Troubling bodies in the fiction of Willa Cather

Troubling Bodies examines Willa Cather's use of the human body as a means of foregrounding a range of economic and social concerns. I argue that for Cather the body provides a vehicle through which she explores potentially volatile issues that both the restrictive cultural climate in which she wrote and her own aesthetic sensibilities made it difficult to pursue rhetorically. In locating these issues on and around characters' mutable bodies, Cather subtly demonstrates a significant engagement with contemporary culture. At the same time, she avoids didactic and discursive rhetoric that might have cluttered her famously smooth prose and overt political stances that could have bound her fiction too closely to contemporary events, rendering it irrelevant and anachronistic to later audiences. Ultimately, Cather's treatment of the body contributes substantially to her status as a modernist, allowing her to resist enclosure within such potentially limiting frameworks as regionalism or local color. Tracing this idea across an array of novels, I consider Cather's treatment of bodies in The Song of the Lark, One of Ours, The Professor's House, My Antonia, and Sapphira and the Slave Girl

Hairpins in the conformations of a confined polymer

If a semiflexible polymer confined to a narrow channel bends around by 180 degrees, the polymer is said to exhibit a hairpin. The equilibrium extension statistics of the confined polymer are well understood when hairpins are vanishingly rare or when they are plentiful. Here we analyze the extension statistics in the intermediate situation via experiments with DNA coated by the protein RecA, which enhances the stiffness of the DNA molecule by approximately one order of magnitude. We find that the extension distribution is highly non-Gaussian, in good agreement with Monte Carlo simulations of confined discrete wormlike chains. We develop a simple model that qualitatively explains the form of the extension distribution. The model shows that the tail of the distribution at short extensions is determined by conformations with one hairpin.Comment: Revised version. 22 pages, 7 figures, 2 tables, supplementary materia

Effects of N,N-diethyl-m-toluamide (DEET) in the cellular processes leading to angiogenesis

National audienc

Pro-angiogenic effet of N,N-diethyl-m-toluamide (DEET) mediated by M3 receptors

National audienc

Plasma cells release membrane microparticles in a mouse model of multiple myeloma.

Microparticles (MPs) released from the plasma membrane play a role in tumor progression. Involvement of MPs in myeloma (MM) has been poorly investigated. Because of the strong interaction of MM cells with bone microenvironment, we hypothesized an implication of MPs in MM using a murine model. Forty-four mice were injected with 5THL-MM cells and compared with 14 non-injected mice. Blood was collected at the early and end stages of MM development (EMM and LMM) to characterize the circulating MPs. At LMM, MPs were isolated from bone marrow (BM) of long bones of 22 mice, after centrifugation. Electron microscopy immunohistochemistry and Western blotting using CD138 were performed on BM-derived MPs. At EMM, MPs circulating level was significantly lower versus controls. In LMM, a significant increase of the total MP number from plasma was observed versus controls. Characterization of circulating MPs showed an increase of leukocyte- and erythrocyte-derived MPs. In LMM, serum M-protein was correlated with circulating MP number. BM-derived MPs increased in LMM and expressed CD138. Anti-CD138 coupled with nanobeads localized at the MP surface. There is evidence of an association between increase of MPs and MM development; the results underscore the participation of plasma cell-derived MPs originating from BM

Melanoma tumour vasculature heterogeneity: from mice models to human

Tumour angiogenesis is defined by an anarchic vasculature and irregularities in alignment of endothelial cells. These structural abnormalities could explain the variability in distribution of nanomedicines in various tumour models. Then, the main goal of this study was to compare and to characterize the tumour vascular structure in different mouse models of melanoma tumours (B16F10 and SK-Mel-28) and in human melanomas from different patients. Tumours were obtained by subcutaneous injection of 106 B16F10 and 3.106 SK-Mel-28 melanoma cells in C57BL/6 and nude mice, respectively. Tumour growth was evaluated weekly, while vasculature was analysed through fluorescent labelling via CD31 and desmin. Significant differences in tumour growth and mice survival were evidenced between the two melanoma models. A fast evolution of tumours was observed for B16F10 melanoma, reaching a tumour size of 100 mm3 in 7 days compared to SK-Mel-28 which needed 21 days to reach the same volumes. Important differences in vascularization were exposed between the melanoma models, characterized by a significant enhancement of vascular density and a significant lumen size for mice melanoma models compared to human. Immunostaining revealed irregularities in endothelium structure for both melanoma models, but structural differences of vasculature were observed, characterized by a stronger expression of desmin in SK-Mel-28 tumours. While human melanoma mainly develops capillaries, structural irregularities are also observed on the samples of this tumour model. Our study revealed an impact of cell type and tumour progression on the structural vasculature of melanoma, which could impact the distribution of drugs in the tumour environment

In vivo comparison of the proangiogenic properties of chlordecone and three of its dechlorinated derivatives formed by in situ chemical reduction

In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by chlordecone (CLD). Evidences provided by the literature indicate an association between the development of prostate cancer and CLD exposure (Multigner et al. 2010). In a previous in vitro study, we demonstrated that the two main dechlorinated CLD derivatives formed by ISCR, CLD-1Cl, and CLD-3Cl have lower cytotoxicity and proangiogenic properties than CLD itself (Legeay et al. 2017). By contrast, nothing is known on the in vivo proangiogenic effect of these dechlorinated derivatives. Based on in vitro data, the aims of this study were therefore to evaluate the in vivo influence of CLD and three of its dechlorinated metabolites in the control of neovascularization in a mice model of prostate cancer. The proangiogenic effect of CLD and three of its dechlorinated derivatives, CLD-1Cl, CLD-3Cl, and CLD-4Cl, was evaluated on a murine model of human prostate tumor (PC-3) treated, at two exposure levels: 33 μg/kg and 1.7 μg/kg respectively reflecting acute and chronic toxic exposure in human. The results of serum measurements show that, for the same ingested dose, the three metabolite concentrations were significantly lower than that of CLD. Dechlorination of CLD lead therefore to molecules that are biologically absorbed or metabolized, or both, faster than the parent molecule. Prostate tumor growth was lower in the groups treated by the three metabolites compared to the one treated by CLD. The vascularization measured on the tumor sections was inversely proportional to the rate of dechlorination, the treatment with CLD-4Cl showing no difference with control animals treated with only the vehicle oil used for all substances tested. We can therefore conclude that the proangiogenic effect of CLD is significantly decreased following the ISCR-resulting dechlorination. Further investigations are needed to elucidate the molecular mechanisms by which dechlorination of CLD reduces proangiogenic effects in prostate tumor

Heme oxygenase-1 induction restores high-blood-flow-dependent remodeling and endothelial function in mesenteric arteries of old rats

BACKGROUND: Aging is associated with reduced structural and functional adaptation to chronic changes in blood flow (shear stress) in small arteries. As heme oxygenase-1 (HO-1) is induced by hemodynamic forces in vascular smooth muscle and endothelial cells, we hypothesized that it might improve flow-dependent remodeling in aging. METHOD: First-order mesenteric arteries from 3 and 16-month-old rats were exposed to high, low, or normal flow by alternate ligation in vivo. Rats were treated with the HO-1 inducer, cobalt protoporphyrin (CoPP, 5 mg/kg) or vehicle. 14 days later, local blood flow was measured in vivo, and arteries were studied in vitro. RESULTS: Despite an equivalent change in blood flow, diameter enlargement in the high-flow arteries was blunted in old compared to young rats and was associated with decreased endothelium-dependent relaxation to acetylcholine. In old rats, HO-1 induction with CoPP restored outward remodeling, via a paradoxical reactive oxygen species-dependent mechanism, and was associated with a Mn-superoxide dismutase (SOD) overexpression, as well as a significant reduction of mitochondrial aconitase activity, used as a biomarker for oxidative stress. The heme oxygenase activity inhibitor, Sn-protoporphyrin, and the SOD-mimetic, TEMPOL, prevented the effect of CoPP on remodeling and oxidative status in old rats. Furthermore, HO-1 induction improved endothelial function, in association with increased endothelial nitric oxide synthase protein expression and phosphorylation (Ser-1177). In low-flow arteries, inward remodeling was unaffected by aging or by CoPP. Thus, in old rats, CoPP-induced up-regulation of HO-1 restored high-flow-dependent remodeling (diameter enlargement) and improved endothelial function in mesenteric arteries. CONCLUSION: This opens new perspectives in the treatment of ischemic diseases in aging