Sibley, Kello, Plaut, and Elman (2008) proposed the sequence encoder as a model that learns fixed‐width distributed representations of variable‐length sequences. In doing so, the sequence encoder overcomes problems that have restricted models of word reading and recognition to processing only monosyllabic words. Bowers and Davis (2009) recently claimed that the sequence encoder does not actually overcome the relevant problems, and hence it is not a useful component of large‐scale word‐reading models. In this reply, (...) it is noted that the sequence encoder has facilitated the creation of large‐scale word‐reading models. The reasons for this success are explained and stand as counterarguments to claims made by Bowers and Davis. (shrink)

We show that the universally axiomatized, induction-free theory equation image is a sequential theory in the sense of Pudlák's 5, in contrast to the closely related Robinson's arithmetic.

Previous studies have found that P1 and P2 components were more sensitive to configural and featural face processing, respectively, when attentional resources were sufficient, suggesting that face processing follows a coarse-to-fine sequence. However, the role of working memory load in the time course of configural and featural face processing is poorly understood, especially whether it differs during encoding and retrieval stages. This study employed a delayed recognition task with varying WM load and face spatial frequency. Our behavioral and ERP (...) results showed that WM load modulated face SF processing. Specifically, for the encoding stage, P1 and P2 were more sensitive to broadband SF faces, while N170 was more sensitive to low SF and BSF faces. For the retrieval stage, P1 on the right hemisphere was more sensitive to BSF faces relative to HSF faces, N170 was more sensitive to LSF faces than HSF faces, especially under the load 1 condition, while P2 was more sensitive to high SF faces than HSF faces, especially under load 3 condition. These results indicate that faces are perceived less finely during the encoding stage, whereas face perception follows a coarse-to-fine sequence during the retrieval stage, which is influenced by WM load. The coarse and fine information were processed especially under the low and high load conditions, respectively. (shrink)

This paper examines a specific kind of part-whole relations that exist in the molecular genetic domain. The central question is under which conditions a particular molecule, such as a DNA sequence, is a biological part of the human genome. I address this question by analyzing how biologists in fact partition the human genome into parts. This paper thus presents a case study in the metaphysics of biological practice. I develop a metaphysical account of genomic parthood by analyzing the investigative (...) and reasoning practices in the ENCODE (ENCyclopedia Of DNA Elements) project. My account reveals two conditions that determine whether a molecule is a part of the human genome (i.e., a genomic part). First, genomic parts must possess a causal role function in the genome as a whole, that is, their functions must contribute to the genome directing the overall functioning of the cell. Second, genomic parts must have a specific chemical structure and be actual segments of the DNA sequence of the genome. (shrink)

Humans possess the ability to extract highly organized perceptual structures from sequences of temporal stimuli. For instance, we can organize specific rhythmical patterns into hierarchical, or metrical, systems. Despite the evidence of a fundamental influence of the motor system in achieving this skill, few studies have attempted to investigate the organization of our motor representation of rhythm. To this aim, we studied—in musicians and non-musicians—the ability to perceive and reproduce different rhythms. In a first experiment participants performed a temporal order-judgment (...) task, for rhythmical sequences presented via auditory or tactile modality. In a second experiment, they were asked to reproduce the same rhythmic sequences, while their tapping force and timing were recorded. We demonstrate that tapping force encodes the metrical aspect of the rhythm, and the strength of the coding correlates with the individual’s perceptual accuracy. We suggest that the similarity between perception and tapping-force organization indicates a common representation of rhythm, shared between the perceptual and motor systems. (shrink)

More and more research on left ventricle quantification skips segmentation due to its requirement of large amounts of pixel-by-pixel labels. In this study, a framework is developed to directly quantify left ventricle multiple indices without the process of segmentation. At first, DenseNet is utilized to extract spatial features for each cardiac frame. Then, in order to take advantage of the time sequence information, the temporal feature for consecutive frames is encoded using gated recurrent unit. After that, the attention mechanism (...) is integrated into the decoder to effectively establish the mappings between the input sequence and corresponding output sequence. Simultaneously, a regression layer with the same decoder output is used to predict multi-indices of the left ventricle. Different weights are set for different types of indices based on experience, and l2-norm is used to avoid model overfitting. Compared with the state-of-the-art, our method can not only produce more competitive results but also be more flexible. This is because the prediction results in our study can be obtained for each frame online while the SOTA only can output results after all frames are analyzed. (shrink)

Protein splicing is an extraordinary post‐translational reaction that removes an intact central “spacer” domain (Sp) from precursor proteins (N‐Sp‐C) while splicing together the N‐ and C‐domains of the precursor, via a peptide bond, to produce a new protein (N‐C). All of the available data on protein splicing fit a model in which these intervening sequences excise at the protein level via a self‐splicing mechanism. Several proteins have recently been discovered that undergo protein splicing, and in two such cases, the excised (...) spacer protein is an endonuclease. Such endonucleases are capable of conferring genetic mobility upon the intervening sequences that encodes them. These intervening sequences define a new family of mobile genetic elements that are translated yet remain phenotypically silent by excising at the protein rather than the RNA level. (shrink)

The forms of words as they appear in text and speech are central to theories and models of lexical processing. Nonetheless, current methods for simulating their learning and representation fail to approach the scale and heterogeneity of real wordform lexicons. A connectionist architecture termed thesequence encoderis used to learn nearly 75,000 wordform representations through exposure to strings of stress‐marked phonemes or letters. First, the mechanisms and efficacy of the sequence encoder are demonstrated and shown to overcome problems with (...) traditional slot‐based codes. Then, two large‐scale simulations are reported that learned to represent lexicons of either phonological or orthographic wordforms. In doing so, the models learned the statistics of their lexicons as shown by better processing of well‐formed pseudowords as opposed to ill‐formed (scrambled) pseudowords, and by accounting for variance in well‐formedness ratings. It is discussed how the sequence encoder may be integrated into broader models of lexical processing. (shrink)

Recent investigations have revealed 1) that the isochores of the human genome group into two super‐families characterized by two different long‐range 3D structures, and 2) that these structures, essentially based on the distribution and topology of short sequences, mold primary chromatin domains (and define nucleosome binding). More specifically, GC‐poor, gene‐poor isochores are low‐heterogeneity sequences with oligo‐A spikes that mold the lamina‐associated domains (LADs), whereas GC‐rich, gene‐rich isochores are characterized by single or multiple GC peaks that mold the topologically associating domains (...) (TADs). The formation of these “primary TADs” may be followed by extrusion under the action of cohesin and CTCF. Finally, the genomic code, which is responsible for the pervasive encoding and molding of primary chromatin domains (LADs and primary TADs, namely the “gene spaces”/“spatial compartments”) resolves the longstanding problems of “non‐coding DNA,” “junk DNA,” and “selfish DNA” leading to a new vision of the genome as shaped by DNA sequences. (shrink)

Although many studies have provided evidence that abstract knowledge can be acquired in artificial grammar learning, it remains unclear how abstract knowledge can be attained in sequence learning. To address this issue, we proposed a dual simple recurrent network model that includes a surface SRN encoding and predicting the surface properties of stimuli and an abstract SRN encoding and predicting the abstract properties of stimuli. The results of Simulations 1 and 2 showed that the DSRN model can account for (...) learning effects in the serial reaction time task under different conditions, and the manipulation of the contribution weight of each SRN accounted for the contribution of conscious and unconscious processes in inclusion and exclusion tests in previous studies. The results of human performance in Simulation 3 provided further evidence that people can implicitly learn both chunking and abstract knowledge in sequence learning, and the results of Simulation 3 confirmed that the DSRN model can account for how people implicitly acquire the two types of knowledge in sequence learning. These findings extend the learning ability of the SRN model and help understand how different types of knowledge can be acquired implicitly in sequence learning. (shrink)

Poly(ADP‐ribosyl)ation is an immediate DNA‐damage‐dependent post‐translational modification of histones and other nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP‐ribose) polymerases (PARPs) now constitute a large family of 18 proteins, encoded by different genes and displaying a conserved catalytic domain in which PARP‐1 (113 kDa), the founding member, and PARP‐2 (62 kDa) are so far the sole enzymes whose catalytic activity has been shown to be immediately stimulated by DNA strand breaks. A large repertoire of sequences encoding (...) novel PARPs now extends considerably the field of poly(ADP‐ribosyl)ation reactions to various aspects of the cell biology including cell proliferation and cell death. Some of these new members interact with each other, share common partners and common subcellular localizations suggesting possible fine tuning in the regulation of this post‐translational modification of proteins. This review summarizes our present knowledge of this emerging superfamily, which might ultimately improve pharmacological strategies to enhance both antitumor efficacy and the treatment of a number of inflammatory and neurodegenerative disorders. A provisional nomenclature is proposed. BioEssays 26:882–893, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The c‐myc proto‐oncogene is believed to be involved in the regulation of cell growth and differentiation. Deregulation of this gene, resulting in an inappropriate increase of gene product, can contribute to cancer formation. One of the ways in which the expression of the c‐myc gene can be deregulated is by the stabilization of the labile c‐myc mRNA. The rapid degradation of the c‐myc transcript appears to be mediated by at least two distinct regions in the mRNA. One lies in the (...) 3' untranslated region, and presumably consists of (A+U)‐rich sequences. The other lies in the C‐terminal part of the coding region and colocalizes with sequences encoding protein‐dimerization motifs. The exact mechanism by which the destabilizing elements function is not yet clear. Shortening of the poly(A) tail of the c‐myc message appears to precede degradation of the transcript. When translation is blocked, this shortening is slowed down and the mRNA is stabilized. This suggests that deadenylation is required before degradation of the mRNA body can take place. (shrink)

Three decades ago Gilbert posited that novel proteins arise by re‐shuffling genomic sequences encoding polypeptide domains. Today, with numerous genomes and countless genes sequenced, it is well established that recombination of sequences encoding polypeptide domains plays a major role in protein evolution. There is, however, less evidence to suggest how the novel polypeptide domains, themselves, arise. Recent comparisons of genomes from closely related species have revealed numerous species‐specific exons, supporting models of domain origin based on “exonization” of intron sequences. Also, (...) a mechanism for the origin of novel polypeptide domains has been proposed based on analyses of insertion‐based polymorphisms between orthologous genes across broad phylogenetic spectra and between allelic variants of genes within species. This review discusses these processes and how each might participate in the evolutionary emergence of novel polypeptide domains. BioEssays 29: 262–270, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Sibley et al. (2008) report a recurrent neural network model designed to learn wordform representations suitable for written and spoken word identification. The authors claim that their sequence encoder network overcomes a key limitation associated with models that code letters by position (e.g., CAT might be coded as C‐in‐position‐1, A‐in‐position‐2, T‐in‐position‐3). The problem with coding letters by position (slot‐coding) is that it is difficult to generalize knowledge across positions; for example, the overlap between CAT and TOMCAT is lost. (...) Although we agree this is a critical problem with many slot‐coding schemes, we question whether the sequence encoder model addresses this limitation, and we highlight another deficiency of the model. We conclude that alternative theories are more promising. (shrink)

Retroviruses encode a small, basic nucleocapsid (NC) protein that is found complexed to genomic RNA within the viral particle. The NC protein appears to function not only in a histone‐like manner in packaging the RNA into the particle but also in specifically selecting the viral genomic RNA for packaging. A cysteine‐histidine (cys‐his) region, usually composed of 14 amino acids and reminiscent of the ‘zinc fingers’ of transcription factors, is the only highly conserved sequence element among the retroviral NC proteins. (...) This review discusses the biochemical properties of NC, and its possible role(s) in retroviral replication. We also speculate on how the biochemical properties may relate to its function in RNA recognition and packaging. (shrink)

Learning the structure of event sequences is a ubiquitous problem in cognition and particularly in language. One possible solution is to learn a probabilistic generative model of sequences that allows making predictions about upcoming events. Though appealing from a neurobiological standpoint, this approach is typically not pursued in connectionist modeling. Here, we investigated a sequential version of the restricted Boltzmann machine, a stochastic recurrent neural network that extracts high-order structure from sensory data through unsupervised generative learning and can encode contextual (...) information in the form of internal, distributed representations. We assessed whether this type of network can extract the orthographic structure of English monosyllables by learning a generative model of the letter sequences forming a word training corpus. We show that the network learned an accurate probabilistic model of English graphotactics, which can be used to make predictions about the letter following a given context as well as to autonomously generate high-quality pseudowords. The model was compared to an extended version of simple recurrent networks, augmented with a stochastic process that allows autonomous generation of sequences, and to non-connectionist probabilistic models. We conclude that sequential RBMs and stochastic simple recurrent networks are promising candidates for modeling cognition in the temporal domain. (shrink)

Eukaryotic mRNAs are monocistronic, and therefore mechanisms exist that coordinate the synthesis of multiprotein complexes in order to obtain proper stoichiometry at the appropriate intracellular locations. RNA‐binding proteins containing low‐complexity sequences are prone to generate liquid droplets via liquid‐liquid phase separation, and in this way create cytoplasmic assemblages of functionally related mRNAs. In a recent iCLIP study, we showed that the Drosophila RNA‐binding protein Imp, which exhibits a C‐terminal low‐complexity sequence, increases the formation of F‐actin by binding to 3′ (...) untranslated regions of mRNAs encoding components participating in F‐actin biogenesis. We hypothesize that phase transition is a mechanism the cell employs to increase the local mRNA concentration considerably, and in this way synchronize protein production in cytoplasmic territories, as discussed in the present review. (shrink)

Given a sequence of sets An⊆{0,…,n−1}, the Furstenberg correspondence principle provides a shift-invariant measure on2N that encodes combinatorial information about infinitely many of the An's. Here it is shown that this process can be inverted, so that for any such measure, ergodic or not, there are finite sets whose combinatorial properties approximate it arbitarily well. The finite approximations are obtained from the measure by an explicit construction, with an explicit upper bound on how large n has to be to (...) yield a sufficiently good approximation. We draw conclusions for computable measure theory, and show, in particular, that given any computable shift-invariant measure on 2N, there is a computable element of 2N that is generic for the measure. We also consider a generalization of the correspondence principle to countable discrete amenable groups, and once again provide an effective inverse. (shrink)

In eukaryotic cells intron sequences are usually spliced out with a high degree of precision from heterogenous nuclear RNA (hnRNA) to give functional mRNA with exons in their right order. Provided with the right substrates, cell extracts can achieve the same. With exotic substrates, on the other hand, the same extracts can cut exons from one RNA and join them to exons from another RNA, a process termed trans‐splicing. In vivo, RNA trans‐splicing could lead to faulty, but also to novel (...) proteins and, through reverse transcription, to genomic rearrangements. So far, in living cells trans‐splicing has only been invoked to occur in trypanosomes. In these unicellular organisms most if not all mRNAs are made discontinuously, so that the mature mRNAs carry, at their 5′ end, a common 35‐nucleotide sequence, called a miniexon, encoded separately in the genome. The miniexon is most likely joined to the body of the mRNA by trans‐splicing. (shrink)

The tower number ${\mathfrak t}$ and the ultrafilter number $\mathfrak {u}$ are cardinal characteristics from set theory. They are based on combinatorial properties of classes of subsets of $\omega $ and the almost inclusion relation $\subseteq ^*$ between such subsets. We consider analogs of these cardinal characteristics in computability theory.We say that a sequence $(G_n)_{n \in {\mathbb N}}$ of computable sets is a tower if $G_0 = {\mathbb N}$, $G_{n+1} \subseteq ^* G_n$, and $G_n\smallsetminus G_{n+1}$ is infinite for each (...) n. A tower is maximal if there is no infinite computable set contained in all $G_n$. A tower ${\left \langle {G_n}\right \rangle }_{n\in \omega }$ is an ultrafilter base if for each computable R, there is n such that $G_n \subseteq ^* R$ or $G_n \subseteq ^* \overline R$ ; this property implies maximality of the tower. A sequence $(G_n)_{n \in {\mathbb N}}$ of sets can be encoded as the “columns” of a set $G\subseteq \mathbb N$. Our analogs of ${\mathfrak t}$ and ${\mathfrak u}$ are the mass problems of sets encoding maximal towers, and of sets encoding towers that are ultrafilter bases, respectively. The relative position of a cardinal characteristic broadly corresponds to the relative computational complexity of the mass problem. We use Medvedev reducibility to formalize relative computational complexity, and thus to compare such mass problems to known ones.We show that the mass problem of ultrafilter bases is equivalent to the mass problem of computing a function that dominates all computable functions, and hence, by Martin’s characterization, it captures highness. On the other hand, the mass problem for maximal towers is below the mass problem of computing a non-low set. We also show that some, but not all, noncomputable low sets compute maximal towers: Every noncomputable (low) c.e. set computes a maximal tower but no 1-generic $\Delta ^0_2$ -set does so.We finally consider the mass problems of maximal almost disjoint, and of maximal independent families. We show that they are Medvedev equivalent to maximal towers, and to ultrafilter bases, respectively. (shrink)

Rhythmic structure in speech is characterized by sequences of stressed and unstressed syllables. A large body of literature suggests that speakers of English attempt to achieve rhythmic harmony by evenly distributing stressed syllables throughout prosodic phrases. The question remains as to how speakers plan metrical structure during speech production and whether it is planned independently of phonemes. To examine this, we designed a tongue twister task consisting of disyllabic word pairs with overlapping phonological segments and either matching or non‐matching metrical (...) structure. Results showed that speakers had more difficulty producing metrically regular word pairs, compared to irregular pairs; that is, word pairs with irregular meter had faster productions and fewer speech errors in this production task. This finding of metrical regularity inhibiting production is inconsistent with an abstract metrical structure that is planned independently of phonemes at the point of phonological encoding. (shrink)

Prior to the genomic sequencing era, the bible for those working in clinical genetics was McKusick’s Mendelian Inheritance in Man, which appeared in multiple editions between the 1960s and the late 1990s. This catalogue was organized according to general patterns of inheritance and focused on phenotypes. Beginning in the mid-1980s, it was replaced by Online Mendelian Inheritance in Man, a continuously updated catalogue documenting molecular relationships between genetic variation and phenotypic expression. This paper explores this resource’s evolution with attention to (...) how disease is distinguished from clinically irrelevant variation and how phenotypic similarities are captured in cases where there is no obvious genotypic association. It is argued that hybrid compromises are encoded into OMIM®; in addition to serving its key original purpose of being a diagnostic catalogue, it also began to record detectable variations in the genome even if they were not known to be associated with phenotypically visible disorders or even phenotypic variations. Although the impacts of geneticization have been well recognized, particularly in popular media, this example allows exploration of some of the historic, epistemic, and methodological causes that underlie tendencies toward disease geneticization in contemporary medicine, while highlighting that such gene-focused strategies may in fact be warranted in some contexts. (shrink)

Plant MADS‐box genes encode transcriptional regulators that are critical for a number of developmental processes. In the angiosperms (the flowering plants), these include the specification of floral organ identities, flowering time and fruit development. It appears that the MADS box gene family has undergone considerable gene duplication and sequence divergence within the angiosperms. Here I discuss the possibility that these events have allowed the recruitment of these genes to new developmental pathways in particular angiosperm lineages. Recent analyses of (...) class='Hi'>sequence changes, expression patterns and, in a few cases, gene function are beginning to provide tantalizing evidence for deciphering when and how such genetic diversification has led to particular morphological innovations. In the future, comparative studies of large numbers of species will be required to assess the extent of such variation as well as to fully understand the mechanisms by which evolution of these developmental regulators has played a role in shaping new morphologies. BioEssays 25:637–646, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

We discuss the role of linguistic metaphors as a cognitive frame for the understanding of genetic information processing. The essential similarity between language and genetic information processing has been recognized since the very beginning, and many prominent scholars have noted the possibility of considering genes and genomes as texts or languages. Most of the core terms in molecular biology are based on linguistic metaphors. The processing of genetic information is understood as some operations on text – writing, reading and editing (...) and their specification (encoding/decoding, proofreading, transcription, translation, reading frame). The concept of gene reading can be traced from the archaic idea of the equation of Life and Nature with the Book. Thus, the genetics itself can be metaphorically represented as some operations on text (deciphering, understanding, codebreaking, transcribing, editing, etc.), which are performed by scientists. At the same time linguistic metaphors portrayed gene entities also as having the ability of reading. In the case of such “bio-reading” some essential features similar to the processes of human reading can be revealed: this is an ability to identify the biochemical sequences based on their function in an abstract system and distinguish between type and its contextual tokens of the same type. Metaphors seem to be an effective instrument for representation, as they make possible a two-dimensional description: biochemical by its experimental empirical results and textual based on the cognitive models of comprehension. In addition to their heuristic value, linguistic metaphors are based on the essential characteristics of genetic information derived from its dual nature: biochemical by its substance, textual (or quasi-textual) by its formal organization. It can be concluded that linguistic metaphors denoting biochemical objects and processes seem to be a method of description and explanation of these heterogeneous properties. (shrink)

In humans, there are two skeletal muscle α‐actinins, encoded by ACTN2 and ACTN3, and the ACTN3 genotype is associated with human athletic performance. Remarkably, approximately 1 billion people worldwide are deficient in α‐actinin‐3 due to the common ACTN3 R577X polymorphism. The α‐actinins are an ancient family of actin‐binding proteins with structural, signalling and metabolic functions. The skeletal muscle α‐actinins diverged ∼250–300 million years ago, and ACTN3 has since developed restricted expression in fast muscle fibres. Despite ACTN2 and ACTN3 retaining considerable (...) sequence similarity, it is likely that following duplication there was a divergence in function explaining why α‐actinin‐2 cannot completely compensate for the absence of α‐actinin‐3. This paper focuses on the role of skeletal muscle α‐actinins, and how possible changes in functions between these duplicates fit in the context of gene duplication paradigms. (shrink)

The gelsolin gene family encodes a number of higher eukaryotic actin-binding proteins that are thought to function in the cytoplasm by severing, capping, nucleating or bundling actin filaments. Recent evidence, however, suggests that several members of the gelsolin family may have adopted unexpected nuclear functions including a role in regulating transcription. In particular, flightless I, supervillin and gelsolin itself have roles as coactivators for nuclear receptors, despite the fact that their divergence appears to predate the evolutionary appearance of nuclear receptors. (...) Flightless I has been shown to bind both actin and the actin-related BAF53a protein, which are subunits of SWI/SNF-like chromatin remodelling complexes. The primary sequences of some actin-related proteins such as BAF53a exhibit conservation of residues that, in actin itself, are known to interact with gelsolin-related proteins. In summary, there is a growing body of evidence supporting a biological role in the nucleus for actin, Arps and actin-binding proteins and, in particular, the gelsolin family of actin-binding proteins. (c) 2005 Wiley Periodicals, Inc. (shrink)

The proportion of the genome encoding intrinsically unstructured proteins increases with the complexity of organisms, which demands specific mechanism(s) for generating novel genetic material of this sort. Here it is suggested that one such mechanism is the expansion of internal repeat regions, i.e., coding micro‐ and minisatellites. An analysis of 126 known unstructured sequences shows the preponderance of repeats: the percentage of proteins with tandemly repeated short segments is much higher in this class (39%) than earlier reported for all Swiss‐Prot (...) (14%), yeast (18%) or human (28%) proteins. Furthermore, prime examples, such as salivary proline‐rich proteins, titin, eukaryotic RNA polymerase II, the prion protein and several others, demonstrate that the repetitive segments carry fundamental function in these proteins. In addition, their repeat numbers show functionally significant interspecies variation and polymorphism, which underlines that these regions have been shaped by intense evolutionary activity. In all, the major point of this paper is that the genetic instability of repetitive regions combined with the structurally and functionally permissive nature of unstructured proteins has powered the extension and possible functional expansion of this newly recognized protein class. BioEssays 25:847–855, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

A representation is a remnant of previous experience that allows that experience to affect later behavior. This paper develops a metatheoretical view of representation and applies it to issues concerning representation in animals. To describe a representational system one must specify the following: thedomainor range of situations in the represented world to which the system applies; thecontentor set of features encoded and preserved by the system; thecodeor transformational rules relating features of the representation to the corresponding features of the represented (...) world; themedium, or the representation's physical instantiation; and thedynamics, or how the system changes with time. In part because of the behaviorist assumption that the hypothetical, covert changes occurring in an organism during learning correspond to the overt physical changes that are observed, issues of representation in animal behavior have been largely ignored as irrelevant or misleading. However, it can be inferred that representations, acting as models of environmental regularities, operate at many levels of behavioral functioning, both cognitive and noncognitive. Objections to the use of this concept in explanations of animal behavior, based on the claim that it is indeterminate and on behaviorist considerations of parsimony, can be answered. Animal representations may be specialized in terms of tasks and species. Data from tasks involving spatial memory, delayed matching-to-sample, and sequence learning suggest some foundations for a general theory of animal representations. (shrink)

The coevolution of humans with their intestinal microflora has resulted in cooperative relationships that have shaped the biology and the genomes of these symbiotic partners. Bacteroides thetaiotaomicron is one such bacterial symbiont that is a dominant member of the intestinal microbiota of humans and other mammals. The recent report of the genome sequence of B. thetaiotaomicron1 is the first reported for an abundant Gram‐negative organism of the human colonic microbiota and, as such, provides the first glimpse on a genomic (...) scale of the genetic arsenal used by a Gram‐negative symbiont to dominate in this ecosystem. The genome has revealed large expansions of many paralogous groups of genes that encode products essential to the organism's ability to successfully compete in this environment. Most noteable is the organism's abundant machinery for utilizing a large variety of complex polysaccharides as a source of carbon and energy. The proteome also reveals the organism's extensive ability to adapt and regulate expression of its genes in response to the changing ecosystem. These factors, as well as others highlighted below, suggest an incredibly flexible and adaptable organism that is exquisitely equipped to dominate in its challenging and competitive niche. BioEssays 25:926–929, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Several groups of large DNA viruses successfully utilise the rich resource provided by insect hosts. Defining the mechanisms that enable these pathogens to optimise their relationships with their hosts is of considerable scientific and practical importance, but our understanding of the processes involved is, as yet, rudimentary. Here we describe an informatics-based approach that uses comparison of viral genomic sequences to identify candidate genes likely to be specifically involved in this process. We hypothesise that such genes should satisfy two essential (...) criteria, namely, that they should be (i) present in those members of a virus family that infect insects, but absent from those that infect other hosts, and (ii) found in at least two unrelated taxa of insect viruses. These criteria currently identify six groups of viral genes, including one that encodes the fusolin/gp37 proteins. Demonstration that the fusolin/gp37 proteins can enhance oral infectivity of insect viruses provides a primary validation of this approach to the examination of insectvirus relationships. BioEssays 23:184–193, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

This paper discusses DNA-based stochastic optimizations under the constraint that the search starts from a given point in a search space. Generally speaking, a stochastic optimization method explores a search space and finds out the optimum or a sub-optimum after many cycles of trials and errors. This search process could be implemented efficiently by ``molecular computing'', which processes DNA molecules by the techniques of molecular biology to generate and evaluate a vast number of solution candidates at a time. We assume (...) the exploration starting from a single point, and propose a method to embody DNA-based optimization under this constraint, because this method has a promising application in the research field of protein engineering. In this application, a string of nucleotide bases encodes a protein possessing a specific activity, which could be given as a value of an objective function. Thus, a problem of obtaining a protein with the optimum or a sub-optimum about the desired activity corresponds to a combinatorial problem of obtaining a base sequence giving the optimum or a sub-optimum in the sequence space. Biologists usually modify a base sequence corresponding to a naturally occurring protein into another sequence giving a desired activity. In other words, they explore the space in the proximity of a natural protein as a start point. We first examined if the optimization methods that involve a single start point, such as simulated annealing, Gibbs sampler, and MH algorithms, can be implemented by DNA-based operations. Then, we proposed an application of genetic algorithm, and examined the performance of this application on a model fitness landscape by computer experiments. These experiments gave helpful guidelines in the embodiments of DNA-based stochastic optimization, including a better design of crossover operator. (shrink)

The causative agent of COVID‐19 SARS‐CoV‐2 has led to over 4 million deaths worldwide. Understanding the origin of this coronavirus is important for the prevention of future outbreaks. The dominant point of view that the virus transferred to humans either directly from bats or through an intermediate mammalian host has been challenged by Segreto and Deigin, who claim that the genome of SARS‐CoV‐2 has certain features suggestive of its artificial creation. Following their response to our commentary, here we continue the (...) discussion of the proposed arguments for this hypothesis. We show that neither the existence of a furin cleavage site in SARS‐CoV‐2, nor the presence of specific sequences within the nucleotide insertion encoding that site are evidence for intelligent design. We also explain why existing genetic data, viral diversity and past human history suggest that a natural origin of the virus is the most likely scenario. Genetic evidence suggesting otherwise is yet to be presented. (shrink)

The ability to initiate DNA replication is a critical step in the proliferation of all organisms. In bacteria, this process is mediated by an ATP‐dependent replication initiator protein, DnaA, which recognizes and melts replication origin (oriC) elements. Despite decades of biochemical and structural work, a mechanistic understanding of how DnaA recognizes and unwinds oriC has remained enigmatic. A recent study by Pelliciari et al. provides important new structural insights into how DnaA from Bacillus subtilis recognizes and processes its cognate oriC, (...) showing how DnaA uses sequence features encoded in the origin to engage melted DNA. Comparison of the DnaA‐oriC structure with archaeal/eukaryl replication origin complexes based on Orc‐family proteins reveals a high degree of similarity in origin engagement by initiators from di domains of life, despite fundamental differences in origin melting mechanisms. These findings provide valuable insights into bacterial replication initiation and highlight the intriguing evolutionary history of this fundamental biological process. (shrink)

Do children’s single words related to motion and change also encode aspects of environmental events highlighted by Talmy’s motion event analysis? If so, these meanings may predict children’s early verb meanings. Analyzing the kinds of meanings expressed in single “dynamic event words” through motion event semantics yields links between early true verbs in sentences and the semantics encoded in these single words. Dynamic event words reflect the sense of temporal and spatial reversibility established in the late sensorimotor period. We propose (...) that these dynamic meanings provide the semantic foundation for the most common verbs included in early sentences, and thus a bootstrap to full development of the verb repertoire. In this study, we followed the spoken language development of five children. We identified dynamic event words as encoding dynamic change in the following dimensions: spatial direction in relation to self; vertical spatial direction; figure/ground relationships; and temporal event sequences. Verbs continuing the semantics previously identified in dynamic event words occurred early and dominated the verb repertoire through 24 months of age. (shrink)

From 1956, when the complex ultrastructure of meiotic chromosomes was discovered, 1 until 1985, when the isolation of meiotic chromosome cores was reported, knowledge of the molecular structure of the meiotic chromosome was at best a dream. The dissection of meiotic chromosome structures has become a realistic challenge through the arrival of isolated symptonemal complexes (SCs), monoclonal and polyclonal antibodies against SCs, the possibility for screening expression libraries for genes that encode SC proteins, the isolation of SC‐associated DNA, and the (...) development of techniques for the in situ recognition of DNA sequences in the context of the meiotic chromosome structure. (shrink)

It has been proposed that somatic mutations make major contributions to aging. The first paper, based on a gene knock‐in mouse, supports a contributory role for mutation in mtDNA1 in aging, but does not support a damaged‐mtDNA‐producing‐more‐damaged‐mtDNA hypothesis.1 The second paper2 indicates some GC‐rich sequences in the nuclear DNA are more sensitive to oxidative damage than mtDNA. As a result, key genes involved in brain function and mitochondrial function are progressively inactivated with age. Failure in these nucleus‐encoded mitochondrial genes may (...) be a primary reason for mitochondrial failure in old age. BioEssays 26:1160–1163, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

A major distinction in the social organization of ant societies is the number of reproductive queens that reside in a single colony. The fire ant Solenopsis invicta exists in two distinct social forms, one with colonies headed by a single reproductive queen and the other containing several to hundreds of egg‐laying queens. This variation in social organization has been shown to be associated with genotypes at the gene Gp‐9. Specifically, single‐queen colonies have only the B allelic variant of this gene, (...) whereas multiple‐queen colonies always have the b variant as well. Subsequent studies revealed that Gp‐9 shares the highest sequence similarity with genes encoding pheromone‐binding proteins (PBPs). In other insects, PBPs serve as central molecular components in the process of chemical recognition of conspecifics. Fire ant workers regulate the number of egg‐laying queens in a colony by accepting queens that produce appropriate chemical signals and destroying those that do not. The likely role of GP‐9 in chemoreception suggests that the essential distinction in colony queen number between the single and multiple‐queen form originates from differences in workers' abilities to recognize queens. Other, closely related fire ant species seem to regulate colony social organization in a similar fashion. BioEssays 27:91–99, 2005. © 2004 Wiley Periodicals, Inc. (shrink)

In order to memorize sentences we use both processes of language comprehension during encoding and processes of language production during maintenance. While the former processes are easily testable via controlled presentation of the input, the latter are more difficult to assess directly as language production is typically initiated and controlled internally. In the present event-related potential (ERP) study we track subvocal rehearsal of sentences, with the goal of studying the concomitant planning processes with the help of a silent cued-production task. (...) Native German participants read different types of sentences word-by-word, then were prompted by a visual cue to silently repeat each individual word, in a rehearsal phase. In order to assess both local and global effects of sentence planning, we presented correct sentences, syntactically or semantically violated sentences, or random word order sequences. Semantic violations during reading elicited an N400 effect at the noun violating the selectional restrictions of the preceding verb. Syntactic violations, induced by a gender incongruency between determiner and noun, led to a P600 effect at the same position. Different ERP patterns occurred during the silent production phase. Here, semantically violated sentences elicited an early fronto-central negativity at the verb, while syntactically violated sentences elicited a late right-frontal positivity at the determiner. Random word order was accompanied by long-lasting slow waves during the production phase. The findings are consistent with models of hierarchical sentence planning and further indicate that the ongoing working memory processes are qualitatively distinct from comprehension mechanisms and neurophysiologically specific for syntactic and lexical-semantic level planning. In conclusion, active working memory maintenance of sentences is likely to comprise specific stages of sentence production that are indicated by ERP correlates of syntactic and semantic planning at the phrasal and clausal level respectively. (shrink)

The regional brain networks and the underlying neurophysiological mechanisms subserving the cognition of visual narrative in humans have largely been studied with non-invasive brain recording. In this study, we specifically investigated how regional and cross-regional cortical activities support visual narrative interpretation using intracranial stereotactic electroencephalograms recordings from thirteen human subjects (6 females, and 7 males). Widely distributed recording sites across the brain were sampled while subjects were explicitly instructed to observe images from fables presented in “sequential” order, and a set (...) of images drawn from multiple fables presented in “scrambled” order. Broadband activity mainly within the frontal and temporal lobes were found to encode if a presented image is part of a visual narrative (sequential) or random image set (scrambled). Moreover, the temporal lobe exhibits strong activation in response to visual narratives while the frontal lobe is more engaged when contextually novel stimuli are presented. We also investigated the dynamics of interregional interactions between visual narratives and contextually novel series of images. Interestingly, the interregional connectivity is also altered between sequential and scrambled sequences. Together, these results suggest that both changes in regional neuronal activity and cross-regional interactions subserve visual narrative and contextual novelty processing. (shrink)

Mitochondrial homeostasis serves as a cornerstone of cellular function, orchestrating a delicate balance between energy production, redox status, and cellular signaling transduction. This equilibrium involves a myriad of interconnected processes, including mitochondrial dynamics, quality control mechanisms, and biogenesis and degradation. Perturbations in mitochondrial homeostasis have been implicated in a wide range of diseases, including neurodegenerative diseases, metabolic syndromes, and aging‐related disorders. In the past decades, the discovery of numerous mitochondrial proteins and signaling has led to a more complete understanding of (...) the intricate mechanisms underlying mitochondrial homeostasis. Recent studies have revealed that Family with sequence similarity 210 member A (FAM210A) is a novel nuclear‐encoded mitochondrial protein involved in multiple aspects of mitochondrial homeostasis, including mitochondrial quality control, dynamics, cristae remodeling, metabolism, and proteostasis. Here, we review the function and physiological role of FAM210A in cellular and organismal health. This review discusses how FAM210A acts as a regulator on mitochondrial inner membrane to coordinate mitochondrial dynamics and metabolism. (shrink)

This book intends to show that, in philosophy of mathematics, radical naturalism (or physicalism), nominalism and strict finitism (which does not assume the reality of infinity in any format, not even potential infinity) can account for the applications of classical mathematics in current scientific theories about the finite physical world above the Planck scale. For that purpose, the book develops some significant applied mathematics in strict finitism, which is essentially quantifier-free elementary recursive arithmetic (with real numbers encoded as elementary recursive (...) Cauchy sequences of rational numbers). Applied mathematical theories developed in the book include the basics of calculus, metric space theory, complex analysis, Lebesgue integration, Hilbert spaces, and semi-Riemann geometry (sufficient for the basic applications in classical quantum mechanics and general relativity). The fact that so much applied mathematics can be developed within such a weak, strictly finitisitc system is perhaps surprising in itself. It also shows that the applications of those classical theories to the finite physical world can be translated into the applications of strict finitism, which demonstrates the applicability of those classical theories without assuming the literal truth of those theories or the reality of infinity. The first chapter of the book contains an informal introduction to its philosophical motivation and technical strategy. The book is intended for students and researchers in philosophy of mathematics. -/- Contents -/- Preface 1 Introduction 2 Strict Finitism 3 Calculus 4 Metric Space 5 Complex Analysis 6 Integration 7 Hilbert Space 8 Semi-Riemann Geometry References Index. (shrink)

Heterotrimeric G proteins, consisting of α, β, and γ subunits, couple ligand-bound seven transmembrane domain receptors to the regulation of effector proteins and production of intracellular second messengers. G protein signaling mediates the perception of environmental cues in all higher eukaryotic organisms, including yeast, Dictyostelium, plants, and animals. The nematode Caenorhabditis elegans is the first animal to have complete descriptions of its cellular anatomy, cell lineage, neuronal wiring diagram, and genomic sequence. In a recent paper, Jansen et al.(1) used (...) sequence searches of the C. elegans genome database to identify all heterotrimeric G protein genes (20 Gα, 2 Gβ, 2 Gγ). C. elegans encodes one ortholog of each of the four Gα classes found in metazoans and 16 new Gα genes. The orthologous genes are widely expressed, whereas 14 of the divergent Gα genes are almost exclusively expressed in sensory neurons where they may regulate perception and chemotaxis.BioEssays 21:713–717, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The traditional verbal/nonverbal dichotomy is inadequate for completely describing cerebral lateralization. Musical functions are not necessarily mediated by the right hemisphere; evidence for a specialist left-hemisphere mechanism dedicated to the encoded speech signal is weakening, and the right hemisphere possesses considerable comprehensional powers. Right-hemisphere processing is often said to be characterized by holistic or gestalt apprehension, and face recognition may be mediated by this hemisphere partly because of these powers, partly because of the right hemisphere's involvement in emotional affect, and (...) possibly through the hypothesized existence of a specialist face processor or processors in the right. The latter hypothesis may, however, suffer the same fate as the one relating to a specialist encodedness processor for speech in the left. Verbal processing is largely the province of the left because of this hemisphere's possession of sequential, analytic, time-dependent mechanisms. Other distinctions are special cases of an analytic/holistic dichotomy. More fundamentally, however, the left hemisphere is characterized by its mediation of discriminations involving duration, temporal order, sequencing, and rhythm, at thesensory level, and especially at themotorlevel. Spatial aspects characterize the right, the mapping of exteroceptive body space, and the positions of fingers, limbs, and perhaps articulators, with respect to actual and target positions. Thus there is a continuum of function between the hemispheres, rather than a rigid dichotomy, the differences being quantitative rather than qualitative, of degree rather than of kind. (shrink)

Knowing how introns originated should greatly enhance our understanding of the information we carry in our DNA. Gilbert’s suggestion that introns initially arose to facilitate recombination still stands, though not for the reason he gave. Reanney’s alternative, that evolution, from the early “RNA world” to today’s DNA-based world, would require the ability to detect and correct errors by recombination, now seems more likely. Consistent with this, introns are richer than exons in the potential to extrude the stem-loop structures needed for (...) the homology search that can lead to heteroduplex formation and the recognition of base mismatches. In nucleic acid sequences that were unable concomitantly to encode sufficient stem-loop potential, protein-encoding potential was constrained to arise as segments (exons) interrupted by segments rich in stem-loop potential (introns). Thus, sequences with properties that we now deem intronic are likely to have preceded the emergence of exons. (shrink)

Villin, a calcium‐regulated actin‐binding protein, modulates the structure and assembly of actin filaments in vitro. It is organized into three domains, the first two of which are homologous. Villin is mainly produced in epithelial cells that develop a brush border and which are responsible for nutrient uptake. Expression of the villin structural gene is precisely regulated during mouse embryogenesis and is restricted in adults, to certain epithelia of the gastrointestinal and urogenital tracts. The function of villin has been assessed by (...) transfecting CV1 cells with a human cDNA encoding wild‐type villin or mutant villin. Synthesis of large amounts of villin in cells which do not normally produce this protein induces the growth of microvilli on the cell surface and the redistribution of F‐actin, concomitant with the disappearance of stress fibers. The complete villin sequence is required for the morphogenic effect. These results suggest that villin plays a key role in the morphogenesis of microvilli. (shrink)