Mental representation of number in different numerical forms

How are numerical operations implemented within the human brain? It has been suggested that there are at least three different codes for representing number: a verbal code that is used to manipulate number words and perform mental numerical operations (e.g., multiplication), a visual code that is used to decode frequently used visual number forms (e.g., Arabic digits), and an abstract analog code that may be used to represent numerical quantities. Furthermore, each of these codes is associated with a different neural substrate. We extend these studies using dense-sensor event-related EEG recording techniques to investigate the temporal pattern of notation-specific effects observed in a parity judgement (odd versus even) task in which single numbers were presented in one of four different numerical notations. Contrasts between different notations demonstrated clear modulations in the visual evoked potentials (VEP) recorded. We observed increased amplitudes for the P1 and N1 components of the VEP that were specific to Arabic numerals and to dot configurations but differed for random and recognizable (die-face) dot configurations. These results demonstrate clear, notation-specific differences in the time course of numerical information processing and provide electrophysiological support for the triple-code model of numerical representation.     

Logic in a Dynamic Brain

The ability of the human brain to carry out logical reasoning can be interpreted, in general, as a by-product of adaptive capacities of complex neural networks. Thus, we seek to base abstract logical operations in the general properties of neural networks designed as learning modules. We show that logical operations executable by McCulloch–Pitts binary networks can also be programmed in analog neural networks built with associative memory modules that process inputs as logical gates. These modules can interact among themselves to generate dynamical systems that extend the repertoire of logical operations. We demonstrate how the operations of the exclusive-OR or the implication appear as outputs of these interacting modules. In particular, we provide a model of the exclusive-OR that succeeds in evaluating an odd number of options (the exclusive-OR of classical logic fails in his case), thus paving the way for a more reasonable biological model of this important logical operator. We propose that a brain trained to compute can associate a complex logical operation to an orderly structured but temporary contingent episode by establishing a codified association among memory modules. This explanation offers an interpretation of complex logical processes (eventually learned) as associations of contingent events in memorized episodes. We suggest, as an example, a cognitive model that describes these “logical episodes”.     

Ubiquitous expression of acetylcholine and its biological functions in life forms without nervous systems

Using a radioimmunoassay (RIA) with high specificity and sensitivity (1 pg/tube) for acetylcholine (ACh), we have been able to measure the ACh content in samples from the bacteria, archaea and eucarya domains of the universal phylogenetic tree. We found detectable levels of ACh to be ubiquitous in bacteria (e.g., Bacillus subtilis), archaea (e.g., Thermococcus kodakaraensis KOD1), fungi (e.g., shiitake mushroom and yeast), plants (e.g., bamboo shoot and fern) and animals (e.g., bloodworm and lugworm). The levels varied considerably, however, with the highest ACh content detected in the top portion of bamboo shoot (2.9 micromol/g), which contained about 80 times that found in rat brain. In addition, using the method of Fonnum, various levels of ACh-synthesizing activity also were detected, a fraction of which was catalyzed by a choline acetyltransferase (ChAT)-like enzyme (sensitive to bromoACh, a selective ChAT inhibitor) in T. kodakaraensis KOD1 (15%), bamboo shoot (91%) and shiitake mushroom (51%), bloodworm (91%) and lugworm (81%). Taken together, these findings demonstrate the ubiquitous expression of ACh and ACh-synthesizing activity among life forms without nervous systems, and support the notion that ACh has been expressed and may be active as a local mediator and modulator of physiological functions since the early beginning of life.     

Multiplexing mechanical and translational cues on genes

The genetic code gives precise instructions on how to translate codons into amino acids. Due to the degeneracy of the genetic code—18 out of 20 amino acids are encoded for by more than one codon—more information can be stored in a basepair sequence. Indeed, various types of additional information have been discussed in the literature, e.g., the positioning of nucleosomes along eukaryotic genomes and the modulation of the translating efficiency in ribosomes to influence cotranslational protein folding. The purpose of this study is to show that it is indeed possible to carry more than one additional layer of information on top of a gene. In particular, we show how much translation efficiency and nucleosome positioning can be adjusted simultaneously without changing the encoded protein. We achieve this by mapping genes on weighted graphs that contain all synonymous genes, and then finding shortest paths through these graphs. This enables us, for example, to readjust the disrupted translational efficiency profile after a gene has been introduced from one organism (e.g., human) into another (e.g., yeast) without greatly changing the nucleosome landscape intrinsically encoded by the DNA molecule.     

Adaptive pattern classification and universal recoding: II. Feedback,expectation, olfaction,illusions

Part I of this paper describes a model for the parallel development and adult coding of neural feature detectors. It shows how any set of arbitrary spatial patterns can be recoded, or transformed, into any other spatial patterns (universal recoding), if there are sufficiently many cells in the network's cortex. This code is, however, unstable through time if arbitrarily many patterns can perturb a fixed number of cortical cells. This paper shows how to stabilize the code in the general case using feedback between cellular sites. A biochemically defined critical period is not necessary to stabilize the code, nor is it sufficient to ensure useful coding properties.We ask how short term memory can be reset in response to temporal sequences of spatial patterns. This leads to a context-dependent code in which no feature detector need uniquely characterize an input pattern; yet unique classification by the pattern of activity across feature detectors is possible. This property uses learned expectation mechanisms whereby unexpected patterns are temporarily suppressed and/or activate nonspecific arousal. The simplest case describes reciprocal interactions via trainable synaptic pathways (long term memory traces) between two recurrent on-center off-surround networks undergoing mass action (shunting) interactions. This unit can establish an adaptive resonance, or reverberation, between two regions if their coded patterns match, and can suppress the reverberation if their patterns do not match. This concept yields a model of olfactory coding within the olfactory bulb and prepyriform cortex. The resonance idea also includes the establishment of reverberation between conditioned reinforcers and generators of contingent negative variation if presently avialable sensory cues are compatible with the network's drive requirements at that time; and a search and lock mechanism whereby the disparity between two patterns can be minimized and the minimal disparity images locked into position. Stabilizing the code uses attentional mechanisms, in particular nonspecific arousal as a tuning and search device. We suggest that arousal is gated by a chemical transmitter system—for example, norepinephrine—whose relative states of accumulation at antagonistic pairs of on-cells and off-cells through time can shift the spatial pattern of STM activity across a field of feature detectors. For example, a sudden arousal increment in response to an un-expected pattern can reverse, or rebound, these relative activities, thereby suppressing incorrectly classified populations. The rebound mechanism has formal properties analogous to negative afterimages and spatial frequency adaptation.Supported in part by the Advanced Research Projects Agency under ONR Contract No. N00014-76-C-0185     

On time-space of nonlinear phenomena with Gompertzian dynamics

This paper describes a universal relationship between time and space for a nonlinear process with Gompertzian dynamics, such as growth. Gompertzian dynamics implicates a coupling between time and space. Those two categories are related to each other through a linear function of their logarithms. Moreover, we demonstrate that the spatial fractal dimension is a function of both scalar time and the temporal fractal dimension. The Gompertz function reflects the equilibrium of regular states, that is, states with dynamics that are predictable for any time-point (e.g., sinusoidal glycolytic oscillations) and chaotic states, that is, states with dynamics that are unpredictable in time, but are characterized by certain regularities (e.g., the existence of strange attractor for any biochemical reaction). We conclude that both this equilibrium and volume of the available complementary Euclidean space determine temporal and spatial expansion of a process with Gompertzian dynamics.     

The Concept of Taxon Invariance in Ecology: Do Diversity Patterns Vary with Changes in Taxonomic Resolution?

Diversity patterns cannot be properly interpreted without a theory providing criteria for their evaluation. We propose a concept to prevent artifictions caused by improper consideration of changes in observed patterns due to variation in taxon delimitation. Most biodiversity patterns concern assemblages of species of given higher taxon (e.g. class). Some patterns seem to be universal, e.g., body size distribution, species-abundance distribution, species-area relationship, or the relationship between diversity and energy availability. However, truly universal patterns should not change when we change taxonomic scope by focusing on subtaxa or when we merge several sister taxa together and analyze patterns in resulting higher taxon. Similarly, some patterns may not change when changing the basic unit of the study e.g., when replacing species by genera or families (or any monophyletic clades), although other patterns may not be invariant against the variation of the basic unit. In fact, there are only two possibilities: biodiversity patterns are either taxon-invariant or they vary systematically with taxonomic resolution, which would indicate some fundamental taxonomic level with interesting implications for biological processes behind those patterns. Here we develop the concept of taxon invariance of diversity patterns and apply it on the abovementioned patterns. We show that simple theoretical considerations markedly constrain the set of possible patterns, as some of them cannot be simultaneously valid for both a taxon and its subtaxa – frequency distributions of abundances cannot be simultaneously lognormal for a given taxon and all its subtaxa, the taxa-area relationship cannot follow a power-law for all levels of taxonomic resolution, and energy availability cannot affect diversity of all taxonomic units in the same way. Analyses of the variation in the form of biodiversity patterns with changing taxonomic resolution thus provide an extremely useful tool for revealing properties of respective patterns, their universality and logical consistency.     

Molecular Detection, Quantification, and Diversity Evaluation of Microalgae

This study reviews the available molecular methods and new high-throughput technologies for their practical use in the molecular detection, quantification, and diversity assessment of microalgae. Molecular methods applied to other groups of organisms can be adopted for microalgal studies because they generally detect universal biomolecules, such as nucleic acids or proteins. These methods are primarily related to species detection and discrimination among various microalgae. Among current molecular methods, some molecular tools are highly valuable for small-scale detection [e.g., single-cell polymerase chain reaction (PCR), quantitative real-time PCR (qPCR), and biosensors], whereas others are more useful for large-scale, high-throughput detection [e.g., terminal restriction length polymorphism, isothermal nucleic acid sequence-based amplification, loop-mediated isothermal amplification, microarray, and next generation sequencing (NGS) techniques]. Each molecular technique has its own strengths in detecting microalgae, but they may sometimes have limitations in terms of detection of other organisms. Among current technologies, qPCR may be considered the best method for molecular quantification of microalgae. Metagenomic microalgal diversity can easily be achieved by 454 pyrosequencing rather than by the clone library method. Current NGS, third and fourth generation technologies pave the way for the high-throughput detection and quantification of microalgal diversity, and have significant potential for future use in field monitoring.     

Early fixation of an optimal genetic code

The evolutionary forces that produced the canonical genetic code before the last universal ancestor remain obscure. One hypothesis is that the arrangement of amino acid/codon assignments results from selection to minimize the effects of errors (e.g., mistranslation and mutation) on resulting proteins. If amino acid similarity is measured as polarity, the canonical code does indeed outperform most theoretical alternatives. However, this finding does not hold for other amino acid properties, ignores plausible restrictions on possible code structure, and does not address the naturally occurring nonstandard genetic codes. Finally, other analyses have shown that significantly better code structures are possible. Here, we show that if theoretically possible code structures are limited to reflect plausible biological constraints, and amino acid similarity is quantified using empirical data of substitution frequencies, the canonical code is at or very close to a global optimum for error minimization across plausible parameter space. This result is robust to variation in the methods and assumptions of the analysis. Although significantly better codes do exist under some assumptions, they are extremely rare and thus consistent with reports of an adaptive code: previous analyses which suggest otherwise derive from a misleading metric. However, all extant, naturally occurring, secondarily derived, nonstandard genetic codes do appear less adaptive. The arrangement of amino acid assignments to the codons of the standard genetic code appears to be a direct product of natural selection for a system that minimizes the phenotypic impact of genetic error. Potential criticisms of previous analyses appear to be without substance. That known variants of the standard genetic code appear less adaptive suggests that different evolutionary factors predominated before and after fixation of the canonical code. While the evidence for an adaptive code is clear, the process by which the code achieved this optimization requires further attention.     

Responses in Primary Somatosensory Cortex of Rhesus Monkey to Controlled Application of Embossed Grating and Bar Patterns

Responses of 66 neurons in primary somatosensory cortex (SI) of three anesthetized monkeys (Macaca mulatto) were characterized with grating patterns of 550- to 2900-mm groove width (Gw) and 250-mm ridge width, and/or pairs of 3-mm-wide ridges (bars) spaced 1-20 mm apart. Surfaces were stroked across single fingertips at parametrically varied levels of force ('25-150 g) and velocity ('25-100 mm/sec). The average firing rates (AFRs) of many cells varied with Gw, but force and velocity altered response functions (e.g., from linear to plateau or inverted). Slowly adapting (SA) cells were more sensitive to force, rapidly adapting (RA) cells to velocity. Force and velocity affected all cells sensitive to Gw, which suggests that response independence (e.g., AFR correlated with Gw but not force or velocity) may require active touch

Discharge intervals of many cells replicated stimulus temporal period. This temporal fidelity in SAs far exceeded examples reported for active touch. However, discharge burst duration and AFR increased with Gw, supporting a neural rate rather than temporal code for roughness. Force and velocity altered the Gw at which some cells fired once in phase to stimulus cycle (“tuning point”). Responses to bar edges suggest cortical replication of peripheral mechanoreceptor sensitivity to skin curvature, leading to this temporal fidelity in some cortical cells. Graded RA responses to Gw without obvious stimulus temporal replication may reflect early stages of integrative processing in supra- and infragranular layers that blur obvious temporal patterning and lead to a rate code correlated with spatial variation and proportional to perceived roughness     

Occurrence, characteristics, and applications of fructosyl amine oxidases (amadoriases)

Amadori compounds, formed by the Maillard reaction between reducing sugars (e.g., glucose) and amines (e.g., lysine residues in proteins), are ubiquitous in nature and have been implicated in aging and several chronic diseases. Fructosyl amine oxidases (FAOXs) are a relatively new class of enzymes that cleave amadori compounds and have been found in fungi, yeast, and bacteria. This mini-review summarizes over a dozen of FAOXs with different substrate specificities have been isolated, characterized, and engineered to date. All known FAOX sequences except one have the consensus motif for the ADP-binding βαβ-fold common to all FAD and NAD enzymes, and a recently solved crystal structure provides important clues for this class of enzymes. FAOXs have been explored for applications in diabetes diagnosis, detergents, and food processing. Given that naturally occurring FAOXs can only react directly with small glycated amino acids or short peptides, it is of great interest to engineer and expand the accessibility of the substrate binding sites of these enzymes.     

Fossil Homo femur from Berg Aukas,northern Namibia

The proximal half of a hominid femur was recovered from deep within a paleokarst feature at the Berg Aukas mine, northern Namibia. The femur is fully mineralized, but it is not possible to place it in geochrono logical context. It has a very large head, an exceptionally thick diaphyseal cortex, and a very low collodiaphyseal angle, which serve to differentiate it from Holocene homologues. The femur is not attributable to Australopithecus, Paranthropus, or early Homo (i.e., H. habilis sensu lato). Homo erectus femora have a relatively longer and AP flatter neck, and a shaft that exhibits less pilaster than the Berg Aukas specimen. Berg Aukas also differs from early modern femora in several features, including diaphyseal cortical thickness and the degree of subtrochanteric AP flattening. The massive diaphyseal cortex of Berg Aukas finds its closest similarity within archaic H. sapiens (e.g., Castel di Guido) and H. erectus (e.g., KNM-ER 736) samples. It has more cortical bone at midshaft than any other specimen, although relative cortical thickness and the asymmetry of its cross-sectional disposition at this level are comparable with those of other Pleistocene fem ora. The closest morphological comparisons with Berg Aukas are in archaic (i.e., Middle Pleistocene) H. sapiens and Neandertal samples. © 1995 Wiley-Liss, Inc.     

Gap junctions in sea anemone, Nematostella vectensis, embryo

Gap junctions (GJs) are composed of membrane proteins that form channels connecting the cytoplasm of adjacent cells and permeable to ions and small molecules. They are considered to be the main or only type of intercellular channels and a universal feature of all multicellular animals (Metazoa). Till recently, sea anemones and corals (Anthozoa, Cnidaria) appeared to be an exception from this rule. There were no structural or physiological data supporting the presence of GJ in Anthozoa. For some time no genes homologous to GJ proteins (connexins or pannexins) were detected in sea anemone Nematostella vectensis (Cnidaria, Anthozoa) or other Anthozoa genomes. Recently, pannexin homolog was found in Nematostella. Our intracellular recordings demonstrate electrical coupling between blastomeres in embryos at the 8-cells stage. At the same time, carboxyfluorescein fluorescent dye did not diffuse between electrically coupled cells, which excludes the possibility that the observed electrical coupling is mediated by incomplete cytoplasm separation during the cleavage. These data support the idea that GJ are ubiquitous for Metazoa, and pannexins are universal GJ proteins.     

Mechanism of teratogenesis: electron transfer, reactive oxygen species, and antioxidants

Teratogenesis has been a topic of increasing interest and concern in recent years, generating controversy in association with danger to humans and other living things. A veritable host of chemicals is known to be involved, encompassing a wide variety of classes, both organic and inorganic. Contact with these chemicals is virtually unavoidable due to contamination of air, water, ground, food, beverages, and household items, as well as exposure to medicinals. The resulting adverse effects on reproduction are numerous. There is uncertainty regarding the mode of action of these chemicals, although various theories have been advanced, e.g., disruption of the central nervous system (CNS), DNA attack, enzyme inhibition, interference with hormonal action, and insult to membranes, proteins, and mitochondria. This review provides extensive evidence for involvement of oxidative stress (OS) and electron transfer (ET) as a unifying theme. Successful application of the mechanistic approach is made to all of the main classes of toxins, in addition to large numbers of miscellaneous types. We believe it is not coincidental that the vast majority of these substances incorporate ET functionalities (quinone, metal complex, ArNO2, or conjugated iminium) either per se or in metabolites, potentially giving rise to reactive oxygen species (ROS) by redox cycling. Some categories, e.g., peroxides and radiation, appear to generate ROS by non-ET routes. Other mechanisms are briefly addressed; a multifaceted approach to mode of action appears to be the most logical. Our framework should increase understanding and contribute to preventative measures, such as use of antioxidants.     

Antenatal diagnosis of neural tube defects in Canada: extension of a collaborative study.

Experience with the diagnosis of neural tube defects from alpha1-fetoprotein (AFP) concentrations in amniotic fluid is reported from a prospective study of five laboratories testing for 13 Canadian genetic centres. The results of the study indicate that antenatal diagnosis of open neural tube defects is being carried out effectively in Canada (in 99.2% of cases the AFP measurements were interpreted correctly). Amniocentesis should be recommended to women at high risk for having a child with a neural tube defect (i.e., those who have a child, a parent or a sibling with a neural tube defect). The rate of neural tube defects in 182 high-risk pregnancies was 2.2% for an open defect and 1.1% for a closed defect, whereas the rate in 673 pregnancies in which amniocentesis was being performed for other reasons was 0.3%. This suggests that the AFP concentration should be measured in any sample of amniotic fluid collected for other reasons (usually fetal karyotyping). There were three instances of false-negative results, for a rate of 0.4%. Two closed neural tube defects were not detected; this limitation of the test has also been found by others. One of the six fetuses with an open neural tube defect, who died in utero, had a large myelocele in the neck that was not recognized. There were also four instances of false-positive results, for a rate of 0.5%. The findings suggest that AFP values that are more than 2 but less than 7 standard deviations (SDs) above the mean may indicate a neural tube defect, and that values 7 or more SDs above the mean very likely indicate such a defect, although other reasons for such high values (e.g., fetal erythrocytes in the amniotic fluid, intrauterine death and mistaken gestational age) must be ruled out by other methods.     

Emotions in Everyday Life

Despite decades of research establishing the causes and consequences of emotions in the laboratory, we know surprisingly little about emotions in everyday life. We developed a smartphone application that monitored real-time emotions of an exceptionally large (N = 11,000+) and heterogeneous participants sample. People’s everyday life seems profoundly emotional: participants experienced at least one emotion 90% of the time. The most frequent emotion was joy, followed by love and anxiety. People experienced positive emotions 2.5 times more often than negative emotions, but also experienced positive and negative emotions simultaneously relatively frequently. We also characterized the interconnections between people’s emotions using network analysis. This novel approach to emotion research suggests that specific emotions can fall into the following categories 1) connector emotions (e.g., joy), which stimulate same valence emotions while inhibiting opposite valence emotions, 2) provincial emotions (e.g., gratitude), which stimulate same valence emotions only, or 3) distal emotions (e.g., embarrassment), which have little interaction with other emotions and are typically experienced in isolation. Providing both basic foundations and novel tools to the study of emotions in everyday life, these findings demonstrate that emotions are ubiquitous to life and can exist together and distinctly, which has important implications for both emotional interventions and theory.     

Short- and long-term streamflow forecasting using wavelet neural networks for complex watersheds: A case study in the Mahanadi River,India

Water plans and operations (e.g., flood control, drought mitigation measures, water allocation, and engineering design) depend on reliable streamflow information. Thus, this study presents a methodology that improves streamflow forecasting using wavelet neural networks (WNN) for the short- (daily) and long-term (weekly, fortnightly, and monthly) in the Mahanadi River basin, India. The WNN model employs multilayer artificial neural networks (NN) to relate streamflows with wavelet-based approximations of previous streamflows and rainfalls. The methodology was validated using data from ten stations and three performance indices: Pearson correlation coefficient (R), percentage of trends (PBIAS), and Nash-Sutcliffe efficiency (NSE). These indices confirmed that adding rainfall data as input provided better estimations than the sole use of streamflows. The WNN approach was superior to all other applications (NSE ranging from 0.299 to 0.987 for all time horizons and stations), especially for long-term forecasts in the Mahanadi River basin, and could be a viable alternative to other catchments.     

A stochastic gene evolution model with time dependent mutations

We develop here a new class of gene evolution models in which the nucleotide mutations are time dependent. These models allow to study nonlinear gene evolution by accelerating or decelerating the mutation rates at different evolutionary times. They generalize the previous ones which are based on constant mutation rates. The stochastic model developed in this class determines at some time t the occurrence probabilities of trinucleotides mutating according to 3 time dependent substitution parameters associated with the 3 trinucleotide sites. Therefore, it allows to simulate the evolution of the circular code recently observed in genes. By varying the class of function for the substitution parameters, 1 among 12 models retrieves after mutation the statistical properties of the observed circular code in the 3 frames of actual genes. In this model, the mutation rate in the 3rd trinucleotide site increases during gene evolution while the mutation rates in the 1st and 2nd sites decrease. This property agrees with the actual degeneracy of the genetic code. This approach can easily be generalized to study evolution of motifs of various lengths, e.g., dicodons, etc., with time dependent mutations.