Epigenetic mechanisms in hepatocellular carcinoma: how environmental factors influence the epigenome

Epigenetic mechanisms maintain heritable changes in gene expression and chromatin organization over many cell generations. Importantly, deregulated epigenetic mechanisms play a key role in a wide range of human malignancies, including liver cancer. Hepatocellular carcinoma (HCC), which originates from the hepatocytes, is by far the most common liver cancer, with rates and aetiology that show considerable geographic variation. Various environmental agents and lifestyles known to be risk factors for HCC (such as infection by hepatitis B virus (HBV) and hepatitis C virus (HCV), chronic alcohol intake, and aflatoxins) are suspected to promote its development by eliciting epigenetic changes, however the precise gene targets and underlying mechanisms have not been elucidated. Many recent studies have exploited conceptual and technological advances in epigenetics and epigenomics to investigate the role of epigenetic events induced by environmental factors in HCC tumors and non-tumor precancerous (cirrhotic) lesions. These studies have identified a large number of genes and pathways that are targeted by epigenetic deregulation (changes in DNA methylation, histone modifications and RNA-mediated gene silencing) during the development and progression of HCC. Frequent identification of aberrant epigenetic changes in specific genes in cirrhotic tissue is consistent with the notion that epigenetic deregulation of selected genes in pre-malignant lesions precedes and promotes the development of HCC. In addition, several lines of evidence argue that some environmental factors (such as HBV virus) may abrogate cellular defense systems, induce silencing of host genes and promote HCC development via an "epigenetic strategy". Finally, profiling studies reveal that HCC tumors and pre-cancerous lesions may exhibit epigenetic signatures associated with specific risk factors and tumor progression stage. Together, recent evidence underscores the importance of aberrant epigenetic events induced by environmental factors in liver cancer and highlights potential targets for biomarker discovery and future preventive and therapeutic strategies.     

Tobacco wars: the bloody battle between good health and good politics

A battle to introduce new antitobacco legislation in Canada has caused political battles within the Liberal Party. While one side is worried about the need to protect people''s health, another is worried about the potential loss of jobs within the tobacco industry--many of which are located in politically volatile Quebec. Charlotte Gray writes about the machinations that led to the introduction of new smoking legislation in the House of Commons in November.     

The second earthquake: how the Italian state generated hope and uncertainty in post‐disaster L'Aquila

Recent analyses of the state have emphasized its inability to generate hope among citizens, suggesting that neoliberalism and globalization erode its protective power. However, this article suggests that the state still features as a coveted agent of support, in particular during unstable times. After the 2009 L'Aquila earthquake, the Italian state became the key actor responsible for emergency aid, restoration, and urban redevelopment. Dedication and the performance of compassion produced expectations of swift improvement. Hope became dependent on state authority. A few years later, uncertainty replaced hope, as promises for recovery remained unrealized. The state morphed from an agent of hope into the source of hopelessness, generating uncertainty and a sense of crisis. Since the state is revealed through its effects, this article highlights the need to trace state power in intimate human emotional experience, such as hope or despair. The production of a specific condition of uncertainty reveals the significance of state power in human life, particularly during times of personal or collective crisis.     

Patent border wars: defining the boundary between scientific discoveries and patentable inventions

Drawing an appropriate boundary between unpatentable natural phenomena and patentable inventions is crucial in preventing the patent laws from unduly restricting access to fundamental scientific discoveries. Some would argue that, particularly in the U.S., patents are being issued that purport to claim a novel product or process but that, in effect, encompass any practical application of a fundamental biological principle. Examples include gene patents, which Congress is considering banning, and patents relating to biological correlations and pathways, such as the patents at issue in the headline-grabbing LabCorp v. Metabolite and Ariad v. Eli Lilly litigations. In view of the mounting concern, it seems likely that Congress and/or the courts will address the issue, and perhaps substantially shift the boundary.     

'Keeping the state away': democracy, politics, and the state in India's Jharkhand

This article explores why in India's Jharkhand, Mundas, often depicted as poor tribals, participate in elections to keep the state away, seeing it as foreign, dangerous, and juxtaposing its self-interested and divisive politics with a sacral polity, the parha . Munda disengagement with the state results from a complex combination of their contrasting the state with the sacral polity, historical experience of exploitation by state officers, and social relations with rural elites who, seeking to maintain dominance, reproduce Munda imaginings. The article thus draws attention to multiple co-existing notions of politics and the importance of a local political economy in the social production of cultural imaginings of the state.     

Speed versus accuracy in decision-making ants: expediting politics and policy implementation

Compromises between speed and accuracy are seemingly inevitable in decision-making when accuracy depends on time-consuming information gathering. In collective decision-making, such compromises are especially likely because information is shared to determine corporate policy. This political process will also take time. Speed–accuracy trade-offs occur among house-hunting rock ants, Temnothorax albipennis. A key aspect of their decision-making is quorum sensing in a potential new nest. Finding a sufficient number of nest-mates, i.e. a quorum threshold (QT), in a potential nest site indicates that many ants find it suitable. Quorum sensing collates information. However, the QT is also used as a switch, from recruitment of nest-mates to their new home by slow tandem running, to recruitment by carrying, which is three times faster. Although tandem running is slow, it effectively enables one successful ant to lead and teach another the route between the nests. Tandem running creates positive feedback; more and more ants are shown the way, as tandem followers become, in turn, tandem leaders. The resulting corps of trained ants can then quickly carry their nest-mates; but carried ants do not learn the route. Therefore, the QT seems to set both the amount of information gathered and the speed of the emigration. Low QTs might cause more errors and a slower emigration—the worst possible outcome. This possible paradox of quick decisions leading to slow implementation might be resolved if the ants could deploy another positive-feedback recruitment process when they have used a low QT. Reverse tandem runs occur after carrying has begun and lead ants back from the new nest to the old one. Here we show experimentally that reverse tandem runs can bring lost scouts into an active role in emigrations and can help to maintain high-speed emigrations. Thus, in rock ants, although quick decision-making and rapid implementation of choices are initially in opposition, a third recruitment method can restore rapid implementation after a snap decision. This work reveals a principle of widespread importance: the dynamics of collective decision-making (i.e. the politics) and the dynamics of policy implementation are sometimes intertwined, and only by analysing the mechanisms of both can we understand certain forms of adaptive organization.     

The state of ethnicity and the ethnicity of the state: Ethnic politics in Southeast Asia

Attitudes about racial inequality in the United States are often viewed through the lenses of discrimination and disadvantage. However, as whiteness studies suggest, systems of racial inequality produce both disadvantage and advantage. National surveys have documented explanations for African American disadvantage but have not collected data on explanations for white advantage. African American disadvantage and white advantage are two sides of the same coin – racial inequality. To understand attitudes about racial inequality, we need to know Americans' beliefs about both sides of the racialized system. This research uses national survey data to examine explanations for both sides of racial inequality and identifies which factors are believed to be most important in explaining white advantage, finding that racial attitudes are complex and are dependent upon the specific situation and context. This research will provide a valuable contribution to both whiteness studies and race relations research.     

Trans-Kemalism: the politics of the Turkish state in the diaspora

Abstract

In contrast to the huge amount of research on Turkish migration and migrants, the diasporic politics of the Turkish Kemalist state constitutes a neglected research subject in the scholarship on Turkish diaspora. How does the Turkish state reach out to its nationals and expatriates abroad? In what ways does the Turkish Republic seek to make Islam (as it does in Turkey) into an instrument legitimizing its politicizing and mobilizing enterprises? To explore these questions, this article investigates the long-distance Kemalism engaged in by the Turkish state to Turkify and secularize its nationals in the diaspora, using its activities in Australia as its case study. In sketching out trans-Kemalism's dimensions, the analysis directs attention to the intimate relationship between the political and religious fields of transnationalism manufactured by the state. The paper concludes that the intense political polarization in Turkey in the present makes the future of trans-Kemalism abroad somewhat uncertain.     

Disaster taxa in microbially mediated metazoans: how endosymbionts and environmental catastrophes influence the adaptive capacity of reef corals

Reef corals are examples of metazoans that engage in mutualisms with a variety of microorganisms, including dinoflagellates, Bacteria, Archaea, and viruses. The high adaptive capacity of these microbial symbionts can be co‐opted by their coral hosts, and various emergent traits of these associations, such as thermotolerance, are undergoing strong selection due to climate change. This selection may spur the rise of microbial ‘disaster taxa’: opportunistic, cosmopolitan generalists that can proliferate and increase host survivorship following disturbances. Coral bleaching (a stress‐induced loss of dinoflagellates) constitutes one type of catastrophic disturbance for resident symbiont communities, and opens novel patches of host for colonization by microbial disaster taxa. Moreover, the compartmentalization of microbial symbionts within coral polyps reduces their effective population size and thus facilitates the spread of disaster taxa during times of environmental change. These phenomena suggest that, despite widespread loss of coral cover as a result of climate disturbances, the potential spread of resilient microbial disaster taxa in surviving colonies can have important implications for coral reef persistence over the coming decades.     

Mapping uncertainty and phylogenetic uncertainty in ancestral character state reconstruction: an example in the moss genus Brachytheciastrum

The evolution of species traits along a phylogeny can be examined through an increasing number of possible, but not necessarily complementary, approaches. In this paper, we assess whether deriving ancestral states of discrete morphological characters from a model whose parameters are (i) optimized by ML on a most likely tree; (II) optimized by ML onto each of a Bayesian sample of trees; and (III) sampled by a MCMC visiting the space of a Bayesian sample of trees affects the reconstruction of ancestral states in the moss genus Brachytheciastrum. In the first two methods, the choice of a single- or two-rate model and of a genetic distance (wherein branch lengths are used to determine the probabilities of change) or speciational (wherein changes are only driven by speciation events) model based upon a likelihood-ratio test strongly depended on the sampled trees. Despite these differences in model selection, reconstructions of ancestral character states were strongly correlated to each others across nodes, often at r > 0.9, for all the characters. The Bayesian approach of ancestral character state reconstruction offers, however, a series of advantages over the single-tree approach or the ML model optimization on a Bayesian sample of trees because it does not involve restricting model parameters prior to reconstructing ancestral states, but rather allows a range of model parameters and ancestral character states to be sampled according to their posterior probabilities. From the distribution of the latter, conclusions on trait evolution can be made in a more satisfactorily way than when a substantial part of the uncertainty of the results is obscured by the focus on a single set of model parameters and associated ancestral states. The reconstructions of ancestral character states in Brachytheciastrum reveal rampant parallel morphological evolution. Most species previously described based on phenetic grounds are thus resolved of polyphyletic origin. Species polyphylly has been increasingly reported among mosses, raising severe reservations regarding current species definition.