Regulation of contextual conditioning by the median raphe nucleus

The median raphe nucleus (MRN) has been suggested as the origin of a behavioral inhibition system that projects to the septum and hippocampus. Electrical stimulation of this mesencephalic area causes behavioral and autonomic manifestations characteristic of fear such as, freezing, defecation and micturition. In this study we extend these observations by analyzing the behavioral and autonomic responses of rats with lesions in the MRN submitted to a contextual conditioning paradigm. The animals underwent electrolytic or sham lesions of the median raphe nucleus. One day (acute) or 7 days (chronic) later they were tested in an experimental chamber where they received 10 foot-shocks (0.7 mA, 1 s with 20-s interval). The next day, sham and MRN-lesioned animals were tested again either in the same or in a different experimental chamber. During this, the duration of freezing, rearings, bouts of micturition and number of fecal boli were recorded. Sham-operated rats placed in the same chamber showed more freezing than rats exposed to a different context. This freezing behavior was clearly suppressed in rats with acute or chronic lesions in the MRN. MRN lesions also reduced the bouts of micturition and number of fecal boli. These rats showed a reduced number of rearings than sham-lesioned rats. This effect is probably the result of the displacement effect provoked by freezing since no significant differences in the number of rearings could be observed between these animals and the NMR-lesioned rats tested in an open field. This lesion produced higher horizontal locomotor activity in this test than the controls (sham-lesioned rats). These results point to the importance of the median raphe nucleus in the processing of fear conditioning with freezing being the most salient feature of it. Behavioral inhibition is also under control of MRN but its neural substrate seems to be dissociated from that of contextual fear. (C) 1998 Elsevier B.V. B.V.

Alianças e desenvolvimento de políticas para o desenvolvimento local: imbricações na mineração de alumínio em Oriximiná-PA

Aborda, por um lado, a relação entre a economia local no Município de Oriximiná - PA e sua inserção no Comércio Internacional do minério de alumínio. E, por outro, os mecanismos de interação e alianças entre os atores locais público e privado com o setor minerador de alumínio, representado pela Companhia MRN, vis à vis a consecução de um projeto de desenvolvimento local em bases endógenas. O estudo busca compreender como a interação entre interesses públicos/privados, coletivos/individuais, orgânicos/corporativos em âmbito local influenciam no desenvolvimento endógeno do Município. Não obstante, avaliar a dimensão das restrições estruturais, condicionadas pela dinâmica das relações comerciais no setor mundial do minério de Alumínio, aos processos internos de articulação para o desenvolvimento local. O Problema proposto está em compreender como as oportunidades e restrição da explotação de uma mina world class impulsiona processos de desenvolvimento local. Partindo-se da Nova Teoria Econômica aliada à Teoria do Comércio Internacional e Geografia Econômica, buscou-se delinear os parâmetros de inserção da economia mineradora do alumínio local no cenário internacional e suas inter-relações resultantes, sejam estas sob o aspecto tecnológico ou mercadológico. Numa perspectiva local, procurou-se identificar os processos interativos e seu grau de convergência entre Setor Público (via Plano Diretor Municipal) com vistas à concretização de um projeto de desenvolvimento endógeno mediado pela formação de alianças (Clusters) que atendessem às suas respectivas exigências tecnológica, econômica e institucional. Para tanto, o trabalho recorreu às Teorias do Crescimento e Desenvolvimento econômico e dos Sistemas para explicitar os mecanismos que regem as interações entre os atores locais e, em última análise, determinam suas ações sociais no processo de desenvolvimento endógeno. O método adotado é o hipotético-dedutivo utilizando-se instrumentos de coleta de dados secundários e primários. Através de um processo de modelagem computacional e, recorrendo aos Relatórios Fiscais da Prefeitura de Oriximiná e Contábeis da Mineração Rio do Norte buscou-se o aprofundamento sobre a natureza e aplicação dos recursos gerenciados por ambas Instituições. Desenvolve-se ainda, um modelo representativo da dinâmica do desenvolvimento endógeno local tendo o PIB Municipal per capita como proxy através do método de análise multivariada utilizando a técnica da regressão linear múltipla. Desenvolve-se também uma análise da autocorrelação da economia de Oriximiná com o seu entorno a partir da técnica de processamento de dados espaciais geograficamente referenciados bem como a técnica de acessibilidade locacional de Oriximiná. A apresentação dos resultados utiliza modelos simbólicos, tabelas e gráficos diversos. A conclusão é de que a atividade minerária encontra-se descolada do processo de crescimento local por não produzir spillover e por não internalizar o grosso da sua renda no Município dada sua estratégia competitiva. Contudo, a dinâmica local também sofre restrições por conta de sua localização espacial à margem do eixo econômico Regional e pela baixa capacidade empreenditiva e articulatória demonstrada pela administração pública local.

Certificações socioambientais: desenvolvimento sustentável e competitividade da indústria mineira na Amazônia

Este estudo trata do crescimento econômico de um setor que consome recursos naturais não-renováveis, o setor minerometálico, e do processo de desenvolvimento sustentável na Amazônia oriental, no estado do Pará. Desde os anos 1980, o segmento minerometálico do Pará vem crescendo de forma acelerada. As empresas ali instaladas - Companhia Vale do Rio Doce (CVRD), Mineração Rio do Norte (MRN) e Alumínio Brasileiro S.A. (Albras) - são líderes globais nas suas respectivas áreas de atuação e necessitam estar ajustadas às normas socioambientais; por isso, quase todas são certificadas social e ambientalmente. A conquista dessas certificações é um forte indício de que essas empresas compartilham dos preceitos da sustentabilidade. Dessa forma, o objetivo deste estudo é verificar a relação entre essas certificações e o processo de desenvolvimento sustentável das áreas onde essas empresas estão instaladas, considerando-se que são regiões carentes. A partir dos fundamentos conceituais do desenvolvimento sustentável e de uma perspectiva espacial e setorial, a pesquisa apresenta os principais indicadores do segmento minerometálico do Pará, além do perfil socioambiental de suas mais importantes empresas. É feito ainda um breve histórico da recente evolução do processo de certificações socioambientais no Brasil. A partir de uma série de indicadores, é discutido não apenas se essas certificações contribuem para o desenvolvimento sustentável, mas se também se são importantes para que essas organizações se mantenham competitivas. A conclusão é que os aspectos positivos dessas ações ainda são muito mais visíveis no desempenho econômico das empresas do que no desenvolvimento socioeconômico do entorno delas. Da mesma forma, é verificado que as certificações socioambientais inspiradas no desenvolvimento sustentável ainda têm um viés muito mais ecológico do que social.

The median raphe nucleus in anxiety revisited

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Interação entre estradiol e receptores 5 - H T 1A no Núcleo Mediano da Rafe em ratas ovariectomizadas: na aquisição da informação aversiva e associação ao contexto

Pós-graduação em Biociências - FCLAS

DIFFERENTIAL INVOLVEMENT OF DORSAL RAPHE SUBNUCLEI IN THE REGULATION OF ANXIETY- AND PANIC-RELATED DEFENSIVE BEHAVIORS

A wealth of evidence indicates that the dorsal raphe nucleus (DR) is not a homogenous structure, but an aggregate of distinctive populations of neurons that may differ anatomically, neurochemically and functionally. Other findings suggest that serotonergic neurons within the mid-caudal and caudal part of the DR are involved in anxiety processing while those within the lateral wings (IwDR) and ventrolateral periaqueductal gray (vIPAG) are responsive to panic-evoking stimuli/situations. However, no study to date has directly compared the activity of 5-HT and non-5HT neurons within different subnuclei of the DR following the expression of anxiety- and panic-related defensive responses. In the present investigation, the number of doubly immunostained cells for Fos protein and tryptophan hydroxylase, a marker of serotonergic neurons, was assessed within the rat DR, median raphe nucleus (MRN) and PAG following inhibitory avoidance and escape performance in the elevated T-maze, behaviors associated with anxiety and panic, respectively. Inhibitory avoidance, but not escape, significantly increased the number of Fos-expressing serotonergic neurons within the mid-caudal part of the dorsal subnucleus, caudal and interfascicular subnuclei of the DR and in the MRN. Escape, on the other hand, caused a marked increase in the activity of non-5HT cells within the IwDR, vIPAG, dorsolateral and dorsomedial columns of the PAG. These results strongly corroborate the view that different subsets of neurons in the DR are activated by anxiety- and panic-relevant stimuli/situations, with important implications for the understanding of the pathophysiology of generalized anxiety and panic disorders. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

The molecular mechanisms of sensing nucleoside analogue-induced DNA damage

Nucleoside analogues are antimetabolites effective in the treatment of a wide variety of solid tumors and hematological malignancies. Upon being metabolized to their active triphosphate form, these agents are incorporated into DNA during replication or excision repair synthesis. Because DNA polymerases have a greatly decreased affinity for primers terminated by most nucleoside analogues, their incorporation causes stalling of replication forks. The molecular mechanisms that recognize blocked replication may contribute to drug resistance but have not yet been elucidated. Here, several molecules involved in sensing nucleoside analogue-induced stalled replication forks have been identified and examined for their contribution to drug resistance. ^ The phosphorylation of the DNA damage sensor, H2AX, was characterized in response to nucleoside analogues and found to be dependent on both time and drug concentration. This response was most evident in the S-phase fraction and was associated with an inhibition of DNA synthesis, S-phase accumulation, and activation of the S-phase checkpoint pathway (Chk1-Cdc25A-Cdk2). Exposure of the Chk1 inhibitor, 7-hydroxystaurosporine (UCN-01), to cultures previously treated with nucleoside analogues caused increased apoptosis, clonogenic death, and a further log-order increase in H2AX phosphorylation, suggesting enhanced DNA damage. Ataxia-telangiectasia mutated (ATM) has been identified as a key DNA damage signaling kinase for initiating cell cycle arrest, DNA repair, and apoptosis while the Mre11-Rad50-Nbs1 (MRN) complex is known for its functions in double-strand break repair. Activated ATM and the MRN complex formed distinct nuclear foci that colocalized with phosphorylated H2AX after inhibition of DNA synthesis by the nucleoside analogues, gemcitabine, ara-C, and troxacitabine. Since double-strand breaks were undetectable, this response was likely due to stalling of replication forks. A similar DNA damage response was observed in human lymphocytes after exposure to ionizing radiation and in acute myelogenous leukemia blasts during therapy with the ara-C prodrug, CP-4055. Deficiencies in ATM, Mre11, and Rad50 led to a two- to five-fold increase in gemcitabine sensitivity, suggesting that these molecules contribute to drug resistance. Based on these results, a model is proposed for the sensing of nucleoside analogue-induced stalled replication forks that includes H2AX, ATM, and the Mre11-Rad50-Nbs1 complex. ^

The connection between E2F and ATM in p53-dependent apoptosis

Programmed cell death is an anticancer mechanism utilized by p53 that when disrupted can accelerate tumor development in response to oncogenic stress. Defects in the RB tumor suppressor cause aberrant cell proliferation as well as apoptosis. The combinatorial loss of the p53 and RB pathways is observed in a large percentage of human tumors. The E2F family of transcription factors primarily mediates the phenotype of Rb loss, since RB is a negative regulator of E2F. Contrary to early expectations, it has now been shown that the ARF (alternative reading frame) tumor suppressor is not required for p53-dependent apoptosis in response to deregulation of the RB/E2F pathway. In this study, we demonstrate that ATM, known as a DNA double-strand break (DSB) sensor, is responsible for ARF-independent apoptosis and p53 activation induced by deregulated E2F1. Moreover, NBS1, a component of the MRN DNA repair complex, is also required for E2F1-induced apoptosis and apparently works in the same pathway as ATM. We further found that endogenous E2F1 and E2F3 both play a role in apoptosis and ATM activation in response to inhibition of RB by the adenoviral E1A oncoprotein. We demonstrate that, unlike deregulated E2F3 and Myc, ATM activation by deregulated E2F1 does not involve the induction of DNA damage, autophosphorylation of ATM on Ser 1981, a marker of ATM activation by DSB, but does depend on the presence of NBS1, suggesting that E2F1 activates ATM in a different manner from E2F3 and Myc. Results from domain mapping studies show that the DNA binding, dimerization, and marked box domains of E2F1 are required to activate ATM and stimulate apoptosis but the transactivation domain is not. This implies that E2F1's DNA binding and interaction with other proteins through the marked box domain are necessary to induce ATM activation leading to apoptosis but transcriptional activation by E2F1 is dispensable. Together these data suggest a model in which E2F1 activates ATM to phosphorylate p53 through a novel mechanism that is independent of DNA damage and transcriptional activation by E2F1.^

Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells from benign and malignant proliferations of the breast

Aims: To analyse the expression of proteins involved in DNA double strand break detection and repair in the luminal and myoepithelial compartments of benign breast lesions and malignant breast tumours with myoepithelial differentiation. Methods: Expression of the ataxia telangiectasia (ATM) and p53 proteins was immunohistochemically evaluated in 18 benign and malignant myoepithelial tumours of the breast. Fifteen benign breast lesions with prominent myoepithelial compartment were also evaluated for these proteins, in addition to those in the MRE11-Rad50-NBS1 (MRN) complex, and the expression profiles were compared with those seen in eight independent non-cancer (normal breast) samples and in the surrounding normal tissues of the benign and malignant tumours examined. Results: ATM expression was higher in the myoepithelial compartment of three of 15 benign breast lesions and lower in the luminal compartment of eight of these lesions compared with that found in the corresponding normal tissue compartments. Malignant myoepithelial tumours overexpressed ATM in one of 18 cases. p53 was consistently negative in benign lesions and was overexpressed in eight of 18 malignant tumours. In benign breast lesions, expression of the MRN complex was significantly more reduced in myoepithelial cells (up to 73%) than in luminal cells (up to 40%) (p = 0.0005). Conclusions: Malignant myoepithelial tumours rarely overexpress ATM but are frequently positive for p53. In benign breast lesions, expression of the MRN complex was more frequently reduced in the myoepithelial than in the luminal epithelial compartment, suggesting different DNA repair capabilities in these two cell types.

Alterações hepáticas na expressão gênica e atividade da catalase e superóxido dimutase em ratos diabéticos induzidos por estreptozootocina

The correlation between the type 1 diabetes mellitus and oxidative stress have been described in several studies, however its underlying mechanisms are not fully elucidated. The present work aimed to evaluate the effects of four weeks of streptozootocin-induced (STZ) diabetes in the redox homeostasis of rat hepatocytes. Thus, the liver of male Wistar rats from control and diabetic groups were collected and the activity and expression of antioxidant enzymes, as well the main markers of oxidative stress and content of H2O2 in these tissues were measured. The diabetes induced the activity of superoxide dismutase (SOD) and the gene expression of its mitochondrial isoform, SOD2. However, the expression of SOD1, the cytoplasmic isoform, was reduced by this disease. The activity and expression of catalase (CAT), as well the expression of glutathione peroxidase 1 (GPX1) and peroxiredoxin 4 (PRX4) were drastically reduced in the hepatocytes of diabetics rats. Even with this debility in the peroxidases mRNA expression, the content of H2O2 was reduced in the liver of diabetics rats when compared to the control group. The diabetes caused an increase of lipid peroxidation and a decrease of protein thiol content, showing that this disease causes distinct oxidative effects in different cell biomolecules. Our results indicate that four week of diabetes induced by STZ is already enough to compromise the enzymatic antioxidant systems of the hepatocytes.

Evaluation of Mobile Telephone Text Message Reminders for People with Antipsychotic Medication

Nonadherence to treatment is a worldwide problem among people with severe mental disorders. Patient treatment adherence may be supported with simple reminding methods e.g. text message reminders. However, there is limited evidence of its benefits. Intervention evaluation is essential in mHealth research. Therefore, this evaluative study was conducted. This study aimed to evaluate text message reminder use in encouraging patients’treatment adherence among people with antipsychotic medication. The data were collected between September 2011 and December 2013. First, a systematic literature review revealed that text message reminders were widely used in healthcare. However, its impacts were conflicting. Second, a sub-sample (n = 562) analysis showed that patients preferred humorous text message reminders and preferred to receive them in the morning, at the beginning of the week. Age, gender and marital status seemed to have different effects on the preferred amount and timing of the selected reminders. Third, a cross-sectional survey revealed that people with antipsychotic medication (n = 408) expressed overall satisfaction towards the reminder system. Finally, the evaluative design showed that patient recruitment for a randomized controlled trial concerning people with antipsychotic medication was challenging due to low rates of eligible participants. Follow-up drop-out rates varied depending on the data collection method. Participants’ demographic characteristics were associated with the risk of dropping out from the trial. This study suggests that text messages are a potential reminder system in healthcare services among people with antipsychotic medication. More research is needed to gain a comprehensive picture of the impacts and effectiveness of text message reminders.

Analytiikkajärjestelmän käyttöönottoprojekti, kustannukset ja kustannusten hallinta

Perinteisten kilpailuetujen katoaminen ja kilpailun kiristyminen haastavat yrityksiä etsimään keinoja kilpailukyvyn säilyttämiseksi. Tietotekniikan nopea kehitys ja liiketoiminnassa syntyvän datan määrän kasvu luovat yrityksille mahdollisuuden hyödyntää analytiikkaa päätöksenteon tukena ja liiketoiminnan tehostamisessa. Työ on kirjallisuuskatsaus ja sen tavoitteena on selvittää analytiikkajärjestelmän käyttöönottoprojektin vaiheet, käyttöönottoon liittyvät kustannukset ja miten kustannuksia voidaan hallita. Lisäksi esitetään tiivis katsaus analytiikan kehitykseen ja nykytilaan sekä tarkastellaan hankintamalleja, hankkeiden taloudellista arviointia ja käyttöönottoprojektin kriittisiä menestystekijöitä. Käyttöönottoprojekti on monivaiheinen ja se alkaa liiketoiminnan analysoinnista sekä järjestelmän suunnittelusta ulottuen aina sen toteutukseen ja jälkiarviointiin. Käyttöönottoon liittyy useita kustannuseriä, joita voidaan luokitella niiden ominaisuuksien perusteella. Projektin kustannusten hallinnan prosesseja ovat kustannusten hallinnan suunnittelu, kustannusten arviointi, budjetin määrittäminen ja kustannusten valvonta, jotka limittyvät käyttöönoton vaiheiden kanssa.

Hyväntekeväisyyteen lahjoittavien käyttäytyminen ja siihen vaikuttavat tekijät. Tapaus: Suomen Evankelisluterilainen Kansanlähetys ry

Hyväntekeväisyysorganisaatiot tarvitsevat toimintansa rahoittamiseen lahjoittajia. Yksityishenkilöiden lahjoittamiskäyttäytymisen ymmärtäminen ja tunteminen on tärkeää, ja auttaa hyväntekeväisyysorganisaatioita markkinointitoimenpiteiden ja varainhankinnan suunnittelussa. Tämän tutkimuksen tarkoituksena on kuvata hyväntekeväisyyteen lahjoittavien lahjoittamiskäyttäytymistä sekä arvojen ja sosio-demografisten ominaisuuksien vaikutusta siihen. Tarkempi tutkimuskysymys on: miten lahjoittajan arvot ja sosio-demografiset ominaisuudet vaikuttavat lahjoittamiskäyttäytymiseen? Tutkimuskysymys sisältää kolme osa-ongelmaa: 1) Miten lahjoittamiskäyttäytymistä voidaan kuvata? 2) Miten lahjoittajan arvot vaikuttavat lahjoittamiskäyttäytymiseen? 3) Miten lahjoittajan sosio-demografiset ominaisuudet vaikuttavat lahjoittamiskäyttäytymiseen? Tutkimuksen tapausorganisaationa on Suomen Evankelisluterilainen Kansanlähetys ry. Tutkimuksen teoreettinen viitekehys rakentuu Sargeantin lahjoittajien käyttäytymisen mallista (1999) ja Schwartzin arvoteoriasta (1992) sekä aiemmasta tutkimuksesta lahjoittamiskäyttäytymisestä, arvoista ja sosio-demografisista ominaisuuksista. Teoriaosan lopuksi esitellään tutkimusmalli. Tutkimuksessa selitettävänä tekijänä on lahjoittamiskäyttäytyminen, joka määriteltiin neljän dimension mukaan: lahjoituskohde, lahjoitettu määrä, lahjoittamistiheys ja lahjoittamistapa. Selittävinä tekijöinä tarkastellaan Schwartzin arvoteorian mukaisia 56 yksittäistä arvoa, jotka tiivistyvät tässä tutkimuksessa yhdeksäksi arvoulottuvuudeksi: Itseohjautuvuus, virikkeisyys, mielihyvä, suoriutuminen, valta, turvallisuus, yhdenmukaisuus/perinteet, hyväntahtoisuus ja universalismi. Lisäksi selittävinä tekijöinä tarkastellaan sosio-demografisista ominaisuuksista sukupuolta, ikää, tuloja ja koulutusta. Tutkimuksen empiirinen osuus perustuu kvantitatiiviseen tutkimukseen. Aineisto kerättiin sähköisenä kyselytutkimuksena, joka oli esillä Kansanlähetyksen verkkosivuilla: suuressamukana.fi ja sekl.fi. Aineisto analysoitiin kvantitatiivisin menetelmin, käyttäen muun muassa ristiintaulukointia, khiin neliö –testiä ja yksisuuntaista varianssianalyysiä. Tulosten mukaan lahjoittajan arvomaailmalla oli vaikutusta lahjoittamiskäyttäytymiseen. Lahjoittajien tärkeimpinä pitämät arvoulottuvuudet olivat hyväntahtoisuus, turvallisuus, universalismi ja yhdenmukaisuus/perinteet. Vähiten tärkeänä pidettiin valtaa ja mielihyvää. Eri kohteisiin lahjoittavien, eri määrän lahjoittavien ja eri tiheydellä lahjoittavien kesken oli eroja kahden tai kolmen arvoulottuvuuden suhteen. Sosio-demografisista tekijöistä sukupuolella ja koulutuksella ei ollut vaikutusta lahjoittamiskäyttäytymiseen, mutta iällä ja tuloilla oli

Data-analytiikan hyödyntäminen yrityksen talouden ohjauksessa

Kandidaatintyö on toteutettu kirjallisuuskatsauksena, jonka tavoitteena on selvittää data-analytiikan käyttökohteita ja datan hyödyntämisen vaikutusta liiketoimintaan. Työ käsittelee data-analytiikan käyttöä ja datan tehokkaan hyödyntämisen haasteita. Työ on rajattu tarkastelemaan yrityksen talouden ohjausta, jossa analytiikkaa käytetään johdon ja rahoituksen laskentatoimessa. Datan määrän eksponentiaalinen kasvunopeus luo data-analytiikan käytölle uusia haasteita ja mahdollisuuksia. Datalla itsessään ei kuitenkaan ole suurta arvoa yritykselle, vaan arvo syntyy prosessoinnin kautta. Vaikka data-analytiikkaa tutkitaan ja käytetään jo runsaasti, se tarjoaa paljon nykyisiä sovelluksia suurempia mahdollisuuksia. Yksi työn keskeisimmistä tuloksista on, että data-analytiikalla voidaan tehostaa johdon laskentatoimea ja helpottaa rahoituksen laskentatoimen tehtäviä. Tarjolla olevan datan määrä kasvaa kuitenkin niin nopeasti, että käytettävissä oleva teknologia ja osaamisen taso eivät pysy kehityksessä mukana. Varsinkin big datan laajempi käyttöönotto ja sen tehokas hyödyntäminen vaikuttavat jatkossa talouden ohjauksen käytäntöihin ja sovelluksiin yhä enemmän.

Role of fibroblast growth factors and their receptors in prostate cancer

Prostate cancer (PCa) is the most common non-cutaneous malignant disease among males in the developed countries. Radical prostatectomy (RP) is an effective therapy for most PCa patients with localized or locally invaded tumors but in some cases the cancer recurs after RP. PCa is a heterogeneous disease, which is regulated by many factors, such as androgen receptor (AR), estrogen receptors and  (ER and ER), fibroblast growth factors (FGFs) and their receptors (FGFRs). In this study, the role of ERβ, FGF8, FGF13 and FGFRL1 was investigated in PCa. Previous studies have suggested that ER is protective against PCa whereas FGF8 has been shown to induce PCa in transgenic mice. FGF13 and FGFRL1 are poorly understood members of the FGF and FGFR families, respectively. Transgenic mouse models were used to investigate the ability of inactivated ERβ to facilitate FGF8-induced prostate tumorigenesis. Human PCa tissue microarrays (TMAs) were used to study the expression pattern of FGF13 and FGFRL1 in PCa and the results were correlated to corresponding patient data. The targets and biological functions of FGF13 and FGFRL1 were characterized using experimental in vivo and in vitro models. The results show that deficiency of ERβ, which had been expected to have tumor suppressing capacity, seemed to influence epithelial differentiation but did not affect FGF8-induced prostate tumorigenesis. Analysis of the TMAs showed increased expression of FGF13 in PCa. The level of cytoplasmic FGF13 was associated with the PCa biochemical recurrence (BCR), demonstrated by increasing serum PSA value, and was able to act as an independent prognostic biomarker for PCa patients after RP. Expression of FGFRL1, the most recently identified FGFR, was also elevated in PCa. Cytoplasmic and nuclear FGFRL1 was associated with high Gleason score and Ki67 level whereas the opposite was true for the cell membrane FGFRL1. Silencing of FGFRL1 in PC-3M cells led to a strongly decreased growth rate of these cells as xenografts in nude mice and the experiments with PCa cell lines showed that FGFRL1 is able to modulate the FGF2- and FGF8-induced signaling pathways. The next generation sequencing (NGS) experiments with FGFRL1-silenced PC-3M cells revealed candidates for FGFRL1 target genes. In summary, these studies provide new data on the FGF/FGFR signaling pathways in normal and malignant prostate and suggest a potential role for FGF13 and FGFRL1 as novel prognostic markers for PCa patients. Keywords: FGF8, FGF13, FGFRL1, ERβ, prostate cancer, prognostic marker