What,if anything,is a social niche?

The term “social niche” is rapidly increasing in usage, particularly in the context of “social niche construction.” But what (if anything) is a social niche? Here, we survey papers that have used the term to uncover commonalities and discrepancies in its definition. We aim to alert researchers to the need for more consistency in how the term is used in the literature, and we provide a working definition of “social niche:” the set of social environments in which the focal individual has non-zero inclusive fitness. We consider the extent to which a social niche is analogous to an ecological niche, discuss whether a population-level social niche can be meaningfully identified, and describe conceptual insights about the properties of social niches, focusing on social niche construction. We highlight questions about social niches that demand more theoretical and empirical attention.     

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).     

What, if anything, does visual asymmetry in fallow deer antlers reveal?

Fluctuating asymmetry (FA), small directionally random deviations from perfect bilateral symmetry, is thought to reflect individual quality. Furthermore, it has been suggested that FA in secondary sexual characters can be used to assess mate or opponent quality during inter- or intrasexual competition. Studies on fallow deer, Dama dama, have suggested that FA in antlers reflects individual dominance, or the existence of a directional asymmetry (DA) with right antlers being consistently more developed than left antlers. To test these conflicting hypotheses, we analysed relationships between age, dominance and asymmetry in the number of antler points on mature fallow deer males during four rutting seasons in a single population. Age and dominance were only weakly correlated. The number of antler points displayed a pattern of DA (more points on the right than on the left side) that increased with age. Although dominance tended to increase with the total number of antler points, there was no relationship between the level of DA and dominance. These results failed to support the hypothesis that antler asymmetry visually reveals individual quality in fallow deer. Copyright 2000 The Association for the Study of Animal Behaviour.     

Ontogeny and the fossil record: what,if anything,is an adult dinosaur?

Identification of the ontogenetic status of an extinct organism is complex, and yet this underpins major areas of research, from taxonomy and systematics to ecology and evolution. In the case of the non-avialan dinosaurs, at least some were reproductively mature before they were skeletally mature, and a lack of consensus on how to define an ‘adult’ animal causes problems for even basic scientific investigations. Here we review the current methods available to determine the age of non-avialan dinosaurs, discuss the definitions of different ontogenetic stages, and summarize the implications of these disparate definitions for dinosaur palaeontology. Most critically, a growing body of evidence suggests that many dinosaurs that would be considered ‘adults’ in a modern-day field study are considered ‘juveniles’ or ‘subadults’ in palaeontological contexts.     

What if there is no prospective,double blind,randomised trial?

Netherlands Heart Journal -     

What is speciation and how should we study it?

To understand speciation, we first need to know what species are. Yet debates over species concepts have seemed endless, with little obvious relevance to the study of speciation. Recently, there has been progress in resolving these debates, favoring a lineage-based, evolutionary species concept. This progress calls for reconsideration of the study of speciation. Traditional speciation research based on the biological species concept has led to great advances in understanding how nonallopatric speciation occurs and how species diverge and remain separate from each other. However, this research has neglected the question of how new species arise in the first place for the most common geographic mode (allopatric). A new and very different research program is needed to understand the ecological and evolutionary processes that split an ancestral species into new allopatric lineages. This research program will connect speciation to many other fundamental questions in evolutionary biology, ecology, biogeography, and conservation biology.     

Will sympatric speciation fail due to stochastic competitive exclusion?

Sympatric speciation requires coexistence of the newly formed species. If divergence proceeds by small mutational steps, the new species utilize almost the same resources initially, and full speciation may be impeded by competitive exclusion in stochastic environments. We investigate this primarily ecological problem of sympatric speciation by studying the population dynamics of a diverging asexual population in a fluctuating environment. Correlation between species responses to environmental fluctuation is assumed to decrease with distance in trait space. Rapidly declining correlation in combination with high environmental variability may delay full speciation or even render it impossible. Stochastic extinctions impeding speciation are most likely when correlation decays faster than competition, for example, when demographic stochasticity is strong or when divergence is not accompanied by niche separation, such as in speciation driven entirely by sexual selection. Our general theoretical results show an interesting connection between short-term ecological dynamics and long-term, large-scale evolution.     

How do natural and sexual selection contribute to sympatric speciation?

I use explicit genetic models to investigate the importance of natural and sexual selection during sympatric speciation and to sort out how genetic architecture influences these processes. Assortative mating alone can lead to speciation, but rare phenotypes' disadvantage in finding mates and intermediate phenotypes' advantage due to stabilizing selection strongly impede speciation. Any increase in the number of loci also decreases the likelihood of speciation. Sympatric speciation is then harder to achieve than previously demonstrated by many theoretical studies which assume no mating disadvantage for rare phenotypes and consider a small number of loci. However, when a high level of assortative mating evolves, sexual selection might allow populations to split into dimorphic distributions with peaks corresponding to nearly extreme phenotypes. Competition then works against speciation by favouring intermediate phenotypes and preventing further divergence. The interplay between natural and sexual selection during speciation is then more complex than previously explained.     

What,if anything,is a Tilapia?-mitochondrial ND2 phylogeny of tilapiines and the evolution of parental care systems in the African cichlid fishes

We estimated a novel phylogeny of tilapiine cichlid fish (an assemblage endemic to Africa and the Near East) within the African cichlid fishes on the basis of complete mitochondrial NADH dehydrogenase subunit 2 (ND2) gene sequences. The ND2 (1,047 bp) gene was sequenced in 39 tilapiine cichlids (38 species and 1 subspecies) and in an additional 14 nontilapiine cichlid species in order to evaluate the traditional morphologically based hypothesis of the respective monophyly of the tilapiine and haplochromine cichlid fish assemblages. The analyses included many additional cichlid lineages, not only the so-called tilapiines, but also lineages from Lake Tanganyika, east Africa, the Neotropics and an out-group from Madagascar with a wide range of parental care and mating systems. Our results suggest, in contrast to the historical morphology-based hypotheses from Regan (1920, 1922 ), Trewavas (1983), and Stiassny (1991), that the tilapiines do not form a monophyletic group because there is strong evidence that the genus Tilapia is not monophyletic but divided into at least five distinct groups. In contrast to this finding, an allozyme analysis of Pouyaud and Agnèse (1995), largely based on the same samples as used here, found a clustering of the Tilapia species into only two groups. This discrepancy is likely caused by the difference in resolution power of the two marker systems used. Our data suggest that only type species Tilapia sparrmanii Smith (1840) should retain the genus name TILAPIA: One particular group of tilapiines (composed of genera Sarotherodon, Oreochromis, Iranocichla, and Tristramella) is more closely related to an evolutionarily highly successful lineage, the haplochromine cichlids that compose the adaptive radiations of cichlid species flocks of east Africa. It appears that the highly adaptable biology of tilapiines is the ancestral state for all African cichlids and that the more stenotypic lifestyle of the haplochromine cichlids is derived from this condition. We reconstructed the evolution of the highly variable parental care systems on the basis of the most inclusive composite phylogeny to date of the African, Neotropical, and Madagascan cichlids with special emphasis on a group of tilapiines comprising the substrate-spawning genus Tilapia, and the mouthbrooding genera Sarotherodon and OREOCHROMIS: We demonstrate several independent origins of derived mouthbrooding behaviors in the family Cichlidae.     

Sympatric speciation in parasites--what is sympatry?

Parasites account for a large part of known species diversity and are considered to have a high potential for sympatric speciation. However, the frequency of sympatric divergence in these organisms will depend on the definition of sympatry that one uses. Like many of our current species concepts, the typical definition of sympatry is not widely applicable to parasites. Revisiting the historically defined conditions for sympatric speciation and considering the situations in which we might regard parasites as being sympatric leads us to question the classic prediction that parasites have a greater tendency to speciate in sympatry than do free-living organisms.     

When is sympatric speciation truly adaptive? An analysis of the joint evolution of resource utilization and assortative mating

The plausibility of sympatric speciation has long been debated among evolutionary ecologists. The process necessarily involves two key elements: the stable coexistence of at least two ecologically distinct types and the emergence of reproductive isolation. Recent theoretical studies within the theoretical framework of adaptive dynamics have shown how both these processes can be driven by natural selection. In the standard scenario, a population first evolves to an evolutionary branching point, next, disruptive selection promotes ecological diversification within the population, and, finally, the fitness disadvantage of intermediate types induces a selection pressure for assortative mating behaviour, which leads to reproductive isolation and full speciation. However, the full speciation process has been mostly studied through computer simulations and only analysed in part. Here I present a complete analysis of the whole speciation process by allowing for the simultaneous evolution of the branching ecological trait as well as a continuous trait controlling mating behaviour. I show how the joint evolution can be understood in terms of a gradient landscape, where the plausibility of different evolutionary paths can be evaluated graphically. I find sympatric speciation unlikely for scenarios with a continuous, unimodal, distribution of resources. Rather, ecological settings where the fitness inferiority of intermediate types is preserved during the ecological branching are more likely to provide opportunity for adaptive, sympatric speciation. Such scenarios include speciation due to predator avoidance or specialization on discrete resources. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Targeted cancer therapy: What if the driver is just a messenger?

“Shoot the driver” is the paradigm of targeted cancer therapy. However, resistance to targeted inhibitors of signaling pathways is a major problem. In part, the redundancy of signaling networks can bypass targeted inhibitors and thereby reduce their biological effect. In this case, the driver turns out to be one of several potential messengers and is easily replaced. Cocktails of multiple targeted inhibitors are an obvious solution. This is limited, however, by the lack of potent inhibitors and may also produce increased toxicity. Therefore, we explored the direct blockade of a key biological activity downstream from multiple converging oncogenic signals. Specifically, several oncogenic signaling pathways, including AKT, MAPK and PIM kinase signals, converge on the activation of cap-dependent translation. In cancer cells, aberrant activation of cap-dependent translation favors the increased expression of short-lived oncoproteins like c-MYC, MCL1, CYCLIND1 and the PIM kinases. Intriguingly, cancer cells are especially sensitive to even temporary reductions in these proteins. We will discuss our findings concerning translational inhibitor therapy in cancer.Key words: targeted therapy, cancer, lymphoma, translation, eIF4ETargeted cancer therapies are designed to block selected pathways or molecules that are required for tumor cell survival. The most successful examples are inhibitors of the BCR-ABL fusion protein that drive chronic myeloid leukemia (CML). By shutting down the activity of a single molecule driving the growth of CML cells, imatinib and its successors dasatinib and nilotinib can produce complete and sustained remissions as single agents (reviewed in ref. ¹). However, it has proven difficult to translate this success to other cancers. In metastatic melanoma, for example, the BRAF inhibitor vemurafenib produces high response rates in patients whose tumors bear the BRAF-V600E activating mutation (reviewed in ref. ²). Excitement generated by these results is well-deserved, as they have opened a new treatment paradigm in a disease with few available options and a grim prognosis. Unfortunately, however, resistance to the drug generally is seen within a few months. Median progression-free survival resulting from vemurafenib for treatment-naïve metastatic melanoma patients with V600E was about six months,³ compared with imatinib in CML, which kept 93% of patients progression-free at five years.⁴ The success of TKIs in CML is still the exception and not the rule in targeted cancer therapeutics.Resistance to targeted inhibitors is an emerging problem with multiple causes and potential solutions. While mechanisms of resistance to BRAF inhibition in melanoma remain to be elucidated, they are well-described for some targets in other cancers. Drugs against the epidermal growth factor receptor (EGFR) kinase, for example, are bypassed both by activation of downstream mediators, most prominently KRAS, and by signaling through parallel pathways like the MET oncogene (reviewed in ref. ⁵). Resistance mechanisms are varied and complex in some ways, but most boil down to the same idea: evolution has provided multiple routes to the crucial endpoints that allow sustained growth and proliferation of cancer cells. Cocktails of multiple inhibitors have been proposed to prevent or thwart resistance (reviewed in ref. ⁶), and this approach appears highly promising based on some recent preclinical studies. In prostate cancer, for example, combined blockade of androgen receptor signaling and the PI3K/AKT/mTOR pathway showed potent synergy in model systems.⁷ Unfortunately, similar approaches against many other cancers are currently limited by the availability of potent, selective inhibitors and a need to identity which combinations will be effective. Moreover, combined toxicities from simultaneous use of multiple inhibitors will pose limits on the number and intensity of drugs that can be used.An alternative and potentially complementary approach is to directly target the downstream biological processes that are activated by signaling pathways and that cancer cells rely on. Experiences with inhibitors of EGFR, BRAF, and other signaling molecules suggest that most tumors can reliably activate parallel or downstream messengers to thwart efficacy. So inhibiting a signaling intermediate (i.e., a messenger) allows resistance if the biological effects can be achieved via an alternate route. Ultimately, tumor cells don''t depend on the messenger, often a kinase, and, instead, require a downstream biological function. This opens the possibility that targeting the critical effect directly may be an effective cancer therapy and could overcome the problem of redundant messengers.Several inherent properties of signaling pathways are relevant to targeted therapies, their side effects and mechanisms of resistance.⁸ For example, signaling pathways frequently converge on key activities. As explained above, this redundancy can produce resistance to targeted agents. Often redundant pathways are induced via feedback mechanisms, which provide robust signals and can also bypass selective inhibitors. Signals also diverge, however, and seemingly parallel pathways therefore also produce pleiotropic and non-overlapping effects. It is possible not all activities are required by cancer cells. Hence, an upstream block may produce toxicities, in part, by blocking activities that are not strictly required by tumor cells as much as by normal tissues. Finally, unlike metabolic pathways, where a limiting substrate is passed down, signaling cascades amplify signals toward a key activity, and the initial signal or message is both energetically “cheap” and infinitely recurrent. Accordingly, it is conceivable that direct block of the downstream effects provide an alternative or complementary approach to targeting upstream signaling molecules.Multiple oncogenic signals, including the PI3K, MAPK/ERK and PIM kinase pathways converge on the activation of cap-dependent translation, the process by which most capped mRNAs are translated into proteins (reviewed in ref. ⁹). Signaling pathways control the availability of the cap-binding protein eIF4E that is the limiting component of the multimeric translation complex eIF4F, which also includes scaffolds (eIF4G) and RNA helicase activities (eIF4A).^10–12 The complex ultimately mediates loading of mRNAs onto ribosomes. Availability of the eIF4E factor is especially important for mRNAs with long and structured 5′ UTRs. These include, in particular, short-lived cell cycle regulators and oncoproteins. Hence, regulation of eIF4E via upstream signals provides an immediate level of expression control that directly controls levels of proteins, including c-MYC, cyclin D1, BCL2, MCL1 and PIM1.^13–17 Cancer cells require continuous expression of these proteins. For example, even brief loss of MYC expression produces widespread cell death in several cancers but only produces reversible cell cycle arrest in normal tissues.¹⁸ Hence, the increased requirement for the continuous translation of oncoproteins in cancer cells may provide a therapeutic window for inhibitors of capdependent translation.We recently investigated the therapeutic potential of directly blocking capdependent translation in non-Hodgkin lymphoma (NHL).^15,16,19 Rapalogs, inhibitors of mTORC1, the upstream activator of cap-dependent translation, have been extensively studied in NHL in clinical trials (reviewed in ref. ²⁰). However, their activity has, overall, been modest, and our results implicate mTORC1-independent activation of translation by PIM kinases as one mechanism of rapalog resistance in NHLs.¹⁶ The PIM family kinases are active upon expression and do not require activating modifications. They have been known for some time to be able to promote phosphorylation of 4E-BP1 in a manner resistant to rapamycin.^21,22 We now report expression of PIM1 and/or PIM2 in more than 60% of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) and more than 75% of mantle cell and small lymphocytic lymphomas. Our study found PIM expression (either PIM1 or PIM2) was associated with worse time to event and overall survival in FL, while another recent report points to PIM2 as a driver of aggressive disease in activated B-cell type DLBCL.²³ In addition, two recent studies of chromosomal translocations mediated by activation-induced deaminase (AID) identified PIM1 as a frequent target.^24,25 In sum, expression of PIM kinases is common in NHLs, may be associated with a more aggressive clinical course and exemplifies how the redundancy of messaging molecules can bypass the clinical activity of selective signaling inhibitors.In experimental systems, we found that direct blockade of cap-dependent translation was highly effective against lymphomas with redundant PI3K/AKT and PIM signals.¹⁶ Briefly, using both a constitutively active mutant 4E-BP1 allele that blocks eIF4E activity and a small molecule inhibitor of the eIF4A helicase, silvestrol, we were able to completely restore rapalog sensitivity in lymphomas engineered to express PIM2 kinase activity. Mechanistically, we found that silvestrol dramatically reduced the translation of critical oncoproteins, including c-MYC, cyclin D1 and MCL1. Interestingly, silvestrol also blocked the translation of both PIM kinases themselves. Moreover, consistent with prior reports, silvestrol treatment at an effective dose was well-tolerated in animals, and we observed no frank toxicity.¹⁹ Hence, blocking cap-dependent translation disrupts upstream signaling molecules, the PIM kinases and also key oncoproteins commonly considered “undruggable” oncoproteins, including c-MYC.Silvestrol worked dramatically better than inhibition of the upstream kinases. Briefly, we tested the SuperGen Inc. PIM kinase inhibitors SGI-1776 and SGI-1773 side by side with silvestrol in a panel of these PIM-expressing human NHL cell lines. Notably, SGI-1776 is the only PIM inhibitor that has entered clinical trials, although these had to be discontinued due to cardiac toxicity of the compound (SuperGen press release, 2010). In any case, silvestrol showed in vitro potency at IC₅₀ of less than 10 nM in all cases, and the PIM kinase inhibitors were 100 to 1,000 times less active. These results highlight some problems associated with the “inhibitor cocktail” approach and indicate a complementary strategy that includes direct blockade of a key biological activity, in this instance, cap-dependent translation of oncoproteins.Silvestrol is not the only means to block cap-dependent translation, and others are reviewed in reference ⁹. These include antisense oligonucleotides against eIF4E and peptide inhibitors of eIF4F complex formation, though neither has entered clinical trials. Silvestrol is the most well-studied of several compounds that emerged from library screens for ability to disrupt the function of the eIF4F subunit eIF4A, an RNA helicase required for its ability to promote mRNA translation. A plant-derived flavagline, silvestrol has shown activity against a variety of tumor types and can be given to mice at high enough concentrations for antitumor activity without major toxicity. The drug shows activity as a single agent against human breast and prostate cancer cell lines in xenograft experiments in nude mice.²⁶ This produced mild transient impairment of hepatic synthetic function but no toxicities producing morbidity or mortality. In genetically defined murine tumor models, silvestrol showed potent synergy with chemotherapy when used against tumors bearing translational activation due to loss of Pten or overexpression of eIf4e.¹⁹ Originally isolated from Aglaia silvestris, silvestrol has a complex structure that has proved difficult to chemically synthesize in quantity. For this reason, the parent compound is not an ideal clinical drug candidate. Efforts are underway by Drs. Pelletier (McGill) and Porco (Boston University) to develop analogs with more efficient synthesis profiles and that retain its biochemical properties. In sum, cap-dependent translation is a promising drug target alternate to mTORC1 and upstream kinase inhibitors.     

What is emotion?

There is no consensus in the literature on a definition of emotion. The term is taken for granted in itself and, most often, emotion is defined with reference to a list: anger, disgust, fear, joy, sadness, and surprise. This article expands on a thesis that motivational states can be compared to each other by means of a common currency (Philos. Trans. Roy. Soc. Lond. 270 (1975) 265-293). I have previously argued that this common currency is pleasure. Such a conclusion is based not on introspective intuition, as with early pre-scientific psychology (), but on experimental methods. As a follow-up to a definition of consciousness (Neurosci. Biobehav. Rev. 20 (1996) 33-40) as a four-dimensional experience (quality, intensity, hedonicity, and duration), I propose here that emotion is any mental experience with high intensity and high hedonic content (pleasure/displeasure).