Is there a role for CEA in innate immunity in the colon?

Carcinoembryonic antigen (CEA) is a well known tumor marker associated with the progression of colorectal tumors. The CEA family of glycoproteins has been fully characterized and the function of some of its members is now beginning to be understood. Here, we advance the hypothesis that, rather than functioning in cell adhesion as has been suggested previously, CEA plays a role in protecting the colonic mucosa from microbial invasion. This hypothesis is based on new microscopic, molecular, phylogenetic and microbiological evidence.     

Is there a common chemical model for life in the universe?

A review of organic chemistry suggests that life, a chemical system capable of Darwinian evolution, may exist in a wide range of environments. These include non-aqueous solvent systems at low temperatures, or even supercritical dihydrogen-helium mixtures. The only absolute requirements may be a thermodynamic disequilibrium and temperatures consistent with chemical bonding. A solvent system, availability of elements such as carbon, hydrogen, oxygen and nitrogen, certain thermodynamic features of metabolic pathways, and the opportunity for isolation, may also define habitable environments. If we constrain life to water, more specific criteria can be proposed, including soluble metabolites, genetic materials with repeating charges, and a well defined temperature range.     

Is there a role for amplifiers in sexual selection?

The amplifier hypothesis states that selection could favour the evolution of traits in signallers that improve the ability of receivers to extract honest information from other signals or cues. We provide a formal definition of amplifiers based on the receiver's mechanisms of signal perception and we present a game-theoretical model in which males advertise their quality and females use sequential-sampling tactics to choose among prospective mates. The main effect of an amplifier on the female mating strategy is to increase her mating threshold, making the female more selective as the effectiveness of the amplifier increases. The effects of the amplifier on male advertising strategy depends both on the context and on the types of the amplifier involved. We consider two different contexts for the evolution of amplifiers (when the effect of amplifiers is on signals and when it is on cues) and two types of amplifiers (the ‘neutral amplifier’, when it improves quality assessment without altering male attractiveness, and the ‘attractive amplifier’, when it improves both quality assessment and male attractiveness). The game-theoretical model provides two main results. First, neutral and attractive amplifiers represent, respectively, a conditional and an unconditional signalling strategy. In fact, at the equilibrium, neutral amplifiers are displayed only by males whose advertising level lays above the female acceptance threshold, whereas attractive amplifiers are displayed by all signalling males, independent of their quality. Second, amplifiers of signals increase the differences in advertising levels between amplifying and not-amplifying males, but they decrease the differences within each group, so that the system converges towards an ‘all-or-nothing’ signalling strategy. By applying concepts from information theory, we show that the increase in information transfer at the perception level due to the amplifier of signals is contrasted by a decrease in information transfer at the emitter level due to the increased stereotypy of male advertising strategy.     

Is there a role for auxin in early embryogenesis?

The very young embryo of a flowering plant is not an idealsystem in which to study the effects of auxin. Conversely, auxin isusually not considered as a major component of developmental processesin early embryogenesis. However, recent findings from both experimentalstudies in Brassica and analyses of developmental mutants inArabidopsis make it worthwhile to examine critically thepossibility that auxin may have a role in early embryogenesis. In thisreview, we will focus on specific processes, such as formation of anapical-basal axis of polarity and the initiation of the primary rootmeristem. To provide a conceptual framework in which to discuss possibleeffects of auxin, we will first briefly summarise essential features ofearly embryogenesis in Arabidopsis. This will be followed by anevaluation of relevant data suggesting a role for auxin in axisformation and root meristem initiation. Finally, we will discuss a fewexperimental approaches that we believe are necessary to examine whetheror not auxin plays a role in fundamental processes of earlyembryogenesis.     

Is there a role for actin in virus budding?

Electrophoretic data from both sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE) and acid-urea gels reveal a protein in purified murine mammary tumor virus (MuMTV) which co-migrates with purified chick skeletal muscle actin. 125I-labeling of intact and disrupted virus preparations shows that the actin-like protein is not artifactually adsorbed to the outside of virions during isolation. Quantitative SDS- PAGE and examination of negatively stained preparations show that the actin cannot be accounted for by a contaminating population of virus- free vesicles. The ultrastructure of mammary epithelial cells and of Rous sarcoma virus-transformed chick embryo fibroblasts shows that virus extrusion is associated with filament-containing cellular processes. In particular, MuMTV is released from the ends of long microvilli which contain a bundle of 6-8-nm microfilaments and share other structural features with intestinal microvilli. We suggest that virus nucleoids require an interaction with host cell contractile proteins for their extrusion from the cell.     

Is there a role for copper in neurodegenerative diseases?

Copper is an essential metal in living organisms; thus, the maintenance of adequate copper levels is of vital importance and is highly regulated. Dysfunction of copper metabolism leading to its excess or deficiency results in severe ailments. Two examples of illnesses related to alterations in copper metabolism are Menkes and Wilson diseases. Several proteins are involved in the maintenance of copper homeostasis, including copper transporters and metal chaperones. In the last several years, the beta-amyloid-precursor protein (beta-APP) and the prion protein (PrP(C)), which are related to the neurodegenerative disorders Alzheimer and prion diseases respectively, have been associated with copper metabolism. Both proteins bind copper through copper-binding domains that also have been shown to reduce copper in vitro. Moreover, this ability to reduce copper is associated with a neuroprotective effect exerted by the copper-binding domain of both proteins against copper in vivo. In addition to a functional link between copper and beta-APP or PrP(C), evidence suggests that copper has a role in Alzheimer and prion diseases. Here, we review the evidence that supports both, the role of beta-APP and PrP(C), in copper metabolism and the putative role of copper in neurodegenerative diseases.     

Is there a dietary requirement for DHA in pregnancy?

The metabolic demand for docosahexaenoic acid (22:6 n-3, DHA) is increased during pregnancy because of the extra needs of the fetus, expanded maternal cell mass and placenta. In Western countries maternal dietary DHA intake in pregnancy is low and it is not clear whether adaptive metabolic mechanisms, such as increased DHA synthesis from precursor fatty acids, are capable of meeting the increased DHA need in pregnancy. Consequently randomized controlled trials are important to determine whether additional dietary DHA in pregnancy modifies maternal or infant health outcomes. The available randomized comparisons of DHA supplements vs placebo have assessed outcomes as diverse as maternal depression, infant visual acuity and development, and infant growth and allergy. The outcomes of these trials have not been conclusive because they have often been limited by small sample size. On the other hand, large-scale trials assessing marine oil supplementation with large doses indicate that DHA supplementation in pregnancy is safe.     

Is there a future for GMOs?

Despite strict regulation and a clean safety record, research and development of genetically modified (GM) crops and other organisms has been confronted with tremendous public hostility. Why has this happened, and how can scientists try to guide the debate into more rational channels? The answers may determine the future of GM technology and our ability to provide for a growing world population.     

Is there a pilot in a pseudopod?

The concept of pilot pseudopodia is reconsidered 30 years after its inauguration (Gerisch, G., Hülser, D., Malchow, D., Wick, U., 1975. Cell communication by periodic cyclic-AMP pulses. Phil. Trans. R. Soc. Lond. B 272, 181-192). The original hypothesis stated that protruding pseudopodia serve as dynamic sensory organelles that aid a cell in perceiving variations of chemoattractant concentration and, consequently, in navigation during chemotaxis. This influential idea is reevaluated in the light of recent findings about the mechanisms governing chemotactic cell motility, morphology and dynamics of pseudopodia, and about molecular constituents and regulators of pseudopod extension and retraction. It is proposed that stimulation by a chemoattractant modulates speed of pseudopod protrusion and thereby increases cell elongation. Elongation further enhances chemotactic sensitivity of the cell to shallow chemoattractant gradients, reinforces cell polarization, and finally leads to suppression of lateral pseudopodia and continuation of cell migration in the gradient direction.     

Is there a place for nuclear medicine in the radioembolization of liver tumors?

This is purposely an ultraprovocative title for the broad nuclear medicine community (including radiophysics and radiopharmacy) which leads us to ask questions about how we should correctly use ⁹⁰Yttrium (MSY90) microspheres in the treatment of liver tumors.     

Is there a role for antibody testing in the diagnosis of invasive candidiasis?

During the last decades, the use of antibody tests for the diagnosis of invasive mycoses has declined as a consequence of the general belief that they are insensitive and non-specific. However, there is a clear evidence that antibodies can be detected in highly immunodeficient patients (such as bone marrow transplant recipients), and that those antibodies are useful for the diagnosis. Antibody tests are currently in use as diagnostic tools for some primary mycoses, such as the endemic mycoses, aspergilloma, allergic bronchopulmonary aspergilosis and sporothrichosis. For invasive candidiasis, diagnostic methods must differentiate Candida colonization of mucous membranes or superficial infection from tissue invasion by this microorganism. Substantial progress has been made in diagnosis of invasive candidiasis with the development of a variety of methods for the detection of antibodies and antigens. However, no single test has found widespread clinical use and there is a consensus that diagnosis based on a single specimen lacks sensitivity. It is necessary to test sequential samples taken while the patient is at greatest risk for developing invasive candidiasis to optimize the diagnosis. Results obtained from a panel of diagnostic tests in association with clinical aspects will likely be the most useful strategy for early diagnosis and therapy.     

Is there a role for GPIs in yeast cell-wall assembly?

Glycosylphosphatidylinositol (GPI) membrane anchors are essential for the integration of yeast cell adhesion proteins into the cell wall, but mature cell-wall proteins are unlikely to be attached directly to the membrane. We thus propose that GPI-anchored glycoprotein forms are intermediates in a process that crosslinks the major components of the cell wall by transglycosylation. This mechanism may be critical for both the biosynthesis and overall architecture of the cell wall.     

Is there a role for eIF5A in translation?

Summary. The putative translation factor eIF5A is essential for cell viability and is highly conserved from archaebacteria to mammals. This factor is the only cellular protein that undergoes an essential posttranslational modification dependent on the polyamine spermidine, called hypusination. This review focuses on the functional characterization of eIF5A. Although this protein was originally identified as a translation initiation factor, subsequent studies did not support a role for eIF5A in general translation initiation. eIF5A has also been implicated in nuclear export of HIV-1 Rev and mRNA decay, but these findings are controversial in the literature and may reflect secondary effects of eIF-5A function. Next, the involvement of eIF5A and hypusination in the control of the cell cycle and proliferation in various organisms is reviewed. Finally, recent evidence in favor of reconsidering the role of eIF5A as a translation factor is discussed. Future studies may reveal the specific mechanism by which eIF5A affects protein synthesis.     

Is there a role for glucocorticoid receptor beta in asthma?

Glucocorticoids (GCs) are routinely used as anti-inflammatory drugs in the treatment of asthma. They act through binding to glucocorticoid receptor α (GRα), which represses numerous genes encoding pro-inflammatory mediators. A hormone binding deficient GR isoform named GRβ has been isolated in humans. When overexpressed by transfection, GRβ may function as a dominant negative modulator of GRα. However, to act as such, GRβ has to be more abundant than GRα, and conflicting data have been obtained concerning the relative levels of the two isoforms in cell lines and freshly isolated cells. Moreover, the dominant negative effect was not confirmed by independent laboratories. In GC-resistant asthmatics, GRβ was expressed by an increased number of peripheral blood mononuclear cells (PBMCs), airway T cells, and cells found in skin biopsies of tuberculin responses. However, the relative amounts of GRα and GRβ in these cells were not determined. In GC-dependent asthmatics, PBMCs expressed GRα predominantly. No cells containing higher levels of GRβ than GRα have yet been reported in asthmatics. Even if the existence of such cells is demonstrated, the role of GRβ in asthma will remain a matter of controversy because functional studies have given discrepant data.     

Is there a role for culture in human behavioral ecology?

Most research in human behavioral ecology has been acultural, which raises the question of how best to incorporate the concept of culture into this approach. A necessary step in this direction is to pare the culture concept down to its ideational elements, excluding behavior and its material products (Durham 1991; Geertz 1973; Keesing 1974). The cultural and reproductive success hypothesis, though empirically successful (Irons 1993), is not a model for all of culture because of widespread discrepancies between behavior and culture to which it does not call attention. Cultural transmission models are also weakened by such discrepancies, but, more importantly, such models are most relevant to phenomena different from those central to human behavioral ecology. A better way to incorporate culture into human behavioral ecology is to see it as the context of human action and as a tool people use in social manipulation. The study of signal systems is a key to an understanding of social manipulation and to the incorporation of culture into human behavioral ecology. Examples of the manipulation of culture for reproductive benefit include Yanomamö kin term manipulation (Chagnon 1988), incest rules (Thornhill 1990, 1991), and the derogation of sexual competitors (Buss and Dedden 1990). The human behavioral ecological study of social manipulation in cultural contexts needs to be expanded. Two phenomena that might shed light on such manipulation are the Rashomon effect and the audience effect.