What Can Ecology Teach Us About Cancer?

In 2008, Pienta et al. (Transl Oncol. 2008;1:158-164) introduced the term ecological therapy for cancer treatment and, in particular, emphasized that destruction of the tumor microenvironment would be more effective than just killing the cells that inhabit it. Proposed here is an expansion on the idea of ecological therapy of cancer, incorporating 1) literature on species invasion, i.e., a right cancerous clone needs to be at the right place at the right time to actually invade its environment, and 2) the literature on niche construction, that is, the idea that once a tumor is formed, cancer cells they modify their microenvironment (niche construction) by changing pH through glycolysis, secreting growth factors and recruiting tumor-associated macrophages to promote cell growth, activating fibroblasts, evading predation from immune system, making the cancer that much more difficult to eradicate. Paleontological literature suggests that the largestmass extinctions occurred when environmental stress that would weaken the population was coupled with some pulse destructive event that caused extensive mortality. To have the same effect on cells in the tumor, rather than, or at least in addition to, killing the cells, one would also need to target the niche that they created for themselves.     

Macroparasite Infections of Amphibians: What Can They Tell Us?

Understanding linkages between environmental changes and disease emergence in human and wildlife populations represents one of the greatest challenges to ecologists and parasitologists. While there is considerable interest in drivers of amphibian microparasite infections and the resulting consequences, comparatively little research has addressed such questions for amphibian macroparasites. What work has been done in this area has largely focused on nematodes of the genus Rhabdias and on two genera of trematodes (Ribeiroia and Echinostoma). Here, we provide a synopsis of amphibian macroparasites, explore how macroparasites may affect amphibian hosts and populations, and evaluate the significance of these parasites in larger community and ecosystem contexts. In addition, we consider environmental influences on amphibian-macroparasite interactions by exploring contemporary ecological factors known or hypothesized to affect patterns of infection. While some macroparasites of amphibians have direct negative effects on individual hosts, no studies have explicitly examined whether such infections can affect amphibian populations. Moreover, due to their complex life cycles and varying degrees of host specificity, amphibian macroparasites have rich potential as bioindicators of environmental modifications, especially providing insights into changes in food webs. Because of their documented pathologies and value as bioindicators, we emphasize the need for broader investigation of this understudied group, noting that ecological drivers affecting these parasites may also influence disease patterns in other aquatic fauna.     

Chlamydia trachomatis ompA Variants in Trachoma: What Do They Tell Us?

Background

Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious cause of blindness. Sequence-based analysis of the multiple strains typically present in endemic communities may be informative for epidemiology, transmission, response to treatment, and understanding the host response.

Methods

Conjunctival and nasal samples from a Gambian community were evaluated before and 2 months after mass azithromycin treatment. Samples were tested for Ct by Amplicor, with infection load determined by quantitative PCR (qPCR). ompA sequences were determined and their diversity analysed using frequency-based tests of neutrality.

Results

Ninety-five of 1,319 (7.2%) individuals from 14 villages were infected with Ct at baseline. Two genovars (A and B) and 10 distinct ompA genotypes were detected. Two genovar A variants (A1 and A2) accounted for most infections. There was an excess of rare ompA mutations, not sustained in the population. Post-treatment, 76 (5.7%) individuals had Ct infection with only three ompA genotypes present. In 12 of 14 villages, infection had cleared, while in two it increased, probably due to mass migration. Infection qPCR loads associated with infection were significantly greater for A1 than for A2. Seven individuals had concurrent ocular and nasal infection, with divergent genotypes in five.

Conclusions

The number of strains was substantially reduced after mass treatment. One common strain was associated with higher infection loads. Discordant genotypes in concurrent infection may indicate distinct infections at ocular and nasal sites. Population genetic analysis suggests the fleeting appearance of rare multiple ompA variants represents purifying selection rather than escape variants from immune pressure. Genotyping systems accessing extra-ompA variation may be more informative.     

What Can Cross-Cultural Correlations Teach Us about Human Nature?

Many recent evolutionary psychology and human behavioral ecology studies have tested hypotheses by examining correlations between variables measured at a group level (e.g., state, country, continent). In such analyses, variables collected for each aggregation are often taken to be representative of the individuals present within them, and relationships between such variables are presumed to reflect individual-level processes. There are multiple reasons to exercise caution when doing so, including: (1) the ecological fallacy, whereby relationships observed at the aggregate level do not accurately represent individual-level processes; (2) non-independence of data points, which violates assumptions of the inferential techniques used in null hypothesis testing; and (3) cross-cultural non-equivalence of measurement (differences in construct validity between groups). We provide examples of how each of these gives rise to problems in the context of testing evolutionary hypotheses about human behavior, and we offer some suggestions for future research.     

Lessons From an Unusual Critter: What Can Unusual Animals Teach Us?

The study of unusual or little‐known animals can pay enormous dividends by providing new insights into fundamental biological processes. One has to consider only the implications of the studies on Aplysia or Caenorhabditis as illustrations, to say nothing of the many examples from the work of Gunter Tembrock, in whose honor this lecture is offered. Recent studies of the hibernation of a small primate from Madagascar, the fat‐tailed dwarf lemur, which may remain in a condition of torpor for weeks at a time, promise a range of similar insights.     

What Do Eye Gaze Metrics Tell Us about Motor Imagery?

Many of the brain structures involved in performing real movements also have increased activity during imagined movements or during motor observation, and this could be the neural substrate underlying the effects of motor imagery in motor learning or motor rehabilitation. In the absence of any objective physiological method of measurement, it is currently impossible to be sure that the patient is indeed performing the task as instructed. Eye gaze recording during a motor imagery task could be a possible way to “spy” on the activity an individual is really engaged in. The aim of the present study was to compare the pattern of eye movement metrics during motor observation, visual and kinesthetic motor imagery (VI, KI), target fixation, and mental calculation. Twenty-two healthy subjects (16 females and 6 males), were required to perform tests in five conditions using imagery in the Box and Block Test tasks following the procedure described by Liepert et al. Eye movements were analysed by a non-invasive oculometric measure (SMI RED250 system). Two parameters describing gaze pattern were calculated: the index of ocular mobility (saccade duration over saccade + fixation duration) and the number of midline crossings (i.e. the number of times the subjects gaze crossed the midline of the screen when performing the different tasks). Both parameters were significantly different between visual imagery and kinesthesic imagery, visual imagery and mental calculation, and visual imagery and target fixation. For the first time we were able to show that eye movement patterns are different during VI and KI tasks. Our results suggest gaze metric parameters could be used as an objective unobtrusive approach to assess engagement in a motor imagery task. Further studies should define how oculomotor parameters could be used as an indicator of the rehabilitation task a patient is engaged in.     

Physiological Trade-Offs Along a Fast-Slow Lifestyle Continuum in Fishes: What Do They Tell Us about Resistance and Resilience to Hypoxia?

It has recently been suggested that general rules of change in ecological communities might be found through the development of functional relationships between species traits and performance. The physiological, behavioural and life-history traits of fishes are often organised along a fast-slow lifestyle continuum (FSLC). With respect to resistance (capacity for population to resist change) and resilience (capacity for population to recover from change) to environmental hypoxia, the literature suggests that traits enhancing resilience may come at the expense of traits promoting resistance to hypoxia; a trade-off may exist. Here I test whether three fishes occupying different positions along the FSLC trade-off resistance and resilience to environmental hypoxia. Static respirometry experiments were used to determine resistance, as measured by critical oxygen tension (P_crit), and capacity for (RC) and magnitude of metabolic reduction (RM). Swimming respirometry experiments were used to determine aspects of resilience: critical (U_crit) and optimal swimming speed (U_opt), and optimal cost of transport (COT_opt). Results pertaining to metabolic reduction suggest a resistance gradient across species described by the inequality Melanotaenia fluviatilis (fast lifestyle) < Hypseleotris sp. (intermediate lifestyle) < Mogurnda adspersa (slow lifestyle). The U_crit and COT_opt data suggest a resilience gradient described by the reverse inequality, and so the experiments generally indicate that three fishes occupying different positions on the FSLC trade-off resistance and resilience to hypoxia. However, the scope of inferences that can be drawn from an individual study is narrow, and so steps towards general, trait-based rules of fish community change along environmental gradients are discussed.     

Cell Penetrating Peptides: How Do They Do It?

Cell penetrating peptides consist of short sequences of amino acids containing a large net positive charge that are able to penetrate almost any cell, carrying with them relatively large cargoes such as proteins, oligonucleotides, and drugs. During the 10 years since their discovery, the question of how they manage to translocate across the membrane has remained unanswered. The main discussion has been centered on whether they follow an energy-independent or an energy-dependent pathway. Recently, we have discovered the possibility of an energy-independent pathway that challenges fundamental concepts associated with protein-membrane interactions (Herce and Garcia, PNAS, 104: 20805 (2007) [1]). It involves the translocation of charged residues across the hydrophobic core of the membrane and the passive diffusion of these highly charged peptides across the membrane through the formation of aqueous toroidal pores. The aim of this review is to discuss the details of the mechanism and interpret some experimental results consistent with this view.     

Sauropod Necks: Are They Really for Heat Loss?

Three-dimensional digital models of 16 different sauropods were used to examine the scaling relationship between metabolism and surface areas of the whole body, the neck, and the tail in an attempt to see if the necks could have functioned as radiators for the elimination of excess body heat. The sauropod taxa sample ranged in body mass from a 639 kg juvenile Camarasaurus to a 25 t adult Brachiosaurus. Metabolism was assumed to be directly proportional to body mass raised to the ¾ power, and estimates of body mass accounted for the presence of lungs and systems of air sacs in the trunk and neck. Surface areas were determined by decomposing the model surfaces into triangles and their areas being computed by vector methods. It was found that total body surface area was almost isometric with body mass, and that it showed negative allometry when plotted against metabolic rate. In contrast, neck area showed positive allometry when plotted against metabolic rate. Tail area show negative allometry with respect to metabolic rate. The many uncertainties about the biology of sauropods, and the variety of environmental conditions that different species experienced during the groups 150 million years of existence, make it difficult to be absolutely certain about the function of the neck as a radiator. However, the functional combination of the allometric increase of neck area, the systems of air sacs in the neck and trunk, the active control of blood flow between the core and surface of the body, changing skin color, and strategic orientation of the neck with respect to wind, make it plausible that the neck could have functioned as a radiator to avoid over-heating.     

What Do Mexican Fruit Flies Learn When They Experience Fruit?

Mexican fruit flies learn fruit characteristics that enable them to distinguish familiar fruits from novel fruits. We investigated whether mature Mexican fruit flies learn fruit color, size or odor. We found no evidence that female flies learn fruit color or size after experience with host fruit, including oviposition. However, green fruit and fruit models were more attractive than yellow and red fruit and fruit models regardless of previous experience. Females with grapefruit experience were more attracted to fruit models with extract of either grapefruit peel or pulp, than to models without extract. Females with no experience with grapefruit were not attracted to models treated with grapefruit extract. These results indicate that females learned fruit odor during exposure to grapefruit.     

What Are the Proteolytic Enzymes of Honey and What They Do Tell Us? A Fingerprint Analysis by 2-D Zymography of Unifloral Honeys

Honey is a sweet and healthy food produced by honeybees (Apis mellifera L.) from flower nectars. Using bidimensional zymography, we have detected the, until now unrevealed, proteolytic activities present in row honey samples. The resulting zymograms were specific for each type of the four unifloral honey under study, and enzymes were identified as serine proteases by the use of specific inhibitors. Further, using bidimensional electrophoresis, we have shown that honey proteases are able to degrade the major Royal Jelly proteins and in particular MRPJ-1, the protein that promotes queen differentiation in honeybees. Our findings open new perspectives for the better understanding of honeybee development, social behaviour and role in honey production. The now discovered honey proteases may influence honey properties and quality, and bidimensional zymograms might be useful to distinguish between different honey types, establish their age and floral origin, and allow honey certification.     

What Can the Brain Teach Us about Winemaking? An fMRI Study of Alcohol Level Preferences

Over the last few decades, wine makers have been producing wines with a higher alcohol content, assuming that they are more appreciated by consumers. To test this hypothesis, we used functional magnetic imaging to compare reactions of human subjects to different types of wine, focusing on brain regions critical for flavor processing and food reward. Participants were presented with carefully matched pairs of high- and low-alcohol content red wines, without informing them of any of the wine attributes. Contrary to expectation, significantly greater activation was found for low-alcohol than for high-alcohol content wines in brain regions that are sensitive to taste intensity, including the insula as well as the cerebellum. Wines were closely matched for all physical attributes except for alcohol content, thus we interpret the preferential response to the low-alcohol content wines as arising from top-down modulation due to the low alcohol content wines inducing greater attentional exploration of aromas and flavours. The findings raise intriguing possibilities for objectively testing hypotheses regarding methods of producing a highly complex product such as wine.     

What Do We Really Know about Cellulose Biosynthesis in Higher Plants?

Cellulose biosynthesis is one of the most important biochemical processes in plant biology. Despite the considerable progress made during the last decade, numerous fundamental questions related to this key process in plant development are outstanding. Numerous models have been proposed through the years to explain the detailed molecular events of cellulose biosynthesis. Almost all models integrate solid experimental data with hypotheses on several of the steps involved in the process. Speculative models are most useful to stimulate further research investigations and bring new exciting ideas to the field. However, it is important to keep their hypothetical nature in mind and be aware of the risk that some undemonstrated hypotheses may progressively become admitted. In this review, we discuss the different steps required for cellulose formation and crystallization, and highlight the most important specific aspects that are supported by solid experimental data.     

What Do We Really Know about Cellulose Biosynthesis in Higher Plants?

Cellulose biosynthesis is one of the most important biochemical processes in plant biology. Despite the considerable progress made during the last decade, numerous fundamental questions related to this key process in plant development are outstanding. Numerous models have been proposed through the years to explain the detailed molecular events of cellulose biosynthesis. Almost all models integrate solid experimental data with hypotheses on several of the steps involved in the process. Speculative models are...     

What Do Aquaporin Knockout Studies Tell Us about Fluid Transport in Epithelia?

The investigation of near-isosmotic water transport in epithelia goes back over 100 years; however, debates over mechanism and pathway remain. Aquaporin (AQP) knockouts have been used by various research groups to test the hypothesis of an osmotic mechanism as well as to explore the paracellular versus transcellular pathway debate. Nonproportional reductions in the water permeability of a water-transporting epithelial cell (e.g., a reduction of around 80–90 %) compared to the reduction in overall water transport rate in the knockout animal (e.g., a reduction of 50–60 %) are commonly found. This nonproportionality has led to controversy over whether AQP knockout studies support or contradict the osmotic mechanism. Arguments raised for and against an interpretation supporting the osmotic mechanism typically have partially specified, implicit, or incorrect assumptions. We present a simple mathematical model of the osmotic mechanism with clear assumptions and, for models based on this mechanism, establish a baseline prediction of AQP knockout studies. We allow for deviations from isotonic/isosmotic conditions and utilize dimensional analysis to reduce the number of parameters that must be considered independently. This enables a single prediction curve to be used for multiple epithelial systems. We find that a simple, transcellular-only osmotic mechanism sufficiently predicts the results of knockout studies and find criticisms of this mechanism to be overstated. We note, however, that AQP knockout studies do not give sufficient information to definitively rule out an additional paracellular pathway.     

Tracking Wetland Restoration: Do Mitigation Sites Follow Desired Trajectories?

Hypothetical models in the scientific literature suggest that ecosystem restoration and creation sites follow a smooth path of development (called a trajectory), rapidly matching natural reference sites (the target). Multi-million-dollar mitigation agreements have been based on the expectation that damages to habitat will be compensated within 5–10 years, and monitoring periods have been set accordingly. Our San Diego Bay study site, the Sweetwater Marsh National Wildlife Refuge, has one of the longest and most detailed records of habitat development at a mitigation site: data on soil organic matter, soil nitrogen, plant growth, and plant canopies for up to 10 years from a 12-year-old site. High interannual variation and lack of directional changes indicate little chance that targets will be reached in the near future. Other papers perpetuate the trajectory model, despite data that corroborate our findings. After reviewing “trajectory models” and presenting our comprehensive data for the first time, we suggest alternative management and mitigation policies.