Effect of alpha tocopherol acetate in Walker 256/B cells-induced oxidative damage in a rat model of breast cancer skeletal metastases

The pathophysiological changes and the oxidative–antioxidative status were evaluated in the bone microenvironment of rat inoculated with Walker 256/B mammary gland carcinoma cells, and used α-tocopherol acetate (ATA) as a countermeasure.Walker 256/B cells were injected into the right femora of aged male rats. Animals were randomized into three groups: 12 rats were injected with saline (control group); 14 rats were injected with Walker 256/B cells (5 × 104) in the medullar cavity (W256 group); 14 rats were inoculated with Walker 256/B cells and treated with ATA (45 mg/kg BW) (W256 + ATA group). After 20 days, rats were euthanized and the femurs were radiographed. Micro architectural parameters were measured by microcomputed tomography and histology. Serum, bone and bone marrow were evaluated for oxidative damage. In parallel, cell cultures were done in the presence of ATA and ROS were measured by fluorescence; apoptotic cells were determined in parallel. W256 groups had osteolytic damages with marked resorption of cortical and trabecular bone. W256 + ATA animals presented marked osteosclerotic areas associated with tumor necrosis areas inside the bone cavity. Levels of lipid peroxidation and protein oxidation were found to increase in W256 rats; a significant reduction in SOD and GSH-p activities was also observed. W256 + ATA group had significantly reduced oxidative damage, but not reversed back to the control levels. The present study shows that Walker 256/B cells induce skeletal metastases associated with oxidative damage in the bone microenvironment. ATA reduced the oxidative stress damage, enhanced osteosclerosis and tumor cell apoptosis both in vitro and in vivo

Charge gap in the one--dimensional dimerized Hubbard model at quarter-filling

We propose a quantitative estimate of the charge gap that opens in the one-dimensional dimerized Hubbard model at quarter-filling due to dimerization, which makes the system effectively half--filled, and to repulsion, which induces umklapp scattering processes. Our estimate is expected to be valid for any value of the repulsion and of the parameter describing the dimerization. It is based on analytical results obtained in various limits (weak coupling, strong coupling, large dimerization) and on numerical results obtained by exact diagonalization of small clusters. We consider two models of dimerization: alternating hopping integrals and alternating on--site energies. The former should be appropriate for the Bechgaard salts, the latter for compounds where the stacks are made of alternating $TMTSF$ and $TMTTF$ molecules. % $(TMTSF)_2 X$ and $(TMTTF)_2 X$ ($X$ denotes $ClO_4$, $PF_6$, $Br$...).Comment: 33 pages, RevTeX 3.0, figures on reques

Attachment style, assertive communication, and safer-sex behavior

This research tested the proposition that the effect of attachment security on safer-sex practice may be mediated by communication patterns. One hundred eighty-five undergraduate students completed questionnaire measures of attachment, assertiveness, and attitudes to communication about AIDS. Eight weeks later, they reported on their practice of safer sex in the period since the first testing session. Hierarchical regressions showed that at Step 1, anxiety about relationships (a measure of insecure attachment) was associated with less safer-sex practice, for all outcome measures. Attitudes to communication about AIDS added to the prediction of general reports of safer-sex practice: in line with the mediational model, anxiety about relationships became unimportant as a predictor when communication variables were included. Communication variables failed to add to the prediction of safer sex on the most recent encounter, and both anxiety about relationships and attitudes to communication about AIDS predicted condom use. Some gender differences in patterns of prediction were noted. The results are discussed in terms of attachment style and its links with the negotiation of sexual practice and relationship issues

A Quantitative and Dynamic Model for Plant Stem Cell Regulation

Plants maintain pools of totipotent stem cells throughout their entire life. These stem cells are embedded within specialized tissues called meristems, which form the growing points of the organism. The shoot apical meristem of the reference plant Arabidopsis thaliana is subdivided into several distinct domains, which execute diverse biological functions, such as tissue organization, cell-proliferation and differentiation. The number of cells required for growth and organ formation changes over the course of a plants life, while the structure of the meristem remains remarkably constant. Thus, regulatory systems must be in place, which allow for an adaptation of cell proliferation within the shoot apical meristem, while maintaining the organization at the tissue level. To advance our understanding of this dynamic tissue behavior, we measured domain sizes as well as cell division rates of the shoot apical meristem under various environmental conditions, which cause adaptations in meristem size. Based on our results we developed a mathematical model to explain the observed changes by a cell pool size dependent regulation of cell proliferation and differentiation, which is able to correctly predict CLV3 and WUS over-expression phenotypes. While the model shows stem cell homeostasis under constant growth conditions, it predicts a variation in stem cell number under changing conditions. Consistent with our experimental data this behavior is correlated with variations in cell proliferation. Therefore, we investigate different signaling mechanisms, which could stabilize stem cell number despite variations in cell proliferation. Our results shed light onto the dynamic constraints of stem cell pool maintenance in the shoot apical meristem of Arabidopsis in different environmental conditions and developmental states

The cellular source for APOBEC3G's incorporation into HIV-1

<p>Abstract</p> <p>Background</p> <p>Human APOBEC3G (hA3G) has been identified as a cellular inhibitor of HIV-1 infectivity. Viral incorporation of hA3G is an essential step for its antiviral activity. Although the mechanism underlying hA3G virion encapsidation has been investigated extensively, the cellular source of viral hA3G remains unclear.</p> <p>Results</p> <p>Previous studies have shown that hA3G forms low-molecular-mass (LMM) and high-molecular-mass (HMM) complexes. Our work herein provides evidence that the majority of newly-synthesized hA3G interacts with membrane lipid raft domains to form Lipid raft-associated hA3G (RA hA3G), which serve as the precursor of the mature HMM hA3G complex, while a minority of newly-synthesized hA3G remains in the cytoplasm as a soluble LMM form. The distribution of hA3G among the soluble LMM form, the RA LMM form and the mature forms of HMM is regulated by a mechanism involving the N-terminal part of the linker region and the C-terminus of hA3G. Mutagenesis studies reveal a direct correlation between the ability of hA3G to form the RA LMM complex and its viral incorporation.</p> <p>Conclusions</p> <p>Together these data suggest that the Lipid raft-associated LMM A3G complex functions as the cellular source of viral hA3G.</p

Structure-Function Analysis of Barley NLR Immune Receptor MLA10 Reveals Its Cell Compartment Specific Activity in Cell Death and Disease Resistance

Plant intracellular immune receptors comprise a large number of multi-domain proteins resembling animal NOD-like receptors (NLRs). Plant NLRs typically recognize isolate-specific pathogen-derived effectors, encoded by avirulence (AVR) genes, and trigger defense responses often associated with localized host cell death. The barley MLA gene is polymorphic in nature and encodes NLRs of the coiled-coil (CC)-NB-LRR type that each detects a cognate isolate-specific effector of the barley powdery mildew fungus. We report the systematic analyses of MLA10 activity in disease resistance and cell death signaling in barley and Nicotiana benthamiana. MLA10 CC domain-triggered cell death is regulated by highly conserved motifs in the CC and the NB-ARC domains and by the C-terminal LRR of the receptor. Enforced MLA10 subcellular localization, by tagging with a nuclear localization sequence (NLS) or a nuclear export sequence (NES), shows that MLA10 activity in cell death signaling is suppressed in the nucleus but enhanced in the cytoplasm. By contrast, nuclear localized MLA10 is sufficient to mediate disease resistance against powdery mildew fungus. MLA10 retention in the cytoplasm was achieved through attachment of a glucocorticoid receptor hormone-binding domain (GR), by which we reinforced the role of cytoplasmic MLA10 in cell death signaling. Together with our data showing an essential and sufficient nuclear MLA10 activity in disease resistance, this suggests a bifurcation of MLA10-triggered cell death and disease resistance signaling in a compartment-dependent manner

Chromosomal Rearrangements Formed by rrn Recombination Do Not Improve Replichore Balance in Host-Specific Salmonella enterica Serovars

operons. One hypothesis explaining these rearrangements suggests that replichore imbalance introduced from horizontal transfer of pathogenicity islands and prophages drives chromosomal rearrangements in an attempt to improve balance.This hypothesis was directly tested by comparing the naturally-occurring chromosomal arrangement types to the theoretically possible arrangement types, and estimating their replichore balance using a calculator. In addition to previously characterized strains belonging to host-specific serovars, the arrangement types of 22 serovar Gallinarum strains was also determined. Only 48 out of 1,440 possible arrangement types were identified in 212 host-specific strains. While the replichores of most naturally-occurring arrangement types were well-balanced, most theoretical arrangement types had imbalanced replichores. Furthermore, the most common types of rearrangements did not change replichore balance.The results did not support the hypothesis that replichore imbalance causes these rearrangements, and suggest that the rearrangements could be explained by aspects of a host-specific lifestyle