 40.4%, PHLA-DQB1*06:02=7.02 × 10(-)(14), Pwhole genome without HLA-DQB1*06:02=1.34 × 10(-)(1), EHS without HLA-DQB1*06:02: 0.4%, Pwhole genome without HLA-DQB1*06:02=3.06 × 10(-)(1)). Meanwhile, the polygenic risks for narcolepsy could not explain the onset of panic disorder and autism, suggesting that our results were reasonable.Journal of Human Genetics advance online publication, 16 June 2016; doi:10.1038/jhg.2016.65.
PMID: 27305985 [PubMed - as supplied by publisher]
Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic.
Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic.
Environ Monit Assess. 2016 Jul;188(7):407
Authors: Dickerson AS, Rahbar MH, Bakian AV, Bilder DA, Harrington RA, Pettygrove S, Kirby RS, Durkin MS, Han I, Moyé LA, Pearson DA, Wingate MS, Zahorodny WM
Lead, mercury, and arsenic are neurotoxicants with known effects on neurodevelopment. Autism spectrum disorder (ASD) is a neurodevelopmental disorder apparent by early childhood. Using data on 4486 children with ASD residing in 2489 census tracts in five sites of the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring (ADDM) Network, we used multi-level negative binomial models to investigate if ambient lead, mercury, and arsenic concentrations, as measured by the US Environmental Protection Agency National-Scale Air Toxics Assessment (EPA-NATA), were associated with ASD prevalence. In unadjusted analyses, ambient metal concentrations were negatively associated with ASD prevalence. After adjusting for confounding factors, tracts with air concentrations of lead in the highest quartile had significantly higher ASD prevalence than tracts with lead concentrations in the lowest quartile (prevalence ratio (PR) = 1.36; 95 '% CI: 1.18, 1.57). In addition, tracts with mercury concentrations above the 75th percentile (>1.7 ng/m(3)) and arsenic concentrations below the 75th percentile (≤0.13 ng/m(3)) had a significantly higher ASD prevalence (adjusted RR = 1.20; 95 % CI: 1.03, 1.40) compared to tracts with arsenic, lead, and mercury concentrations below the 75th percentile. Our results suggest a possible association between ambient lead concentrations and ASD prevalence and demonstrate that exposure to multiple metals may have synergistic effects on ASD prevalence.
PMID: 27301968 [PubMed - in process]
Mouse pups lacking collapsin response mediator protein 4 manifest impaired olfactory function and hyperactivity in the olfactory bulb.
Mouse pups lacking collapsin response mediator protein 4 manifest impaired olfactory function and hyperactivity in the olfactory bulb.
Eur J Neurosci. 2015 Sep;42(6):2335-45
Authors: Tsutiya A, Nishihara M, Goshima Y, Ohtani-Kaneko R
Members of the collapsin response mediator protein (CRMP) family are reported to be involved in the pathogenesis of various neuronal disorders, including schizophrenia and autism. One of them, CRMP4, is reported to participate in aspects of neuronal development, such as axonal guidance and dendritic development. However, no physiological or behavioral phenotypes in Crmp4 knockout (Crmp4-KO) mice have been identified, making it difficult to elucidate the in vivo roles of CRMP4. Focusing on the olfaction process because of the previous study showing strong expression of Crmp4 mRNA in the olfactory bulb (OB) during the early postnatal period, it was aimed to test the hypothesis that Crmp4-KO pups would exhibit abnormal olfaction. Based on measurements of their ultrasonic vocalizations, impaired olfactory ability in Crmp4-KO pups was found. In addition, c-Fos expression, a marker of neuron activity, revealed hyperactivity in the OB of Crmp4-KO pups compared with wild-types following exposure to an odorant. Moreover, the mRNA and protein expression levels of glutamate receptor 1 (GluR1) and 2 (GluR2) were exaggerated in Crmp4-KO pups relative to other excitatory and inhibitory receptors and transporters, raising the possibility that enhanced expression of these excitatory receptors contributes to the hyperactivity phenotype and impairs olfactory ability. This study provides evidence for an animal model for elucidating the roles of CRMP4 in the development of higher brain functions as well as for elucidating the developmental regulatory mechanisms controlling the activity of the neural circuitry.
PMID: 26118640 [PubMed - indexed for MEDLINE]
Duplications of SLC1A3: Associated with ADHD and autism.
Duplications of SLC1A3: Associated with ADHD and autism.
Eur J Med Genet. 2016 Jun 10;
Authors: van Amen-Hellebrekers CJ, Jansen S, Pfundt R, Schuurs-Hoeijmakers JH, Koolen DA, Marcelis CL, de Leeuw N, de Vries BB
We report four patients with a similar gain in 5p13.2 encompassing a single gene: SLC1A3. Behavioural problems resembling ADHD and/or autism-like features are observed which is in line with the glial glutamate transporter role of SLC1A3. We consider an association between SLC1A3 and the behavioural problems which can also be considered a contributing factor to behavioural problems in larger duplications overlapping the 5p13 microduplication syndrome region.
PMID: 27296938 [PubMed - as supplied by publisher]
KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome.
KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome.
Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):751-6
Authors: Tang X, Kim J, Zhou L, Wengert E, Zhang L, Wu Z, Carromeu C, Muotri AR, Marchetto MC, Gage FH, Chen G
Rett syndrome is a severe form of autism spectrum disorder, mainly caused by mutations of a single gene methyl CpG binding protein 2 (MeCP2) on the X chromosome. Patients with Rett syndrome exhibit a period of normal development followed by regression of brain function and the emergence of autistic behaviors. However, the mechanism behind the delayed onset of symptoms is largely unknown. Here we demonstrate that neuron-specific K(+)-Cl(-) cotransporter2 (KCC2) is a critical downstream gene target of MeCP2. We found that human neurons differentiated from induced pluripotent stem cells from patients with Rett syndrome showed a significant deficit in KCC2 expression and consequently a delayed GABA functional switch from excitation to inhibition. Interestingly, overexpression of KCC2 in MeCP2-deficient neurons rescued GABA functional deficits, suggesting an important role of KCC2 in Rett syndrome. We further identified that RE1-silencing transcriptional factor, REST, a neuronal gene repressor, mediates the MeCP2 regulation of KCC2. Because KCC2 is a slow onset molecule with expression level reaching maximum later in development, the functional deficit of KCC2 may offer an explanation for the delayed onset of Rett symptoms. Our studies suggest that restoring KCC2 function in Rett neurons may lead to a potential treatment for Rett syndrome.
PMID: 26733678 [PubMed - indexed for MEDLINE]
Increased Cortical Inhibition in Autism-Linked Neuroligin-3R451C Mice Is Due in Part to Loss of Endocannabinoid Signaling.
Increased Cortical Inhibition in Autism-Linked Neuroligin-3R451C Mice Is Due in Part to Loss of Endocannabinoid Signaling.
PLoS One. 2015;10(10):e0140638
Authors: Speed HE, Masiulis I, Gibson JR, Powell CM
A single, maternally inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C) of Neuroligin 3 (NLGN3R451C) is a likely cause of autism in two brothers. Knockin mice expressing the Nlgn3R451C mutation in place of wild-type Nlgn3 demonstrate increased inhibitory synaptic strength in somatosensory cortex, resulting in an excitatory/inhibitory (E/I) imbalance that is potentially relevant for autism-associated behavioral deficits characteristic of these mice. We have replicated the increase in evoked inhibitory postsynaptic currents (eIPSCs) onto layer II/III cortical pyramidal neurons. We also find that increased frequency of spontaneous mIPSCs in Nlgn3R451C mice occurs in the absence of action potential-driven transmission. This suggests the E/I imbalance is due to changes at the synapse level, as opposed to the network level. Next, we use paired whole-cell recordings in an attempt to identify specific interneuron subtypes affected by the Nlgn3R451C mutation. Curiously, we observe no change in the amplitude of cell-to-cell, unitary IPSCs (uIPSCs) from parvalbumin-positive (PV) or somatostatin-positive (SOM) interneurons onto pyramidal neurons. We also observe no change in the number or density of PV and SOM interneurons in LII/III of somatosensory cortex. This effectively rules out a role for these particular interneurons in the increased inhibitory synaptic transmission, pointing to perhaps alternative interneuron subtypes. Lastly, impaired endocannabinoid signaling has been implicated in hippocampal synaptic dysfunction in Nlgn3R451C mice, but has not been investigated at cortical synapses. We find that bath application of the CB1 antagonist, AM 251 in WT mice eliminates the Nlgn3R451C increase in eIPSC amplitude and mIPSC frequency, indicating that increased inhibitory transmission in mutant mice is due, at least in part, to a loss of endocannabinoid signaling through CB1 receptors likely acting at interneurons other than PV or SOM.
PMID: 26469287 [PubMed - indexed for MEDLINE]
Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection.
Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection.
PLoS One. 2015;10(10):e0137725
Authors: Son JS, Zheng LJ, Rowehl LM, Tian X, Zhang Y, Zhu W, Litcher-Kelly L, Gadow KD, Gathungu G, Robertson CE, Ir D, Frank DN, Li E
In order to assess potential associations between autism spectrum disorder (ASD) phenotype, functional GI disorders and fecal microbiota, we recruited simplex families, which had only a single ASD proband and neurotypical (NT) siblings, through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN). Fecal samples and metadata related to functional GI disorders and diet were collected from ASD probands and NT siblings of ASD probands (age 7-14). Functional gastrointestinal disorders (FGID) were assessed using the parent-completed ROME III questionnaire for pediatric FGIDs, and problem behaviors were assessed using the Child Behavior Check List (CBCL). Targeted quantitative polymerase chain reaction (qPCR) assays were conducted on selected taxa implicated in ASD, including Sutterella spp., Bacteroidetes spp. and Prevotella spp. Illumina sequencing of the V1V2 and the V1V3 regions of the bacterial 16S rRNA genes from fecal DNA was performed to an average depth of 208,000 and 107,000 high-quality reads respectively. Twenty-five of 59 ASD children and 13 of 44 NT siblings met ROME III criteria for at least one FGID. Functional constipation was more prevalent in ASD (17 of 59) compared to NT siblings (6 of 44, P = 0.035). The mean CBCL scores in NT siblings with FGID, ASD children with FGID and ASD without FGID were comparably higher (58-62 vs. 44, P < 0.0001) when compared to NT children without FGID. There was no significant difference in macronutrient intake between ASD and NT siblings. There was no significant difference in ASD severity scores between ASD children with and without FGID. No significant difference in diversity or overall microbial composition was detected between ASD children with NT siblings. Exploratory analysis of the 16S rRNA sequencing data, however, identified several low abundance taxa binned at the genus level that were associated with ASD and/or first order ASD*FGID interactions (FDR <0.1).
PMID: 26427004 [PubMed - indexed for MEDLINE]
Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population.
Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population.
PLoS One. 2015;10(9):e0138695
Authors: Kuo PH, Chuang LC, Su MH, Chen CH, Chen CH, Wu JY, Yen CJ, Wu YY, Liu SK, Chou MC, Chou WJ, Chiu YN, Tsai WC, Gau SS
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic components. Several recent genome-wide association (GWA) studies in Caucasian samples have reported a number of gene regions and loci correlated with the risk of ASD--albeit with very little consensus across studies.
METHODS: A two-stage GWA study was employed to identify common genetic variants for ASD in the Taiwanese Han population. The discovery stage included 315 patients with ASD and 1,115 healthy controls, using the Affymetrix SNP array 6.0 platform for genotyping. Several gene regions were then selected for fine-mapping and top markers were examined in extended samples. Single marker, haplotype, gene-based, and pathway analyses were conducted for associations.
RESULTS: Seven SNPs had p-values ranging from 3.4~9.9*10-6, but none reached the genome-wide significant level. Five of them were mapped to three known genes (OR2M4, STYK1, and MNT) with significant empirical gene-based p-values in OR2M4 (p = 3.4*10(-5)) and MNT (p = 0.0008). Results of the fine-mapping study showed single-marker associations in the GLIS1 (rs12082358 and rs12080993) and NAALADL2 (rs3914502 and rs2222447) genes, and gene-based associations for the OR2M3-OR2T5 (olfactory receptor genes, p = 0.02), and GLIPR1/KRR1 gene regions (p = 0.015). Pathway analyses revealed important pathways for ASD, such as olfactory and G protein-coupled receptors signaling pathways.
CONCLUSIONS: We reported Taiwanese Han specific susceptibility genes and variants for ASD. However, further replication in other Asian populations is warranted to validate our findings. Investigation in the biological functions of our reported genetic variants might also allow for better understanding on the underlying pathogenesis of autism.
PMID: 26398136 [PubMed - indexed for MEDLINE]
PBAP: a pipeline for file processing and quality control of pedigree data with dense genetic markers.
PBAP: a pipeline for file processing and quality control of pedigree data with dense genetic markers.
Bioinformatics. 2015 Dec 1;31(23):3790-8
Authors: Nato AQ, Chapman NH, Sohi HK, Nguyen HD, Brkanac Z, Wijsman EM
MOTIVATION: Huge genetic datasets with dense marker panels are now common. With the availability of sequence data and recognition of importance of rare variants, smaller studies based on pedigrees are again also common. Pedigree-based samples often start with a dense marker panel, a subset of which may be used for linkage analysis to reduce computational burden and to limit linkage disequilibrium between single-nucleotide polymorphisms (SNPs). Programs attempting to select markers for linkage panels exist but lack flexibility.
RESULTS: We developed a pedigree-based analysis pipeline (PBAP) suite of programs geared towards SNPs and sequence data. PBAP performs quality control, marker selection and file preparation. PBAP sets up files for MORGAN, which can handle analyses for small and large pedigrees, typically human, and results can be used with other programs and for downstream analyses. We evaluate and illustrate its features with two real datasets.
AVAILABILITY AND IMPLEMENTATION: PBAP scripts may be downloaded from http://faculty.washington.edu/wijsman/software.shtml.
CONTACT: email@example.com.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
PMID: 26231429 [PubMed - indexed for MEDLINE]
Behavioral characteristics associated with 19p13.2 microdeletions.
Behavioral characteristics associated with 19p13.2 microdeletions.
Am J Med Genet A. 2015 Oct;167A(10):2334-43
Authors: Welham A, Barth B, Moss J, Penhallow J, Sheth K, Wilde L, Wynn S, Oliver C
A small number of recent papers have described individuals with intellectual disabilities and microdeletions in chromosome band 19p13.2. However, little is known about the behavioral characteristics of individuals with microdeletions in this area. The current study examines behavioral characteristics of a series of 10 participants ranging in age from 2 to 20 years with 19p13.2 microdeletions. Parents/caregivers completed a series of established behavioral measures which have aided the elucidation of the behavioral phenotypes of a number of genetic neurodevelopmental syndromes. All but the youngest two participants (aged 2 and 3 years) were verbal, ambulant, and classified as "partly able" or "able" with regard to self-help skills. Six of eight participants for whom a screening measure for autism spectrum disorders (ASD) could be deployed met criteria for an ASD. Six of the 10 participants had displayed self-injurious behavior in the month prior to assessment, eight had displayed destruction/disruption of property, and eight had shown physically aggressive behaviors. Repetitive behaviors were prevalent in the sample (with all participants displaying at least one repetitive behavior to a clinically relevant level), as were problems with sleep. Low mood was not prevalent in this group, and nor were overactivity or impulsivity. Full determination of a behavioral phenotype for this group would require a larger sample size, distinguishing between genetic subtypes. However, the current data suggest that ASD characteristics, repetitive, and challenging behaviors (such as aggression and self-injury) might be associated with 19p13.2 microdeletions, providing a basis for future investigation.
PMID: 26189583 [PubMed - indexed for MEDLINE]
VoICE: A semi-automated pipeline for standardizing vocal analysis across models.
VoICE: A semi-automated pipeline for standardizing vocal analysis across models.
Sci Rep. 2015;5:10237
Authors: Burkett ZD, Day NF, Peñagarikano O, Geschwind DH, White SA
The study of vocal communication in animal models provides key insight to the neurogenetic basis for speech and communication disorders. Current methods for vocal analysis suffer from a lack of standardization, creating ambiguity in cross-laboratory and cross-species comparisons. Here, we present VoICE (Vocal Inventory Clustering Engine), an approach to grouping vocal elements by creating a high dimensionality dataset through scoring spectral similarity between all vocalizations within a recording session. This dataset is then subjected to hierarchical clustering, generating a dendrogram that is pruned into meaningful vocalization "types" by an automated algorithm. When applied to birdsong, a key model for vocal learning, VoICE captures the known deterioration in acoustic properties that follows deafening, including altered sequencing. In a mammalian neurodevelopmental model, we uncover a reduced vocal repertoire of mice lacking the autism susceptibility gene, Cntnap2. VoICE will be useful to the scientific community as it can standardize vocalization analyses across species and laboratories.
PMID: 26018425 [PubMed - indexed for MEDLINE]
Genetic Mapping in Mice Reveals the Involvement of Pcdh9 in Long-Term Social and Object Recognition and Sensorimotor Development.
Genetic Mapping in Mice Reveals the Involvement of Pcdh9 in Long-Term Social and Object Recognition and Sensorimotor Development.
Biol Psychiatry. 2015 Oct 1;78(7):485-95
Authors: Bruining H, Matsui A, Oguro-Ando A, Kahn RS, Van't Spijker HM, Akkermans G, Stiedl O, van Engeland H, Koopmans B, van Lith HA, Oppelaar H, Tieland L, Nonkes LJ, Yagi T, Kaneko R, Burbach JP, Yamamoto N, Kas MJ
BACKGROUND: Quantitative genetic analysis of basic mouse behaviors is a powerful tool to identify novel genetic phenotypes contributing to neurobehavioral disorders. Here, we analyzed genetic contributions to single-trial, long-term social and nonsocial recognition and subsequently studied the functional impact of an identified candidate gene on behavioral development.
METHODS: Genetic mapping of single-trial social recognition was performed in chromosome substitution strains, a sophisticated tool for detecting quantitative trait loci (QTL) of complex traits. Follow-up occurred by generating and testing knockout (KO) mice of a selected QTL candidate gene. Functional characterization of these mice was performed through behavioral and neurological assessments across developmental stages and analyses of gene expression and brain morphology.
RESULTS: Chromosome substitution strain 14 mapping studies revealed an overlapping QTL related to long-term social and object recognition harboring Pcdh9, a cell-adhesion gene previously associated with autism spectrum disorder. Specific long-term social and object recognition deficits were confirmed in homozygous (KO) Pcdh9-deficient mice, while heterozygous mice only showed long-term social recognition impairment. The recognition deficits in KO mice were not associated with alterations in perception, multi-trial discrimination learning, sociability, behavioral flexibility, or fear memory. Rather, KO mice showed additional impairments in sensorimotor development reflected by early touch-evoked biting, rotarod performance, and sensory gating deficits. This profile emerged with structural changes in deep layers of sensory cortices, where Pcdh9 is selectively expressed.
CONCLUSIONS: This behavior-to-gene study implicates Pcdh9 in cognitive functions required for long-term social and nonsocial recognition. This role is supported by the involvement of Pcdh9 in sensory cortex development and sensorimotor phenotypes.
PMID: 25802080 [PubMed - indexed for MEDLINE]
Executive functioning in autism spectrum disorders: influence of task and sample characteristics and relation to symptom severity.
Executive functioning in autism spectrum disorders: influence of task and sample characteristics and relation to symptom severity.
Eur Child Adolesc Psychiatry. 2015 Nov;24(11):1399-417
Authors: Van Eylen L, Boets B, Steyaert J, Wagemans J, Noens I
Impaired executive functioning (EF) has been proposed to underlie symptoms of autism spectrum disorders (ASD). However, insight in the EF profile of ASD individuals is hampered due to task impurity and inconsistent findings. To elucidate these inconsistencies, we investigated the influence of task and sample characteristics on EF in ASD, with an extended test battery designed to reduce task impurity. Additionally, we studied the relation between EF and ASD symptoms. EF (inhibition, cognitive flexibility, generativity, working memory and planning) was measured in open-ended versus structured assessment situations, while controlling for possible confounding EF and non-EF variables. The performance of 50 individuals with ASD was compared with that of 50 age, gender and IQ matched typically developing (TD) individuals. The effects of group (ASD versus TD), age (children versus adolescents) and gender were examined, as well as the correlation between age, IQ, ASD symptoms and EF. Individuals with ASD showed impairments in all EF domains, but deficits were more pronounced in open-ended compared to structured settings. Group differences did not depend on gender and only occasionally on participants' age. This suggests that inconsistencies between studies largely result from differences in task characteristics and less from differences in the investigated sample features. However, age and IQ strongly correlated with EF, indicating that group differences in these factors should be controlled for when studying EF. Finally, EF correlated with both social and non-social ASD symptoms, but further research is needed to clarify the nature of this relationship.
PMID: 25697266 [PubMed - indexed for MEDLINE]


text:
Showing Results 1 - 10 of 1000
UMMC's quality and safety team uses SWOT analysis to identify improvement opportunities.
» Read the case: HTML | PDF
Posted on 7/28/16
In this issue, we talk with Anthony J. Scuderi, MD, who serves as medical director of Conemaugh Advanced Imaging in Johnstown, PA, and chair of the ACR Committee on Accreditation Chairs.
What's new and what's exciting in the world of ACR accreditation?
We're focused on streamlining ACR accreditation...
The ACR has developed an electronic platform — known as Transfer of Images and Data (TRIAD™) — that makes submitting images and data faster, simpler and more secure.
TRIAD (Transfer of Images and Data) is a software application that provides secure, efficient and robust transmission of medical images and related electronic data.
A focused team is resolving quality and safety issues within the radiology department at the University of Mississippi Medical Center.
» Read the case: HTML | PDF
Posted on 7/28/16
Whether image sharing through TRIAD or helping members effectively engage in the latest regulatory agendas and resolutions through the AMCLC Web Portal, our diverse array of systems and applications equips and facilitates progressive exchange.
Ezequiel Silva, MD, FACR, Gregory Nicola, MD, and Joshua Hirsch, MD, FACR – all experienced members of the American College of Radiology's leadership team – have been appointed to the Centers for Medicare and Medicaid Services' (CMS') Medicare Access and CHIP Reauthorization...
The award-winning, monthly JACR is the profession's only peer-reviewed journal that focuses on issues relating to clinical practice, practice management, health services and policy, and education and training. ACR members receive the JACR free of charge.

subset: commoncrawl


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She might pin herself as the pint-sized powerhouse from the year 3000, but Zowie is very much the girl of the moment.
The one-time Bengal Lights drummer and Bionic Pixie star, Zowie (real name Zoe Fleury) is now well and truly comfortable in her alter-ego's skin and has a debut album to cement it.
Love Demolition has been two years in the making and is the Auckland singer's pride and joy.
Her first single Broken Machine was one of the songs of 2010 - it was picked up for advertising campaigns and Hollywood blogger Perez Hilton invited Zowie to play at one of his legendary showcases and has continued to support her via his website.
"Perez posted Broken Machine before anyone knew about us," Zowie says. "Our social media, everything went insane. Twitter nearly crashed... we just got hundreds and hundreds and hundreds of plays and there were people in New Zealand who were saying 'who is this chick? We've never heard of her'."
Kiwis soon discovered who she was during Katy Perry's tour last year. Even before she had an album under her belt, Zowie was invited to support Perry on both her New Zealand and Australian tours, which meant playing to more than 150,000 people.
Her live shows highlight her energy as a performer - complete with outlandish outfits and live band. While she doesn't think pop is a dirty word, Zowie is adamant she wants to be more than just a pop princess; more than just blatant sexuality and no substance.
"I definitely embrace the pop side [of music]. For example, my favourite band is Nine Inch Nails, who are super industrial, super dark, but they mixed in, sometimes I think without people noticing, these really beautiful pop elements. And that's what I wanted to achieve with this album - having it dark and pretty.
"I just don't want people to be staring at my legs or my body when I'm like 'you should be listening to the music'. Of course I like fashion and I like to make a statement with it, but I don't want it to be boobs hanging out or anything - it just doesn't interest me."
But she does like to be mischievous. Within the catchy concoction of electronic hip-hop, industrial pop and eclectic beats, there are some cheeky, clever lyrics.
"My lyrics are definitely full of double entendres, or probably triple entendres. There's one of the songs on the album that says 'I want you here tonight, I don't want nobody else', but the whole idea behind it was about people coming to our show. But when you hear it, it sounds super sexy - so people relate to it in all these different ways."
And with Love Demolition, Zowie is sure to knock down some preconceptions and open more than a few doors.
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Is it true that Vatican II was a complete break with the past? Is authority in society optional? Is it primarily a matter of the intellect or the will? Question: This year the Church is celebrating the 50th anniversary of the … [Read more...]
Questions Answered
Can you explain what the general rights and duties are of the state in regard to the family? What does the Leadership Conference of Women Religious (LCWR) mean by their term "Creative Fidelity"? Question: Can you explain what the … [Read more...]
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Does the Church state that there is an ideal form of government? What Magisterial status does the teaching of the popes on contraception enjoy? Can it be changed? Must we believe it? Plato, St. Thomas Aquinas, and … [Read more...]
Competing Theories of Christ's Atonement: Penal Substitution, Economic Transaction, or Obediential Love?
The Passion is understood as an act of a personal God atoning for the personal offense of sin. The personalist understanding of the atonement is deeply linked to the framework of the relationship between Christ and the members of his … [Read more...]
Teaching the Faith: Contributions from Thomas Aquinas
God's love, mediated through the articles of faith, is a communication of God's love speaking to us. Those who hear, and cling to the merciful speech of God, in faith, are the ones who attain this saving knowledge. "But when the Son of … [Read more...]
Preaching the Truth in Love and Wisdom: Pope Francis' 2013 Apostolic Exhortation "Evangelii Gaudium"
...conversion occurs when the Gospel speaks to the deepest yearnings of our hearts, and the desires present within us are filled by a supernatural grace that comes from God. "The joy of the Gospel fills the hearts and lives of all who … [Read more...]
An Essay on Natural Family Planning
The Catholic Church has never opposed family planning, but she teaches through her Magisterium, or teaching authority, that man may not, of his own volition, separate the two meanings of the conjugal act, the unitive and the procreative, … [Read more...]
Toward a Theology of Infertility: The Trinity in Richard of St. Victor
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The Dumb Ox on Evolution
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text:
Masters of the Universe Info
1987 | Thriller, Sci-Fi, Action, Fantasy, Adventure
106 minutes /
Synopsis:A prince turned warrior named He-Man battles against the dark lord Skeletor on the planet Eternia. He-Man and his comrades arrive on Earth and discover two teenage lovers to find the magical Cosmic Key.
Masters of the Universe Review
Planet Eternia and the Castle of Greyskull are under threat from the evil Skeletor who wants to take over the planet. A group of freedom fighters, led by the heroic He-Man are accidentally transported to Earth by a mysterious Cosmic Key which holds the power to make Skeletor all-powerful. Once on Earth, He-Man joins alliances with two teenagers as they attempt to find the key and return home.
About Masters of the Universe (1987)
Original Title: Masters of the Universe: The Motion Picture
Year: 1987
Runtime: 106 minutes
Type: Movie
Genre: Thriller, Sci-Fi, Action, Fantasy, Adventure
Total Avg. Votes: 7
Writers: David Odell, Gary Goddard, Stephen Tolkin
Director: Gary Goddard


text:
High braking index pulsar PSR J1640-4631: low-mass neutron star with a large inclination angle?
Received: 10 June 2016 / Accepted: 24 July 2016
Astronomy & Astrophysics gives online access to unedited preprint version of accepted papers several weeks ahead of publication, on author's consent. This online version does not take into account corrections made during the production process.
Online access to PDF files is granted to subscribers.


text:
The Green Monkey, the most expensive sales purchase in racing history, arrived at trainer Todd Pletcher's Churchill Downs' barn Friday.The 2-year-old colt was bought for $16 million by Michael Tabor, John Magnier and Derrick Smith at the Fasig-Tipton Calder sale Feb. 28.Pletcher says it's anyone's guess as to when the expensive colt will be ready to make his racing debut."We don't really have a schedule," he said. "We just got him in and he hasn't really been doing too much since the sale. We'll just take it day by day and get him into a steady program and let him tell us when he's ready."The son of Forestry is named for a golf course at the Sandy Lane Hotel in Barbados.The sales price eclipsed the previous record bid of $13.1 million for Seattle Dancer at the Keeneland July Sale in 1985. Pletcher, winner of the last two Eclipse Awards as America's top trainer, has never had a young horse quite like this one in his stable."I would say he's certainly the most anticipated arrival we've ever had," said Pletcher. "It goes without saying that we'll be under a lot more scrutiny with a horse like that, but at the end of the day you've got to treat him like the rest of them. Otherwise, you'll drive yourself crazy."To purchase a photo of The Green Monkey, click here.
The Green Monkey Arrives at Churchill Downs
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text:
Politics News
Clinton leads Trump by 6 points after Democratic confab: Reuters/Ipsos poll
NEW YORK Democratic presidential candidate Hillary Clinton held a 6- percentage-point lead over Republican rival Donald Trump, according to a Reuters/Ipsos poll with new wording that was released on Friday, the day after she formally accepted her party's nomination for the Nov. 8 election.
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Recent Politics News
The year of 'Neither': Why Reuters/Ipsos is tweaking its U.S. presidential poll
NEW YORK In a presidential campaign notable for its negativity, the option of "Neither" candidate appears to be an appealing alternative, at least to participants in the Reuters/Ipsos opinion poll.
U.S., Cuba hold 'substantive' second round talks on claims
WASHINGTON/HAVANA The United States and Cuba have concluded a "substantive" second round of talks on multibillion-dollar claims against one another in Washington and agreed to hold more regular meetings on the matter, a State Department Official said on Friday.
Obama to showcase TPP after trade deal demonized in campaign
WASHINGTON During a visit from Singapore's prime minister on Tuesday, President Barack Obama will extol the Trans-Pacific Partnership (TPP) trade deal and commit to getting the deal done, a top White House official said on Friday, even though Obama's fellow Democrats panned it at their convention this week.
U.S. court rejects NJ Senator Menendez's bid to end corruption case
A federal appeals court on Friday refused to dismiss a corruption indictment against Senator Robert Menendez of New Jersey, rejecting the Democrat's claim that the U.S. Constitution shielded him from prosecution.


text: Like the monsters who lived under many of our beds when we were kids (mine was an alligator!), when we turn on the light, the monster magically disappears. I know this, but gosh! It's hard to do when you're scared. To "turn on the light" on a ferocious, scary problem, there are five steps brave grown-ups can take.


text:
nhs co ordinator jobs
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Admissions Clerk - Receptionist
Birmingham Women's NHS Foundation Trust - Birmingham
Previous experience of working in the NHS would be preferable. Both trusts are currently working towards becoming a single organisation and the earliest this...
Waiting List Co-ordinator
Taunton and Somerset NHS Foundation Trust - Taunton
Are you up for a challenge? Would you like to work in a team dedicated to patients and the organisation of their pending operation or procedure? If so we are
Support, Time and Recovery Worker
South London and Maudsley NHS Foundation Trust - Southwark
An excellent opportunity has arisen for two experienced and motivated Support, Time and Recovery workers to join the Early Intervention Pathway. The
Personal Assistant/Project Co-ordinator
University Hospitals of North Midlands NHS Trust - Stoke-on-Trent
Please note that non-NHS applicants with no previous NHS experience will ordinarily be appointed to the minimum of the band....
Care Co-ordinator - Band 5
NHS - Liskeard
In submitting an application form, you authorise Cornwall Partnership NHS Foundation Trust to confirm any previous NHS service details via the Electronic Staff...
Administration Assistant
Sussex Partnership NHS Foundation Trust - Newhaven
We provide NHS care and treatment for people living in south east England. However, where previous or equivalent NHS experience in a similar role can be...
Orthoptic Helper
Guy's and St. Thomas' NHS Foundation Trust - London
We are part of King's Health Partners Academic Health Sciences Centre (AHSC), a pioneering collaboration between one of the world's leading research-led...
Service Co-ordinator
British Red Cross - South East
You should also have experience of delivering high quality services to the public, together with knowledge of services provided by the NHS and Social Care....
Discharge Assistant
Calderdale and Huddersfield NHS Foundation Trust - Huddersfield
If you should be shortlisted for this post, you will be contacted by email via NHS Jobs. They must also be able to use their own initiative whilst working under...
Activity Co-Ordinator
NHS - Tamworth
Band 1 and 2 - 1/3 of the overall cost Band 3 - 2/3 of the overall cost Band 4 or above - 100% of the overall cost South Staffordshire and Shropshire Healthcare...


text:
Workshop fixture die casting aluminum 80w good price led high bay lights
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Hl-dt-st bddvdrw ch10ls20 driver
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text:
Norfolk Pick N Pull
1. Diggers Pick & Pull
5117 Bainbridge BlvdChesapeake, VA 23320
2. Pick-n-PullProducts
great place to go and get your used parts from, people are friendly and knowledgeable of the cars you are looking for, alot cleaner than most junk y…
3. Pick-N-Pull
love this place "Pick & Pocket" Lol never buy anything takes to long and they charge to much
4. Cash For Junk Cars
From Business: Pick-n-Pull Cash For Junk Cars: We Pay Top $$$ For Your Car All Makes & Models – Foreign and Domestic Running or Not! Towing Services Open 7 Days A Week– Se Habla E…
5. Hawkins Auto Recycle Center-GLENDALE
From Business: All Honda-Acura-Nissan-Infiniti Auto Recycling carries an extensive selection of new and used auto parts that are carefully inspected by our knowledgeable staff. Al…
6. All BMW Parts -- Bavarian Auto Recycling Inc.
Serving the Norfolk Area.
From Business: As one of the largest BMW parts recyclers in the US, we specialize in rebuilt, new, and used BMW parts for all BMW car models. Our recycled BMW parts inventory incl…
7. All European Engines & Transmissions - Bavarian Engine Exchange, Inc
Serving the Norfolk Area.
From Business: Thank you for choosing Bavarian Engine Exchange to help with your used and rebuilt European Engine & Transmission needs. We are committed to providing you with cons…
8. Used Tire Depot
Just bought 2 used tires that looked brand spanking new from Used Tire Depot for haft the price. No hidden charges or disposal fee. Professional and…
9. Triple Decker Auto Parts
2601 S Military HwyChesapeake, VA 23324
From Business: Come to the Web site of Triple Decker Auto Parts (TDAP). Triple Decker Auto Parts has been serving customers since 1969. We consider ourselves a leader in recycled …
10. AAA Auto Salvage
Newport News, VA 23609
11. Complete Auto Parts
1320 Portsmouth BlvdSuffolk, VA 23434
From Business: We pay cash for cars. We carry New, Used, OEM and after market automobile parts and accessories.
12. Advance Auto Parts
2500 Monticello AveNorfolk, VA 23517
13. Ingram Auto Parts
DO NOT USE TERRIBLE CUSTOMER SERVICE!!!!! THEY DO NOT MEET APPOINTMENTS ON TIME AND WXPECT TO WAIT AROUND ALL DAY BECAUSE THEY HAVE OTHER WORK. Tha…
14. Tubbs Auto Parts Inc
2215 E Indian River RdNorfolk, VA 23523
15. Downtown Used Auto Parts - CLOSED
5600 Brickell RdNorfolk, VA 23502
16. Ingram Auto Mall
Serving the Norfolk Area.
17. Always Used Auto Parts
I don't usually do reviews, but I just could not keep this to myself. I've been a customer for years. I got my parts at a great price today. They …
18. Clayton's Auto Parts
15465 Carrollton BlvdCarrollton, VA 23314
19. Carlson & Carlson Inc
5325 Cleveland St # 302Virginia Beach, VA 23462
20. Norfolk Recycling
5415 W Military HwyChesapeake, VA 23321
21. Scrap 58 Inc
5324 W Military HwyChesapeake, VA 23321
22. Ross Auto Parts - CLOSED
14 Nettles LnHampton, VA 23666
From Business: Ross Auto Parts, located in Hampton, Va., is a dealer of automobile parts. It maintains a comprehensive inventory of parts and accessories, such as condenser fans, …
23. D Moss Auto Sales
4521 Bainbridge BlvdChesapeake, VA 23320
1326 Portsmouth BlvdSuffolk, VA 23434
25. Nick's Auto Supermart
128 W Pembroke AveHampton, VA 23669
26. T & S Used Auto - CLOSED
604 Shell RdHampton, VA 23661
27. Cooling Systems & Flexibles
3920 Cook BlvdChesapeake, VA 23323
28. Virginia Auto Parts
1325 Portsmouth BlvdSuffolk, VA 23434
29. Joe's Auto Parts Inc
22251 Brewers Neck BlvdCarrollton, VA 23314
30. Budget Lodge Beach Quarters
300 Atlantic AveVirginia Beach, VA 23451


text:
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The Government of Canada supports the development of new health technologies to address the rising rates of chronic disease. As part of this program, York University, Southlake Regional Healthcare Centre and the University Health Network will receive an investment of up to $15 million.
Canadians will soon benefit from improved healthcare options to support the management of chronic disease as a result of a $15 million investment to York University and partners, Southlake Regional Health Centre and the University Health Network.
The Government of Canada recognizes the importance of delivering a single ship support contract to service the Royal Canadian Navy. This contract will provide the best value to Canadian taxpayers, while supporting Canada's shipbuilding industry.
The Honourable Carolyn Bennett, Minister of Indigenous and Northern Affairs, today released a report by Thomas Isaac, Ministerial Special Representative on Reconciliation with Métis.
The Honourable MaryAnn Mihychuk along with the Honourable Gerry Byrne will sign the agreement on Foreign Credentials Recognition
The Honourable MaryAnn Mihychuk, Minister of Employment, Workforce Development and Labour, along with the Honourable Gerry Byrne, Minister of Advanced Education and Skills, will sign the agreement on Foreign Credentials Recognition in St. John's, Newfoundland and Labrador.
Celebrate the Group of Seven at artESCAPE
The Honourable Stéphane Dion, Minister of Foreign Affairs, today issued the following statement:
Canada supports a democratic Turkey and respects the need for thorough investigations and prosecutions against the perpetrators of the recent attempted coup. This must be done in accordance with Turkish and international law. Given this imperative, Canada is concerned by the state of emergency declared by President Erdogan today.
Indigenous peoples play an important role in Canada's economic prosperity. The Government of Canada is working hard to better Indigenous Peoples' future and improve their economic opportunities.
Release of report by Thomas Isaac, Ministerial Special Representative on Reconciliation with Métis: Section 35 Métis Rights and the Manitoba Métis Federation Decision
Indigenous and Northern Affairs Canada will be issuing a report by Thomas Isaac, Ministerial Special Representative on Reconciliation with Métis: Section 35 Métis Rights and the Manitoba Métis Federation Decision.
Nishikawa Rubber Co., Ltd. (Nishikawa), a Japanese manufacturer of automotive parts, was charged in the United States (US), and has agreed to plead guilty and pay a fine of US$130 million, for its participation in an international bid‑rigging conspiracy affecting Canada and the United States.
Fisheries and Oceans Canada, Quebec region, wants to inform the Lower North Shore population that the harvesting of shellfish is now forbidden due to toxicity, in accordance with the prohibition order mentioned below, and pursuant to subsection 3(1) of the Management of Contaminated Fisheries Regulations, in the following shellfish area:
The Competition Bureau and Transport Canada's Policy Group have acknowledged their important relationship and the value of cooperation by signing a memorandum of understanding (MOU).
The Government of Canada announced through Budget 2016 a new benefit to help parents with the high costs of raising their children.
Canadian Beef has built a reputation as being some of the tastiest and best quality beef in the world.
Minister Sajjan tables the Communications Security Establishment (CSE) Commissioner's 2015-2016 Annual Report
As part of the Government of Canada's commitment to openness and transparency, the Minister of National Defence today tabled in Parliament the 2015-2016 CSE Commissioner's Annual Report.
- RT @RonaAmbrose: Liberals consider imposing Australian-style electoral system on Canadians – what does it mean? https://t.co/PcwIeVRgZe — 21 hours 33 min ago
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markstrahl channel


text:
Photonovels and Movies / Re: RE #11 - Siege on Rhen Var« on: June 26, 2005, 11:22 PM »
Wonderful, wonderful stuff! I loved the stuff taken from Battlefront, it just made everything seem more "SW Realistic". Not much else to say, everything was really top notch! Loved the ending as well!


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An area outside of Kalona city hall looks brighter thanks to work done by Iowa Mennonite School's Horticulture Class.
Keywords: Ag Teacher, City Hall, Horticulture Class, IMS
Columbus Community High School's horticulture class is selling vegetables, herbs, bedding and household plants this week.
Keywords: Columbus Junction High School, Horticulture Class
Half of Americans believe that men and women have equal job opportunities, and half don't. Do you?
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I always order from MJM Magic but made the mistake of ordering from a well known magic company which runs constant sales of up to 60% off, thinking I...
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These things make MJM Magic my first stop for book purchases:
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The Almost have been added to the Starting Line Tour which makes a stop at the Intersection December 8th
|Saturday, December 8
18+. $16 Advance $18 Day os show. 5:30pm Doors, 6pm Show.
The Almost have been added to the Starting Line Tour which makes a stop at the Intersection December 8th
|Saturday, December 8
18+. $16 Advance $18 Day os show. 5:30pm Doors, 6pm Show.
Tags: concert venues, the almost, the intersection, the starting line
Paramore with The Starting Line and The Almost have announced their Fall 2007 tour schedule nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn
Tags: flicker records, jon mclaughlin, paramore, Sept. 2007 concerts, the almost, the send, the starting line
Back on Tooth & Nail Records, Starflyer 59's Slow is available on vinyl Source: SLOW : TANR : MerchNOW – Your Favorite Band Merch, Music and More
This is great news for those that thought Mae's The Everglow was a great album and needed to be released on vinyl. ( Get a Pre- order notification from Spartan Records) Not so good news for those who paid $150+ for their RSD limited edition version. The Everglow is finally returning to vinyl later this […]
With Fathers day approaching here is the perfect gift for that special dad who also loves to spin vinyl. From Luno the EGB2 Record Console. In case you are worried about sound quality it looks like it has a quality turntable ( the Pro-ject Debut) LUNO's flagship model, EGB2, is a timely update of the […]
One of Denison Witmer's best records Are you a Dreamer is now released on vinyl. Get it at New Granada Records TRACKLISTING: 01. Little Flowers 02. Everything But Sleep 03. Ringing Of The Bell Tower 04. Are You A Dreamer? 05. East From West 06. California Brown And Blue 07. Castle And Cathedral 08. Worry […]
Like a Baby is the new single from Starflyer 59. You can get it at itunes. It is also available as a 7″ single at flannelgraph records Source: Starflyer 59
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Tom Brady Cheering Up "The Comebacks"
It will be another comedic work for Tom Brady. Fox Atomic has tapped "The Hot Chick" helmer to direct its new sports comedy feature entitled "The Comebacks", the first project developed from the ground up at the fledgling studio division, Variety has learned.
Brady previously wrote the latest draft of the script with Kevin Sabbe who also serves as the film's producers alongside Tapestry Films' execs Peter Abrams, Robert L. Levy and Andrew Panay. Meanwhile, cast includes "Anchorman" star David Koechner who will play the worst football coach in the history of the sport going for a shot at redemption with a ragtag college team.
An alumnus of the University of Hawaii, Brady has written as well as produced numerous well-known TV shows before making his foray into directing field. Apart from "The Comebacks", his upcoming big screen projects include "Untitled Nick Cannon Project" and "The Retreat."
- 'The Walking Dead' Was Supposed to End in Alexandria, but It Has Changed
- Disney's New 'Nutcracker' Movie Casts Mackenzie Foy as Clara
- Video: Kanye West Disses Taylor Swift While Crashing Drake's Concert
- Ben Affleck Risks His Life in New 'The Accountant' Trailer
- An Uber Driver Failing to Recognize Lorde Brags About Another Celebrity Passenger
- Scott Disick and Khloe Kardashian Make Fun of Dating Rumors While Posing for a Selfie
- Demi Lovato and Joe Jonas Bring 'Camp Rock' Back to D.C. Concert. See Their Onstage Reunion
- Is Lindsay Lohan Really Pregnant? See Picture of Her Smoking in Sardinia


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- Editor's PickKathy Cherpelis•3 hours agoHere's a bunch of interesting things companies said about the world this week
"Clearly, it's been fairly well documented on the consumer slowdown across most consumer segments… We're not immune from what's happening in the outside world… I think, generally, there's just a broader level of uncertainty in consumers' minds… People are slightly mindful of an unsettled world. "We face some challenges in Greater China, as the economic environment has slowed down since the beginning of the year.
Impressive Driving Range
Go the distance in America's longest-lasting pickups with an impressive driving range and capability to spare.
- Editor's PickRayhanul Ibrahim•6 hours agoHere's what the stock market does during the summer Olympic Games
The summer Olympic Games start in a week, which means it's time to get ready for 17 days of sports, fan enthusiasm, sun and … stock market gains? Factset's Andrew Birstingl found the Dow Jones Industrial Average (^DJI) has actually risen during 69% of Summer Olympics. Including the years the Dow Jones was negative during the Summer Olympics, the average gain for the Dow has been an astounding 3.9%.
The Coca-Cola CompanyNYSE
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When i come to a Complete stop, then I step on the gas, my vehicle starts to shake violently and the sounds are just horrible. I checked for all the signs for blown head gaskets and checked my tranny fluid. Nothing seemed out of the ordinary.It also has major power loss on take off. and forget about uphills; it goes about 5 miles an hour. It happens about 85% of the time.
Whats the violent shaking and sounds coming from my engine? on 1998 Kia Sephia
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2 answers
i would start with basics like plugs, coils and look for obvious vacuum lines broken or disconnected.
if not, then you need a shop to help you out and give you a bid.
if not, then you need a shop to help you out and give you a bid.
One possibility can be the engine mounts are shot causing them to rumble against there metal housing. That can cause a poor engine performance and shaking. If the cars automatic, put on the parking brake hold down the brake pedal then put the car in gear and do slight acceleration either you or someone can visually look at the engine mounts when you accelerate to see how badly they move ... a good sign of failure would be that the engine looks like it wants to jump out of the engine bay.


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