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Phylogeographic inferences concerning evolution of Brazilian Passiflora actinia and P. elegans (Passifloraceae) based on ITS (nrDNA) variation.

BACKGROUND AND AIMS: Passiflora actinia and P. elegans, two markedly parapatric species, have their southern and northern distribution limits, respectively, in the most southern part of the Brazilian Atlantic Rain Forest. Despite the fact that they are classified in different taxonomic series, previous phylogenetic studies of this genus revealed a high genetic similarity between them. The aim of the present work was to analyse in more detail their geographical range in this region of overlap, to investigate intraspecific genetic variability and phylogeographic structure, and to search for possible hybrids. METHODS: Eighty-two localities were searched for these species, and nuclear internal transcribed spacer (ITS) sequences were investigated for 32 individuals of P. actinia, 20 of P. elegans and one putative interspecific hybrid. Plastid trnL-trnF and psbA-trnH were examined for 12 plants of each species and the putative hybrid. KEY RESULTS: Both species showed a high level of intraspecific and intra-individual ITS variability. Network analysis revealed a north-south geographic gradient in their intra and interspecific relationships. Mismatch analyses suggested a recent population expansion of P. elegans. The plastid markers showed restricted variability but, together with the nuclear data, they contributed to the identification of an interspecific hybrid of intermediate morphology at the border of the distribution of these two species. Both genetic and morphological data indicate the absence of an extensive hybridization zone between these species. CONCLUSIONS: Gene flow between lineages is the possible cause for the presence of different ITS sequences within a given plant, the absence of homogenization being due to the high degree of vegetative reproduction in the two species. Differentiation of P. actinia into geographic groups and the origin of P. elegans may have been influenced by the Atlantic Forest migration towards southern Brazil. The genetic pattern of the interspecific hybrid indicates that plastid inheritance in these species is at least sometimes paternal.

Base Sequence↗

Making sense of discourse: an fMRI study of causal inferencing across sentences.

To build up coherence between sentences (comprehend discourse), we must draw inferences, i.e. activate and integrate information that is not actually stated. We used event-related fMRI to determine the localization and extent of brain activity mediating causal inferencing across short, three-sentence scenarios. Participants read and made causal coherence judgments to sentences that were highly causally related, intermediately related or unrelated to their preceding two-sentence contexts. The highly related and intermediately related scenarios were matched in terms of semantic similarities between their individual component words. A pre-rating study established that causal inferences were generated to the intermediately related but not to the highly related or unrelated scenarios. In the scanner, sentences that were intermediately related (relative to highly related or unrelated) to their preceding contexts were associated with longer judgment reaction times and sustained increases in hemodynamic activity within left lateral temporal/inferior parietal/prefrontal cortices, the right inferior prefrontal gyrus and bilateral superior medial prefrontal cortices. In contrast, sentences that were unrelated (relative to highly related) to their preceding contexts were associated with only transient increases in activity (at, but not after, the peak of the hemodynamic response) within the right lateral temporal cortex and the right inferior prefrontal gyrus. These data suggest that, to make sense of discourse, we activate a large bilateral cortical network in response to what is not explicitly stated. We suggest that this network reflects the activation, retrieval and integration of information from long-term semantic memory into incoming discourse structure during causal inferencing.

Adult↗

Orientational order of the lamellipodial actin network as demonstrated in living motile cells.

Lamellipodia of crawling cells represent both the motor for cell advance and the primary building site for the actin cytoskeleton. The organization of actin in the lamellipodium reflects actin dynamics and is of critical importance for the mechanism of cell motility. In previous structural studies, the lamellipodial actin network was analyzed primarily by electron microscopy (EM). An understanding of lamellipodial organization would benefit significantly if the EM data were complemented and put into a kinetic context by establishing correspondence with structural features observable at the light microscopic level in living cells. Here, we use an enhanced phase contrast microscopy technique to visualize an apparent long-range diagonal actin meshwork in the advancing lamellipodia of living cells. Visualization of this meshwork permitted a correlative light and electron microscopic approach that validated the underlying organization of lamellipodia. The linear features in the light microscopic meshwork corresponded to regions of greater actin filament density. Orientation of features was analyzed quantitatively and compared with the orientation of actin filaments at the EM level. We infer that the light microscopic meshwork reflects the orientational order of actin filaments which, in turn, is related to their branching angle.

Actins↗

'Switching-off' of an auditory interneuron during stridulation in the acridid grasshopper Chorthippus biguttulus L.

In freely moving grasshoppers of the species Chorthippus biguttulus compound potentials were recorded from the neck connectives with chronically implanted hook electrodes. The spikes of one large auditory interneuron, known as the G-neuron (Kalmring 1975a, b) were clearly distinguishable in the recordings and the neuron was identified by its physiology and morphology. In quiescent grasshoppers the G-neuron responds to auditory and vibratory stimuli, but responses to both stimuli are suppressed during stridulation in males. When a male's wings were removed so that the stridulatory movements of its hindlegs produced no sound, the suppression of the G-neuron response still occurred. When proprioceptive feedback from the hindlegs was reduced, by forced autotomy of the legs, the switching-off remained incomplete (production of stridulatory patterns was inferred on the basis of electromyograms from the relevant thoracic musculature). Imposed movement of the hindlegs, on the other hand, suppressed the G-neuron response in a graded fashion, depending on the frequency of the movement. These experiments suggest that the switching-off is brought about by a combination of proprioceptive feedback and central efferences. The switching-off phenomenon could either protect the grasshopper's auditory pathway from undesired effects of overloading by its own intense song (e.g. self-induced habituation as described by Krasne and Wine 1977) and should therefore apply for most auditory neurons. Alternatively it could prevent escape reflexes from being triggered by stridulatory self-stimulation and consequently might apply only for neurons involved in such networks (as the G-neuron might be).

Animals↗

[Tuberculosis: suffering and illusions in interrupted treatment].

This study of tuberculosis patients who interrupt their treatment was carried out in the city of Porto Velho (RO) motivated by my belief that the interruption of this treatment is a challenge to collective health, due to the difficulties which health professional face with respect to the treatment and control of tuberculosis. The adopted qualitative approach and the use of the dialectic-hermeneutic method of analysis of the material, collected through interviews, led me to infer that the subjects of this study possessed little knowledge of tuberculosis, revealing the adoption of attitudes related to the impact which to the diagnosis and the prolonged treatment caused them and the social environment in which they live. For the twelve patients who participated in this study, the motives for interruption of treatment were related to reasons rooted in the non-spoken and in causes like the collateral effects of medicines, the disorganization of services and the illusion of being cured. This has important implications for our technical-methodological positions and for the patient-professional relationship, in our search for an approach which allows us to face the binomial tuberculosis-interruption of treatment as experiences undergone by patients, families and the social networks constructed by them over time.

Humans↗

Mirror neurons and imitation: a computationally guided review.

Neurophysiology reveals the properties of individual mirror neurons in the macaque while brain imaging reveals the presence of 'mirror systems' (not individual neurons) in the human. Current conceptual models attribute high level functions such as action understanding, imitation, and language to mirror neurons. However, only the first of these three functions is well-developed in monkeys. We thus distinguish current opinions (conceptual models) on mirror neuron function from more detailed computational models. We assess the strengths and weaknesses of current computational models in addressing the data and speculations on mirror neurons (macaque) and mirror systems (human). In particular, our mirror neuron system (MNS), mental state inference (MSI) and modular selection and identification for control (MOSAIC) models are analyzed in more detail. Conceptual models often overlook the computational requirements for posited functions, while too many computational models adopt the erroneous hypothesis that mirror neurons are interchangeable with imitation ability. Our meta-analysis underlines the gap between conceptual and computational models and points out the research effort required from both sides to reduce this gap.

Animals↗

Molecular change signal-to-noise criteria for interpreting experiments involving exposure of biological systems to weakly interacting electromagnetic fields.

We describe an approach to aiding the design and interpretation of experiments involving biological effects of weakly interacting electromagnetic fields that range from steady (dc) to microwave frequencies. We propose that if known biophysical mechanisms cannot account for an inferred, underlying molecular change signal-to-noise ratio, (S/N)gen, of a observed result, then there are two interpretation choices: (1) there is an unknown biophysical mechanism with stronger coupling between the field exposure and the ongoing biochemical process, or (2) the experiment is responding to something other than the field exposure. Our approach is based on classical detection theory, the recognition that weakly interacting fields cannot break chemical bonds, and the consequence that such fields can only alter rates of ongoing, metabolically driven biochemical reactions, and transport processes. The approach includes both fundamental chemical noise (molecular shot noise) and other sources of competing chemical change, to be compared quantitatively to the field induced change for the basic case that the field alters a single step in a biochemical network. Consistent with pharmacology and toxicology, we estimate the molecular dose (mass associated with field induced molecular change per mass tissue) resulting from illustrative low frequency field exposures for the biophysical mechanism of voltage gated channels. For perspective, we then consider electric field-mediated delivery of small molecules across human skin and into individual cells. Specifically, we consider the examples of iontophoretic and electroporative delivery of fentanyl through skin and electroporative delivery of bleomycin into individual cells. The total delivered amount corresponds to a molecular change signal and the delivery variability corresponds to generalized chemical noise. Viewed broadly, biological effects due to nonionizing fields may include animal navigation, medical applications, and environmental hazards. Understanding necessary conditions for such effects can be based on a unified approach: quantitative comparison of the estimated chemical change due to a particular electromagnetic field exposure to that due to competing influences, with both estimates based on a biophysical mechanism model within the context of a model of a biological system.

Animals↗

Refined 2.3 A X-ray crystal structure of bovine thrombin complexes formed with the benzamidine and arginine-based thrombin inhibitors NAPAP, 4-TAPAP and MQPA. A starting point for improving antithrombotics.

Well-diffracting crystals of bovine epsilon-thrombin in complex with several "non-peptidic" benzamidine and arginine-based thrombin inhibitors have been obtained by co-crystallization. The 2.3 A crystal structures of three complexes formed either with NAPAP, 4-TAPAP, or MQPA, were solved by Patterson search methods and refined to crystallographic R-values of 0.167 to 0.178. The active-site environment of thrombin is only slightly affected by binding of the different inhibitors; in particular, the exposed "60-insertion loop" essentially maintains its typical projecting structure. The D-stereoisomer of NAPAP and the L-stereoisomer of MQPA bind to thrombin with very similar conformations, as previously inferred from their binding to bovine trypsin; the arginine side-chain of the latter inserts into the specificity pocket in a "non-canonical" manner. The L-stereoisomer of 4-TAPAP, whose binding geometry towards trypsin was only poorly defined, is bound to the thrombin active-site in a compact conformation. In contrast to NAPAP, the distal p-amidino/guanidino groups of 4-TAPAP and MQPA do not interact with the carboxylate group of Asp189 in the thrombin specificity pocket in a "symmetrical" twin N-twin O manner, but through "lateral" single N-twin O contacts; in contrast to the p-amidino group of 4-TAPAP, however, the guanidyl group of MQPA packs favourably in the pocket due to an elaborate hydrogen bond network, which includes two entrapped water molecules. These thrombin structures confirm previous conclusions of the important role of the intermolecular hydrogen bonds formed with Gly216, and of the good sterical fit of the terminal bulky hydrophobic inhibitor groups with the hydrophobic aryl binding site and the S2-cavity, respectively, for tight thrombin active site binding of these non-peptidic inhibitors. These accurate crystal structures are presumed to be excellent starting points for the design and the elaboration of improved antithrombotics.

Amidines↗

Review of operation of urban drainage systems in cold weather: water quality considerations.

Cold climate imposes special requirements on urban drainage systems, arising from extended storage of precipitation and pollutants in the catchment snowpack, processes occurring in the snowpack, and changes in catchment surface and transport network by snow and ice. Consequently, the resulting catchment response and runoff quantity differ from those experienced in snow- and ice-free seasons. Sources of pollutants entering urban snowpacks include airborne fallout, pavement and roadside deposits, and applications of de-icing and anti-skid agents. In the snowpack, snow, water and chemicals are subject to various processes, which affect their movement through the pack and eventual release during the melting process. Soluble constituents are flushed from the snowpack early during the melt; hydrophobic substances generally stay in the pack until the very end of melt and coarse solids with adsorbed pollutants stay on the ground after the melt is finished. The impacts of snowmelt on receiving waters have been measured mostly by the snowmelt chemical composition and inferences about its environmental significance. Recently, snowmelt has been tested by standard bioassays and often found toxic. Toxicity was attributed mostly to chloride and trace metals, and contributed to reduced diversity of benthic and plant communities. Thus, snowmelt and winter runoff discharged from urban drainage threaten aquatic ecosystems in many locations and require further studies with respect to advancing their understanding and development of best management practices.

Cities↗

Online tuning of fuzzy inference systems using dynamic fuzzy Q-learning.

This paper presents a dynamic fuzzy Q-learning (DFQL) method that is capable of tuning fuzzy inference systems (FIS) online. A novel online self-organizing learning algorithm is developed so that structure and parameters identification are accomplished automatically and simultaneously based only on Q-learning. Self-organizing fuzzy inference is introduced to calculate actions and Q-functions so as to enable us to deal with continuous-valued states and actions. Fuzzy rules provide a natural mean of incorporating the bias components for rapid reinforcement learning. Experimental results and comparative studies with the fuzzy Q-learning (FQL) and continuous-action Q-learning in the wall-following task of mobile robots demonstrate that the proposed DFQL method is superior.

Algorithms↗

Construction of an in vitro bistable circuit from synthetic transcriptional switches.

Information processing using biochemical circuits is essential for survival and reproduction of natural organisms. As stripped-down analogs of genetic regulatory networks in cells, we engineered artificial transcriptional networks consisting of synthetic DNA switches, regulated by RNA signals acting as transcription repressors, and two enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H. The synthetic switch design is modular with programmable connectivity and allows dynamic control of RNA signals through enzyme-mediated production and degradation. The switches support sharp and adjustable thresholds using a competitive hybridization mechanism, allowing arbitrary analog or digital circuits to be created in principle. As an example, we constructed an in vitro bistable memory by wiring together two synthetic switches and performed a systematic quantitative characterization. Good agreement between experimental data and a simple mathematical model was obtained for switch input/output functions, phase plane trajectories, and the bifurcation diagram for bistability. Construction of larger synthetic circuits provides a unique opportunity for evaluating model inference, prediction, and design of complex biochemical systems and could be used to control nanoscale devices and artificial cells.

Escherichia coli↗

Stochastic models of neuronal dynamics.

Cortical activity is the product of interactions among neuronal populations. Macroscopic electrophysiological phenomena are generated by these interactions. In principle, the mechanisms of these interactions afford constraints on biologically plausible models of electrophysiological responses. In other words, the macroscopic features of cortical activity can be modelled in terms of the microscopic behaviour of neurons. An evoked response potential (ERP) is the mean electrical potential measured from an electrode on the scalp, in response to some event. The purpose of this paper is to outline a population density approach to modelling ERPs. We propose a biologically plausible model of neuronal activity that enables the estimation of physiologically meaningful parameters from electrophysiological data. The model encompasses four basic characteristics of neuronal activity and organization: (i) neurons are dynamic units, (ii) driven by stochastic forces, (iii) organized into populations with similar biophysical properties and response characteristics and (iv) multiple populations interact to form functional networks. This leads to a formulation of population dynamics in terms of the Fokker-Planck equation. The solution of this equation is the temporal evolution of a probability density over state-space, representing the distribution of an ensemble of trajectories. Each trajectory corresponds to the changing state of a neuron. Measurements can be modelled by taking expectations over this density, e.g. mean membrane potential, firing rate or energy consumption per neuron. The key motivation behind our approach is that ERPs represent an average response over many neurons. This means it is sufficient to model the probability density over neurons, because this implicitly models their average state. Although the dynamics of each neuron can be highly stochastic, the dynamics of the density is not. This means we can use Bayesian inference and estimation tools that have already been established for deterministic systems. The potential importance of modelling density dynamics (as opposed to more conventional neural mass models) is that they include interactions among the moments of neuronal states (e.g. the mean depolarization may depend on the variance of synaptic currents through nonlinear mechanisms).Here, we formulate a population model, based on biologically informed model-neurons with spike-rate adaptation and synaptic dynamics. Neuronal sub-populations are coupled to form an observation model, with the aim of estimating and making inferences about coupling among sub-populations using real data. We approximate the time-dependent solution of the system using a bi-orthogonal set and first-order perturbation expansion. For didactic purposes, the model is developed first in the context of deterministic input, and then extended to include stochastic effects. The approach is demonstrated using synthetic data, where model parameters are identified using a Bayesian estimation scheme we have described previously.

Bayes Theorem↗

Restricted gene flow between two social forms in the ant Formica truncorum.

We studied genetic differentiation between two social forms (M-type: single queen, independent nest founding; P-type: multiple queens, dependent nest founding, building of colonial networks) of the ant Formica truncorum in a locality where the social types characterize two sympatric populations. The genetic results indicate restricted gene flow between the social forms. Female gene flow between the forms appears to be absent as they did not share mitochondrial haplotypes. Significant nuclear differentiation and the distribution of private alleles suggest that male gene flow between the forms is weak. However, the assignment analysis indicates some gene flow with P males mating with M females. The results have potentially important implications concerning social evolution within the forms but they need to be confirmed in other localities before they can be generalized. The colonies in the M-type population have earlier been shown to produce split sex ratios, depending on the mating frequency of the queens. The inferred gene flow from the P to the M type means that the split sex ratio is partly suboptimal, possibly because the P populations are not long-lived enough to influence the behavioural decisions in the M colonies.

Animals↗

Recent speciation in the Formica rufa group ants (Hymenoptera, Formicidae): inference from mitochondrial DNA phylogeny.

This study examines phylogenetic relationships among six species of the Formica rufa group ants (F. polyctena, F. rufa, F. lugubris, F. paralugubris, F. aquilonia, and F. pratensis). The phylogeny based on a 2051bp fragment of mtDNA including cyt b, tRNASer, and ND1 genes supports the division of the group into three major clusters: one with the species F. polyctena and F. rufa, one with F. aquilonia, F. lugubris, and F. paralugubris, and the third one with F. pratensis. The interspecific divergence estimates (mean 0.98 +/- 0.15% for the main phylogenetic groups) imply that radiation took place during the Pleistocene. Comparison of the divergence estimates among the F. rufa group species with divergence estimates among other closely related species of insects suggests that speciation in the group was relatively fast, and the mitochondrial lineages of F. polyctena and F. rufa have not fully separated. The haplotype tree shows also signs of transfer of mtDNA between species through hybridisation. The distribution of polygyny (multiple queens per nest) along the branches of the tree indicates that the social type characterised by highly polygynous societies and large colonial networks, has originated at least three times. The species F. aquilonia and F. paralugubris that build such large supercolonies, cluster tightly together with very little nucleotide variation, suggesting that this type of social organisation could be a factor promoting speciation in the ants.

Animals↗

Comparing dynamic causal models.

This article describes the use of Bayes factors for comparing dynamic causal models (DCMs). DCMs are used to make inferences about effective connectivity from functional magnetic resonance imaging (fMRI) data. These inferences, however, are contingent upon assumptions about model structure, that is, the connectivity pattern between the regions included in the model. Given the current lack of detailed knowledge on anatomical connectivity in the human brain, there are often considerable degrees of freedom when defining the connectional structure of DCMs. In addition, many plausible scientific hypotheses may exist about which connections are changed by experimental manipulation, and a formal procedure for directly comparing these competing hypotheses is highly desirable. In this article, we show how Bayes factors can be used to guide choices about model structure, both concerning the intrinsic connectivity pattern and the contextual modulation of individual connections. The combined use of Bayes factors and DCM thus allows one to evaluate competing scientific theories about the architecture of large-scale neural networks and the neuronal interactions that mediate perception and cognition.

Attention↗

comK encodes the competence transcription factor, the key regulatory protein for competence development in Bacillus subtilis.

comK is a positive autoregulatory gene occupying a central position in the competence-signal-transduction network. All regulatory routes identified in this network converge at the level of comK expression. The ComK protein is required for the transcriptional induction of comK and the late competence genes, which specify morphogenetic and structural proteins necessary for construction of the DNA-binding and uptake apparatus. In this report we demonstrate that ComK specifically binds to DNA fragments containing promoter and upstream sequences of the genes it affects (comC, comE, comF, comG and comK). Using portions of the region upstream of comC we show that the ComK-binding sequences are essential for the expression of competence. Moreover, we demonstrate that the presence of ComK stimulates the expression of comF-lacZ and comG-lacZ translational fusions in vivo in Escherichia coli. These results indicate that the gene product of comK is identical to the previously inferred competence transcription factor (CTF).

Amino Acid Sequence↗

Matrilineal fertility inheritance detected in hunter-gatherer populations using the imbalance of gene genealogies.

Fertility inheritance, a phenomenon in which an individual's number of offspring is positively correlated with his or her number of siblings, is a cultural process that can have a strong impact on genetic diversity. Until now, fertility inheritance has been detected primarily using genealogical databases. In this study, we develop a new method to infer fertility inheritance from genetic data in human populations. The method is based on the reconstruction of the gene genealogy of a sample of sequences from a given population and on the computation of the degree of imbalance in this genealogy. We show indeed that this level of imbalance increases with the level of fertility inheritance, and that other phenomena such as hidden population structure are unlikely to generate a signal of imbalance in the genealogy that would be confounded with fertility inheritance. By applying our method to mtDNA samples from 37 human populations, we show that matrilineal fertility inheritance is more frequent in hunter-gatherer populations than in food-producer populations. One possible explanation for this result is that in hunter-gatherer populations, individuals belonging to large kin networks may benefit from stronger social support and may be more likely to have a large number of offspring.

Allelic Imbalance↗

An oscillatory short-term memory buffer model can account for data on the Sternberg task.

A limited number (7 +/- 2) of items can be held in human short-term memory (STM). We have previously suggested that observed dual (theta and gamma) oscillations could underlie a multiplexing mechanism that enables a single network to actively store up to seven memories. Here we have asked whether models of this kind can account for the data on the Sternberg task, the most quantitative measurements of memory search available. We have found several variants of the oscillatory search model that account for the quantitative dependence of the reaction time distribution on the number of items (S) held in STM. The models differ on the issues of (1) whether theta frequency varies with S and (2) whether the phase of ongoing oscillations is reset by the probe. Using these models the frequencies of dual oscillations can be derived from psychophysical data. The derived values (ftheta = 6-10 Hz; fgamma = 45-60 Hz) are in reasonable agreement with experimental values. The exhaustive nature of the serial search that has been inferred from psychophysical measurements can be plausibly explained by these oscillatory models. One argument against exhaustive serial search has been the existence of serial position effects. We find that these effects can be explained by short-term repetition priming in the context of serial scanning models. Our results strengthen the case for serial processing and point to experiments that discriminate between variants of the serial scanning process.

Biological Clocks↗