511 research outputs found

    TRIADIC EXCHANGE RELATIONS: AN ILLUSTRATION FROM SOUTH INDIA

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    Summary An issue which has attracted considerable attention in the study of agrarian structure is the phenomenon of interlinked markets. Amit Bhaduri has integrated interlinkage into an analytical explanation for stagnation in Indian agriculture. While Bhaduri's model of interlinkage provides important insights into the mechanisms for perpetuation of backward agrarian relations, it serves the thesis of technological stagnation rather poorly. This paper shows that interlinkage is not in any sense an exclusive characteristic of a backward or static, agrarian economy. To the contrary interlinkage has been found to be an integral feature of a dynamic regime which embodies emerging forces of capitalist development: one in which traditional methods of irrigation have given place to modern methods; there has been technological upgrading in all aspects of farm economy; heavy demand for production loans and heavy transactions in the product market. While the agents involved in exploitation ? at both the dispensing and the receiving ends ? may be different from those in Bhaduri's semi?feudal setting, it will be observed that the instrument of interlinkage has an important role to play in establishing social relations of oppression and dependence which bear a strong family resemblance to those which obtain in his model. These issues are studied in the concrete context of a village in Tamil Nadu (South India). Resumé Les relations de l'échange triadique: une illustration tirée de l'Inde du sud Une question qui a attiré beaucoup d'attention dans l'étude de la structure agraire est le phénomène de l'interconnexion des marchés. Amit Bhaduri a intégré le concept de l'interconnexion dans une explication analytique de la stagnation de l'agriculture en Inde. Si le modèle de Bhaduri offre d'importants aperçus sur les mécanismes de perpétuation des relations agraires arriérées, il est peu utile comme modèle pour expliquer la thèse de la stagnation technologique. Le présent article démontre que l'interconnexion n'est en aucun sens une caractéristique exclusive d'une économie agraire arriérée ou stagnante. Au contraire, l'on constate que l'interconnexion est une caractéristique intégrale d'un régime dynamique qui englobe les forces émergeantes du développement capitaliste: régime dans lequel les méthodes d'irrigation traditionnelles ont cédé à des méthodes modernes; il s'est produit une revalorisation technologique de tous les aspects de l'économie agricole; un accroissement de la demande en prêts de production, et un important niveau de transactions dans le marché des produits générés. S'il se peut que les agents concernés dans l'exploitation – en même temps côté distribution et côté réception – ne soient pas les mêmes que dans le cadre semi?féodal proposé par Bhaduri, l'on constatera néanmoins que l'instrument d'interconnexion joue un rôle crucial dans l'établissement des relations sociales de l'oppression et de la dépendance qui ont une forte ressemblance familiale à celles qui sont proposées dans son modèle. L'étude de ces questions est fermement contextualisée dans un village du Tamil Nadu (Inde du sud). Resumen Relaciones triadicas de intercambio: un ejemplo de la India Un asunto que ha atraído considerable atención en el estudio de la estructura agraria es el fenómeno de los mercados interconectados. Amit Bhaduri ha incluído la interconexión dentro de una explicación analítica del estancamiento de la agricultura india. Si bien su modelo de interconexión da una idea bastante clara de los mecanismos que perpetúan relaciones agrarias retrógradas, no sustenta la tesis del estancamiento tecnológico de manera muy convincente. Este artículo demuestra que la interconexión no es de ninguna manera una característica exclusiva de un tipo de economía agraria estática o retrógrada. Por el contrario, la interconexión es un rasgo integral de un régimen dinámico que contiene fuerzas emergentes de desarrollo capitalista; en el cual los métodos tradicionales de irrigación han dado paso a métodos modernos; ha habido avances tecnológicos en todos los aspectos de la economía rural; y gran demanda de préstamos de producción e importantes transacciones en plaza. Aunque los agentes involucrados en la explotación – en los dos extremos del proceso – son diferentes de los ilustrados por Bhaduri como en un marco semi?feudal, se observará que el instrumento de interconexión tiene un papel importante en el establecimiento de relaciones sociales de opresión y dependencia que tienen una gran similitud con las presentadas en su modelo. Estas cuestiones se estudian en el artículo en el contexto de un pueblo de Tamil Nadu (India del Sur)

    CT angiography, MR angiography and rotational digital subtraction angiography for volumetric assessment of intracranial aneurysms. An experimental study

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    The purpose of our experimental study was to assess the accuracy and precision of CT angiography (CTA), MR angiography (MRA) and rotational digital subtraction angiography (DSA) for measuring the volume of an in vitro aneurysm model. A rigid model of the anterior cerebral circulation harbouring an anterior communicating aneurysm was connected to a pulsatile circuit. It was studied using unenhanced 3D time-of-flight MRA, contrast-enhanced CTA and rotational DSA angiography. The source images were then postprocessed on dedicated workstations to calculate the volume of the aneurysm. CTA was more accurate than MRA (P=0.0019). Rotational DSA was more accurate than CTA, although the difference did not reach statistical significance (P=0.1605), and significantly more accurate than MRA (P<0.00001). CTA was more precise than MRA (P=0.12), although this did not reach statistical significance. Rotational DSA can be part of the diagnosis, treatment planning and support endovascular treatment of intracranial aneurysms. The emerging endovascular treatment techniques which consist of using liquid polymers as implants to exclude aneurysms from arterial circulation would certainly benefit from this precise measurement of the volume of aneurysm

    Efficient Drug Delivery of Paclitaxel Glycoside: A Novel Solubility Gradient Encapsulation into Liposomes Coupled with Immunoliposomes Preparation

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    Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside

    Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.

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    The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a parental sex bias related to Cre expression in sperm or oocytes. Slight differences among Cre driver lines utilizing common transcriptional control elements affect germline recombination rates. Specific target loci demonstrated differential recombination; thus, reporters are not reliable proxies for another locus of interest. Similar principles apply to other recombinase systems and other genetically targeted organisms. We hereby draw attention to the prevalence of germline recombination and provide guidelines to inform future research for the neuroscience and broader molecular genetics communities

    Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression

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    BACKGROUND: Paired-like homeodomain 2 (PITX2) is a bicoid homeodomain transcription factor which plays an essential role in maintaining embryonic left-right asymmetry during vertebrate embryogenesis. However, emerging evidence suggests that the aberrant upregulation of PITX2 may be associated with tumor progression, yet the functional role that PITX2 plays in tumorigenesis remains unknown. PRINCIPAL FINDINGS: Using real-time quantitative RT-PCR (Q-PCR), Western blot and immunohistochemical (IHC) analyses, we demonstrated that PITX2 was frequently overexpressed in ovarian cancer samples and cell lines. Clinicopathological correlation showed that the upregulated PITX2 was significantly associated with high-grade (P = 0.023) and clear cell subtype (P = 0.011) using Q-PCR and high-grade (P<0.001) ovarian cancer by IHC analysis. Functionally, enforced expression of PITX2 could promote ovarian cancer cell proliferation, anchorage-independent growth ability, migration/invasion and tumor growth in xenograft model mice. Moreover, enforced expression of PITX2 elevated the cell cycle regulatory proteins such as Cyclin-D1 and C-myc. Conversely, RNAi mediated knockdown of PITX2 in PITX2-high expressing ovarian cancer cells had the opposite effect. CONCLUSION: Our findings suggest that the increased expression PITX2 is involved in ovarian cancer progression through promoting cell growth and cell migration/invasion. Thus, targeting PITX2 may serve as a potential therapeutic modality in the management of high-grade ovarian tumor.published_or_final_versio

    Dysregulation of Cell Polarity Proteins Synergize with Oncogenes or the Microenvironment to Induce Invasive Behavior in Epithelial Cells

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    Changes in expression and localization of proteins that regulate cell and tissue polarity are frequently observed in carcinoma. However, the mechanisms by which changes in cell polarity proteins regulate carcinoma progression are not well understood. Here, we report that loss of polarity protein expression in epithelial cells primes them for cooperation with oncogenes or changes in tissue microenvironment to promote invasive behavior. Activation of ErbB2 in cells lacking the polarity regulators Scribble, Dlg1 or AF-6, induced invasive properties. This cooperation required the ability of ErbB2 to regulate the Par6/aPKC polarity complex. Inhibition of the ErbB2-Par6 pathway was sufficient to block ErbB2-induced invasion suggesting that two polarity hits may be needed for ErbB2 to promote invasion. Interestingly, in the absence of ErbB2 activation, either a combined loss of two polarity proteins, or exposure of cells lacking one polarity protein to cytokines IL-6 or TNFα induced invasive behavior in epithelial cells. We observed the invasive behavior only when cells were plated on a stiff matrix (Matrigel/Collagen-1) and not when plated on a soft matrix (Matrigel alone). Cells lacking two polarity proteins upregulated expression of EGFR and activated Akt. Inhibition of Akt activity blocked the invasive behavior identifying a mechanism by which loss of polarity promotes invasion of epithelial cells. Thus, we demonstrate that loss of polarity proteins confers phenotypic plasticity to epithelial cells such that they display normal behavior under normal culture conditions but display aggressive behavior in response to activation of oncogenes or exposure to cytokines

    PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherin

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    The pleckstrin-homology-domain-containing protein PLEKHA7 was recently identified as a protein linking the E-cadherin-p120 ctn complex to the microtubule cytoskeleton. Here we characterize the expression, tissue distribution and subcellular localization of PLEKHA7 by immunoblotting, immunofluorescence microscopy, immunoelectron microscopy, and northern blotting in mammalian tissues. Anti-PLEKHA7 antibodies label the junctional regions of cultured kidney epithelial cells by immunofluorescence microscopy, and major polypeptides of Mr ∼135 kDa and ∼145 kDa by immunoblotting of lysates of cells and tissues. Two PLEKHA7 transcripts (∼5.5 kb and ∼6.5 kb) are detected in epithelial tissues. PLEKHA7 is detected at epithelial junctions in sections of kidney, liver, pancreas, intestine, retina, and cornea, and its tissue distribution and subcellular localization are distinct from ZO-1. For example, PLEKHA7 is not detected within kidney glomeruli. Similarly to E-cadherin, p120 ctn, β-catenin and α-catenin, PLEKHA7 is concentrated in the apical junctional belt, but unlike these adherens junction markers, and similarly to afadin, PLEKHA7 is not localized along the lateral region of polarized epithelial cells. Immunoelectron microscopy definitively establishes that PLEKHA7 is localized at the adherens junctions in colonic epithelial cells, at a mean distance of 28 nm from the plasma membrane. In summary, we show that PLEKHA7 is a cytoplasmic component of the epithelial adherens junction belt, with a subcellular localization and tissue distribution that is distinct from that of ZO-1 and most AJ proteins, and we provide the first description of its distribution and localization in several tissues

    Differential Analysis of Ovarian and Endometrial Cancers Identifies a Methylator Phenotype

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    Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison within the endometrioid subtype we added 6 primary uterine endometrioid tumors and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578 CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We identified 36 locations with significant increases or decreases in methylation in comparisons of serous tumors and normal fallopian tube samples. Moreover, unsupervised clustering techniques applied to all samples showed three major profiles comprising mostly normal samples, serous tumors, and endometrioid tumors including ovarian, uterine and metastatic origins. The clustering analysis identified 60 differentially methylated sites between the serous group and the normal group. An unrelated set of 25 serous tumors validated the reproducibility of the methylation patterns. In contrast, >1,000 genes were differentially methylated between endometrioid tumors and normal samples. This finding is consistent with a generalized regulatory disruption caused by a methylator phenotype. Through DNA methylation analyses we have identified genes with known roles in ovarian carcinoma etiology, whereas pathway analyses provided biological insight to the role of novel genes. Our finding of differences between serous and endometrioid ovarian tumors indicates that intervention strategies could be developed to specifically address subtypes of epithelial ovarian cancer
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