Subject Learning Options Analysis

In the article the author considers the problem of the reducingof number of surrendered individual works by educational subject.Analyzing the possible causes of this problem, the author of the workexplores the needs of age of the students, didactic principles, which aremainly used by the teacher in teaching practice. The author of thisarticle studies the impact of new technology on the thinking of youngpeople as well. At result of research the hypothesis of individual workdivision into smaller parts is proposed and tested. This article presentsthe results of testing this hypothesis.

Offer Opportunities of Levelling Online Courses for Latvia

Currently, all European countries, including Latvian, there is a decrease of students' mathematical knowledge. As a result, universities and high schools face the challenge of filling the knowledge in mathematics among students. This has resulted in increasing the level of knowledge disparity in study groups. And experience shows that many students need extra - levelling courses. One of solution of such courses would be a free on-line levelling courses

Kasvajaseoselise mutsiini-sarnase leukosialiini (CD43) funktsioonidest inimese kasvajarakkudes

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Kasvajates on rakud kaotanud kontrolli jagunemise üle, paljunedes valel ajal ja vales kohas sõltumata välistest signaalidest. Kasvajarakkude piiramatu jagunemine on tingitud kasvu ja ellujäämist soodustavate valkude ehk onkovalkude aktivatsioonist ning samaaegsest rakusurma reguleerivate valkude ehk tuumorsupressorite inaktivatsioonist. Kasvajaseoseliste valkude hulk kasvab pidevalt, kuid normaalse raku transformeerumine kasvajarakuks toimub tänu muutustele peamistes signaaliülekande radades, mis vastutavad raku surma ja kasvu eest. Seega on kasvajaseoseliste valkude identifitseerimine ja nende funktsioonide uurimine keskse tähtsusega vähivastaste ravistrateegiate väljatöötamisel. Käesolevas töös uuriti potentsiaalse onkovalgu leukosialiini (CD43) funktsioone inimese kasvajarakkudes. CD43 peeti pikka aega ainult vererakkudele omaseks pinnamolekuliks, kuid järjest enam vihjeid koguneb selle kohta, et CD43 võiks käituda soodustava faktorina mitte-verepäritolu kasvajate tekkes. Mitmed tööd on kirjeldanud kõrget CD43 taset erinevates kasvajarakuliinides ja -kudedes, sealhulgas käärsoolekasvajates. Samas ei ole CD43 leitud normaalsetest soolerakkudest. Samuti on näidatud CD43 seost erinevate signaaliradade komponentidega, mis rakkude elulemust või paljunemist mõjutavad. Antud töö tulemused viitavad, et koostöös tuntud onkovalgu β-kateniiniga soodustab CD43 rakkude ellujäämist ja kasvu. Paljude kasvajate üheks peamiseks tekkepõhjuseks on häired β-kateniini funktsioneerimises, mille tulemusena käivitab β-kateniin rakkude jagunemist stimuleerivate geenide avaldumist. Rakkudes, kus tuumorsupressorite rada on rikutud, võib suurenenud CD43 hulk β-kateniini signaaliraja kaudu viia rakkude kontrollimatu paljunemiseni, mis on aluseks kasvaja moodustumisele. Samas, CD43 ja β-kateniinist lähtuvad liigsed kasvusignaalid kutsuvad rakus esile surmaprotsessi, mis on peamine mehhanism kasvaja tekke takistamisel. Lisaks sellele vähendavad tuumorsupressorid omakorda CD43 hulka rakus. Kokkuvõttes näitavad töö tulemused uusimaid aspekte seoses CD43 võimega rakukasvu soodustada ning seeläbi kasvajat tekitada, ning varem kirjeldamata tagasisidet CD43 ja tuumorsupressorite talitluse vahel, mis võiks olla olulise tähtsusega kasvajate tekke vältimisel

In Vivo Characterization of the Activation and Interaction of the VanR-VanS Two-Component Regulatory System Controlling Glycopeptide Antibiotic Resistance in Two Related Streptomyces Species.

This is the author accepted manuscript. The final version is available from the American Society for Microbiology via http://dx.doi.org/10.1128/AAC.01367-15The VanR-VanS two-component system is responsible for inducing resistance to glycopeptide antibiotics in various bacteria. We have performed a comparative study of the VanR-VanS systems from two streptomyces strains, Streptomyces coelicolor and Streptomyces toyocaensis, to characterize how the two proteins cooperate to signal the presence of antibiotics and to define the functional nature of each protein in each strain background. The results indicate that the glycopeptide antibiotic inducer specificity is determined solely by the differences between the amino acid sequences of the VanR-VanS two-component systems present in each strain rather than by any inherent differences in general cell properties, including cell wall structure and biosynthesis. VanR of S. coelicolor (VanRsc) functioned with either sensor kinase partner, while VanR of S. toyocaensis (VanRst) functioned only with its cognate partner, S. toyocaensis VanS (VanSst). In contrast to VanRsc, which is known to be capable of phosphorylation by acetylphosphate, VanRst could not be activated in vivo independently of a VanS sensor kinase. A series of amino acid sequence modifications changing residues in the N-terminal receiver (REC) domain of VanRst to the corresponding residues present in VanRsc failed to create a protein capable of being activated by VanS of S. coelicolor (VanSsc), which suggests that interaction of the response regulator with its cognate sensor kinase may require a region more extended than the REC domain. A T69S amino acid substitution in the REC domain of VanRst produced a strain exhibiting weak constitutive resistance, indicating that this particular amino acid may play a key role for VanS-independent phosphorylation in the response regulator protein.This work was supported by funding from the Medical Research Council, UK (G0700141) and the Royal Society, UK (516002.K5877/ROG). the American Society for Microbiology

Microcoria due to first duplication of 13q32.1 including the GPR180 gene and maternal mosaicism

Congenital microcoria (MCOR) is an eye anomaly characterized by a pupil with diameter below 2 mm, and is caused by underdevelopment or absence of the dilator muscle of the pupil. Two types have been described: a recessive, syndromic (Pierson syndrome OMIM 609049) and a dominant, isolated form (MCOR syndrome OMIM 156600). Fares-Taie and colleagues described inherited microdeletions in chromosome band 13q32.1 segregating with dominant microcoria in several families. The GPR180 gene is located within the smallest commonly deleted region and encodes a G protein-coupled receptor involved in smooth muscle cells growth. We here describe a patient with isolated, non-syndromic MCOR. The patient presented with a blue iris and small pupils, non-reactive to cycloplegic agents. Her mother had a milder ocular phenotype, namely a blue iris with hypoplastic crypts and mild myopia. We present a detailed clinical examination and follow up. DNA from the index patient was analyzed for the presence of chromosomal imbalances using molecular karyotyping. The genetic test revealed a small duplication of chromosome band 13q32.1. The duplication affected a 289 kb region, encompassing 11 genes including GPR180. Interestingly, the patient displays only MCOR in contrast to patients with the reciprocal deletion who present with MCOR and iridocorneal angle dysgenesis. This genetic anomaly was inherited from the mother who carries the duplication in mosaic form, which should be considered when offering genetic counselling. In summary, we describe the first 13q32.1 duplication encompassing GPR180 associated with MCOR

Three cases of molecularly confirmed Knobloch syndrome

Background: Knobloch syndrome (OMIM 267750) is a rare autosomal recessive disorder due to genetic defects in the COL18A1 gene. The triad of high myopia, occipital defect, vitreoretinal degeneration has been described as pathognomonic for this condition. Patients with Knobloch syndrome have also extraocular problems as brain and kidney malformations. High genetic and phenotypic variation has been reported in the affected patients. Materials and Methods: Here we provide detailed clinical description of 3 individuals with Knobloch syndrome. Ocular examination and fundus imaging have been performed. Detailed information about systemic conditions has been provided. Results: Mutations in COL18A1 were identified in all three patients. Patient 1 had congenital hip dislocation and patient 2 had renal atrophy, cardiac insufficiency and difficult skin healing. Conclusions: With this report we add to the clinical and genetic knowledge of this rare condition

Microduplication of 4p16.3 due to an unbalanced translocation resulting in a mild phenotype

With the widespread clinical use of comparative genomic hybridization chromosomal microarray technology, several previously unidentified clinically significant submicroscopic chromosome abnormalities have been discovered. Specifically, there have been reports of clinically significant microduplications found in regions of known microdeletion syndromes. In general, these microduplications have distinct features from those described in the corresponding microdeletion syndromes. We present a 5½-year-old patient with normal growth, borderline normal IQ, borderline hypertelorism, and speech and language delay who was found to have a submicroscopic 2.3 Mb terminal duplication involving the two proposed Wolf–Hirschhorn syndrome (WHS) critical regions at chromosome 4p16.3. This duplication was the result of a maternally inherited reciprocal translocation involving the breakpoints 4p16.3 and 17q25.3. Our patient's features are distinct from those described in WHS and are not as severe as those described in partial trisomy 4p. There are two other patients in the medical literature with 4p16.3 microduplications of similar size also involving the WHS critical regions. Our patient shows clinical overlap with these two patients, although overall her features are milder than what has been previously described. Our patient's features expand the knowledge of the clinical phenotype of a 4p16.3 microduplication and highlight the need for further information about it. © 2011 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83462/1/33916_ftp.pd

The majority of autosomal recessive nanophthalmos and posterior microphthalmia can be attributed to biallelic sequence and structural variants in MFRP and PRSS56

This study aimed to genetically and clinically characterize a unique cohort of 25 individuals from 21 unrelated families with autosomal recessive nanophthalmos (NNO) and posterior microphthalmia (MCOP) from diferent ethnicities. An ophthalmological assessment in all families was followed by targeted MFRP and PRSS56 testing in 20 families and whole-genome sequencing in one family. Three families underwent homozygosity mapping using SNP arrays. Eight distinct MFRP mutations were found in 10/21 families (47.6%), fve of which are novel including a deletion spanning the 5′ untranslated region and the frst coding part of exon 1. Most cases harbored homozygous mutations (8/10), while a compound heterozygous and a monoallelic genotype were identifed in the remaining ones (2/10). Six distinct PRSS56 mutations were found in 9/21 (42.9%) families, three of which are novel. Similarly, homozygous mutations were found in all but one, leaving 2/21 families (9.5%) without a molecular diagnosis. Clinically, all patients had reduced visual acuity, hyperopia, short axial length and crowded optic discs. Retinitis pigmentosa was observed in 5/10 (50%) of the MFRP group, papillomacular folds in 12/19 (63.2%) of MCOP and in 3/6 (50%) of NNO cases. A considerable phenotypic variability was observed, with no clear genotype-phenotype correlations. Overall, our study represents the largest NNO and MCOP cohort reported to date and provides a genetic diagnosis in 19/21 families (90.5%), including the frst MFRP genomic rearrangement, ofering opportunities for gene-based therapies in MFRP-associated disease. Finally, our study underscores the importance of sequence and copy number analysis of the MFRP and PRSS56 genes in MCOP and NNO