The use of the Internet in the teaching of mathematics

Diplomová práce je zaměřena na problematiku využívání informačních a komunikačních technologií ve vzdělávání. Zabývá se zejména využitím internetu při výuce matematiky na základních a středních školách. Cílem práce je shrnout některé poznatky týkající se informačních a komunikačních technologií ve vzdělávání a jejich vlivu na vzdělávací proces, uvést různé možnosti využití internetu v práci učitele matematiky a formou dotazníku zmapovat současný stav využívání internetu učiteli matematiky. Práce informuje o zajímavých internetových matematických zdrojích a uvádí příklady jejich konkrétního využití v domácí přípravě učitele i při výuce matematiky. Jedná se o zdroje, které by měly přispívat ke zlepšení efektivity vyučování matematiky. Práce ukazuje, že internet je přínosným zdrojem, který může zlepšit kvalitu matematické výuky a vzdělávání.The thesis focuses on information and communication technologies in education. It mainly deals with the use of the Internet in the teaching of mathematics at lower and upper secondary schools. The aim of the thesis is to summarize some information concerning the present knowledge of information and communication technologies in education and their impact on the process of education, to present various ways of using the Internet by maths teachers and to conduct an enquiry into the present state of the use of the Internet by maths teachers at lower and upper secondary schools. The thesis provides information about interesting mathematical Internet resources and examples of their use in a teacher's preparation for lessons and in mathematics lessons, too. The resources mentioned in the work should contribute to the improvement in the efficiency of the teaching of mathematics. The thesis shows that the Internet is a beneficial source which could improve the quality of the teaching of mathematics and education in general.Katedra matematiky a didaktiky matematikyFaculty of EducationPedagogická fakult

Uneven distribution of potential triplex sequences in the human genome. In silico study using the R/Bioconductor package triplex.

Eukaryotic genomes are rich in sequences capable of forming non-B DNA structures. These structures are expected to play important roles in natural regulatory processes at levels above those of individual genes, such as whole genome dynamics or chromatin organization, as well as in processes leading to the loss of these functions, such as cancer development. Recently, a number of authors have mapped the occurrence of potential quadruplex sequences in the human genome and found them to be associated with promoters. In this paper, we set out to map the distribution and characteristics of potential triplex-forming sequences in human genome DNA sequences. Using the R/Bioconductor package {\it triplex}, we found these sequences to be excluded from exons, while present mostly in a small number of repetitive sequence classes, especially short sequence tandem repeats (microsatellites), Alu and combined elements, such as SVA. We also introduce a novel way of classifying potential triplex sequences, using a lexicographically minimal rotation of the most frequent k-mer to assign class membership automatically. Members of such classes typically have different propensities to form parallel and antiparallel intramolecular triplexes (H-DNA). We observed an interesting pattern, where the predicted third strands of antiparallel H-DNA were much less likely to contain a deletion against their duplex structural counterpart than were their parallel versions

P53 binds preferentially to non-B DNA structures formed by the pyrimidine-rich strands of GaA·TTC trinucleotide repeats associated with Friedreich’s ataxia

Expansions of trinucleotide repeats (TNRs) are associated with genetic disorders such as Friedreich’s ataxia. The tumor suppressor p53 is a central regulator of cell fate in response to different types of insults. Sequence and structure-selective modes of DNA recognition are among the main attributes of p53 protein. The focus of this work was analysis of the p53 structure-selective recognition of TNRs associated with human neurodegenerative diseases. Here, we studied binding of full length p53 and several deletion variants to TNRs folded into DNA hairpins or loops. We demonstrate that p53 binds to all studied non-B DNA structures, with a preference for non-B DNA structures formed by pyrimidine (Py) rich strands. Using deletion mutants, we determined the C-terminal DNA binding domain of p53 to be crucial for recognition of such non-B DNA structures. We also observed that p53 in vitro prefers binding to the Py-rich strand over the purine (Pu) rich strand in non-B DNA substrates formed by sequence derived from the first intron of the frataxin gene. The binding of p53 to this region was confirmed using chromatin immunoprecipitation in human Friedreich’s ataxia fibroblast and adenocarcinoma cells. Altogether these observations provide further evidence that p53 binds to TNRs’ non-B DNA structures

Modulation of gene expression in U251 glioblastoma cells by binding of mutant p53 R273H to intronic and intergenic sequences

Missense point mutations in the TP53 gene are frequent genetic alterations in human tumor tissue and cell lines derived thereof. Mutant p53 (mutp53) proteins have lost sequence-specific DNA binding, but have retained the ability to interact in a structure-selective manner with non-B DNA and to act as regulators of transcription. To identify functional binding sites of mutp53, we established a small library of genomic sequences bound by p53R273H in U251 human glioblastoma cells using chromatin immunoprecipitation (ChIP). Mutp53 binding to isolated DNA fragments confirmed the specificity of the ChIP. The mutp53 bound DNA sequences are rich in repetitive DNA elements, which are dispersed over non-coding DNA regions. Stable down-regulation of mutp53 expression strongly suggested that mutp53 binding to genomic DNA is functional. We identified the PPARGC1A and FRMD5 genes as p53R273H targets regulated by binding to intronic and intra-genic sequences. We propose a model that attributes the oncogenic functions of mutp53 to its ability to interact with intronic and intergenic non-B DNA sequences and modulate gene transcription via re-organization of chromatin

The use of the Internet in the teaching of mathematics

The thesis focuses on information and communication technologies in education. It mainly deals with the use of the Internet in the teaching of mathematics at lower and upper secondary schools. The aim of the thesis is to summarize some information concerning the present knowledge of information and communication technologies in education and their impact on the process of education, to present various ways of using the Internet by maths teachers and to conduct an enquiry into the present state of the use of the Internet by maths teachers at lower and upper secondary schools. The thesis provides information about interesting mathematical Internet resources and examples of their use in a teacher's preparation for lessons and in mathematics lessons, too. The resources mentioned in the work should contribute to the improvement in the efficiency of the teaching of mathematics. The thesis shows that the Internet is a beneficial source which could improve the quality of the teaching of mathematics and education in general

Differential Salt-Induced Dissociation of the p53 Protein Complexes with Circular and Linear Plasmid DNA Substrates Suggest Involvement of a Sliding Mechanism

A study of the effects of salt conditions on the association and dissociation of wild type p53 with different ~3 kbp long plasmid DNA substrates (supercoiled, relaxed circular and linear, containing or lacking a specific p53 binding site, p53CON) using immunoprecipitation at magnetic beads is presented. Salt concentrations above 200 mM strongly affected association of the p53 protein to any plasmid DNA substrate. Strikingly different behavior was observed when dissociation of pre-formed p53-DNA complexes in increased salt concentrations was studied. While contribution from the p53CON to the stability of the p53-DNA complexes was detected between 100 and 170 mM KCl, p53 complexes with circular DNAs (but not linear) exhibited considerable resistance towards salt treatment for KCl concentrations as high as 2 M provided that the p53 basic C-terminal DNA binding site (CTDBS) was available for DNA binding. On the contrary, when the CTDBS was blocked by antibody used for immunoprecipitation, all p53-DNA complexes were completely dissociated from the p53 protein in KCl concentrations ≥200 mM under the same conditions. These observations suggest: (a) different ways for association and dissociation of the p53-DNA complexes in the presence of the CTDBS; and (b) a critical role for a sliding mechanism, mediated by the C-terminal domain, in the dissociation process

Carrot populations in France and Spain host a complex virome rich in previously uncharacterized viruses

High-throughput sequencing (HTS) has proven a powerful tool to uncover the virome of cultivated and wild plants and offers the opportunity to study virus movements across the agroecological interface. The carrot model consisting of cultivated (Daucus carota ssp. sativus) and wild carrot (Daucus carota ssp. carota) populations, is particularly interesting with respect to comparisons of virus communities due to the low genetic barrier to virus flow since both population types belong to the same plant species. Using a highly purified double-stranded RNA-based HTS approach, we analyzed on a large scale the virome of 45 carrot populations including cultivated, wild and off-type carrots (carrots growing within the field and likely representing hybrids between cultivated and wild carrots) in France and six additional carrot populations from central Spain. Globally, we identified a very rich virome comprising 45 viruses of which 25 are novel or tentatively novel. Most of the identified novel viruses showed preferential associations with wild carrots, either occurring exclusively in wild populations or infecting only a small proportion of cultivated populations, indicating the role of wild carrots as reservoir of viral diversity. The carrot virome proved particularly rich in viruses involved in complex mutual interdependencies for aphid transmission such as poleroviruses, umbraviruses and associated satellites, which can be the basis for further investigations of synergistic or antagonistic virus-vector-host relationships.Horizon 2020 Marie Skłodowska-Curie Actions Innovative Training Network (H2020 MSCA-60 ITN)INEXTVIR GA 81354

Carrot populations in France and Spain host a complex virome rich in previously uncharacterized viruses

High-throughput sequencing (HTS) has proven a powerful tool to uncover the virome of cultivated and wild plants and offers the opportunity to study virus movements across the agroecological interface. The carrot model consisting of cultivated (Daucus carota ssp. sativus) and wild carrot (Daucus carota ssp. carota) populations, is particularly interesting with respect to comparisons of virus communities due to the low genetic barrier to virus flow since both population types belong to the same plant species. Using a highly purified double-stranded RNA-based HTS approach, we analyzed on a large scale the virome of 45 carrot populations including cultivated, wild and off-type carrots (carrots growing within the field and likely representing hybrids between cultivated and wild carrots) in France and six additional carrot populations from central Spain. Globally, we identified a very rich virome comprising 45 viruses of which 25 are novel or tentatively novel. Most of the identified novel viruses showed preferential associations with wild carrots, either occurring exclusively in wild populations or infecting only a small proportion of cultivated populations, indicating the role of wild carrots as reservoir of viral diversity. The carrot virome proved particularly rich in viruses involved in complex mutual interdependencies for aphid transmission such as poleroviruses, umbraviruses and associated satellites, which can be the basis for further investigations of synergistic or antagonistic virus-vector-host relationships

Role of tumor suppressor p53 domains in selective binding to supercoiled DNA

We showed previously that bacterially expressed full-length human wild-type p53b(1–393) binds selectively to supercoiled (sc)DNA in sc/linear DNA competition experiments, a process we termed supercoil-selective (SCS) binding. Using p53 deletion mutants and pBluescript scDNA (lacking the p53 recognition sequence) at native superhelix density we demonstrate here that the p53 C-terminal domain (amino acids 347–382) and a p53 oligomeric state are important for SCS binding. Monomeric p53(361–393) protein (lacking the p53 tetramerization domain, amino acids 325–356) did not exhibit SCS binding while both dimeric mutant p53(319– 393)L344A and fusion protein GCN4–p53(347–393) were effective in SCS binding. Supershifting of p53(320–393)–scDNA complexes with monoclonal antibodies revealed that the amino acid region 375–378, constituting the epitope of the Bp53-10.1 antibody, plays a role in binding of the p53(320–393) protein to scDNA. Using electron microscopy we observed p53–scDNA nucleoprotein filaments produced by all the C-terminal proteins that displayed SCS binding in the gel electrophoresis experiments; no filaments formed with the monomeric p53(361– 393) protein. We propose a model according to which two DNA duplexes are compacted into p53–scDNA filaments and discuss a role for filament formation in recombination