Identification of New Genes Related to Virulence of Xanthomonas axonopodis Pv. Citri during Citrus Host Interactions

A mutant library of the bacterium Xanthomonas citri subsp. citri strain 306 pathotype A (Xac), the causative agent of most aggressive Asiatic type A citrus canker, was screened regarding altered canker symptoms after inoculations into Citrus sinensis and Citrus limonia host leaves. Twenty-six mutants have shown phenotypic virulence changes and have respectively knocked out gene identified by sequencing. In vivo growth curves were obtained for nine mutants to quantify how the mutations could affect pathogen's adaptability to growth inside and attack host plant infected tissue. Among identified genes in mutated strains, we could find those that until now had not been reported as being involved in Xac adaptation and/or virulence, such as predicted to encode for xylose repressor-like protein (XAC Delta xylR), Fe-S oxidoredutase (XAC Delta aslB), helicase IV (XAC Delta helD), ubiquinol cytochrome c oxidoreductase iron-sulfur subunit (XAC Delta petA), chromosome partitioning protein (XAC Delta parB) and cell division protein FtsB (XAC Delta ftsB), in addition to genes predicted to encode for hypothetical proteins. The new genes found in this study as being relevant to adaptation and virulence, improve the understanding of Xac fitness during citrus plant attack and canker symptoms development.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior-CAPESCNPqFundo de Defesa da Citricultura (FUNDECITRUS)CAPESFUNDECITRUSFAPESPSao Paulo State Univ UNESP, Fac Agr Sci & Vet, Dept Technol, Jaboticabal, SP, BrazilCitriculture Res Ctr Sylvio Moreira IAC Campinas, Campinas, SP, BrazilUniv Fed Ouro Preto, Inst Exact & Biol Sci, Dept Biol Sci, Ouro Preto, MG, BrazilUniv Fed Ouro Preto, Res Ctr Biol Sci NUPEB, Inst Exact & Biol Sci, Dept Biol Sci, Ouro Preto, MG, BrazilSao Paulo State Univ UNESP, Fac Agr Sci & Vet, Plant Hlth Dept, Jaboticabal, SP, BrazilFed Univ Sao Paulo UNIFESP, Dept Biol Sci, Diadema, SP, BrazilFed Univ Sao Paulo UNIFESP, Dept Biol Sci, Diadema, SP, BrazilFAPESP: 04/02006-7Web of Scienc

The force of events: the 'Brexit interval' and popular aspirations for Gibraltarian diplomacy

This paper highlights both an overreliance on legal perspectives in the study of paradiplomacy at the expense of more dynamic understandings of agency, and also the affective force of waiting and other temporal states on political subject formation. Empirically, it reports the results of a longitudinal study on Gibraltarians’ concerns over the Gibraltar–Spain frontier. By comparing data from two identical surveys conducted a year apart during the period between the Brexit referendum and the (as yet incomplete) legal withdrawal, we trace the force of the incomplete event on political subjectivities. Conceptualizing our findings through assemblage theory and paradiplomacy, we highlight that the intensity of the event has heightened Gibraltarians’ dissatisfaction with their constitutional reliance on the UK to resolve Brexit in a way advantageous for Gibraltar. A minor shift occurred in the year studied towards more agentic proscriptions of what the Government of Gibraltar ought to do to resolve Brexit. Quantitative analysis reveals that younger respondents tend to emphasize this more agentic view, while older respondents tend to advocate further lobbying of the UK or feel Gibraltar has a complete lack of agency. Qualitative analysis of the respondents’ policy proscriptions reveals a complex set of views within each perspective on agency

Angiostatin anti-angiogenesis requires IL-12: The innate immune system as a key target

© 2009 Albini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Tyrosine kinase inhibitors reprogramming immunity in renal cell carcinoma: rethinking cancer immunotherapy

Review article[Abstract] The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity. Given the antitumor activity of selected TKIs in metastatic RCC (mRCC), it seems relevant to assess their effect on the immune system. The confirmation that TKIs improve cell cytokine response in mRCC provides a basis for the rational combination and sequential treatment of TKIs and immunotherapy

Gene Expression Profiling of Liver Cancer Stem Cells by RNA-Sequencing

Background: Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90 + liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90 + cells sorted from tumor (CD90 +CSCs) with parallel non-tumorous liver tissues (CD90 +NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis. Methodology/Principal Findings: CD90 + cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90 + cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90 +CSCs and CD90 +NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90 +CSCs and CD90 +NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90 +CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90 +CSCs compared to CD90 +NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90 +CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90 +CSCs in liver tumor tissues. Conclusions/Significance: The identified genes, such as GPC3 that are distinctly expressed in liver CD90 +CSCs, may be promising gene candidates for HCC therapy without inducing damages to normal liver stem cells. © 2012 Ho et al.published_or_final_versio

The Tumor Microenvironment: The Making of a Paradigm

What has been will be again, what has been done will be done again; there is nothing new under the su