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Computing prokaryotic gene ubiquity: rescuing the core from extinction.

The genomic core concept has found several uses in comparative and evolutionary genomics. Defined as the set of all genes common to (ubiquitous among) all genomes in a phylogenetically coherent group, core size decreases as the number and phylogenetic diversity of the relevant group increases. Here, we focus on methods for defining the size and composition of the core of all genes shared by sequenced genomes of prokaryotes (Bacteria and Archaea). There are few (almost certainly less than 50) genes shared by all of the 147 genomes compared, surely insufficient to conduct all essential functions. Sequencing and annotation errors are responsible for the apparent absence of some genes, while very limited but genuine disappearances (from just one or a few genomes) can account for several others. Core size will continue to decrease as more genome sequences appear, unless the requirement for ubiquity is relaxed. Such relaxation seems consistent with any reasonable biological purpose for seeking a core, but it renders the problem of definition more problematic. We propose an alternative approach (the phylogenetically balanced core), which preserves some of the biological utility of the core concept. Cores, however delimited, preferentially contain informational rather than operational genes; we present a new hypothesis for why this might be so.

Conserved Sequence↗

A comparison of cortical elastic properties in the craniofacial skeletons of three primate species and its relevance to the study of human evolution.

When a force is applied to an object, the resulting pattern of strain is a function of both the object's geometry and its elastic properties. Thus, knowledge of elastic properties in craniofacial cortical bone is indispensable for exploring the biomechanics and adaptation of primate skulls. However, elastic properties, such as density and stiffness, cannot be measured in all species, particularly extinct species known only from fossils. In order for advanced engineering techniques such as finite element analysis (FEA) to be applied to questions of primate and hominid craniofacial functional morphology, it is important to understand interspecific patterns of variation in elastic properties. We hypothesized that closely related species would have similar patterns of bone elastic properties, and that similarities with extant species should allow reasonable predictions of elastic properties in the skeletons of extinct primate species. In this study, we tested this hypothesis by measuring elastic properties in five areas of the external cortex of the baboon craniofacial skeleton using an ultrasonic technique, and by comparing the results to existing data from macaque and human crania. Results showed that cortical density, thickness, elastic and shear moduli, and anisotropy varied among areas in the baboon cranium. Similar variation had previously been found in rhesus and human crania, suggesting area-specific elastic patterns in the skulls of each species. Comparison among species showed differences, suggesting species-specific patterns. These patterns were more similar between macaques and baboons for density, maximum elastic and shear stiffness, and anisotropy than between either of these and humans. This finding demonstrates that patterns of cortical elastic properties are generally similar in closely related primate species with similar craniofacial morphology. Thus, reasonable estimates of cortical bone elastic properties should be possible for extinct species through the study of phylogenetically related and functionally similar modern forms. For example, reasonable elastic property estimates of cortical bone from fossil hominid skulls should be possible once adequate information about such properties in extant great apes is added to our current data from humans, macaques, and baboons. Such data should eventually allow FEA of craniofacial function in fossil hominids.

Animals↗

An individual-based model of Plasmodium falciparum malaria transmission on the coast of Kenya.

Individual-based models provide powerful tools to model complex interactions characterized by individual variability. This paper presents an object-oriented design for individual-based modelling of Plasmodium falciparum malaria transmission. Two kinds of objects, human and mosquito, that exhibit variability among individuals for parameters such as recovery and survival rates are defined. The model tracks the dynamics of human hosts and adult female mosquitoes individually. Immunity, modelled as a function of exposure history, is represented by reduced susceptibility and increased recovery rate. The model was calibrated using epidemiological data collected at 30 sites along the coast of Kenya. The sites were grouped into low, intermediate and high transmission based on mean daily human-biting rates. Simulation results show that malaria transmission was stable even in low transmission areas where the human-biting rate is approximately 0.5 bite per day. The model was used to examine the effect of infection control programmes that aim at interrupting transmission by reducing human-vector contact rates and implementing active case detection and drug treatment of infections. With this intervention, local elimination of malaria is likely with a probability of extinction of approximately 0.8 in low transmission areas. However, a small amount of immigration (> 0.3%) by infected people into the community could prevent local extinction of the parasite. In intermediate and high transmission areas, reduction in prevalence is short-lived and the probability of local elimination is low, even at high coverage levels of the intervention.

Age Distribution↗

Isolation and characterization of a basic encephalitogenic protein from the central nervous system of sheep.

A basic protein has been purified from sheep brain. The purified protein sedimented in the analytical centrifuge at 56,000 r.p.m. as an homogenous product. This protein induced an allergic encephalitis when injected into guinea pigs. Some physiochemical properties of the protein were studied: the sedimentation coefficient was 1.52 and the molecular weight was 20,000 +/- 2,000, as estimated by electrophoresis in acrylamide gels containing SDS and urea; the specific extinction coefficient (see article) was 6.01 +/- 0.20. The aminoacid composition of the molecule was determined and its most prominent aspects are a high content of arginine and lysine, the presence of a single tryptophan, the total absence of cysteine and cystine and a blocked N-terminal residue. All these properties are very close to those of human and bovine encephalitogenic proteins.

Amino Acids↗

New ages for human occupation and climatic change at Lake Mungo, Australia.

Australia's oldest human remains, found at Lake Mungo, include the world's oldest ritual ochre burial (Mungo III) and the first recorded cremation (Mungo I). Until now, the importance of these finds has been constrained by limited chronologies and palaeoenvironmental information. Mungo III, the source of the world's oldest human mitochondrial DNA, has been variously estimated at 30 thousand years (kyr) old, 42-45 kyr old and 62 +/- 6 kyr old, while radiocarbon estimates placed the Mungo I cremation near 20-26 kyr ago. Here we report a new series of 25 optical ages showing that both burials occurred at 40 +/- 2 kyr ago and that humans were present at Lake Mungo by 50-46 kyr ago, synchronously with, or soon after, initial occupation of northern and western Australia. Stratigraphic evidence indicates fluctuations between lake-full and drier conditions from 50 to 40 kyr ago, simultaneously with increased dust deposition, human arrival and continent-wide extinction of the megafauna. This was followed by sustained aridity between 40 and 30 kyr ago. This new chronology corrects previous estimates for human burials at this important site and provides a new picture of Homo sapiens adapting to deteriorating climate in the world's driest inhabited continent.

Adaptation, Physiological↗

Selection for intermediate mortality and reproduction rates in a spatially structured population.

How local interactions influence both population and evolutionary dynamics is currently a key topic in theoretical ecology. We use a 'well-mixed' analytical model and spatially explicit individual-based models to investigate a system where a population is subject to rare disturbance events. The disturbance can only propagate through regions of the population where the density of individuals is sufficiently high and individuals affected by the disturbance die shortly after. We find that populations where individuals are sessile often exhibit very different dynamic behaviour when compared to populations where individuals are mobile and spatially well mixed. When mutations are allowed which affect either offspring birth rates or mortality rates, the well-mixed populations always evolve to a state where a single disturbance event leads to extinction. Populations often persist substantially longer if individuals are sessile and they disperse their offspring locally. We also find that for sessile populations selection may favour short-lived individuals with limited offspring production. Population dynamics are found to be strongly influenced by the host characters that are evolving and the rate at which host variation is introduced into the system.

Animals↗

Several million years of stability among insect species because of, or in spite of, Ice Age climatic instability?

There is a curious paradox in the evolutionary legacy of Ice Ages. Studies of modern species suggest that they are currently evolving in response to changing environments. If extrapolated into the context of Quaternary Ice Ages, this evidence would suggest that the frequent climatic changes should have stimulated the evolutionary process and thus increased the rates of change within species and the number of speciation events. Extinction rates would, similarly, be high. Quaternary insect studies call into question these interpretations. They indicate that insect species show a remarkable degree of stability throughout the Ice Age climatic oscillations. The paradox arises from the apparent contradiction between abundant evidence of incipient speciation in insect populations at the present day and the evidence that, in the geological past, this apparently did not lead to sustained evolution.

Animals↗

Distributed delays stabilize ecological feedback systems.

We consider the effect of distributed delays in predator-prey models and ecological food webs. Whereas the occurrence of delays in population dynamics is usually regarded a destabilizing factor leading to the extinction of species, we here demonstrate complementarily that delay distributions yield larger stability regimes than single delays. Food webs with distributed delays closely resemble nondelayed systems in terms of ecological stability measures. Thus, we state that dependence of dynamics on multiple instances in the past is an important, but so far underestimated, factor for stability in dynamical systems.

Animals↗

Visualization by a matrix of light-emitting diodes of interference effects from a radiative four-applicator hyperthermia system.

A simple, unique tool has been constructed at a very low cost for visualization of the electric field distribution in a phantom exposed to radiofrequency fields from a four-applicator hyperthermia system. The tool consists of a thin Perspex plate to which light-emitting diodes (LEDs) have been attached in a regular pattern. The leads of these LEDs have been bent in the form of dipoles. Electric field distributions can be made visible, because the light intensity from an individual LED dipole in a RF field is a function of the local electric field strength. The LED dipoles were arranged in a 11 x 15 matrix with a mutual distance of 2 cm. Experiments have been performed in a cylinder with a length of 100 cm and with an elliptical cross-section of 24 cm x 36 cm. The cylinder was filled with saline to simulate the electric properties of biological tissue. The matrix plate was shaped like the cross-section inside the phantom, and could be moved to any position under the externally applied antennae. In our department the applicators installed form a system of four coherent waveguide radiators operating at a frequency of 70 MHz. Photographs have been taken from the distribution of the light intensity through transparent windows at the outer ends of the phantom. The advantage of the LED matrix is the fact that the effect of changing phase relations, amplitudes or position of any applicator on the electric field distribution can be seen instantaneously. The interference effects of multiple fields, i.e. extinction and reinforcement, become easily visible. Typical examples demonstrate the necessity to obtain the field distribution not only along some previously chosen lines, but in the whole transversal midplane. The attenuation of field strength due to the presence of the matrix varies only slightly from the edge to the centre of the matrix, so the pattern of light intensity is in good qualitative agreement with the pattern of field strength. The LED matrix has been very useful in the verification of pretreatment planning calculations, and is already used for intercomparison and evaluation studies of similar hyperthermia equipment.

Biophysical Phenomena↗

Single-species models of the Allee effect: extinction boundaries, sex ratios and mate encounters.

We critically review and classify models of single-species population dynamics subject to the demographic Allee effect with emphasis on non-spatial, deterministic approach. Inclusion of spatial movement and stochastic phenomena does not substantially change the behaviour; stochasticity only "blurs" step-like character of the Allee effect into a sigmoidal form. The outcome of all non-spatial, deterministic models is either unconditional extinction, extinction-survival scenario (ES), or unconditional survival. Three major model classes are recognized: (1) one-dimensional heuristic models, (2) one-dimensional models with mating probability and fixed sex ratio, and (3) two-sex models with variable adult sex ratio. Each class is characterized by the shape of extinction boundary which separates extinction from survival in the ES scenario. The latter two classes may give better predictions of extinction thresholds than heuristic models but require specific information and are data intensive. In one-dimensional models with fixed sex ratio, population cannot survive if density/number of males decreases below some threshold while there is no such restriction on females. Individual-based models seem to be most capable of explaining mechanisms leading to the Allee effect.

Animals↗

Biochemistry, mutagenesis, and oligomerization of DsRed, a red fluorescent protein from coral.

DsRed is a recently cloned 28-kDa fluorescent protein responsible for the red coloration around the oral disk of a coral of the Discosoma genus. DsRed has attracted tremendous interest as a potential expression tracer and fusion partner that would be complementary to the homologous green fluorescent protein from Aequorea, but very little is known of the biochemistry of DsRed. We now show that DsRed has a much higher extinction coefficient and quantum yield than previously reported, plus excellent resistance to pH extremes and photobleaching. In addition, its 583-nm emission maximum can be further shifted to 602 nm by mutation of Lys-83 to Met. However, DsRed has major drawbacks, such as strong oligomerization and slow maturation. Analytical ultracentrifugation proves DsRed to be an obligate tetramer in vitro, and fluorescence resonance energy transfer measurements and yeast two-hybrid assays verify oligomerization in live cells. Also, DsRed takes days to ripen fully from green to red in vitro or in vivo, and mutations such as Lys-83 to Arg prevent the color change. Many potential cell biological applications of DsRed will require suppression of the tetramerization and acceleration of the maturation.

Amino Acid Sequence↗

Body size and species-richness in carnivores and primates.

We use complete species-level phylogenies of extant Carnivora and Primates to perform the first thorough phylogenetic tests, in mammals, of the hypothesis that small body size is associated with species-richness. Our overall results, based on comparisons between sister clades, indicate a weak tendency for lineages with smaller bodies to contain more species. The tendency is much stronger within caniform carnivores (canids, procyonids, pinnipeds, ursids and mustelids), perhaps relating to the dietary flexibility and hence lower extinction rates in small, meat-eating species. We find significant heterogeneity in the size-diversity relationship within and among carnivore families. There is no significant association between body mass and species-richness in primates or feliform carnivores. Although body size is implicated as a correlate of species-richness in mammals, much of the variation in diversity cannot be attributed to size differences.

Animals↗

Pollination decays in biodiversity hotspots.

As pollinators decline globally, competition for their services is expected to intensify, and this antagonism may be most severe where the number of plant species is the greatest. Using meta-analysis and comparative phylogenetic analysis, we provide a global-scale test of whether reproduction becomes more limited by pollen receipt (pollen limitation) as the number of coexisting plant species increases. As predicted, we find a significant positive relationship between pollen limitation and species richness. In addition, this pattern is particularly strong for species that are obligately outcrossing and for trees relative to herbs or shrubs. We suggest that plants occurring in species-rich communities may be more prone to pollen limitation because of interspecific competition for pollinators. As a consequence, plants in biodiversity hotspots may have a higher risk of extinction and/or experience increased selection pressure to specialize on certain pollinators or diversify into different phenological niches. The combination of higher pollen limitation and habitat destruction represents a dual risk to tropical plant species that has not been previously identified.

Biodiversity↗

Some results for an SEIR epidemic model with density dependence in the death rate.

This paper deals with an SEIR epidemic model for an infectious disease where the death rate depends on the number of individuals in the population. It is also assumed that there is an additional death rate suffered by infected individuals. It is found that there are three steady-state values: one where the population is extinct, one where the population maintains itself at a constant level and the disease is extinct, and one where there is a unique equilibrium with disease present. An interesting and unusual feature is that it is possible for this third equilibrium to exist and be locally unstable. Numerical work and simulation show that we can have cycles of disease incidence with increasing amplitude, a constant amplitude, and a decreasing amplitude, depending on the parameter values of the model.

Animals↗

Compensating for our load of mutations: freezing the meltdown of small populations.

We have investigated the reduction of fitness caused by the fixation of new deleterious mutations in small populations within the framework of Fisher's geometrical model of adaptation. In Fisher's model, a population evolves in an n-dimensional character space with an adaptive optimum at the origin. The model allows us to investigate compensatory mutations, which restore fitness losses incurred by other mutations, in a context-dependent manner. We have conducted a moment analysis of the model, supplemented by the numerical results of computer simulations. The mean reduction of fitness (i.e., expected load) scaled to one is approximately n/(n+2Ne), where Ne is the effective population size. The reciprocal relationship between the load and Ne implies that the fixation of deleterious mutations is unlikely to cause extinction when there is a broad scope for compensatory mutations, except in very small populations. Furthermore, the dependence of load on n implies that pleiotropy plays a large role in determining the extinction risk of small populations. Differences and similarities between our results and those of a previous study on the effects of Ne and n are explored. That the predictions of this model are qualitatively different from studies ignoring compensatory mutations implies that we must be cautious in predicting the evolutionary fate of small populations and that additional data on the nature of mutations is of critical importance.

Animals↗

Non-invasive imaging of carcinogen-induced early neoplasia using ultrahigh-resolution optical coherence tomography.

BACKGROUND AND OBJECTIVE: Improved diagnostics capable of non-invasive detection of early stage carcinogenesis would benefit basic research, and potentially aid in clinical cancer diagnosis and management. The two-stage carcinogenesis protocol is widely used for studying the multi-stage nature of tumor development in mice and provides insight into tumor development in other animal models and humans. The objective of this study was to investigate the feasibility of non-invasive optical coherence tomography (OCT) for in vivo imaging of microanatomical changes in the epidermis and dermis during early carcinogenesis using a mouse skin model. MATERIALS AND METHODS: 10 NIH mice were treated with DMBA and TPA following the well-established two-stage carcinogenesis protocol. OCT imaging of treated skin from live mice was performed at five time points (Week 4-8) after tumor initiation to reveal the structural changes in the epidermis and dermis associated with the earliest, premalignant stages of tumor development. OCT images were compared with histology findings. In addition, OCT signals were quantitatively analyzed to evaluate tissue optical property changes during early carcinogenesis. RESULTS: Early structural changes in the epidermis, dermis and hair follicles during carcinogenesis were clearly delineated in vivo using OCT. OCT images correlated well with histological findings. Quantitative OCT signal analysis revealed a statistically significant change in the extinction coefficient for untreated (40.5 +/- 17.0 mm(-1)) and treated (9.6 +/- 3.6 mm(-1)) mouse epidermis (P < 0.005). The dermis extinction coefficient for the treated mouse skin (3.7 +/- 0.9 mm(-1)) was lower than the untreated one (4.7 +/- 1.6 mm(-1)), but was not statistically significant (P > 0.10). Furthermore, the papilloma extinction coefficient (2.9 +/- 0.3 mm(-1)) was significantly lower than the extinction coefficient for the treated epidermis (P < 0.005) and dermis (P < 0.01). CONCLUSION: OCT is a viable tool for assessing the earliest stages of carcinogenesis and has potential for early detection of neoplasia in skin, as well as in epithelial linings of other organs.

9,10-Dimethyl-1,2-benzanthracene↗

High-order behaviour in learning gate networks with lateral inhibition.

In this work we present a neural network model incorporating activity-dependent presynaptic facilitation with multidimensional inputs. The processing unit used is based on a slightly simplified version of the Learning Gate Model proposed by Ciaccia et al. (1992). The network topology integrates a well-known biological neural circuit with a lateral inhibition connection subnet. By means of simulation experiments, we show that the proposed networks exhibit basic and high-order features of associative learning. In particular, overshadowing and blocking are reproduced in the presence of both noise-free and noisy inputs. The role of noise in the development of high-order learning capabilities is also discussed.

Animals↗

Continuous measurement of mitochondrial pH gradients in isolated hepatocytes by difference ratio spectroscopy.

The pH gradient, delta pH, present across the inner mitochondrial membrane in isolated rat hepatocytes was continuously monitored with a novel spectroscopic technique that utilizes the weak acid fluorescein. Unlike most cytosolic pH indicators, such as 2',7'-bis(carboxyethyl)-5,(6)-carboxyfluorescein (BCECF), fluorescein freely distributes between the cytosolic and mitochondrial compartments. As is typical for weak acids, the distribution between these two compartments is governed by the magnitude of the pH gradient. Since fluorescein has two ionizable groups, the fluorescein dianion is concentrated in the mitochondrial compartment 100-fold per delta pH unit. In this compartment, fluorescein absorbance (or excitation) spectra are red-shifted about 6-8 nm in the matrix environment, as compared to the cytosolic dye at equivalent pH values. The combination of favorable mitochondrial accumulation and red-shifted spectra enables mitochondrial pH to be continuously monitored qualitatively in whole cells by dual wavelength spectroscopy (510 minus 540 nm). When the cytosolic pH is determined by independent means, the mitochondrial pH can be quantitated, based on the theoretical dependence of the fluorescein distribution ratio on delta pH, the ratio of cytosolic to mitochondrial volumes, and the known extinction coefficients for the dye in the cytosolic and mitochondrial compartments. The sensitivity of the method for following kinetic responses in mitochondrial pH is especially noteworthy; a 0.1-unit change in delta pH is easily distinguished, with a time resolution of less than a second.

Animals↗