G. I. Chulkov: problemy nauainoj biografii pisatelja s 1879 g. do Oktjabraiskoj revoljucii (na materiale neizdannoj semejnoj perepiski 1901-1938 gg.)

My thesis is a monographic work devoted to the reconstruction of the biography of the writer Georgy Ivanovich Chulkov (1879-1939), one of the protagonists of the Russian literary scene in the first decades of the 20th century. Chulkov should be considered as a rather singular figure whose production, despite the multiplicity and originality that characterize it, is often unfairly neglected, if not forgotten: his name rarely appears among the greatest exponents of the Silver Age. Chulkov was a poet, novelist, playwright, literary critic, biographer and, above all, a tireless organizer of Russian literary life of that time. His interests ranged from the meticulous study of Russian classics (in particular Pushkin and Dostoevsky) to that of the literary and cultural movements of the time, from poetry to narrative, from literary criticism to journalism. Only in the last few decades of the past century, within the Russian academic community, Chulkov's work has become the object of numerous reissues and publications of previously unpublished works. Within the studies about the Silver Age of Russian culture, however, Chulkov's life and work have never been thoroughly investigated and reconstructed as a whole and, therefore, there is no monographic work devoted to the scientific study of his biography. Our intent is to overcome this gap by starting to create a first scientific biography of this writer. This work is divided into three parts. The first part is a review of the studies on the formulation and theorization of the genre of scientific biography, in which particular attention is paid to the reception of this genre within the Russian academic community. Here are also presented the main theoretical aspects concerning a scientific work of biographical writing. These principles are then applied to the particular context of the reconstruction of biographical events in Chulkov's life. The corpus of texts that formed the primary documentary base used for writing his biography is widely described. Among these texts needs to be highlighted the correspondence between Chulkov and his wife, as it is a biographical source of great significance, that allows a complete and reliable reconstruction of facts and circumstances only superficially known. The second part presents the reconstruction of Chulkov's biography. The time span that has been examined is from 1879, the writer's birth year, to the October Revolution, which, however, does not correspond to the year of the writer's death, happened in 1939. This choice has been dictated by the fact that the 1920's represent, in the writer's life, a sort of watershed. As a result of these events, in fact, he radically changed his way of being and perceiving the surrounding world, leaving behind his revolutionary past. The events' historical extent drove him back to the principles of orthodox Christianity, in full harmony with his spiritual evolution (caused, in part, by the loss of his son Vladimir in 1920). The biography consists of eight chapters: the first four cover respectively the period of childhood, school education, university studies up to the Siberian confinement; the fifth chapter introduces a transitional period during which the writer was forced to live under close surveillance in Nizhny Novgorod. The sixth and seventh chapters illustrate the so-called "St Petersburg period", which focuses on the mystical anarchism's theory, formulated and promoted by the writer between 1905 and 1906 and which sparked a burning controversy on the country's literary scene, and on its following re-elaboration through the conception of "realistic symbolism". The last chapter is devoted to the "years of travelling", that compelled the writer to spend much of those years abroad. It also includes Chulkov's experience as a soldier at the front during World War I, where he spent about a year as a medical assistant. The dissertation was carried out on the basis of several writer's unpublished materials, conserved in the main literary archives in Moscow. These materials constitute the third part of this work and they are: the correspondence between Chulkov and his wife (over 1400 sheets), transcribed and supplied with a short textual preamble that provides most of the autographs' fundamental details, and a few among the most complete autobiographies and biographies found among the writer's personal documents

Cell Cycle-dependent Metabolism of Pyrimidine Deoxynucleoside Triphosphates in CEM Cells

We incorporated 3H-labeled thymidine, deoxycytidine, or cytidine into dNTPs and DNA of exponentially growing CEM cells. G1 and S phase cells were separated by centrifugal elutriation, and the size and specific activity of dNTP pools were determined to study the cell cycle-dependent regulation of specific dNTP synthesizing enzymes in their metabolic context. With [3H]thymidine, we confirm the earlier demonstrated S phase specificity of thymidine kinase. Incorporation of radioactivity from [5-3H]deoxycytidine into dCTP occurred almost exclusively in G1 cells. During S phase, de novo synthesis by ribonucleotide reductase was switched on, resulting in a 70-fold dilution of [3H]dCTP, confirming that ribonucleotide reductase is an S phase-specific enzyme, whereas deoxycytidine kinase is not. [5-3H]Cytidine appeared in dCTP almost to the same extent in G1 as in S phase, despite the S phase specificity of ribonucleotide reductase. During S phase, DNA replication greatly increased the turnover of dCTP, requiring a corresponding increase in ribonucleotide reductase activity. During G1, the enzyme maintained activity to provide dNTPs for DNA repair and mitochondrial DNA synthesis. The poor incorporation of isotope from deoxycytidine into DNA earlier led to the suggestion that the nucleoside is used only for DNA repair (Xu, Y-Z., Peng, H., and Plunkett, W. (1995) J. Biol. Chem. 270, 631-637). The poor phosphorylation of deoxycytidine in S phase provides a better explanation

Human mitochondrial 5'-deoxyribonucleotidase. Overproduction in cultured cells and functional aspects.

Deoxynucleoside triphosphates (dNTPs) used for mitochondrial DNA replication are mainly formed by phosphorylation of deoxynucleosides imported into mitochondria from the cytosol. We earlier obtained evidence for a mitochondrial 5′-nucleotidase (dNT2) with a pronounced specificity for dUMP and dTMP and suggested that the enzyme protects mitochondrial DNA replication from excess dTTP. In humans, accumulation of dTTP causes a mitochondrial genetic disease. We now establish that dNT2 in vivo indeed is located in mitochondria. The native enzyme shows the same substrate specificity and affinity for inhibitors as the recombinant dNT2. We constructed ponasterone-inducible cell lines overproducing dNT2 with and without the green fluorescent protein (GFP) linked to its C terminus. The fusion protein occurred in mitochondria mostly in an inactive truncated form, with only a short C-terminal fragment of dNT2 linked to GFP. No truncation occurred when dNT2 and GFP were not linked. The cell mitochondria then contained a large excess of active dNT2 with or without the mitochondrial presequence. After removal of ponasterone overproduced dNT2 disappeared only slowly from the cells, whereas dNT2-mRNA was lost rapidly. Overproduction of dNT2 did not lead to an increased excretion of pyrimidine deoxyribonucleosides, in contrast to overproduction of the corresponding cytosolic deoxynucleotidase, suggesting that the mitochondrial enzyme does not affect overall cellular deoxynucleotide turnover

Mouse cytosolic and mitochondrial deoxyribonucleotidases: cDNA cloning of the mitochondrial enzyme, gene structures, chromosomal mapping and comparison with the human orthologs

Abstract Two of the five known mammalian 5 0 -nucleotidases show a preference for the dephosphorylation of deoxynucleoside-5 0 -phosphates. One is a cytoplasmic enzyme (dNT-1), the other occurs in mitochondria (dNT-2). The human mitochondrial enzyme, recently discovered and cloned by us, is encoded by a nuclear gene located on chromosome 17 p11.2 in the critical region deleted in the Smith-Magenis syndrome (SMS), a genetic disease of unknown etiology. Looking for a model system to study the possible involvement of dNT-2 in the disease, we have cloned the cDNA of the mouse ortholog. The deduced protein sequence is 84% identical to the human ortholog, has a very basic NH 2 -terminus, a very high calculated probability of being imported into mitochondria and contains the DXDXT/V motif conserved among nucleotidases. Expression in Escherichia coli of the predicted processed form of the protein produced an active deoxyribonucleotidase. We also identified in genomic sequences present in the data base the structures of the murine genes for the cytosolic and mitochondrial deoxyribonucleotidases (Nt5c and Nt5m). PAC clones for the two loci were isolated from a library and used for chromosomal localization by fluorescent in situ hybridization. Both genes map on chromosome 11: Nt5c at 11E and Nt5m at 11B, demonstrating the presence of the dNT-2 locus in the mouse shaker-2 critical region, the murine counterpart of the human SMS region. We performed pair-wise dot-plot and PIP (percent identity plot) analyses of mouse and human deoxyribonucleotidase genes, and found a strong conservation that extends also to some intronic sequences of possible regulatory significance.

Clinical efficacy of Enzyme Replacement Therapy in paediatric Hunter patients, an independent study of 3.5 years

BACKGROUND: Hunter Syndrome is an X-linked lysosomal storage disorder due to the deficit of iduronate 2-sulfatase, an enzyme catalysing the degradation of the glycosaminoglycans (GAG) dermatan- and heparan-sulfate. Treatment of the disease is mainly performed by Enzyme Replacement Therapy (ERT) with idursulfase, in use since 2006. Clinical efficacy of ERT has been monitored mainly by the Hunter Outcome Survey (HOS) while very few independent studies have been so far conducted. The present study is a 3.5-years independent follow-up of 27 Hunter patients, starting ERT between 1.6 and 27 years of age, with the primary aim to evaluate efficacy of the therapy started at an early age (<12 years). METHODS: In this study, we evaluated: urinary GAG content, hepato/splenomegaly, heart valvulopathies, otorinolaryngological symptoms, joint range of motion, growth, distance covered in the 6-minute walk test, neurological involvement. For data analysis, the 27 patients were divided into three groups according to the age at start of ERT: ≤5 years, >5 and ≤ 12 years and > 12 years. Patients were analysed both as 3 separate groups and also as one group; in addition, the 20 patients who started ERT up to 12 years of age were analysed as one group. Finally, patients presenting a “severe” phenotype were compared with “attenuated” ones. RESULTS: Data analysis revealed a statistically significant reduction of the urinary GAG in patients ≤5 years and ≤ 12 years and of the hepatomegaly in the group aged >5 and ≤ 12 years. Although other clinical signs improved in some of the patients monitored, statistical analysis of their variation did not reveal any significant changes following enzyme administration. The evaluation of ERT efficacy in relation to the severity of the disease evidenced slightly higher improvements as for hepatomegaly, splenomegaly, otological disorders and adenotonsillar hypertrophy in severe vs attenuated patients. CONCLUSIONS: Although the present protocol of idursulfase administration may result efficacious in delaying the MPS II somatic disease progression at some extent, in this study we observed that several signs and symptoms did not improve during the therapy. Therefore, a strict monitoring of the efficacy obtained in the patients under ERT is becoming mandatory for clinical, ethical and economic reasons. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-014-0129-1) contains supplementary material, which is available to authorized users

Ultra diffuse galaxies in the Hydra I cluster from the LEWIS Project: Phase-Space distribution and globular cluster richness

Although ultra diffuse galaxies (UDGs) are found in large numbers in clusters of galaxies, the role of the cluster environment in shaping their low surface brightness and large sizes is still uncertain. Here we examine a sample of UDGs in the Hydra I cluster (D = 51 Mpc) with new radial velocities obtained as part of the LEWIS (Looking into the faintest with MUSE) project using VLT/MUSE data. Using a phase-space, or infall diagnostic, diagram we compare the UDGs to other known galaxies in the Hydra I cluster and to UDGs in other clusters. The UDGs, along with the bulk of regular Hydra I galaxies, have low relative velocities and are located near the cluster core, and thus consistent with very early infall into the cluster. Combining with literature data, we do not find the expected trend of GC-rich UDGs associated with earlier infall times. This result suggests that quenching mechanisms other than cluster infall should be further considered, e.g. quenching by strong feedback or in cosmic sheets and filaments. Tidal stripping of GCs in the cluster environment also warrants further modelling.Comment: 6 pages, 2 figures, MNRAS, 525, 9

Looking into the faintEst WIth MUSE (LEWIS): on the nature of ultra-diffuse galaxies in the Hydra-I cluster.I. Project description and preliminary results

Looking into the faintEst WIth MUSE (LEWIS) is an ESO large observing programme aimed at obtaining the first homogeneous integral-field spectroscopic survey of 30 extremely low-surface brightness (LSB) galaxies in the Hydra I cluster of galaxies, with MUSE at ESO-VLT. The majority of LSB galaxies in the sample (22 in total) are ultra-diffuse galaxies (UDGs). The distribution of systemic velocities Vsys ranges between 2317 km/s and 5198 km/s and is centred on the mean velocity of Hydra I (Vsys = 3683 $\pm$ 46 km/s). Considering the mean velocity and the velocity dispersion of the cluster, 17 out of 20 targets are confirmed cluster members. To assess the quality of the data and demonstrate the feasibility of the science goals, we report the preliminary results obtained for one of the sample galaxies, UDG11. For this target, we derived the stellar kinematics, including the 2-dimensional maps of line-of-sight velocity and velocity dispersion, constrained age and metallicity, and studied the globular cluster (GC) population hosted by the UDG. Results are compared with the available measurements for UDGs and dwarf galaxies in literature. By fitting the stacked spectrum inside one effective radius, we find that UDG11 has a velocity dispersion $\sigma = 20 \pm 8$ km/s, it is old ($10\pm1$ Gyr), metal-poor ([M/H]=-1.17$\pm$0.11 dex) and has a total dynamical mass-to-light ratio M$/L_V\sim 14$, comparable to those observed for classical dwarf galaxies. The spatially resolved stellar kinematics maps suggest that UDG11 does not show a significant velocity gradient along either major or minor photometric axes. We find two GCs kinematically associated with UDG11. The estimated total number of GCs in UDG11, corrected for the spectroscopic completeness limit, is $N_{GC}= 5.9^{+2.2}_ {-1.8}$, which corresponds to a GC specific frequency of $S_N = 8.4^{+3.2}_{-2.7}$.Comment: Accepted for publication in Astronomy and Astrophysic