Six-dimensional Davidson potential as a dynamical symmetry of the symplectic Interacting Vector Boson Model

A six-dimensional Davidson potential, introduced within the framework of the Interacting Vector Boson Model (IVBM), is used to describe nuclei that exhibit transitional spectra between the purely rotational and vibrational limits of the theory. The results are shown to relate to a new dynamical symmetry that starts with the $Sp(12,R) \supset SU(1,1) \times SO(6)$ reduction. Exact solutions for the eigenstates of the model Hamiltonian in the basis defined by a convenient subgroup chain of SO(6) are obtained. A comparison of the theoretical results with experimental data for heavy nuclei with transitional spectra illustrates the applicability of the theory.Comment: 9 pages, 4 figure

Energy Systematics of Low-lying Collective States within the Framework of the Interacting Vector Boson Model

In a new application of the algebraic Interacting Vector Boson Model (IVBM), we exploit the reduction of its Sp(12,R) dynamical symmetry group to Sp(4,R) x SO(3), which defines basis states with fixed values of the angular momentum L. The relationship of the latter to $U(6) \subset U(3)x U(2), which is the rotational limit of the model, means the energy distribution of collective states with fixed angular momentum can be studied. Results for low-lying spectra of rare-earth nuclei show that the energies of collective positive parity states with L=0,2,4,6... lie on second order curves with respect to the number of collective phonons n or vector bosons N=4n out of which the states are built. The analysis of this behavior leads to insight regarding the common nature of collective states, tracking vibrational as well as rotational features.Comment: 8 pages, 5 figures, 4 table

Evaluation of topotecan and 10-hydroxycamptothecin on Toxoplasma gondii: Implications on baseline DNA damage and repair efficiency

Toxoplasma gondii is an obligate intracellular parasite in the phylum Apicomplexa that causes toxoplasmosis in humans and animals worldwide. Despite its prevalence, there is currently no effective vaccine or treatment for chronic infection. Although there are therapies against the acute stage, prolonged use is toxic and poorly tolerated. This study aims to explore the potential of repurposing topotecan and 10-hydroxycamptothecin (HCPT) as drugs producing double strand breaks (DSBs) in T. gondii. DSBs are mainly repaired by Homologous Recombination Repair (HRR) and Non-Homologous End Joining (NHEJ). Two T. gondii strains, RHΔHXGPRT and RHΔKU80, were used to compare the drug's effects on parasites. RHΔHXGPRT parasites may use both HRR and NHEJ pathways but RHΔKU80 lacks the KU80 protein needed for NHEJ, leaving only the HRR pathway. Here we demonstrate that topotecan and HCPT, both topoisomerase I venoms, affected parasite replication in a concentration-dependent manner. Moreover, variations in fluorescence intensity measurements for the H2A.X phosphorylation mark (γH2A.X), an indicator of DNA damage, were observed in intracellular parasites under drug treatment conditions. Interestingly, intracellular replicative parasites without drug treatment show a strong positive staining for γH2A.X, suggesting inherent DNA damage. Extracellular (non-replicating) parasites did not exhibit γH2A.X staining, indicating that the basal level of DNA damage is likely to be associated with replicative stress. A high rate of DNA replication stress possibly prompted the evolution of an efficient repair machinery in the parasite, making it an attractive target. Our findings show that topoisomerase 1 venoms are effective antiparasitics blocking T. gondii replication.Fil: Cristaldi, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Saldarriaga Cartagena, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Ganuza, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Sullivan, William J.. Indiana University School Of Medicine; Estados UnidosFil: Angel, Sergio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Vanagas, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentin

Emerging Therapeutic Targets Against Toxoplasma gondii: Update on DNA Repair Response Inhibitors and Genotoxic Drugs

Toxoplasma gondii is the causative agent of toxoplasmosis in animals and humans. This infection is transmitted to humans through oocysts released in the feces of the felines into the environment or by ingestion of undercooked meat. This implies that toxoplasmosis is a zoonotic disease and T. gondii is a foodborne pathogen. In addition, chronic toxoplasmosis in goats and sheep is the cause of recurrent abortions with economic losses in the sector. It is also a health problem in pets such as cats and dogs. Although there are therapies against this infection in its acute stage, they are not able to permanently eliminate the parasite and sometimes they are not well tolerated. To develop better, safer drugs, we need to elucidate key aspects of the biology of T. gondii. In this review, we will discuss the importance of the homologous recombination repair (HRR) pathway in the parasite's lytic cycle and how components of these processes can be potential molecular targets for new drug development programs. In that sense, the effect of different DNA damage agents or HHR inhibitors on the growth and replication of T. gondii will be described. Multitarget drugs that were either associated with other targets or were part of general screenings are included in the list, providing a thorough revision of the drugs that can be tested in other scenarios.Fil: Ángel, Sergio Oscar. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; ArgentinaFil: Vanagas, Laura. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; ArgentinaFil: Ruiz, Diego Mario. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; ArgentinaFil: Cristaldi, Constanza. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; ArgentinaFil: Saldarriaga Cartagena, Ana María. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; ArgentinaFil: Sullivan, William J.. Indiana University. School of Medicine; Estados Unido

Canonical histone H2Ba and H2A.X dimerize in an opposite genomic localization to H2A.Z/H2B.Z dimers in Toxoplasma gondii

Histone H2Ba of Toxoplasma gondii was expressed as recombinant protein (rH2Ba) and used to generate antibody in mouse that is highly specific. Antibody recognizing rH2Ba detects a single band in tachyzoite lysate of the expected molecular weight (12kDa). By indirect immunofluorescence (IFA) in in vitro grown tachyzoites and bradyzoites, the signal was detected only in the parasite nucleus. The nucleosome composition of H2Ba was determined through co-immunoprecipitation assays. H2Ba was detected in the same immunocomplex as H2A.X, but not with H2A.Z. Through chromatin immunoprecipitation (ChIP) assays and qPCR, it was observed that H2Ba is preferentially located at promoters of inactive genes and silent regions, accompanying H2A.X and opposed to H2A.Z/H2B.Z dimers

The factors associated to psychosocial stress among general practitioners in Lithuania. Cross-sectional study

BACKGROUND: There are number of studies showing that general practice is one of the most stressful workplace among health care workers. Since Baltic States regained independence in 1990, the reform of the health care system took place in which new role and more responsibilities were allocated to general practitioners' in Lithuania. This study aimed to explore the psychosocial stress level among Lithuanian general practitioner's and examine the relationship between psychosocial stress and work characteristics. METHODS: The cross-sectional study of 300 Lithuanian General practitioners. Psychosocial stress was investigated with a questionnaire based on the Reeder scale. Job demands were investigated with the R. Karasek scale. The analysis included descriptive statistics; interrelationship analysis between characteristics and multivariate logistic regression to estimate odds ratios for each of the independent variables in the model. RESULTS: Response rate 66% (N = 197). Our study highlighted highest prevalence of psychosocial stress among widowed, single and female general practitioners. Lowest prevalence of psychosocial stress was among males and older age general practitioners. Psychosocial stress occurs when job demands are high and job decision latitude is low (χ(2 )= 18,9; p < 0,01). The multivariate analysis shows that high job demands (OR 4,128; CI 2,102–8,104; p < 0,001), patient load more than 18 patients per day (OR 5,863; CI 1,549–22,188; p < 0,01) and young age of GP's (OR 6,874; CI 1,292–36,582; p < 0,05) can be assigned as significant predictors for psychosocial stress. CONCLUSION: One half of respondents suffering from work related psychosocial stress. High psychological workload demands combined with low decision latitude has the greatest impact to stress caseness among GP's. High job demands, high patient load and young age of GP's can be assigned as significant predictors of psychosocial stress among GP's

Genome-wide localization of histone variants in Toxoplasma gondii implicates variant exchange in stage-specific gene expression.

BACKGROUND: Toxoplasma gondii is a protozoan parasite that differentiates from acute tachyzoite stages to latent bradyzoite forms in response to environmental cues that modify the epigenome. We studied the distribution of the histone variants CenH3, H3.3, H2A.X, H2A.Z and H2B.Z, by genome-wide chromatin immunoprecipitation to understand the role of variant histones in developmental transitions of T. gondii parasites. RESULTS: H3.3 and H2A.X were detected in telomere and telomere associated sequences, whereas H3.3, H2A.X and CenH3 were enriched in centromeres. Histones H2A.Z and H2B.Z colocalize with the transcriptional activation mark H3K4me3 in promoter regions surrounding the nucleosome-free region upstream of the transcription start site. The H2B.Z/H2A.Z histone pair also localizes to the gene bodies of genes that are silent but poised for activation, including bradyzoite stage-specific genes. The majority of H2A.X and H2A.Z/H2B.Z loci do not overlap, consistent with variant histones demarcating specific functional regions of chromatin. The extent of enrichment of H2A.Z/H2B.Z (and H3.3 and H2A.X) within the entire gene (5'UTR and gene body) reflects the timing of gene expression during the cell cycle, suggesting that dynamic turnover of H2B.Z/H2A.Z occurs during the tachyzoite cell cycle. Thus, the distribution of the variant histone H2A.Z/H2B.Z dimer defines active and developmentally silenced regions of the T. gondii epigenome including genes that are poised for expression. CONCLUSIONS: Histone variants mark functional regions of parasite genomes with the dynamic placement of the H2A.Z/H2B.Z dimer implicated as an evolutionarily conserved regulator of parasite and eukaryotic differentiation

Evaluation of ATM Kinase Inhibitor KU-55933 as Potential Anti-Toxoplasma gondii Agent

Toxoplasma gondii is an apicomplexan protozoan parasite with a complex life cycle composed of multiple stages that infect mammals and birds. Tachyzoites rapidly replicate within host cells to produce acute infection during which the parasite disseminates to tissues and organs. Highly replicative cells are subject to Double Strand Breaks (DSBs) by replication fork collapse and ATM, a member of the phosphatidylinositol 3-kinase (PI3K) family, is a key factor that initiates DNA repair and activates cell cycle checkpoints. Here we demonstrate that the treatment of intracellular tachyzoites with the PI3K inhibitor caffeine or ATM kinase-inhibitor KU-55933 affects parasite replication rate in a dose-dependent manner. KU-55933 affects intracellular tachyzoite growth and induces G1-phase arrest. Addition of KU-55933 to extracellular tachyzoites also leads to a significant reduction of tachyzoite replication upon infection of host cells. ATM kinase phosphorylates H2A.X (γH2AX) to promote DSB damage repair. The level of γH2AX increases in tachyzoites treated with camptothecin (CPT), a drug that generates fork collapse, but this increase was not observed when co-administered with KU-55933. These findings support that KU-55933 is affecting the Toxoplasma ATM-like kinase (TgATM). The combination of KU-55933 and other DNA damaging agents such as methyl methane sulfonate (MMS) and CPT produce a synergic effect, suggesting that TgATM kinase inhibition sensitizes the parasite to damaged DNA. By contrast, hydroxyurea (HU) did not further inhibit tachyzoite replication when combined with KU-55933

An Evaluative Model to Assess the Organizational Efficiency in Training Corporations

In an organisation any optimization process of its issues faces increasing challenges and requires new approaches to the organizational phenomenon. Indeed, in this work it is addressed the problematic of efficiency dynamics through intangible variables that may support a different view of the corporations. It focuses on the challenges that information management and the incorporation of context brings to competitiveness. Thus, in this work it is presented the analysis and development of an intelligent decision support system in terms of a formal agenda built on a Logic Programming based methodology to problem solving, complemented with an attitude to computing grounded on Artificial Neural Networks. The proposed model is in itself fairly precise, with an overall accuracy, sensitivity and specificity with values higher than 90 %. The proposed solution is indeed unique, catering for the explicit treatment of incomplete, unknown, or even self-contradictory information, either in a quantitative or qualitative arrangement

Fast cyclic stimulus flashing modulates perception of bi-stable figure

Many experiments have demonstrated that the rhythms in the brain influence the initial perceptual information processing. We investigated whether the alternation rate of the perception of a Necker cube depends on the frequency and duration of a flashing Necker cube. We hypothesize that synchronization between the external rhythm of a flashing stimulus and the internal rhythm of neuronal processing should change the alternation rate of a Necker cube. Knowing how a flickering stimulus with a given frequency and duration affects the alternation rate of bistable perception, we could estimate the frequency of the internal neuronal processing. Our results show that the perception time of the dominant stimulus depends on the frequency or duration of the flashing stimuli. The duration of the stimuli, at which the duration of the perceived image was maximal, was repeated periodically at 4 ms intervals. We suppose that such results could be explained by the existence of an internal rhythm of 125 cycles/s for bistable visual perception. We can also suppose that it is not the stimulus duration but the precise timing of the moments of switching on of external stimuli to match the internal stimuli which explains our experimental results. Similarity between the effects of flashing frequency on alternation rate of stimuli perception in present and previously performed experiment on binocular rivalry support the existence of a common mechanism for binocular rivalry and monocular perception of ambiguous figures