Metabolic alterations in the cortex of a mouse model with glutathione deficit - relevance to schizophrenia

Background: Glutathione (GSH) is a major redox regulator and antioxidant and is decreased in cerebrospinal fluid and prefrontal cortex of schizophrenia patients [Do et al. (2000) Eur J Neurosci 12:3721]. The genes of the key GSH-synthesizing enzyme, glutamate- cysteine ligase catalytic (GCLC) and modifier (GCLM) subunits, are associated with schizophrenia, suggesting that the deficit in GSH synthesis is of genetic origin [Gysin et al. (2007) PNAS 104:16621]. GCLM knock-out (KO) mice, which display an 80% decrease in brain GSH levels, have abnormal brain morphology and function [Do et al. (2009) Curr Opin Neurobiol 19:220]. Developmental redox deregulation by impaired GSH synthesis and environmental risk factors generating oxidative stress may have a central role in schizophrenia. Here, we used GCLM KO mice to investigate the impact of a genetically dysregulated redox system on the neurochemical profile of the developing brain. Methods: The neurochemical profile of the anterior and posterior cortical areas of male and female GCLM KO and wild-type mice was determined by in vivo 1H NMR spectroscopy on postnatal days 10, 20, 30, 60 and 90, under 1 to 1.5% isoflurane anaesthesia. Localised 1H NMR spectroscopy was performed on a 14.1 T, 26 cm VNMRS spectrometer (Varian, Magnex) using a home-built 8 mm diameter quadrature surface coil (used both for RF excitation and signal reception). Spectra were acquired using SPECIAL with TE of 2.8 ms and TR of 4 s from VOIs placed in anterior or posterior regions of the cortex [Mlynárik et al. (2006) MRM 56:965]. LCModel analysis allowed in vivo quantification of a neurochemical profile composed of 18 metabolites. Results: GCLM KO mice displayed nearly undetectable GSH levels as compared to WT mice, demonstrating their drastic redox deregulation. Depletion of GSH triggered alteration of metabolites related to its synthesis, namely increase of glycine and glutamate levels during development (P20 and P30). Concentrations of glutamine and aspartate that are produced from glutamate were also increased in GCLM KO animals relative to WT. In addition, GCLM KO mice also showed higher levels of N-acetylaspartate that originates from the acetylation of aspartate. These metabolites are particularly implicated in neurotransmission processes and in mitochondrial oxidative metabolism. Their increase may indicate impaired mitochondrial metabolism with concomitant accumulation of lactate in the adult mice (P60 and P90). In addition, the GSH depletion triggers reduction of GABA concentration in anterior cortex of the P60 mice, which is in accordance with known impairment of GABAergic interneurons in that area. Changes were generally more pronounced in males than in females at P60, which is consistent with earlier disease onset in male patients. Discussion: In conclusion, the observed metabolic alterations in the cortex of a mouse model of redox deregulation suggest impaired mitochondrial metabolism and altered neurotransmission. The results also highlight the age between P20 and P30 as a sensitive period during the development for these alterations.

Increased male offspring's risk of metabolic-neuroendocrine dysfunction and overweight after fructose-rich diet intake by the lactating mother.

An adverse endogenous environment during early life predisposes the organism to develop metabolic disorders. We evaluated the impact of intake of an iso-caloric fructose rich diet (FRD) by lactating mothers (LM) on several metabolic functions of their male offspring. On postnatal d 1, ad libitum eating, lactating Sprague-Dawley rats received either 10% F (wt/vol; FRD-LM) or tap water (controls, CTR-LM) to drink throughout lactation. Weaned male offspring were fed ad libitum a normal diet, and body weight (BW) and food intake were registered until experimentation (60 d of age). Basal circulating levels of metabolic markers were evaluated. Both iv glucose tolerance and hypothalamic leptin sensitivity tests were performed. The hypothalamus was dissected for isolation of total RNA and Western blot analysis. Retroperitoneal (RP) adipose tissue was dissected and either kept frozen for gene analysis or digested to isolate adipocytes or for histological studies. FRD rats showed increased BW and decreased hypothalamic sensitivity to exogenous leptin, enhanced food intake (between 49-60 d), and decreased hypothalamic expression of several anorexigenic signals. FRD rats developed increased insulin and leptin peripheral levels and decreased adiponectinemia; although FRD rats normally tolerated glucose excess, it was associated with enhanced insulin secretion. FRD RP adipocytes were enlarged and spontaneously released high leptin, although they were less sensitive to insulin-induced leptin release. Accordingly, RP fat leptin gene expression was high in FRD rats. Excessive fructose consumption by lactating mothers resulted in deep neuroendocrine-metabolic disorders of their male offspring, probably enhancing the susceptibility to develop overweight/obesity during adult life.

A unique role for Kv3 voltage-gated potassium channels in starburst amacrine cell signaling in mouse retina

Direction-selective retinal ganglion cells show an increased activity evoked by light stimuli moving in the preferred direction. This selectivity is governed by direction-selective inhibition from starburst amacrine cells occurring during stimulus movement in the opposite or null direction. To understand the intrinsic membrane properties of starburst cells responsible for direction-selective GABA release, we performed whole-cell recordings from starburst cells in mouse retina. Voltage-clamp recordings revealed prominent voltage-dependent K+ currents. The currents were mostly blocked by 1 mm TEA, activated rapidly at voltages more positive than -20 mV, and deactivated quickly, properties reminiscent of the currents carried by the Kv3 subfamily of K+ channels. Immunoblots confirmed the presence of Kv3.1 and Kv3.2 proteins in retina and immunohistochemistry revealed their expression in starburst cell somata and dendrites. The Kv3-like current in starburst cells was absent in Kv3.1-Kv3.2 knock-out mice. Current-clamp recordings showed that the fast activation of the Kv3 channels provides a voltage-dependent shunt that limits depolarization of the soma to potentials more positive than -20 mV. This provides a mechanism likely to contribute to the electrical isolation of individual starburst cell dendrites, a property thought essential for direction selectivity. This function of Kv3 channels differs from that in other neurons where they facilitate high-frequency repetitive firing. Moreover, we found a gradient in the intensity of Kv3.1b immunolabeling favoring proximal regions of starburst cells. We hypothesize that this Kv3 channel gradient contributes to the preference for centrifugal signal flow in dendrites underlying direction-selective GABA release from starburst amacrine cells.

The fetal hypothalamus has the potential to generate cells with a gonadotropin releasing hormone (GnRH) phenotype.

BACKGROUND: Neurospheres (NS) are colonies of neural stem and precursor cells capable of differentiating into the central nervous system (CNS) cell lineages upon appropriate culture conditions: neurons, and glial cells. NS were originally derived from the embryonic and adult mouse striatum subventricular zone. More recently, experimental evidence substantiated the isolation of NS from almost any region of the CNS, including the hypothalamus. METHODOLOGY/FINDINGS: Here we report a protocol that enables to generate large quantities of NS from both fetal and adult rat hypothalami. We found that either FGF-2 or EGF were capable of inducing NS formation from fetal hypothalamic cultures, but that only FGF-2 is effective in the adult cultures. The hypothalamic-derived NS are capable of differentiating into neurons and glial cells and most notably, as demonstrated by immunocytochemical detection with a specific anti-GnRH antibody, the fetal cultures contain cells that exhibit a GnRH phenotype upon differentiation. CONCLUSIONS/SIGNIFICANCE: This in vitro model should be useful to study the molecular mechanisms involved in GnRH neuronal differentiation.

Acúmulo e distribuição de nutrientes em banana 'Mysore' em desenvolvimento

Foram determinados o acúmulo de matérias fresca e seca e dos nutrientes N, P, K, Ca, Mg, Zn, Fe e Mn em bananas 'Mysore', desde a antese floral da primeira penca feminina até o completo amadurecimento. O desenvolvimento dos frutos foi lento até o 42º dia após a antese, acelerando-se posteriormente. A fase de acúmulo máximo de minerais coincidiu com a de acúmulo máximo de matéria fresca, ou seja, 112 dias após a antese. A ordem de exportação de macronutrientes pelos frutos, em seu estádio de máximo acúmulo de matéria fresca, expressa em kg t-1 de fruto fresco, foi 3,61 para K; 0,98 para N; 0,27 para Mg; 0,19 para P e 0,12 para Ca. Quanto aos micronutrientes, a ordem de exportação, expressa em g t-1 de fruto fresco, foi 7,92 para Mn; 5,99 para Fe e 2,92 para Zn. Em frutos plenamente desenvolvidos, à exceção de Ca, Mn e Zn, todos os nutrientes acumularam-se mais na polpa do que na casca.

Suscetibilidade à queda natural e caracterização dos frutos de diversos genótipos de bananeiras

A queda natural de frutos maduros da bananeira, resultado da separação individual de frutos da coroa da penca, também chamada despencamento, é uma característica indesejável, que pode limitar o lançamento de uma nova cultivar. O fruto destacado da penca tem vida de prateleira reduzida, além de não demonstrar boa aparência aos olhos do consumidor. Os objetivos do presente trabalho foram quantificar a suscetibilidade à queda natural dos frutos de bananeiras de grupos genômicos e ploidias diferentes, e identificar correlações entre a queda natural e diversas características físicas dos frutos. Foram utilizados 37 genótipos de bananeiras. De acordo com análise de variância e teste de Scott-Knott, os resultados evidenciaram a alta resistência ao despencamento dos genótipos pertencentes ao grupo genômico BB (Butuhan, Piraí e BB França), Terra (AAB), Poteau Nain (tipo figo) (ABB) e Thap Maeo (AAB), enquanto Prata-Anã (AAB), Grande Naine (AAA), Ambrósia (AAAA), Ouro (AA) e FHIA 18 (AAAB) obtiveram valores intermediários de resistência ao despencamento. Com relação às bananeiras suscetíveis, destacam-se os híbridos melhorados Pioneira (AAAB), YB42-21 (AAAB), Buccaneer (AAAA) e Calypso (AAAA) e a cultivar Ouro da Mata (AAAB). Verificou-se associação de 74% entre a firmeza do fruto e a resistência ao despencamento. Os estudos de grupos genômicos e ploidias indicaram maior resistência ao despencamento das bananeiras pertencentes ao grupo BB e dos genótipos triplóides ABB e AAB.

Tipos e intensidade de danos mecânicos em bananas 'prata-anã' ao longo da cadeia de comercialização

Atualmente, a maior parte da produção brasileira de banana é destinada ao mercado interno e, geralmente, é colhida, manuseada e transportada de forma deficiente e inadequada, contribuindo para perdas substanciais na fase pós-colheita. Objetivou-se identificar os tipos e a intensidade de danos mecânicos após a colheita da banana 'Prata-Anã', produzida no Município de Verdelândia (MG) e embalada em caixas de papelão, madeira e plástico. Foram amostradas quatro caixas de banana 'Prata-Anã' em cada etapa da cadeia de comercialização, a saber: antes da colheita, após a primeira lavagem e pré-seleção (1ª piscina da casa de embalagem), após embalagem, após transporte e após distribuição ao mercado varejista em Montes Claros (MG), onde os frutos permaneceram em exposição para vendas por 8 horas. A porcentagem de frutos, área da casca e porcentagem da área da casca danificados aumentou ao longo da cadeia de comercialização. O uso da caixa de papelão proporcionou redução na incidência e intensidade de dano mecânico em relação aos demais tipos de embalagem. Houve alta incidência do dano por abrasão em todas as etapas da cadeia de comercialização. O dano por compressão apresentou grande importância relativa no varejo.

”Ilmarisen Suomi” ja sen tekijät. Matematiikkakonekomitea ja tietokoneen rakentaminen kansallisena kysymyksenä 1950-luvulla

Tutkimus ”Ilmarisen Suomi” ja sen tekijät tarjoaa uutta tietoa ja historiallisen tulkinnan huipputeknologisen Suomen rakentamisesta sodanjälkeisenä aikana. Kirja kertoo ESKO-tietokoneen tekijöiden monipuolisesta toiminnasta sekä koneen kohtalosta 1950-luvulla. ESKOa rakennuttanut Matematiikkakonekomitea (1954­1960) suunnitteli laitteesta Suomen ensimmäistä tietokonetta, mutta kirjassa esitetyn tulkinnan mukaan komitealla oli myös laajempia, kansallisia ihanteita ja tavoitteita, kuten kansallisen keskuslaskutoimiston perustaminen. Varhaisia tietokoneita kutsuttiin niiden käyttöä kuvaavasti matematiikkakoneiksi. Kirja on ensimmäinen perusteellinen esitys ja samalla ensimmäinen tutkimus ESKOsta ja sen tekijöiden hankkeesta 1950-luvulla. Matematiikkakonekomitean johdossa toimivat aikansa huipputiedemiehet Rolf Nevanlinna ja Erkki Laurila. Väitöstutkimuksessa kysytään, miten maan ensimmäisen tietokoneen hankkimista perusteltiin, mitä Matematiikkakonekomitea oikeastaan teki ja millaisia erityisesti kansallisia motiiveja koneen tekijöiden toiminta ilmaisi. Tutkimuksessa käytetään monipuolisesti arkistoaineistoa, kirjallisuutta ja haastatteluja Suomesta, Saksasta ja Ruotsista. Tarkastelussa hyödynnetään erityisesti teknologian historian ja yhteiskuntatieteellisen tieteen- ja teknologiantutkimuksen tutkimuskirjallisuutta. Kirjassa tarkastellaan yksityiskohtaisesti sitä, miten ESKOn tekijät yhdistivät tekniikan ja kansalliset perustelut sekä rakensivat uudenlaista, teknisesti taitavaa ”Ilmarisen Suomea” yhdessä ja kilvan muiden tahojen kanssa tuottaen teknologiasta kansallista projektia suomalaisille. Matematiikkakonekomitean ja ESKO-hankkeen tutkimisen perusteella suomalaisten ja teknologian suhteesta voidaan sanoa, että tekniikasta ei vain tullut kansallinen asia suomalaisille, vaan tekniikasta nimenomaan tehtiin kansallinen projekti, joka ei suinkaan ollut erityisen yksimielinen edes sodanjälkeisenä aikana. Tutkimuksen mukaan kotimainen komitea sai paljon aikaan ja tuotti vielä merkittävämpiä seurauksia. Näin siitä huolimatta, että ESKO valmistui pahasti myöhässä, vuonna 1960. Komitea myötävaikutti niin IBM:n menestykseen Suomessa, valtiojohtoisen tiedepolitiikan alkuun kuin Nokian edeltäjän Kaapelitehtaan elektroniikkaosaamisen syntyyn.

Tilastotiede

Kartunta on vähäistä. Se johtunee osin siitä, että pääosa valtiotieteellisen tiedekunnan tilastotieteen tutkijoista työskentelee Kumpulan kampuksella, jonne he muuttivat vuonna 2004, jolloin HY:n matemaatikan laitos, tilastotieteen laitos ja Rolf Nevanlinna instituutti yhdistyivät matematiikan ja tilastotieteen laitokseksi. Tuolloin (tiedekunnan kirjastosta erillisen) tilastotieteen laitoksen kirjaston kokoelmia karsittiin ja jaettiin sekä sovittiin linjauksesta, jonka mukaan valtiotieteellisen tiedekunnan kirjaston tilastotieteen kokoelmaan hankitaan lähinnä tiedekunnan metodiopetuksen kannalta keskeistä tilastotieteellistä kirjallisuutta. Kirjastossa kokoelmassa on runsaat 700 nidettä, joista 15.8.2008 mennessä on Helkaan luetteloituina 703. Kokoelma sisältää pääosin (n. 80%) oppikirjoja tai sellaisiksi hyvin sopivia teoksia. Kokoelma tukeekin enemmän perustutkintoa suorittavien opintoja kuin tieteellistä tutkimusta. Nimekkeiden joukossa on myös jonkun verran matematiikan kirjoja. Kirjojen keski-ikä on varsin vanha. Pääosin kokoelma sisältää 1960-1989 ilmestyneitä teoksia (71%)mediaanin ollessa 1975. 2000-luvulla julkaistua kirjallisuutta on sangen vähän (9%). Kirjoista englanninkielisiä on 82%. Suomeksi julkaistuja on 9%. Tilastotiedettä sovelletaan monilla eri tieteenaloilla. Soveltavaa tilastotiedettä löytyy kirjaston muista kokoelmista etenkin kansantalouden ja sosiologian kokoelmista.

Prospective motion correction with FID-triggered image navigators

In this work, we propose a method for prospective motion correction in MRI using a novel image navigator module, which is triggered by a free induction decay (FID) navigator. Only when motion occurs, the image navigator is run and new positional information is obtained through image registration. The image navigator was specifically designed to match the impact on the magnetization and the acoustic noise of the host sequence. This detection-correction scheme was implemented for an MP-RAGE sequence and 5 healthy volunteers were scanned at 3T while performing various head movements. The correction performance was demonstrated through automated brain segmentation and an image quality index whose results are sensitive to motion artifacts.