Bis[μ-4-(2-oxidobenzyl­idene)thio­semi­carbazidato-κ4 S,N 1,O:O]bis­[(pyridine-κN)zinc]

In the title compound, [Zn2(C8H7N3OS)2(C5H5N)2], the Zn2O2 ring has a flattened roof shape, with the roof angle equal to 10.10 (6)°. The thio­semicarbazones act as tridentate ligands to one ZnII atom, with the O atoms additionally in bridging positions to the second ZnII atom. Both ZnII atoms are five-coordinated; the coordination polyhedra are close to square pyramids, with the pyridine N atoms at apical positions. Two inter­molecular N—H⋯N and one relatively weak N—H⋯S hydrogen bond, together with C—H⋯S weak inter­actions, connect the mol­ecules into a three-dimensional network

Behind the silence of harmony: risk factors for physical and sexual violence among women in rural Indonesia

BACKGROUND: Indonesia has the fourth largest population in the world. Few studies have identified the risk factors of Indonesian women for domestic violence. Such research will be useful for the development of prevention programs aiming at reducing domestic violence. Our study examines associations between physical and sexual violence among rural Javanese Indonesian women and sociodemographic factors, husband's psychosocial and behavioral characteristics and attitudes toward violence and gender roles. METHODS: A cohort of pregnant women within the Demographic Surveillance Site (DSS) in Purworejo district, Central Java, Indonesia, was enrolled in a longitudinal study between 1996 and 1998. In the following year (1999), a cross-sectional domestic violence household survey was conducted with 765 consenting women from that cohort. Female field workers, trained using the WHO Multi-Country study instrument on domestic violence, conducted interviews. Crude and adjusted odds ratios at 95% CI were applied for analysis. RESULTS: Lifetime exposure to sexual and physical violence was 22% and 11%. Sexual violence was associated with husbands' demographic characteristics (less than 35 years and educated less than 9 years) and women's economic independence. Exposure to physical violence among a small group of women (2-6%) was strongly associated with husbands' personal characteristics; being unfaithful, using alcohol, fighting with other men and having witnessed domestic violence as a child. The attitudes and norms expressed by the women confirm that unequal gender relationships are more common among women living in the highlands and being married to poorly educated men. Slightly more than half of the women (59%) considered it justifiable to refuse coercive sex. This attitude was also more common among financially independent women (71%), who also had a higher risk of exposure to sexual violence. CONCLUSIONS: Women who did not support the right of women to refuse sex were more likely to experience physical violence, while those who justified hitting for some reasons were more likely to experience sexual violence. Our study suggests that Javanese women live in a high degree of gender-based subordination within marriage relationships, maintained and reinforced through physical and sexual violence. Our findings indicate that women's risk of physical and sexual violence is related to traditional gender norms

Development of monoclonal antibodies against Plasmodium falciparum thioredoxin peroxidase 1 and its possible application for malaria diagnosis

Rapid diagnostic tests (RDTs) have been considered as an ideal alternative for light microscopy to detect malaria parasites especially in remote areas. The development and improvement of RDTs is an area of intensive research in the last decade. To date, few parasite proteins have been targeted in RDTs which are known to have certain deficiencies and made the researchers to look for other promising candidates to address this problem. Plasmodium falciparum thioredoxin peroxidase 1 (PfTPx-1) is abundantly expressed in the cytoplasm of the parasite and well conserved across Plasmodium species, making this antigen a promising target for malaria diagnosis. Several monoclonal antibodies (mAbs) were produced against PfTPx-1. The binding affinities of mAbs were measured. Several immunochromatographic tests (ICTs) were developed using different combination of mAbs. All mAbs showed promising affinities to be used for diagnosis. The sensitivities of ICTs were evaluated using recombinant PfTPx-1 whose results lead us to the preparation of 4 different ICTs. These tests showed positive reaction with P. falciparum in vitro culture supernatant indicating the release of PfTPx-1 during schizont rupture. Altogether, these findings suggest that PfTPx-1 is a promising biomarker to diagnose P. falciparum infection. However, the diagnostic performance of this antigen should be further validated using clinical samples

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically

PURPOSE: To assess the association between obstructive sleep apnea (OSA) and Fuhrman grade in patients with clear cell renal cell carcinoma (ccRCC). As secondary endpoints, we studied its association with tumor size, metastasis-free survival (MFS) and cancer-specific survival (CSS). METHODS: We reviewed the databases of two tertiary care centers, identifying 2579 patients who underwent partial or radical nephrectomy for ccRCC between 1991 and 2014. Descriptive statistics were used to compare pathologic variables between patients with and without OSA. Linear and logistic regression models were used to assess the association of OSA with Fuhrman grade and tumor size. A Cox proportional hazards model was used to determine OSA association with MFS and CSS. A pathway analysis was performed on a cohort with available gene expression data. RESULTS: In total, 172 patients (7 %) had self-reported OSA at diagnosis. More patients with OSA had high Fuhrman grade compared to those without OSA [51 vs. 38 %; 13 % risk difference; 95 % confidence interval (CI), 5-20 %; p = 0.003]. On multivariable analysis, the association remained significant (OR 1.41; 95 % CI 1.00-1.99; p = 0.048). OSA was not associated with tumor size (p > 0.5), MFS (p = 0.5) or CSS (p = 0.4). A trend toward vascular endothelial growth factor pathway enrichment was seen in OSA patients (p = 0.08). CONCLUSIONS: OSA is associated with high Fuhrman grade in patients undergoing surgery for ccRCC. Pending validation of this novel finding in further prospective studies, it could help shape future research to better understand etiological mechanisms associated

The role of clathrin in post-golgi trafficking in toxoplasma gondii

Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle

Energy Linearity and Resolution of the ATLAS Electromagnetic Barrel Calorimeter in an Electron Test-Beam

A module of the ATLAS electromagnetic barrel liquid argon calorimeter was exposed to the CERN electron test-beam at the H8 beam line upgraded for precision momentum measurement. The available energies of the electron beam ranged from 10 to 245 GeV. The electron beam impinged at one point corresponding to a pseudo-rapidity of eta=0.687 and an azimuthal angle of phi=0.28 in the ATLAS coordinate system. A detailed study of several effects biasing the electron energy measurement allowed an energy reconstruction procedure to be developed that ensures a good linearity and a good resolution. Use is made of detailed Monte Carlo simulations based on Geant which describe the longitudinal and transverse shower profiles as well as the energy distributions. For electron energies between 15 GeV and 180 GeV the deviation of the measured incident electron energy over the beam energy is within 0.1%. The systematic uncertainty of the measurement is about 0.1% at low energies and negligible at high energies. The energy resolution is found to be about 10% sqrt(E) for the sampling term and about 0.2% for the local constant term

Three Toxoplasma gondii dense granule proteins are required for induction of Lewis rat macrophage pyroptosis

Upon invasion of Lewis rat macrophages, Toxoplasma rapidly induces programmed cell death (pyroptosis), which prevents Toxoplasma replication, possibly explaining the resistance of the Lewis rat to Toxoplasma Using a chemical mutagenesis screen, we identified Toxoplasma mutants that no longer induced pyroptosis. Whole-genome sequencing led to the identification of three Toxoplasma parasitophorous vacuole-localized dense granule proteins, GRA35, GRA42, and GRA43, that are individually required for induction of Lewis rat macrophage pyroptosis. Macrophage infection with Δgra35, Δgra42, and Δgra43 parasites led to greatly reduced cell death rates and enhanced parasite replication. Lewis rat macrophages infected with parasites containing a single, double, or triple deletion of these GRAs showed similar levels of cell viability, suggesting that the three GRAs function in the same pathway. Deletion of GRA42 or GRA43 resulted in GRA35 (and other GRAs) being retained inside the parasitophorous vacuole instead of being localized to the parasitophorous vacuole membrane. Despite having greatly enhanced replication in Lewis rat macrophages in vitro, Δgra35, Δgra42, and Δgra43 parasites did not establish a chronic infection in Lewis rats. Toxoplasma did not induce F344 rat macrophage pyroptosis, but F344 rats infected with Δgra35, Δgra42, and Δgra43 parasites had reduced cyst numbers. Thus, these GRAs determined parasite in vivo fitness in F344 rats. Overall, our data suggest that these three Toxoplasma dense granule proteins play a critical role in establishing a chronic infection in vivo, independently of their role in mediating macrophage pyroptosis, likely due to their importance in regulating protein localization to the parasitophorous vacuole membrane.IMPORTANCE Inflammasomes are major components of the innate immune system and are responsible for detecting various microbial and environmental danger signals. Upon invasion of Lewis rat macrophages, the parasite rapidly activates the NLRP1 inflammasome, resulting in pyroptosis and elimination of the parasite's replication niche. The work reported here revealed that Toxoplasma GRA35, GRA42, and GRA43 are required for induction of Lewis rat macrophage pyroptosis. GRA42 and GRA43 mediate the correct localization of other GRAs, including GRA35, to the parasitophorous vacuole membrane. These three GRAs were also found to be important for parasite in vivo fitness in a Toxoplasma-susceptible rat strain, independently of their role in NLRP1 inflammasome activation, suggesting that they perform other important functions. Thus, this study identified three GRAs that mediate the induction of Lewis rat macrophage pyroptosis and are required for pathogenesis of the parasite

Position resolution and particle identification with the ATLAS EM calorimeter

In the years between 2000 and 2002 several pre-series and series modules of the ATLAS EM barrel and end-cap calorimeter were exposed to electron, photon and pion beams. The performance of the calorimeter with respect to its finely segmented first sampling has been studied. The polar angle resolution has been found to be in the range 50-60 mrad/sqrt(E (GeV)). The neutral pion rejection has been measured to be about 3.5 for 90% photon selection efficiency at pT=50 GeV/c. Electron-pion separation studies have indicated that a pion fake rate of (0.07-0.5)% can be achieved while maintaining 90% electron identification efficiency for energies up to 40 GeV.Comment: 32 pages, 22 figures, to be published in NIM