Widespread Repression Research Articles

Recent Insights into Plant–Virus Interactions through Proteomic Analysis

Plant viruses represent a major threat for a wide range of host species causing severe losses in agricultural practices. The full comprehension of mechanisms underlying events of virus-host plant interaction is crucial to devise novel plant resistance strategies. Until now, functional genomics studies in plant-virus interaction have been limited mainly on transcriptomic analysis. Only recently are proteomic approaches starting to provide important contributions to this area of research. Classical two-dimensional electrophoresis (2-DE) coupled to mass spectrometry (MS) is still the most widely used platform in plant proteome analysis, although in the last years the application of quantitative "second generation" proteomic techniques (such as differential in gel electrophoresis, DIGE, and gel-free protein separation methods) are emerging as more powerful analytical approaches. Apparently simple, plant-virus interactions reveal a really complex pathophysiological context, in which resistance, defense and susceptibility, and direct virus-induced reactions interplay to trigger expression responses of hundreds of genes. Given that, this review is specifically focused on comparative proteome-based studies on pathogenesis of several viral genera, including some of the most important and widespread plant viruses of the genus Tobamovirus, Sobemovirus, Cucumovirus and Potyvirus. In all, this overview reveals a widespread repression of proteins associated with the photosynthetic apparatus, while energy metabolism/protein synthesis and turnover are typically up-regulated, indicating a major redirection of cell metabolism. Other common features include the modulation of metabolisms concerning sugars, cell wall, and reactive oxigen species as well as pathogenesis-related (PR) proteins. The fine-tuning between plant development and antiviral defense mechanisms determines new patterns of regulation of common metabolic pathways. By offering a 360-degree view of protein modulation, all proteomic tools reveal the extraordinary intricacy of mechanisms with which a simple viral genome perturbs the plant cell molecular networks. This "omic" approach, while providing a global perspective and useful information to the understanding of the plant host-virus interactome, may possibly reveal protein targets/markers useful in the design of future diagnosis and/or plant protection strategies.

Oil, Coalitions, and Regime Durability: the Origins and Persistence of Popular Rentierism in Kuwait

While the canonical literature on oil wealth suggests that hydrocarbon windfalls encourage repressive despotism, Kuwait provides a case of an oil-rich autocracy governing instead through popular rentierism—that is, through a broad coalition of social forces, one that furnishes enduring loyalty from below while constraining abuses of state power from above. This paper provides a theoretically guided explanation for this exceptional outcome. I argue that the Kuwaiti regime’s coalitional bargains originated in the pre-oil era, when domestic opposition and geopolitical constrictions compelled it to forge new social alliances at the dawn of modern statehood. This inclusionary strategy mediated the subsequent effect of oil rents, which the regime used to institutionalize its mass base with costly material and symbolic side payments. Such popular incorporation bound large constituent classes to the regime’s survival, precluding the need for widespread repression. After 50 years, these coalitional bargains have also proven remarkably resilient, as social actors have continued to endorse the autocratic leadership despite economic crisis and wartime defeat.

Political Opportunities, Constraints, and Mobilizing Structures: An Integrated Approach to Different Levels of Ethno-Political Contention in Northeast India

The article examines why some ethnic groups seeking ethno-political autonomy engage in violence while others respond with relative quiescence. It compares and contrasts the ethno-political movements of the Bodos and Misings in northeast India and adopts an integrated approach in which the mobilizing structure and state responses assume equal and important roles that determine the correlation between the mobilizing process and levels of contention. A fundamental claim is that popular support and participation are crucial to shape the trajectories and strategies of ethnic movements. What determines the level of popular following is long-term commitment, legitimacy, and effective communicative strategies adopted by activist organizations. This in turn, generates collective mobilization and produces mechanisms for violence. The absence thereof leads to less disruptive contention. Further, the level of ethnic contention is determined by consistency and extent of ethnic accommodation and the nature of state repression. Consistent accommodation can have a countervailing effect on the activists to launch violent rebellion. Accommodation may range from implementing particular ethno-linguistic policies to selective incentives or cooptation of core political activists by the government. Contrarily, inconsistent accommodation and widespread state repression leads to high levels of violence.

The Global Consequence of Disruption of the AcrAB-TolC Efflux Pump in Salmonella enterica Includes Reduced Expression of SPI-1 and Other Attributes Required To Infect the Host

The mechanisms by which RND pumps contribute to pathogenicity are currently not understood. Using the AcrAB-TolC system as a paradigm multidrug-resistant efflux pump and Salmonella enterica serovar Typhimurium as a model pathogen, we have demonstrated that AcrA, AcrB, and TolC are each required for efficient adhesion to and invasion of epithelial cells and macrophages by Salmonella in vitro. In addition, AcrB and TolC are necessary for Salmonella to colonize poultry. Mutants lacking acrA, acrB, or tolC showed differential expression of major operons and proteins involved in pathogenesis. These included chemotaxis and motility genes, including cheWY and flgLMK and 14 Salmonella pathogenicity island (SPI)-1-encoded type III secretion system genes, including sopE, and associated effector proteins. Reverse transcription-PCR confirmed these data for identical mutants in two other S. Typhimurium backgrounds. Western blotting showed reduced production of SipA, SipB, and SipC. The absence of AcrB or TolC also caused widespread repression of chemotaxis and motility genes in these mutants, and for acrB::aph, this was associated with decreased motility. For mutants lacking a functional acrA or acrB gene, the nap and nir operons were repressed, and both mutants grew poorly in anaerobic conditions. All phenotypes were restored to that of the wild type by trans-complementation with the wild-type allele of the respective inactivated gene. These data explain how mutants lacking a component of AcrAB-TolC are attenuated and that this phenotype is a result of decreased expression of numerous genes encoding proteins involved in pathogenicity. The link between antibiotic resistance and pathogenicity establishes the AcrAB-TolC system as fundamental to the biology of Salmonella.

Repression of C. elegans microRNA targets at the initiation level of translation requires GW182 proteins

MicroRNAs (miRNAs) repress target genes through a poorly defined antisense mechanism. Cell-free and cell-based assays have supported the idea that miRNAs repress their target mRNAs by blocking initiation of translation, whereas studies in animal models argued against this possibility. We examined endogenous targets of the let-7 miRNA, an important regulator of stem cell fates. We report that let-7 represses translation initiation in Caenorhabditis elegans, demonstrating this mode of action for the first time in an organism. Unexpectedly, although the lin-4 miRNA was previously reported to repress its targets at a step downstream of translation initiation, we also observe repression of translation initiation for this miRNA. This repressive mechanism, which frequently but not always coincides with transcript degradation, requires the GW182 proteins AIN-1 and AIN-2, and acts on several mRNAs targeted by different miRNAs. Our analysis of an expanded set of endogenous miRNA targets therefore indicates widespread repression of translation initiation under physiological conditions and establishes C. elegans as a genetic system for dissection of the underlying mechanisms.

Hypoxia induces a novel signature of chromatin modifications and global repression of transcription

Tumor cells respond to the harsh hypoxic microenvironment, in part, by transcriptional regulation of specific target genes. We found that hypoxia-mediated activation of selected genes occurs amidst widespread repression of transcription that is neither cell type-specific nor HIF-1-dependent. Despite overall repression, hypoxia induces a pool of histone modifications typically associated with transcriptional activation or repression. Chromatin immunoprecipitation analyses showed that this global mixture of hypoxia-modified histones is sorted in a gene-specific manner to correlate with transcriptional response to hypoxia. Exceptions to this were unexpected increases in H3K4me3 levels, typically associated with transcriptional activation, and decreased H3K27me3 levels, generally a marker of transcriptional silencing, at core promoters of both hypoxia-activated and -repressed genes. These data suggest that a novel signature of chromatin modifications is induced under hypoxic stress, which may play a role in gene regulatory switches active in proliferating tumor cells undergoing cycles of hypoxia and reoxygenation.

Widespread microRNA repression by Myc contributes to tumorigenesis

The c-Myc oncogenic transcription factor (Myc) is pathologically activated in many human malignancies. Myc is known to directly upregulate a pro-tumorigenic group of microRNAs (miRNAs) known as the miR-17-92 cluster. Through the analysis of human and mouse models of B cell lymphoma, we show here that Myc regulates a much broader set of miRNAs than previously anticipated. Unexpectedly, the predominant consequence of activation of Myc is widespread repression of miRNA expression. Chromatin immunoprecipitation reveals that much of this repression is likely to be a direct result of Myc binding to miRNA promoters. We further show that enforced expression of repressed miRNAs diminishes the tumorigenic potential of lymphoma cells. These results demonstrate that extensive reprogramming of the miRNA transcriptome by Myc contributes to tumorigenesis.

Comparative Expression Profiling of Nicotiana benthamiana Leaves Systemically Infected with Three Fruit Tree Viruses

Plant viruses cause a wide array of disease symptoms and cytopathic effects. Although some of these changes are virus specific, many appear to be common even among diverse viruses. Currently, little is known about the underlying molecular determinants. To identify gene expression changes that are concomitant with virus symptoms, we performed comparative expression profiling experiments on Nicotiana benthamiana leaves infected with one of three different fruit tree viruses that produce distinct symptoms: Plum pox potyvirus (PPV; leaf distortion and mosaic), Tomato ringspot nepovirus (ToRSV; tissue necrosis and general chlorosis), and Prunus necrotic ringspot ilarvirus (PNRSV; subtle chlorotic mottling). The numbers of statistically significant genes identified were consistent with the severity of the observed symptoms: 1,082 (ToRSV), 744 (PPV), and 89 (PNRSV). In all, 56% of the gene expression changes found in PPV-infected leaves also were altered by ToRSV, 87% of which changed in the same direction. Both PPV- and ToRSV-infected leaves showed widespread repression of genes associated with plastid functions. PPV uniquely induced the expression of large numbers of cytosolic ribosomal genes whereas ToRSV repressed the expression of plastidic ribosomal genes. How these and other observed expression changes might be associated with symptom development are discussed.

Destabilization of ΔNp63α by Nedd4-Mediated Ubiquitination Ubc9-Mediated Sumoylation, and Its Implications on Dorsoventral Patterning of the Zebrafish Embryo

We have recently identified the p53-related ΔNp63α gene as a transcriptional target ofBmp signaling that encodes a transcriptional repressor blocking neural developmentin the zebrafish ectoderm. However, in contrast to Bmps, the neural-repressing effectof forced ΔNp63α expression is restricted to the presumptive forebrain, whileposterior regions of the brain are not affected. Here, we show that this is due toinstability of ΔNp63α protein on the dorsal side of the embryo. In a yeast-two-hybridscreen, we isolated two ΔNp63α-modifying enzymes, the SUMO-conjugating enzymeUbc9 and the ubiquitin ligase Nedd4. The proteins bind to distinct sites in the Cterminalregion of ΔNp63α, which are absent in the shorter and more stable ΔNp63αisoform. Similarly, mutant versions of ΔNp63α unable to bind Nedd4 or Ubc9 arestabilized. ΔNp63α is sumoylated and ubiquitinated both in HEK293 cells and inzebrafish embryos, and Nedd4 promotes ubiquitination and instability of ?Np63?protein, with lysine residue 637 serving as a potential alternative sumoylation andubiquitination site that is crucial forΔNp63α destabilization. In zebrafish, ubc9.1 andnedd4 show restricted expression on the dorsal side of the embryo, where ΔNp63αinstability can be overcome upon blockage of endogenous Nedd4 activity, or uponinjection of mutant versions of ΔNp63α that are unable to bind Nedd4 or Ubc9. Thisresults in a more widespread neural repression, affecting the entire Bmp-sensitiveneuroectoderm. In sum, our data indicate that ΔNp63α is ubiquitinated in a Nedd4-and sumoylated in a Ubc9-dependent fashion, and that these modifications canregulate ΔNp63α stability in the zebrafish ectoderm.

The reemergence of the Venezuelan Armed Forces as a political actor

On the evening of 11 April 2002, the third day of a general strike, the Venezuelan armed forces rebelled against their president, Hugo Chavez Frías. Reacting to the bloody outcome of clashes between pro- and antigovernment demonstrators near the presidential palace, the commander of the Army, General Efraím Vásquez Velasco, announced in a nationally televised address that he would no longer obey presidential orders. General Vásquez accused Hugo Chávez of preparing widespread repression of antigovernment strikers and demonstrators and he ordered military units under his command to disregard further government orders and remain confined to base. High-ranking generals and admirals soon followed Vásquez onto the airwaves, expressing their solidarity with his position and their refusal to support President Chávez. In the early hours of 12 April 2002, the senior military officer in the Venezuelan armed forces, General Lucas Rincón Romero, announced the resignation of President Chávez and the formation of a transitional government under the leadership of Pedro Carmona Estanga, president of the National Federation of Chambers of Commerce (FEDECAMARAS).1

A variety of RNA polymerases II and III-dependent promoter classes is repressed by factors containing the Krüppel-associated/finger preceding box of zinc finger proteins.

KRAB/FPB (Krüppel-associated/finger preceding box) domains are small, portable transcriptional repression motifs, encoded by hundreds of vertebrates C2-H2-type zinc finger genes. We report that KRAB/FPB domains feature an unprecedented, highly promiscuous DNA-binding dependent transcriptional repressing activity. Indeed, template bound chimeric factors containing KRAB/FPB modules actively repress in vivo the transcription of distinct promoter classes that depend on different core elements, recruit distinct basal transcriptional apparatuses and are transcribed either by RNA polymerase II or III. The promoter types repressed in transient assays in a dose- and DNA-binding dependent, but position- and orientation-independent manner, by GAL4-KRAB/FPB fusions include an RNA polymerase II-dependent small nuclear RNA promoter (U1) as well as RNA polymerase III-dependent class 2 (adenovirus VA1), class 3 (human U6) and atypical (human 7SL) promoters. Down-modulation of all of these templates depended on factors containing the A module of the KRAB/FPB domain. Data provide further insights into the properties and mode of action of this widespread repression motif, and support the notion that genes belonging to distinct classes may be repressed in vivo by KRAB/FPB containing zinc finger proteins. The exquisitely DNA-binding dependent transcriptional promiscuity exhibited by KRAB/FPB domains may provide a unique model system for studying the mechanism by which a promoter recruited repression motif can down-modulate a large variety of promoter types.

Hyperactivation of the silencing proteins, Sir2p and Sir3p, causes chromosome loss.

The SIRgene products maintain transcriptional repression at the silent mating type loci and telomeres in Saccharomyces cerevisiae, although no enzymatic or structural activity has been assigned to any of the Sir proteins nor has the role of any of these proteins in transcriptional silencing been clearly defined. We have investigated the functions and interactions of the Sir2, Sir3, and Sir4 proteins by overexpressing them in yeast cells. We find that Sir2p and Sir3p are toxic when overexpressed, while high Sir4p levels have no toxic effect. Epistasis experiments indicate that Sir2p-induced toxicity is diminished in strains lacking the SIR3 gene, while both Sir2p and Sir4p are required for Sir3p to manifest its full toxic effect. In addition, the effects of Sir2 or Sir3 overexpression are exacerbated by specific mutations in the N-terminus of the histone H4 gene. These results are consistent with a model in which Sir2p, Sir3p and Sir4p function as a complex and interact with histones to modify chromatin structure. We find no evidence that toxicity from high levels of the Sir proteins results from widespread repression of transcription. Instead, we find that high levels of Sir2p and/or Sir3p cause a profound decrease in chromosome stability. These results can be appreciated in the context of the effects of Sir2p in histone acetylation and of chromatin structure on chromosome stability.

Government and Opposition in Kenya, 1966–9

Littleexists to document the widespread repression of opposition in Africa since independence. Current studies of the rise of capitalism and the post-colonial state largely ignore institutionalised authoritarianism, which characterises the political side of this process. This article discusses the restraints placed on opposition in Kenya up to 1969. Its salience continues with the creation of ade jureone-party state since the abortive coup of 1982.

Campus Disruptions and the Liberal-Left

As students get busted physically and by the law in increasingly brutal ways, and in rising numbers, the thirtyish and older "real" liberals and radicals, whom we will call the liberal-left, side with the student left on most of the issues. But the problem they see is that the student left may well bring on widespread repression, so much so as to end hopes even for reform. The student left knows this well, but to their elders their words might well be Cleaver's dictum: "You're part of the solution, or you're part of the problem." Up to now, the liberal-left has been part of the problem.This article can also be found at the Monthly Review website, where most recent articles are published in full.Click here to purchase a PDF version of this article at the Monthly Review website.