Can conscientious objection lead to eugenic practices against LGBT individuals?

In a recent article in this journal, Abram Brummett argues that new and future assisted reproductive technologies will provide challenging ethical questions relating to lesbian, gay, bisexual and transgender (LGBT) persons. Brummett notes that it is likely that some clinicians may wish to conscientiously object to offering assisted reproductive technologies to LGBT couples on moral or religious grounds, and argues that such appeals to conscience should be constrained. We argue that Brummett's case is unsuccessful because he: does not adequately interact with his opponents’ views; equivocates on the meaning of ‘natural’; fails to show that the practice he opposes is eugenic in any non‐trivial sense; and fails to justify and explicate the relevance of the naturalism he proposes. We do not argue that conscience protections should exist for those objecting to providing LGBT people with artificial reproductive technologies, but only show that Brummett's arguments are insufficient to prove that they should not.     

Modelling Thrombin Generation in Human Ovarian Follicular Fluid

A mathematical model is constructed to study thrombin production in human ovarian follicular fluid. The model results show that the amount of thrombin that can be produced in ovarian follicular fluid is much lower than that in blood plasma, failing to reach the level required for fibrin formation, and thereby supporting the hypothesis that in follicular fluid thrombin functions to initiate cellular activities via intracellular signalling receptors. It is also concluded that the absence of the amplification pathway to thrombin production in follicular fluid is a major factor in restricting the amount of thrombin that can be produced. Titration of the initial concentrations of the various reactants in the model lead to predictions for the amount of tissue factor and phospholipid that is required to maintain thrombin production in the follicle, as well as to the conclusion that tissue factor pathway inhibitor has little effect on the time that thrombin generation is sustained. Numerical experiments to determine the effect of factor V, which is at a much reduced level in follicular fluid compared to plasma, and thrombomodulin, illustrate the importance for further experimental work to determine values for several parameters that have yet to be reported in the literature.     

CONSPIRATORIAL WHISPERS AND CONSPICUOUS DISPLAYS: GAMES OF SIGNAL DETECTION

Recent models of signaling have assumed that the expenditure required to ensure detection of a display is negligible and have concentrated instead on the costs that may be necessary to maintain honesty. Such models predict that individuals who share the same interests are likely to communicate using “conspiratorial whispers,” signals that are cheap and inconspicuous. Here, I present a game-theoretical model of signal detection (in a noisy environment, in the presence of potential eavesdroppers), which demonstrates that the idea of conspiratorial whispers is far too simplistic. It is true that in “cooperative” signaling systems (where signalers attempt to elicit responses that are beneficial for receivers), signal cost is not required to maintain honesty. However, some level of expenditure is still needed to ensure that a signal is reliably detected. Moreover, there exists a conflict of interest between signalers and receivers over the division of this expenditure. To predict the stable level of display in such cases, one needs to know how this conflict of interest will be resolved. The model reveals that the outcome may range from a whisper to a conspicuous and costly (though still conspiratorial) display. The more closely related the receiver is to the signaler, the greater the level of signal exaggeration that is expected—the opposite prediction to that of honest signaling models.     

Endosomal microdomains: Formation and function

It is widely recognized that after endocytosis, internalized cargo is delivered to endosomes that act as sorting stations. The limiting membrane of endosomes contain specialized subregions, or microdomains, that represent distinct functions of the endosome, including regions competing for cargo capture leading to degradation or recycling. Great progress has been made in defining the endosomal protein coats that sort cargo in these domains, including Retromer that recycles transmembrane cargo, and ESCRT (endosomal sorting complex required for transport) that degrades transmembrane cargo. In this review, we discuss recent work that is beginning to unravel how such coat complexes contribute to the creation and maintenance of endosomal microdomains. We highlight data that indicates that adjacent microdomains do not act independently but rather interact to cross-regulate. We posit that these interactions provide an agile means for the cell to adjust sorting in response to extracellular signals and intracellular metabolic cues.     

Two kinds of physician‐assisted death

I argue that the concept ‘physician‐assisted suicide’ covers two procedures that should be distinguished: giving someone access to humane means to end his own life, and taking co‐responsibility for the safe and effective execution of that plan. In the first section I explain the distinction, in the following sections I show why it is important. To begin with I argue that we should expect the laws that permit these two kinds of ‘assistance’ to be different in their justificatory structure. Laws that permit giving access only presuppose that the right to self‐determination implies a right to suicide, but laws that permit doctors to take co‐responsibility may have to appeal to a principle of mercy or beneficence. Actually this difference in justificatory structure can to some extent be found in existing regulatory systems, though far from consistently. Finally I argue that if one recognizes a right to suicide, as Oregon and other American states implicitly do, and as the European Court of Human Rights has recently done explicitly, one is committed to permit the first kind of ‘assistance’ under some conditions.     

Ectogenesis and gender-based oppression: Resisting the ideal of assimilation

In a recent article in this journal, Kathryn MacKay advances a defence of ectogenesis that is grounded in this technology’s potential to end—or at least mitigate the effects of—gender-based oppression. MacKay raises important issues concerning the socialization of women as ‘mothers’, and the harms that this socialization causes. She also considers ectogenesis as an ethically preferable alternative to gestational surrogacy and uterine transplantation, one that is less harmful to women and less subject to being co-opted to further oppressive ends. In this article, I challenge some of the assumptions that underlie MacKay’s case in favour of ectogenesis by questioning whether the relationship between women’s capacity to gestate and birth children and gender-based oppression is as strong as MacKay makes it out to be. I subsequently argue that—even if MacKay’s reading of this relationship is accurate—ectogenesis is not a desirable means to end gender-based oppression. It embodies a strategy that could be used to pursue liberating projects that follow what Iris Marion Young defines as ‘the ideal of assimilation’, but that must be resisted. I then concur with MacKay’s contention that ectogenesis is better than gestational surrogacy and uterine transplantation. My argument is that many of the problematic issues that MacKay herself sees as features of these practices will not disappear with ectogenesis. Finally, I conclude that MacKay’s narrow focus on women’s biology and ectogenesis as a solution to gender-based oppression results in the overlooking of broader systemic issues that contribute to the upholding of oppressive norms.     

Human cytotrophoblasts promote endothelial survival and vascular remodeling through secretion of Ang2, PlGF, and VEGF-C

Cytotrophoblasts are specialized epithelial cells of the human placenta that differentiate to acquire tumor-like properties that allow them to invade the uterus. Concurrently, they develop endothelial-like characteristics. This transformation allows cytotrophoblasts to replace the maternal cells that line uterine vessels, thereby diverting maternal blood to the placenta. Previously, we showed that invading cytotrophoblasts secrete VEGF-C and PlGF, factors that regulate their acquisition of an endothelial-like phenotype. Here, we examined the cells' expression of angiopoietin ligands and their Tie receptors. The data show that cytotrophoblasts predominantly expressed Ang2. We also studied the paracrine functions of Ang2 and the VEGFs by culturing uterine microvascular endothelial cells in cytotrophoblast-conditioned medium, which supported their growth. Removal of VEGF-C, PlGF, and/or Ang2 from the medium caused a marked reduction in cell number due to massive apoptosis. We also assayed the angiogenic potential of cytotrophoblast-derived factors in the chick chorioallantoic membrane assay. The results showed that they stimulated angiogenesis to a level comparable to that of basic FGF. These data suggest that invasive human cytotrophoblasts use an unusual repertoire of factors to influence the angiogenic state of maternal blood vessels and that this cross talk plays an important part in the endovascular component of uterine invasion.     

Site of graviperception in roots: a re-examination

Two lines of evidence have been cited to support the assertion that the root cap is the sole site of graviperception in the root. The first evidence is based on surgical removal of the cap, which abolishes the response to gravity. This is sufficient to conclude that the cap is involved in gravitropism, but not to conclude that the cap is the site of graviperception. The second is based on the results of centrifugation experiments, in which different parts of the plant are subjected to different centrifugal forces. The data from such experiments have been cited to support the conclusion that the perception of gravity is limited to the rootcap. However, these data actually support the conclusion that gravity is perceived throughout the root tip, and not only in the root cap. We believe that the data support the conclusion that the root cap is involved in root gravitropism, but that there is inadequate evidence to conclude that the cap is the sole site of graviperception.     

Multiple functional domains are involved in tomosyn regulation of exocytosis

Tomosyn is a cytoplasmic protein that was shown to bind to Syntaxin1 and SNAP-25 through an R-SNARE domain, forming a complex that is almost identical in structure to the neuronal SNARE complex. Tomosyn inhibits exocytosis in various cell types and these effects were attributed to direct competition between tomosyn's SNARE domain and Synaptobrevin/VAMP. In the present study, we investigated the contribution of different domains of tomosyn to its activity. We show that a tomosyn mutant that lacks the entire SNARE domain is a potent inhibitor of vesicle priming, similar to the full-length tomosyn. The SNARE domain of tomosyn failed to inhibit exocytosis, indicating that this domain is not required for the inhibition. In contrast, over-expression of a N-terminally truncated mutant did not lead to inhibition of exocytosis although this mutant still bound to Syntaxin. Our results indicate that tomosyn can inhibit exocytosis independently of its SNARE interaction with Syntaxin and that the integrity of the WD40-domain is crucial for tomosyn's inhibitory function. Furthermore, we demonstrate that the entire N-terminal region of tomosyn, the WD40-repeats and the linker, is required for tomosyn's inhibitory effect.     

Convergent setal morphology in sand-covering spiders suggests a design principle for particle capture

Sicarius and Homalonychus are unrelated, desert-dwelling spiders that independently evolved the ability to cover themselves in fine sand particles, making them cryptic against their background. Observations that particles associate with these spiders' setae inspired us to investigate the role of setal microstructure in particle capture and retention. Here we report that Sicarius and Homalonychus convergently evolved numerous high aspect ratio, flexible fibres that we call 'hairlettes' protruding from the setal shaft. We demonstrate that particles attach more densely to regions of Homalonychus with hairlettes than to other regions of the same animal where hairlettes are absent, and document close contact of hairlettes to sand particles that persists after applying force. Mathematical models further suggest that adhesion of hairlettes to sand particles is a sufficient mechanism of particle capture and retention. Together, these data provide the first evidence that hairlettes facilitate sand retention through intermolecular adhesion to particles. Their independent evolutionary origins in Sicarius and Homalonychus suggest that the unique setal structure is adaptive and represents a general biomechanical mechanism for sand capture to cuticle. This discovery has implications for the design of inventions inspired by this system, from camouflage to the management of granular systems.     

Cancer Development and Progression: A Non-Adaptive Process Driven by Genetic Drift

The current mainstream in cancer research favours the idea that malignant tumour initiation is the result of a genetic mutation. Tumour development and progression is then explained as a sort of micro-evolutionary process, whereby an initial genetic alteration leads to abnormal proliferation of a single cell that leads to a population of clonally derived cells. It is widely claimed that tumour progression is driven by natural selection, based on the assumption that the initial tumour cells acquire some properties that endow such cells with a selective advantage over the normal cells from which the tumour cells are derived. The standard view assumes that the transformed bodily cell somehow acquires "responsiveness" to natural selection independently of the whole organism to which the cell belongs. Yet, it is never explained where such an acquired capacity to respond to natural selection by the individual bodily cell comes from. This situation poses many difficult questions that so far have been left unanswered. For example, there is no explanation why some cells belonging to an organised whole and as such having no independent capacity for survival, apparently become 'independent' entities, able to respond to selective pressures in an autonomous fashion and then to be evaluated by natural selection. Hereunder it is argued that such a qualitative change cannot be the consequence of specific genetic mutations. Moreover, it is shown that natural selection is unlikely to be acting within the organism during tumour development and progression and that tumour evolution is a random, non-adaptive process, driven by no fundamental biological principle. Thus, mutations in the so-called oncogenes and tumour suppressor genes observed in epithelial cancers (that constitute more than 90% of all cancers) are not the result of selection for better cellular growth or survival under restrictive conditions. Instead, here it is suggested that they are the consequence of genetic drift acting upon gene functions that become non-relevant, either for the individual or the species fitness, once the organism is past its reproductive prime and as such, they also become superfluous for cell survival in the short term. It is proposed that the origin of cancer is epigenetic and it is a consequence of the need for a continued turnover of the individuals that constitute a species.     

Solutions to the New Threats to Academic Freedom?

In my commentary on Francesca Minerva's article ‘New Threats to Academic Freedom’, I agree with her contention that the existence of the Internet has given rise to new and very serious threats to academic freedom. I think that it is crucial that we confront those threats, and find ways to eliminate them, which I believe can be done. The threats in question involve both authors and editors. In the case of authors, I argue that the best solution is not anonymous publication, but publication using pseudonyms, and I describe how that would work. In the case of editors, my proposal is a website that a number of journals would have access to, where papers that editors judge to be clearly worthy of publication, but whose publication seems likely to set off a firestorm of public and media protest, could be published without any indication of the journal that had accepted the paper for publication.     

How plants manipulate the scatter-hoarding behaviour of seed-dispersing animals

Some plants that are dispersed by scatter-hoarding animals appear to have evolved the ability to manipulate the behaviour of those animals to increase the likelihood that seeds and nuts will be stored and that a portion of those items will not be recovered. Plants have achieved this in at least four ways. First, by producing large, nutritious seeds and nuts that are attractive to animals and that stimulate hoarding behaviour. Second, by imposing handling costs that cause animals to hoard rather than to eat items immediately. These handling costs can take one of two forms: physical barriers (e.g. hard seed coats) that take time to remove and secondary chemicals (e.g. tannins) that impose metabolic costs. Third, by masting, where a population of plants synchronizes reproductive effort, producing large nut crops at intervals of several years. Mast crops not only satiate seed predators, but also increase the amount of seed dispersal because scatter-hoarding animals are not easily satiated during caching (causing animals to store more food than they can consume) but are satiated during cache recovery. And fourth, by producing seeds that do not emit strong odours so that buried seeds are less likely to be discovered. These, and perhaps other, traits have increased the relative success of plant species with seeds dispersed by scatter-hoarding animals.     

Changing the specificity of a bacterial chemoreceptor

The methyl-accepting chemotaxis proteins are a family of receptors in bacteria that mediate chemotaxis to diverse signals. To explore the plasticity of these proteins, we have developed a simple method for selecting cells that swim to target attractants. The procedure is based on establishing a diffusive gradient in semi-soft agar plates and does not require that the attractant be metabolized or degraded. We have applied this method to select for variants of the Escherichia coli aspartate receptor, Tar, that have a new or improved response to different amino acids. We found that Tar can be readily mutated to respond to new chemical signals. However, the overall change in specificity depended on the target compound. A Tar variant that could detect cysteic acid still showed a strong sensitivity to aspartate, indicating that the new receptor had a broadened specificity relative to wild-type Tar. Tar variants that responded to phenylalanine or N-methyl aspartate, or that had an increased sensitivity to glutamate showed a strong decrease in their response to aspartate. In at least some of the cases, the maximal level of sensitivity that was obtained could not be attributed solely to substitutions within the binding pocket. The new tar alleles and the techniques described here provide a new approach for exploring the relationship between ligand binding and signal transduction by chemoreceptors and for engineering new receptors for applications in biotechnology.     

Rationality, biology and optimality*

A historical theory of rational norms claims that, if we are supposed to think rationally, this is because it is biologically normal for us to do so. The historical theorist is committed to the view that we are supposed to think rationally only if, in the past, adult humans sometimes thought rationally. I consider whether there is any plausible model of rational norms that can be adopted by the historical theorist that is compatible with the claim that adult human beings are subject to rational norms, given certain plausible empirical assumptions about our history and capabilities. I suggest that there is one such model: this model centres on the idea that a procedure is rational if it has been endorsed (or at least not rejected) by mechanisms that have the function to ensure that the subject learns to reason in a way that approaches a certain kind of optimality. This revised version was published online in July 2006 with corrections to the Cover Date.     

The interpretation of habitat preference metrics under use�Cavailability designs

Models of habitat preference are widely used to quantify animal–habitat relationships, to describe and predict differential space use by animals, and to identify habitat that is important to an animal (i.e. that is assumed to influence fitness). Quantifying habitat preference involves the statistical comparison of samples of habitat use and availability. Preference is therefore contingent upon both of these samples. The inferences that can be made from use versus availability designs are influenced by subjectivity in defining what is available to the animal, the problem of quantifying the accessibility of available resources and the framework in which preference is modelled. Here, we describe these issues, document the conditional nature of preference and establish the limits of inferences that can be drawn from these analyses. We argue that preference is not interpretable as reflecting the intrinsic behavioural motivations of the animal, that estimates of preference are not directly comparable among different samples of availability and that preference is not necessarily correlated with the value of habitat to the animal. We also suggest that preference is context-dependent and that functional responses in preference resulting from changing availability are expected. We conclude by describing advances in analytical methods that begin to resolve these issues.     

Morphological plasticity in the kelp Nereocystis luetkeana (Phaeophyceae) is sensitive to the magnitude,direction, and location of mechanical loading

Nereocystis luetkeana is a canopy-forming kelp that exhibits morphological plasticity across hydrodynamic gradients, producing broad, undulate blades in slow flow and narrow, flattened blades in fast flow, enabling thalli to reduce drag while optimizing photosynthesis. While the functional significance of this phenomenon has been well studied, the developmental and physiological mechanisms that facilitate the plasticity remain poorly understood. In this study, we conducted three experiments to characterize how the (1) magnitude, (2) direction, and (3) location of plasticity-inducing mechanical stimuli affect the morphology of Nereocystis blades. We found that applying a gradient of tensile force caused blades to grow progressively longer, narrower, less ruffled, and heavier in a linear fashion, suggesting that Nereocystis is equally well adapted for all conditions within its hydrodynamic niche. We also found that applying tension transversely across blades caused the growth response to rotate 90°, indicating that there is no substantial separation between the sites of stimulus perception and response and suggesting that a long-distance signaling mechanism, such as a hormone, is unlikely to mediate this phenomenon. Meristoderm cells showed morphological changes that paralleled those of their respective blades in this experiment, implying that tissue-level morphology is influenced by cell growth. Finally, we found that plasticity was only induced when tension was applied directly to the growing tissue, reinforcing that long-distance signaling is probably not involved and possibly indicating that the mechanism on display generally requires an intercalary meristem to facilitate mechanoperception.     

Phylogenetic distributions of British birds of conservation concern

Recent studies suggest that species' life histories and ecology can be used to forecast future extinction risk. Threatened species often share similar traits such that if a trait predisposing a species to decline or extinction is evolutionarily conserved, then close relatives of threatened species are themselves likely to be at risk. The phylogenetic distribution of current threat has been argued to provide insight into the species that could be threatened in the future when trait data are not available. Conservation criteria are typically based on multiple indices that capture different symptoms of threat including population trends and range contraction. However, there is no reason to assume consistent phylogenetic distributions of different symptoms. I construct a molecular phylogeny of 249 species of British birds (more than 93% of the breeding and wintering species) and use this to show that the species that are threatened due to population declines are phylogenetically more closely related than expected by chance alone. However, species that are listed for other reasons, including range contraction, are distributed randomly with respect to phylogeny. I suggest that while phylogeny can be informative with respect to identifying clades that are susceptible to some measures of extinction risk, such patterns are likely to be idiosyncratic with respect to symptom and taxa.     

When cytoprotective autophagy isn’t… and even when it is

Multiple papers have been published that have identified and/or characterized the cytoprotective function of autophagy, primarily in tumor cells exposed to chemotherapy or radiation. These studies have relied on pharmacological and/or genetic interference with autophagy to establish its protective function, often primarily by demonstrating that cells in which autophagy has been suppressed undergo increased apoptosis. The purpose of this Editor’s Corner is to emphasize that these approaches, while absolutely necessary, are of themselves insufficient to support the conclusion that autophagy is cytoprotective in a given experimental tumor line exposed to a particular agent; complementary studies are required that demonstrate that autophagy inhibition sensitizes the tumor cell to the autophagy-inducing treatment. Otherwise, autophagy may be responsible for the growth arrest and/or cell death that is observed with the drug or radiation treatment alone, and autophagy inhibition may simply be converting one form of growth inhibition/cell death to an alternative pathway that achieves the same end result in terms of sensitivity to the treatment.