The effects of external K+ and Na+ on the chemotaxis of rabbit peritoneal neutrophils.

Extracellular K+ enhances the chemotactic responsiveness and spontaneous movememt of rabbit peritoneal neutrophils but is not required for these functions. Other monovalent cations act the same; the rank order of their effectiveness is K+ = NH4 greater than Rb+ Cs+ greater than Li = Na. The K+ specific ionophore, valinomycin (10-7 M) inhances chemotaxis in the presence of K+ but not in its absence; another K+ specific ionophore, nigericin (10-7 M) inhibits chemotaxis in the absence of K+ but not in its presence. Ouabain (5 x 10-6 M) prevents the enhancing effects of K+ on chemotaxis. Removing the Na+ of the buffer and substituting it with K+, choline or glucose greatly enhances spontaneous motility but depresses chemotactic activity. One hypothesis suggested by the above results is that as a part of their action, chemotactic factors stimulate a net influx of K+ into the neutrophil; an alternative or additional hypothesis is that chemotactic factors stimulate a net efflux of Na+ from the neutrophil.     

Use it or lose it: reproductive implications of ecological specialization in a haematophagous ectoparasite

Using experimentally induced disruptive selection, we tested two hypotheses regarding the evolution of specialization in parasites. The 'trade-off' hypothesis suggests that adaptation to a specific host may come at the expense of a reduced performance when exploiting another host. The alternative 'relaxed selection' hypothesis suggests that the ability to exploit a given host would deteriorate when becoming obsolete. Three replicate populations of a flea Xenopsylla ramesis were maintained on each of two rodent hosts, Meriones crassus and Dipodillus dasyurus, for nine generations. Fleas maintained on a specific host species for a few generations substantially decreased their reproductive performance when transferred to an alternative host species, whereas they generally did not increase their performance on their maintenance host. The results support the 'relaxed selection' hypothesis of the evolution of ecological specialization in haematophagous ectoparasites, while suggesting that trade-offs are unlikely drivers of specialization. Further work is needed to study the extent by which the observed specializations are based on epigenetic or genetic modifications.     

Simulation of the fertilization Ca2+ wave in Xenopus laevis eggs.

In the preceding paper Fontanilla and Nuccitelli (Biophysical Journal 75:2079-2087 (1998)) present detailed measurements of the shape and speed of the fertilization Ca2+ wave in Xenopus laevis eggs. In order to help interpret their results, we develop here a computational technique based on the finite element method that allows us to carry out realistic simulations of the fertilization wave. Our simulations support the hypothesis that the physiological state of the mature egg is bistable, i.e., that its cytoplasm can accommodate two alternative physiological Ca2+ concentrations: a low concentration characteristic of the prefertilization state and a greatly elevated concentration characteristic of the state following the passage of the wave. We explore this hypothesis by assuming that the bistability is due to the release and re-uptake properties of the endoplasmic reticulum (ER) as determined by inositol trisphosphate (IP3) receptor/Ca2+ channels and sarcoendoplasmic reticulum calcium ATPase (SERCA) pumps. When combined with buffered diffusion of Ca2+ in the cytoplasm, our simulations show that inhomogeneities in the Ca2+ release properties near the plasma membrane are required to explain the temporal and spatial dependences of the shape and speed of these waves. Our results are consistent with an elevated IP3 concentration near the plasma membrane in the unfertilized egg that is augmented significantly near the site of fertilization. These gradients are essential in determining the concave shape of the Ca2+ fertilization wave front.     

A comment on testing for a decline in upper Cretaceous dinosaur diversity

A common problem in ecology is to determine whether the diversity of a biological community has changed over time or in response to a disturbance. This involves testing the null hypothesis that diversity is constant against the alternative hypothesis that it has changed. As the power of this test may be low, Fritsch and Hsu (1999, Biometrics 55, 1300-1305) proposed reversing the null and alternative hypothesis. Here, I return to the original formulation and point out that power can be improved by adopting a parametric model for relative abundances and by testing against an ordered alternative.     

Flooded forests: Death by drowning,not herbivory

Abstract. Trees on small islands formed when a new hydroelectric dam was filled are said to have been killed by leaf‐cutter ants that were no longer regulated by their armadillo predators. This top‐down hypothesis is questioned and an alternative bottom‐up hypothesis is proposed: the trees died because their roots were flooded.     

The role of larval aggression and mobility in the transition between solitary and gregarious development in parasitoid wasps

Models explaining the appearance of gregariousness in insect parasitoids assume the presence of a tolerance gene that enables nonsiblicidal behaviour in gregarious larvae. Under this assumption, nontolerant individuals should attack and kill tolerant individuals when sharing a host, making this behaviour susceptible to invasion by nontolerant individuals. We propose an alternative hypothesis where gregarious larvae retain their aggressiveness but are less mobile. We tested this hypothesis with two sympatric and congeneric species of Mymaridae, Anaphes victus and Anaphes listronoti , respectively, solitary and gregarious egg parasitoids of a Curculionidae, Listronotus oregonensis . Results obtained in competition experiments and from direct observation of movement in mymariform larvae of both species support the reduced mobility hypothesis. By being immobile while retaining their fighting capacity, A. listronoti mymariform larvae appear to optimize host utilization through gregarious development, but can still defend themselves against sympatric aggressive species.     

Ethnicity and fertility in Liberia: a test of the minority group status hypothesis

This study examines the relationship between ethnicity and fertility in Liberia, within the context of the minority group status hypothesis. The hypothesis argues that minority group status exerts an independent effect on fertility, net of controls for socioeconomic and demographic variables. Using a subsample of women from the 1974 Liberian census, the study examines interethnic variations in fertility by comparing five ethnic minorities--Bassa, Vai, Grebo, Kru, Kpelle--with the majority group, Americo-Liberian. With the possible exception of Bassa women, the findings do not support the minority group status hypothesis. Instead, the findings are more congruent with the alternative assimilationist hypothesis which argues that when sociodemographic differences between majority and minority groups are controlled, their fertility levels should converge. The implications of these findings are explored.     

Polyterritorialitytion in passerine birds

In some birds, males defend two spatially separated territories and attract females to each one in turn. it has been proposed that this behaviour, referred to as polyterritoriality, allows males to conceal their marital status, thereby deceiving females into accepting polygyny against their best interests. The deception hypothesis has gained general acceptance as an explanation for polyterritoriality in birds, but until recently the empirical basis for the hypothesis rested almost entirely on studies of Swedish populations of the pied flycatcher (Ficedula hypoleuca). New findings, emerging from further studies of the pied flycatcher and of other species, suggest several alternative selection pressures that may have favoured polyterritoriality.     

A database for the analysis of immunity genes in Drosophila

While microarray experiments generate voluminous data, discerning trends that support an existing or alternative paradigm is challenging. To synergize hypothesis building and testing, we designed the Pathogen Associated Drosophila MicroArray (PADMA) database for easy retrieval and comparison of microarray results from immunity-related experiments (www.padmadatabase.org). PADMA also allows biologists to upload their microarray-results and compare it with datasets housed within PADMA. We tested PADMA using a preliminary dataset from Ganaspis xanthopoda-infected fly larvae, and uncovered unexpected trends in gene expression, reshaping our hypothesis. Thus, the PADMA database will be a useful resource to fly researchers to evaluate, revise, and refine hypotheses.     

The problem of a covariate-time qualitative interaction in a survival study

We introduce a test for the equality of two survival distributions against the specific alternative of crossing hazards. Although this kind of alternative is somewhat rare, designing a test specifically aimed at detecting such departures from the null hypothesis in this direction leads to powerful procedures, upon which we can call in those few cases where such departures are suspected. Furthermore, the proposed test and an approximate version of the test are seen to suffer only moderate losses in power, when compared with their optimal counterparts, should the alternative be one of proportional hazards. Our interest in the problem is motivated by clinical studies on the role of acute graft versus host disease as a risk factor in leukemic children and we discuss the analysis of this study in detail. The model we use in this work is a special case of the one introduced by Anderson and Senthilselvan (1982. Applied Statistics 31, 44-51). We propose overcoming an inferential problem stemming from their model by using the methods of Davies (1977, Biometrika 64, 247-254; 1987, Biometrika 74, 33-43) backed up by resampling techniques. We also look at an approach relying directly on resampling techniques. The distributional aspects of this approach under the null hypothesis are interesting but, practically, its behaviour is such that its use cannot be generally recommended. Outlines of the necessary asymptotic theory are presented and for this we use the tools of martingale theory.     

Empirical Bayes interval estimates that are conditionally equal to unadjusted confidence intervals or to default prior credibility intervals

Problems involving thousands of null hypotheses have been addressed by estimating the local false discovery rate (LFDR). A previous LFDR approach to reporting point and interval estimates of an effect-size parameter uses an estimate of the prior distribution of the parameter conditional on the alternative hypothesis. That estimated prior is often unreliable, and yet strongly influences the posterior intervals and point estimates, causing the posterior intervals to differ from fixed-parameter confidence intervals, even for arbitrarily small estimates of the LFDR. That influence of the estimated prior manifests the failure of the conditional posterior intervals, given the truth of the alternative hypothesis, to match the confidence intervals. Those problems are overcome by changing the posterior distribution conditional on the alternative hypothesis from a Bayesian posterior to a confidence posterior. Unlike the Bayesian posterior, the confidence posterior equates the posterior probability that the parameter lies in a fixed interval with the coverage rate of the coinciding confidence interval. The resulting confidence-Bayes hybrid posterior supplies interval and point estimates that shrink toward the null hypothesis value. The confidence intervals tend to be much shorter than their fixed-parameter counterparts, as illustrated with gene expression data. Simulations nonetheless confirm that the shrunken confidence intervals cover the parameter more frequently than stated. Generally applicable sufficient conditions for correct coverage are given. In addition to having those frequentist properties, the hybrid posterior can also be motivated from an objective Bayesian perspective by requiring coherence with some default prior conditional on the alternative hypothesis. That requirement generates a new class of approximate posteriors that supplement Bayes factors modified for improper priors and that dampen the influence of proper priors on the credibility intervals. While that class of posteriors intersects the class of confidence-Bayes posteriors, neither class is a subset of the other. In short, two first principles generate both classes of posteriors: a coherence principle and a relevance principle. The coherence principle requires that all effect size estimates comply with the same probability distribution. The relevance principle means effect size estimates given the truth of an alternative hypothesis cannot depend on whether that truth was known prior to observing the data or whether it was learned from the data.     

Ethnicity and fertility in Liberia: A test of the minority group status hypothesis

Abstract

This study examines the relationship between ethnicity and fertility in Liberia, within the context of the minority group status hypothesis. The hypothesis argues that minority group status exerts an independent effect on fertility, net of controls for socioeconomic and demographic variables. Using a subsample of women from the 1974 Liberian census, the study examines interethnic variations in fertility by comparing five ethnic minorities—Bassa, Vai, Grebo, Kru, Kpelle—with the majority group, Americo‐Liberian. With the possible exception of Bassa women, the findings do not support the minority group status hypothesis. Instead, the findings are more congruent with the alternative assimilationist hypothesis which argues that when sociodemographic differences between majority and minority groups are controlled, their fertility levels should converge. The implications of these findings are explored.     

Bateman's principle and immunity

The immunocompetence handicap hypothesis (ICHH) of Folstad and Karter has inspired a large number of studies that have tried to understand the causal basis of parasite-mediated sexual selection. Even though this hypothesis is based on the double function of testosterone, a hormone restricted to vertebrates, studies of invertebrates have tended to provide central support for specific predictions of the ICHH. I propose an alternative hypothesis that explains many of the findings without relying on testosterone or other biochemical feedback loops. This alternative is based on Bateman's principle, that males gain fitness by increasing their mating success whilst females increase fitness through longevity because their reproductive effort is much higher. Consequently, I predict that females should invest more in immunity than males. The extent of this dimorphism is determined by the mating system and the genetic correlation between males and females in immune traits. In support of my arguments, I mainly use studies on insects that share innate immunity with vertebrates and have the advantage that they are easier to study.     

A database for the analysis of immunity genes in Drosophila: PADMA database

While microarray experiments generate voluminous data, discerning trends that support an existing or alternative paradigm is challenging. To synergize hypothesis building and testing, we designed the Pathogen Associated Drosophila MicroArray (PADMA) database for easy retrieval and comparison of microarray results from immunity-related experiments (www.padmadatabase.org). PADMA also allows biologists to upload their microarray-results and compare it with datasets housed within PADMA. We tested PADMA using a preliminary dataset from Ganaspis xanthopoda-infected fly larvae, and uncovered unexpected trends in gene expression, reshaping our hypothesis. Thus, the PADMA database will be a useful resource to fly researchers to evaluate, revise, and refine hypotheses.     

The evolutionary ecology of alternative migratory tactics in salmonid fishes

Extensive individual variation in spatial behaviour is a common feature among species that exhibit migratory life cycles. Nowhere is this more evident than in salmonid fishes; individual fish may complete their entire life cycle in freshwater streams, others may migrate variable distances at sea and yet others limit their migrations to larger rivers or lakes before returning to freshwater streams to spawn. This review presents evidence that individual variation in migratory behaviour and physiology in salmonid fishes is controlled by developmental thresholds and that part of the variation in proximal traits activating the development of alternative migratory tactics is genetically based. We summarize evidence that alternative migratory tactics co‐exist within populations and that all individuals may potentially adopt any of the alternative phenotypes. Even though intra‐specific genetic divergence of migratory tactics is uncommon, it may occur if female competition for oviposition sites results in spawning segregation of alternative phenotypes. Because of their polygenic nature, alternative migratory tactics are considered as threshold traits. Threshold traits have two characteristics: an underlying 'liability' trait that varies in a continuous fashion, and a threshold value which is responsible for the discreetness observed in phenotypic distribution. We review evidence demonstrating that body size is an adequate proxy for the liability trait controlling the decision to migrate, but that the same phenotypic outcome (anadromy or residency) may be reached by different developmental pathways. The evidence suggesting a significant heritable component in the development of alternative migratory tactics is subsequently reviewed, leading us to conclude that alternative migratory tactics have considerable potential to respond to selection and evolve. We review what is known about the proximal physiological mechanisms mediating the translation of the continuous value of the liability trait into a discontinuous migratory tactic. We conclude by identifying several avenues for future research, including testing the frequency‐dependent selection hypothesis, establishing the relative importance of adaptive phenotypic plasticity in explaining some geographic gradients in migratory behaviour and identifying the physiological and genetic basis of the switching mechanisms responsible for alternative migratory tactics.     

Detecting the molecular signature of social conflict: theory and a test with bacterial quorum sensing genes

Extending social evolution theory to the molecular level opens the door to an unparalleled abundance of data and statistical tools for testing alternative hypotheses about the long-term evolutionary dynamics of cooperation and conflict. To this end, we take a collection of known sociality genes (bacterial quorum sensing [QS] genes), model their evolution in terms of patterns that are detectable using gene sequence data, and then test model predictions using available genetic data sets. Specifically, we test two alternative hypotheses of social conflict: (1) the "adaptive" hypothesis that cheaters are maintained in natural populations by frequency-dependent balancing selection as an evolutionarily stable strategy and (2) the "evolutionary null" hypothesis that cheaters are opposed by purifying kin selection yet exist transiently because of their recurrent introduction into populations by mutation (i.e., kin selection-mutation balance). We find that QS genes have elevated within- and among-species sequence variation, nonsignificant signatures of natural selection, and putatively small effect sizes of mutant alleles, all patterns predicted by our evolutionary null model but not by the stable cheater hypothesis. These empirical findings support our theoretical prediction that QS genes experience relaxed selection due to nonclonality of social groups, conditional expression, and the individual-level advantage enjoyed by cheaters. Furthermore, cheaters are evolutionarily transient, persisting in populations because of their recurrent introduction by mutation and not because they enjoy a frequency-dependent fitness advantage.     

Reappraisal of the electron spin resonance spectra of maleimide and iodoacetamide spin labels in erythrocyte ghosts.

The effects of sulfhydryl inhibitors (iodoacetamide and N-ethylmaleimide) on the electron spin resonance spectra of two maleimide and two iodoacetamide spin labels in erythrocyte ghosts were found to correlate with their relative “lipid”/water partition coefficients. But the spectral characteristics of the maleimide spin labels, and their ghost concentrations after iodoacetamide inhibition, are not consistent with the hypothesis that interprets their spectra solely on the basis of a heterogenous membrane distribution. An alternative hypothesis is suggested which is compatible with relative “lipid solubilities” and the iodoacetamide inhibition spectra.     

Histochemical localization of Mg2+-activated ATPases on microtubule bundles in epidermal cells of Carausius morosus: Possible significance to pigment migration

We have demonstrated the presence of Mg²⁺-stimulated ATPases on microtubule bundles in the epidermal cells at the light microscope level, using specific histochemical techniques. This method provides an alternative method to immunohistochemistry for identifying microtubule bundles in the epidermal cells of Carausius morosus using the light microscope. The close association between ommochrome granules and the microtubule bundles support the hypothesis, that these ATPases play an important role in force generation, required to move ommochrome granules during physiological colour change.     

Misfolding of HLA-B27 as a result of its B pocket suggests a novel mechanism for its role in susceptibility to spondyloarthropathies

The MHC class I protein HLA-B27 is strongly associated with susceptibility to spondyloarthropathies and can cause arthritis when expressed in rats and mice, implying a direct role in disease pathogenesis. A prominent hypothesis to explain this role suggests that the unique peptide binding specificity of HLA-B27 confers an ability to present arthritogenic peptides. The B pocket, a region of the peptide binding groove that is an important determinant of allele-specific peptide binding, is thought to be critical for arthritogenicity. However, this hypothesis remains unproven. We show that in addition to its role in peptide selection, the B pocket causes a portion of the pool of assembling HLA-B27 heavy chains in the endoplasmic reticulum to misfold, resulting in their degradation in the cytosol. The misfolding phenotype is corrected by replacing the HLA-B27 B pocket with one from HLA-A2. Our results suggest an alternative to the arthritogenic peptide hypothesis. Misfolding and its consequences, rather than allele-specific peptide presentation, may underlie the strong link between the HLA-B27 B pocket and susceptibility to spondyloarthropathies.     

Calibration of molecular clocks and the biogeographic history of Crypteroniaceae

A recent molecular clock analysis concluded that Gondwanan vicariance and out-of-India dispersal best explained the distribution of Crypteroniaceae and its allies (Conti et al. 2002). A reanalysis of their data using a different molecular dating technique and calibration point is congruent with an alternative hypothesis, namely dispersal between India, Africa, and South America long after the initial break-up of Gondwana.