364 research outputs found

    Resources for Sale: Corruption, Democracy and the Natural Resource Curse

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    A puzzling piece of empirical evidence suggests that resource-abundant countries tend to grow slower than their resource-poor counterparts. We attempt to explain this phenomenon by developing a lobbying game in which rent seeking firms interact with corrupt governments. The presence or absence of political competition, as well as the potential costs of political transitions, turn out to be key elements in generating the `resource curse.¿ These variables define the degree of freedom that incumbent governments have in pursuing development policies that maximize surplus in the lobbying game, but put the economy off its optimal path. We test our predictions by adding measures of democracy and authoritarianism to existing regression models of the resource curse, and obtain support for our hypothese

    The Viral Interferon Regulatory Factors of KSHV: Immunosuppressors or Oncogenes?

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    Kaposi’s sarcoma-associated herpesvirus (KSHV) is a large double-stranded DNA gammaherpesvirus, and the etiological agent for three human malignancies: Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. To establish and maintain infection, KSHV has evolved unique mechanisms to evade the host immune response. Cellular interferon regulatory factors (IRFs) are a critical part of the host anti-viral immune response. KSHV encodes four homologs of IRFs, vIRF1–4, which inhibit the activity of their cellular counterparts. vIRF1, 2, and 3 have been shown to interact directly with cellular IRFs. Additionally, the vIRFs have other functions such as modulation of Myc, p53, Notch, transforming growth factor-β, and NF-κB signaling. These activities of vIRFs may contribute to KSHV tumorigenesis. KSHV vIRF1 and vIRF3 have been implicated as oncogenes, making the understanding of KSHV vIRF function vital to understanding KSHV pathogenesis

    Prenatal diagnosis of congenital megalourethra: a rare anomaly

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    Congenital megalourethra is a rare urogenital malformation characterised by pathological elongation and dilatation of penile urethra. It is a form of functional obstructive uropathy which is associated with significant urological and sexual dysfunction secondary to hypoplasia or absence of corpora cavernosa and spongiosa. We report a case of megalourethra in one of the dichorionic diamniotic twin diagnosed prenatally in a young primigravida. Initial ultrasound report suggested two different diagnoses i.e. omphalocoele and gastroschisis. Later, diagnosis of congenital megalourethra was made on detailed ultrasound examination by our fetal medicine consultant. Postnatal gross and ultrasonographic examination confirmed the prenatal diagnosis. In the present case report, we have emphasized proper perineal anatomical ultrasound examination which revealed a megalourethra. Although this anomaly is not lethal in isolation, but it has worse prognosis in presence of other associated structural anomalies. This anomaly also raises the controversy regarding disclosure of sex of foetus in countries like India where sex disclosure is prohibited by law. As this condition typically affects male foetuses and significantly affects sexual function, it may be necessary to reveal fetal sex for appropriate counselling and prognostication to prospective parents. Ethical dilemma arises for practising clinicians while dealing with isolated forms of megalourethra whether to offer termination of pregnancy on the grounds of having significant impact on sexual life due to erectile dysfunction. Anorectal malformation is often associated with megalourethra, although suspected in the present case, can be difficult to identify antenatally prior to 20 weeks (the time limit up to which legal termination can be performed in India). These issues have been highlighted in the present report

    Simulating the Macroeconomic Impact of Future Water Scarcity

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    In this chapter, the macroeconomic implications of possible future water scarcity are assessed. In order to do so, the sustainability of a number of economic growth scenarios in terms of water resources are considered. The analysis is based on a comparison between potential demand for water and estimated water availability

    Mdm2 mediated neddylation of pVHL blocks the induction of anti-angiogenic factors.

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    Mutations in the tumor suppressor TP53 are rare in renal cell carcinomas. p53 is a key factor for inducing anti-angiogenic genes and RCC are highly vascularized, which suggests that p53 is inactive in these tumors. One regulator of p53 is the Mdm2 oncogene, which is correlated with high-grade, metastatic tumors. However, the sole activity of Mdm2 is not just to regulate p53, but it can also function independent of p53 to regulate the early stages of metastasis. Here, we report that the oncoprotein Mdm2 can bind directly to the tumor suppressor VHL, and conjugate nedd8 to VHL within a region that is important for the p53-VHL interaction. Nedd8 conjugated VHL is unable to bind to p53 thereby preventing the induction of anti-angiogenic factors. These results highlight a previously unknown oncogenic function of Mdm2 during the progression of cancer to promote angiogenesis through the regulation of VHL. Thus, the Mdm2-VHL interaction represents a pathway that impacts tumor angiogenesis

    Understanding Urban Demand for Wild Meat in Vietnam: Implications for Conservation Actions

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    Vietnam is a significant consumer of wildlife, particularly wild meat, in urban restaurant settings. To meet this demand, poaching of wildlife is widespread, threatening regional and international biodiversity. Previous interventions to tackle illegal and potentially unsustainable consumption of wild meat in Vietnam have generally focused on limiting supply. While critical, they have been impeded by a lack of resources, the presence of increasingly organised criminal networks and corruption. Attention is, therefore, turning to the consumer, but a paucity of research investigating consumer demand for wild meat will impede the creation of effective consumer-centred interventions. Here we used a mixed-methods research approach comprising a hypothetical choice modelling survey and qualitative interviews to explore the drivers of wild meat consumption and consumer preferences among residents of Ho Chi Minh City, Vietnam. Our findings indicate that demand for wild meat is heterogeneous and highly context specific. Wild-sourced, rare, and expensive wild meat-types are eaten by those situated towards the top of the societal hierarchy to convey wealth and status and are commonly consumed in lucrative business contexts. Cheaper, legal and farmed substitutes for wild-sourced meats are also consumed, but typically in more casual consumption or social drinking settings. We explore the implications of our results for current conservation interventions in Vietnam that attempt to tackle illegal and potentially unsustainable trade in and consumption of wild meat and detail how our research informs future consumer-centric conservation actions

    Kaposi’s Sarcoma-Associated Herpesvirus Increases PD-L1 and Proinflammatory Cytokine Expression in Human Monocytes

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    ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with the human malignancy Kaposi’s sarcoma and the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman’s disease. KSHV establishes lytic infection of monocytes in vivo , which may represent an important cellular reservoir during KS disease progression. KS tumors consist of latently infected endothelial cells; however, lytic phase gene products are important for KS onset. Early KS lesion progression is driven by proinflammatory cytokines supplied by immune cell infiltrates including T cells and monocytes. KSHV-infected monocytes may supply the lytic viral products and the inflammatory milieu conducive to KS tumor progression. To establish successful infection, KSHV extensively modulates the host immune system. KSHV antigens activate both innate and adaptive immune responses including KSHV-specific T cells, but lifelong infection is still established. Programmed death ligand 1 (PD-L1) is a prosurvival cell surface protein that suppresses T-cell-mediated killing. PD-L1 is variably present on various tumor cells and is a targetable marker for cancer treatment. We show that KSHV infection of human monocytes increases PD-L1 expression and transcription in a dose-dependent manner. We also saw evidence of lytic gene expression in the KSHV-infected monocytes. Intact KSHV is needed for full PD-L1 response in human monocytes. KSHV induces a general proinflammatory cytokine milieu including interleukins 1α, 1β, and 6, which have been implicated in early KS lesion progression. KSHV-mediated PD-L1 increase may represent a novel mechanism of KSHV-mediated immune modulation to allow for virus survival and eventually malignant progression. IMPORTANCE KSHV is the etiologic agent of Kaposi’s sarcoma and the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman’s disease. Programmed death ligand 1 (PD-L1) is an immunosuppressive cell surface marker that inhibits T cell activation. We report that KSHV infection of primary human monocytes upregulates PD-L1 transcription and protein expression. Analysis of the cytokine and chemokine milieu following KSHV infection of monocytes revealed that KSHV induces interleukins 1α, 1β, and 6, all of which have been implicated in KS development. Our work has identified another potential immune evasion strategy for KSHV and a potential target for immunotherapy of KSHV-derived disease

    Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells

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    MicroRNAs (miRNAs) are an endogenously encoded class of small RNAs that have been proposed to function as key posttranscriptional regulators of gene expression in a range of eukaryotic species, including humans. The small size of miRNA precursors makes them potentially ideal for use by viruses as inhibitors of host cell defense pathways. Here, we demonstrate that the pathogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) encodes an array of 11 distinct miRNAs, all of which are expressed at readily detectable levels in latently KSHV infected cells. Individual KSHV miRNAs were expressed at up to 2,200 copies per cell. The KSHV miRNAs are expressed from what appears to be a single genetic locus that largely coincides with an ≈4-kb noncoding sequence located between the KSHV v-cyclin and K12/Kaposin genes, both of which are also expressed in latently infected cells. Computer analysis of potential mRNA targets for these viral miRNAs identified a number of interesting candidate genes, including several mRNAs previously shown to be down-regulated in KSHV-infected cells. We hypothesize that these viral miRNAs play a critical role in the establishment and/or maintenance of KSHV latent infection in vivo and, hence, in KSHV-induced oncogenesis
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