Ultrafast Charge Transfer and Recombination Dynamics in Monolayer-Multilayer WSe Junctions Revealed by Time-Resolved Photoemission Electron Microscopy.

The ultrafast carrier dynamics of junctions between two chemically identical, but electronically distinct, transition metal dichalcogenides (TMDs) remains largely unknown. Here, we employ time-resolved photoemission electron microscopy (TR-PEEM) to probe the ultrafast carrier dynamics of a monolayer-to-multilayer (1L-ML) WSe junction. The TR-PEEM signals recorded for the individual components of the junction reveal the sub-ps carrier cooling dynamics of 1L- and 7L-WSe, as well as few-ps exciton-exciton annihilation occurring on 1L-WSe.

Correction to: Abstracts from the NIHR INVOLVE Conference 2017.

[This corrects the article DOI: 10.1186/s40900-017-0075-x.].

Stress induces altered CRE/CREB pathway activity and BDNF expression in the hippocampus of glucocorticoid receptor-impaired mice.

The gene coding for the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) is a stress-responsive gene. Changes in its expression may underlie some of the pathological effects of stress-related disorders like depression. Data on the stress-induced regulation of the expression of BDNF in pathological conditions are rare because often research is conducted using healthy animals.

Behavioural and neuroplastic effects of the new-generation antidepressant agomelatine compared to fluoxetine in glucocorticoid receptor-impaired mice.

Major depression is associated with reduced hippocampal volume linked to stress and high glucocorticoid secretion. Glucocorticoid receptor-impaired (GR-i) mice, a transgenic model for affective disorders with hypothalamic-pituitary-adrenal (HPA) axis feedback control deficit, were used to assess the antidepressant-like effects of the mixed melatonin receptor agonist/5-HT(2C) receptor antagonist, agomelatine, compared to the selective 5-HT reuptake inhibitor (SSRI), fluoxetine, on hippocampal neurogenesis, GR and BDNF expression and antidepressant-responsive behaviour (tail suspension test, TST). GR-i and paired wild-type (WT) mice were given acute or chronic (21 d) treatment with these drugs.

Polymorphisms in the neuronal isoform of tryptophan hydroxylase 2 are associated with bipolar disorder in French Canadian pedigrees.

Objective: Tryptophan hydroxylase is the rate-limiting enzyme in the serotonin biosynthetic pathway and plays an important role in the regulation of serotonin levels. Recently, a brain-specific isoform, tryptophan hydroxylase 2 or n-tryptophan hydroxylase, has been discovered. Some studies reported genetic and functional associations between this isoform and bipolar disorder and/or major depressive disorder.

P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder.

The P2RX7 gene is located within a region on chromosome 12q24.31 that has been identified as a susceptibility locus for affective disorders by linkage and association studies. P2RX7 is a purinergic ATP-binding calcium channel expressed in neurons as well as in microglial cells in various brain regions.

Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder.

Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers on chromosome 12, D12S86 and D12S378, was the most probable genomic region to contain a susceptibility gene for affective disorders. Association studies with microsatellite markers using a case/control sample from the same population (n = 427) revealed significant allelic associations between the bipolar phenotype and marker NBG6. Since this marker is located in intron 9 of the P2RX7 gene, we analyzed the surrounding genomic region for the presence of polymorphisms in regulatory, coding and intron/exon junction sequences.

Glucocorticoid receptor-dependent desensitization of 5-HT1A autoreceptors by sleep deprivation: studies in GR-i transgenic mice.

Unlabelled: Sleep deprivation for one night induces mood improvement in depressed patients, an action that probably involves the serotonergic (5-HT) system. In animals, sleep deprivation and pharmacologic treatment with antidepressants exert similar effects on 5-HT neurotransmission, notably functional desensitization of 5-HT1A autoreceptors located on 5-HT neurons in the dorsal raphe nucleus (DRN). However, in stressful conditions, corticosterone can also induce a desensitization of these autoreceptors.

Antidepressant action of agomelatine (S 20098) in a transgenic mouse model.

The aim of this study was to evaluate the efficacy of agomelatine (S 20098) to accelerate reversal of the neuroendocrinological, behavioural and cyclical changes seen in a transgenic mouse model of the neuroendocrine characteristics of depression. The effects of agomelatine were assessed in transgenic mice with low glucocorticoid receptor (GR) function, after acute stress or induced phase shift, and compared to desipramine and melatonin. Mice were injected 2 h before the onset of the dark period with agomelatine (10 mg/kg, i.

Glucocorticoid receptor-nitric oxide crosstalk and vulnerability to experimental parkinsonism: pivotal role for glia-neuron interactions.

Inflammation and oxidative stress have been closely associated with the pathogenesis of neurodegenerative disorders, including Parkinson's disease (PD). The expression of inducible nitric oxide synthase (iNOS) in astrocytes and microglia and the production of large amounts of nitric oxide (NO) are thought to contribute to dopaminergic neuron demise. Increasing evidence, however, indicates that activated astroglial cells play key roles in neuroprotection and can promote recovery of CNS functions.

Analysis of microsatellite markers and single nucleotide polymorphisms in candidate genes for susceptibility to bipolar affective disorder in the chromosome 12Q24.31 region.

Previous results from our genetic analyses using pedigrees from a French Canadian population suggested that the interval delimited by markers D12S86 and D12S378 on chromosome 12 was the most probable genomic region to contain a susceptibility gene for affective disorders. Here we present a more detailed genetic analysis of a 7.7 Mb genomic region located on 12q24.

Exclusion of non-synonymous SNPs and a polyglutamine tract in SMRT/N-CoR2 as common deleterious mutation for bipolar disorder in the Sagnenay-Lac-St-Jean population.

Bipolar disorder (BP) is a psychiatric illness with both genetic and environmental components occurring with a prevalence of slightly more than 1%. Our previous linkage and case/control studies have pointed to a susceptibility locus for BP in the 12q24.31 chromosomal region.

Analysis of a variable number tandem repeat polymorphism in the huntingtin interacting protein-1 related gene for anticipation in bipolar affective disorder.

The anticipation phenomenon, described as either an increase in disease severity, a decrease in age at onset, or both, in successive generations, has been suggested as a possibility of genetic transmission for bipolar affective disorder. We report here investigation of the stability of intergenerational transmission of a variable number tandem repeat (VNTR) polymorphism, found in the Huntingtin interacting protein-1 related gene (HIP12/HIP1R) that is mapped to the chromosome 12q24.31 region, in nine pedigrees showing decreased age at onset in successive generations.

Decreased hypothalamic and adrenal angiotensin II receptor expression and adrenomedullary catecholamines in transgenic mice with impaired glucocorticoid receptor function.

In transgenic mice expressing an antisense mRNA against the glucocorticoid receptor (GR), which partially blocks GR expression, impaired glucocorticoid feedback efficacy is accompanied by reduced hypothalamic corticotropin-releasing hormone (CRH) and vasopressin (AVP) activity and reduced peripheral sympathetic tone, indications of a shift in the balance of hypothalamic CRH and sympathetic regulation. As angiotensin II (Ang II) regulates CRH, AVP and sympathetic activity, we studied the expression of Ang II receptors in the hypothalamus and adrenal gland of GR transgenic and wild-type mice, adrenal catecholamines and mRNA for their rate-limiting enzyme, tyrosine hydroxylase (TH). We found that transgenic mice expressed significantly less numbers of Ang II AT(1) receptors in the hypothalamic paraventricular nucleus and median eminence, lower numbers of AT(2) receptors in supraoptic and paraventricular nuclei and lower numbers of AT(2) receptors in the adrenal medulla when compared with wild-type controls.

Chronic treatment with desipramine and fluoxetine modulate BDNF, CaMKKalpha and CaMKKbeta mRNA levels in the hippocampus of transgenic mice expressing antisense RNA against the glucocorticoid receptor.

Antidepressants up-regulate the cAMP response element binding protein (CREB) and the brain-derived neurotrophic factor (BDNF) in hippocampus and these effects contribute to the protection of hippocampal neurons from stressful stimuli such as high glucocorticoid levels. CREB can be activated by both protein kinase A and by Ca2+-calmodulin-dependent protein kinases (CaMKs), which are in turn phosphorylated by their upstream activators CaMKKalpha and CaMMKKbeta. Using in situ hybridization, we examined the effects of chronic treatment with fluoxetine (FLU) or desipramine (DMI) on BDNF, CaMKKalpha and CaMKKbeta mRNAs in the hippocampus of wild-type (Wt) and transgenic (TG) mice characterized by glucocorticoid receptor (GR) dysfunction.

A genome-wide scan points to a susceptibility locus for bipolar disorder on chromosome 12.

Our previous results pointed to a putative gene for susceptibility to bipolar affective disorder located on the chromosomal region 12q23-q24 that segregated in the Saguenay-Lac-St-Jean population of Quebec. We report here results from a second genome-wide scan based on the analysis of 380 polymorphic microsatellite markers. For the purpose of this analysis, an additional 18 families were recruited from the Saguenay-Lac-St-Jean region and pooled to our previous sample to improve its statistical power, giving a total of 394 sampled individuals.

Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression.

Major alterations of the hypothalamic-pituitary-adrenocortical (HPA) system that can be reversed by successful antidepressant therapy are often seen in depressed patients. Persuasive evidence points to the involvement of a dysfunctional glucocorticoid receptor (GR) system in these changes. Support for this also comes from studies of transgenic mice that express an antisense RNA, complementary to the GR mRNA, and have numerous neuroendocrine characteristics of human depression as well as altered behaviour.

Neurochemical and behavioral alterations in glucocorticoid receptor-impaired transgenic mice after chronic mild stress.

Mice (GR-i) bearing a transgene encoding a glucocorticoid receptor (GR) antisense RNA under the control of a neuron-specific neurofilament promoter were used to investigate the effects of a 4 week chronic mild stress (CMS) on the hypothalamo-pituitary-adrenocortical (HPA) axis and the serotoninergic system in a transgenic model of vulnerability to affective disorders. GR-i mice showed a decrease in both GR-specific binding (hippocampus and cerebral cortex) and GR mRNA levels [hippocampus, cerebral cortex, and dorsal raphe nucleus (DRN)] as well as a deficit in HPA axis feedback control (dexamethasone test) compared with paired wild-type (WT) mice. In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the density of cytosolic GR binding sites in the hippocampus, whereas, in the DRN, GR mRNA levels tended to increase.

Glucocorticoid receptor deficiency increases vulnerability of the nigrostriatal dopaminergic system: critical role of glial nitric oxide.

Glucocorticoids (GCs) exert via glucocorticoid receptors (GRs) potent anti-inflammatory and immunosuppressive effects. Emerging evidence indicates that an inflammatory process is involved in dopaminergic nigro-striatal neuronal loss in Parkinson's disease. We here report that the GR deficiency of transgenic (Tg) mice expressing GR antisense RNA from early embryonic life has a dramatic impact in "programming" the vulnerability of dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder.

Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very narrow" (i.

Genetic heterogeneity in a very large bipolar affective disorder pedigree from Quebec.

We previously reported a genome-wide scan for bipolar affective disorder based on a multigenerational family sampled from a relatively homogeneous population derived from founding families that migrated to an isolated area of Quebec from the early 1830s onwards. For the genome scan, the pedigree was split into five branches to facilitate calculation and a second family was added to more specifically analyze chromosome 12 results. In the present study, we reanalyzed the undivided pedigree after genealogical links were reconstructed over ten generations to investigate a founder effect using an algorithm in the SIMWALK2 package.

Cloning of mouse Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKKbeta) and characterization of CaMKKbeta and CaMKKalpha distribution in the adult mouse brain.

The Ca(2+)/calmodulin-dependent protein kinase kinases alpha and beta (CaMKKs alpha and beta) are novel members of the CaM kinase family. The CaMKKbeta was cloned from mouse brain. The deduced amino acid sequence shared 96.