The enemy release hypothesis as a hierarchy of hypotheses

In ecology, a hypothesis is usually not discarded if a few studies reject it, as long as there are other studies supporting it. How to assess the usefulness of ecological hypotheses is therefore not straightforward. Using the enemy release hypothesis as an example, we show how creating a hierarchy of hypotheses (HoH) can help reviewing and evaluating evidence for and against an ecological hypothesis. In a HoH, a broad, overarching hypothesis branches into more specific and better testable sub‐hypotheses. The enemy release hypothesis is a major hypothesis in invasion ecology and posits that the absence of enemies in the exotic range of an alien species is a cause of its invasion success. Based on a systematic review of empirical tests of this hypothesis, we divided it into sub‐hypotheses, differentiating among 1) indicators for enemy release, 2) types of comparisons, and 3) types of enemies. We identified 176 empirical tests and weighted each test according to the number of alien species studied and the research method (experimental vs observational, field vs enclosure vs laboratory). For the broadly formulated enemy release hypothesis, we found nearly as much supporting (36%) as questioning evidence (43%). At the sub‐hypotheses level, however, we found that some sub‐hypotheses are strongly supported by empirical evidence, whereas others receive hardly any support. These differences are further emphasized for some types of habitat and focal taxonomic groups. Our findings suggest that several specific formulations (i.e. sub‐hypotheses) of the broad enemy release hypothesis are useful, whereas other formulations should be viewed more critically. In general, the approach outlined here can help evaluate major ecological hypotheses and their specific sub‐hypotheses. Our study also highlights the need for a scientific debate on how much supporting evidence is sufficient to consider an ecological hypothesis to be useful.     

A quantitative analysis of the cytotoxic action of chemical mutagens

A quantitative hypothesis is developed to explain the cytotoxic action of chemical mutagens on eukaryotic cells. The hypothesis forms an extrapolation of previously developed concepts used to explain the effect of ionizing radiation and the cytotoxic action of UV light. The crucial potentially lethal lesion is assumed to be a DNA double-strand lesion which may be an interstrand cross-link or a pair of DNA single-strand alkylations, for example. The effect of repair processes is included in the analytical equation derived to describe cell survival. The analysis of several sets of cell survival data for different chemical mutagens is used to demonstrate the applicability of the hypothesis. The logical extension of the hypothesis permits a division of chemical mutagens into 4 separate classes on the basis of the mechanisms proposed for the cytotoxic activity, and the relative importance of the risk associated with low-level exposure to each class is discussed. The hypothesis is amenable to further experimental verification.     

Sun exposure and skin cancer,and the puzzle of cutaneous melanoma: A perspective on Fears et al. Mathematical models of age and ultraviolet effects on the incidence of skin cancer among whites in the United States. American Journal of Epidemiology 1977; 105: 420–427

Sunlight has been known as an important cause of skin cancer since around the turn of the 20th Century. A 1977 landmark paper of US scientists Fears, Scotto, and Schneiderman advanced a novel hypothesis whereby cutaneous melanoma was primarily caused by intermittent sun exposure (i.e. periodic, brief episodes of exposure to high-intensity ultraviolet radiation) while the keratinocyte cancers, squamous cell carcinoma and basal cell carcinoma, were primarily caused by progressive accumulation of sun exposure. With respect to cutaneous melanoma, this became known as the intermittent exposure hypothesis. The hypothesis stemmed from analysis of measured ambient ultraviolet radiation and age-specific incidence rates of melanoma and keratinocyte cancers collected as an extension to the US Third National Cancer Survey in several US States. In this perspective paper, we put this novel hypothesis into the context of knowledge at the time, and describe subsequent epidemiological and molecular research into melanoma that elaborated the intermittent exposure hypothesis and ultimately replaced it with a dual pathway hypothesis. Our present understanding is of two distinct biological pathways by which cutaneous melanoma might develop; a nevus prone pathway initiated by early sun exposure and promoted by intermittent sun exposure or possibly host factors; and a chronic sun exposure pathway in sun sensitive people who progressively accumulate sun exposure to the sites of future melanomas.     

The origin of the pelagobenthic metazoan life cycle: what's sex got to do with it?

The biphasic (pelagobenthic) life cycle is found throughoutthe animal kingdom, and includes gametogenesis, embryogenesis,and metamorphosis. From a tangled web of hypotheses on the originand evolution of the metazoan pelagobenthic life cycle, currentopinion appears to favor a simple, larval-like holopelagic ancestorthat independently settled multiple times to incorporate a benthicphase into the life cycle. This hypothesis derives originallyfrom Haeckel's (1874) Gastraea theory of ontogeny recapitulatingphylogeny, in which the gastrula is viewed as the recapitulationof a gastraean ancestor that evolved via selection on a simple,planktonic hollow ball of cells to develop the capacity to feed.Here, we propose an equally plausible hypothesis that the originof the metazoan pelagobenthic life cycle was a direct consequenceof sexual reproduction in a likely holobenthic ancestor. Indoing so, we take into account new insights from poriferan developmentand from molecular phylogenies. In this scenario, the gastruladoes not represent a recapitulation, but simply an embryologicalstage that is an outcome of sexual reproduction. The embryocan itself be considered as the precursor to a biphasic lifestyle,with the embryo representing one phase and the adult anotherphase. This hypothesis is more parsimonious because it precludesthe need for multiple, independent origins of the benthic form.It is then reasonable to consider that multilayered, ciliatedembryos ultimately released into the water column are subjectto natural selection for dispersal/longevity/feeding that setsthem on the evolutionary trajectory towards the crown metazoanplanktonic larvae. These new insights from poriferan developmentthus clearly support the intercalation hypothesis of bilaterianlarval evolution, which we now believe should be extended todiscussions of the origin of biphasy in the metazoan last commonancestor.     

A Micellar On-Pathway Intermediate Step Explains the Kinetics of Prion Amyloid Formation

In a previous work by Alvarez-Martinez et al. (2011), the authors pointed out some fallacies in the mainstream interpretation of the prion amyloid formation. It appeared necessary to propose an original hypothesis able to reconcile the in vitro data with the predictions of a mathematical model describing the problem. Here, a model is developed accordingly with the hypothesis that an intermediate on-pathway leads to the conformation of the prion protein into an amyloid competent isoform thanks to a structure, called micelles, formed from hydrodynamic interaction. The authors also compare data to the prediction of their model and propose a new hypothesis for the formation of infectious prion amyloids.     

高原鼠兔个性特征的地理变异及其对环境的适应

个性特征是指动物稳定且可遗传的综合行为特征,反映出其对特定环境的适应。限制性假说认为个性特征主要受遗传因素制约,个体间行为的表达差异不以环境条件而发生随意性改变;然而,适应性假说则认为个性特征主要由环境因素决定,生活于相同环境中的物种,其个性特征将产生趋同现象。本研究通过比较2个高原鼠兔地理种群的个性特征,检验适应性假说和限制性假说的相关预测。结果表明,刚察县高原鼠兔野外种群个体的行为特征聚为3类,玛沁县则为2类。实验室内驯化2-3个月后,两个地理种群个体行为特征聚为1类。两地理种群个体的观察、攀爬行为及边缘区域活动、移动累计时间均无显著差异,但静止累计时间存在明显地理差异。个体的中心区域活动累计时间在野外和驯化后均存在明显差异,且与地理空间的交互作用不显著。两地理种群之间个体的温顺性无明显差异;心率亦无显著差异。高原鼠兔个性特征中主要行为参数无显著的地理差异,主要由遗传因素决定,验证了限制性假说的相关预测。     

The Alzheimer's disease mitochondrial cascade hypothesis: Progress and perspectives

Ten years ago we first proposed the Alzheimer's disease (AD) mitochondrial cascade hypothesis. This hypothesis maintains that gene inheritance defines an individual's baseline mitochondrial function; inherited and environmental factors determine rates at which mitochondrial function changes over time; and baseline mitochondrial function and mitochondrial change rates influence AD chronology. Our hypothesis unequivocally states in sporadic, late-onset AD, mitochondrial function affects amyloid precursor protein (APP) expression, APP processing, or beta amyloid (Aβ) accumulation and argues if an amyloid cascade truly exists, mitochondrial function triggers it. We now review the state of the mitochondrial cascade hypothesis, and discuss it in the context of recent AD biomarker studies, diagnostic criteria, and clinical trials. Our hypothesis predicts that biomarker changes reflect brain aging, new AD definitions clinically stage brain aging, and removing brain Aβ at any point will marginally impact cognitive trajectories. Our hypothesis, therefore, offers unique perspective into what sporadic, late-onset AD is and how to best treat it. This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction, and Neurodegenerative Diseases.     

Dissociated mechanisms of extracting perceptual information into visual working memory

Background

The processing mechanisms of visual working memory (VWM) have been extensively explored in the recent decade. However, how the perceptual information is extracted into VWM remains largely unclear. The current study investigated this issue by testing whether the perceptual information was extracted into VWM via an integrated-object manner so that all the irrelevant information would be extracted (object hypothesis), or via a feature-based manner so that only the target-relevant information would be extracted (feature hypothesis), or via an analogous processing manner as that in visual perception (analogy hypothesis).

Methodology/Principal Findings

High-discriminable information which is processed at the parallel stage of visual perception and fine-grained information which is processed via focal attention were selected as the representatives of perceptual information. The analogy hypothesis predicted that whereas high-discriminable information is extracted into VWM automatically, fine-grained information will be extracted only if it is task-relevant. By manipulating the information type of the irrelevant dimension in a change-detection task, we found that the performance was affected and the ERP component N270 was enhanced if a change between the probe and the memorized stimulus consisted of irrelevant high-discriminable information, but not if it consisted of irrelevant fine-grained information.

Conclusions/Significance

We conclude that dissociated extraction mechanisms exist in VWM for information resolved via dissociated processes in visual perception (at least for the information tested in the current study), supporting the analogy hypothesis.     

DNA Repair and the Evolution of Transformation in Haemophilus Influenzae

Under certain environmental conditions, naturally transforming bacteria are induced to pick up DNA released into the environment by other cells of the same or closely related species and, by homologous recombination, integrate that DNA into their chromosome. The selective pressures responsible for the evolution and maintenance of this form of genetic outcrossing, or sex, in bacteria are not known. A prominent hypothesis is that transformation, and sex in general, evolved as a means of obtaining DNA templates to repair damaged regions of the chromosome. Previous results obtained with Bacillus subtilis were consistent with the repair hypothesis. In an effort to explore the generality of those results, I have tested the repair hypothesis with Haemophilus influenzae, a naturally transforming, gram-negative species of bacteria. The results of UV damage-survivorship experiments with H. influenzae were also consistent with that hypothesis. However, additional experiments demonstrate that the higher survival of transformed cultures cannot be accounted for by use of the transforming DNA as templates for repair. I consider alternative hypotheses for the means by which transformation can increase cell survival following UV exposure and discuss the implications of these results with respect to the DNA repair hypothesis and the evolution of transformation.     

Testing the nutrition hypothesis for the adaptive nature of insect galls: does a non‐adapted herbivore perform better in galls?

Abstract.  1. The nutrition hypothesis for the adaptive nature of galls states that gall-inducing insects control the nutrient levels in galls to their own benefit. Although the nutrition hypothesis is widely accepted, there have been few empirical tests of this idea.
2. A novel method is presented for testing the nutrition hypothesis that links manipulation of gall nutrient levels by the gall inducer to herbivore performance. The effects of adaptation and nutritional advantage are separated by using a herbivore that is adapted to a host plant susceptible to galling but one which never enters the gall environment.
3.  Hellinsia glenni (Cashatt), a plume moth (Pterophoridae) and one of its host plants provide an excellent system for testing the nutrition hypothesis because H. glenni larvae feed internally on the relatively nutrient-poor stems of a goldenrod, Solidago gigantea , but do not venture into the nutrient-rich galls induced on that plant by a tephritid fly, Eurosta solidaginis . The nutrition hypothesis was tested by transplanting early-instar H. glenni larvae into galls and stems of S. gigantea to determine if the larvae transplanted to galls would perform better compared with those larvae transplanted to stems.
4. The results support the nutrition hypothesis for the adaptive nature of galls. Hellinsia glenni achieved greater final mass in the gall environment compared with the final mass larvae achieved in the stem environment. There was also evidence that the quality of gall tissue is controlled by the gall inducer, which has not been previously demonstrated for mature E. solidaginis galls.     

Canalization without flux sensors: a traveling-wave hypothesis

In 1969, Tsvi Sachs published his seminal hypothesis of vascular development in plants: the canalization hypothesis. A positive feedback loop between the flux of the phytohormone auxin and the cells' auxin transport capacity would canalize auxin progressively into discrete channels, which would then differentiate into vascular tissues. Recent experimental studies confirm the central role of polar auxin flux in plant vasculogenesis, but it is unclear if and by which mechanism plant cells could respond to auxin flux. In this Opinion article, we review auxin perception mechanisms and argue that these respond more likely to auxin concentrations than to auxin flux. We propose an alternative mechanism for polar auxin channeling, which is more consistent with recent molecular observations.     

THE MAINTENANCE OF SEX BY PARASITISM AND MUTATION ACCUMULATION UNDER EPISTATIC FITNESS FUNCTIONS

The mutation accumulation hypothesis predicts that sex functions to reduce the population mutational load, while the Red Queen hypothesis holds that sex is adaptive as a defense against coevolving pathogens. We used computer simulations to examine the combined and separate effects of selection against deleterious mutations and host-parasite coevolution on the spread of a clone into an outcrossing sexual population. The results suggest that the two processes operating simultaneously may select for sex independent of the exact shape of the function that maps mutation number onto host fitness.     

Sex and the eukaryotic cell cycle is consistent with a viral ancestry for the eukaryotic nucleus

The origin of the eukaryotic cell cycle, including mitosis, meiosis, and sex are as yet unresolved aspects of the evolution of the eukaryotes. The wide phylogenetic distribution of both mitosis and meiosis suggest that these processes are integrally related to the origin of the earliest eukaryotic cells. According to the viral eukaryogenesis (VE) hypothesis, the eukaryotes are a composite of three phylogenetically unrelated organisms: a viral lysogen that evolved into the nucleus, an archaeal cell that evolved into the eukaryotic cytoplasm, and an alpha-proteobacterium that evolved into the mitochondria. In the extended VE hypothesis presented here, the eukaryotic cell cycle arises as a consequence of the derivation of the nucleus from a lysogenic DNA virus.     

Cellular redox potential and the biomolecular electrochemical series: a systems hypothesis

The role of cellular redox potential in the regulation of protein activity is becoming increasingly appreciated and characterized. In this paper we put forward a new hypothesis relating to redox regulation of cellular physiology. We have exemplified our hypothesis using apoptosis since its redox phenomenology is well established, but believe that it is equally applicable to several other pathways. Our hypothesis is that since multiple proteins in the apoptosis pathway are thought to be regulated via oxidation/reduction reactions and since cellular redox potentials have been shown to become progressively more oxidative during apoptosis, that the proteins could be arranged in an electrochemical series where the protein's standard potential correlates with its position in the pathway. Since the most stable oxidation state of the protein is determined by its standard potential and the redox potential of its environment (in a way predictable by the Nernst equation), a quantitative model of the redox regulation of the pathway could be developed. We have outlined our hypothesis, illustrating it using a pathway map which assembles a selection of the literature on apoptosis into a readable graphical format. We have also outlined experimental approaches suitable for testing our hypothesis.     

Revisiting the seed and soil in cancer metastasis

Metastasis remains the overwhelming cause of death for cancer patients. During metastasis, cancer cells will leave the primary tumor, intravasate into the bloodstream, arrest at a distant organ, and eventually develop into gross lesions at the secondary sites. This intricate process is influenced by innumerable factors and complex cellular interactions described in 1889 by Stephen Paget as the seed and soil hypothesis. In this review, we revisit this seed and soil hypothesis with an emerging understanding of the cancer cell (i.e. seed) and its microenvironment (i.e. soil). We will provide background to suggest that a critical outcome of the seed–soil interaction is resistance of the stresses that would otherwise impede metastasis.     

Reassessment of the lineage fusion hypothesis for the origin of double membrane bacteria

In 2009, James Lake introduced a new hypothesis in which reticulate phylogeny reconstruction is used to elucidate the origin of gram-negative bacteria (Nature 460: 967-971). The presented data supported the gram-negative bacteria originating from an ancient endosymbiosis between the Actinobacteria and Clostridia. His conclusion was based on a presence-absence analysis of protein families that divided all prokaryotes into five groups: Actinobacteria, Double Membrane bacteria (DM), Clostridia, Archaea and Bacilli. Of these five groups, the DM are by far the largest and most diverse group compared to the other groupings. While the fusion hypothesis for the origin of double membrane bacteria is enticing, we show that the signal supporting an ancient symbiosis is lost when the DM group is broken down into smaller subgroups. We conclude that the signal detected in James Lake's analysis in part results from a systematic artifact due to group size and diversity combined with low levels of horizontal gene transfer.     

Translocation hypothesis of insulin action on glucose transport

This article reviews the experimental data that support the translocation hypothesis of insulin action on glucose transport in adipocytes. According to this hypothesis, 1) most of the glucose transport mechanism in the basal (no insulin) form of fat cells is associated with an unidentified subcellular structure (the storage site), which is separated into the Golgi-rich fraction by centrifugation, and 2) the function of insulin is to induce translocation of the glucose transport mechanism from the above storage site to the plasma membrane. This translocation of the transport mechanism is reversible, dependent on metabolic energy, and independent of protein synthesis.     

Testing adaptive significance of host manipulation with a parasitoid wasp

According to the extended phenotype hypothesis, certain parasites manipulate the host's behaviour which ultimately enhances the transmission of parasite genes into the next generation. The parasitoid wasp Ampulex compressa attacks and stings its cockroach Periplaneta americana host and lays an egg on the cockroach's leg. Before the wasp's oviposition, the stung cockroach engages in excessive self-grooming for about 30 min. The prey location hypothesis posits that self-grooming may allow the wasp to easily locate its host before transporting it to the nest. To test this hypothesis, we manipulated the mobility of the stung cockroach under different spatial constraints. Latencies to locate stung cockroaches with unlimited movement were similar than latencies to locate stung, but motionless cockroaches irrespectively of spatial constraints. Wasps were less willing to lay eggs and seal an entrance to the burrow in treatments with motionless cockroaches which suggests that if the expected reproductive success is low, then parental investment decreases. Our results provide no support for the location hypothesis and call for further experimental investigation of the extended phenotype hypothesis in parasite–host interactions.     

A simulation of anthropogenic Columbian mammoth (Mammuthus columbi) extinction

The cause of the extinction of the Columbian mammoth (Mammuthus columbi) and other species of megafauna during the end of the Pleistocene epoch is an ongoing debate. In this study, we used mathematical modelling to test the overkill hypothesis first proposed by Martin in 1973. The overkill hypothesis claims that early humans migrating from Asia through Beringia and into North America hunted the majority of the continent’s megafauna to extinction. Previous research has been conducted on the overkill hypothesis for the Columbian mammoth using a continuous differential equations model. We improved on this work by developing a computationally more efficient and more realistic discrete stochastic model. Most model parameters were obtained directly from the literature; migration parameters were informed by the literature and calibrated for the model. Our results provide evidence in support of the overkill hypothesis.