Signaling of need, sibling competition, and the cost of honesty

Young birds and mammals frequently solicit food by means of extravagant and apparently costly begging displays. Much attention has been devoted to the idea that these displays are honest signals of need, and that their apparent cost serves to maintain their honesty. Recent analyses, however, have shown that the cost needed to maintain a fully informative, honest signal may often be so great that both offspring (signaler) and parent (receiver) would do better to refrain from communication. This apparently calls into question the relevance of the costly signaling hypothesis. Here, I show that this argument overlooks the impact of sibling competition. When multiple signalers must compete for the attention of a receiver (as is commonly the case in parent–offspring interactions), I show that (all other things being equal) individual equilibrium signal costs will typically be lower. The greater the number of competitors, the smaller the mean cost, though the maximum level of signal intensity employed by very needy signalers may actually increase with the number of competitors. At the same time, costs become increasingly sensitive to relatedness among signalers as opposed to relatedness between signalers and receivers. As a result of these trends, signaling proves profitable for signalers under a much wider range of conditions when there is competition (though it is still likely to be unprofitable for receivers).

The efficiency of propulsion by a rotating flagellum

[At very low Reynolds number, the regime in which fluid dynamics is governed by Stokes equations, a helix that translates along its axis under an external force but without an external torque will necessarily rotate. By the linearity of the Stokes equations, the same helix that is caused to rotate due to an external torque will necessarily translate. This is the physics that underlies the mechanism of flagellar propulsion employed by many microorganisms. Here, I examine the linear relationships between forces and torques and translational and angular velocities of helical objects to understand the nature of flagellar propulsion.]

Conserved circadian elements in phylogenetically diverse algae

Circadian expression of the luciferin-binding protein (LBP) from the dinoflagellate Gonyaulax polyedra is regulated at the translational level. A small interval in the lbp 3′-untranslated region, which contains seven UG-repeats, serves as a cis-acting element to which a trans-acting factor (CCTR) binds in a circadian manner. Its binding activity correlates negatively with the circadian expression of LBP. Here I report the identification of a protein in the green alga Chlamydomonas reinhardtii that represents a CCTR analog. It binds both specifically and under control of the circadian clock to the UG-repeat region. The data show for the first time that circadian cis-elements implicated in translational regulation have been conserved during evolution.

The shape of female mating preferences

The “shape” of a female mating preference is the relationship between a male trait and the probability of acceptance as a mating partner. The shape of preferences is important in many models of sexual selection, mate recognition, communication, and speciation, yet it has rarely been measured precisely. Here I examine preference shape for male calling song in a bushcricket (katydid). Preferences change dramatically between races of a species, from strongly directional to broadly stabilizing (but with a net directional effect). Preference shape generally matches the distribution of the male trait. This is compatible with a coevolutionary model of signal-preference evolution, although it does not rule out an alternative model, sensory exploitation. Preference shapes are shown to be genetic in origin.

Rhesus monkeys know when they remember

Humans are consciously aware of some memories and can make verbal reports about these memories. Other memories cannot be brought to consciousness, even though they influence behavior. This conspicuous difference in access to memories is central in taxonomies of human memory systems but has been difficult to document in animal studies, suggesting that some forms of memory may be unique to humans. Here I show that rhesus macaque monkeys can report the presence or absence of memory. Although it is probably impossible to document subjective, conscious properties of memory in nonverbal animals, this result objectively demonstrates an important functional parallel with human conscious memory. Animals able to discern the presence and absence of memory should improve accuracy if allowed to decline memory tests when they have forgotten, and should decline tests most frequently when memory is attenuated experimentally. One of two monkeys examined unequivocally met these criteria under all test conditions, whereas the second monkey met them in all but one case. Probe tests were used to rule out “cueing” by a wide variety of environmental and behavioral stimuli, leaving detection of the absence of memory per se as the most likely mechanism underlying the monkeys' abilities to selectively decline memory tests when they had forgotten.

Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions

The evolution of novelty in tightly integrated biological systems, such as hormones and their receptors, seems to challenge the theory of natural selection: it has not been clear how a new function for any one part (such as a ligand) can be selected for unless the other members of the system (e.g., a receptor) are already present. Here I show—based on identification and phylogenetic analysis of steroid receptors in basal vertebrates and reconstruction of the sequences and functional attributes of ancestral proteins—that the first steroid receptor was an estrogen receptor, followed by a progesterone receptor. Genome mapping and phylogenetic analyses indicate that the full complement of mammalian steroid receptors evolved from these ancient receptors by two large-scale genome expansions, one before the advent of jawed vertebrates and one after. Specific regulation of physiological processes by androgens and corticoids are relatively recent innovations that emerged after these duplications. These findings support a model of ligand exploitation in which the terminal ligand in a biosynthetic pathway is the first for which a receptor evolves; selection for this hormone also selects for the synthesis of intermediates despite the absence of receptors, and duplicated receptors then evolve affinity for these substances. In this way, novel hormone-receptor pairs are created, and an integrated system of increasing complexity elaborated. This model suggests that ligands for some “orphan” receptors may be found among intermediates in the synthesis of ligands for phylogenetically related receptors.

Regional and cellular fractionation of working memory

This chapter recounts efforts to dissect the cellular and circuit basis of a memory system in the primate cortex with the goal of extending the insights gained from the study of normal brain organization in animal models to an understanding of human cognition and related memory disorders. Primates and humans have developed an extraordinary capacity to process information “on line,” a capacity that is widely considered to underlay comprehension, thinking, and so-called executive functions. Understanding the interactions between the major cellular constituents of cortical circuits—pyramidal and nonpyramidal cells—is considered a necessary step in unraveling the cellular mechanisms subserving working memory mechanisms and, ultimately, cognitive processes. Evidence from a variety of sources is accumulating to indicate that dopamine has a major role in regulating the excitability of the cortical circuitry upon which the working memory function of prefrontal cortex depends. Here, I describe several direct and indirect intercellular mechanisms for modulating working memory function in prefrontal cortex based on the localization of dopamine receptors on the distal dendrites and spines of pyramidal cells and on interneurons in the prefrontal cortex. Interactions between monoamines and a compromised cortical circuitry may hold the key to understanding the variety of memory disorders associated with aging and disease.

Galaxies and large scale structure at high redshifts

It is now straightforward to assemble large samples of very high redshift (z ∼ 3) field galaxies selected by their pronounced spectral discontinuity at the rest frame Lyman limit of hydrogen (at 912 Å). This makes possible both statistical analyses of the properties of the galaxies and the first direct glimpse of the progression of the growth of their large-scale distribution at such an early epoch. Here I present a summary of the progress made in these areas to date and some preliminary results of and future plans for a targeted redshift survey at z = 2.7–3.4. Also discussed is how the same discovery method may be used to obtain a “census” of star formation in the high redshift Universe, and the current implications for the history of galaxy formation as a function of cosmic epoch.

Hypothesis testing and earthquake prediction.

Requirements for testing include advance specification of the conditional rate density (probability per unit time, area, and magnitude) or, alternatively, probabilities for specified intervals of time, space, and magnitude. Here I consider testing fully specified hypotheses, with no parameter adjustments or arbitrary decisions allowed during the test period. Because it may take decades to validate prediction methods, it is worthwhile to formulate testable hypotheses carefully in advance. Earthquake prediction generally implies that the probability will be temporarily higher than normal. Such a statement requires knowledge of "normal behavior"--that is, it requires a null hypothesis. Hypotheses can be tested in three ways: (i) by comparing the number of actual earth-quakes to the number predicted, (ii) by comparing the likelihood score of actual earthquakes to the predicted distribution, and (iii) by comparing the likelihood ratio to that of a null hypothesis. The first two tests are purely self-consistency tests, while the third is a direct comparison of two hypotheses. Predictions made without a statement of probability are very difficult to test, and any test must be based on the ratio of earthquakes in and out of the forecast regions.

Interface between culturally based preferences and genetic preferences: female mate choice in Poecilia reticulata.

The relative contribution of genetic and socio-cultural factors in the shaping of behavior is of fundamental importance to biologists and social scientists, yet it has proven to be extremely difficult to study in a controlled, experimental fashion. Here I describe experiments that examined the strength of genetic and cultural (imitative) factors in determining female mate choice in the guppy, Poecilia reticulata. Female guppies from the Paria River in Trinidad have a genetic, heritable preference for the amount of orange body color possessed by males. Female guppies will, however, also copy (imitate) the mate choice of other females in that when two males are matched for orange color, an "observer" female will copy the mate choice of another ("model") female. Three treatments were undertaken in which males differed by an average of 12%, 24%, or 40% of the total orange body color. In all cases, observer females viewed a model female prefer the less colorful male. When males differed by 12% or 24%, observer females preferred the less colorful male and thus copied the mate choice of others, despite a strong heritable preference for orange body color in males. When males differed by 40% orange body color, however, observer females preferred the more colorful male and did not copy the mate choice of the other female. In this system, then, imitation can "override" genetic preferences when the difference between orange body color in males is small or moderate, but genetic factors block out imitation effects when the difference in orange body color in males is large. This experiment provides the first attempt to experimentally examine the relative strength of cultural and genetic preferences for a particular trait and suggests that these two factors moderate one another in shaping social behavior.

Adaptive mutations in Escherichia coli as a model for the multiple mutational origins of tumors.

The cells in most tumors are found to carry multiple mutations; however, based upon mutation rates determined by fluctuation tests, the frequency of such multiple mutations should be so low that tumors are never detected within human populations. Fluctuation tests, which determine the cell-division-dependent mutation rate per cell generation in growing cells, may not be appropriate for estimating mutation rates in nondividing or very slowly dividing cells. Recent studies of time-dependent, "adaptive" mutations in nondividing populations of microorganisms suggest that similar measurements may be more appropriate to understanding the mutation origins of tumors. Here I use the ebgR and ebgA genes of Escherichia coli to measure adaptive mutation rates where multiple mutations are required for rapid growth. Mutations in either ebgA or ebgR allow very slow growth on lactulose (4-O-beta-D-galactosyl-D-fructose), with doubling times of 3.2 and 17.3 days, respectively. However, when both mutations are present, cells can grow rapidly with doubling times of 2.7 hr. I show that during prolonged (28-day) selection for growth on lactulose, the number of lactulose-utilizing mutants that accumulate is 40,000 times greater than can be accounted for on the basis of mutation rates measured by fluctuation tests, but is entirely consistent with the time-dependent adaptive mutation rates measured under the same conditions of prolonged selection.

HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy

The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease pathogenesis. HTLV-I-associated myelopathy (HAM/TSP) patients have a high virus load compared with asymptomatic HTLV-I carriers. We hypothesized that HLA alleles control HTLV-I provirus load and thus influence susceptibility to HAM/TSP. Here we show that, after infection with HTLV-I, the class I allele HLA-A*02 halves the odds of HAM/TSP (P < 0.0001), preventing 28% of potential cases of HAM/TSP. Furthermore, HLA-A*02+ healthy HTLV-I carriers have a proviral load one-third that (P = 0.014) of HLA-A*02− HTLV-I carriers. An association of HLA-DRB1*0101 with disease susceptibility also was identified, which doubled the odds of HAM/TSP in the absence of the protective effect of HLA-A*02. These data have implications for other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response can reduce virus load and so prevent disease in persistent virus infections.

Ubiquitin-dependent degradation of IκBα is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1

Activation of the transcription factor nuclear factor kappa B (NF-κB) is controlled by proteolysis of its inhibitory subunit (IκB) via the ubiquitin-proteasome pathway. Signal-induced phosphorylation of IκBα by a large multisubunit complex containing IκB kinases is a prerequisite for ubiquitination. Here, we show that FWD1 (a mouse homologue of Slimb/βTrCP), a member of the F-box/WD40-repeat proteins, is associated specifically with IκBα only when IκBα is phosphorylated. The introduction of FWD1 into cells significantly promotes ubiquitination and degradation of IκBα in concert with IκB kinases, resulting in nuclear translocation of NF-κB. In addition, FWD1 strikingly evoked the ubiquitination of IκBα in the in vitro system. In contrast, a dominant-negative form of FWD1 inhibits the ubiquitination, leading to stabilization of IκBα. These results suggest that the substrate-specific degradation of IκBα is mediated by a Skp1/Cull 1/F-box protein (SCF) FWD1 ubiquitin-ligase complex and that FWD1 serves as an intracellular receptor for phosphorylated IκBα. Skp1/Cullin/F-box protein FWD1 might play a critical role in transcriptional regulation of NF-κB through control of IκB protein stability.

Direct evidence for a predominantly exolytic processive mechanism for depolymerization of heparin-like glycosaminoglycans by heparinase I

Heparinase I from Flavobacterium heparinum has important uses for elucidating the complex sequence heterogeneity of heparin-like glycosaminoglycans (HLGAGs). Understanding the biological function of HLGAGs has been impaired by the limited methods for analysis of pure or mixed oligosaccharide fragments. Here, we use methodologies involving MS and capillary electrophoresis to investigate the sequence of events during heparinase I depolymerization of HLGAGs. In an initial step, heparinase I preferentially cleaves exolytically at the nonreducing terminal linkage of the HLGAG chain, although it also cleaves internal linkages at a detectable rate. In a second step, heparinase I has a strong preference for cleaving the same substrate molecule processively, i.e., to cleave the next site toward the reducing end of the HLGAG chain. Computer simulation showed that the experimental results presented here from analysis of oligosaccharide degradation were consistent with literature data for degradation of polymeric HLGAG by heparinase I. This study presents direct evidence for a predominantly exolytic and processive mechanism of depolymerization of HLGAG by heparinase I.

Defining the domains of type I collagen involved in heparin- binding and endothelial tube formation

Cell surface heparan sulfate proteoglycan (HSPG) interactions with type I collagen may be a ubiquitous cell adhesion mechanism. However, the HSPG binding sites on type I collagen are unknown. Previously we mapped heparin binding to the vicinity of the type I collagen N terminus by electron microscopy. The present study has identified type I collagen sequences used for heparin binding and endothelial cell–collagen interactions. Using affinity coelectrophoresis, we found heparin to bind as follows: to type I collagen with high affinity (Kd ≈ 150 nM); triple-helical peptides (THPs) including the basic N-terminal sequence α1(I)87–92, KGHRGF, with intermediate affinities (Kd ≈ 2 μM); and THPs including other collagenous sequences, or single-stranded sequences, negligibly (Kd ≫ 10 μM). Thus, heparin–type I collagen binding likely relies on an N-terminal basic triple-helical domain represented once within each monomer, and at multiple sites within fibrils. We next defined the features of type I collagen necessary for angiogenesis in a system in which type I collagen and heparin rapidly induce endothelial tube formation in vitro. When peptides, denatured or monomeric type I collagen, or type V collagen was substituted for type I collagen, no tubes formed. However, when peptides and type I collagen were tested together, only the most heparin-avid THPs inhibited tube formation, likely by influencing cell interactions with collagen–heparin complexes. Thus, induction of endothelial tube morphogenesis by type I collagen may depend upon its triple-helical and fibrillar conformations and on the N-terminal heparin-binding site identified here.