If neuroimaging is the answer,what is the question?

It is unclear that we will come to a better understanding of mental processes simply by observing which neural loci are activated while subjects perform a task. Rather, I suggest here that it is better to come armed with a question that directs one to design tasks in ways that take advantage of the strengths of neuroimaging techniques (particularly positron emission tomography and functional magnetic resonance imaging). Here I develop a taxonomy of types of questions that can be easily addressed by such techniques. The first class of questions focuses on how information processing is implemented in the brain; these questions can be posed at a very coarse scale, focusing on the entire system that confers a particular ability, or at increasingly more specific scales, ultimately focusing on individual structures or processes. The second class of questions focuses on specifying when particular processes and structures are invoked; these questions focus on how one can use patterns of activation to infer that specific processes and structures were invoked, and on how processing changes in different circumstances. The use of neuroimaging to address these questions is illustrated with results from experiments on visual cognition, and caveats regarding the logic of inference in each case are noted. Finally, the necessary interplay between neuroimaging and behavioural studies is stressed.     

Vaults are the answer, what is the question?

Vaults are large cytoplasmic ribonucleoprotein (RNP) particles of eukaryotic cells, whose considerable abundance and striking evolutionary conservation argue for an important general cellular function. Early studies on vaults focused on the structural features and cellular distribution of the particle and will only be summarized briefly here. In this article, we discuss the molecular characterization of vault components and describe genetic studies carried out in Dictyostelium. The recent finding that the major vault protein is elevated in non-P-glycoprotein multidrug resistant cancer cells has direct implications concerning the function of the vault particle and indicates a potential role for vaults in resistance of tumour cells to anticancer drugs.     

Vaccination against shigellosis: is it the path that is difficult or is it the difficult that is the path?

Following several decades of research, there is not yet a convincing vaccine against shigellosis. It is still difficult, in spite of the breadth of strategies (i.e. live attenuated oral, killed oral, subunit parenteral) to select an optimal option. Two approaches are clearly emerging: (i) live attenuated deletion mutants based on rational selection of genes that are key in the pathogenic process, and (ii) conjugated detoxified polysaccharide parenteral vaccines, or more recently conjugated synthetic carbohydrates. Some of these approaches have already undergone phase I and II clinical trials with promising results, but important issues have also emerged, particularly the discrepancy between colonization and immunogenic potential of live attenuated vaccine candidates depending upon the population concerned (i.e. non endemic vs. endemic areas). Efforts are needed to definitely establish the proof of concept of these approaches, and thus the need for clinical trials which should also soon explore the possibility to associate different serotypes, in response to serotype specific protection against shigellosis. More basic research is also required to improve what we can still consider as first-generation vaccines, and to explore possible new paradigms including the search for cross-protective antigens.     

What, if anything, is the adaptive function of countershading?

Countershading, the gradation of colour from dark on the dorsum to light on the ventrum, is generally considered to have the effect of making organisms difficult to detect. The mechanism that facilitates this form of crypsis is often considered to be concealment of shadows cast on the body of the animal. We review the current empirical evidence for the cryptic function of countershading and for the mechanism underlying it. We argue that there is no conclusive evidence that countershading per se provides any selective advantage in terrestrial or aerial environments. However, the highly refined adaptations of some marine organisms to match the different background light conditions against which they are set when viewed from different aspects strongly suggest an adaptive advantage to countershading in these environments. In none of the cases discussed in this review was the conventional explanation of self-shadow concealment a more plausible explanation for countershading than the alternative explanation that the dorsum and ventrum experience different selection pressures (often associated with background matching).     

Genetics of the human metabolome,what is next?

Increases in throughput and decreases in costs have facilitated large scale metabolomics studies, the simultaneous measurement of large numbers of biochemical components in biological samples. Initial large scale studies focused on biomarker discovery for disease or disease progression and helped to understand biochemical pathways underlying disease. The first population-based studies that combined metabolomics and genome wide association studies (mGWAS) have increased our understanding of the (genetic) regulation of biochemical conversions. Measurements of metabolites as intermediate phenotypes are a potentially very powerful approach to uncover how genetic variation affects disease susceptibility and progression. However, we still face many hurdles in the interpretation of mGWAS data. Due to the composite nature of many metabolites, single enzymes may affect the levels of multiple metabolites and, conversely, levels of single metabolites may be affected by multiple enzymes. Here, we will provide a global review of the current status of mGWAS. We will specifically discuss the application of prior biological knowledge present in databases to the interpretation of mGWAS results and discuss the potential of mathematical models. As the technology continuously improves to detect metabolites and to measure genetic variation, it is clear that comprehensive systems biology based approaches are required to further our insight in the association between genes, metabolites and disease. This article is part of a Special Issue entitled: From Genome to Function.     

To be or NUCB2, is nesfatin the answer?

Signals from the hypothalamus govern food intake and energy balance. A new study describes nesfatin-1, a hypothalamic and brainstem peptide whose expression decreases during fasting. Although central treatment with nesfatin-1 inhibited food intake and nesfatin-1 blockade increased food intake, the role and mechanism of nesfatin in energy balance remains unclear.     

What, Exactly, is Cladistics? Re-writing the History of Systematics and Biogeography

The development of comparative biology (systematics) has been of interest to philosophers and historians. Particular attention has been placed on the 'war' of the 1970s and 1980s, the apparent dispute among those who preferred this or that methodology. In this contribution we examine the history of comparative biology from the perspective of fundamentals rather than methodologies. Our examination is framed within the artificial-natural classification dichotomy, a viewpoint currently lost from view but worth resurrecting.     

Tissue transglutaminase, inflammation, and cancer: how intimate is the relationship?

Despite significant advances in surgery and biology, cancer remains a major health problem. It is now well accepted that metastasis and cancer cells’ acquired or inherent resistance to conventional therapies are major roadblocks to successful treatment. Chronic inflammation is an important driving force that provides a favorable platform for cancer’s progression and development and suggests a link between inflammation and metastatic transformation. However, how chronic inflammation contributes to metastatic cell transformation is not well understood. According to the current theory of cancer progression, a small subpopulation of cancer stem cells (CSCs) in tumors is responsible for their metastasis, resistance, and sustenance. Whether CSCs originate from normal stem cells or from dedifferentiation of terminally differentiated cells remains unknown. Recent evidence indicates that stem cells are not unique; malignant or nonmalignant cells can reprogram and de-differentiate to acquire a stemness phenotype. Thus, phenotypic plasticity may exist between stem cells and non-stem cells, and a dynamic equilibrium may exist between the two phenotypes. Moreover, this equilibrium may shift in one direction or another on the basis of contextual signals in the microenvironment that influence the interconversion between stem and non-stem cell compartments. Whether the inflammatory microenvironment influences this interconversion and shifts the dynamic equilibrium towards stem cell compartments remains unknown. We recently found that aberrant tissue transglutaminase (TG2) expression induces the mesenchymal transition (EMT) and stem cell characteristics in epithelial cells. This finding, in conjunction with the observation that inflammatory signals (e.g., TGFβ, TNFα, and NF-κB) which induce EMT, also induce TG2 expression, suggests a possible link between TG2, inflammation, and cancer progression. In this review, we summarize TG2-driven processes in inflammation and their implications in cancer progression.     

What is the function of the claustrum?

The claustrum is a thin, irregular, sheet-like neuronal structure hidden beneath the inner surface of the neocortex in the general region of the insula. Its function is enigmatic. Its anatomy is quite remarkable in that it receives input from almost all regions of cortex and projects back to almost all regions of cortex. We here briefly summarize what is known about the claustrum, speculate on its possible relationship to the processes that give rise to integrated conscious percepts, propose mechanisms that enable information to travel widely within the claustrum and discuss experiments to address these questions.