The Structure of the Anuran Amphibian Notochord and a Re-evaluation of its Presumed Role in Early Embryogenesis

For almost a century the amphibian notochord has been analyzed from either the structural or functional point of view. Relatively complete data have been collected concerning several aspects of its structure. Some of that data will be reviewed in this report. The functional role of the notochord has also occasionally been analyzed. Only recently, however, have extensive data begun to emerge which deal directly with cause-effect relationships which may or may not exist between the notochord and surrounding tissues of the embryonic axial structure system. This report will re-evaluate the role of the notochord in amphibian embryogenesis, and provide a review of the historical perspective in which recent discoveries should be interpreted.     

The death of dignity is greatly exaggerated: Reflections 15 years after the declaration of dignity as a useless concept

Fifteen years ago, Ruth Macklin shook the medical community with her claim in the BMJ that dignity is a useless concept. Her essay provoked a storm of reactions. What have we learned from the debate? In this article I analyse the responses to her essay and the following debate to investigate whether she was right that “[d]ignity is a useless concept in medical ethics and can be eliminated without any loss of content.” While some of the commentaries misconstrued her claim and argue against strawmen, others forcefully maintained that the concept of dignity has functions beyond “respect for persons and their autonomy.” One important point that came out of the debate is that dignity is a generic concept that covers more ground than “respect for persons or their autonomy.” In particular, dignity seems to have a wide range of protective functions as well as having reciprocal, relational, and social aspects. Dignity appears more attributional and norm-formative than respect for persons and autonomy. While the claim that dignity is unclear, vague, and can be used sloganistically seems highly relevant, it is argued that this vagueness fulfils important functions in ethics. Moreover, dismissing dignity because of its lack of clarity has implications for “respect for persons” and “autonomy,” which are also used vaguely and sloganistically. No doubt medical ethics should use as a clear concept as the context requires. Nonetheless, dignity still seems to be a widely used generic concept in ethical debates and doing as much ethical work as “respect for persons” or “respect for autonomy.” Therefore, the death of dignity seems to be greatly exaggerated.     

Presuming patient autonomy in the face of therapeutic misconception

Therapeutic misconception involves the failure of subjects either to understand or to incorporate into their own expectations the distinctions in nature and purpose of personally responsive therapeutic care, and the generic relationship between subject and investigator which is constrained by research protocols. Researchers cannot disregard this phenomenon if they are to ensure that subjects engage in research on the basis of genuine informed consent. However, our presumption of patient autonomy must be sustained unless we have compelling evidence of serious misunderstanding. This article argues that the mere expression of aspects of therapeutic misconception should not necessarily displace the presumption of subject autonomy or undermine ethical inclusion in research for at least three reasons. First, some interpretations of the empirical data do not suggest misunderstanding. Second, assessment of misestimation and optimism are delicate and value‐laden, and turn quickly from questions of autonomy to questions of judgment. Third, incomplete understanding may yet be sufficient to allow a subject to engage in a substantially autonomous decision‐making process. Our point is not to dismiss the possibility of genuine therapeutic misconception, but to question its frequency and fatality to the consent process.     

An in vitro-selected RNA receptor for the GAAC loop: modular receptor for non–GNRA-type tetraloop

Although artificial RNA motifs that can functionally replace the GNRA/receptor interaction, a class of RNA–RNA interacting motifs, were isolated from RNA libraries and used to generate designer RNA structures, receptors for non-GNRA tetraloops have not been found in nature or selected from RNA libraries. In this study, we report successful isolation of a receptor motif interacting with GAAC, a non-GNRA tetraloop, from randomized sequences embedded in a catalytic RNA. Biochemical characterization of the GAAC/receptor interacting motif within three structural contexts showed its binding affinity, selectivity and structural autonomy. The motif has binding affinity comparable with that of a GNRA/receptor, selectivity orthogonal to GNRA/receptors and structural autonomy even in a large RNA context. These features would be advantageous for usage of the motif as a building block for designer RNAs. The isolated motif can also be used as a query sequence to search for unidentified naturally occurring GANC receptor motifs.     

Values at stake: autonomy, responsibility, and trustworthiness in relation to genetic testing and personalized nutrition advice

Personalized nutrition has the potential to enhance individual health control. It could be seen as a means to strengthen people’s autonomy as they learn more about their personal health risks, and receive dietary advice accordingly. We examine in what sense personalized nutrition strengthens or weakens individual autonomy. The impact of personalized nutrition on autonomy is analyzed in relation to responsibility and trustworthiness. On a societal level, individualization of health promotion may be accompanied by the attribution of extended individual responsibility for one’s health. This constitutes a dilemma of individualization, caused by a conflict between the right to individual freedom and societal interests. The extent to which personalized nutrition strengthens autonomy is consequently influenced by how responsibility for health is allocated to individuals. Ethically adequate allocation of responsibility should focus on prospective responsibility and be differentiated with regard to individual differences concerning the capacity of adults to take responsibility. The impact of personalized nutrition on autonomy also depends on its methodological design. Owing to the complexity of information received, personalized nutrition through genetic testing (PNTGT) is open to misinterpretation and may not facilitate informed choices and autonomy. As new technologies, personalized nutrition and PNTGT are subject to issues of trust. To strengthen autonomy, trust should be approached in terms of trustworthiness. Trustworthiness implies that an organization that develops or introduces personalized nutrition can show that it is competent to deal with both the technical and moral dimensions at stake and that its decisions are motivated by the interests and expectations of the truster.     

Does Gender Inequity Increase the Risk of Intimate Partner Violence among Women? Evidence from a National Bangladeshi Sample

Background

Evidence from developing countries regarding the association between gender inequity and intimate partner violence (IPV) victimization in women has been suggestive but inconclusive. Using nationally representative population-based data from Bangladesh, we examined the association between multidimensional aspects of gender inequity and the risk of IPV.

Methods

We used data from the 2007 Bangladesh Demographic Health Survey. The analyses were based on the responses of 4,467 married women. The main explanatory variable was gender inequity, which reflects the multidimensional aspects of women''s autonomy and the relationship inequality between women and their partner. The experience of physical and/or sexual IPV was the main outcome variable of interest.

Results

Over 53% of married Bangladeshi women experienced physical and/or sexual violence from their husbands. In the adjusted models, women who had a higher level of autonomy (adjusted odds ratio [AOR] 0.48; 99% confidence interval [CI] 0.37–0.61), a particularly high level of economic-decision-making autonomy (AOR 0.12; 99% CI 0.08–0.17), and a higher level of non-supportive attitudes towards wife beating or raping (AOR 0.61; 99% CI 0.47–0.83) were less likely to report having experienced IPV. Education level, age at marriage, and occupational discrepancy between spouses were also found to be significant predictors of IPV.

Conclusions

In conclusion, dimensions of gender inequities were significant predictors of IPV among married women in Bangladesh. An investigation of the causal link between multidimensional aspects of gender inequity and IPV will be critical to developing interventions to reduce the risk of IPV and should be considered a public health research priority.     

The evolution of multicellularity in animals as a shift in biological autonomy

The hypothesis is advanced that major evolutionary innovations are characterized by an increase of organismal autonomy in the sense of an emancipation from the environment. After a brief overview of the literature on this concept, increasing autonomy is defined as the evolutionary shift in the individual system-environment relationship, so that the direct influences of the environment are gradually reduced and a stabilization of self-referential, intrinsic functions within the system is generated. This is described as relative autonomy because numerous interconnections with the environment and dependencies upon it are retained. Elements of an increasing autonomy are spatial separations, an increase in homeostatic functions, internalizations and an increase in physiological and behavioral flexibility. These elements are described by taking the transition from single cells to metazoans as a case study. The principle of increasing autonomy is of central relevance for understanding this transition. The hypothesis does not contradict the principle of adaptation, but rather contributes to a further understanding of its elements as it supplies aspects for a reconsideration of the relationship between the outside and the inside, between organism and environment.     

Interpreting the behavior of enzymes: purpose or pedigree?

To interpret the growing body of data describing the structural, physical, and chemical behaviors of biological macromolecules, some understanding must be developed to relate these behaviors to the evolutionary processes that created them. Behaviors that are the products of natural selection reflect biological function and offer clues to the underlying chemical principles. Nonselected behaviors reflect historical accident and random drift. This review considers experimental data relevant to distinguishing between nonfunctional and functional behaviors in biological macromolecules. In the first segment, tools are developed for building functional and historical models to explain macromolecular behavior. These tools are then used with recent experimental data to develop a general outline of the relationship between structure, behavior, and natural selection in proteins and nucleic acids. In segments published elsewhere, specific functional and historical models for three properties of enzymes--kinetics, stereospecificity, and specificity for cofactor structures--are examined. Functional models appear most suitable for explaining the kinetic behavior of proteins. A mixture of functional and historical models appears necessary to understand the stereospecificity of enzyme reactions. Specificity for cofactor structures appears best understood in light of purely historical models based on a hypothesis of an early form of life exclusively using RNA catalysis.     

Structural overshoot of tree growth with climate variability and the global spectrum of drought‐induced forest dieback

Ongoing climate change poses significant threats to plant function and distribution. Increased temperatures and altered precipitation regimes amplify drought frequency and intensity, elevating plant stress and mortality. Large‐scale forest mortality events will have far‐reaching impacts on carbon and hydrological cycling, biodiversity, and ecosystem services. However, biogeographical theory and global vegetation models poorly represent recent forest die‐off patterns. Furthermore, as trees are sessile and long‐lived, their responses to climate extremes are substantially dependent on historical factors. We show that periods of favourable climatic and management conditions that facilitate abundant tree growth can lead to structural overshoot of aboveground tree biomass due to a subsequent temporal mismatch between water demand and availability. When environmental favourability declines, increases in water and temperature stress that are protracted, rapid, or both, drive a gradient of tree structural responses that can modify forest self‐thinning relationships. Responses ranging from premature leaf senescence and partial canopy dieback to whole‐tree mortality reduce canopy leaf area during the stress period and for a lagged recovery window thereafter. Such temporal mismatches of water requirements from availability can occur at local to regional scales throughout a species geographical range. As climate change projections predict large future fluctuations in both wet and dry conditions, we expect forests to become increasingly structurally mismatched to water availability and thus overbuilt during more stressful episodes. By accounting for the historical context of biomass development, our approach can explain previously problematic aspects of large‐scale forest mortality, such as why it can occur throughout the range of a species and yet still be locally highly variable, and why some events seem readily attributable to an ongoing drought while others do not. This refined understanding can facilitate better projections of structural overshoot responses, enabling improved prediction of changes in forest distribution and function from regional to global scales.     

Spatiotemporally explicit demographic modelling supports a joint effect of historical barriers to dispersal and contemporary landscape composition on structuring genomic variation in a red‐listed grasshopper

Inferring the processes underlying spatial patterns of genomic variation is fundamental to understand how organisms interact with landscape heterogeneity and to identify the factors determining species distributional shifts. Here, we use genomic data (restriction site‐associated DNA sequencing) to test biologically informed models representing historical and contemporary demographic scenarios of population connectivity for the Iberian cross‐backed grasshopper Dociostaurus hispanicus, a species with a narrow distribution that currently forms highly fragmented populations. All models incorporated biological aspects of the focal taxon that could hypothetically impact its geographical patterns of genomic variation, including (a) spatial configuration of impassable barriers to dispersal defined by topographic landscapes not occupied by the species; (b) distributional shifts resulting from the interaction between the species bioclimatic envelope and Pleistocene glacial cycles; and (c) contemporary distribution of suitable habitats after extensive land clearing for agriculture. Spatiotemporally explicit simulations under different scenarios considering these aspects and statistical evaluation of competing models within an Approximate Bayesian Computation framework supported spatial configuration of topographic barriers to dispersal and human‐driven habitat fragmentation as the main factors explaining the geographical distribution of genomic variation in the species, with no apparent impact of hypothetical distributional shifts linked to Pleistocene climatic oscillations. Collectively, this study supports that both historical (i.e., topographic barriers) and contemporary (i.e., anthropogenic habitat fragmentation) aspects of landscape composition have shaped major axes of genomic variation in the studied species and emphasizes the potential of model‐based approaches to gain insights into the temporal scale at which different processes impact the demography of natural populations.     

Historical and phylogenetic constraints on the incidence of entire leaf margins: insights from a new South American model

Aim The relationship between the proportion of species with an entire leaf margin (pE) and mean annual temperature (MAT) is one of the most powerful tools for estimating palaeotemperatures. However, phylogenetic and phytogeographic constraints on this relationship have remained unexplored. Here we investigate the pE–MAT relationship for modern floristic assemblages from southern South American forests, assess its conformity to other models and test for the existence of historical constraints on pE–MAT models. Location South America. Methods We used samples from 30 sites located in Chile between 32° and 44° S to test for a pE–MAT relationship and compared it with four regional models. We assessed the reliability of these models for predicting MAT from instrumental records in eight modern temperate‐forest localities in Chile. Additionally, palaeotemperatures for Cenozoic fossil floras were estimated. To assess historical constraints in pE, we measured the phylogenetic signal in leaf margin type and the association between leaf margin and phytogeographic affiliation, defined by the distribution of genera. Results We found a significant pE–MAT relationship for Chilean forest species that differed from Australia and Northern Hemisphere models, but not from tropical South America (TSA). Temperatures for southern South American localities predicted from the new regional model – combining Chilean and TSA datasets – were more accurate than those from previous models. We also showed that leaf margin type has a strong phylogenetic signal, which was further confirmed by the highly significant effect of phytogeographic element on leaf margin type. Main conclusions Differences between the Chilean and other regional models are explained by historical legacy, as Chilean leaf margin types are strongly affected by phylogenetic closeness and phytogeographic elements. We highlight that leaf margin analyses should be conducted within the context of a flora with a shared history. Thus, we propose a new model for South America to estimate palaeotemperatures for regional fossil floras.     

The Semiotics of Culture and the Concept of a Text

Two tendencies are ascertainable in the development of semiotics over the past 15 years. One has been toward refinement of the initial concepts and definition of procedures of generation. The striving for precise modeling procedures has led to the creation of metasemiotics: the object of study becomes not texts as such, but models of texts, models of models, etc. The second tendency concentrates its attention on the semiotic functioning of a real text. Whereas in the first case contradiction, structural inconsistency, the accommodation of differently structured texts within single textual formation, and semantic indeterminacy are random and nonfunctional attributes that can be removed at the metalevel of text modeling, from the second standpoint they are the object of special attention. Using Saussurean terminology, we might say that in the first case it is langage that interests the investigator as a materialization of the structural laws of a langue; in the second case it is those semiotic aspects of a text that diverge from the linguistic structure that are the object of attention. Whereas the first tendency is materialized in metasemiotics, the second by nature gives birth to the semiotics of culture.     

Conceptualizing the Person: Hierarchical Society and Individual Autonomy in India

Explanations by social scientists of the Indian person have emphasized the subordination of the individual to caste and family and the compelling influence of hierarchy for explaining motivations for behavior. They have asserted there is no room for individuation and personal autonomy in Indian society. If correct, personal goals should be rare among Indians, rebellion against family and caste should be unusual, and deviation from the etiquette of hierarchy should be infrequent. Based on 23 life histories, the findings of this article contradict this view. As Indians age, achieving a degree of autonomy is an increasingly important theme in adult life and is closely associated with rebellions against hierarchy and with these Indians' perception of responsibility for how their lives turn out. The article concludes that hierarchy has been given such a dominant role in describing Indian society that the significance of personal explanations of autonomy and motivation has been discounted.     

Cognizing "Cognized Models"

In his later work Rappaport acknowledged that his earlier efforts had overemphasized organic and ecological functions in the explanation of cultural phenomena. He then distanced himself from both idealism and reductive materialism and set out to understand the complexities of cultural understandings and ritual. Specifically, he shifted from functionalism to formalism in an effort to understand ritual and its language in relation to cultural norms. Ultimately his analysis was implicitly structural, understanding the part as a constituent of an overarching arrangement and in terms of what Althusser would have called "structural causality." Although his work benefited from this shift from function to structure, Rappaport did not use it to explore the political dimension. However, a holistic ecology such as the one Rappaport essayed must ultimately embrace both political ecology and historical ecology, [cognized models, ritual, political ecology, structural causality-]     

How (not) to model autonomous behaviour

Autonomous systems are the result of self-sustaining processes of constitution of an identity under precarious circumstances. They may transit through different modes of dynamical engagement with their environment, from committed ongoing coping to open susceptibility to external demands. This paper discusses these two statements and presents examples of models of autonomous behaviour using methods in evolutionary robotics. A model of an agent capable of issuing self-instructions demonstrates the fragility of modelling autonomy as a function rather than as a property of a system's organization. An alternative model of behavioural preference based on homeostatic adaptation avoids this problem by establishing a mutual constraining between lower-level processes (neural dynamics and sensorimotor interaction) and higher-level metadynamics (experience-dependent, homeostatic triggering of local plasticity and re-organization). The results of these models are lessons about how strong autonomy should be approached: neither as a function, nor as a matter of external vs. internal determination.     

Would Industrial Ecology Exist without Sustainability in the Background?

Industrial ecology rests historically—even in a short lifetime of 15 years or so—on the metaphorical power of natural ecosystems. Its evolution parallels the rise of concerns over unsustainability, that is, the threats to our world's ability to support human life the emergence of sustainability as a normative goal on a global scale. This article examines the relationships between industrial ecology and sustainability and argues that, in its historical relationship to classical ecology models, the field lacks power to address the full range of goals of sustainability, however defined. The classical ecosystem analogy omits aspects of human social and cultural life central to sustainability. But by moving beyond this model to more recent ecosystem models based on complexity theory, the field can expand its purview to address sustainability more broadly and powerfully. Complexity models of living systems can also ground alternative normative models for sustainability as an emergent property rather than the output of a mechanistic economic model for society's workings.     

Working model for the structural basis for KCNE1 modulation of the KCNQ1 potassium channel

The voltage-gated potassium channel KCNQ1 (Kv7.1) is modulated by KCNE1 (minK) to generate the I(Ks) current crucial to heartbeat. Defects in either protein result in serious cardiac arrhythmias. Recently developed structural models of the open and closed state KCNQ1/KCNE1 complexes offer a compelling explanation for how KCNE1 slows channel opening and provides a platform from which to refine and test hypotheses for other aspects of KCNE1 modulation. These working models were developed using an integrative approach based on results from nuclear magnetic resonance spectroscopy, electrophysiology, biochemistry, and computational methods-an approach that can be applied iteratively for model testing and revision. We present a critical review of these structural models, illustrating the strengths and challenges of the integrative approach.     

区域旅游形象构建与景观规划--以临海市为例

区域旅游形象的构建包括旅游感知引导和区域景观规划两个方面,区域景观是旅游感知的基础,旅游感知则可以对区域景观的建设进行修正。区域景观规划需要分析区域的自然、社会、经济和历史背景,尤其是旅游资源的特色。本文应用景观生态学的原理和空间分析方法,进行区域内视觉体系的景观规划和构建,尤其是在区域内合适的地点建立相应的景观,并以浙江省临海市为案例,进行理论的实践研究。     

Do crystal structures obviate the need for theoretical models of GPCRs for structure‐based virtual screening?

Recent highly expected structural characterizations of agonist-bound and antagonist-bound beta-2 adrenoreceptor (β2AR) by X-ray crystallography have been widely regarded as critical advances to enable more effective structure-based discovery of GPCRs ligands. It appears that this very important development may have undermined many previous efforts to develop 3D theoretical models of GPCRs. To address this question directly, we have compared several historical β2AR models versus the inactive state and nanobody-stabilized active state of β2AR crystal structures in terms of their structural similarity and effectiveness of use in virtual screening for β2AR specific agonists and antagonists. Theoretical models, incluing both homology and de novo types, were collected from five different groups who have published extensively in the field of GPCRs modeling. All models were built before X-ray structures became available. In general, β2AR theoretical models differ significantly from the crystal structure in terms of TMH definition and the global packing. Nevertheless, surprisingly, several models afforded hit rates resulting from virtual screening of large chemical library enriched by known β2AR ligands that exceeded those using X-ray structures. The hit rates were particularly higher for agonists. Furthemore, the screening performance of models is associated with local structural quality, such as the RMSDs for binding pocket residues and the ability to capture accurately, most if not all critical protein/ligand interactions. These results suggest that carefully built models of GPCRs could capture critical chemical and structural features of the binding pocket, and thus may be even more useful for practical structure-based drug discovery than X-ray structures.