Neurocognitive changes in early-stage Parkinson's disease : functional and structural brain correlates of memory and verbal functions

Resultaten påvisade små, men mätbara försämringar i minnes- och verbal förmåga hos personer som haft Parkinsons sjukdom under tre år. Jämfört med en kontrollgrupp uppvisade Parkinsonpatienter avvikande responser i hjärnans elektriska aktivitet under en korttidsminnesuppgift, och de presterade även sämre i olika typer av andra minnesuppgifter. Försämring i en specifik typ av minnesuppgift korrelerade med förminskad volym i höger hjärnhalva. Samband hittades också mellan sämre verbal förmåga och förminskad volym i djupa hjärnstrukturer. Förminskad hjärnvolym har tidigare påvisats hos dementa patienter i senare sjukdomsstadier. Forskningsresultaten bidrar med ny kunskap om kognitiva symptom och deras neurala bakgrund vid Parkinsons sjukdom. De tyder också på att tidig kognitiv funktionsnedsättning kan identifieras, vilket kan bidra till utvecklingen av sjukdomens behandling. Parkinsons sjukdom är den näst vanligaste neurogeriatriska sjukdomen efter Alzheimers sjukdom. Symptomen uppstår som följd av förminskad produktion av hjärnans transmittorämne dopamin. Parkinsons sjukdom har traditionellt betraktats som en progressiv motorisk sjukdom. Ny forskning tyder på att multipla hjärnsystem skadas, vilket resulterar i att även tankeprocesser påverkas. 75-80% uppskattas insjukna i demens 10-15 år efter diagnos, men det kognitiva sjukdomsförloppet och orsaken till demenssymptomen är tillsvidare okänd. I Finland uppskattas ca 10-12 000 personer ha Parkinsons sjukdom, varav ca 3 000 uppskattas ha demens. ----------------------------------------------------------------------------------------------------------------------------------------------------- Tutkimuksessa todettiin lieviä muutoksia muisti- ja kielellisissä toiminnoissa alle kolme vuotta sairastaneilla Parkinson-potilailla. Potilailla havaittiin poikkeavia aivosähkötoiminnan vasteita lyhytkestoista muistia mittaavan tehtävän aikana. Potilaat suoriutuivat myös verrokkiryhmää heikommin useissa muistitehtävissä. Heikentynyt tahaton muisti liittyi pienempään aivokuoren harmaan aineen paikalliseen tilavuuteen. Heikompi kielellinen suoriutuminen liittyi pienempään harmaan aineen tilavuuteen aivojen syvissä rakenteissa. Pienentyneitä aivorakenteiden tilavuuksia on aiemmin todettu dementoituneilla Parkinson-potilailla sairauden myöhemmissä vaiheissa. Tutkimustulokset tuovat uutta tietoa Parkinsonin taudin kognitiivisista oireista ja niiden aivoperäisestä taustasta. Tulosten perusteella on mahdollista tunnistaa jo varhaisia kognitiivisia muutoksia, mikä voi mahdollistaa tehokkaamman hoidon kohdentamisen. Parkinsonin tauti on Alzheimerin taudin jälkeen toiseksi yleisin neurogeriatrinen sairaus. Oirekuva liittyy aivojen dopaminergisen järjestelmän rappeutumiseen. Perinteisesti liikehäiriösairaudeksi luokiteltu sairaus vaurioittaa lukuisia muita aivojärjestelmiä aiheuttaen muutoksia myös mm. ajattelutoiminnoissa. Pitkään sairastaneista 75–80 prosentilla esiintyy dementiaoireita, mutta oireiden syy ja kehityskaari tunnetaan toistaiseksi huonosti. Suomessa on arviolta 10–12 000 Parkinson-potilasta, joista noin 3 000 arvioidaan kärsivän dementiaoireista.

Die Beendigung von finnischen und deutschen Telefonaten. Eine interaktionslinguistische, kontrastierende Untersuchung

Suomalaisten ja saksalaisten arkikeskustelujen välillä on sekä yhtäläisyyksiä että eroja. Tässä saksalaisen filologian alaan kuuluvassa tutkimuksessa tarkastellaan yhtä keskeistä arkikeskustelun toimintoa, puhelinkeskustelun lopetusta, suomen- ja saksanpuhujien tuottamana. Aineistona on käytetty suomen- ja saksankielisten äidinkielisten puhujien tätä tutkimusta varten nauhoittamia henkilökohtaisia luonnollisia puhelinkeskusteluja. Aineistoon valikoitui 12 suomalaista ja 12 saksalaista puhelua. Nauhoitteiden käyttöön on saatu asianmukainen lupa kaikilta osapuolilta. Puhelut on litteroitu saksalaisella kielialueella vakiintuneen GAT-litterointisysteemin mukaan. Teoreettis-metodisena kehyksenä on kaksi tutkimusalaa, vuorovaikutuslingvistiikka ja kielten vertailu. Vuorovaikutuslingvistinen tarkastelu keskittyy havaintoihin vuorojen ja puheen sekvenssien rakenteesta. Vuorojen merkitysten tulkinnassa hyödynnetään systemaattisesti prosodian antamia vihjeitä. Tuloksena on yksittäisten lopetusten keskustelunanalyyttinen lähikuvaus, jonka pohjalta määritellään kulloisenkin lopetuksen sekvenssirakenne. Kaikki lopetukset olivat siltä osin yhteneväisiä, että niissä kaikissa havaittiin ainakin aloittava, tulevaan tapaamiseen viittaava sekä lopputervehdyksiin johtava sekvenssi. Sekvenssirakenteen variaatioiden pohjalta aineiston lopetukset voidaan kuitenkin jaotella ryhmiin. Sekä suomen- että saksankielisessä aineistossa havaittiin kolmentyyppisiä lopetuksia: kompakteja, komplekseja ja keskeytettyjä lopetuksia. Ryhmittely kolmeen tyyppiin on avuksi seuraavassa kuvausvaiheessa, jossa verrataan suomen- ja saksankielisiä lopetuksia toisiinsa. Samanaikaisesti kun tutkimus valottaa kohtia, joissa kaksi aineistosettiä yhtenevät ja eroavat, se myös esittää, mitkä vuorovaikutuksen tasot soveltuvat kieltenvälisen vertailun kohteiksi. Pohdintaa siitä, mitä vuorovaikutuksen tasoja kieltenväliseen vertailuun voidaan sisällyttää, onkin toistaiseksi esitetty verrattain vähän. Työ siis rakentaa siltaa vuorovaikutuslingvistisen ja kontrastiivisen kielitieteen välille.

Structural studies and in vivo characterisation of Oct4:PORE and Oct4/Sox2:UTF1 complexes

Monikykyiset kantasolut pystyvät erilaistumaan alkion kehityksen aikana miksi tahansa kehittyvän eläimen kudokseksi. Alkion kehitystä on tutkittu vuosikymmeniä ja ensimmäisen kerran kantasoluja viljeltiin 1980-luvulla. Noin vuosikymmen myöhemmin kloonattiin ensimmäinen nisäkäs, Dolly-lammas, mikä oli läpimurto perimän kloonauksessa. Vajaa kymmenen vuotta sitten japanilaiset tutkijat pystyivät ensimmäisen kerran tuottamaan indusoituja monikykyisiä kantasoluja. Nämä kantasolut tuotettiin ilmentämällä neljää geeniä, jotka uudelleenohjelmoivat erilaistuneet solut takaisin kantasoluiksi. Geenien ilmentymistä säätelevä ja DNA:han sitoutuvan proteiinin Oct4:n on todettu olevan tärkeä tekijä uudelleenohjelmissa. Oct4 kuuluu transkriptiotekijäperheeseen, joka säätelee geenien ilmentymistä kantasoluissa. Tässä työssä kiteytin Oct4-proteiinin sen kohde-DNA:n kanssa sekä tutkin sen sitoutumista ja atomitason rakennetta röntgensädekristallografian avulla. Tutkimuksessamme paljastui useita Oct4:n atomitason rakenteellisia ominaisuuksia, jotka selittävät sen säätelymekanismeja kantasoluissa.

Floristic and structural variation of weeds in eucalyptus plantations as influenced by relief and time of year

The objective of this work was to analyze the floristic variation and phytosociological structure of weeds as influenced by relief and time of year in eucalyptus plantations in Santana do Paraíso and Guanhães - MG. The total area sampled for each locality was approximately 10 ± 3 hectares, comprising three types of relief: lowland, slope, and upper area. In each type of relief, 10 plots of 1 m² were sampled, corresponding to 30 plots per locality, where they were randomly allocated in a zigzag. The taxonomic identification was performed in four assessments, corresponding to the months of November and March, comprising two ratings each season, always at the same points, and geo-referenced using the Global Positioning System (GPS). A total of 3,893 individuals, 18 families and 61 species, were identified in Santana do Paraiso and a total of 1,166 individuals, 13 families and 58 species, in Guanhães. In both localities, the most representative families in terms of wealth were: Poaceae, Asteraceae, and Fabaceae. Galinsoga parviflora was the most abundant species. The Vernonia polyantes was identified only in the lowlands, while Arrabida florida was identified in the slope and upper area. On the other hand, Emilia coccinea, Sida rhombifolia, S. paniculatum and Spermacoce latifolia were common to all three environments. Commelina benghalensis was present only in the month of March, while G. parviflora was present only in the month of November. It was concluded that the floristic and phytosociological variation of weeds in eucalyptus plantations is influenced by the type of relief and time of year, which should guide the management practices used in the culture.

Similarity among periphyton algal communities in a lentic-lotic gradient of the upper Paraná river floodplain, Brazil

Floristic comparison of periphyton communities from three systems with different hydrodynamic regimes (lentic, semilotic, and lotic) was carried out during high and low water periods on the Upper Paraná River floodplain. For each period and system, glass slides were sampled every two days during 18-day periods, and Eichhornia azurea Kunth petioles were sampled three times. A total of 228 species was collected, representing 12 classes, mainly diatoms and desmids. The highest species-richness was found in communities from lentic system and during high water. Species richness in the lotic system was more stable over succession and hydrological periods. Algal taxonomic structure in river community was clearly separated from the other two systems, with 43% of similarity level. The hydrological period was next in importance, followed last by the substratum type, with communities associated at 65-78% similarity levels, depending on system and hydrological period. The type of system, but not the water levels,was the main factor that influenced community richness, followed by disturbances caused by flood pulses and the operation of reservoirs upstream. The periphyton on artificial and natural substrata presented high degree of similarity.

Horizontal and vertical tree community structure in a lowland atlantic rain forest, southeastern Brazil

The horizontal and vertical tree community structure in a lowland Atlantic Rain Forest was investigated through a phytosociological survey in two 0.99 ha plots in the Intervales State Park, São Paulo State. All trees > 5 cm diameter at breast height were recorded. 3,078 individuals belonging to 172 species were identified and recorded. The Shannon diversity index was H' = 3.85 nat.ind.-1. The Myrtaceae family showed the greatest floristic richness (38 species) and the highest density (745 individuals) in the stand. Euterpe edulis Mart. had the highest importance value (33.98%) accounting for 21.8% of all individuals recorded. The quantitative similarity index was higher than the qualitative index, showing little structural variation between plots. However, the large number of uncommon species resulted in pronounced floristic differences. A detrended correspondence analysis (DCA) generated three arbitrary vertical strata. Stratum A (> 26 m), where Sloanea guianensis (Aubl.) Benth. and Virola bicuhyba (Schott. ex A.DC.) Warb. were predominant showed the lowest density. Stratum B (8 m < h < 26 m) had the greatest richness and diversity, and stratum C (< 8 m) showed the highest density. Euterpe edulis, Guapira opposita (Vell.) Reitz, Garcinia gardneriana (Planch. & Triana) Zappi, and Eugenia mosenii (Kausel) Sobral were abundant in strata B and C. The occurrence of strata in tropical forests is discussed and we recommend the use of DCA for others studies of the vertical distribution of tropical forest tree communities.

Floristic and vegetation structure of a granitic grassland in Southern Brazil

A floristic and structural survey of a natural grassland community was conducted on Morro do Osso, a granitic hill in Porto Alegre, RS, Brazil. Structural data were surveyed in 39 one square meter plots placed over two major grassland areas. An accidental fire has occurred in one of the areas approximately one year prior to our survey, leading to further analysis of parameters differences between sites. The floristic list contains 282 species, whereas the structural survey has found 161 species. Families with highest accumulated importance values were Poaceae, Asteraceae and Fabaceae. The diversity and evenness indexes were 4.51 nats ind-1 and 0.86, respectively. Cluster analysis denoted two groups coinciding with the areas distinguished by the fire disturbance. A similarity analysis between our data and two other data sets from nearby granitic hills resulted in 28% to 35% similarity, with equivalent species-family distribution and many common dominant species, corroborating the concept of a continuous flora along the South Brazilian granitic hills.

Floristic composition and similarity analysis of an Atlantic rain forest fragment in Cananéia, São Paulo State, Brazil

The aim of this study is to investigate the floristic composition of an Atlantic rain forest fragment located in Cananéia, São Paulo, Brazil, and to contribute to the knowledge on Atlantic forest through the comparative analysis of this and other floristic surveys both on the southern and southeastern Brazil, in different soil and relief types. We surveyed 215 species in 132 genera and 51 families. Classification and ordination analysis were applied to a binary matrix in order to analyze the similarity among 24 surveys, including the present one, of Atlantic forest from the south and southeast coast of Brazil. Higher floristic similarity was observed among this area and the ones where there was marine influence and more rugged relief. The surveys in areas with greater marine influence (sandy soil) were separated from those in other conditions, possibly indicating a species replacement gradient from the steep slopes towards the lowland and were probably related to different edaphic conditions. A latitudinal gradient was found among the surveys apparently confirming a continuous species replacement along the Atlantic forest, related to a restricted distribution of the species. This suggests that it is essential to preserve areas from the whole Atlantic coast. Atlantic forest distribution is quite complex and its composition cannot be adequately represented by small localized areas.

Structural basis for the pathophysiology of lipoprotein(a) in the athero-thrombotic process

Lipoprotein Lp(a) is a major and independent genetic risk factor for atherosclerosis and cardiovascular disease. The essential difference between Lp(a) and low density lipoproteins (LDL) is apolipoprotein apo(a), a glycoprotein structurally similar to plasminogen, the precursor of plasmin, the fibrinolytic enzyme. This structural homology endows Lp(a) with the capacity to bind to fibrin and to membrane proteins of endothelial cells and monocytes, and thereby to inhibit plasminogen binding and plasmin generation. The inhibition of plasmin generation and the accumulation of Lp(a) on the surface of fibrin and cell membranes favor fibrin and cholesterol deposition at sites of vascular injury. Moreover, insufficient activation of TGF-ß due to low plasmin activity may result in migration and proliferation of smooth muscle cells into the vascular intima. These mechanisms may constitute the basis of the athero-thrombogenic mode of action of Lp(a). It is currently accepted that this effect of Lp(a) is linked to its concentration in plasma. An inverse relationship between Lp(a) concentration and apo(a) isoform size, which is under genetic control, has been documented. Recently, it has been shown that inhibition of plasminogen binding to fibrin by apo(a) is also inversely associated with isoform size. Specific point mutations may also affect the lysine-binding function of apo(a). These results support the existence of functional heterogeneity in apolipoprotein(a) isoforms and suggest that the predictive value of Lp(a) as a risk factor for vascular occlusive disease would depend on the relative concentration of the isoform with the highest affinity for fibrin

Antigenic characterization of Brazilian bovine viral diarrhea virus isolates by monoclonal antibodies and cross-neutralization

Nineteen Brazilian isolates of bovine viral diarrhea virus (BVDV) were characterized antigenically with a panel of 19 monoclonal antibodies (mAbs) (Corapi WV, Donis RO and Dubovi EJ (1990) American Journal of Veterinary Research, 55: 1388-1394). Eight isolates were further characterized by cross-neutralization using sheep monospecific antisera. Analysis of mAb binding to viral antigens by indirect immunofluorescence revealed distinct patterns of reactivity among the native viruses. Local isolates differed from the prototype Singer strain in recognition by up to 14 mAbs. Only two mAbs - one to the non-structural protein NS23/p125 and another to the envelope glycoprotein E0/gp48 - recognized 100% of the isolates. No isolate was recognized by more than 14 mAbs and twelve viruses reacted with 10 or less mAbs. mAbs to the major envelope glycoprotein E2/gp53 revealed a particularly high degree of antigenic variability in this glycoprotein. Nine isolates (47.3%) reacted with three or less of 10 E2/gp53 mAbs, and one isolate was not recognized by any of these mAbs. Virus-specific antisera to eight isolates plus three standard BVDV strains raised in lambs had virus-neutralizing titers ranging from 400 to 3200 against the homologous virus. Nonetheless, many antisera showed significantly reduced neutralizing activity when tested against heterologous viruses. Up to 128-fold differences in cross-neutralization titers were observed for some pairs of viruses. When the coefficient of antigenic similarity (R) was calculated, 49 of 66 comparisons (74.24%) between viruses resulted in R values that antigenically distinguish strains. Moreover, one isolate had R values suggesting that it belongs to a distinct serologic group. The marked antigenic diversity observed among Brazilian BVDV isolates should be considered when planning diagnostic and immunization strategies.

Structural, functional and immunological studies on a polymeric bacterial protein

The characterization of proteins from Brucella spp, the causative agent of brucellosis, has been the subject of intensive research. We have described an 18-kDa cytoplasmic protein of Brucella abortus and shown the potential usefulness of this protein as an antigen for the serologic diagnosis of brucellosis. The amino acid sequence of the protein showed a low but significant homology with that of lumazine synthases. Lumazine is an intermediate product in bacterial riboflavin biosynthesis. The recombinant form of the 18-kDa protein (expressed in E. coli) folds like the native Brucella protein and has lumazine-synthase enzymatic activity. Three-dimensional analysis by X-ray crystallography of the homolog Bacillus subtilis lumazine synthase has revealed that the enzyme forms an icosahedral capsid. Recombinant lumazine synthase from B. abortus was crystallized, diffracted X rays to 2.7-Å resolution at room temperature, and the structure successfully solved by molecular replacement procedures. The macromolecular assembly of the enzyme differs from that of the enzyme from B. subtilis. The Brucella enzyme remains pentameric (90 kDa) in its crystallographic form. Nonetheless, the active sites of the two enzymes are virtually identical at the structural level, indicating that inhibitors of these enzymes could be viable pharmaceuticals across a broad species range. We describe the structural reasons for the differences in their quaternary arrangement and also discuss the potential use of this protein as a target for the development of acellular vaccines.

alpha-Globin genes: thalassemic and structural alterations in a Brazilian population

Seven unrelated patients with hemoglobin (Hb) H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha-globin gene mutations present in the population of Southeast Brazil. The -alpha3.7, --MED and -(alpha)20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, aaNcoI, alphaIcalpha and alphaTSaudialpha) was screened with restriction enzymes and by nested PCR. Structural alterations were identified by direct DNA sequencing. Of the seven patients with Hb H disease, all of Italian descent, two had the -(alpha)20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and three showed interaction of the -alpha3.7 deletion with an unusual, unidentified form of non-deletional alpha-thalassemia [-alpha3.7/(aa)T]. Among the 27 patients with structural alterations, 15 (of Italian descent) had Hb Hasharon (alpha47Asp->His) associated with the -alpha3.7 deletion, 4 (of Italian descent) were heterozygous for Hb J-Rovigo (alpha53Ala->Asp), 4 (3 Blacks and 1 Caucasian) were heterozygous for Hb Stanleyville-II (alpha78Asn->Lys) associated with the alpha+-thalassemia, 1 (Black) was heterozygous for Hb G-Pest (alpha74Asp->Asn), 1 (Caucasian) was heterozygous for Hb Kurosaki (alpha7Lys->Glu), 1 (Caucasian) was heterozygous for Hb Westmead (alpha122His->Gln), and 1 (Caucasian) was the carrier of a novel silent variant (Hb Campinas, alpha26Ala->Val). Most of the mutations found reflected the Mediterranean and African origins of the population. Hbs G-Pest and Kurosaki, very rare, and Hb Westmead, common in southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.

Extracellular calcium-sensing receptor: structural and functional features and association with diseases

The recently cloned extracellular calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays an essential role in the regulation of extracellular calcium homeostasis. This receptor is expressed in all tissues related to this control (parathyroid glands, thyroid C-cells, kidneys, intestine and bones) and also in tissues with apparently no role in the maintenance of extracellular calcium levels, such as brain, skin and pancreas. The CaR amino acid sequence is compatible with three major domains: a long and hydrophilic aminoterminal extracellular domain, where most of the activating and inactivating mutations described to date are located and where the dimerization process occurs, and the agonist-binding site is located, a hydrophobic transmembrane domain involved in the signal transduction mechanism from the extracellular domain to its respective G protein, and a carboxyterminal intracellular tail, with a well-established role for cell surface CaR expression and for signal transduction. CaR cloning was immediately followed by the association of genetic human diseases with inactivating and activating CaR mutations: familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are caused by CaR-inactivating mutations, whereas autosomal dominant hypoparathyroidism is secondary to CaR-activating mutations. Finally, we will comment on the development of drugs that modulate CaR function by either activating (calcimimetic drugs) or antagonizing it (calcilytic drugs), and on their potential therapeutic implications, such as medical control of specific cases of primary and uremic hyperparathyroidism with calcimimetic drugs and a potential treatment for osteoporosis with a calcilytic drug.