Role of γ1 Laminin and Its KDI Peptide in the Central Nervous System

Since the 1980 s, laminin-1 has been linked to regeneration of the central nervous system (CNS) and promotion of neuronal migration and axon guidance during CNS development. In this thesis, we clarify the role of γ1 laminin and its KDI tripeptide in development of human embryonic spinal cord, in regeneration of adult rat spinal cord injury (SCI), in kainic acid-induced neuronal death, and in the spinal cord tissue of amyotrophic lateral sclerosis (ALS). We demonstrated that γ1 laminin together with α1, β1, and β3 laminins localize at the floor plate region in human embryonic spinal cord. This localization of γ1 laminin is in spatial and temporal correlation with development of the spinal cord and indicates that γ1 laminin may participate in commissural axon guidance during the embryonic development of the human CNS. With in vitro studies using the Matrigel culture system, we demonstrated that the KDI tripeptide of γ1 laminin provides a chemotrophic guidance cue for neurites of the human embryonic dorsal spinal cord, verifying the functional ability of γ1 laminin to guide commissural axons. Results from our experimental SCI model demonstrate that the KDI tripeptide enhanced functional recovery and promoted neurite outgrowth across the mechanically injured area in the adult rat spinal cord. Furthermore, our findings indicate that the KDI tripeptide as a non-competitive inhibitor of the ionotropic glutamate receptors can provide when administered in adequate concentrations an effective method to protect neurons against glutamate-induced excitotoxic cell death. Human postmortem samples were used to study motor neuron disease, ALS (IV), and the study revealed that in human ALS spinal cord, γ1 laminin was selectively over-expressed by reactive astrocytes, and that this over-expression may correlate with disease severity. The multiple ways by which γ1 laminin and its KDI tripeptide provide neurotrophic protection and enhance neuronal viability suggest that the over-expression of γ1 laminin may be a glial attempt to provide protection for neurons against ALS pathology. The KDI tripeptide is effective therapeutically thus far in animal models only. However, because KDI containing γ1 laminin exists naturally in the human CNS, KDI therapies are unlikely to be toxic or allergenic. Results from our animal models are encouraging, with no toxic side-effects detected even at high concentrations, but the ultimate confirmation can be achieved only after clinical trials. More research is still needed until the KDI tripeptide is refined into a clinically applicable method to treat various neurological disorders.

Analysis of Atmospheric Particle Formation Events

Atmospheric aerosol particle formation events can be a significant source for tropospheric aerosols and thus influence the radiative properties and cloud cover of the atmosphere. This thesis investigates the analysis of aerosol size distribution data containing particle formation events, describes the methodology of the analysis and presents time series data measured inside the Boreal forest. This thesis presents a methodology to identify regional-scale particle formation, and to derive the basic characteristics such as growth and formation rates. The methodology can also be used to estimate concentration and source rates of the vapour causing particle growth. Particle formation was found to occur frequently in the boreal forest area over areas covering up to hundreds of kilometers. Particle formation rates of boreal events were found to be of the order of 0.01-5 cm^-3 s^-1, while the nucleation rates of 1 nm particles can be a few orders of magnitude higher. The growth rates of over 3 nm sized particles were of the order of a few nanometers per hour. The vapor concentration needed to sustain such growth is of the order of 10^7--10^8 cm^-3, approximately one order of magnitude higher than sulphuric acid concentrations found in the atmosphere. Therefore, one has to assume that other vapours, such as organics, have a key role in growing newborn particles to sizes where they can become climatically active. Formation event occurrence shows a clear annual variation with peaks in summer and autumns. This variation is similar to the variation exhibited the obtained formation rates of particles. The growth rate, on the other hand, reaches its highest values during summer. This difference in the annual behavior, and the fact that no coupling between the growth and formation process could be identified, suggest that these processes might be different ones, and that both are needed for a particle formation burst to be observed.

Studies on structural and electrical properties of sprayed SnO2 : Sb films

Thin films of antimony-doped tin oxide (SnO2:Sb) were prepared by spray pyrolysis using stannous chloride (SnCl2) and antimony trichloride (SbCl3) as precursors. The antimony doping was varied from 0 to 4 wt%. Scanning electron microscopy (SEM) revealed the surface morphology to be very smooth, yet grainy in nature. X-ray diffraction (XRD) shows films to have preferred orientation, which varies with the extent of antimony doping: undoped films prefer the (2 1 1) orientation, while the (3 0 1) orientation is preferred for doping levels of 0.5 and 1.0 wt%. For higher doping levels, the (2 0 0) orientation is preferred. This difference in preferred orientations is reflected in the SEM of the films. Atomic force microscopy (AFM) reveals that film roughness is not affected by antimony doping. The minimum sheet resistance (2.17 ohm/square) achieved in the present study is lower than values reported to date in SnO2:Sb films prepared from SnCl2 precursor. The Hall mobility of undoped SnO2 films was found to be 109.52 cm(2)/V s, which reduces to 2.55 cm(2)/ Vs for the films doped with 4 wt% of Sb. On the other hand, the carrier concentration, which is 1.23 x 10(19) cm(-3) in undoped films, increases to 2.89 x 10(21) cm(-3) for the films doped with 4 wt% of Sb. (c) 2004 Elsevier B.V. All rights reserved.

Thermodynamics of monosaccharide binding to concanavalin A, pea (Pisum sativum) lectin, and lentil (Lens culinaris) lectin

Titration calorimetry measurements of the binding of methyl alpha-D-mannopyranoside (Me alpha Man), D-mannopyranoside (Man), methyl alpha-D-glucopyranoside (Me alpha Glu), and D-glucopyranoside (Glu) to concanavalin A (Con A), pea lectin, and lentil lectin were performed at 281 and 292 K in 0.01 M dimethylglutaric acid-NaOH buffer (pH 6.9) containing 0.15 M NaCl and Mn+2 and Ca+2 ions. The site binding enthalpies, delta H, are the same at both temperatures and range from -28.4 +/- 0.9 (Me alpha Man) to -16.6 +/- 0.5 kJ mol-1 (Glu) for Con A, from -26.2 +/- 1.1 (Me alpha Man) to -12.8 +/- 0.4 kJ mol-1 (Me alpha Glu) for pea lectin, and from -16.6 +/- 0.7 (Me alpha Man) to -8.0 +/- 0.2 kJ mol-1 (Me alpha Glu) for lentil lectin. The site binding constants range from 17 +/- 1 x 10(3) M-1 (Me alpha Man to Con A at 281.2 K) to 230 +/- 20 M-1 (Glu to lentil lectin at 292.6 K) and exhibit high specificity for Con A where they are in the Me alpha Man:Man:Me alpha Glu:Glu ratio of 21:4:5:1, while the corresponding ratio is 5:2:1.5:1 for pea lectin and 4:2:2:1 for lentil lectin. The higher specificity for Con A indicates more interactions between the amino acid residues at the binding site and the carbohydrate ligand than for the pea and lentil lectin-carbohydrate complexes. The carbohydrate-lectin binding results exhibit enthalpy-entropy compensation in that delta Hb (kJ mol-1) = -1.67 +/- 0.06 x 10(4) + (1.30 +/- 0.12)T(K) delta Sb (J mol-1K-1). Differential scanning calorimetry measurements on the thermal denaturation of the lectins and their carbohydrate complexes show that the Con A tetramer dissociates into monomers, while the pea and lentil lectin dimers dissociate into two submonomer fragments. At the denaturation temperature, one carbohydrate binds to each monomer of Con A and the pea and lentil lectins. Complexation with the carbohydrate increases the denaturation temperature of the lectin and the magnitude of the increases yield binding constants in agreement with the determinations from titration calorimetry.

Charge distribution, dipole moments and infrared spectra of some thiol and thio acids

The dipole moments of thioglycollic (2.28 D), β-mereaptopropionic (2.25 D), thiomalic (2.47 D), malic (3.12 D), and dithiodiacetic (3.17 D) acids have been measured in dioxan at 35° C. Using the scheme of Smith, Ree, Magee and Eyring, the formal charge distribution in and hence the electric moments of these acids have been evaluated, compared with the theoretical moments, and discussed in terms of their various possible structures. Infrared spectra of these acids (liquid and nujol mull) indicate association through hydrogen bonding. These bonds are broken in solution. © 1969.

Charge distribution, dipole moments and infrared spectra of some thiol and thio acids

The dipole moments of thioglycollic (2.28 D), β-mereaptopropionic (2.25 D), thiomalic (2.47 D), malic (3.12 D), and dithiodiacetic (3.17 D) acids have been measured in dioxan at 35° C. Using the scheme of Smith, Ree, Magee and Eyring, the formal charge distribution in and hence the electric moments of these acids have been evaluated, compared with the theoretical moments, and discussed in terms of their various possible structures. Infrared spectra of these acids (liquid and nujol mull) indicate association through hydrogen bonding. These bonds are broken in solution.

The conversion of 3-hydroxyanthranilic acid to cinnabarinic acid by the nuclear fraction of rat liver

Although several authors have implicated 3-hydroxyanthranilic acid (3-OHA) as an intermediate in tryptophaniacin pathway in animals (Kaplan, 1961), alternative pathways of metabolism of this compound have not been fully explored. Madhusudanan Nair obtained an enzyme from spinach leaves which could convert 3-OHA to cinnabarinic acid (private communication). Viollier and Süllmann (1950) reported the conversion of 3-OHA to an unidentified red compound by rat liver homogenates. The present investigation describes the identification of this product as cinnabarinic acid (2-amino-3-H-isophenoxazine-3-one-1,9-dicarboxylic acid). Cinnabarinic acid is known to occur in nature along with cinnabarin is olated from the fungus Polystictus sanguineus (Gripenberg et al., 1957; Gripenberg, 1958).

Italian ja Veneton läänin kolmas sektori. Maaraportti maaseutualueiden palvelutuotannon haasteista ja hyvistä käytännöistä.

Tiivistelmä Maaraportin tavoitteena on luoda yleiskatsaus Italian kolmanteen sektoriin ja tutkimus kohdistuu erityisesti Pohjois-Italiassa sijaitsevan Veneton läänin kolmannen sektorin palvelutuotantoon. Raportissa tarkastellaan erityisesti kolmannen sektorin ja julkisen palvelutuotantosektorin sekä julkishallinnon toiminnallisia suhteita. Kolmannen sektorin mahdollisuuksia vastata maaseutualueiden palvelujen tarjonnan haasteisiin on pyritty analysoimaan. Italia on julkishallinnon ja kolmannen sektorin palvelutuotannon kannalta tarkasteltuna nykytilanteessa mielenkiintoinen testilaboratorio koko Euroopan mittakaavassa johtuen maan historiallisista, kulttuuri-sista, kieli- ja maantieteellisistä sekä itse väestöpohjan tarjoamista haasteista. Italiasta ei voida puhua yhden homogeenisen valtiokäsitteen alla, koska maa toimii kulttuurisista perinteistään johtuen kolmella eri nopeudella. Itse valtio käsitettäkin tulkitaan Italiassa monin eri tavoin pohjautuen ”valtiona” nähdyn organisaation käytännön funktioon sitoutuneena alueellisiin ja kulttuurisiin tekijöihin. Teollinen, dynaaminen yritysten varakas Pohjois-Italia henkilöityneenä Milanoon, hallinnon ja kulttuurin leimaama Keski-Italia kiteytyneenä ikuiseen kaupunkiin Roomaan ja Napolin alapuolinen Etelä-Italia, joka painii ”järjestelmässä sisällä olevan järjestelmänsä” kanssa eivät ole koskaan muodos-taneet oikeasti yhtenäistä Italian valtiota. Italiassa erillisinä itsehallinnollisina alueina toimivat lääneiksi luettavat Sisilia, Trentino Alto-Adige, Val di Aosta, Sardegna ja Friuli-Venezia Giulia, mikä lisää hallinnollista kirjavuutta. Viimeisten vuosien aikana Italian julkishallinto on ollut jatkuvassa transitiotilassa yrittäessään kohdata uudistumisen vaateita globalisoituvassa maailmassa. Italiassa on meneillään hidas siirtyminen liittovaltiomaiseen järjestelmään ja jopa syvempään paikallisuuteen. Massiivinen ja raskas julkishallintokoneisto neljällä eri tasolla (valtio - lääninhallinnolliset alueet - vahvat maakunnat - kunnat) on erittäin hankalasti modernisoitavissa, mutta poliittinen tahtotila on vaihtumassa klassista vahvaa keskushallintoa kannattavasta ajattelutavasta hyväksymään federalistisia, alueellisia hallintoratkaisuja. Italiassa on herätty havaitsemaan, että ongelmien ratkaisu täytyy viedä itse alueille ja niiden ihmisille, koska unilateraalinen keskushallinnointitapa ei enää vastaa monikerroksisiin, moniulotteisiin alueellisiin haasteisiin. Jokaisella alueella on erilaiset lähtökohdat ongelmien ratkaisuihin myös globalisoitumisen asettamissa yhteisissä haasteissa. Kolmannen sektorin asema arvostettuna italialaisten kansalaispalvelujen täydentäjänä ja tuottajana alkaa olla nykypäivää. Kolmannen sektorin elintärkeä osuus uusien palvelutarpeiden tunnistamisessa on jo yleisesti tunnustettu tosiasia Italiassa. Vapaaehtoisjärjestöt toimivat eturivissä kansalaisten arkipäivässä ja pystyvät näin kanavoimaan ensimmäisinä sosiaalista kehityskulkua ja kohottamaan esiin erilaisia marginaalistenkin ryhmien tarpeita sekä vastaamaan niihin. Kolmas sektori laajentaa, tuottaa ja paikkaa paikallista julkista palvelutuotantoa. Ratkaiseva askel lainsäädännölliseltä kannalta on ollut rahoitusvirtojen ohjaaminen kolmannen sektorin ns. ONLUS-organisaatioille ja ONLUS-statuksen perustaminen vuonna 1997. Italiassa on 60 231.214 asukasta (31.7.2009) ja se on hallinnollisesti jakaantuneena 8 100 kuntaan. Suomessa vastaavat luvut ovat 5 350 712 asukasta ja 348 kuntaa (11/2009). Maantieteelliseltä kooltaan Italia ei eroa 301 338 km2:n pinta-alallaan paljonkaan Suomesta (338 424 km2). Väestömäärän erojen vuoksi Italiassa on keskimäärin 199,9 asukasta neliökilometrillä ja Suomessa 17,1. Maiden välinen suora vertailu ei ollut mittakaavaerojen vuoksi järkevää. Kuntien hallinnollinen rooli on Italiassa painotukseltaan erilainen kuin Suomessa. Suomessa kuntien vastuulla oleva sosiaali-, terveydenhuolto- ja koulutoimi eivät ole samassa laajuudessa italialaisten kuntien vastuulla vaan näiden toimialojen vastuulliset tahot ovat läänit terveydenhoitopiireineen sekä maakuntahallinto koulupiirien osalta. Italialaisten kuntien vastuualueet voivat myös vaihdella mittavasti perustuslaissa määriteltyjen perustoimien lisäksi. Tutkimuksen kohteeksi on rajattu Koillis-Italiassa sijaitseva Veneton läänin alue, koska se on väkimäärältään lähes yhtä suuri kuin Suomi, 4 893 309 asukasta (31.3.2009). Kuntien lukumäärä on huimaava 581 kpl. Veneto on maantieteelliseltä alueeltaan pieni ja harvaan asuttua maaseutua on pinta-alasta melko niukasti. Pohjoisen osan vuoristoalueet karuine olosuhteineen muodostavat palvelutuotannollisesti haas-teellisen ympäristön, joka on verrattavissa suomalaisten maaseutualueiden tilanteeseen. Venetossa on omaksuttu Italian mittakaavassa innovatiivisia ratkaisuja julkishallinnon palvelutuotannon ja kolmannen sektorin toiminnan osalta. Veneton alue on luokiteltu maailman pienyritysintensiivisimmäksi alueeksi, mikä heijastuu myös alueen palvelutuotantoratkaisuissa. Raportti esittelee ensin Italian hallintoa, keskushallinnon, paikallishallinnon ja tutkimuksen asettelulle olennaisten kolmannen sektorin toimijoiden osalta. Tämä on välttämätöntä, sillä kolmannen sektorin toiminta on Italiassa hyvin pitkälle lainsäädännöllä ohjattua ja rajattua. Kolmannen sektorin käsitteistöä, toimijoita, järjestäytymistä ja sen toimintaa säätelevää lainsäädäntöä esitellään tarkemmin. Veneton läänin osalta kolmanteen sektoriin perehdytään sekä hallinnon että toimijakentän näkökulmia tulkiten. Raportin lopussa esitellään kolmannen sektorin palvelutuotantoon ja hallinnointiin liittyviä case-esimerkkitapauksia.

Heterocyclic Steroids .7. Rearrangement Of 1-Diethylamino-5-(Met-Methoxyphenoxy)-Pent-2-Yne

Thermal rearrangement of diethylamino5-(m methoxyphenoxy)-pent-2-yne (3) gives 1-(m-methexyphenoxy)-pent-3,4-diene (14) in about 8% yield. Hydration of the latter yields 1-(m-methoxyphenoxy)-pentan-4-one (6), which has been synthesised by an unambiguous route. A mechanism of formation of the allene (14) from the amine (3) has been suggested.

Purification and characterization of endo-1,4-β-xylanase from Paecilomyces varioti Bainier

An endo-xylanase (1,4-β-d-xylanxylanohydrolase EC 3.2.1.8) was isolated from the culture filtrate of Paecilomyces varioti Bainier. The enzyme was purified 3.2 fold with a 60% yield by gel filtration and ion exchange chromatography. The purified enzyme had a molecular weight of 25,000 with a sedimentation coefficient of 2.2 S. The isoelectric point of the enzyme was 3.9. The enzyme was obtained in crystalline form. The optimum pH range was 5.5–7.0 and the temperature, 65°C. The Michaelis constant was 2.5 mg larchwood xylan/ml. The enzyme was found to degrade xylan by an endo mechanism producing arabinose, xylobiose, xylo- and arabinosylxylo-oligosaccharides, during the initial stages of hydrolysis. On prolonged incubation, xylotriose, arabinosylxylotriose and xylobiose were the major products with traces of xylotetraose, xylose and arabinose.

cis-trans Enantiomerism in the Diels-Alder cycloadducts of 6-arylfulvenes with maleic anhydride: resolution of the exo adducts via the N-((1S)-1-(naphth-1-yl)ethyl)imide derivatives: assignment of the absolute configurations based on the crystal structure of an imide diastereomer

A new case of the uncommon cis-trans enantiomerism is presented. The titled anhydride adducts were prepared in good yields by the known reaction of three 6-arylfulvenes with maleic anhydride (aryl = phenyl, p-tolyl and p-anisyl). The exo adducts were converted to the corresponding imides by reaction with (1S)-1-(naphth-1-yl)ethylamine in similar to 80% yields, and the resulting diastereomeric imides separated by silica gel column chromatography. They were hydrolysed and recyclised to the chiral anhydrides, in `one-pot' with 10% NaOH-EtOH, followed by treatment with 2 M HCl, in similar to 40% yields. The titled anhydrides were thus obtained in homochiral form, in enantiomeric purities (generally) of similar to 90% as indicated by chiral HPLC. The chiral anhydrides were also converted to the corresponding imides (presumably stereospecifically), by treatment with ammonia solution in excellent yields. The crystal structure of one of the above diastereomeric imides (derived from 6-phenylfulvene) was determined, and based on the known (S)-configuration of the naphthylethylamine moiety, the `configurations' of the original anhydride adducts were assigned. (c) 2005 Elsevier Ltd. All rights reserved.

Silva Fennica Vol. 16, 1982.

Julkaistu Silva Fennica Vol. 17(1) -numeron liitteenä.

X-ray studies on crystalline complexes involving amino acids and peptides. XXI. Structure of a (1:1) complex between L-phenylalanine and D-valine

CsHllNO2.C9HilNO2, Mr = 282.3, P1, a = 5.245 (1), b = 5.424 (1), c = 14.414 (2) A, a = 97.86 (1), fl = 93-69 (2), y = 70-48 (2) °, V= 356 A 3, Z = 1, O m = 1-32 (2), Dx = 1.32 g cm-3, h(Mo Ka) = 0-7107 A, g = 5-9 cm-1, F(000) = 158, T= 298 K, R=0.035 for 1518 observed reflections with I>2tr(I). The molecules aggregate in double layers, one ayer made up of L-phenylalanine molecules and the other of D-valine molecules. Each double layer is stabilized by interactions involving main-chain atoms of both types of molecules. The interactions include hydrogen bonds which give rise to two head-to-tail sequences. The arrangement of molecules in the complex is almost the same as that in the structure of DL-valine (and DL-leucine and DL-isoleucine) except for the change in the side chain of L molecules. The molecules in crystals containing an equal number of L and O hydrophobic amino-acid molecules thus appear to aggregate in a similar fashion, irrespective of the precise details of the side chain.

Stereochemical properties and x-ray structure of a water-soluble diastereomeric (arene)ruthenium(II) Schiff-base complex: [Ru(.eta.-MeC6H4Pri-p)(H2O)(L*)](ClO4), containing a weakly bound aqua ligand [HL* = (S)-(.alpha.-methylbenzyl)salicylaldimine]

An air-stable and water-soluble diastereomeric half-sandwich ruthenium(I1) complex, [Ru(s-MeCsH4Pr'-p)(H*O)-(L*)] (C104) (l), has been isolated and structurally characterized [HL* = (27)-(a methylbenzyl)salicylaldimine,2-HOC6H4CH-NCHMePhI. Complex 1, Czd-I3oNO&lRu, crystallizes in the noncentric triclinic space group P1 with a = 9.885(1) A, b = 10.185(1) A, c = 14.187(2) A, a = 110.32(1)', 6 = 102.17(1)', y = 102.41(1)O, V=1243( 1) A3, and 2 = 2. The X-ray structure shows the presence of two diastereomers in a 1:l ratio having RR,,,SCand SR,,,&c onfigurations. The Ru-OHz bond distances are considerably long, and the values for RR, - a~n d SRu-1isomers are 2.1 19(5) and 2.203(5) A, respectively. The aqua complex (1) exists as a single diastereomer in solution,and it forms stable adducts with P-, N-, and halide-donor ligands. The stereochemical changes associated with adduct-forming reactions follow an inversion order: PPhs >> P(OMe)3 > pyridine bases >> halides (I, Br, Cl) >H20.

Dynamics of I-asterisk(P-2(1/2)) production inthe ultraviolet photodissociation of alkyn iodides

The relative quantum yields, phi*, for the production of I*(P-2(1/2)) at 266, 280, and similar to 305 nm are reported for a series of primary alkyl iodides using the technique of two-photon laser-induced fluorescence for the detection of I(P-2(3/2)) and I*(P-2(1/2)) atoms. Results are analyzed by invoking the impulsive energy disposal model, which summarizes the dynamics of dissociation as a single parameter. Comparison of our data with those calculated by a more sophisticated time-dependent quantum mechanical model is also made. Near the red edge of the alkyl iodide A band, absorption contribution from the (3)Q(1) state is important and the dynamics near the (3)Q(0)-(1)Q(1) curve-crossing region seem to be influenced by the kinematics of the dissociation process