What obesity research tells us about epigenetic mechanisms

The pathophysiology of obesity is extremely complex and is associated with extensive gene expression changes in tissues throughout the body. This situation, combined with the fact that all gene expression changes are thought to have associated epigenetic changes, means that the links between obesity and epigenetics will undoubtedly be vast. Much progress in identifying epigenetic changes induced by (or inducing) obesity has already been made, with candidate and genome-wide approaches. These discoveries will aid the clinician through increasing our understanding of the inheritance, development and treatment of obesity. However, they are also of great value for epigenetic researchers, as they have revealed mechanisms of environmental interactions with epigenetics that can produce or perpetuate a disease state. Here, we will review the evidence for four mechanisms through which epigenetics contributes to obesity: as downstream effectors of environmental signals; through abnormal global epigenetic state driving obesogenic expression patterns; through facilitating developmental programming and through transgenerational epigenetic inheritance.     

What messenger RNA capping tells us about eukaryotic evolution

The 5' cap is a unique feature of eukaryotic cellular and viral messenger RNA that is absent from the bacterial and archaeal domains of life. The cap is formed by three enzymatic reactions at the 5' terminus of nascent mRNAs. Although the capping pathway is conserved in all eukaryotes, the structure and genetic organization of the component enzymes vary between species. These differences provide insights into the evolution of eukaryotes and eukaryotic viruses.     

What failure in collective decision-making tells us about metacognition

Condorcet (1785) proposed that a majority vote drawn from individual, independent and fallible (but not totally uninformed) opinions provides near-perfect accuracy if the number of voters is adequately large. Research in social psychology has since then repeatedly demonstrated that collectives can and do fail more often than expected by Condorcet. Since human collective decisions often follow from exchange of opinions, these failures provide an exquisite opportunity to understand human communication of metacognitive confidence. This question can be addressed by recasting collective decision-making as an information-integration problem similar to multisensory (cross-modal) perception. Previous research in systems neuroscience shows that one brain can integrate information from multiple senses nearly optimally. Inverting the question, we ask: under what conditions can two brains integrate information about one sensory modality optimally? We review recent work that has taken this approach and report discoveries about the quantitative limits of collective perceptual decision-making, and the role of the mode of communication and feedback in collective decision-making. We propose that shared metacognitive confidence conveys the strength of an individual's opinion and its reliability inseparably. We further suggest that a functional role of shared metacognition is to provide substitute signals in situations where outcome is necessary for learning but unavailable or impossible to establish.     

Decision-making in a social world: Integrating cognitive ecology and social neuroscience

Understanding animal decision-making involves simultaneously dissecting and reconstructing processes across levels of biological organization, such as behavior, physiology, and brain function, as well as considering the environment in which decisions are made. Over the past few decades, foundational breakthroughs originating from a variety of model systems and disciplines have painted an increasingly comprehensive picture of how individuals sense information, process it, and subsequently modify behavior or states. Still, our understanding of decision-making in social contexts is far from complete and requires integrating novel approaches and perspectives. The fields of social neuroscience and cognitive ecology have approached social decision-making from orthogonal perspectives. The integration of these perspectives (and fields) is critical in developing comprehensive and testable theories of the brain.     

What the protein data bank tells us about the evolutionary conservation of protein conformational diversity

Proteins sample a multitude of different conformations by undergoing small‐ and large‐scale conformational changes that are often intrinsic to their functions. Information about these changes is often captured in the Protein Data Bank by the apparently redundant deposition of independent structural solutions of identical proteins. Here, we mine these data to examine the conservation of large‐scale conformational changes between homologous proteins. This is important for both practical reasons, such as predicting alternative conformations of a protein by comparative modeling, and conceptual reasons, such as understanding the extent of conservation of different features in evolution. To study this question, we introduce a novel approach to compare conformational changes between proteins by the comparison of their difference distance maps (DDMs). We found that proteins undergoing similar conformational changes have similar DDMs and that this similarity could be quantified by the correlation between the DDMs. By comparing the DDMs of homologous protein pairs, we found that large‐scale conformational changes show a high level of conservation across a broad range of sequence identities. This shows that conformational space is usually conserved between homologs, even relatively distant ones.     

Polycystins: what polycystic kidney disease tells us about sperm

Experimental evidence indicates that the membrane-associated proteins polycystin-1 and polycystin-2 operate as a receptor-calcium channel complex that regulates signaling pathways essential for modulation of renal tubulogenesis. Polycystic kidney disease is characterized by defective renal tubular structure and results from mutations in either PKD1 or PKD2 genes. Recent data suggest that polycystin-1 and polycystin-2 might localize to primary cilium in principal cells of renal collecting tubules and are thought to act as mechanosensors of fluid flow and contents. Ciliary bending by fluid flow or mechanical stimulation induce Ca(2+) release from intracellular stores, presumably to modulate ion influx in response to tubular fluid flow. Polycystins are also emerging as playing a significant role in sperm development and function. Drosophila polycystin-2 is associated with the head and tail of mature sperm. Targeted disruption of the PKD2 homolog results in nearly complete male sterility without disrupting spermatogenesis. Mutant sperm are motile but are unable to reach the female storage organs (seminal receptacles and spermathecae). The sea urchin polycystin-1-equivalent suPC2 colocalizes with the polycystin-1 homolog REJ3 to the plasma membrane over the acrosomal vesicle. This localization site suggests that the suPC2-REJ3 complex may function as a cation channel mediating acrosome reaction when sperm contact the jelly layer surrounding the egg at fertilization. Future studies leading to the identification of specific ligands for polycystins, including the signaling pathways, might define the puzzling relationship between renal tubular morphogenesis and sperm development and function.     

What the evolution of the amyloid protein precursor supergene family tells us about its function

The Alzheimer's disease amyloid protein precursor (APP) gene is part of a multi-gene super-family from which sixteen homologous amyloid precursor-like proteins (APLP) and APP species homologues have been isolated and characterised. Comparison of exon structure (including the uncharacterised APL-1 gene), construction of phylogenetic trees, and analysis of the protein sequence alignment of known homologues of the APP super-family were performed to reconstruct the evolution of the family and to assess the functional significance of conserved protein sequences between homologues. This analysis supports an adhesion function for all members of the APP super family, with specificity determined by those sequences which are not conserved between APLP lineages, and provides evidence for an increasingly complex APP superfamily during evolution. The analysis also suggests that Drosophila APPL and Caenorhabditis elegans APL-1 may be a fourth APLP lineage indicating that these proteins, while not functional homologues of human APP, are similarly likely to regulate cell adhesion. Furthermore, the betaA4 sequence is highly conserved only in APP orthologues, strongly suggesting this sequence is of significant functional importance in this lineage.     

What behaviour in economic games tells us about the evolution of non-human species' economic decision-making behaviour

In the past decade, there has been a surge of interest in using games derived from experimental economics to test decision-making behaviour across species. In most cases, researchers are using the games as a tool, for instance, to understand what factors influence decision-making, how decision-making differs across species or contexts, or to ask broader questions about species’ propensities to cooperate or compete. These games have been quite successful in this regard. To what degree, however, do these games tap into species'' economic decision-making? For the purpose of understanding the evolution of economic systems in humans, this is the key question. To study this, we can break economic decision-making down into smaller components, each of which is a potential step in the evolution of human economic behaviour. We can then use data from economic games, which are simplified, highly structured models of decision-making and therefore ideal for the comparative approach, to directly compare these components across species and contexts, as well as in relation to more naturalistic behaviours, to better understand the evolution of economic behaviour and the social and ecological contexts that influenced it. The comparative approach has successfully informed us about the evolution of other complex traits, such as language and morality, and should help us more deeply understand why and how human economic systems evolved.This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates’.     

What the Penaeaceae alliance (Myrtales) tells us about the nature of vestured pits in xylem

Molecular studies indicate that Penaeaceae, Oliniaceae, and the monospecific families Alzateaceae and Rhynchocalycaceae form a clade of Myrtales. Of these four families, Penaeaceae have tracheids with vestured pits, whereas the others have septate fibers lacking vestures; all have vestured pits in vessels. Tracheid presence in Penaeaceae may be related to the arid South African habitats of the family. Presence of vestures on tracheids in families with vestured vessel pits is one indication that imperforate elements are tracheids and are conductive cells, whereas fiber-tracheids and libriform fibers are non-conductive. Tracheids occur widely in angiosperms and may be plesiomorphies or apomorphies. Combretaceae, the first branch of the Myrtales clade, has a great diversity of vesture features in vessels compared to the Penaeaceae alliance families. Alzatea has vestures that spread over the inside of the vessels, whereas in most taxa of the alliance, vestures are confined to the pit cavities and pit apertures. Vestures in the alliance tend to be globular in shape, and are bridged together by strands of wall material. Lignotubers and roots in Penaeaceae have vestures much like those in stems. Only a few species and genera (notably Alzatea) of the alliance have vesture features the pattern of which correlates with the current taxonomic system. Vestured pits should be viewed from the inside surface of vessels as well as the outer surface, and although sectional views of vestured pits are infrequent, they are very informative. Studies that explore diversity from one order or family to another are needed and offer opportunities for understanding the evolutionary significance of this feature.     

Creative cognition: the diverse operations and the prospect of applying a cognitive neuroscience perspective

Creativity is defined quite simply as "the ability to create" in most lexicons, but, in reality, this is a complex and heterogeneous construct about which there is much to be discovered. The cognitive approach to investigating creativity recognizes and seeks to understand this complexity by investigating the component processes involved in creative thinking. The cognitive neuroscience approach, which has only limitedly been applied in the study of creativity, should ideally build on these ideas in uncovering the neural substrates of these processes. Following an introduction into the early experimental ideas and the cognitive approach to creativity, we discuss the theoretical background and behavioral methods for testing various processes of creative cognition, including conceptual expansion, the constraining influence of examples, creative imagery and insight. The complex relations between the underlying component processes of originality and relevance across these tasks are presented thereafter. We then outline how some of these conceptual distinctions can be evaluated by neuroscientific evidence and elaborate on the neuropsychological approach in the study of creativity. Given the current state of affairs, our recommendation is that despite methodological difficulties that are associated with investigating creativity, adopting the cognitive neuroscience perspective is a highly promising framework for validating and expanding on the critical issues that have been raised in this paper.