Substrate-Assisted Catalysis Unifies Two Families of Chitinolytic Enzymes

Hen egg-white lysozyme has long been the paradigm for enzymatic glycosyl hydrolysis with retention of configuration, with a protonated carboxylic acid and a deprotonated carboxylate participating in general acid-base catalysis. In marked contrast, the retaining chitin degrading enzymes from glycosyl hydrolase families 18 and 20 all have a single glutamic acid as the catalytic acid but lack a nucleophile on the enzyme. Both families have a catalytic (βα)8-barrel domain in common. X-ray structures of three different chitinolytic enzymes complexed with substrates or inhibitors identify a retaining mechanism involving a protein acid and the carbonyl oxygen atom of the substrate’s C2 N-acetyl group as the nucleophile. These studies unambiguously demonstrate the distortion of the sugar ring toward a sofa conformation, long postulated as being close to that of the transition state in glycosyl hydrolysis.

Diversity in sound pressure levels and estimated active space of resident killer whale vocalizations

Author Posting. © The Author, 2005. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Comparative Physiology A: Sensory, Neural, and Behavioral Physiology 192 (2006): 449-459, doi:10.1007/s00359-005-0085-2.Signal source intensity and detection range, which integrates source intensity with propagation loss, background noise and receiver hearing abilities, are important characteristics of communication signals. Apparent source levels were calculated for 819 pulsed calls and 24 whistles produced by free-ranging resident killer whales by triangulating the angles-of-arrival of sounds on two beamforming arrays towed in series. Levels in the 1-20 kHz band ranged from 131-168 dB re 1μPa @1m, with differences in the means of different sound classes (whistles: 140.2 ± 4.1 dB; variable calls: 146.6 ± 6.6 dB; stereotyped calls: 152.6 ± 5.9 dB), and among stereotyped call types. Repertoire diversity carried through to estimates of active space, with “long-range” stereotyped calls all containing overlapping, independently-modulated high-frequency components (mean estimated active space of 10-16km in sea state zero) and “short-range” sounds (5-9 km) included all stereotyped calls without a high-frequency component, whistles, and variable calls. Short-range sounds are reported to be more common during social and resting behaviors, while long-range stereotyped calls predominate in dispersed travel and foraging behaviors. These results suggest that variability in sound pressure levels may reflect diverse social and ecological functions of the acoustic repertoire of killer whales.Funding was provided by WHOI’s Ocean Ventures Fund and Rinehart Coastal Research Center and a Royal Society fellowship

Genomic variation in tomato, from wild ancestors to contemporary breeding accessions

[EN] Background: Domestication modifies the genomic variation of species. Quantifying this variation provides insights into the domestication process, facilitates the management of resources used by breeders and germplasm centers, and enables the design of experiments to associate traits with genes. We described and analyzed the genetic diversity of 1,008 tomato accessions including Solanum lycopersicum var. lycopersicum (SLL), S. lycopersicum var. cerasiforme (SLC), and S. pimpinellifolium (SP) that were genotyped using 7,720 SNPs. Additionally, we explored the allelic frequency of six loci affecting fruit weight and shape to infer patterns of selection. Results: Our results revealed a pattern of variation that strongly supported a two-step domestication process, occasional hybridization in the wild, and differentiation through human selection. These interpretations were consistent with the observed allele frequencies for the six loci affecting fruit weight and shape. Fruit weight was strongly selected in SLC in the Andean region of Ecuador and Northern Peru prior to the domestication of tomato in Mesoamerica. Alleles affecting fruit shape were differentially selected among SLL genetic subgroups. Our results also clarified the biological status of SLC. True SLC was phylogenetically positioned between SP and SLL and its fruit morphology was diverse. SLC and “cherry tomato” are not synonymous terms. The morphologically-based term “cherry tomato” included some SLC, contemporary varieties, as well as many admixtures between SP and SLL. Contemporary SLL showed a moderate increase in nucleotide diversity, when compared with vintage groups. Conclusions: This study presents a broad and detailed representation of the genomic variation in tomato. Tomato domestication seems to have followed a two step-process; a first domestication in South America and a second step in Mesoamerica. The distribution of fruit weight and shape alleles supports that domestication of SLC occurred in the Andean region. Our results also clarify the biological status of SLC as true phylogenetic group within tomato. We detect Ecuadorian and Peruvian accessions that may represent a pool of unexplored variation that could be of interest for crop improvement.We are grateful to the gene banks for their collections that made this study possible. We thank Syngenta Seeds for providing genotyping data for 42 accessions. We would like to thank the Supercomputing and Bioinnovation Center (Universidad de Malaga, Spain) for providing computational resources to process the SNAPP phylogenetic tree. This research was supported in part by the USDA/NIFA funded SolCAP project under contract number to DF and USDA AFRI 2013-67013-21229 to EvdK and DF.Blanca Postigo, JM.; Montero Pau, J.; Sauvage, C.; Bauchet, G.; Illa, E.; Díez Niclós, MJTDJ.; Francis, D.... (2015). 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Whose Rights? A Critique of Individual Agency as the Basis of Rights * First version ("Whose Rights?

Abstract I argue that individuals may be as problematic political agents as groups. In doing so, I draw on theory from economics, philosophy and computer science and evidence from psychology, neuroscience and biology. If successful this argument undermines agency-based justifications for embracing strong notions of individual rights while rejecting the possibility of similar rights for groups. For concreteness, I critique these mistaken views by rebutting arguments given by Chandran Kukathas in his essay "Are There Any Cultural Rights?" that groups lack the temporal coherence, political independence and indivisibility of individuals. I also show how formal critiques of group agency from social science (in particular, Arrow's Impossibility Theorem) can be applied as reasonably to individuals as groups. Because these symmetries between groups and individuals undermine common implicit assumptions in political philosophy, I argue that they may have broader implications for liberal political theory, as they emphasize the importance of intra-personal justice. Keywords: moral individualism, group rights, social choice theory, liberal-communitarianism debate, behavioral economics * The first version of this paper was prepared for PHI419 The Ethics of Identity taught by Kwame Anthony Appiah at Princeton University in the fall of 2005. His guidance on this paper as well as through the broader process of philosophical discovery has been invaluable. I would also like to acknowledge the helpful comments of Lara Buchak, Sean Corner, Avinash Dixit, Jerry Green, David Individual human beings -their choices, agency, rights and reason -are the basic units of analysis in most modern philosophy and social science. From the rational agent model to the moral individualism, the individual has become something of a mascot for the modern Anglo-American academy. Debate over the nature and proper understanding of the individual and her relationship to political community has been a dominant force in political philosophy over the last quarter century. The first three decades of post-war political theory primarily focused on providing an analytic account of liberal, non-utilitarian Western political discourse, culminating in the seminal egalitarian and libertarian theses of John Rawls and Robert Nozick, respectively. 2 The liberal thesis, characterized by Allen Buchanan as the view that "the state is to enforce the basic individual civil and political rights", came under vigorous attack from a number of communitarian critiques during the 1980's. 3 Several thinkers found fault with liberal theory along various contrasting avenues. Michael Sandel targeted the flawed and internally inconsistent metaphysical conception of the self that he claimed is fundamental to the liberal, and particularly Rawlsian, conception of justice. 4 Alisdair MacIntyre alleged that liberalism lacks a coherent moral underpinning, while Michael Walzer took issue with what he saw as the reductive, unitary liberal conception of justice. 5 In response, liberals sought firmer and more broadly appealing foundations for their core arguments as well as means of synthesizing into liberal political theory important ideas suggested by the communitarian critics. 6 As issues of multiculturalism and the appropriate treatment of minorities have played an increasingly prominent role in modern political discourse, liberals and their critics have worked to develop accounts of notions like "group rights" and "ethno-linguistic minority protections" consistent with their broader political vision. One current running through these debates, usually taking the form of an implicit assumption, is the primary status of individual rather than collective agency. Liberals, communitarians and their synthetic progeny often disagree about the nature of the good for the individual, whether collective good is a sensible notion, the importance of the community to individual identity and well-being and many other matters. However, they seem to implicitly agree that individuals, but not groups, can sensibly be thought of as unitary agents or selves. my purpose here is to argue that this justification, more plausibly integral to rights individualism than to liberalism more broadly, is invalid. I will take aim at two types of arguments for the individualism of agency. The first type of argument is philosophical; for concreteness I address a case put forward by Chandran Kukathas in his essay "Are There Any Cultural Rights?", which begins with a defense of rights individualism through the individualism of agency. Kukathas's broad case is composed of three related arguments covering the relationship between groups and the political system, temporal problems of groups and challenges arising from divisions within groups. The second class of arguments is related to the first, but is phrased in the language of rational choice theory in social science. Again for specificity, I focus on Arrow's classic Impossibility Theorem demonstrating the general incoherence of group decisions, though I briefly discuss other formal critiques of group agency. 11 I focus on using a variety of theory and evidence to demonstrate the ways in which these arguments against group agency can be brought to bear on individual agency and therefore demonstrating the qualitative This analogy is apt, given that the field of social choice theory in economics and political science has extensively addressed the problems of group agency that arises from the inherent flaws of voting systems. The seminal result in this field, and the one I focus on primarily below, is Arrow's Impossibility Theorem. However, it is important to note that I focus on Arrow's result not because it is the definitive or even most important such formal critique. In fact, the Gibbard-Satterthwaite Theorem, which I mention briefly below, shows that under weaker conditions if voters are strategic, the limits on group agency are severe. 8 Impossible Choices In his classic 1951 dissertation Social Choice and Individual Values, Kenneth Arrow took formal aim at group agency. He demonstrated mathematically that group decision-making is an inherently troubled process. In particular, he showed that it is impossible to devise a means of aggregating individual preferences into group decisions which are both consistent and satisfy basic axioms of social choice. By "consistent", Arrow meant that these choices obey the most basic principles of rational choice: the group must have some preference between any two possible courses of action, X and Y (prefer X, prefer Y, or be indifferent) and such preferences must obey transitivity (if the group prefers X to Y and Y to Z, it must prefer X to Z). No individual should act as a dictator, unilaterally determining the group's preferences. Independence of Irrelevant Alternatives: In deciding whether the group should prefer X or Y, only individuals' rankings of X against Y should matter. Unanimity: If all individuals prefer X to Y then the group should. Universal Domain: The method of social choice must be defined (must give some answer) for any arrangement of individual preferences. Additionally, Arrow's theorem requires two basic assumptions about the environment being considered, which are easily satisfied in most situations of social choice: 1. Ordinality: Preferences are known in determining social preference only as rankings of alternatives, not as cardinal numbers or degrees of preference. Non-ordinal social choice systems would require knowing the degree of individuals' preferences, which they would always try to exaggerate. This would also make comparisons of "degree of preference" 9 across individuals necessary, thereby potentially valuing some individuals more than others in voting. Each of these is sufficiently unpalatable or impractical, Arrow argued, so as to rule it out. Richness of Setting: The social choice rule continues to work if there are more than two alternatives and more than two individuals. Thus, Arrow showed that, in most reasonable settings, the concept of collective choice cannot be well-defined. [T]he only methods of passing from individual tastes to social preferences which will be satisfactory (in the sense defined above) and which will be defined for a wide range of sets of individual orderings are either imposed or dictatorial. 24 Any non-pathological method of group decision-making will be susceptible to incoherence or will only be applicable to a limited set of social choices. Even if we are willing to restrict the domain of situations (arrangements of preferences) in which the group may make a decision, this is simply a hack. Presented with other situations (if individuals change their preferences) the group will be unable to choose or will choose in an inconsistent or pathological manner. Thus granting cultural groups the right to self-determination, or anything else, seems deeply misguided. Because Arrow's critique fundamentally undermines group agency, it also undermines the capacity for groups for groups to bear rights, at least of one who views rights as closely tied to agency. While Arrow's theorem may seem the ultimate watertight critique of group agency, a closer examination of the result, first suggested by Kenneth May in his 1953 essay "Intransitivity, Utility and the Aggregation of Preference Patterns", shows that it may pose equally serious challenges to individual agency. These problems have roots in the conception of the individual that Arrow and classical economic theory more generally, assumes. This "rational agent" suffers none of the problems of inconsistency that beset groups. She can easily rank all possible social outcomes in 10 expressing her preferences and these rankings constitute the basis of consistent choices. What is so surprising about Arrow's theorem, in fact, is that the problem of making a group decision can cause such chaos when the individuals that compose the group are perfectly rational. Such an idealization of individuals, however, is poorly instantiated by humans. An extensive psychological literature inspired by the path-breaking work of Amos Tversky and Daniel Kahneman has catalogued hundreds of situations in which individuals act in ways that clearly violate the most basic principles of rational choice. Nonetheless, one might argue that whereas groups are inherently given to inconsistency and incoherence, individuals have the capacity for rational choice, which they can and should exercise, even if they sometimes fail to do so. The view that the inconsistency we observe in individuals is, in Tversky and Kahneman's words, "normatively distasteful" and essentially a form of confusion on the part of actors is one widely held within the psychological community. 27 Inconsistent decisions are described as "biases" or as the consequences of "heuristics". Incoherence in decision-making is often considered intimately related to errors in positive judgments. This limited "judgmental psychology" view of inconsistency tells only part of the story, however. Individuals do not deviate from being rational agents merely through small inconsistencies with others, her material well-being, etc. And suppose that she can (at least in theory), like a rational agent, rank every conceivable outcome according to how well it satisfies these desires (as I will refer to them henceforth). 36 If the individual considers several relatively independent (or independently computed) attributes there is no guarantee that these various desires can be brought into some common currency of "utility" that allows the expression of a consistent preference. If we are to take this idea seriously, we must substantially alter our normative and positive expectations for individuals. Even if each of the selves that make up an individual is rational and has coherent preferences, a person attempting to make decisions may fall prey to the same problems of social choice that Arrow details in the context of group decision-making. That is, we should not expect an individual to be able to aggregate the preferences of multiple selves fundamentally better than groups are able to aggregate the preferences of the individuals that they comprise. 37 It is important, however, to remember that Arrow's theorem is not an immediate or universal result. It follows only if one requires certain axioms of choice, as discussed above. These axioms may or may not be fully compelling in the context of social choice; this has been a long topic of debate in the economic and philosophic communities. 14 When each conflicting self provides an important input to optimal decision-making, the axiom of non-dictatorship becomes immediately compelling. If we accept dictatorship of one desire within the individual, why should we be troubled by the imposed or dictatorial social choices that Arrow rules out? If there is some easily calculable overriding moral principle by which individuals should make all decisions and to which all other desires should be subservient, then might we not simply say the same about groups? Perhaps groups, too, should follow some consistent ethical principle, but fail to; if so why should this fact detract from their agency any more than in the case of an individual? Despite the preceding arguments, it still seems that the unity of the human body offers an important basis for differentiating individual from group choice. Individuals always must make a single, unified choice; groups often may choose not to choose and allow a particular matter to be handled by its members independently. Yet the necessity of unified action does not logically imply the reasonableness of assuming unified decision-making. To see this sharply, consider the case of Siamese twins. 44 The two individuals that share a body clearly may have different preferences. Clearly they may also have to coordinate their decision-making, either because they directly share control over some organ or because any effective action requires them acting in concert. It seems unjust, impractical and implausible that one of the two twins would ever act as a dictator over the other. The fact that they will be paralyzed during any conflict does not imply that such conflicts are impossible nor does it imply that it would be reasonable that one individual's preferences should dictate the actions of the pair. By analogy, the simple fact that divisions among preference orderings held by different selves or contained in different desires reside within the same brain does not imply that it is reasonable to think of these desires as unified or to think of one as being an appropriate or actual dictator over the others. 15 A further challenge to the dictatorship axiom (and the notion of internal conflict more broadly) in the context of individual choice is the notion that individuals may possess more effective, non-coercive means than groups for confronting the problem of disunity by exerting effort in order to bring various parts of the self into agreement. It may very well be the case that individuals more often than groups have effective means of achieving such internal concertation than do groups. However, it is certainly not the case that groups entirely lack such mechanisms, nor is it the case that the mechanisms within individuals are uniformly more efficacious than those within groups. At least since the time of the Greeks straight through to Barack Obama's presidential campaign, political rhetoric has played a crucial and effective role in achieving consensus around directions of social action. 45 The faith-based calls of religion, as well as secular ideologies, to self-sacrifice have also proven powerful forces for unifying individuals with seemingly disparate interests around common cause. In fact a major theme of modern social psychology is the study of the various mechanism, such as conformity, obedience and social learning, through which groups achieve unity of, unfortunately often sinister, purpose. 46 Recent work in economics has similarly emphasized the tendency of individuals in group to sacrifice their independent processing of information and choices in favor of various forms of group-think. Furthermore, it is not the case that individuals are uniformly more effective at exerting effort to peacefully overcome internal conflict than are groups. Literature has long featured characters from, Hamlet to Scrooge, whose internal struggles provide the dominant drama. Casual observations reinforces this theme: most of us know someone whose struggles to achieve internal 16 cohesion when confronting troubles with drug abuse, career choice or romance can, even when heroic efforts are made, outlast and eclipse their inter-personal conflicts. Post-war debates about stimulating savings tended to focus on capital taxation or social security. However, recent evidence suggests policies aimed at resolving internal conflict, such as adjusting default settings on retirement plans or adjusting individuals' ability to prohibit themselves from withdrawing from an account, rather than large-scale social policies may be most effective. 49 None of this argues that individuals are usually or on average more divided than groups; such a question would be an empirical question difficult to even pose coherently. But it does demonstrate that it is difficult to draw a qualitative distinction between individuals and groups in their capacity to achieve unification through purposeful effort. After all, given that difficulty internal motives have in effectually expressing their dissent, the importance to a dominant self of cohesion within an individual at any particular time may be less than that for a group. Thus this final objection to the dictatorship axiom is not categorically stronger in its applications to individuals than groups. The axiom that is perhaps most deceptive is independence of irrelevant alternatives (IIA), which requires that changes to the preferences of selves or desires over possibilities other than X or Y from do not affect the unified individual ranking of X against Y. One potential objection to IIA in the context of individual decision-making is that the various desires or selves may not constitute merely ordinal preferences; rather there may be some extent of cardinality or "degree" to these preferences. There are a few reasons to believe this is the case, many of them hinted at above. Accepting ordinality, the case for IIA becomes much stronger. Because we have excluded any notion of degrees of preference, violation of IIA can be seen as a reversal of aggregated preference on the basis of the addition or subtraction of some item from the choice set. On the face of it, that behavior seems deeply strange and inconsistent with rational choice. Unanimity seems immediately compelling and does not merit much analysis. Would it be reasonable for an individual to make a choice which every imaginable desire, consideration or self ranked as inferior to another choice? The last of Arrow's axioms is equally immediate in its appeal. Universal domain states that we cannot, a priori, rule out any ranking over the set of actions by various selves. While this appears a stringent condition, it is actually very intuitive: we cannot ahead of time say anything in particular about the alignment of preferences of various selves or desires with respect to one another. If we are now satisfied that Arrow's axioms seem reasonable in the context of aggregating various desires or the preferences of various selves, then Arrow's theorem implies that there may be no coherent way to take these various things that they value and join them into an overall preference. Since its birth, modern formal economics has simply maintained this counter-intuitive assumption that various desires are fungible with one another. When considering a complex problem where many different, independent desires are important, it is often hard to find a means of trading these various considerations off. Only economists find it a natural concept that years of life are commensurable, through some utility function, with dollars and cents. Arrow's theorem demonstrates decisively that this unstated assumption of fungiblity in economics, long criticized by anthropologists and sociologists, is far from innocuous. 55 Nor does the mere fact that an individual makes some decision imply that this action represents a choice in the sense of embodying a coherent preference. If an individual makes intransitive choices, there is no sense in which these "choices" reflect anything about what the individual would choose or prefer among the options involved. These choices no more reflect meaningful individual agency than the oft-derided actions of an alleged group representative can be 20 thought to report the preferences of a group. If we permit intransitivity in individual choice, then Arrow's critique of collective agency wilts. Even when an individual is simply incapable of making a choice, we will usually observe this as a choice in favor of the status quo. In fact, I provide much evidence below that this sort of tendency to choose default options is strongly prevalent in individual choice, just as Arrow argued it was in social choice. The Livnat and Pippenger computational argument for multiple selves suggests an important parallel between multiple selves within an individual and individuals within a group. Many, if not most, groups are constituted to advance some measu