Plasticity between visual input pathways and the head direction system

Animals can maintain a stable sense of direction even when they navigate in novel environments, but how the animal's brain interprets and encodes unfamiliar sensory information in its navigation system to maintain a stable sense of direction is a mystery. Recent studies have suggested that distinct brain structures of mammals and insects have evolved to solve this common problem with strategies that share computational principles; specifically, a network structure called a ring attractor maintains the sense of direction. Initially, in a novel environment, the animal's sense of direction relies on self-motion cues. Over time, the mapping from visual inputs to head direction cells, responsible for the sense of direction, is established via experience-dependent plasticity. Yet the mechanisms that facilitate acquiring a world-centered sense of direction, how many environments can be stored in memory, and what visual features are selected, all remain unknown. Thanks to recent advances in large scale physiological recording, genetic tools, and theory, these mechanisms may soon be revealed.     

How does selfing affect the genetic variance of quantitative traits? An updated meta‐analysis on empirical results in angiosperm species

Most theoretical works predict that selfing should reduce the level of additive genetic variance available for quantitative traits within natural populations. Despite a growing number of quantitative genetic studies undertaken during the last two decades, this prediction is still not well supported empirically. To resolve this issue and confirm or reject theoretical predictions, we reviewed quantitative trait heritability estimates from natural plant populations with different rates of self‐fertilization and carried out a meta‐analysis. In accordance with models of polygenic traits under stabilizing selection, we found that the fraction of additive genetic variance is negatively correlated with the selfing rate. Although the mating system explains a moderate fraction of the variance, the mean reduction of narrow‐sense heritability values between strictly allogamous and predominantly selfing populations is strong, around 60%. Because some nonadditive components of genetic variance become selectable under inbreeding, we determine whether self‐fertilization affects the relative contribution of these components to genetic variance by comparing narrow‐sense heritability estimates from outcrossing populations with broad‐sense heritability estimated in autogamous populations. Results suggest that these nonadditive components of variance may restore some genetic variance in predominantly selfing populations; it remains, however, uncertain how these nonadditive components will contribute to adaptation.     

Behavioral plasticity in C. elegans: paradigms,circuits, genes

Life in the soil is an intellectual and practical challenge that the nematode Caenorhabditis elegans masters by utilizing 302 neurons. The nervous system assembled by these 302 neurons is capable of executing a variety of behaviors, some of respectable complexity. The simplicity of the nervous system, its thoroughly characterized structure, several sets of well-defined behaviors, and its genetic amenability combined with its isogenic background make C. elegans an attractive model organism to study the genetics of behavior. This review describes several behavioral plasticity paradigms in C. elegans and their underlying neuronal circuits and then goes on to review the forward genetic analysis that has been undertaken to identify genes involved in the execution of these behaviors. Lastly, the review outlines how reverse genetics and genomic approaches can guide the analysis of the role of genes in behavior and why and how they will complement the forward genetic analysis of behavior.     

Chance, explanation, and causation in evolutionary theory

Chance comes into plays at many levels of the explanation of the evolutionary process; but the unity of sense of this category is problematic. The purpose of this talk is to clarify the meaning of chance at various levels in evolutionary theory: mutations, genetic drift, genetic revolutions, ecosystems, macroevolution. Three main concepts of chance are found at these various levels: luck (popular concept), randomness (probabilistic concept), and contingency relative to a given theoretical system (epistemological concept). After identifying which concept(s) of chance fit(s) with these levels, the question is raised whether these concepts can be reduced to a smaller number, and whether chance in evolutionary theory has a subjective or an objective sense.     

Expression and function of the empty spiracles gene in olfactory sense organ development of Drosophila melanogaster

In Drosophila, the cephalic gap gene empty spiracles plays key roles in embryonic patterning of the peripheral and central nervous system. During postembryonic development, it is involved in the development of central olfactory circuitry in the antennal lobe of the adult. However, its possible role in the postembryonic development of peripheral olfactory sense organs has not been investigated. Here, we show that empty spiracles acts in a subset of precursors that generate the olfactory sense organs of the adult antenna. All empty spiracles-expressing precursor cells co-express the proneural gene amos and the early patterning gene lozenge. Moreover, the expression of empty spiracles in these precursor cells is dependent on both amos and lozenge. Functional analysis reveals two distinct roles of empty spiracles in the development of olfactory sense organs. Genetic interaction studies in a lozenge-sensitized background uncover a requirement of empty spiracles in the formation of trichoid and basiconic olfactory sensilla. MARCM-based clonal mutant analysis reveals an additional role during axonal targeting of olfactory sensory neurons to glomeruli within the antennal lobe. Our findings on empty spiracles action in olfactory sense organ development complement previous studies that demonstrate its requirement in olfactory interneurons and, taken together with studies on the murine homologs of empty spiracles, suggest that conserved molecular genetic programs might be responsible for the formation of both peripheral and central olfactory circuitry in insects and mammals.     

In Defense of Prenatal Genetic Interventions

Jürgen Habermas has argued against prenatal genetic interventions used to influence traits on the grounds that only biogenetic contingency in the conception of children preserves the conditions that make the presumption of moral equality possible. This argument fails for a number of reasons. The contingency that Habermas points to as the condition of moral equality is an artifact of evolutionary contingency and not inviolable in itself. Moreover, as a precedent for genetic interventions, parents and society already affect children's traits, which is to say there is moral precedent for influencing the traits of descendants. A veil‐of‐ignorance methodology can also be used to justify prenatal interventions through its method of advance consent and its preservation of the contingency of human identities in a moral sense. In any case, the selection of children's traits does not undermine the prospects of authoring a life since their future remains just as contingent morally as if no trait had been selected. Ironically, the prospect of preserving human beings as they are – to counteract genetic drift – might even require interventions to preserve the ability to author a life in a moral sense. In light of these analyses, Habermas' concerns about prenatal genetic interventions cannot succeed as objections to their practice as a matter of principle; the merits of these interventions must be evaluated individually.     

Cryptochromes in the field: how blue light influences crop development

Light is a pivotal environmental element capable of influencing multiple physiological processes across the entire plant life cycle. Over the course of their evolution, plants have developed several families of photoreceptors such as phytochromes, phototropins, ultraviolet (UV) resistance locus 8 and cryptochromes (crys), in order to sense light stimuli and respond to their changes. Numerous genetic studies have demonstrated that functional alterations to these photoreceptors cause a change in important agronomical traits. In particular, crys, which absorb UVA/blue light, can influence seed germination, flowering induction, plant architecture, fruit metabolic content and resistance to biotic and abiotic stresses. In the years to come, the rising temperatures and alterations to precipitation patterns generated by climate change will present a dramatic challenge for our agricultural system, with its few varieties characterized by a narrow genetic pool derived from artificial selection. Here, we review the main roles of crys in determining important agronomic traits in crops, we discuss the opportunities of using these photoreceptors as genetic targets for tuning plant physiological responses to environmental change, and the molecular strategies used so far to manipulate this family of photoreceptors.     

二元信号转导系统与细菌的致病性

二元信号转导系统是广泛存在于细菌中的信号传导机制。病原菌在感染宿主的过程中,能通过该系统密切感受和响应体内外各种微环境的变化,进而调节各种基因表达以完成其致病过程。由于二元信号转导系统在病原菌的致病性方面具有重要作用,将其作为抗感染治疗中的靶点具有良好的应用前景。     

Ribosome structure: revisiting the connection between translational accuracy and unconventional decoding

The ribosome is a molecular machine that converts genetic information in the form of RNA, into protein. Recent structural studies reveal a complex set of interactions between the ribosome and its ligands, mRNA and tRNA, that indicate ways in which the ribosome could avoid costly translational errors. Ribosomes must decode each successive codon accurately, and structural data provide a clear indication of how ribosomes limit recruitment of the wrong tRNA (sense errors). In a triplet-based genetic code there are three potential forward reading frames, only one of which encodes the correct protein. Errors in which the ribosome reads a codon out of the normal reading frame (frameshift errors) occur less frequently than sense errors, although it is not clear from structural data how these errors are avoided. Some mRNA sequences, termed programmed-frameshift sites, cause the ribosome to change reading frame. Based on recent work on these sites, this article proposes that the ribosome uses the structure of the codon-anticodon complex formed by the peptidyl-tRNA, especially its wobble interaction, to constrain the incoming aminoacyl-tRNA to the correct reading frame.     

The formation of sense organs in Drosophila: a logical approach

The genetic analysis of development has revealed the importance of small sets of interacting genes in most morphogenetic processes. The results of gene interactions have so far been examined intuitively. This approach is largely sufficient when one deals with simple interactions, a feedback circuit for example. As more components become involved, however, it is difficult to make sure that the intuitive approach gives a comprehensive view of the behaviour of the system. In this paper, we illustrate the use of a logical approach to describe the genetic circuit that underlies the singling out of sense organ precursor cells in Drosophila. We show how to apply logical modelling to a realistic problem, and how this approach allows an easy assessment of the dynamic properties of the system, i.e., of its possible evolutions and of its reactions to fluctuations and perturbations.     

Microsatellite markers for the cushion rock jasmine, Androsace tapete (Primulaceae), a species endemic to the Qinghai-Tibetan Plateau

? Premise of the study: Microsatellite markers were developed in an alpine plant endemic to the Qinghai-Tibetan Plateau, Androsace tapete, to investigate its spatial genetic structure, gene flow, and mating patterns. ? Methods and Results: Using the combined biotin capture method, 16 microsatellite primer sets were isolated and characterized. Fifteen of these markers showed polymorphism, and the number of alleles per locus ranged from three to 13 across 56 individuals from six Tibetan populations. ? Conclusions: These markers provide a useful tool to investigate the spatial genetic structure, gene flow, and mating system of A. tapete.     

Peripheral somatosensation: a touch of genetics

The somatosensory system processes information that organisms 'feel': joint position, muscle stretch, pain, pressure, temperature, and touch. The system is composed of a diverse array of peripheral nerve endings specialized to detect these sensory modalities. Several recent discoveries have shed light on the genetic pathways that control specification and differentiation of these neurons, how they accurately innervate their central and peripheral targets, and the molecules that enable them to detect mechanical stimuli. Here, we review the cadre of genes that control these processes, focusing on mechanosensitive neurons and support cells of the skin that mediate different aspects of the sense of touch.     

A system architecture for genomic data analysis

MOTIVATION: Most of diseases are caused by a set of gene defects, which occur in a complex association. The association scheme of expressed genes can be modelled by genetic networks. Genetic networks are efficiently facilities to understand the dynamic of pathogenic processes by modelling molecular reality of cell conditions. In this sense a genetic network consists of first, a set of genes of specified cells, tissues or species and second, causal relations between these genes determining the functional condition of the biological system, i. e. under disease. A relation between two genes will exist if they both are directly or indirectly associated with disease [8]. Our goal is to characterize diseases (especially autoimmune diseases like chronic pancreatitis CP, multiple sclerosis MS, rheumatoid arthritis RA) by genetic networks generated by a computer system. We want to introduce this practice as a bioinformatic approach for finding targets.     

In vitro selection for sense codon suppression

The universal genetic code links the 20 naturally occurring amino acids to the 61 sense codons. Previously, the UAG amber stop codon (a nonsense codon) has been used as a blank in the code to insert natural and unnatural amino acids via nonsense suppression. We have developed a selection methodology to investigate whether the unnatural amino acid biocytin could be incorporated into an mRNA display library at sense codons. In these experiments we probed a single randomized NNN codon with a library of 16 orthogonal, biocytin-acylated tRNAs. In vitro selection for efficient incorporation of the unnatural amino acid resulted in templates containing the GUA codon at the randomized position. This sense suppression occurs via Watson-Crick pairing with similar efficiency to UAG-mediated nonsense suppression. These experiments suggest that sense codon suppression is a viable means to expand the chemical and functional diversity of the genetic code.     

Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes

Invadosomes support cell invasion by coupling both acto-adhesive and extracellular matrix degradative functions, which are apparently antagonistic. β1-integrin dynamics regulate this coupling, but the actual sensing mechanism and effectors involved have not yet been elucidated. Using genetic and reverse genetic approaches combined with biochemical and imaging techniques, we now show that the calcium channel TRPV4 colocalizes with β1-integrins at the invadosome periphery and regulates its activation and the coupling of acto-adhesive and degradative functions. TRPV4-mediated regulation of podosome function depends on its ability to sense reactive oxygen species (ROS) in invadosomes’ microenvironment and involves activation of the ROS/calcium-sensitive kinase Ask1 and binding of the motor MYO1C. Furthermore, disease-associated TRPV4 gain-of-function mutations that modulate ECM degradation are also implicated in the ROS response, which provides new perspectives in our understanding of the pathophysiology of TRPV4 channelopathies.     

Genetic regulation of bone mineral density in mice

Peak bone mass is a major determinant of risk of osteoporotic fracture. Family and twin studies have found a strong genetic component to the determination of bone mineral density (BMD). However, BMD is a complex trait whose expression is confounded by environmental influences and polygenic inheritance. The number, locations and effects of the individual genes contributing to natural variation in this trait are all unknown. The extreme difficulty of dissecting out environmental factors from genetic ones in humans has motivated the investigation of animal models. Genetically distinct animal strains raised under strict environmental control are critical tools for defining genetic regulation. The availability of inbred strains, combined with its relative fecundity, has established the mouse as the best model system for the study of mammalian genetics and physiology. Importantly, genes identified in murine analyses can usually be readily mapped to particular human chromosomal regions because of the high degree of synteny that exists between the mouse and human genomes. We employed quantitative trait locus (QTL) analysis to examine peak BMD in 24 recombinant inbred (RI) mouse strains, derived from a cross between C57BL/6 (B6) and DBA/2 (D2) progenitors (BXD RI). The distribution of BMD values among these strains clearly indicated the presence of strong genetic influences, with an estimated narrow sense heritability of 35%. The differences in peak whole body BMD in the BXD strains were integrated with a large database of genetic markers previously defined in the RI BXD strains to generate chromosome map sites for QTL locations. This QTL analysis provisionally identified a number of chromosomal sites linked to BMD. In the second phase of our BMD QTL mapping efforts, we used three independent mouse populations (all derived from B6 and D2 progenitor strains) to confirm and narrow the genetic locations of 4 QTLs (on chromosomes 1, 2, 4, and 11) that strongly influence the acquisition of peak BMD in mice. Using a novel, fine-mapping approach (recombinant inbred segregation testing), we have succeeded in narrowing two of the BMD-related chromosomal regions and in the process eliminated a number of candidate genes. The homologous regions in the human genome for each of these murine QTLs have been identified in recent human genetic studies. In light of this, we believe that findings in mice should aid in the identification of specific candidate genes for study in humans.     

Physicochemical Optimization in the Genetic Code Origin as the Number of Codified Amino Acids Increases

We have assumed that the coevolution theory of genetic code origin (Wong JT, Proc Natl Acad Sci USA 72:1909–1912, 1975) is essentially correct. This theory makes it possible to identify at least 10 evolutionary stages through which genetic code organization might have passed prior to reaching its current form. The calculation of the minimization level of all these evolutionary stages leads to the following conclusions. (1) The minimization percentages increased linearly with the number of amino acids codified in the codes of the various evolutionary stages when only the sense changes are considered in the analysis. This seems to favor the physicochemical theory of genetic code origin even if, as discussed in the paper, this observation is also compatible with the coevolution theory. (2) For the first seven evolutionary stages of the genetic code, this trend is less clear and indeed is inverted when we consider the global optimisation of the codes due to both sense changes and synonymous changes. This inverse correlation between minimization percentages and the number of amino acids codified in the codes of the intermediate stages seems to favor neither the physicochemical nor the stereochemical theories of genetic code origin, as it is in the early and intermediate stages of code development that these theories would expect minimization to have played a crucial role, and this does not seem to be the case. However, these results are in agreement with the coevolution theory, which attributes a role to the physicochemical properties of amino acids that, while important, is nevertheless subordinate to the mechanism which concedes codons from the precursor amino acids to the product amino acids as the primary factor determining the evolutionary structuring of the genetic code. The results are therefore discussed in the context of the various theories proposed to explain genetic code origin. Received: 25 October 1998 / Accepted: 19 February 1999     

Inference of biological S-system using the separable estimation method and the genetic algorithm

Reconstruction of a biological system from its experimental time series data is a challenging task in systems biology. The S-system which consists of a group of nonlinear ordinary differential equations (ODEs) is an effective model to characterize molecular biological systems and analyze the system dynamics. However, inference of S-systems without the knowledge of system structure is not a trivial task due to its nonlinearity and complexity. In this paper, a pruning separable parameter estimation algorithm (PSPEA) is proposed for inferring S-systems. This novel algorithm combines the separable parameter estimation method (SPEM) and a pruning strategy, which includes adding an l? regularization term to the objective function and pruning the solution with a threshold value. Then, this algorithm is combined with the continuous genetic algorithm (CGA) to form a hybrid algorithm that owns the properties of these two combined algorithms. The performance of the pruning strategy in the proposed algorithm is evaluated from two aspects: the parameter estimation error and structure identification accuracy. The results show that the proposed algorithm with the pruning strategy has much lower estimation error and much higher identification accuracy than the existing method.     

Orientation-dependent recombination hotspot activity in bacteriophage lambda.

Promoters of genetic exchange by the Escherichia coli Rec system, Chi elements, have been analyzed in λ phages carrying bacterial EcoRI restriction fragments. Some fragments confer Chi⁺ phenotype in one orientation and Chi^? in the opposite orientation. The inactivity of Chi in one orientation explains why all active Chi elements in λ manifest a certain recombinational bias of the same sense.When these studies were undertaken, we rather expected to find two classes of Chi, one class which stimulated recombinant formation stronger to its left and one class stimulating recombinant formation more strongly to its right. The failure to find the second class is now understandable by supposing that the orientation of Chi which would have permitted it to act rightward is the orientation in which Chi has no activity at all. Several models are proposed for the orientation dependence of Chi activity.     

Genetic factors and malaria in the Temuan.

The jungle habitat of the Temuan aborigines harbors a variety of infectious diseases, the most notable being malaria. Our study of 15 genetic systems in the Temuan revealed substantial polymorphism and within-population genetic diversity. The polymorphisms for Hb beta, G6PD, and El are of interest in regard to genetic adaptation to malaria. Among the polymorphisms investigated we conclude that G6PD deficiency and elliptocytosis are likely to have malaria-resistant effects as evidenced by their low association with malarial parasitemia or their higher frequency in adults than in children. These findings suggest that the malarial habitat of the Temuans is livable in the long range sense for them because of the cluster of malaria-resistant alleles in their gene pool (G6PD)-, El, and possibly, but not tested here because of its low frequency, Hb beta E). The same condition probably holds for the Semai, the nearest aborigine neighbors of the Temuan (although the Semai have not been tested for malarial parasitemia and for these polymorphisms simultaneously), since the Semai have substantial Hb betaE, G6PD-, and El. The Temuan have a cultural identity system of rituals, beliefs, and certain aspects of language which effectively isolates them genetically from Malays and other nonaborigines. This system hinders the dilution of the malaria-resistant alleles of the Temuan gene pool with the malaria-susceptible alleles of the nonaborigine gene pools.