Dissecting bipolar disorder complexity through epigenomic approach.

In recent years, numerous studies of gene regulation mechanisms have emerged in neuroscience. Epigenetic modifications, described as heritable but reversible changes, include DNA methylation, DNA hydroxymethylation, histone modifications and noncoding RNAs. The pathogenesis of psychiatric disorders, such as bipolar disorder, may be ascribed to a complex gene-environment interaction (G × E) model, linking the genome, environmental factors and epigenetic marks. Both the high complexity and the high heritability of bipolar disorder make it a compelling candidate for neurobiological analyses beyond DNA sequencing. Questions that are being raised in this review are the precise phenotype of the disorder in question, and also the trait versus state debate and how these concepts are being implemented in a variety of study designs.

Advances in rare earth spectroscopy and applications.

Rare earth (RE) elements are prime constituents in a large amount of innovative materials and several technological advances would not be possible without their contribution. In this review, recent progress in the field of rare earth spectroscopy is highlighted, with a special emphasis on clean energy, sensors and telecommunications, providing a broad view on past and recent developments.

Infrared cascade and cooperative multicolor upconversion emissions in Y8V2O17:Eu:Yb nanophosphors.

This work reports on the efficient cooperative upconversion and infrared cascade downconversion emissions in a novel Y8V2O17:Eu:Yb nanophosphor. The excitation with UV light produces emission in the 950-1000 nm region, corresponding to the Yb³âº:²F5/2-->²F7/2 transition, as well as visible emissions of the Eu³âº ion. Time-resolved spectroscopy measurements revealed that the mechanism responsible for this transition is the efficient cascade nonresonant energy transfer from VO4³-->Eu-->Yb. When the same nanophosphor is excited with 976 nm radiation, bright reddish upconversion emission of the Eu³âº:5DJ-->7FJ transition is observed as consequence of the Yb + Yb-->Eu cooperative energy transfer mechanism, which was established by analyzing the emission power dependence and the time-resolved spectroscopy of radiative transitions.

Comparative spectroscopic study of Tb:Ce(Sal)3Phen complex inhibited PVA nanofibres for flexible moisture sensor.

In the present work, we report a systematic study on optical alteration in Tb:Ce(Sal)3Phen, Tb(Sal)3Phen complexes, and TbCl3·6H2O inhibited in polyvinyl alcohol (PVA) polymeric nanofibres. We also report the feasibility of Tb:Ce(Sal)3Phen complex dispersed electrospun nanofibres for opto-humidity sensor. Structural, morphological, and spectroscopic properties of the synthesized nanofibres were systematically compared using Fourier transform infrared spectroscopy, scanning electron microscopy, and Photoluminescence analysis. Synthesized Tb(Sal)3Phen complex inhibited in nanofibres yields characteristic bright green photoluminescence of Tb3+ under UV excitations, which is at least two manifolds enhanced on the addition of Ce3+ ions in the same complex. The presence of Ce3+ ions, the salicylate ligand, and the Tb3+ ion help to expand the absorption range (290 nm-400 nm) and, subsequently, the photoluminescence in blue and green regions. Our analysis revealed the linear enhancement of photoluminescence intensity with the addition of Ce3+ ions. Upon exposing the flexible Tb:Ce(Sal)3Phen complex dispersed nanofibres mat in different humidity environments, photoluminescence intensity shows a linear variation. The prepared nanofibres film shows good reversibility, small hysteresis, cyclic stability, and acceptable response and recovery times i.e. 35 and 45 s. The humidity sensing mechanism was proposed on the basis of infrared absorption analysis of dry and humid nanofibres.

Gd3+ sensitized enhanced green luminescence in Gd:Tb(Sal)3Phen complex in PVA.

Ternary and tertiary complexes of Tb(Sal)(3)Phen and Gd:Tb(Sal)(3)Phen were synthesized and characterized in PVA polymer. The structural properties of these systems were evaluated on the basis of NMR and FT-IR techniques. The absorption, excitation and emissive properties of the Tb(3+) ion were improved when coordinated with Sal and Phen ligands. Photoluminescence properties of the complexes in solution, crystals and dispersed in PVA film were explored in steady state and in time domain. Selective excitations (487, 355, 310 and 266 nm) of Tb(3+), Sal and Gd(3+) ions reveal an intramolecular energy transfer process. The emission of Gd:Tb(Sal)(3)Phen complex in PVA indicates the contribution of Gd(3+) ion to enhance the emission intensity of Tb(3+) ion. On the basis of these investigations, photophysics was widely discussed in terms of energy transfer and encapsulation effect.

Synthesis, physicochemical and optical characterization of novel fluorescing complex: o-phenylenediamine-benzoin.

The complex of o-phenylenediamine (o-PDA) and benzoin (BN) was synthesized adopting solid state reaction by mixing of their melt together followed by chilling. The phase diagram study shows the formation of a complex in 1:1 molar ratio with congruent melting point and two eutectics lying on either side of complex. The formation of complex was confirmed using the FTIR, NMR, mass spectroscopy, powder XRD and DSC studies. The optical properties of the parent component, their complex and few other compositions nearby the complex were studied using absorption and laser luminescence techniques. The significantly higher green/yellow emission was noted with newly synthesized complex as compared to that of their parents as well as other compositions of o- PDA and BN.

Dual interactions and thermo-optical analysis of YAGG:Ce/Eu nanophosphor.

Present article report on structural and optical investigations of doubly doped Y3(Al5-xGax)O12:Ce/Eu nanophosphor. Efforts have been made to explore the interaction between the Ce3+ and Eu3+ ions and subsequently variation in overall color perception. Experimental techniques namely XRD, HR-TEM, and SEM reveal precipitation of tiny particles with diameter ~22 nm. Structural refinement has been carried out by Rietveld refinement. Photo-excitation by 342, 405, 450, and 464 nm wavelengths triggers the emission from Eu3+ and Ce3+ ions. Further, the laser excitations by 405 nm and 450 nm radiations, induced YAGG:Ce/Eu nanophosphor to yield combinatorial emission of both Ce3+ and Eu3+ ions; though, the intensity was found to be altered due to the two-way ionic interaction between the doped ions. The resultant emission extended in the red region. Also, the doubly doped sample exhibits strong temperature reliance on the emission intensity in the temperature range extended over 273-388 K. The color perception of the nanophosphor was observed to be significantly modified at different excitation wavelengths, temperatures, and laser powers as reflected by CIE coordinates.

Overtone spectroscopy of chlorine substituted benzene derivatives.

The absorption spectra of di-, tri- and tetra-derivatives of chlorobenzene have been studied in their pure form in the spectral range 400-20,000 cm(-1). A large number of bands associated with the fundamental, the overtones and the combination frequencies of C-H stretching mode have been observed. Vibrational frequencies, anharmonicity constants and dissociation energies, for the C-H stretch vibrations for the six molecules have been determined using local mode model. The C-H stretch frequencies obtained from experiments are compared with the corresponding frequency determined theoretically using RHF and DFT methods with same 6-31+G* basis set. This information has been used for the assignment of several combination bands as well as some weak overtone bands. Effect of hydrogen atom substitution by chlorine atom has been studied by measuring changes in the vibrational frequency of the C-H stretching mode and the C-H bond length. Frequency changes have been well correlated with the change in charge density on carbon as well as chlorine atoms.

White light color tuning ability of hybrid Dibenzoylmethane/YAG:Ce nanophosphor.

In this study, we have considered the synthesis of a novel hybrid material consisting of cerium-doped yttrium aluminium garnet (YAG:Ce) nanophosphor surface decorated by UV/blue sensitizing Dibenzoylmethane (DBM) organic molecule. A comparative evaluation of synthesized hybrid material YAG:Ce/DBM nanophosphor and YAG:Ce nanophosphors was made using a combination of different analytical techniques like X-ray diffraction, Scanning electron microscopy, UV-Visible-Infrared absorption, Photoluminescence techniques etc. Due to the presence of organic ligand, the hybrid nanophosphor has extended excitation. We have monitored the emission spectra at excitation with 355 nm, 375 nm, 405 nm, and 465 nm. The synthesized luminescent hybrid material was characterized by various spectroscopic techniques and its photophysical properties were thoroughly investigated. The color perception of hybrid YAG:Ce/DBM nanophosphor is significantly modified due to the mixing of blue color in the green-yellow emission of YAG:Ce nanophosphor at different excitations which yield CIE coordinates (0.37, 0.59).

Optical properties of Rh 6G dye in liquid and solid polymer.

Rhodamine 6G dye doped in liquid MMA (monomer) and solid polymer (PMMA) has been studied and its spectra compared with the one dissolved in n-BA solvent. The effect of temperature and laser power on the emissive characteristics of dye in polymer and in solvent has also been compared.

Vibrational and spectroscopic analysis of white light emitting Bi2SiO5 nanophosphor.

A series of Dy3+ ion activated Bi2SiO5 nanophosphors were synthesized by the hydrothermal and coprecipitation methods. Various structural and optical characterizations were made using X-ray diffraction, Scanning and Transmission electron microscopy, UV-Visible-Infrared absorption, Raman Spectroscopy, Photoluminescence, Time resolved luminescence techniques etc. Dy3+ ion doped samples yields characteristic bright yellow and blue emissions, on resonant excitation with 349nm and 386nm. The intensity ratio of the yellow/blue peaks was found to be function of Dy ion concentration and synthesis method. We have achieved white colour emission at 1.5mol% Dy concentration, CIE coordinate (0.36, 0.4) of which fall well within gamut of white light. The time-resolved fluorescence reveals decrease in radiative lifetime values with increasing Dy3+ ions concentration. A comparison between the samples synthesized by different methods, and Dy ion concentrations has been made and detail photo-physics involved is presented in the article.

Animal models to improve our understanding and treatment of suicidal behavior.

Worldwide, suicide is a leading cause of death. Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations. Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes. Animal models are similarly a critical resource to help delineate treatment targets and pharmacological means to improve our ability to manage the risk of suicide. In particular, certain pathophysiological pathways to suicidal behavior, including stress and hypothalamic-pituitary-adrenal axis dysfunction, neurotransmitter system abnormalities, endocrine and neuroimmune changes, aggression, impulsivity and decision-making deficits, as well as the role of critical interactions between genetic and epigenetic factors, development and environmental risk factors can be modeled in laboratory animals. We broadly describe human biological findings, as well as protective effects of medications such as lithium, clozapine, and ketamine associated with modifying risk of engaging in suicidal behavior that are readily translatable to animal models. Endophenotypes of suicidal behavior, studied in animal models, are further useful for moving observed associations with harmful environmental factors (for example, childhood adversity, mechanical trauma aeroallergens, pathogens, inflammation triggers) from association to causation, and developing preventative strategies. Further study in animals will contribute to a more informed, comprehensive, accelerated and ultimately impactful suicide research portfolio.

Antidepressants reverse corticosterone-mediated decrease in brain-derived neurotrophic factor expression: differential regulation of specific exons by antidepressants and corticosterone.

Earlier studies have implicated brain-derived neurotrophic factor in stress and in the mechanism of action of antidepressants. It has been shown that antidepressants upregulate, whereas corticosterone downregulates, brain-derived neurotrophic factor expression in rat brain. Whether various classes of antidepressants reverse corticosterone-mediated downregulation of brain-derived neurotrophic factor is unclear. Also not known is how antidepressants or corticosterone regulates brain-derived neurotrophic factor expression. To clarify this, we examined the effects of various classes of antidepressants and corticosterone, alone and in combination, on the mRNA expression of total brain-derived neurotrophic factor and of individual brain-derived neurotrophic factor exons, in rat brain. Normal or corticosterone pellet-implanted (100 mg, 21 days) rats were injected with different classes of antidepressants, fluoxetine, desipramine, or phenelzine, intraperitoneally for 21 days and killed 2 h after the last injection. mRNA expression of total brain-derived neurotrophic factor and of exons I-IV was measured in frontal cortex and hippocampus. Given to normal rats, fluoxetine increased total brain-derived neurotrophic factor mRNA only in hippocampus, whereas desipramine or phenelzine increased brain-derived neurotrophic factor mRNA in both frontal cortex and hippocampus. When specific exons were examined, desipramine increased expression of exons I and III in both brain areas, whereas phenelzine increased exon I in both frontal cortex and hippocampus but exon IV only in hippocampus. On the other hand, fluoxetine increased only exon II in hippocampus. Corticosterone treatment of normal rats decreased expression of total brain-derived neurotrophic factor mRNA in both brain areas, specifically decreasing exons II and IV. Treatment with desipramine or phenelzine of corticosterone pellet-implanted rats reversed the corticosterone-induced decrease in total brain-derived neurotrophic factor expression in both brain areas; however, fluoxetine reversed the decrease only partially in hippocampus. Interestingly, antidepressant treatment of corticosterone pellet-implanted rats increased only those specific exons that are increased during treatment of normal rats with each particular antidepressant. We found that although corticosterone and antidepressants both modulate brain-derived neurotrophic factor expression, and antidepressants reverse the corticosterone-induced brain-derived neurotrophic factor decrease, antidepressants and corticosterone differ in how they regulate the expression of brain-derived neurotrophic factor exon(s).

Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study.

BACKGROUND: Reelin (RELN) is a glycoprotein secreted preferentially by cortical gamma-aminobutyric acid-ergic (GABAergic) interneurons (layers I and II) that binds to integrin receptors located on dendritic spines of pyramidal neurons or on GABAergic interneurons of layers III through V expressing the disabled-1 gene product (DAB1), a cytosolic adaptor protein that mediates RELN action. To replicate earlier findings that RELN and glutamic acid decarboxylase (GAD)(67), but not DAB1 expression, are down-regulated in schizophrenic brains, and to verify whether other psychiatric disorders express similar deficits, we analyzed, blind, an entirely new cohort of 60 postmortem brains, including equal numbers of patients matched for schizophrenia, unipolar depression, and bipolar disorder with nonpsychiatric subjects. METHODS: Reelin, GAD(65), GAD(67), DAB1, and neuron-specific-enolase messenger RNAs (mRNAs) and respective proteins were measured with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or Western blot analyses. Reelin-positive neurons were identified by immunohistochemistry using a monoclonal antibody. RESULTS: Prefrontal cortex and cerebellar expression of RELN mRNA, GAD(67) protein and mRNA, and prefrontal cortex RELN-positive cells was significantly decreased by 30% to 50% in patients with schizophrenia or bipolar disorder with psychosis, but not in those with unipolar depression without psychosis when compared with nonpsychiatric subjects. Group differences were absent for DAB1,GAD(65) and neuron-specific-enolase expression implying that RELN and GAD(67) down-regulations were unrelated to neuronal damage. Reelin and GAD(67) were also unrelated to postmortem intervals, dose, duration, or presence of antipsychotic medication. CONCLUSIONS: The selective down-regulation of RELN and GAD(67) in prefrontal cortex of patients with schizophrenia and bipolar disorder who have psychosis is consistent with the hypothesis that these parameters are vulnerability factors in psychosis; this plus the loss of the correlation between these 2 parameters that exists in nonpsychotic subjects support the hypothesis that these changes may be liability factors underlying psychosis.

Chronic corticosterone-mediated dysregulation of microRNA network in prefrontal cortex of rats: relevance to depression pathophysiology.

Stress plays a major role in inducing depression, which may arise from interplay between complex cascades of molecular and cellular events that influence gene expression leading to altered connectivity and neural plasticity. In recent years, microRNAs (miRNAs) have carved their own niche owing to their innate ability to induce disease phenotype by regulating expression of a large number of genes in a cohesive and coordinated manner. In this study, we examined whether miRNAs and associated gene networks have a role in chronic corticosterone (CORT; 50 mg kg(-1) × 21 days)-mediated depression in rats. Rats given chronic CORT showed key behavioral features that resembled depression phenotype. Expression analysis revealed differential regulation of 26 miRNAs (19 upregulated, 7 downregulated) in prefrontal cortex of CORT-treated rats. Interaction between altered miRNAs and target genes showed dense interconnected molecular network, in which multiple genes were predicated to be targeted by the same miRNA. A majority of altered miRNAs showed binding sites for glucocorticoid receptor element, suggesting that there may be a common regulatory mechanism of miRNA regulation by CORT. Functional clustering of predicated target genes yielded disorders such as developmental, inflammatory and psychological that could be relevant to depression. Prediction analysis of the two most prominently affected miRNAs miR-124 and miR-218 resulted into target genes that have been shown to be associated with depression and stress-related disorders. Altogether, our study suggests miRNA-mediated novel mechanism by which chronic CORT may be involved in depression pathophysiology.

Protein kinase C in platelets of depressed patients.

BACKGROUND: We studied the role of protein kinase C (PKC), a major regulatory enzyme and an important component of the phosphoinositide signaling system, in depression. METHODS: PKC was determined using [3H]phorbol dibutyrate (PDBu) as the radioligand in the membranal and cytosolic fractions of platelets obtained from hospitalized drug-free depressed patients during a baseline period and from drug-free normal control subjects. RESULTS: We observed that the [3H]PDBu binding was significantly higher in the cytosolic fraction obtained from platelets of depressed patients compared to normal control subjects. CONCLUSIONS: Our studies indicate increased formation of PKC in platelets of depressed patients. The significance and mechanisms involved in increased PKC in the cytosolic fraction of platelets are unclear, but they suggest that increased PKC may be associated with the pathophysiology of depressive illness.

Platelet serotonin-2A receptors: a potential biological marker for suicidal behavior.

OBJECTIVE: Abnormalities in the serotonergic system have been implicated in suicidal behavior. Higher numbers of serotonin-2 (5-HT2) receptors have been reported in the post-mortem brain of suicide victims. In order to further examine the role of 5-HT2A receptors in suicidal behavior, the authors studied 5-HT2A receptors in platelets of suicidal and nonsuicidal patients as well as normal comparison subjects. METHOD: 5-HT2A receptor levels were determined by using [125I]LSD as a radioligand in platelets obtained from hospitalized psychiatric patients (N = 131) and nonhospitalized normal comparison subjects (N = 40) during a drug-free baseline period. Patients were diagnosed according to DSM-III-R criteria, and suicidal behavior was identified by using the Hamilton Depression Rating Scale. RESULTS: The mean maximum number of binding sites (Bmax) of platelet 5-HT2A receptors for all suicidal patients was significantly higher than for nonsuicidal patients or normal comparison subjects. This significant difference remained when subgroups of suicidal patients with depression, schizophrenia, schizoaffective disorder, or bipolar illness were compared to the other two subject groups. The higher number of platelet 5-HT2A receptors in suicidal patients was independent of diagnosis. While there was no significant difference in Bmax between patients with serious suicidal ideation and those who made suicidal attempts, both groups had significantly higher Bmax than normal comparison subjects. CONCLUSIONS: The observed higher number of platelet 5-HT2A receptors in suicidal patients is independent of diagnosis and appears to be associated with both the brain and the platelets of suicidal patients. These results thus suggest the potential usefulness of platelet 5-HT2A receptors as a biological marker for identifying suicide-prone patients.

Low phosphoinositide-specific phospholipase C activity and expression of phospholipase C beta1 protein in the prefrontal cortex of teenage suicide subjects.

OBJECTIVE: The enzyme phosphoinositide-specific phospholipase C (PI-PLC) is a component of the phosphoinositide signal transduction system. Other components of this system have been found to be abnormal in adults and adolescents who have committed suicide, and so the authors examined whether PI-PLC activity and protein expression of PLC isozymes are abnormal in postmortem brains of teenage suicide subjects. METHOD: PI-PLC activity and protein expression of the PLC beta1, delta1, and gamma1 isozymes were examined in Brodmann's areas 8 and 9 of postmortem brains obtained from 18 teenage suicide subjects and 18 matched comparison subjects. PI-PLC activity was determined by enzymatic assay, and protein expression of the PLC isozymes was determined by the Western blot technique. RESULTS: Compared with the normal subjects, the teenage suicide subjects had significantly lower PI-PLC activity and immunolabeling of the specific PLC beta1 isozyme in both membrane and cytosol fractions of Brodmann's areas 8 and 9 combined (prefrontal cortex). There was also a significant correlation between PI-PLC activity and protein levels of the PLC beta1 isozyme in the brains of the teenage suicide subjects. There was no significant difference in PI-PLC activity or level of PLC beta1 protein between the suicide subjects with a history of mental disorders and those with no history of mental disorders; however, both groups had significantly lower PI-PLC activity and expression of PLC beta1 protein than the normal subjects. CONCLUSIONS: Low PI-PLC activity and expressed levels of the PLC beta1 isozyme in postmortem brains of suicide subjects may have clinical relevance in the pathophysiology of suicidal behavior.

Antidepressants reduce phosphoinositide-specific phospholipase C (PI-PLC) activity and the mRNA and protein expression of selective PLC beta 1 isozyme in rat brain.

In order to examine whether antidepressants mediate their action by interacting with one of the key components of the phosphoinositide (PI) signaling pathway, i.e. PI-specific phospholipase C (PLC), and whether this represents a common mechanism of action of antidepressants, we determined the effects of antidepressants of various classes on PI-PLC activity and on the expression of PLC isozymes in rat brain. It was observed that chronic (21-day) but not acute (1-day) administration with desipramine (DMI), fluoxetine (FLX) and phenelzine (PHLZ), decreased PI-PLC activity in membrane and cytosol fractions of cortex and hippocampus. Similar changes were observed with alprazolam (ALP) and buspirone (BUS), who possess anxiolytic and antidepressant properties. On the other hand, an anxiogenic drug, metachlorophenylpiperazine (MCPP), increased PI-PLC activity in both membrane and cytosol fractions of cortex and hippocampus. The immunolabeling studies showed that all the antidepressants and anxiolytics that caused a decrease in PI-PLC activity also selectively decreased the protein levels of a specific isozyme of PLC, i.e. PLCbeta(1), in membrane and cytosol fractions of cortex and hippocampus, whereas MCPP increased the levels of this particular isozyme. These changes were accompained with changes in the mRNA levels of PLCbeta(1), as determined by quantitative RT-PCR. These antidepressants and anxiolytics did not cause significant changes in the expression of PLC delta(1) or gamma(1) isozyme. Our results thus suggest that modulation of PI-PLC may be common to all classes of antidepressants, which in turn, may be associated with their mechanisms of action.

Elevated [3H]inositol 1,4,5-trisphosphate binding sites and expressed inositol 1,4,5-trisphosphate receptor protein level in platelets of depressed patients.

Several reports suggest that serotonin2A (5HT2A) receptors and this receptor-mediated phosphatidyl inositol (PI) hydrolysis signal transduction system are altered in platelets of depressed patients. Inositol 1,4,5-trisphosphate (Ins[1,4,5]P3), an important component of the PI signaling system, plays a crucial role in various physiological processes by releasing Ca2+ from intracellular stores after binding with Ins(1,4,5)P3 receptors. To examine the role of Ins(1,4,5)P3 receptors in depression, we determined [3H]Ins(1,4,5)P3 binding sites and expressed protein levels of Ins(1,4,5)P3 receptors in platelets of depressed patients (n=15) and normal control subjects (n=17). We observed that the mean Bmax of [3H]Ins(1,4,5)P3 binding to Ins(1,4,5)P3 receptors was significantly higher in platelets of depressed subjects compared with normal control subjects, whereas there was no significant difference in K(D) between these two groups. The immuno-detectable expressed level of Ins(1,4,5)P3 receptor protein was also significantly increased in depressed patients in contrast to the levels of normal control subjects. Moreover, a significant correlation was observed in Bmax and the protein level of Ins(1,4,5)P3 receptors. The increase in the number of [3H]Ins(1,4,5)P3 binding sites in platelets of depressed subjects appears to be due to an increase in the amount of Ins(1,4,5)P3 receptor proteins. These results suggest that Ins(1,4,5)P3 receptors may be involved in the pathophysiology of depression.