30 research outputs found
Chromosome territory position of chromosome X and 11 is non-random and cell-type specific in mouse cells of B cell lineage
The interphase nucleus of a cell is organized into non-random, cell-type specific
chromosome territolies (CTs). In lymphocytes, a gene-density correlated radial arrangement has
been identified, with gene-dense CTs located more in the nuclear interior and gene-poor CTs
located towards the periphery. However, other factors such as chromosome size, transcription
and interactions of the nuclear membrane and matrix are also involved in the final ammgement of
CTs within a nucleus. In this project, the CTs of chromosome 11 and X were studied in five
different cell types of mouse B cell lineage: diploid preB cells, primary B cells of
[T38HxBALB/c]N wild-type mice, primary B cells of [T38HxBALB/c]N with rcpT(X;l1) mice,
primary B cells of BALB/c mice and a Wehi 231 mouse B lymphoma line. These two
chromosomes have not been studied before in the mouse. 3D FISH experiments that labeled the
CTs of chromosome 11 and X with chromosome-specific paints were carried out for each cell
type. The karyotype regarding these two chromosomes and specificity of the chromosome paints
was first confim1ed through 2D FISH experiments. The radial distance from the centre of each
CT to the centre of the nucleus was measured lIsing AxioVision 4.8 software. The results show a
non-random, statistically significant and cell-type specific nuclear distribution of these two
chromosomes. Altered nuclear positions of translocation chromosomes in normal healthy mice
and as a result of tumorigenesis were observed in the primary B cells of [T38HxBALB/c]N with
rcpT(X;l1) mice and in the Wehi 231 mouse B lymphoma line, respectively.October 201
Three-dimensional nuclear organization in cancer: examples from mouse plasmacytoma and human neuroblastoma
Three-dimensional (3D) nuclear organization is the study of the spatial distribution of nuclear contents and components. Aspects of nuclear organization that are examined in this thesis were chromosome territories, chromosomal sub-regions and telomeres.
We began by examining nuclear disorganization in a transgenic mouse model. Fast-onset PCTs, compared to slow-onset PCTs and wild-type mice, had higher numbers of telomeres and telomeric aggregates per cell, more short telomeres, an altered distribution of telomeres throughout the nucleus, and a larger nuclear volume (P < 0.0001).
We further examined this in a human context, looking for changes in nuclear organization in MYCN amplified compared to non-amplified neuroblastomas. Using dual-colored FISH and MYCN immunofluorescence on 16 neuroblastoma tissue samples, the unbalanced gain of 17q was found to be associated with high MYCN expression, no gain of 17q to be associated with medium MYCN expression, and numerical gain of chromosome 17 to be associated with low expression (P < 0.0001). The nuclear location of 17q also correlated with chromosome 17 copy number status. Telomere Q-FISH on 74 neuroblastoma tissue samples identified three tumor subgroups based on the measured telomere parameters, which represented unique levels of telomere dysfunction and genomic instability. Subgroups with higher levels of telomere dysfunction had more telomeres and telomeric aggregates per cell, and greater percentages of short and long telomeres (P < 0.0001); these subgroups also were associated with poor prognostic clinical features (P < 0.001).
This thesis illustrates the significance of multiple parameters of 3D nuclear organization in both PCT and neuroblastoma. The changes observed in the nuclear architecture of these cancers reflect increased telomere-mediated genomic instability that is driven by MYC and MYCN. Furthermore, the differences between aggressive and less-aggressive forms of the tumors suggest 3D nuclear organization could be used as a novel biomarker in cancer.May 201
Selected Telomere Length Changes and Aberrant Three-dimensional Nuclear Telomere Organization during Fast-Onset Mouse Plasmacytomas
Mouse plasmacytoma (PCT) can develop within 45 days when induced by a v-abl/myc replication-deficient retrovirus. This fast-onset PCT development is always associated with trisomy of cytoband E2 of mouse chromosome 11 (11E2). Trisomy of 11E2 was identified as the sole aberration in all fast-onset mouse PCTs in [T38HxBALB/c]N congenic mice, with a reciprocal translocation between chromosome X and 11 (rcpT(X;11)) (Genes Cancer 2010;1:847–858). Using this mouse model, we have now examined the overall and individual telomere lengths in fast-onset PCTs compared with normal B cells using two-dimensional and three-dimensional quantitative fluorescent in situ hybridization of telomeres. We found fast-onset PCTs to have a significantly different three-dimensional telomere profile, compared with primary B cells of wild-type littermates with and without rcpT(X;11) (P < .0001 and P = .006, respectively). Our data also indicate for primary PCT cells, from the above mouse strain, that the translocation chromosome carrying 11E2 is the only chromosome with telomere lengthening (P = 4 x 10-16). This trend is not seen for T(X;11) in primary B cells of control [T38HxBALB/c]N mice with the rcpT(X;11). This finding supports the concept of individual telomere lengthening of chromosomes that are functionally important for the tumorigenic process
Членські внески у споживчому товаристві : порядок сплати та правові наслідки несплати
The scientific article is devoted to the study of the legal regime and features of payment of membership fees in non-entrepreneurial societies. The specifics of the legal regulation of the payment of membership fees, concepts and types of membership fees according to the legislation of Ukraine have been analyzed. The author of the scientific work also analyzed the doctrinal approaches developed in this field of scientific research.The author of the article analyzes the provisions on the payment of membership fees, as well as the agreement on the payment of membership fees. The specifics of paying membership fees based on the contract were determined, and the legal consequences of non-payment were analyzed.Current civil legislation in the field of non-entrepreneurial legal entities uses a dispositive approach to the procedure for paying membership fees, in connection with which their payment can be determined in the charters of the consumer association and on the basis of an agreement on the payment of membership fees. The legal nature of the agreement on the payment of membership fees is manifested in the fact that it is a bilateral accession agreement.The types of share contributions in consumer societies are the initial contribution, mandatory share and additional share contributions, targeted contributions. Contributions can be the following objects: money, property, property rights, land plots, contributions are not subject to taxation, but cooperative payments are taxed in accordance with dividends. The legal consequence of non-payment of share contributions is exclusion from the consumer association. The recovery of unpaid contributions can be enforced through the use of a judicial form of protection, a similar situation with share payments, cooperative payments and dividends. As a general rule, payment of membership fees is voluntary, however, in some cases, membership fees may be collected in a compulsory manner.Наукова стаття присвячена аналізу проблематики сплати членських внесків у споживчих товариствах та визначенні їх правового режиму. Відповідно до положень чинного цивільного законодавства та доктринальних напрацювань, які склалися у даній сфері, авторка статті проаналізувала порядок сплати, склад та види членських внесків, а також правові наслідки несплати членських внесків.Чинне цивільне законодавство у сфері непідприємницьких юридичних осіб використовує диспозитивний підхід до порядку сплати членських внесків, у зв’язку з чим їх сплата може визначатися у статутах громадських об’єднань та на підставі договору про сплату членських внесків. Правова природа договору про сплату членських внесків проявляється у тому, що двохсторонній договор приєднання. Основними видами пайових внесків у споживчих товариствах є вступний внесок, обов’язковий пайовий та додатковий пайовий внески, цільові внески. Внеском можуть бути такі об’єкти: гроші, майно, майнові права, земельні ділянки. Внески не підлягають оподаткуванню, однак кооперативні виплати оподатковуються відповідно до дивідендів.У випадку несплати внесків може бути використаний такий спосіб відповідальності, як виключення із громадського об’єднання.За загальним правилом, сплата членських внесків є добровільною, проте, в деяких випадках членські внески можуть стягуватися у примусовому порядку
Identification of Neuroblastoma Subgroups Based on Three-Dimensional Telomere Organization
AbstractUsing 3D telomere quantitative fluorescence in situ hybridization, we determined the 3D telomere organization of 74 neuroblastoma tissue samples. Hierarchical cluster analysis of the measured telomere parameters identified three subgroups from our patient cohort. These subgroups have unique telomere profiles based on telomere length and nuclear architecture. Subgroups with higher levels of telomere dysfunction were comprised of tumors with greater numbers of telomeres, telomeric aggregates, and short telomeres (P<.0001). Tumors with greater telomere dysfunction were associated with unfavorable tumor characteristics (greater age at diagnosis, unfavorable histology, higher stage of disease, MYCN amplification, and higher MYCN expression) and poor prognostic risk (P<.001). Subgroups with greater telomere dysfunction also had higher intratumor heterogeneity. MYCN overexpression in two neuroblastoma cell lines with constitutively low MYCN expression induced changes in their telomere profile that were consistent with increased telomere dysfunction; this illustrates a functional relationship between MYCN and 3D telomere organization. This study demonstrates the ability to classify neuroblastomas based on the level of telomere dysfunction, which is a novel approach for this cancer
Членські та корпоративні права у непідприємницькому товаристві: співвідношення понять
The article is devoted to the theoretical and legal analysis of membership and corporate rights in non-business societies as legal entities of corporate type.The author of the article analyzed the concepts of understanding the essence of membership relations in non-business societies, in particular the concept of distinguishing between the concepts of «membership rights» and «corporate rights» and the concept of identifying the studied concepts.It is determined that the heterogeneity of the legal nature of non-business companies determines the fact of emergence of corporate rights in some of them, and in some - membership rights.The peculiarities of membership and corporate rights in non-business societies are outlined: membership rights in public associations as non-business societies do not have property content, and therefore are not identical to corporate rights; membership rights in consumer and service cooperatives as non-business associations may be endowed with property content and are identical to the concept of corporate rights; emphasis is placed on the tendency to expand the content of membership rights in non-business associations.Emphasis is placed on the need to take into account the peculiarities of membership rights, which are formed in certain types of non-business associations in improving the relevant legislation in this area.Стаття присвячена теоретико-правовому аналізу членських та корпоративних прав у непідприємницьких товариствах як юридичних особах корпоративного типу.Автор статті проаналізував концепції щодо розуміння сутності членських відносин у непідприємницьких товариствах, зокрема концепцію щодо розмежування понять «членські права» та «корпоративні права» та концепцію щодо ототожнення досліджуваних понять. Визначено, що неоднорідність правової природи непідприємницьких товариств обумовлює факт виникнення в окремих з них корпоративних прав, а в окремих - членських прав. Окреслено особливості членських та корпоративних прав у непідприємницьких товариствах: членські права в громадських об’єднаннях як непідприємницьких товариствах не мають майнового змісту, а тому не є тотожними корпоративним правам; членські права в споживчих та обслуговуючих кооперативах як непідприємницьких товариствах можуть бути наділені майновим змістом і є тотожними до поняття корпоративних прав; наголошено на тенденції до розширення змісту членських прав у непідприємницьких товариствах.Наголошено на потребі врахування особливостей членських прав, що складаються у певних різновидах непідприємницьких товариств при удосконаленні профільного законодавства у цій сфері
Повернення через півстоліття. Відвідини родинної садиби Валеріяном Ревуцьким
The article is dedicated to Valerian Dmytrovych Revutsky, the son of the outstanding scientist-culturologist, folklorist, art critic Dmytro Mykolayovych Revutsky and the nephew of the classic composer Levko Mykolayovych Revutsky. It deals with the arrival of Mr. Valerian in the Homeland half a century after the beginning of emigration in 1943. The scientist lived for more than 100 years, about 60 of them in Vancouver, Canada. He owns a number of books on the development of the Ukrainian theater and outstanding actors of the national stage with the selection of the central figure – Les Kurbas. V. Revutsky wrote numerous articles for the Encyclopedia of Ukrainian Studies, the English-language edition of the Encyclopedia of Ukraine, scientific collections and journals (over 400), gave public lectures, and so on. After the proclamation of Ukraine’s independence in 1991, his art studies actively flowed into the general development of Ukrainian theatrical culture as a foreign member of the National Academy of Arts of Ukraine. Despite his advanced age, V. Revutsky visitedUkraine several times (1992, 1993, 1996 and 1997), visited Kyiv, Lviv, Kharkiv, Pryluky, the village of Irzhavets and Kachanivka. The author of the article filmed these visits of the scientist with his family to Ukraine and presented to the conference participants several fragments from a video disc (а copy of the CD is stored in the Memorial Estate-Museum of LM Revutsky in Irzhavets).Стаття присвячена Валеріяну Дмитровичу Ревуцькому – сину видатного вченого-культуролога, фольклориста, лисенкознавця Дмитра Миколайовича Ревуцького та небожу композитора-класика Левка Миколайовича Ревуцького. У ній йдеться про приїзд п. Валеріяна на Батьківщину через півстоліття після початку еміграції в 1943 році. Вчений прожив понад 100 років, з них близько 60 у Канаді, м. Ванкувер. Йому належить низка книжокз розвитку українського театру та видатних акторів національної сцени з виокремленням центральної постаті – Лесь Курбас. В. Ревуцький написавчисленні статті до «Енциклопедії українознавства», англомовного видання «Енциклопедії України», наукових збірників та журналів (понад 400),виступав з публічними лекціями тощо. Після проголошення незалежності України 1991 року його мистецтвознавча діяльність активно влилася у річище загального розвитку української театральної культури як зарубіжного члена Національної академії мистецтв України. Незважаючи на похилий вік, В. Ревуцький кілька разів відвідав Україну (1992, 1993, 1996 і 1997), побував у Києві, Львові, Харкові, Прилуках, селі Іржавець і Качанівці.Автор статті відзняв ці візити вченого з родиною до України та представив учасникам конференції кілька фрагментів з диску відеофільму (копія CD зберігається у Меморіальній садибі-музеї Л. М. Ревуцького в Іржавці)
Changes in Nuclear Orientation Patterns of Chromosome 11 during Mouse Plasmacytoma Development
AbstractStudying changes in nuclear architecture is a unique approach toward the understanding of nuclear remodeling during tumor development. One aspect of nuclear architecture is the orientation of chromosomes in the three-dimensional nuclear space. We studied mouse chromosome 11 in lymphocytes of [T38HxBALB/c]N mice with a reciprocal translocation between chromosome X and 11 (T38HT(X;11)) exhibiting a long chromosome T(11;X) and a short chromosome T(X;11) and in fast-onset plasmacytomas (PCTs) induced in the same strain. We determined the three-dimensional orientation of chromosome 11 using a mouse chromosome 11 specific multicolor banding probe. We also examined the nuclear position of the small translocation chromosome T(X;11) which contains cytoband 11E2 and parts of E1. Chromosomes can point either with their centromeric or with their telomeric end toward the nuclear center or periphery, or their position is found in parallel to the nuclear border. In T38HT(X;11) nuclei, the most frequently observed orientation pattern was with both chromosomes 11 in parallel to the nuclear border (“PP”). PCT cells showed nuclei with two or more copies of chromosome 11. In PCTs, the most frequent orientation pattern was with one chromosome in parallel and the other pointing with its centromeric end toward the nuclear periphery (“CP”). There is a significant difference between the orientation patterns observed in T38HT(X;11) and in PCT nuclei (P < .0001)
Distinct nuclear orientation patterns for mouse chromosome 11 in normal B lymphocytes
Background Characterizing the nuclear orientation of chromosomes in the three-dimensional (3D) nucleus by multicolor banding (mBANDing) is a new approach towards understanding nuclear organization of chromosome territories. An mBANDing paint is composed of multiple overlapping subchromosomal probes that represent different regions of a single chromosome. In this study, we used it for the analysis of chromosome orientation in 3D interphase nuclei. We determined whether the nuclear orientation of the two chromosome 11 homologs was random or preferential, and if it was conserved between diploid mouse Pre B lymphocytes of BALB/c origin and primary B lymphocytes of congenic [T38HxBALB/c]N wild-type mice. The chromosome orientation was assessed visually and through a semi-automated quantitative analysis of the radial and angular orientation patterns observed in both B cell types. Results Our data indicate that there are different preferential patterns of chromosome 11 orientation, which are not significantly different between both mouse cell types (p?>?0.05). In the most common case for both cell types, both copies of chromosome 11 were oriented in parallel with the nuclear border. The second most common pattern in both types of B lymphocytes was with one homolog of chromosome 11 positioned with its telomeric end towards the nuclear center and with its centromeric end towards the periphery, while the other chromosome 11 was found parallel with the nuclear border. In addition to these two most common orientations present in approximately 50% of nuclei from each cell type, other orientations were observed at lower frequencies. Conclusions We conclude that there are probabilistic, non-random orientation patterns for mouse chromosome 11 in the mouse B lymphocytes we investigated (p?<?0.0001).ImPhys/Imaging PhysicsApplied Science
