The Retinal TNAP

Accumulating evidence from recent literature underline the important roles of tissue non specific alkaline phosphatase (TNAP) in diverse functions as well as diseases of the nervous system. Exploration of TNAP in well characterized neural circuits such as the retina, might significantly advance our understanding regarding neural TNAP’s roles. This chapter reviews the scarce literature as well as our findings on retinal TNAP. We found that retinal TNAP activity was preserved and followed diverse patterns throughout vertebrate evolution. We have consistently observed TNAP activity (1) in retinal vessels, (2) in photoreceptors and (3) in the majority of the studied species in the outer (OPL) and inner plexiform layers (IPL), where synaptic transmission occurs. Importantly, in some species the IPL exhibits several TNAP positive strata. These strata exactly corresponded those seen after quadruple immunohistochemistry with four canonical IPL markers (tyrosine hydroxylase, choline acetyltransferase, calretinin, protein kinase C α). Diabetes results in diminishing retinal TNAP activity before changes in canonical markers

Transzformáló növekedési faktor béta fehérjék szerepe a központi idegrendszer működésében = The Function of Transforming Growth Factor beta Proteins in the Central Nervous System

A pályázat keretében megmutattuk, hogy a transzformáló növekedési faktorok (TGF-béta1, -béta2 és -béta3) kifejeződnek az agyszövetben ischemiás léziót követően, és hogy jelentős különbségek vannak az egyes altípusok időbeli és térbeli mintázata között. Az a további felfedezésünk, hogy a különböző TGF-béta altípusok eltérő típusú sejtekben fejeződnek ki, és más azonnali korai génekkel kolokalizálnak arra utal, hogy a különböző TGF-béta altípusok eltérő mechanizmussal aktiválódnak az agyban ischemia után. Ebből következően időben és térben eltérően szabályozott gyulladásos és neuroprotektív folyamatokban vehetnek részt. Az ischemiát követő védelmi szerephez hasonlóan a TGF-béta fehérjék más szöveti károsodással szemben is védelmet nyújthatnak. A pályázat keretében a neuroprotekció lehetséges mechanizmusait is leírtuk. A TGF-béta fehérjék a patológiás folyamatok mellett fiziológiás szabályozásokban is szerepet kaphatnak. Eredményeink arra utaltak, hogy a TGF-béta1 fehérje szerepet játszhat a szülés utáni anyai adaptációkban, mivel annak elhelyezkedése hasonló volt egy anyai neuropeptidéhez, az amylinhez a preoptikus területen, aminek a léziója az anyai viselkedések kiesését okozza. Azonban a további kísérleteink azt valószínűsítik, hogy a TGF-béta fehérjéknek nem az anyai viselkedések, hanem esetleg a gonadotropin hormon releasing hormon elválasztásának szabályozásában vehetnek részt. | We showed that transforming growth factors (TGF-beta1, -beta2 and -beta3) were expressed in brain tissue following ischemic lesion and that significant differences exist between the spatial and temporal patterns of expression of TGF-beta subtypes. The additional finding that TGF-beta subtypes are expressed in separate cell types, and co-localize with different immediate early genes imply that endogenous TGF-betas are induced by different mechanisms following an ischemic attack in the brain. Consequently, they may be involved in distinct spatially and temporally regulated inflammatory and neuroprotective processes. Thus, the different subtypes of TGF-betas may participate in different aspects of neural tissue protection. Apart from neuroprotection following ischemia, TGF-betas were suggested to have neuroprotective actions in a variety of additional insults to the nervous tissue. The different mechanisms involved in the neuroprotective actions of TGF-beta subunits for the different disorders are described. Physiological functions of TGF-betas were also suggested. Our results also pointed to a possible role of TGF-betas in maternal alterations as the expression of TGF-beta1 is very similar to the maternal peptide amylin in the preoptic area, a brain region whose lesion leads to the elimination of maternal care. However, a variety of approaches indicate that TGF-betas may not be involved in maternal adaptations but rather could play a role in the regulation of GnRH function in the preoptic area

Strategic Positioning of Connexin36 Gap Junctions Across Human Retinal Ganglion Cell Dendritic Arbors

Connexin36 (Cx36) subunits form gap junctions (GJ) between neurons throughout the central nervous system. Such GJs of the mammalian retina serve the transmission, averaging and correlation of signals prior to conveying visual information to the brain. Retinal GJs have been exhaustively studied in various animal species, however, there is still a perplexing paucity of information regarding the presence and function of human retinal GJs. Particularly little is known about GJ formation of human retinal ganglion cells (hRGCs) due to the limited number of suitable experimental approaches. Compared to the neuronal coupling studies in animal models, where GJ permeable tracer injection is the gold standard method, the post-mortem nature of scarcely available human retinal samples leaves immunohistochemistry as a sole approach to obtain information on hRGC GJs. In this study Lucifer Yellow (LY) dye injections and Cx36 immunohistochemistry were performed in fixed short-post-mortem samples to stain hRGCs with complete dendritic arbors and locate dendritic Cx36 GJs. Subsequent neuronal reconstructions and morphometric analyses revealed that Cx36 plaques had a clear tendency to form clusters and particularly favored terminal dendritic segments

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals

PACAP was discovered 30 years ago in Dr. Akira Arimura's laboratory. In the past three decades since then, it has become evident that this peptide plays numerous crucial roles in mammalian organisms. The most important functions of PACAP are the following: 1. neurotransmitter, 2. neuromodulator, 3. hypophysiotropic hormone, 4. neuroprotector. This paper reviews the accumulated data regarding the distribution of PACAP and its receptors in the mammalian hypothalamus and pituitary gland, the role of PACAP in the gonadotropin hormone secretion of females and males. The review also summarizes the interaction between PACAP, GnRH, and sex steroids as well as hypothalamic peptides including kisspeptin. The possible role of PACAP in reproductive functions through the biological clock is also discussed. Finally, the significance of PACAP in the hypothalamo-hypophysial system is considered and the facts missing, that would help better understand the function of PACAP in this system, are also highlighted

Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison

Much knowledge about interconnection of human retinal neurons is inferred from results on animal models. Likewise, there is a lack of information on human retinal electrical synapses/gap junctions (GJ). Connexin36 (Cx36) forms GJs in both the inner and outer plexiform layers (IPL and OPL) in most species including humans. However, a comparison of Cx36 GJ distribution in retinas of humans and popular animal models has not been presented. To this end a multiple-species comparison was performed in retinas of 12 mammals including humans to survey the Cx36 distribution. Areas of retinal specializations were avoided (e.g., fovea, visual streak, area centralis), thus observed Cx36 distribution differences were not attributed to these species-specific architecture of central retinal areas. Cx36 was expressed in both synaptic layers in all examined retinas. Cx36 plaques displayed an inhomogenous IPL distribution favoring the ON sublamina, however, this feature was more pronounced in the human, swine and guinea pig while it was less obvious in the rabbit, squirrel monkey, and ferret retinas. In contrast to the relative conservative Cx36 distribution in the IPL, the labels in the OPL varied considerably among mammals. In general, OPL plaques were rare and rather small in rod dominant carnivores and rodents, whereas the human and the cone rich guinea pig retinas displayed robust Cx36 labels. This survey presented that the human retina displayed two characteristic features, a pronounced ON dominance of Cx36 plaques in the IPL and prevalent Cx36 plaque conglomerates in the OPL. While many species showed either of these features, only the guinea pig retina shared both. The observed similarities and subtle differences in Cx36 plaque distribution across mammals do not correspond to evolutionary distances but may reflect accomodation to lifestyles of examined species

Statistical analysis of logarithmic asset returns

In the study, we conducted a statistical analysis of asset returns of 16 companies during the period from 2000 to 2015. We used the Shapiro-Wilk test and determined that time series are not from a normal distribution. We detect structural breaks in time series with the Chow test, and then the correlation coefficients between asset returns were calculated. We found the first four moments of correlation coefficients. Data collection and statistical computing have been done in the programming language R

Magyar generatív történeti mondattan = Hungarian generative diachronic syntax

Elkészítettük a kéziratos ómagyar és korai középmagyar szövegek, köztük 47 kódex digitális adatbázisát, egy kétmillió szavas korpuszt. 11 kódexszöveghez normalizált helyesírású változatot is illesztettünk. Négy kódexet morfológiailag is annotáltunk. Az adatbázishoz felhasználóbarát keresőt készítettünk. Elemeztük az ómagyar szövegek mondattanát, olykor az ősmagyar korig visszanyúlva. Egyes változásokat a középmagyar koron át az újmagyar korig követtük. Amellett érveltünk, hogy az ősmagyar mondat SOV szórendű volt, és az ősmagyar/ómagyar kor fordulóján változott SVO-vé. Hipotézist állítottunk fel a változás okáról és lefolyásáról. Végigkísértük a határozott névelő kialakulását és a birtokos szerkezet változásait. Kimutattuk , hogy míg az ősmagyart az adverbiális kvantifikáció jellemezte, az ómagyar kor közepére a determinánsi kvantifikáció vált általánossá. A névutós szerkezeteket a relációs főnevet tartalmazó birtokos szerkezetektől a határozóragokig vezető grammatikalizációs út állomásaként elemeztük. Vizsgáltuk az ősmagyar SOV örökségeként továbbélő sokféle korai ómagyar igeneves szerkezetet, és megmutattuk, hogyan szorította ki őket a véges alárendelés. A változásokban kimutattuk a nyelvi változások univerzális válfajait: az újraelemzést, a grammatikalizációt, és megmutattunk a változások ciklikus voltát. Eredményeinket egy magyar és egy angol kötetben foglaltuk össze; előbbi az Akadémiai Kiadónál, utóbbi az Oxford University Pressnél áll megjelenés alatt. | We compiled a 2-million-word corpus of Old and Early Middle Hungarian manuscripts, among them 47 codices. In the case of 11 codices, we also prepared a paleographically normalized version. 4 codices were morphologically parsed and annotated. We prepared a user-friendly corpus query tool. We analyzed the syntax of Old Hungarian texts, often also reconstructing the Proto-Hungarian antecedents. We have followed some of the changes up to the present. We concluded that the Proto-Hungarian sentence was SOV, which changed into SOV at the turn of the Proto-Hungarian/Old Hungarian periods. We have set up a hypothesis about the causes and the process of this change. We analyzed the stages of the emergence of the definite article and the changes of the possessive construction. We pointed out a shift from adverbial quantification to determiner quantification. We analyzed postpositional constructions as intermediate steps on the grammaticalization path leading from possessive constructions with a relational head noun to adverbial suffixes. We investigated the rich system of non-finite subordination surviving from the SOV Proto-Hungarian era, and its gradual replacement by finite subordination. We pointed out the universal mechanisms of change, among them reanalysis and grammaticalization, and we showed the cyclic nature of changes. We summarized our results in a Hungarian and in an English book. The former is being published by Akadémiai Kiadó, the latter, by Oxford University Press