Intraosseous angiosarcoma with secondary aneurysmal bone cysts presenting as an elusive diagnostic challenge

Angiosarcoma of bone is an exceedingly rare primary bone malignancy that can present as an aggressive osteolytic lesion. Histological diagnosis can be extremely challenging, as the pathological features often resemble that of aneurysmal bone cysts. We report an interesting and peculiar case of an intraosseous angiosarcoma that presented as a diagnostic dilemma and discuss the relevant radiological and pathologic findings.     

The fitness consequences of the autotomous blue tail in lizards: an empirical test of predator response using clay models

Numerous vertebrates employ one or more autotomous body parts as an anti-predation mechanism. Many lizards possess an autotomous tail that is brightly colored blue, which has been suggested to either serve as a decoy mechanism to divert predator attention to the autotomous body part, as an interspecific signal, or as an aposematic signal to predators that it is distasteful or dangerous. While theoretical studies suggest that a conspicuous autotomous body part that increases the probability of escape while not increasing the rate of detection will be favorable over a completely cryptic form, there is little empirical evidence supporting the adaptive benefit of an autotomous blue tail. We used in situ clay models of a scincid lizard to test the fitness consequences of blue coloration. Lizard models with a dark base color and blue decoy coloration experienced no measurable difference in avian predation relative to an all-dark model, which suggests that blue coloration neither serves as an aposematic signal nor increases the conspicuousness of the lizard model. Despite statistically similar attack rates, avian attacks on models with blue coloration were indeed focused on body sections that were colored blue. Our results suggest that the blue tail in lizards serves as an effective decoy, and that avian predation has possibly played a role in the evolution of the blue tail.     

Acting to Let Someone Die

This paper examines the recent prominent view in medical ethics that withdrawing life‐sustaining treatment (LST) is an act of killing. I trace this view to the rejection of the traditional claim that withdrawing LST is an omission rather than an act. Although that traditional claim is not as problematic as this recent prominent view suggests, my main claim is that even if we accepted that withdrawing LST should be classified as an act rather than as an omission, it could still be classified as letting die rather than killing. Even though omissions are contrasted with acts, letting die need not be, for one can let die by means of acts. The remainder of the paper is devoted to establishing this claim and addresses certain objections to it.     

The histochemical demonstration of myoglobin in muscle spindles

Synopsis Muscle spindles from skeletal muscles of the rat and the guinea pig were stained to demonstrate their myoglobin content.Large intrafusal muscle fibres stained strongly for this pigment whilst the small intrafusal fibres showed little staining. This staining pattern contrasts strongly with that of the extrafusal muscle fibres.It has been suggested that myoglobin may act either as an oxygen storing or as an oxygen transporting pigment. The staining pattern present in muscle spindles indicates that myoglobin may act more as an oxygen transporting pigment than as an oxygen storing pigment.     

Metaphors of glaucoma

In a phenomenological study of glaucoma as an illness, 31 patients were interviewed. The goal of the study was an explication of the meanings of the experience of glaucoma, in a twofold sense: (1) the face, the role, or the self of the patient that responds to the illness; (2) the visage that the illness presents to the patient. This twofold explication was achieved by generating a classification of the interviews in terms of the dominant metaphor that emerged in each interview. The following basic metaphors are presented through case material: glaucoma as an accompaniment of aging, as blindness, as pressure, as an abstraction (and a weapon), and as fate. Variations on these themes demonstrate the necessity, in such work and for enhanced communication with patients, of paying attention to both the face that the illness presents and to the self that responds.     

Effect of dietary tomatine on cholesterol metabolism in the rat

Tomatine is a virtually nonabsorbable saponin which has been used as an antifungal agent and analytically as a cholesterol precipitant. It was used in this study to determine whether or not it can form a complex with cholesterol in vivo in the rat intestine and what effects such complex formation would have on cholesterol metabolism. Rats that were fed tomatine as 1% of the diet had a decreased uptake of dietary cholesterol by the liver, an increased rate of hepatic and intestinal cholesterol synthesis as well as a partial offsetting of the dietary cholesterol-induced decrease in hepatic cholesterogenesis, and an apparent increase in sterol excretion without an effect on bile acid excretion. In vitro, tomatine did not sequester cholic acid as did cholestyramine. The results show that tomatine has an effect on cholesterol absorption and on other aspects of lipid metabolism in the rat similar to that of cholestyramine, with the notable exception that tomatine increased sterol excretion while cholestyramine increased bile acid excretion. It was suggested that tomatine forms a nonabsorbable complex with cholesterol in the rat intestine.     

The Temporality of “Chronic” Mental Illness

Although multiple concepts of time can be found in psychiatric discourses and practices, the notion of time as an absolute category seems to predominate. In particular, the notion of “chronicity” implies the persistence of symptoms over the temporal course of a disease, thereby following a logic that conceptualizes time as an objective and universal measure. I argue that such a notion of time impedes the development of patients and the metrics by which to map change. This article, therefore, aims to present a different concept of time that should enable dealing with "chronic" mental illness in more flexible and creative ways. A case study of an everyday psychiatric routine is presented, followed by an in-depth analysis of its temporal implications. I conceptualize the notion of time as an extended field, being relationally and intersubjectively structured and linked to performed activities. Such a notion of time needs to be seen as a flexible and fluid matrix that possesses the character of an event-oriented and productive space. This conception favors an individualized temporality of change, suggesting concrete therapeutic procedures that can be implemented in clinical practice.     

Calcium as an extracellular signalling molecule: perspectives on the Calcium Sensing Receptor in the brain

Calcium acts as a universal signal that is responsible for controlling a spectrum of cellular processes ranging from fertilization to apoptosis. For a long time, calcium was regarded solely as an intracellular second messenger. However, the discovery that calcium can also act as an external ligand together with the molecular cloning of its cell surface receptor, the Calcium Sensing Receptor (CaSR), demonstrated that calcium also acts as an important extracellular or first messenger. Here, we give an overview of the main structural, pharmacological and physiological features of the CaSR and provide an assessment of its functions and cellular and molecular mechanisms of action. In addition, we propose possible avenues for future research into the trafficking of CaSR and the role(s) of this receptor in the central nervous system.     

Genomic imprinting and the units of adaptation

Two guiding principles identify which biological entities are able to evolve adaptations. Williams'' principle holds that, in order for an entity to evolve adaptations, there must be selection between such entities. Maynard Smith''s principle holds that, in order for an entity to evolve adaptations, selection within such entities must be absent or negligible. However, although the kinship theory of genomic imprinting suggests that parent-of-origin-specific gene expression evolves as a consequence of natural selection acting between—rather than within—individuals, it evades adaptive interpretation at the individual level and is instead viewed as an outcome of an intragenomic conflict of interest between an individual''s genes. Here, I formalize the idea that natural selection drives intragenomic conflicts of interest between genes originating from different parents. Specifically, I establish mathematical links between the dynamics of natural selection and the idea of the gene as an intentional, inclusive-fitness-maximizing agent, and I clarify the role that information about parent of origin plays in mediating conflicts of interest between genes residing in the same genome. These results highlight that the suppression of divisive information may be as important as the suppression of lower levels of selection in maintaining the integrity of units of adaptation.     

Mitotic chromosome condensation requires Brn1p, the yeast homologue of Barren

In vitro studies suggest that the Barren protein may function as an activator of DNA topoisomerase II and/or as a component of the Xenopus condensin complex. To better understand the role of Barren in vivo, we generated conditional alleles of the structural gene for Barren (BRN1) in Saccharomyces cerevisiae. We show that Barren is an essential protein required for chromosome condensation in vivo and that it is likely to function as an intrinsic component of the yeast condensation machinery. Consistent with this view, we show that Barren performs an essential function during a period of the cell cycle when chromosome condensation is established and maintained. In contrast, Barren does not serve as an essential activator of DNA topoisomerase II in vivo. Finally, brn1 mutants display additional phenotypes such as stretched chromosomes, aberrant anaphase spindles, and the accumulation of cells with >2C DNA content, suggesting that Barren function influences multiple aspects of chromosome transmission and dynamics.     

Interpretations of retrograde amnesia: old problems redux

Recent evidence indicates that an old memory reactivated by cueing becomes labile and vulnerable to an amnesic treatment. Although the 'reconsolidation' concept derived from these findings challenges the traditional consolidation theory, here we argue that the new concept suffers from some of the same limitations as the earlier model. We propose an alternative retrieval-based theory that accommodates the recent data, as well as other puzzling related observations.     

Lottery Spending: A Non-Parametric Analysis

We analyze the spending of individuals in the United States on lottery tickets in an average month, as reported in surveys. We view these surveys as sampling from an unknown distribution, and we use non-parametric methods to compare properties of this distribution for various demographic groups, as well as claims that some properties of this distribution are constant across surveys. We find that the observed higher spending by Hispanic lottery players can be attributed to differences in education levels, and we dispute previous claims that the top 10% of lottery players consistently account for 50% of lottery sales.     

The art of arteriogenesis

The identification of collateral artery growth (arteriogenesis) as the only mechanism to compensate for the loss of an occluded artery forced us to define the mechanisms responsible for this type of vessel growth. To achieve this, a variety of coronary as well as peripheral models of arteriogenesis have been developed. Based on these studies it is obvious that arteriogenesis obeys different mechanisms than angiogenesis, the sprouting of capillaries. Upon occlusion of an artery, the blood flow is redirected into preexisting arteriolar anastomoses that experience increased mechanical forces such as shear stress and circum ferential wall stress. The endothelium of the arteriolar connections is then activated, resulting in an increased release of monocyte-attracting proteins as well as an upregulation of adhesion molecules. Upon adherence and extravasation, monocytes promote arteriogenesis by supplying growth factors and cytokines that bind to receptors that are expressed on vascular cells within a limited time frame. Animal studies evidenced that factors, such as monocyte chemoattractant protein-1, granulocyte-monocyte colony-stimulating factor, or transforming growth factor-β₁, that either attract or prolong the lifetime of monocytes efficiently enhance collateral artery growth, an effect that was seen only to a minor degree after application of a single growth factor. Bone marrow-derived stems cells and endothelial progenitor cells do not incorporate in growing arteries but, rather, function as supporting cells. Complete elucidation of the mechanisms of arteriogenesis may lead to efficacious therapies counteracting the devastating consequences of vascular occlusive diseases.     

Lessons from Cryptococcal Laccase: From Environmental Saprophyte to Pathogen

Cryptococcus is an opportunistic pathogen that lives in the environment as a free-living yeast and inflicts disease in humans, primarily in immunocompromised patients such as organ-transplant recipients and people with HIV/AIDS. A key factor allowing emergence of this fungal pathogen is a copper-containing laccase enzyme that facilitates nutrient foraging as a saprophyte and offers protection against environmental dangers such as free-living amoebae and mammalian macrophages during infection. The promiscuous substrate specificity of laccase facilitates the degradation of hard plant lignin polymers as well as the synthesis of lignin-like pigments from plant flavonoids and melanin pigments from dopamine. The enzyme also possesses an iron oxidase activity that prevents Fenton product formation in macrophages and another activity that allows synthesis of immune-modulatory prostaglandins that fool the host, shutting off an effective immune response. This review provides a brief overview of key points in laccase function and its role in virulence, as well as regulation and trafficking of the enzyme during the interconversion between saprophyte and pathogen, yielding insights into pathogenesis from this adaptable pathogen.     

Evolutionary stable sets in mixed-strategist models

Evolutionary stable sets are used as an extension of the concept of an evolutionarily stable strategy (ESS). They have, as sets, essentially the same properties as ordinary ESSs. Here, ES sets are applied to the characterization of what will happen in an asexual population of mixed-strategists under frequency-dependent selection. Such a population will tend to establish some state, usually not a unique one, that belongs to an ES set. For an important class of widely used mixed-strategist models, ES sets are found to comprise just those population states that allow the possible behavioural acts to be equally successful, or, to put it more precisely, that establish an evolutionarily stable population strategy.     

Phosphorylation of annexin A1 by TRPM7 kinase: a switch regulating the induction of an α-helix

TRPM7 is an unusual bifunctional protein consisting of an α-kinase domain fused to a TRP ion channel. Previously, we have identified annexin A1 as a substrate for TRPM7 kinase and found that TRPM7 phosphorylates annexin A1 at Ser5 within the N-terminal α-helix. Annexin A1 is a Ca(2+)-dependent membrane binding protein, which has been implicated in membrane trafficking and reorganization. The N-terminal tail of annexin A1 can interact with either membranes or S100A11 protein, and it adopts the conformation of an amphipathic α-helix upon these interactions. Moreover, the existing evidence indicates that the formation of an α-helix is essential for these interactions. Here we show that phosphorylation at Ser5 prevents the N-terminal peptide of annexin A1 from adopting an α-helical conformation in the presence of membrane-mimetic micelles as well as phospholipid vesicles. We also show that phosphorylation at Ser5 dramatically weakens the binding of the peptide to S100A11. Our data suggest that phosphorylation at Ser5 regulates the interaction of annexin A1 with membranes as well as S100A11 protein.     

RNA unwinding activity of SV40 large T antigen

Large T antigen, the regulatory protein encoded by simian virus 40, has DNA helicase activity and unwinds double-stranded DNA at the expense of ATP. T antigen also functions as an RNA helicase separating duplex regions in partially double-stranded RNA substrates. Surprisingly, T antigen RNA helicase activity requires UTP, CTP, or GTP as a cofactor, whereas ATP is an inefficient energy source for the RNA unwinding reaction. Accordingly, T antigen has both an intrinsic non-ATP NTPase activity that is stimulated by single-stranded RNA and an ATPase activity stimulated by single-stranded DNA. Thus, it appears that the bound nucleotide determines whether T antigen acts as an RNA helicase or as a DNA helicase.     

Identifying the ecological conditions that select for intermediate levels of aposematic signalling

Chemically defended species often have conspicuous signals that warn potential predators of these defences. Recent evidence suggests that some such aposematic prey are not as conspicuous as possible, even though increased conspicuousness would bring additional anti-predator benefits. Here we present a simple model to explore the generality of these observations. Our model predicts that optimal fitness will often be achieved at an intermediate level of conspicuousness and not simply by maximising conspicuousness. This comes about because of the ubiquitous trade-off that increased conspicuousness has an ecological cost in increasing the encounter rate with predators, as well as a benefit in terms of enhancing learned aversion by predators of defended prey. However, importantly, we also predict that a small deviation away from maximal crypsis generally causes a decrease in fitness, even if a larger deviation would lead to an intermediate level of conspicuousness that maximises fitness. Hence, further consideration of whether intermediate levels of aposematism are as common in nature as predicted in this model will require consideration of the underlying evolution of appearance, and the plausibility of evolution across the fitness trough, from maximal crypsis to an intermediate level of aposematism.     

Imagining 'reactivity': allergy within the history of immunology

An allergy is commonly understood to be an overreaction of the immune system to harmless substances that are misrecognised as foreign. This concept of allergy as an abnormal, misdirected immune response-a biological fault-stems from the idea that the immune system is an inherently defensive operation designed to protect the individual through an innate capacity to discriminate between the benign and toxic, or self and nonself. However, this definition of allergy represents a radical departure from its original formulation. Literally meaning 'altered reactivity', the term was coined in 1906 by Austrian paediatrician Clemens von Pirquet, to describe the fundamentally mutable nature of the immune response. This paper argues that the conventional interpretation of allergy-as-pathology derives from specific concepts of 'organism', 'response', and 'normal' immune function that have-for over a century-governed the perception and study of immune phenomena within immunology. Through an examination of Louis Pasteur's conceptualisation of the host body/microorganism relationship, I argue that immunology is founded on a view of the organism as a discrete, autonomous entity, and on a concomitant notion of the immune response as essentially reactive. Revisiting the concept of 'altered reactivity', this paper points to the fact that allergy was initially posited as a general theory of immune responsiveness and, importantly, one that poses a significant challenge to orthodox notions of immunopathology. It suggests that Pirquet's unique view of immune responsiveness presents an account of organismic or biological identity that encapsulates, rather than reduces, its ecological complexity.     

Beta-alanine but not taurine can function as an organic osmolyte in preimplantation mouse embryos cultured from fertilized eggs

Early preimplantation mouse embryos are susceptible to the detrimental effects of increased osmolarity and, paradoxically, their in vitro development is significantly compromised by osmolarities near that of oviductal fluid. In vitro development can be restored, however, by several compounds that are accumulated by 1-cell embryos to act as organic osmolytes, providing intracellular osmotic support and cell volume regulation. Taurine, a substrate of the beta-amino acid transporter that functions as an organic osmolyte transporter in other cells, had been proposed to function as an organic osmolyte in mouse embryos. Here, however, we found that taurine is neither able to provide protection for in vitro embryo development against increased osmolarity nor is it accumulated to higher intracellular levels as osmolarity is increased, indicating that it cannot function as an organic osmolyte in early preimplantation embryos. In contrast, beta-alanine, the other major substrate of the beta-amino acid transporter, both protects against increased osmolarity and is accumulated to somewhat higher levels as osmolarity is increased, indicating that it is able to function as an organic osmolyte in embryos. However, we also found that beta-alanine is displaced from embryos by glycine-the most effective organic osmolyte in embryos previously identified-and beta-alanine does not increase protection above that afforded by glycine at concentrations near those in vivo. Thus, the beta-amino acid transporter is likely present in early preimplantation embryos to supply beta-amino acids such as taurine for purposes other than to serve as organic osmolytes.