Wyniki wyszukiwania

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Epigenetic mechanisms of gene expression regulation in neurological diseases

100%

Gos M.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Neurological diseases are a heterogenous group of disorders that are related to alterations in nervous system function. The genetic background of neurological diseases is heterogenous and may include chromosomal aberrations, specific gene mutations and epigenetic defects. This review is aimed at presenting of selected diseases that are associated with different epigenetic alterations. The imprinting defects on chromosome 15 are the cause of Prader-Willi and Angelman syndromes that both are characterized by intellectual disability, developmental delay and specific behavioral phenotype. Besides the imprinting defect, these diseases can also be caused by deletion of chromosome 15 or uniparental disomy. Aberrant epigenetic regulation is also specific for Fragile X syndrome that is caused by expansion of CGG repeats in the FMR1 gene that leads to global methylation of the promoter region and repression of FMR1 transcription. A number of neurological diseases, mainly associated with intellectual impairment, may be caused by mutations in genes encoding proteins involved in epigenetic regulation. The number of such diseases is rapidly growing thanks to the implementation of genomic sequencing for the identification of their molecular causes. One of the best known diseases linked to defects in epigenetic modifiers is Rett syndrome caused by a mutation in the MECP2 gene or its variant - Rett-like syndrome caused by a mutation in CDKL5 or FOXG1 genes. As the epigenetic signature is potentially reversible, much attention is focused on possible therapies with drugs that influence DNA or histone modifications. This is especially important in the case of neurological disorders in which epigenetic changes are observed as the effect of the disease.

2

Splicing mutations in human genetic disorders: examples, detection, and confirmation

63%

Abramowicz A., Gos M.

Journal of Applied Genetics

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2018

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tom 59

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nr 3

3

Zmiany szaty roslinnej torfowiska weglanowego Sawin po jego pelnym zagospodarowaniu rolniczym

63%

Fijalkowski D., Gos M.

Annales Universitatis Mariae Curie-Sklodowska. Sectio C, Biologia

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1995

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tom 50

91-111

4

Correction to: Splicing mutations in human genetic disorders: examples, detection, and confirmation

63%

Abramowicz A., Gos M.

Journal of Applied Genetics

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2019

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tom 60

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nr 2

5

Plonowanie i jakosc ziarna pszenicy jarej uprawianej w zmianowaniach o roznym jej udziale

51%

Wozniak A., Gontarz D., Staniszewski M., Gos M.

Biuletyn Instytutu Hodowli i Aklimatyzacji Roślin

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2006

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nr 242

45-55

6

Metody molekularne w ocenie czynników rokowniczych w przewlekłej białaczce limfocytowej/chłoniaku limfocytarnym (CLL/SLL)

51%

Gos M., Grygalewicz B., Pieńkowska B., Malecki M.

Diagnostyka Laboratoryjna

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2008

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tom 44

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nr 4

7

Identification of mutations in the NF2 gene in Polish patients with neurofibromatosis type 2

51%

Laniewski-Wollk M., Gos M., Koziarski A., Szpecht-Potocka A.

Journal of Applied Genetics

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2008

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tom 49

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nr 3

297-300

Point mutation and loss of heterozygosity (LOH) analyses were performed in 12 Polish patients with a classic symptom of NF2 - bilateral vestibular schwannomas (BVS). In 5 patients (41.7%), germline mutations were found in the NF2 gene: 2 previously reported substitutions (c.592C>T and c.52C>T) and 3 novel mutations (c,1001_1002insG, c,1029_1030insCC, c.774_778dupGAATG). In addition, LOH analysis of 30 tumour samples from 10 patients revealed a molecular basis of NF2 in 3 patients (25%) that did not have any germline mutation. The molecular defects in sporadic cases of NF2 are still being discussed.

8

Craniosynostosis as a clinical and diagnostic problem: molecular pathology and genetic counseling

51%

Kutkowska-Kazmierczak A., Gos M., Obersztyn E.

Journal of Applied Genetics

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2018

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tom 59

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nr 2

9

Mutations in the methyl CpG binding protein 2 (MECP2) gene as a cause of the Rett syndrome

51%

Abramowicz A., Gos M., Bal J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

The methyl CpG binding protein 2 (MECP2), protein that binds to methylated DNA sequences and represses the expression of specific genes, is essential for normal function of mature nerve cells. The protein is encoded by MECP2 gene and its mutations are responsible for approximately 90% of all Rett syndrome (RTT) cases. RTT is a neurodevelopmental disorder that affects mainly girls. Its characteristic features include arrested psychomotor development (6–18 months), congenital impairment, loss of speech, characteristic stereotypical movements, regression of gained skills and other neuropsychiatric abnormalities. Nineteen patients with primary clinical diagnosis of RTT were referred for molecular examination. The analysis of MECP2 gene included direct sequencing of exons 2–4 and deletion/ duplication analysis using MLPA method. In nine patients we have found seven known point mutations, including three nonsense substitutions in four individuals (p.R168X, p.R255X, and p.R270X in 2 cases) and three missense changes leading to amino acids substitutions in the methyl-binding domain (p.R133C, p.K135E, p.T158M) or in the transcriptional repression domain (p.R306C in 2 cases). In three other patients, a partial deletion of MECP2 was found, including a deletion of exons 3 and 4 (encompassing 2 to 67 kb) and two different deletions of exon 4, encompassing 44 bp and 1 to 7.3 kb, respectively. Together, we were able to confirm the clinical diagnosis of Rett syndrome in 12 cases. The significant presence of large deletions encompassing entire exons suggests that the MLPA analysis should be performed as an important part of the molecular diagnosis in Rett syndrome.

10

Rola przejścia epitelialno-mezenchymalnego w progresji nowotworu

51%

Gos M., Miloszewska J., Przybyszewska M.

Postępy Biochemii

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2009

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tom 55

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nr 2

11

Loop G of the GABAA receptor orthosteric binding site is involved in the final stages of channel gating

51%

Brodzki M., Michalowski M. A., Gos M., Mozrzymas J. W.

Acta Neurobiologiae Experimentalis

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2019

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tom 79

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nr Suppl.1

INTRODUCTION: Inhibition of neuronal activity is shaped primarily by GABAA receptors. Agonist binding site (BS) at the β+/α‑ intersubunit interface is composed of 7 loops (A‑C from β and D‑G from α subunit), and the Loop G has been reported to play a major role in receptor activation, however the exact mechanism is not clear. α1F45 residue at Loop G has been shown to be engaged in receptor activation despite not directly contacting the agonist, and is well positioned for interactions with other crucial BS residues. Since this loop spans from the BS to the extracellular-transmembrane domain interface, it might have an important role in transferring energy of BS conformational transitions to the pore region. AIM(S): This study aims to reveal the role of loop G in distinct steps of receptor activation. METHOD(S): We used rapid agonist application to elicit macroscopic responses and single-channel recordings of GABA-evoked currents for wild-type (WT) and mutated (α1F45C/L/K/G) receptors. Model simulations of macroscopic and single-channel activity and in silico structural analysis have been performed. RESULTS: Mutated receptors showed a different kinetic profile of macroscopic currents (except α1F45L) with faster deactivation (α1F45C/K/G) and impaired desensitization (α1F45C/G). Single‑channel currents showed profound differences in all mutants; that is, closures were prolonged, openings were shortened, and Popen within bursts was reduced. Model simulations revealed changes primarily in opening/closing transitions. The homology model of WT showed loop G energy minimum at the α1F45 position, underlining its role in loop stability. In α1F45G/K mutants, this minimum declined. In α1F45G mutant, it can be attributed to the BS aromatic box disruption and α1F45K substitution could impair the GABA – α1R66 interaction. CONCLUSIONS: Mutations of the α1F45 residue in loop G of the BS affects final gating stages. This indicates the role of loop G in linking binding and gating processes. FINANCIAL SUPPORT: Supported by NCN grant UMO‑2015/18/A/NZ1/00395.

12

Correction to: Craniosynostosis as a clinical and diagnostic problem: molecular pathology and genetic counseling

51%

Kutkowska-Kazmierczak A., Gos M., Obersztyn E.

Journal of Applied Genetics

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2018

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tom 59

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nr 2

13

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Forecasting daily meteorological time series using ARIMA and regression models

51%

Murat M., Malinowska I., Gos M., Krzyszczak J.

International Agrophysics

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2018

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tom 32

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nr 2

14

Mutation incidence in folate metabolism genes and regulatory genes in Polish families with neural tube defects

51%

Gos M., Sliwerska E., Szpecht-Potocka A.

Journal of Applied Genetics

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2004

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tom 45

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nr 3

15

CT substitution in the promoter region of CYP17 gene and prostate cancer risk

45%

Gos M., Sadowska M., Grzegrzolka M., Demkow T., Janik P.

Acta Biochimica Polonica

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2003

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tom 50

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nr Supplement 1

16

The role of FNIII/10 and FNIII/10 RGD fibronectin ragments in contant inhibition of C3H10T1/2 cells

45%

Miloszewska J., Gos M., Trembacz H., Przybyszewska M., Janik P.

Acta Biochimica Polonica

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2003

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tom 50

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nr Supplement 1

17

Epigenetic mechanisms of gene expression regulation in neurological diseases

45%

Gos M., Rzonca S., Szopa D., Abramowicz A., Bal J.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Neurological diseases, including intellectual disability (ID), can be caused by disturbances in epigenetic regulation of specific genes that encode proteins necessary for appropriate central nervous system functioning. The “epigenetically caused” diseases can be due to the imprinting defects formed during germinal cells development or gained throughout life as a somatic changes. They can also result from abnormal functioning of transcriptional machinery caused by mutations in genes coding for specific proteins. Two most classical examples of disease caused by imprinting defect in germinal cells are Prader-Willi and Angelman syndromes, both characterized by ID and developmental delay. Both these diseases are caused by altered epigenetic regulation of genes localized on chromosome 15 (region q11–q13) that can be due to chromosome deletion or uniparental disomy. The other neurological disease that is related to abnormal epigenetic regulation is Fragile X syndrome characterized by ID and specific behavior. Almost all disease cases are due to the expansion of CGG repeat (>200) in the 5’UTR of FMR1 gene that leads to promoter methylation and lack of FMRP protein that is indispensable for neuron development and signaling. The example of neurological “epigenetic diseases” caused by altered transcriptional regulation is Rett syndrome caused by the mutation presence in MECP2 gene or its variant – Rett-like syndrome caused by the mutation in CDKL5 gene. Both these diseases are characterized by ID and childhood epilepsy. Herein, we present our experience from the research and diagnosis of above mentioned disorders in the context of neurological pathways altered by improper epigenetic regulation.

18

Cancer stem cells from mouse sarcoma cell line- L1: preliminary results

45%

Miloszewska J., Gos M., Przybyszewska M., Szaniawska B., Trembacz H.

Acta Biochimica Polonica

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2006

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tom 53

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nr Supplement 1

19

Metastatic capacity stimulated by cancer cells cultivation in non-adhesive conditions

45%

Gos M., Miloszewska J., Trembacz H., Przybyszewska M., Janik P.

Acta Biochimica Polonica

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2006

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tom 53

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nr Supplement 1

20

Znaczenie cystometrii przepływowej w diagnostyce białaczki z dużych ziarnistych limfocytów T

39%

Blachnio K., Rymkiewicz G., Gos M., Sadowski T., Borawska A., Ptaszynski K.

Diagnostyka Laboratoryjna

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2009

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tom 45

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nr 2

Ograniczanie wyników

Epigenetic mechanisms of gene expression regulation in neurological diseases

Splicing mutations in human genetic disorders: examples, detection, and confirmation

Zmiany szaty roslinnej torfowiska weglanowego Sawin po jego pelnym zagospodarowaniu rolniczym

Correction to: Splicing mutations in human genetic disorders: examples, detection, and confirmation

Plonowanie i jakosc ziarna pszenicy jarej uprawianej w zmianowaniach o roznym jej udziale

Metody molekularne w ocenie czynników rokowniczych w przewlekłej białaczce limfocytowej/chłoniaku limfocytarnym (CLL/SLL)

Identification of mutations in the NF2 gene in Polish patients with neurofibromatosis type 2

Craniosynostosis as a clinical and diagnostic problem: molecular pathology and genetic counseling

Mutations in the methyl CpG binding protein 2 (MECP2) gene as a cause of the Rett syndrome

Rola przejścia epitelialno-mezenchymalnego w progresji nowotworu

Loop G of the GABAA receptor orthosteric binding site is involved in the final stages of channel gating

Correction to: Craniosynostosis as a clinical and diagnostic problem: molecular pathology and genetic counseling

Forecasting daily meteorological time series using ARIMA and regression models

Mutation incidence in folate metabolism genes and regulatory genes in Polish families with neural tube defects

CT substitution in the promoter region of CYP17 gene and prostate cancer risk

The role of FNIII/10 and FNIII/10 RGD fibronectin ragments in contant inhibition of C3H10T1/2 cells

Epigenetic mechanisms of gene expression regulation in neurological diseases

Cancer stem cells from mouse sarcoma cell line- L1: preliminary results

Metastatic capacity stimulated by cancer cells cultivation in non-adhesive conditions

Znaczenie cystometrii przepływowej w diagnostyce białaczki z dużych ziarnistych limfocytów T