Croatian Institute for Brain Research

Salata, Croatia

Croatian Institute for Brain Research

Salata, Croatia

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Vladusic T.,University of Zagreb | Hrascan R.,University of Zagreb | Kruslin B.,University of Zagreb | Pecina- Slaus N.,Croatian Institute for Brain Research | And 6 more authors.
Anticancer Research | Year: 2014

Background: Testicular germ cell tumours are the most common malignancies in young males. Molecular biology studies of these tumours are often contradictory. Two histological groups, seminoma and non-seminoma, differ both morphologically and in malignant behaviour. Although a common cytogenetic feature is seen, namely the amplification of the 12p chromosomal region, the development mechanisms of less aggressive seminomas and more aggressive non-seminomas are unknown. Materials and Methods: Occurrence of structural genetic alterations was analyzed in 18 seminomas and 22 non-seminomas for genes involved in the malignant tumour phenotype: cadherin 1, Type 1, E-cadherin (Epithelial), CDH1; adenomatous polyposis coli, APC; NME/NM23 nucleoside diphosphate kinase 1, NME1; tumour protein P53, TP53; cyclindependent kinase inhibitor 2A, CDKN2A; retinoblastoma 1, RB1; RAD51 recombinase, RAD51; mutS homolog 2, MSH2; MutL homolog 1, MLH1; breast cancer 1, early onset, BRCA1; BCL2-Associated X Protein, BAX; ATP-Binding Cassette, Sub-Family G (WHITE), Member 2, ABCG2. Genetic alterations, loss of heterozygosity and microsatellite instability, were analyzed using restriction fragment or microsatellite repeat length polymorphisms. Results: A difference in genetic alteration occurrence between seminomas and non-seminomas was observed. Conclusion: Occurrence of genetic alterations correlates with clinical behaviour of these tumours and may indicate that such alterations could occur early in the development of seminomas and non-seminomas. © 2014, International Institute of Anticancer Research. All rights reserved.


Fuller H.R.,RJAH Orthopaedic Hospital | Fuller H.R.,Keele University | Slade R.,Keele University | Jovanov-Milosevic N.,Croatian Institute for Brain Research | And 7 more authors.
Molecular and Cellular Neuroscience | Year: 2015

Understanding the intra- and extracellular proteins involved in the development of the corticospinal tract (CST) may offer insights into how the pathway could be regenerated following traumatic spinal cord injury. Currently, however, little is known about the proteome of the developing corticospinal system. The present study, therefore, has used quantitative proteomics and bioinformatics to detail the protein profile of the rat CST during its formation in the spinal cord. This analysis identified increased expression of 65 proteins during the early ingrowth of corticospinal axons into the spinal cord, and 36 proteins at the period of heightened CST growth. A majority of these proteins were involved in cellular assembly and organization, with annotations being most highly associated with cytoskeletal organization, microtubule dynamics, neurite outgrowth, and the formation, polymerization and quantity of microtubules. In addition, 22 proteins were more highly expressed within the developing CST in comparison to other developing white matter tracts of the spinal cord of age-matched animals. Of these differentially expressed proteins, only one, stathmin 1 (a protein known to be involved in microtubule dynamics), was both highly enriched in the developing CST and relatively sparse in other developing descending and ascending spinal tracts. Immunohistochemical analyses of the developing rat spinal cord and fetal human brain stem confirmed the enriched pattern of stathmin expression along the developing CST, and in vitro growth assays of rat corticospinal neurons showed a reduced length of neurite processes in response to pharmacological perturbation of stathmin activity. Combined, these findings suggest that stathmin activity may modulate axonal growth during development of the corticospinal projection, and reinforces the notion that microtubule dynamics could play an important role in the generation and regeneration of the CST. © 2015 Elsevier Inc.


PubMed | University of Zagreb, Croatian Institute For Brain Research Kaikaila@Helsinkifi, Croatian Institute for Brain Research and University of Helsinki
Type: Journal Article | Journal: Cerebral cortex (New York, N.Y. : 1991) | Year: 2015

Work on rodents demonstrated that steep upregulation of KCC2, a neuron-specific Cl


PubMed | Keele University, Croatian Institute for Brain Research and Andrews University
Type: | Journal: Molecular and cellular neurosciences | Year: 2015

Understanding the intra- and extracellular proteins involved in the development of the corticospinal tract (CST) may offer insights into how the pathway could be regenerated following traumatic spinal cord injury. Currently, however, little is known about the proteome of the developing corticospinal system. The present study, therefore, has used quantitative proteomics and bioinformatics to detail the protein profile of the rat CST during its formation in the spinal cord. This analysis identified increased expression of 65 proteins during the early ingrowth of corticospinal axons into the spinal cord, and 36 proteins at the period of heightened CST growth. A majority of these proteins were involved in cellular assembly and organization, with annotations being most highly associated with cytoskeletal organization, microtubule dynamics, neurite outgrowth, and the formation, polymerization and quantity of microtubules. In addition, 22 proteins were more highly expressed within the developing CST in comparison to other developing white matter tracts of the spinal cord of age-matched animals. Of these differentially expressed proteins, only one, stathmin 1 (a protein known to be involved in microtubule dynamics), was both highly enriched in the developing CST and relatively sparse in other developing descending and ascending spinal tracts. Immunohistochemical analyses of the developing rat spinal cord and fetal human brain stem confirmed the enriched pattern of stathmin expression along the developing CST, and in vitro growth assays of rat corticospinal neurons showed a reduced length of neurite processes in response to pharmacological perturbation of stathmin activity. Combined, these findings suggest that stathmin activity may modulate axonal growth during development of the corticospinal projection, and reinforces the notion that microtubule dynamics could play an important role in the generation and regeneration of the CST.


Boban M.,University of Zagreb | Malojcic B.,University of Zagreb | Mimica N.,University of Zagreb | Mimica N.,University Psychiatric Hospital | And 5 more authors.
Dementia and Geriatric Cognitive Disorders | Year: 2012

Aim: The aim of this study was standardization and validation of the Mini-Mental State Examination (MMSE) in the general Croatian aging population. Methods: Three-hundred and forty-four participants underwent the MMSE test, 217 cognitively healthy subjects without neurological and psychiatric disorders and 127 patients with mild cognitive impairment (MCI) or dementia. Results: The optimal cutoff point for screening of the general Croatian population (cognitively healthy vs. MCI and dementia) is 26/27; in the Croatian population aged ≥65 years, the cutoff point is 24/25, whereas for screening of highly educated persons (≥14 years of education) aged ≥65 years a higher cutoff point should be used (26/27). Conclusions: MMSE results when standardized and validated in a certain population might better contribute to recognition of the individuals at risk that should be directed to dementia outpatient clinics. Copyright © 2012 S. Karger AG, Basel.


Vladusic T.,University of Zagreb | Hrascan R.,University of Zagreb | Vrhovac I.,University of Zagreb | Kruslin B.,University of Zagreb | And 5 more authors.
Pathology Research and Practice | Year: 2010

Human testicular germ cell tumors (TGCTs) are histologically heterogenous neoplasms with a variable malignant potential. Two main groups of germ cell tumors occur in men: seminomas and nonseminomas. In the present study, a set of four tumor suppressor genes was investigated in testicular cancers. CDH1, APC, p53, and nm23-H1 genes were tested for loss of heterozygosity (LOH). Thirty-eight testicular germ cell tumors (17 seminomas and 21 nonseminomas) were analyzed by PCR using restriction fragment length polymorphism or the dinucleotide/tetranucleotide repeat polymorphism method. An allelic loss of p53 at exon 4 was detected in five nonseminomas, whereas LOH of p53 at intron 6 occurred in one of the seminoma and two of the nonseminoma samples. Allelic losses of the APC gene were present in three seminomas and one nonseminoma, whereas one seminoma and three nonseminomas showed LOH of CDH1. The analysis of allelic losses showed no common structural genetic alterations in tumor tissues, although a different pattern of LOH was observed between the two main histological groups of TGCTs. © 2009 Elsevier GmbH. All rights reserved.


Slade N.,Ruder Boskovic Institute | Zoric A.,Ruder Boskovic Institute | Horvat B.,French Institute of Health and Medical Research | Vuksic M.,Croatian Institute for Brain Research | And 2 more authors.
Immunobiology | Year: 2015

The aim of this study was to find out how NF-κB and Smad-mediated signaling influenced the expression of astrogliogenic versus neurogenic markers of brain development in U4C cells which were either enriched (Tg Jak-1) or deprived in Jak-1 molecule (Jak-1 KO). Genetically modified U4C cells were transfected with NF-kB reporter plasmid in order to follow its activation when cells were cotransfected with different combinations of Smads constructs.In wild type cells no significant activation of NF-κB was observed while genetically modified cells exhibited somewhat different pattern of NF-κB activation depending on the Smad constructs combination used. The absence of NF-κB activation in Jak-1 transgenic cells transfected with Smad-1 plus Smad-3 was accompanied by the appearance of apoptotic cells as revealed by DAPI staining. Smad-1 expression was undetectable in Jak-1 transgenic cells and was downregulated in wild type cells upon transfection with Smad-2. The absence of p65 nuclear translocation in Smad-2 transfected cells and the presence of Smad-4 in nucleus of the same cells indicates dichotomy in NF-κB and Smads mediated signaling pathways.The significance of this study is that helps to elucidate the point of collaboration among three different signaling pathways - Jak-1 mediated cytokine signaling, NF-κB and Smads mediated pathways. © 2014 Elsevier GmbH.


Grosic V.,Psychiatric Hospital Sveti Ivan | Grosic P.F.,University of Zagreb | Kalember P.,Croatian Institute for Brain Research | Kalember P.,University of Zagreb | And 6 more authors.
Neuropsychiatric Disease and Treatment | Year: 2014

Purpose: To investigate the correlates of a clinical therapeutic response by using the parameters measured by proton magnetic resonance spectroscopy after the administration of atypical antipsychotics. Patients and methods: Twenty-five antipsychotic-naïve first-episode patients with schizophrenia were monitored for 12 months. The patients were evaluated using 1H magnetic resonance spectroscopy in the dorsolateral prefrontal cortex and Positive and Negative Syndrome Scale, Clinical Global Impression Scale of Severity, Tower of London - Drexel University, Letter-Number Span Test, Trail Making Test A, and Personal and Social Performance Scale. They were administered atypical antipsychotics, starting with quetiapine. In the absence of a therapeutic response, another antipsychotic was introduced. Results: After 12 study months, the N-acetylaspartate/creatine (NAA/Cr) level did not significantly change at the whole-group level. Additional analysis revealed a significant rise in the NAA/Cr level in the study group that stayed on the same antipsychotic throughout the study course (P=0.008) and a significant drop in NAA/Cr in the study group that switched antipsychotics (P=0.005). On the whole-group level, no significant correlations between NAA/Cr values and other scores were found at either baseline or after 12 study months. Conclusion: One-year treatment with atypical antipsychotics administered to antipsychotic-naïve patients didn't result in a significant rise in the NAA/Cr ratio. However, a significant rise was witnessed in the study group in which a satisfactory therapeutic response had been achieved with a single antipsychotic administration. © 2014 Grošić et al.


Bosnjak J.,University of Zagreb | Mikula I.,University of Zagreb | Miskov S.,University of Zagreb | Budisic M.,University of Zagreb | And 2 more authors.
Wiener Klinische Wochenschrift | Year: 2012

Aims: The functional effect of the pineal gland cyst is difficult to evaluate with visual field examination. The aim of this study is to investigate the usefulness of visual evoked potentials (VEP) in patients with pineal gland cyst due to the possible compression on the visual pathway. Subjects and methods: Black-and-white pattern-reversal checkerboard VEP were recorded in 75 patients (50 females and 25 males, mean age 26.3 ± 15.7 and 25.6 ± 17.6 years, respectively) with pineal gland cyst detected on magnetic resonance of the brain (subject group) and 75 age and sex-matched control subjects (control group). Amplitudes and P100 latencies were collected and later grouped as: (1) normal finding; (2) prechiasmal; (3) prechiasmal and postchiasmal; and (4) postchiasmal dysfunction. Results: P100 latencies differed significantly between subject (110.26 ± 13.23 ms) and control group (101.01 ± 5.36 ms) (p < 0.01). Findings of the VEP differed significantly (p < 0.01) between subject and control group, mainly due to the postchiasmal dysfunction frequency in subject group. Findings of the VEP differed significantly according to the pineal gland cyst volume (p = 0.006) with more frequent postchiasmal dysfunctions among subjects with larger cysts. Postchiasmal changes were significantly more frequent in patients with described compression of the cyst on surrounding brain structures (p = 0.016). Conclusions: Postchiasmal dysfunction on VEP can be seen in patients with pineal gland cyst, mostly with larger cysts and with compression of the cyst on surrounding brain structures. VEP serve as a useful method to determine functional impairment of the visual pathway in patients with pineal gland cyst. © Springer-Verlag Wien 2012.


PubMed | University of Zagreb, Ruder Boskovic Institute, Croatian Institute for Brain Research and French Institute of Health and Medical Research
Type: Journal Article | Journal: Immunobiology | Year: 2014

The aim of this study was to find out how NF-B and Smad-mediated signaling influenced the expression of astrogliogenic versus neurogenic markers of brain development in U4C cells which were either enriched (Tg Jak-1) or deprived in Jak-1 molecule (Jak-1 KO). Genetically modified U4C cells were transfected with NF-kB reporter plasmid in order to follow its activation when cells were cotransfected with different combinations of Smads constructs. In wild type cells no significant activation of NF-B was observed while genetically modified cells exhibited somewhat different pattern of NF-B activation depending on the Smad constructs combination used. The absence of NF-B activation in Jak-1 transgenic cells transfected with Smad-1 plus Smad-3 was accompanied by the appearance of apoptotic cells as revealed by DAPI staining. Smad-1 expression was undetectable in Jak-1 transgenic cells and was downregulated in wild type cells upon transfection with Smad-2. The absence of p65 nuclear translocation in Smad-2 transfected cells and the presence of Smad-4 in nucleus of the same cells indicates dichotomy in NF-B and Smads mediated signaling pathways. The significance of this study is that helps to elucidate the point of collaboration among three different signaling pathways - Jak-1 mediated cytokine signaling, NF-B and Smads mediated pathways.

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