Atmospheric neutrino oscillations with three neutrinos and a mass hierarchy

A comprehensive formalism for the description of neutrino oscillations in the Earth in a general scheme with three massive neutrinos and the mass hierarchy m_1<<m_2<<m_3 is presented. Using this formalism, which is valid both in vacuum and in a medium, the matter effect on the oscillations of low-energy neutrinos is discussed, pointing out the existence of very long oscillations which are independent of the neutrino masses and the neutrino energy, and are very sensitive to the matter density along the neutrino trajectory. As an example of application of the formulation, a fit of the Kamiokande atmospheric neutrino data with the matter effect taken into account for neutrinos propagating in the Earth is presented. The results of the fit indicate that 4*10^{-3} eV^2 < m_3^2 nu_e, nu_munu_tau, nu_enu_tau) could be large. Hence, long-baseline experiments with reactor (CHOOZ and Palo Verde) and accelerator (K2K, MINOS and ICARUS) neutrinos could observe neutrino oscillations in all channels with a relatively large statistics.Comment: 42 pages, including 7 figure

Plasma Fibrinogen: Now Also An Antidepressant Response Marker?

Major depressive disorder (MDD) is one of the leading causes of global disability. It is a risk factor for noncompliance with medical treatment, with about 40% of patients not responding to currently used antidepressant drugs. The identification and clinical implementation of biomarkers that can indicate the likelihood of treatment response are needed in order to predict which patients will benefit from an antidepressant drug. While analyzing the blood plasma proteome collected from MDD patients before the initiation of antidepressant medication, we observed different fibrinogen alpha (FGA) levels between drug responders and nonresponders. These results were replicated in a second set of patients. Our findings lend further support to a recently identified association between MDD and fibrinogen levels from a large-scale study. © 2014 Macmillan Publishers Limited.4DiMatteo, M.R., Lepper, H.S., Croghan, T.W., Depression is a risk factor for noncompliance with medical treatment meta-analysis of the effects of anxiety and depression on patient adherence (2000) Archives of Internal Medicine, 160 (14), pp. 2101-2107Rosenzweig-Lipson, S., Beyer, C.E., Hughes, Z.A., Khawaja, X., Rajarao, S.J., Malberg, J.E., Rahman, Z., Schechter, L.E., Differentiating antidepressants of the future: Efficacy and safety (2007) Pharmacology and Therapeutics, 113 (1), pp. 134-153. , DOI 10.1016/j.pharmthera.2006.07.002, PII S0163725806001331Nrugham, L., Holen, A., Sund, A.M., Suicide attempters and repeaters: Depression and coping: A prospective study of early adolescents followed up as young adults (2012) J Nerv Ment Dis, 200, pp. 197-203Martins-de-Souza, D., Harris, L.W., Guest, P.C., Turck, C.W., Bahn, S., The role of proteomics in depression research (2010) Eur Arch Psy Clin Neurosci, 260, pp. 499-506Wium-Andersen, M.K., Orsted, D.D., Nordestgaard, B.G., Association between elevated plasma fibrinogen and psychological distress, and depression in 73 367 individuals from the general population (2012) Mol Psychiatry, 18, pp. 854-855Hennings, J.M., Owashi, T., Binder, E.B., Horstmann, S., Menke, A., Kloiber, S., Clinical characteristics and treatment outcome in a representative sample of depressed inpatients -Findings from the munich antidepressant response signature (mars) project (2009) J Psychiatr Res, 43, pp. 215-229Wium-Andersen, M.K., Orsted, D.D., Nordestgaard, B.G., Elevated plasma fibrinogen, psychological distress, antidepressant use, and hospitalization with depression: Two large population-based studies (2012) Psychoneuroendocrinology, 38, pp. 638-647Panagiotakos, D.B., Pitsavos, C., Chrysohoou, C., Tsetsekou, E., Papageorgiou, C., Christodoulou, G., Stefanadis, C., Inflammation, coagulation, and depressive symptomatology in cardiovascular disease-free peoplethe ATTICA study (2004) European Heart Journal, 25 (6), pp. 492-499. , DOI 10.1016/j.ehj.2004.01.018Maes, M., Delange, J., Ranjan, R., Meltzer, H.Y., Desnyder, R., Cooremans, W., Scharpe, S., Acute phase proteins in schizophrenia, mania and major depression: Modulation by psychotropic drugs (1997) Psychiatry Research, 66 (1), pp. 1-11. , DOI 10.1016/S0165-1781(96)02915-0, PII S016517819602915Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E.K., A metaanalysis of cytokines in major depression (2010) Biol Psychiatry, 67, pp. 446-457Howren, M.B., Lamkin, D.M., Suls, J., Associations of depression with c-reactive protein, il-1, and il-6: A meta-analysis (2009) Psychosom Med, 71, pp. 171-186Krishnadas, R., Cavanagh, J., Depression: An inflammatory illness? (2012) J Neurol Neurosurg Psychiatry, 83, pp. 495-502Muller, N., Myint, A.M., Schwarz, M.J., Inflammatory biomarkers and depression (2011) Neurotox Res, 19, pp. 308-318Dantzer, R., O'Connor, J.C., Lawson, M.A., Kelley, K.W., Inflammation-associated depression: From serotonin to kynurenine (2011) Psychoneuroendocrinology, 36, pp. 426-436Duivis, H.E., De Jonge, P., Penninx, B.W., Na, B.Y., Cohen, B.E., Whooley, M.A., Depressive symptoms, health behaviors, and subsequent inflammation in patients with coronary heart disease: Prospective findings from the heart and soul study (2011) Am J Psychiatry, 168, pp. 913-920Baune, B.T., Neuhauser, H., Ellert, U., Berger, K., The role of the inflammatory markers ferritin, transferrin and fibrinogen in the relationship between major depression and cardiovascular disorders -The german health interview and examination survey (2010) Acta Psychiatr Scand, 121, pp. 135-142Vasse, M., Paysant, J., Soria, J., Collet, J.P., Vannier, J.P., Soria, C., Regulation of fibrinogen biosynthesis by cytokines, consequences on the vascular risk (1996) Haemostasis, 26 (SUPPL. 4), pp. 331-339Miller, A.H., Maletic, V., Raison, C.L., Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression (2009) Biol Psychiatry, 65, pp. 732-741Catena-Dell'Osso, M., Rotella, F., Dell'Osso, A., Fagiolini, A., Marazziti, D., Inflammation, serotonin and major depression (2013) Curr Drug Targets, 14, pp. 571-577Fish, R.J., Neerman-Arbez, M., Fibrinogen gene regulation (2012) Thromb Haemost, 108, pp. 419-426Yusuf, S., Lessem, J., Jha, P., Lonn, E., Primary and secondary prevention of myocardial infarction and strokes: An update of randomly allocated, controlled trials (1993) Journal of Hypertension, 11 (SUPPL. 4), pp. S61-S73Meade, T.W., Haemostatic function and arterial disease (1994) British Medical Bulletin, 50 (4), pp. 755-775Shu, H., Blomback, M., Gina, Y., Sinha, R., Henschen -Edman, A.H., Modified clotting properties of fibrinogen in the presence of acetylsalicylic acid in a purified system (2001) Annals of the New York Academy of Sciences, 936, pp. 531-535Caspary, E.A., Studies on the acetylation of human fibrinogen (1956) Biochem J, 62, pp. 507-51

Supplementary Material for: NextGen Brain Microdialysis: Applying Modern Metabolomics Technology to the Analysis of Extracellular Fluid in the Central Nervous System

Microdialysis is a powerful method for in vivo neurochemical analyses. It allows fluid sampling in a dynamic manner in specific brain regions over an extended period of time. A particular focus has been the neurochemical analysis of extracellular fluids to explore central nervous system functions. Brain microdialysis recovers neurotransmitters, low-molecular-weight neuromodulators and neuropeptides of special interest when studying behavior and drug effects. Other small molecules, such as central metabolites, are typically not assessed despite their potential to yield important information related to brain metabolism and activity in selected brain regions. We have implemented a liquid chromatography online mass spectrometry metabolomics platform for an expanded analysis of mouse brain microdialysates. The method is sensitive and delivers information for a far greater number of analytes than commonly used electrochemical and fluorescent detection or biochemical assays. The metabolomics platform was applied to the analysis of microdialysates in a foot shock-induced mouse model of posttraumatic stress disorder (PTSD). The rich metabolite data information was then used to delineate affected prefrontal molecular pathways that reflect individual susceptibility for developing PTSD-like symptoms. We demonstrate that hypothesis-free metabolomics can be adapted to the analysis of microdialysates for the discovery of small molecules with functional significance

Blood Mononuclear Cell Proteome Suggests Integrin And Ras Signaling As Critical Pathways For Antidepressant Treatment Response

[No abstract available]767e15e17Fava, G.A., Subclinical symptoms in mood disorders: Pathophysiological and therapeutic implications (1999) Psychol Med, 29, pp. 47-61Rosenzweig-Lipson, S., Beyer, C.E., Hughes, Z.A., Khawaja, X., Rajarao, S.J., Malberg, J.E., Differentiating antidepressants of the future: Efficacy and safety (2007) Pharmacol Ther, 113, pp. 134-153Martins-De-Souza, D., Biomarkers for psychiatric disorders: Where are we standing? (2013) Dis Markers, 35, pp. 1-2Labermaier, C., Masana, M., Mueller, M., Biomarkers predicting antidepressant treatment response: How can we advance the field? (2013) Dis Markers, 35, pp. 23-31Oliveira, B.M., Schmitt, A., Falkai, P., Martins-De-Souza, D., Is clinical proteomics heading towards to bench to bedside? (2013) Transl Proteomics, 1, p. 3Hennings, J.M., Owashi, T., Binder, E.B., Horstmann, S., Menke, A., Kloiber, S., Clinical characteristics and treatment outcome in a representative sample of depressed inpatients-findings from the Munich Antidepressant Response Signature (MARS) project (2009) J Psychiatr Res, 43, pp. 215-229Maccarrone, G., Rewerts, C., Lebar, M., Turck, C.W., Martins-De-Souza, D., Proteome profiling of peripheral mononuclear cells from human blood (2013) Proteomics, 13, pp. 893-897Maccarrone, G., Turck, C.W., Martins-De-Souza, D., Shotgun mass spectrometry workflow combining IEF and LC-MALDI-TOF/TOF (2010) Protein J, 29, pp. 99-102Martins-De-Souza, D., Is the word 'biomarker' being properly used by proteomics research in neuroscience? (2010) Eur Arch Psychiatry Clin Neurosci, 260, pp. 561-562McGeachie, A.B., Cingolani, L.A., Goda, Y., Stabilising influence: Integrins in regulation of synaptic plasticity (2011) Neurosci Res, 70, pp. 24-29McGeachie, A.B., Skrzypiec, A.E., Cingolani, L.A., Letellier, M., Pawlak, R., Goda, Y., Beta3 integrin is dispensable for conditioned fear and hebbian forms of plasticity in the hippocampus (2012) Eur J Neurosci, 36, pp. 2461-2469Carter, M.D., Shah, C.R., Muller, C.L., Crawley, J.N., Carneiro, A.M., Veenstra-Vanderweele, J., Absence of preference for social novelty and increased grooming in integrin beta3 knockout mice: Initial studies and future directions (2011) Autism Res, 4, pp. 57-67Cingolani, L.A., Thalhammer, A., Yu, L.M., Catalano, M., Ramos, T., Colicos, M.A., Activity-dependent regulation of synaptic AMPA receptor composition and abundance by beta3 integrins (2008) Neuron, 58, pp. 749-762Carneiro, A.M., Cook, E.H., Murphy, D.L., Blakely, R.D., Interactions between integrin alphaIIbbeta3 and the serotonin transporter regulate serotonin transport and platelet aggregation in mice and humans (2008) J Clin Invest, 118, pp. 1544-1552Chain, D.G., Schwartz, J.H., Hegde, A.N., Ubiquitin-mediated proteolysis in learning and memory (1999) Mol Neurobiol, 20, pp. 125-142Fukuo, Y., Kishi, T., Kushima, I., Yoshimura, R., Okochi, T., Kitajima, T., Possible association between ubiquitin-specific peptidase 46 gene and major depressive disorders in the Japanese population (2011) J Affect Disord, 133, pp. 150-157Matthys, A., Van Craenenbroeck, K., Lintermans, B., Haegeman, G., Vanhoenacker, P., RhoBTB3 interacts with the 5-HT7a receptor and inhibits its proteasomal degradation (2012) Cell Signal, 24, pp. 1053-1063Mouri, A., Sasaki, A., Watanabe, K., Sogawa, C., Kitayama, S., Mamiya, T., MAGE-D1 regulates expression of depression-like behavior through serotonin transporter ubiquitylation (2012) J Neurosci, 32, pp. 4562-4580Elias, M., Brighouse, A., Gabernet-Castello, C., Field, M.C., Dacks, J.B., Sculpting the endomembrane system in deep time: High resolution phylogenetics of Rab GTPases (2012) J Cell Sci, 125, pp. 2500-2508McCormick, F., Ras-related proteins in signal transduction and growth control (1995) Mol Reprod Dev, 42, pp. 500-506Golden, S.A., Christoffel, D.J., Heshmati, M., Hodes, G.E., Magida, J., Davis, K., Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression (2013) Nat Med, 19, pp. 337-344Lopez-Munoz, F., Alamo, C., Monoaminergic neurotransmission: The history of the discovery of antidepressants from 1950s until today (2009) Curr Pharm des, 15, pp. 1563-1586Penn, E., Tracy, D.K., The drugs don't work? Antidepressants and the current and future pharmacological management of depression (2012) Ther Adv Psychopharmacol, 2, pp. 179-188Kumamaru, E., Numakawa, T., Adachi, N., Kunugi, H., Glucocorticoid suppresses BDNF-stimulated MAPK/ERK pathway via inhibiting interaction of Shp2 with TrkB (2011) FEBS Lett, 585, pp. 3224-3228Kerman, I.A., New insights into BDNF signaling: Relevance to major depression and antidepressant action (2012) Am J Psychiatry, 169, pp. 1137-1140Niciu, M.J., Ionescu, D.F., Mathews, D.C., Richards, E.M., Zarate, C.A., Second messenger/signal transduction pathways in major mood disorders: Moving from membrane to mechanism of action, part I: Major depressive disorder (2013) CNS Spectr, 18, pp. 231-241Duric, V., Banasr, M., Licznerski, P., Schmidt, H.D., Stockmeier, C.A., Simen, A.A., A negative regulator of MAP kinase causes depressive behavior (2010) Nat Med, 16, pp. 1328-1332Di Benedetto, B., Radecke, J., Schmidt, M.V., Rupprecht, R., Acute antidepressant treatment differently modulates ERK/MAPK activation in neurons and astrocytes of the adult mouse prefrontal cortex (2013) Neuroscience, 232, pp. 161-168Akbarian, S., Davis, R.J., Keep the 'phospho' on MAPK, be happy (2010) Nat Med, 16, pp. 1187-1188Yaniv, S.P., Lucki, A., Klein, E., Ben-Shachar, D., Dexamethasone enhances the norepinephrine-induced ERK/MAPK intracellular pathway possibly via dysregulation of the alpha2-adrenergic receptor: Implications for antidepressant drug mechanism of action (2010) Eur J Cell Biol, 89, pp. 712-72

Prediction of photoperiodic regulators from quantitative gene circuit models

Photoperiod sensors allow physiological adaptation to the changing seasons. The external coincidence hypothesis postulates that a light-responsive regulator is modulated by a circadian rhythm. Sufficient data are available to test this quantitatively in plants, though not yet in animals. In Arabidopsis, the clock-regulated genes CONSTANS (CO) and FLAVIN, KELCH, F-BOX (FKF1) and their lightsensitive proteins are thought to form an external coincidence sensor. We use 40 timeseries of molecular data to model the integration of light and timing information by CO, its target gene FLOWERING LOCUS T (FT), and the circadian clock. Among other predictions, the models show that FKF1 activates FT. We demonstrate experimentally that this effect is independent of the known activation of CO by FKF1, thus we locate a major, novel controller of photoperiodism. External coincidence is part of a complex photoperiod sensor: modelling makes this complexity explicit and may thus contribute to crop improvement

Erratum To Proteomic Analysis Of Dorsolateral Prefrontal Cortex Indicates The Involvement Of Cytoskeleton, Oligodendrocyte, Energy Metabolism And New Potential Markers In Schizophrenia [journal Of Psychiatric Research (2009); 43(11): 978-86]

[No abstract available]452283Liang, P., MacRae, T.H., Molecular chaperones and the cytoskeleton (1997) Journal of Cell Science, 110, pp. 1431-1440Nicholl, I.D., Quinlan, R.A., Chaperone activity of alpha-crystallins modulates intermediate filament assembly (1994) The EMBO Journal, 13 (4), pp. 945-95