Hallmarks of cancer: of all cancer cells,all the time?

In two landmark articles, Hanahan and Weinberg synthesized into one conceptual framework 'the hallmarks of cancer', a massive amount of information describing the characteristics of a cancer cell. Although this is neither the intention nor the belief of the authors, hallmarks are often interpreted as applying to a canonic cancer cell, or equally to all cells within a cancer. In this article, we clarify the separate concepts of causes, oncogenic events, signal transduction programs, and hallmarks to show that there is no unimodal relation between these concepts but a complex network of interrelations that vary in different cells, between cells, and at different times in any given cell. We consider cancer as an evolving, dynamic, and heterogeneous system, explaining, at least in part, the difficulty of treating cancer and supporting the use of simultaneous, multitarget therapies.     

Are all fishes ancient polyploids?

Euteleost fishes seem to have more copies of many genes than their tetrapod relatives. Three different mechanisms could explain the origin of these 'extra' fish genes. The duplicates may have been produced during a fish-specific genome duplication event. A second explanation is an increased rate of independent gene duplications in fish. A third possibility is that after gene or genome duplication events in the common ancestor of fish and tetrapods, the latter lost more genes. These three hypotheses have been tested by phylogenetic tree reconstruction. Phylogenetic analyses of sequences from human, mouse, chicken, frog (Xenopus laevis), zebrafish (Danio rerio) and pufferfish (Takifugu rubripes) suggest that ray-finned fishes are likely to have undergone a whole genome duplication event between 200 and 450 million years ago. We also comment here on the evolutionary consequences of this ancient genome duplication.     

Are all MRSA made equal?

The health and economic burden of methicillin-resistant Staphylococcus aureus (MRSA) in the medical realm is considerable. Although there is ample clinical and laboratory evidence indicating that methicillin-susceptible S. aureus (MSSA) is heterogeneous in disease causation, the same heterogeneity has not been well documented for MRSA. Data from animal models and human studies suggest that MRSA is at least as pathogenic as MSSA. Many comparative clinical studies, mainly retrospective, have assessed the virulence of MSSA and MRSA. Whereas the majority of these studies may be deficient in some aspects of clinical design, there has been a definite trend towards implicating MRSA as the more aggressive pathogen. Such an observation, however, must be tempered with the fact that few such studies have attempted to establish clonality among MRSA isolates. Thus, it is conceivable that hypervirulent clones may represent an important proportion of MRSA from hospital studies where patient-patient spread is likely and, accordingly, comparative studies may be biased. Future clinical studies should be prospective and should use well-defined and homogeneous patient groups. As well, for comparison of MRSA and MSSA, an understanding of clonality is essential.     

Are all genes regulatory genes?

Although much has been learned about hereditary mechanisms since Gregor Mendel’s famous experiments, gene concepts have always remained vague, notwithstanding their central role in biology. During over hundred years of genetic research, gene concepts have often and dynamically changed to accommodate novel experimental findings, without ever providing a generally accepted definition of the ‘gene.’ Yet, the distinction between ‘regulatory genes’ and ‘structural genes’ has remained a common theme in modern gene concepts since the definition of the operon-model. This distinction is now challenged by recent findings which suggest that, at least in eukaryotes, structural genes may in many situations have a regulatory function that is independent of the function of the gene product (protein or non-coding RNA molecule). This brief paper discusses these new findings and some possible implications for the notion of the ‘regulatory gene.’     

On Are we all postracial yet?

ABSTRACT

If the postracial is a coherent formation, it is produced not by ideological lock-step but by distributed affinities and relations in a transnational space of interconnection and exchange. The neoliberal erasure of ‘?…?the structural conditions of racial reproduction and racist articulation’ (34) and the clouding of the historicity of racisms produces postraciality as ‘the illusion that the dream of the nonracial has already been realized’ (180). This illusion is familiar in writing on the postracial that focuses on the denial – be it through the averted gaze of ‘color-blindness’, or the official state prohibition of racism, or the triumphalism of strategic declarations of the ‘end of racism’ – of enduring racialized inequality. Goldberg’s advance is to explore how the illusion has become increasingly weaponized; that far from signalling the end of race, it represents an emergent ‘neo-raciality, racism’s extension if not resurrection’ (24).     

ACE for all – a molecular perspective

Angiotensin-I converting enzyme (ACE, EC 3.4.15.1) is a zinc dependent dipeptidyl carboxypeptidase with an essential role in mammalian blood pressure regulation as part of the renin-angiotensin aldosterone system (RAAS). As such, it has long been targeted in the treatment of hypertension through the use of ACE inhibitors. Although ACE has been studied since the 1950s, only recently have the full range of functions of this enzyme begun to truly be appreciated. ACE homologues have been found in a host of other organisms, and are now known to be conserved in insects. Insect ACE homologues typically share over 30 % amino acid sequence identity with human ACE. Given that insects lack a mammalian type circulatory system, they must have crucial roles in other physiological processes. The first ACE crystal structures were reported during the last decade and have enabled these enzymes to be studied from an entirely different perspective. Here we review many of these key developments and the implications that they have had on our understanding of the diverse functions of these enzymes. Specifically, we consider how structural information is being used in the design of a new generation of ACE inhibitors with increased specificity, and how the structures of ACE homologues are related to their functions. The Anopheles gambiae genome is predicted to code for ten ACE homologues, more than any genome studied so far. We have modelled the active sites of some of these as yet uncharacterised enzymes to try and infer more about their potential roles at the molecular level.