Understanding mutational and selective processes that govern gene duplication in mammals

Abstract : Gene duplication is an essential source of material for the origin of genetic novelties. The reverse transcription of source gene mRNA followed by the genomic insertion of the resulting cDNA - retroposition - has provided the human genome with at least ~3600 detectable retrocopies. We find that ~30% of these retrocopies are transcribed, generally in testes. Their transcription often relies on preexisting regulatory elements (or open chromatin) close to their insertion site, which is illustrated by mRNA molecules containing retrocopies fused to their neighboring genes. Retrocopies appear to have been profoundly shaped by selection. Consistently, human retrocopies with an intact open reading (ORF) are more often transcribed than retropseudogenes, which leads to a minimal estimate of 120 functional retrogenes present in our genome. We also performed an analysis of Ka/Ks for human retrocopies. This analysis demonstrates that several intact retrocopies evolved under purifying selection and yields an estimated formation rate of ~1 retrogene per million year in the primate lineage. Using DNA sequencing and evolutionary simulations, we have identified 7 such primate-specific retrogenes that emerged on the lineage leading to humans In therian genomes, we found an excess of retrogenes with X-linked parents. Expression analyses support the idea that this "out of X" movement was driven by natural selection to produce autosomal functional counterparts for X-linked genes, which are silenced during male meiosis. Phylogenetic dating of this "out of X" movement suggests that our sex chromosomes arose about 180 MYA ago and are thus much younger than previously thought. Finally, we have also analyzed young gene duplications (and deletions) that arose by non allelic-homologous recombination and are not fixed in species. Using wild-caught and laboratory animals, we detected thousands of DNA segments that are polymorphic in copy number in mice. These copy number variants were found to profoundly alter the transcriptome of several mouse tissues. Strikingly, their influence on gene expression is not limited to the gene they contain but seems to extend to genes located up to 1.5 million bases away.

Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.

Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α(V)β(3) integrin in trans eliciting responses in astrocytes. Nonetheless, whether α(V)β(3) integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α(V)β(3) integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α(V)β(3) integrin restricted neurite outgrowth. Likewise, α(V)β(3)-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(-) CAD cells. In differentiating primary neurons exposed to α(V)β(3)-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, α(V)β(3)-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α(V)β(3) integrin. Binding of α(V)β(3)-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α(V)β(3)-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α(V)β(3) integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.

Stochastic models and numerical algorithms for a class of regulatory gene networks.

Regulatory gene networks contain generic modules, like those involving feedback loops, which are essential for the regulation of many biological functions (Guido et al. in Nature 439:856-860, 2006). We consider a class of self-regulated genes which are the building blocks of many regulatory gene networks, and study the steady-state distribution of the associated Gillespie algorithm by providing efficient numerical algorithms. We also study a regulatory gene network of interest in gene therapy, using mean-field models with time delays. Convergence of the related time-nonhomogeneous Markov chain is established for a class of linear catalytic networks with feedback loops.

Psychosocial analysis of the collective processes in the United States after September 11

This article studies alterations in the values, attitudes, and behaviors that emerged among U.S. citizens as a consequence of, and as a response to, the attacks of September 11, 2001. The study briefly examines the immediate reaction to the attack, before focusing on the collective reactions that characterized the behavior of the majority of the population between the events of 9/11 and the response to it in the form of intervention in Afghanistan. In studying this period an eight-phase sequential model (Botcharova, 2001) is used, where the initial phases center on the nation as the ingroup and the latter focus on the enemy who carried out the attack as the outgroup. The study is conducted from a psychosocial perspective and uses "social identity theory" (Tajfel & Turner, 1979, 1986) as the basic framework for interpreting and accounting for the collective reactions recorded. The main purpose of this paper is to show that the interpretation of these collective reactions is consistent with the postulates of social identity theory. The application of this theory provides a different and specific analysis of events. The study is based on data obtained from a variety of rigorous academic studies and opinion polls conducted in relation to the events of 9/11. In line with social identity theory, 9/11 had a marked impact on the importance attached by the majority of U.S. citizens to their identity as members of a nation. This in turn accentuated group differentiation and activated ingroup favoritism and outgroup discrimination (Tajfel & Turner, 1979, 1986). Ingroup favoritism strengthened group cohesion, feelings of solidarity, and identification with the most emblematic values of the U.S. nation, while outgroup discrimination induced U.S. citizens to conceive the enemy (al-Qaeda and its protectors) as the incarnation of evil, depersonalizing the group and venting their anger on it, and to give their backing to a military response, the eventual intervention in Afghanistan. Finally, and also in line with the postulates of social identity theory, as an alternative to the virtual bipolarization of the conflict (U.S. vs al-Qaeda), the activation of a higher level of identity in the ingroup is proposed, a group that includes the United States and the largest possible number of countries¿ including Islamic states¿in the search for a common, more legitimate and effective solution.

Effect of orthographic processes on letter identity and letter-position encoding in dyslexic children.

The ability to identify letters and encode their position is a crucial step of the word recognition process. However and despite their word identification problem, the ability of dyslexic children to encode letter identity and letter-position within strings was not systematically investigated. This study aimed at filling this gap and further explored how letter identity and letter-position encoding is modulated by letter context in developmental dyslexia. For this purpose, a letter-string comparison task was administered to French dyslexic children and two chronological age (CA) and reading age (RA)-matched control groups. Children had to judge whether two successively and briefly presented four-letter strings were identical or different. Letter-position and letter identity were manipulated through the transposition (e.g., RTGM vs. RMGT) or substitution of two letters (e.g., TSHF vs. TGHD). Non-words, pseudo-words, and words were used as stimuli to investigate sub-lexical and lexical effects on letter encoding. Dyslexic children showed both substitution and transposition detection problems relative to CA-controls. A substitution advantage over transpositions was only found for words in dyslexic children whereas it extended to pseudo-words in RA-controls and to all type of items in CA-controls. Letters were better identified in the dyslexic group when belonging to orthographically familiar strings. Letter-position encoding was very impaired in dyslexic children who did not show any word context effect in contrast to CA-controls. Overall, the current findings point to a strong letter identity and letter-position encoding disorder in developmental dyslexia.

Psychosocial analysis of the collective processes in the United States after September 11

This article studies alterations in the values, attitudes, and behaviors that emerged among U.S. citizens as a consequence of, and as a response to, the attacks of September 11, 2001. The study briefly examines the immediate reaction to the attack, before focusing on the collective reactions that characterized the behavior of the majority of the population between the events of 9/11 and the response to it in the form of intervention in Afghanistan. In studying this period an eight-phase sequential model (Botcharova, 2001) is used, where the initial phases center on the nation as the ingroup and the latter focus on the enemy who carried out the attack as the outgroup. The study is conducted from a psychosocial perspective and uses "social identity theory" (Tajfel & Turner, 1979, 1986) as the basic framework for interpreting and accounting for the collective reactions recorded. The main purpose of this paper is to show that the interpretation of these collective reactions is consistent with the postulates of social identity theory. The application of this theory provides a different and specific analysis of events. The study is based on data obtained from a variety of rigorous academic studies and opinion polls conducted in relation to the events of 9/11. In line with social identity theory, 9/11 had a marked impact on the importance attached by the majority of U.S. citizens to their identity as members of a nation. This in turn accentuated group differentiation and activated ingroup favoritism and outgroup discrimination (Tajfel & Turner, 1979, 1986). Ingroup favoritism strengthened group cohesion, feelings of solidarity, and identification with the most emblematic values of the U.S. nation, while outgroup discrimination induced U.S. citizens to conceive the enemy (al-Qaeda and its protectors) as the incarnation of evil, depersonalizing the group and venting their anger on it, and to give their backing to a military response, the eventual intervention in Afghanistan. Finally, and also in line with the postulates of social identity theory, as an alternative to the virtual bipolarization of the conflict (U.S. vs al-Qaeda), the activation of a higher level of identity in the ingroup is proposed, a group that includes the United States and the largest possible number of countries¿ including Islamic states¿in the search for a common, more legitimate and effective solution.

Chemodiversity and molecular plasticity: recognition processes as explored by property spaces.

In the last few years, a need to account for molecular flexibility in drug-design methodologies has emerged, even if the dynamic behavior of molecular properties is seldom made explicit. For a flexible molecule, it is indeed possible to compute different values for a given conformation-dependent property and the ensemble of such values defines a property space that can be used to describe its molecular variability; a most representative case is the lipophilicity space. In this review, a number of applications of lipophilicity space and other property spaces are presented, showing that this concept can be fruitfully exploited: to investigate the constraints exerted by media of different levels of structural organization, to examine processes of molecular recognition and binding at an atomic level, to derive informative descriptors to be included in quantitative structure--activity relationships and to analyze protein simulations extracting the relevant information. Much molecular information is neglected in the descriptors used by medicinal chemists, while the concept of property space can fill this gap by accounting for the often-disregarded dynamic behavior of both small ligands and biomacromolecules. Property space also introduces some innovative concepts such as molecular sensitivity and plasticity, which appear best suited to explore the ability of a molecule to adapt itself to the environment variously modulating its property and conformational profiles. Globally, such concepts can enhance our understanding of biological phenomena providing fruitful descriptors in drug-design and pharmaceutical sciences.

Report on a review of State employee grievance processes, settlement agreements entered into by the State and payments made during the period July 1, 2010 through June 30, 2014

Report on a review of State employee grievance processes, settlement agreements entered into by the State and payments made during the period July 1, 2010 through June 30, 2014

Role of homer 1 proteins in the calcium signaling pathway(s) underlying exo-endocytosis processes of glutamatergic slmvs in astrocytes

The discovery that astrocytes possess a nonelectrical form of excitability (calcium excitability) that leads to the release of chemical transmitters, an activity called gliotransmission, indicates that these cells may have additional important roles in brain function. Elucidating the stimulussecretion coupling leading to the exocytic release of chemical transmitters (such as glutamate, Bezzi et al., Nature Neurosci, 2004) may therefore clarify i) whether astrocytes represent in full a new class of secretory cells in the brain and ii) whether they can participate to the fast brain signaling in the brain. We have recently discovered the existence in astrocytes of functional sub-membrane microdomains of calcium release from the internal stores in response to mGluR5 activation (Marchaland et al., J of Neurosci., 2008). Such sub-plasma membrane calcium microdomains control exocytosis of astrocytic glutamate signaling to neurons. Homer proteins are scaffold proteins controlling calcium signaling in different cellular microdomains, including dendritic spines in neurons (Sala et al., J of Neurosci., 2005). Thus, similarly to dendritic pines, Homer1 could be implicated in the coupling between astrocytic mGluR5 and IP3Rs on the ER. Here, by using a recently developed approach for studying vesicle recycling dynamics at synapses (Voglmaier et al., Neuron, 2006; Balaji and Ryan, PNAS, 2007) combined with epifluorescence and total internal reflection fluorescence (TIRF) imaging, we investigated the involvement of Homer1 proteins in the calcium dependent stimulus-secretion coupling leading glutamate exocytosis of synaptic-like microvesicles (SLMVs) in astrocytes.

Selection processes in a citrus hybrid population using RAPD markers

The objective of this work was to evaluate the processes of selection in a citrus hybrid population using segregation analysis of RAPD markers. The segregation of 123 RAPD markers between 'Cravo' mandarin (Citrus reticulata Blanco) and 'Pêra' sweet orange (C. sinensis (L.) Osbeck) was analysed in a F1 progeny of 94 hybrids. Genetic composition, diversity, heterozygosity, differences in chromosomal structure and the presence of deleterious recessive genes are discussed based on the segregation ratios obtained. A high percentage of markers had a skeweness of the 1:1 expected segregation ratio in the F1 population. Many markers showed a 3:1 segregation ratio in both varieties and 1:3 in 'Pêra' sweet orange, probably due to directional selection processes. The distribution analysis of the frequencies of the segregant markers in a hybrid population is a simple method which allows a better understanding of the genetics of citrus group.

H2O-δD-Fe-III relations of dehydrogenation and dehydration processes in magmatic amphiboles

Stable isotope compositions of a suite of magmatic amphiboles from alkaline basalts and andesitic rocks were examined to constrain the effects of degassing processes on the hydrogen isotope compositions. The Fe3+ (as Fe3+/Fe-total) and H2O contents, as well as the H isotope compositions of the amphiboles, differ markedly (27-58%, 0.5-2.2 wt%, -107 to -15 parts per thousand, respectively) but indicate systematic variations. The observed trends can be explained either as dehydrogenation or dehydration processes, both of which are coupled to oxidation processes, the latter most probably related to O2- substitution within amphiboles. The dehydrogenation-dehydration models can be used to assess the primary compositions of the magmas. As an important example, delta D values of amphiboles of Martian meteorites are discussed in a similar context. Copyright (c) 2006 John Wiley & Sons, Ltd.

External forcings, oceanographic processes and particle flux dynamics in Cap de Creus submarine canyon, NW Mediterranean Sea

Particle fluxes (including major components and grain size), and oceanographic parameters (near-bottom water temperature, current speed and suspended sediment concentration) were measured along the Cap de Creus submarine canyon in the Gulf of Lions (GoL; NW Mediterranean Sea) during two consecutive winter-spring periods (2009 2010 and 2010 2011). The comparison of data obtained with the measurements of meteorological and hydrological parameters (wind speed, turbulent heat flux, river discharge) have shown the important role of atmospheric forcings in transporting particulate matter through the submarine canyon and towards the deep sea. Indeed, atmospheric forcing during 2009 2010 and 2010 2011 winter months showed differences in both intensity and persistence that led to distinct oceanographic responses. Persistent dry northern winds caused strong heat losses (14.2 × 103 W m−2) in winter 2009 2010 that triggered a pronounced sea surface cooling compared to winter 2010 2011 (1.6 × 103 W m−2 lower). As a consequence, a large volume of dense shelf water formed in winter 2009 2010, which cascaded at high speed (up to ∼1 m s−1) down Cap de Creus Canyon as measured by a current-meter in the head of the canyon. The lower heat losses recorded in winter 2010 2011, together with an increased river discharge, resulted in lowered density waters over the shelf, thus preventing the formation and downslope transport of dense shelf water. High total mass fluxes (up to 84.9 g m−2 d−1) recorded in winter-spring 2009 2010 indicate that dense shelf water cascading resuspended and transported sediments at least down to the middle canyon. Sediment fluxes were lower (28.9 g m−2 d−1) under the quieter conditions of winter 2010 2011. The dominance of the lithogenic fraction in mass fluxes during the two winter-spring periods points to a resuspension origin for most of the particles transported down canyon. The variability in organic matter and opal contents relates to seasonally controlled inputs associated with the plankton spring bloom during March and April of both years.

Information sharing and social network dynamics : a coevolutionary approach

The capacity to interact socially and share information underlies the success of many animal species, humans included. Researchers of many fields have emphasized the evo¬lutionary significance of how patterns of connections between individuals, or the social networks, and learning abilities affect the information obtained by animal societies. To date, studies have focused on the dynamics either of social networks, or of the spread of information. The present work aims to study them together. We make use of mathematical and computational models to study the dynamics of networks, where social learning and information sharing affect the structure of the population the individuals belong to. The number and strength of the relationships between individuals, in turn, impact the accessibility and the diffusion of the shared information. Moreover, we inves¬tigate how different strategies in the evaluation and choice of interacting partners impact the processes of knowledge acquisition and social structure rearrangement. First, we look at how different evaluations of social interactions affect the availability of the information and the network topology. We compare a first case, where individuals evaluate social exchanges by the amount of information that can be shared by the partner, with a second case, where they evaluate interactions by considering their partners' social status. We show that, even if both strategies take into account the knowledge endowments of the partners, they have very different effects on the system. In particular, we find that the first case generally enables individuals to accumulate higher amounts of information, thanks to the more efficient patterns of social connections they are able to build. Then, we study the effects that homophily, or the tendency to interact with similar partners, has on knowledge accumulation and social structure. We compare the case where individuals who know the same information are more likely to learn socially from each other, to the opposite case, where individuals who know different information are instead more likely to learn socially from each other. We find that it is not trivial to claim which strategy is better than the other. Depending on the possibility of forgetting information, the way new social partners can be chosen, and the population size, we delineate the conditions for which each strategy allows accumulating more information, or in a faster way For these conditions, we also discuss the topological characteristics of the resulting social structure, relating them to the information dynamics outcome. In conclusion, this work paves the road for modeling the joint dynamics of the spread of information among individuals and their social interactions. It also provides a formal framework to study jointly the effects of different strategies in the choice of partners on social structure, and how they favor the accumulation of knowledge in the population. - La capacité d'interagir socialement et de partager des informations est à la base de la réussite de nombreuses espèces animales, y compris les humains. Les chercheurs de nombreux domaines ont souligné l'importance évolutive de la façon dont les modes de connexions entre individus, ou réseaux sociaux et les capacités d'apprentissage affectent les informations obtenues par les sociétés animales. À ce jour, les études se sont concentrées sur la dynamique soit des réseaux sociaux, soit de la diffusion de l'information. Le présent travail a pour but de les étudier ensemble. Nous utilisons des modèles mathématiques et informatiques pour étudier la dynamique des réseaux, où l'apprentissage social et le partage d'information affectent la structure de la population à laquelle les individus appartiennent. Le nombre et la solidité des relations entre les individus ont à leurs tours un impact sur l'accessibilité et la diffusion de l'informa¬tion partagée. Par ailleurs, nous étudions comment les différentes stratégies d'évaluation et de choix des partenaires d'interaction ont une incidence sur les processus d'acquisition des connaissances ainsi que le réarrangement de la structure sociale. Tout d'abord, nous examinons comment des évaluations différentes des interactions sociales influent sur la disponibilité de l'information ainsi que sur la topologie du réseau. Nous comparons un premier cas, où les individus évaluent les échanges sociaux par la quantité d'information qui peut être partagée par le partenaire, avec un second cas, où ils évaluent les interactions en tenant compte du statut social de leurs partenaires. Nous montrons que, même si les deux stratégies prennent en compte le montant de connaissances des partenaires, elles ont des effets très différents sur le système. En particulier, nous constatons que le premier cas permet généralement aux individus d'accumuler de plus grandes quantités d'information, grâce à des modèles de connexions sociales plus efficaces qu'ils sont capables de construire. Ensuite, nous étudions les effets que l'homophilie, ou la tendance à interagir avec des partenaires similaires, a sur l'accumulation des connaissances et la structure sociale. Nous comparons le cas où des personnes qui connaissent les mêmes informations sont plus sus¬ceptibles d'apprendre socialement l'une de l'autre, au cas où les individus qui connaissent des informations différentes sont au contraire plus susceptibles d'apprendre socialement l'un de l'autre. Nous constatons qu'il n'est pas trivial de déterminer quelle stratégie est meilleure que l'autre. En fonction de la possibilité d'oublier l'information, la façon dont les nouveaux partenaires sociaux peuvent être choisis, et la taille de la population, nous déterminons les conditions pour lesquelles chaque stratégie permet d'accumuler plus d'in¬formations, ou d'une manière plus rapide. Pour ces conditions, nous discutons également les caractéristiques topologiques de la structure sociale qui en résulte, les reliant au résultat de la dynamique de l'information. En conclusion, ce travail ouvre la route pour la modélisation de la dynamique conjointe de la diffusion de l'information entre les individus et leurs interactions sociales. Il fournit également un cadre formel pour étudier conjointement les effets de différentes stratégies de choix des partenaires sur la structure sociale et comment elles favorisent l'accumulation de connaissances dans la population.