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Sample records for accelerated foxp2 evolution

  1. Accelerated FoxP2 Evolution in Echolocating Bats

    PubMed Central

    Li, Gang; Wang, Jinhong; Rossiter, Stephen J.; Jones, Gareth; Zhang, Shuyi

    2007-01-01

    FOXP2 is a transcription factor implicated in the development and neural control of orofacial coordination, particularly with respect to vocalisation. Observations that orthologues show almost no variation across vertebrates yet differ by two amino acids between humans and chimpanzees have led to speculation that recent evolutionary changes might relate to the emergence of language. Echolocating bats face especially challenging sensorimotor demands, using vocal signals for orientation and often for prey capture. To determine whether mutations in the FoxP2 gene could be associated with echolocation, we sequenced FoxP2 from echolocating and non-echolocating bats as well as a range of other mammal species. We found that contrary to previous reports, FoxP2 is not highly conserved across all nonhuman mammals but is extremely diverse in echolocating bats. We detected divergent selection (a change in selective pressure) at FoxP2 between bats with contrasting sonar systems, suggesting the intriguing possibility of a role for FoxP2 in the evolution and development of echolocation. We speculate that observed accelerated evolution of FoxP2 in bats supports a previously proposed function in sensorimotor coordination. PMID:17878935

  2. Accelerated protein evolution and origins of human-specific features: Foxp2 as an example.

    PubMed

    Zhang, Jianzhi; Webb, David M; Podlaha, Ondrej

    2002-12-01

    Genes responsible for human-specific phenotypes may have been under altered selective pressures in human evolution and thus exhibit changes in substitution rate and pattern at the protein sequence level. Using comparative analysis of human, chimpanzee, and mouse protein sequences, we identified two genes (PRM2 and FOXP2) with significantly enhanced evolutionary rates in the hominid lineage. PRM2 is a histone-like protein essential to spermatogenesis and was previously reported to be a likely target of sexual selection in humans and chimpanzees. FOXP2 is a transcription factor involved in speech and language development. Human FOXP2 experienced a >60-fold increase in substitution rate and incorporated two fixed amino acid changes in a broadly defined transcription suppression domain. A survey of a diverse group of placental mammals reveals the uniqueness of the human FOXP2 sequence and a population genetic analysis indicates possible adaptive selection behind the accelerated evolution. Taken together, our results suggest an important role that FOXP2 may have played in the origin of human speech and demonstrate a strategy for identifying candidate genes underlying the emergences of human-specific features.

  3. Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance.

    PubMed

    Schreiweis, Christiane; Bornschein, Ulrich; Burguière, Eric; Kerimoglu, Cemil; Schreiter, Sven; Dannemann, Michael; Goyal, Shubhi; Rea, Ellis; French, Catherine A; Puliyadi, Rathi; Groszer, Matthias; Fisher, Simon E; Mundry, Roger; Winter, Christine; Hevers, Wulf; Pääbo, Svante; Enard, Wolfgang; Graybiel, Ann M

    2014-09-30

    The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2(hum)), cortico-basal ganglia circuits are specifically affected. Here we demonstrate marked effects of this humanization of Foxp2 on learning and striatal neuroplasticity. Foxp2(hum/hum) mice learn stimulus-response associations faster than their WT littermates in situations in which declarative (i.e., place-based) and procedural (i.e., response-based) forms of learning could compete during transitions toward proceduralization of action sequences. Striatal districts known to be differently related to these two modes of learning are affected differently in the Foxp2(hum/hum) mice, as judged by measures of dopamine levels, gene expression patterns, and synaptic plasticity, including an NMDA receptor-dependent form of long-term depression. These findings raise the possibility that the humanized Foxp2 phenotype reflects a different tuning of corticostriatal systems involved in declarative and procedural learning, a capacity potentially contributing to adapting the human brain for speech and language acquisition.

  4. Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance

    PubMed Central

    Schreiweis, Christiane; Bornschein, Ulrich; Burguière, Eric; Kerimoglu, Cemil; Schreiter, Sven; Dannemann, Michael; Goyal, Shubhi; Rea, Ellis; French, Catherine A.; Puliyadi, Rathi; Groszer, Matthias; Fisher, Simon E.; Mundry, Roger; Winter, Christine; Hevers, Wulf; Pääbo, Svante; Enard, Wolfgang; Graybiel, Ann M.

    2014-01-01

    The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2hum), cortico-basal ganglia circuits are specifically affected. Here we demonstrate marked effects of this humanization of Foxp2 on learning and striatal neuroplasticity. Foxp2hum/hum mice learn stimulus–response associations faster than their WT littermates in situations in which declarative (i.e., place-based) and procedural (i.e., response-based) forms of learning could compete during transitions toward proceduralization of action sequences. Striatal districts known to be differently related to these two modes of learning are affected differently in the Foxp2hum/hum mice, as judged by measures of dopamine levels, gene expression patterns, and synaptic plasticity, including an NMDA receptor-dependent form of long-term depression. These findings raise the possibility that the humanized Foxp2 phenotype reflects a different tuning of corticostriatal systems involved in declarative and procedural learning, a capacity potentially contributing to adapting the human brain for speech and language acquisition. PMID:25225386

  5. FOXP2

    PubMed Central

    Nudel, Ron; Newbury, Dianne F

    2013-01-01

    The forkhead box P2 gene, designated FOXP2, is the first gene implicated in a speech and language disorder. Since its discovery, many studies have been carried out in an attempt to explain the mechanism by which it influences these characteristically human traits. This review presents the story of the discovery of the FOXP2 gene, including early studies of the phenotypic implications of a disruption in the gene. We then discuss recent investigations into the molecular function of the FOXP2 gene, including functional and gene expression studies. We conclude this review by presenting the fascinating results of recent studies of the FOXP2 ortholog in other species that are capable of vocal communication. WIREs Cogn Sci 2013, 4:547–560. doi: 10.1002/wcs.1247 PMID:24765219

  6. FOXP2.

    PubMed

    Nudel, Ron; Newbury, Dianne F

    2013-09-01

    The forkhead box P2 gene, designated FOXP2, is the first gene implicated in a speech and language disorder. Since its discovery, many studies have been carried out in an attempt to explain the mechanism by which it influences these characteristically human traits. This review presents the story of the discovery of the FOXP2 gene, including early studies of the phenotypic implications of a disruption in the gene. We then discuss recent investigations into the molecular function of the FOXP2 gene, including functional and gene expression studies. We conclude this review by presenting the fascinating results of recent studies of the FOXP2 ortholog in other species that are capable of vocal communication. WIREs Cogn Sci 2013, 4:547-560. doi: 10.1002/wcs.1247.

  7. Evo-devo, deep homology and FoxP2: implications for the evolution of speech and language.

    PubMed

    Scharff, Constance; Petri, Jana

    2011-07-27

    The evolution of novel morphological features, such as feathers, involves the modification of developmental processes regulated by gene networks. The fact that genetic novelty operates within developmental constraints is the central tenet of the 'evo-devo' conceptual framework. It is supported by findings that certain molecular regulatory pathways act in a similar manner in the development of morphological adaptations, which are not directly related by common ancestry but evolved convergently. The Pax6 gene, important for vision in molluscs, insects and vertebrates, and Hox genes, important for tetrapod limbs and fish fins, exemplify this 'deep homology'. Recently, 'evo-devo' has expanded to the molecular analysis of behavioural traits, including social behaviour, learning and memory. Here, we apply this approach to the evolution of human language. Human speech is a form of auditory-guided, learned vocal motor behaviour that also evolved in certain species of birds, bats and ocean mammals. Genes relevant for language, including the transcription factor FOXP2, have been identified. We review evidence that FoxP2 and its regulatory gene network shapes neural plasticity in cortico-basal ganglia circuits underlying the sensory-guided motor learning in animal models. The emerging picture can help us understand how complex cognitive traits can 'descend with modification'.

  8. Evo-devo, deep homology and FoxP2: implications for the evolution of speech and language

    PubMed Central

    Scharff, Constance; Petri, Jana

    2011-01-01

    The evolution of novel morphological features, such as feathers, involves the modification of developmental processes regulated by gene networks. The fact that genetic novelty operates within developmental constraints is the central tenet of the ‘evo-devo’ conceptual framework. It is supported by findings that certain molecular regulatory pathways act in a similar manner in the development of morphological adaptations, which are not directly related by common ancestry but evolved convergently. The Pax6 gene, important for vision in molluscs, insects and vertebrates, and Hox genes, important for tetrapod limbs and fish fins, exemplify this ‘deep homology’. Recently, ‘evo-devo’ has expanded to the molecular analysis of behavioural traits, including social behaviour, learning and memory. Here, we apply this approach to the evolution of human language. Human speech is a form of auditory-guided, learned vocal motor behaviour that also evolved in certain species of birds, bats and ocean mammals. Genes relevant for language, including the transcription factor FOXP2, have been identified. We review evidence that FoxP2 and its regulatory gene network shapes neural plasticity in cortico-basal ganglia circuits underlying the sensory-guided motor learning in animal models. The emerging picture can help us understand how complex cognitive traits can ‘descend with modification’. PMID:21690130

  9. Rapid Diversification of FoxP2 in Teleosts through Gene Duplication in the Teleost-Specific Whole Genome Duplication Event

    PubMed Central

    Song, Xiaowei; Wang, Yajun; Tang, Yezhong

    2013-01-01

    As one of the most conserved genes in vertebrates, FoxP2 is widely involved in a number of important physiological and developmental processes. We systematically studied the evolutionary history and functional adaptations of FoxP2 in teleosts. The duplicated FoxP2 genes (FoxP2a and FoxP2b), which were identified in teleosts using synteny and paralogon analysis on genome databases of eight organisms, were probably generated in the teleost-specific whole genome duplication event. A credible classification with FoxP2, FoxP2a and FoxP2b in phylogenetic reconstructions confirmed the teleost-specific FoxP2 duplication. The unavailability of FoxP2b in Danio rerio suggests that the gene was deleted through nonfunctionalization of the redundant copy after the Otocephala-Euteleostei split. Heterogeneity in evolutionary rates among clusters consisting of FoxP2 in Sarcopterygii (Cluster 1), FoxP2a in Teleostei (Cluster 2) and FoxP2b in Teleostei (Cluster 3), particularly between Clusters 2 and 3, reveals asymmetric functional divergence after the gene duplication. Hierarchical cluster analyses of hydrophobicity profiles demonstrated significant structural divergence among the three clusters with verification of subsequent stepwise discriminant analysis, in which FoxP2 of Leucoraja erinacea and Lepisosteus oculatus were classified into Cluster 1, whereas FoxP2b of Salmo salar was grouped into Cluster 2 rather than Cluster 3. The simulated thermodynamic stability variations of the forkhead box domain (monomer and homodimer) showed remarkable divergence in FoxP2, FoxP2a and FoxP2b clusters. Relaxed purifying selection and positive Darwinian selection probably were complementary driving forces for the accelerated evolution of FoxP2 in ray-finned fishes, especially for the adaptive evolution of FoxP2a and FoxP2b in teleosts subsequent to the teleost-specific gene duplication. PMID:24349554

  10. Human-specific transcriptional regulation of CNS development genes by FOXP2.

    PubMed

    Konopka, Genevieve; Bomar, Jamee M; Winden, Kellen; Coppola, Giovanni; Jonsson, Zophonias O; Gao, Fuying; Peng, Sophia; Preuss, Todd M; Wohlschlegel, James A; Geschwind, Daniel H

    2009-11-12

    The signalling pathways controlling both the evolution and development of language in the human brain remain unknown. So far, the transcription factor FOXP2 (forkhead box P2) is the only gene implicated in Mendelian forms of human speech and language dysfunction. It has been proposed that the amino acid composition in the human variant of FOXP2 has undergone accelerated evolution, and this two-amino-acid change occurred around the time of language emergence in humans. However, this remains controversial, and whether the acquisition of these amino acids in human FOXP2 has any functional consequence in human neurons remains untested. Here we demonstrate that these two human-specific amino acids alter FOXP2 function by conferring differential transcriptional regulation in vitro. We extend these observations in vivo to human and chimpanzee brain, and use network analysis to identify novel relationships among the differentially expressed genes. These data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (CNS). Because FOXP2 has an important role in speech and language in humans, the identified targets may have a critical function in the development and evolution of language circuitry in humans.

  11. FoxP2 regulates neurogenesis during embryonic cortical development.

    PubMed

    Tsui, David; Vessey, John P; Tomita, Hideaki; Kaplan, David R; Miller, Freda D

    2013-01-02

    The transcription factor FoxP2 has been associated with the development of human speech but the underlying cellular function of FoxP2 is still unclear. Here we provide evidence that FoxP2 regulates genesis of some intermediate progenitors and neurons in the mammalian cortex, one of the key centers for human speech. Specifically, knockdown of FoxP2 in embryonic cortical precursors inhibits neurogenesis, at least in part by inhibiting the transition from radial glial precursors to neurogenic intermediate progenitors. Moreover, overexpression of human, but not mouse, FoxP2 enhances the genesis of intermediate progenitors and neurons. In contrast, expression of a human FoxP2 mutant that causes vocalization deficits decreases neurogenesis, suggesting that in the murine system human FoxP2 acts as a gain-of-function protein, while a human FoxP2 mutant acts as a dominant-inhibitory protein. These results support the idea that FoxP2 regulates the transition from neural precursors to transit-amplifying progenitors and ultimately neurons, and shed light upon the molecular changes that might contribute to evolution of the mammalian cortex.

  12. The medaka FoxP2, a homologue of human language gene FOXP2, has a diverged structure and function.

    PubMed

    Itakura, Tatsuo; Chandra, Abhishek; Yang, Zhi; Xue, Xiaodong; Wang, Bo; Kimura, Wataru; Hikosaka, Keisuke; Inohaya, Keiji; Kudo, Akira; Uezato, Tadayoshi; Miura, Naoyuki

    2008-03-01

    Forkhead box (Fox) genes are involved in organogenesis and cell differentiation. A mutation of FOXP2 was discovered in patients with severe defects in speech and language. The medaka FoxP2 was cloned in order to clarify the molecular evolution and difference in the protein structure and function by comparing human/mouse and medaka genes. The result showed that medaka FoxP2 had a 73.7% homology to the human and mouse counterparts, and its zinc finger, leucine zipper and forkhead domain structures were conserved. However, medaka FoxP2 lacked a long polyglutamine repeat and had two insertions of unique amino acid sequences. FoxP2 expression was found in the epiphysis and retina, in addition to the midbrain and cerebellum. The transcriptional assay revealed that medaka FoxP2 showed a very weak repressive activity to the CC10 promoter while mouse Foxp2 exhibited a strong repressive activity. Mutational analyses of medaka FoxP2 showed that the three amino acids of forkhead domain were responsible for the weak repressive activity. These results suggest that medaka FoxP2 may play a different function in the development of the medaka fish.

  13. FoxP2 in songbirds.

    PubMed

    Wohlgemuth, Sandra; Adam, Iris; Scharff, Constance

    2014-10-01

    Humans with mutations in the transcription factor FOXP2 display a severe speech disorder. Songbirds are a powerful model system to study FoxP2. Like humans, songbirds communicate via vocalizations that are imitatively learned during critical periods and this learning is influenced by social factors and relies on functionally lateralized neural circuits. During the past five years significant progress has been made moving from a descriptive to a more mechanistic understanding of how FoxP2 functions in songbirds. Current evidence from molecular and electrophysiological studies indicates that FoxP2 is important for shaping synaptic plasticity of specific neuron populations. One future goal will be to identify the transcriptional regulation orchestrated by FoxP2 and its associated molecular network that brings about these physiological effects. This will be key to further unravel how FoxP2 influences synaptic function and thereby contributes to auditory guided vocal motor behavior in the songbird model.

  14. A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.

    PubMed

    Enard, Wolfgang; Gehre, Sabine; Hammerschmidt, Kurt; Hölter, Sabine M; Blass, Torsten; Somel, Mehmet; Brückner, Martina K; Schreiweis, Christiane; Winter, Christine; Sohr, Reinhard; Becker, Lore; Wiebe, Victor; Nickel, Birgit; Giger, Thomas; Müller, Uwe; Groszer, Matthias; Adler, Thure; Aguilar, Antonio; Bolle, Ines; Calzada-Wack, Julia; Dalke, Claudia; Ehrhardt, Nicole; Favor, Jack; Fuchs, Helmut; Gailus-Durner, Valérie; Hans, Wolfgang; Hölzlwimmer, Gabriele; Javaheri, Anahita; Kalaydjiev, Svetoslav; Kallnik, Magdalena; Kling, Eva; Kunder, Sandra; Mossbrugger, Ilona; Naton, Beatrix; Racz, Ildikó; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Busch, Dirk H; Graw, Jochen; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Quintanilla-Martinez, Leticia; Schulz, Holger; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Fisher, Simon E; Morgenstern, Rudolf; Arendt, Thomas; de Angelis, Martin Hrabé; Fischer, Julia; Schwarz, Johannes; Pääbo, Svante

    2009-05-29

    It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting that the humanized Foxp2 allele affects basal ganglia. In the striatum, a part of the basal ganglia affected in humans with a speech deficit due to a nonfunctional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one nonfunctional Foxp2 allele show opposite effects, this suggests that alterations in cortico-basal ganglia circuits might have been important for the evolution of speech and language in humans.

  15. An evolutionary perspective on FoxP2: strictly for the birds?

    PubMed

    Scharff, Constance; Haesler, Sebastian

    2005-12-01

    FoxP2 mutations in humans are associated with a disorder that affects both the comprehension of language and its production, speech. This discovery provided the first opportunity to analyze the genetics of language with molecular and neurobiological tools. The amino acid sequence and the neural expression pattern of FoxP2 are extremely conserved, from reptile to man. This suggests an important role for FoxP2 in vertebrate brains, regardless of whether they support imitative vocal learning or not. Its expression pattern pinpoints neural circuits that might have been crucial for the evolution of speech and language, including the basal ganglia and the cerebellum. Recent studies in songbirds show that during times of song plasticity FoxP2 is upregulated in a striatal region essential for song learning. This suggests that FoxP2 plays important roles both in the development of neural circuits and in the postnatal behaviors they mediate.

  16. Multiple transcription start sites for FOXP2 with varying cellular specificities.

    PubMed

    Schroeder, Diane I; Myers, Richard M

    2008-04-30

    FOXP2 is a forkhead transcription factor implicated in developmental verbal dyspraxia, a human speech and language disorder. FOXP2 is expressed in complex patterns during brain, lung, heart, and gut development and on into adulthood. Both the protein sequence and brain expression patterns are highly conserved through much of vertebrate evolution. FOXP2 also contains six ultraconserved regions in its introns, consistent with the idea that FOXP2 is tightly regulated. Previous evidence suggested the presence of three transcription start sites for FOXP2, and we sought to characterize them and determine their cell and tissue specificity. We used 5' RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) and RT-PCR to identify four transcription start sites for human FOXP2, the fourth being in a novel exon. Two of the transcription start sites, including the one in the novel exon, appear to be more cell line specific and lie in an area of remarkably high conservation. We propose that these two transcription start sites may be of great interest in future studies of FOXP2 regulation.

  17. A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

    PubMed

    Hammerschmidt, K; Schreiweis, C; Minge, C; Pääbo, S; Fischer, J; Enard, W

    2015-11-01

    The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms.

  18. Humanized Foxp2 specifically affects cortico-basal ganglia circuits.

    PubMed

    Reimers-Kipping, S; Hevers, W; Pääbo, S; Enard, W

    2011-02-23

    It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution and influence aspects of speech and language. Recently it was shown that when these substitutions are introduced into the endogenous Foxp2 gene of mice, they increase dendrite length and long-term depression (LTD) in medium spiny neurons of the striatum. Here we investigated if these effects are found in other brain regions. We found that neurons in the cerebral cortex, the thalamus and the striatum have increased dendrite lengths in the humanized mice whereas neurons in the amygdala and the cerebellum do not. In agreement with previous work we found increased LTD in medium spiny neurons, but did not detect alterations of synaptic plasticity in Purkinje cells. We conclude that although Foxp2 is expressed in many brain regions and has multiple roles during mammalian development, the evolutionary changes that occurred in the protein in human ancestors specifically affect brain regions that are connected via cortico-basal ganglia circuits.

  19. Conservation and diversity of Foxp2 expression in muroid rodents: functional implications.

    PubMed

    Campbell, Polly; Reep, Roger L; Stoll, Margaret L; Ophir, Alexander G; Phelps, Steven M

    2009-01-01

    FOXP2, the first gene causally linked to a human language disorder, is implicated in song acquisition, production, and perception in oscine songbirds, the evolution of speech and language in hominids, and the evolution of echolocation in bats. Despite the evident relevance of Foxp2 to vertebrate acoustic communication, a comprehensive description of neural expression patterns is currently lacking in mammals. Here we use immunocytochemistry to systematically describe the neural distribution of Foxp2 protein in four species of muroid rodents: Scotinomys teguina and S. xerampelinus ("singing mice"), the deer mouse, Peromyscus maniculatus, and the lab mouse, Mus musculus. While expression patterns were generally highly conserved across brain regions, we identified subtle but consistent interspecific differences in Foxp2 distribution, most notably in the medial amygdala and nucleus accumbens, and in layer V cortex throughout the brain. Throughout the brain, Foxp2 was highly enriched in areas involved in modulation of fine motor output (striatum, mesolimbic dopamine circuit, olivocerebellar system) and in multimodal sensory processing and sensorimotor integration (thalamus, cortex). We propose a generalized model for Foxp2-modulated pathways in the adult brain including, but not limited to, fine motor production and auditory perception.

  20. FoxP2 in song-learning birds and vocal-learning mammals.

    PubMed

    Webb, D M; Zhang, J

    2005-01-01

    FoxP2 is the first identified gene that is specifically involved in speech and language development in humans. Population genetic studies of FoxP2 revealed a selective sweep in recent human history associated with two amino acid substitutions in exon 7. Avian song learning and human language acquisition share many behavioral and neurological similarities. To determine whether FoxP2 plays a similar role in song-learning birds, we sequenced exon 7 of FoxP2 in multiple song-learning and nonlearning birds. We show extreme conservation of FoxP2 sequences in birds, including unusually low rates of synonymous substitutions. However, no amino acid substitutions are shared between the song-learning birds and humans. Furthermore, sequences from vocal-learning whales, dolphins, and bats do not share the human-unique substitutions. While FoxP2 appears to be under strong functional constraints in mammals and birds, we find no evidence for its role during the evolution of vocal learning in nonhuman animals as in humans.

  1. FOXP2 targets show evidence of positive selection in European populations.

    PubMed

    Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C; Fisher, Simon E; Tyler-Smith, Chris

    2013-05-02

    Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction.

  2. Imaging genetics of FOXP2 in dyslexia.

    PubMed

    Wilcke, Arndt; Ligges, Carolin; Burkhardt, Jana; Alexander, Michael; Wolf, Christiane; Quente, Elfi; Ahnert, Peter; Hoffmann, Per; Becker, Albert; Müller-Myhsok, Bertram; Cichon, Sven; Boltze, Johannes; Kirsten, Holger

    2012-02-01

    Dyslexia is a developmental disorder characterised by extensive difficulties in the acquisition of reading or spelling. Genetic influence is estimated at 50-70%. However, the link between genetic variants and phenotypic deficits is largely unknown. Our aim was to investigate a role of genetic variants of FOXP2, a prominent speech and language gene, in dyslexia using imaging genetics. This technique combines functional magnetic resonance imaging (fMRI) and genetics to investigate relevance of genetic variants on brain activation. To our knowledge, this represents the first usage of fMRI-based imaging genetics in dyslexia. In an initial case/control study (n = 245) for prioritisation of FOXP2 polymorphisms for later use in imaging genetics, nine SNPs were selected. A non-synonymously coding mutation involved in verbal dyspraxia was also investigated. SNP rs12533005 showed nominally significant association with dyslexia (genotype GG odds ratio recessive model = 2.1 (95% confidence interval 1.1-3.9), P = 0.016). A correlated SNP was associated with altered expression of FOXP2 in vivo in human hippocampal tissue. Therefore, influence of the rs12533005-G risk variant on brain activity was studied. fMRI revealed a significant main effect for the factor 'genetic risk' in a temporo-parietal area involved in phonological processing as well as a significant interaction effect between the factors 'disorder' and 'genetic risk' in activation of inferior frontal brain areas. Hence, our data may hint at a role of FOXP2 genetic variants in dyslexia-specific brain activation and demonstrate use of imaging genetics in dyslexia research.

  3. Imaging genetics of FOXP2 in dyslexia

    PubMed Central

    Wilcke, Arndt; Ligges, Carolin; Burkhardt, Jana; Alexander, Michael; Wolf, Christiane; Quente, Elfi; Ahnert, Peter; Hoffmann, Per; Becker, Albert; Müller-Myhsok, Bertram; Cichon, Sven; Boltze, Johannes; Kirsten, Holger

    2012-01-01

    Dyslexia is a developmental disorder characterised by extensive difficulties in the acquisition of reading or spelling. Genetic influence is estimated at 50–70%. However, the link between genetic variants and phenotypic deficits is largely unknown. Our aim was to investigate a role of genetic variants of FOXP2, a prominent speech and language gene, in dyslexia using imaging genetics. This technique combines functional magnetic resonance imaging (fMRI) and genetics to investigate relevance of genetic variants on brain activation. To our knowledge, this represents the first usage of fMRI-based imaging genetics in dyslexia. In an initial case/control study (n=245) for prioritisation of FOXP2 polymorphisms for later use in imaging genetics, nine SNPs were selected. A non-synonymously coding mutation involved in verbal dyspraxia was also investigated. SNP rs12533005 showed nominally significant association with dyslexia (genotype GG odds ratio recessive model=2.1 (95% confidence interval 1.1–3.9), P=0.016). A correlated SNP was associated with altered expression of FOXP2 in vivo in human hippocampal tissue. Therefore, influence of the rs12533005-G risk variant on brain activity was studied. fMRI revealed a significant main effect for the factor ‘genetic risk' in a temporo-parietal area involved in phonological processing as well as a significant interaction effect between the factors ‘disorder' and ‘genetic risk' in activation of inferior frontal brain areas. Hence, our data may hint at a role of FOXP2 genetic variants in dyslexia-specific brain activation and demonstrate use of imaging genetics in dyslexia research. PMID:21897444

  4. Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion.

    PubMed

    Yan, Xia; Zhou, Huiling; Zhang, Tingting; Xu, Pan; Zhang, Shusen; Huang, Wei; Yang, Linlin; Gu, Xingxing; Ni, Runzhou; Zhang, Tianyi

    2015-12-01

    Hepatocellular carcinoma (HCC) is a major health concern with a high morbidity and mortality rate worldwide. However, the mechanism underlying hepatocarcinogenesis remains unclear. Forkhead box P2 (FOXP2) has been implicated in various human cancer types. However, the role of FOXP2 in HCC remains unknown. Western blot and immunohistochemistry were used to measure the expression of FOXP2 protein in HCC and adjacent normal tissues in 50 patients. Wound healing and transwell assays were used to determine the cell invasion ability. We showed that the level of FOXP2 was significantly reduced in HCC compared with the adjacent non-tumorous tissue. There was statistical significance between the expression of FOXP2 and vein invasion (P = 0.017), number of tumor nodes (P = 0.028), and AFP (P = 0.033). Low expression of FOXP2 correlated with poor survival. Moreover, wound healing and transwell assays showed that FOXP2 could decrease cell invasion and affect the expression of vimentin and E-cadherin. Our results suggested that FOXP2 expression was downregulated in HCC tumor tissues, and reduced FOXP2 expression was associated with poor overall survival. In addition, downregulation of FOXP2 significantly enhanced cell invasiveness. These findings uncover that FOXP2 might be a new prognostic factor and be closely correlated with HCC cell invasion.

  5. Early neuroimaging markers of FOXP2 intragenic deletion

    PubMed Central

    Liégeois, Frédérique J.; Hildebrand, Michael S.; Bonthrone, Alexandra; Turner, Samantha J.; Scheffer, Ingrid E.; Bahlo, Melanie; Connelly, Alan; Morgan, Angela T.

    2016-01-01

    FOXP2 is the major gene associated with severe, persistent, developmental speech and language disorders. While studies in the original family in which a FOXP2 mutation was found showed volume reduction and reduced activation in core language and speech networks, there have been no imaging studies of different FOXP2 mutations. We conducted a multimodal MRI study in an eight-year-old boy (A-II) with a de novo FOXP2 intragenic deletion. A-II showed marked bilateral volume reductions in the hippocampus, thalamus, globus pallidus, and caudate nucleus compared with 26 control males (effect sizes from −1 to −3). He showed no detectable functional MRI activity when repeating nonsense words. The hippocampus is implicated for the first time in FOXP2 diseases. We conclude that FOXP2 anomaly is either directly or indirectly associated with atypical development of widespread subcortical networks early in life. PMID:27734906

  6. Microfluidic affinity and ChIP-seq analyses converge on a conserved FOXP2-binding motif in chimp and human, which enables the detection of evolutionarily novel targets.

    PubMed

    Nelson, Christopher S; Fuller, Chris K; Fordyce, Polly M; Greninger, Alexander L; Li, Hao; DeRisi, Joseph L

    2013-07-01

    The transcription factor forkhead box P2 (FOXP2) is believed to be important in the evolution of human speech. A mutation in its DNA-binding domain causes severe speech impairment. Humans have acquired two coding changes relative to the conserved mammalian sequence. Despite intense interest in FOXP2, it has remained an open question whether the human protein's DNA-binding specificity and chromatin localization are conserved. Previous in vitro and ChIP-chip studies have provided conflicting consensus sequences for the FOXP2-binding site. Using MITOMI 2.0 microfluidic affinity assays, we describe the binding site of FOXP2 and its affinity profile in base-specific detail for all substitutions of the strongest binding site. We find that human and chimp FOXP2 have similar binding sites that are distinct from previously suggested consensus binding sites. Additionally, through analysis of FOXP2 ChIP-seq data from cultured neurons, we find strong overrepresentation of a motif that matches our in vitro results and identifies a set of genes with FOXP2 binding sites. The FOXP2-binding sites tend to be conserved, yet we identified 38 instances of evolutionarily novel sites in humans. Combined, these data present a comprehensive portrait of FOXP2's-binding properties and imply that although its sequence specificity has been conserved, some of its genomic binding sites are newly evolved.

  7. Knockout of Foxp2 disrupts vocal development in mice

    PubMed Central

    Castellucci, Gregg A.; McGinley, Matthew J.; McCormick, David A.

    2016-01-01

    The FOXP2 gene is important for the development of proper speech motor control in humans. However, the role of the gene in general vocal behavior in other mammals, including mice, is unclear. Here, we track the vocal development of Foxp2 heterozygous knockout (Foxp2+/−) mice and their wildtype (WT) littermates from juvenile to adult ages, and observe severe abnormalities in the courtship song of Foxp2+/− mice. In comparison to their WT littermates, Foxp2+/− mice vocalized less, produced shorter syllable sequences, and possessed an abnormal syllable inventory. In addition, Foxp2+/− song also exhibited irregular rhythmic structure, and its development did not follow the consistent trajectories observed in WT vocalizations. These results demonstrate that the Foxp2 gene is critical for normal vocal behavior in juvenile and adult mice, and that Foxp2 mutant mice may provide a tractable model system for the study of the gene’s role in general vocal motor control. PMID:26980647

  8. Monoallelic expression of the human FOXP2 speech gene.

    PubMed

    Adegbola, Abidemi A; Cox, Gerald F; Bradshaw, Elizabeth M; Hafler, David A; Gimelbrant, Alexander; Chess, Andrew

    2015-06-02

    The recent descriptions of widespread random monoallelic expression (RMAE) of genes distributed throughout the autosomal genome indicate that there are more genes subject to RMAE on autosomes than the number of genes on the X chromosome where X-inactivation dictates RMAE of X-linked genes. Several of the autosomal genes that undergo RMAE have independently been implicated in human Mendelian disorders. Thus, parsing the relationship between allele-specific expression of these genes and disease is of interest. Mutations in the human forkhead box P2 gene, FOXP2, cause developmental verbal dyspraxia with profound speech and language deficits. Here, we show that the human FOXP2 gene undergoes RMAE. Studying an individual with developmental verbal dyspraxia, we identify a deletion 3 Mb away from the FOXP2 gene, which impacts FOXP2 gene expression in cis. Together these data suggest the intriguing possibility that RMAE impacts the haploinsufficiency phenotypes observed for FOXP2 mutations.

  9. Monoallelic expression of the human FOXP2 speech gene

    PubMed Central

    Adegbola, Abidemi A.; Cox, Gerald F.; Bradshaw, Elizabeth M.; Hafler, David A.; Gimelbrant, Alexander; Chess, Andrew

    2015-01-01

    The recent descriptions of widespread random monoallelic expression (RMAE) of genes distributed throughout the autosomal genome indicate that there are more genes subject to RMAE on autosomes than the number of genes on the X chromosome where X-inactivation dictates RMAE of X-linked genes. Several of the autosomal genes that undergo RMAE have independently been implicated in human Mendelian disorders. Thus, parsing the relationship between allele-specific expression of these genes and disease is of interest. Mutations in the human forkhead box P2 gene, FOXP2, cause developmental verbal dyspraxia with profound speech and language deficits. Here, we show that the human FOXP2 gene undergoes RMAE. Studying an individual with developmental verbal dyspraxia, we identify a deletion 3 Mb away from the FOXP2 gene, which impacts FOXP2 gene expression in cis. Together these data suggest the intriguing possibility that RMAE impacts the haploinsufficiency phenotypes observed for FOXP2 mutations. PMID:25422445

  10. Phenotype of FOXP2 Haploinsufficiency in a Mother and Son

    PubMed Central

    Rice, Gregory M.; Raca, Gordana; Jakielski, Kathy J.; Laffin, Jennifer J.; Iyama-Kurtycz, Christina M.; Hartley, Sigan L.; Sprague, Rae E.; Heintzelman, Anne T.; Shriberg, Lawrence D.

    2011-01-01

    Disruptions in FOXP2, a transcription factor, are the only known monogenic cause of speech and language impairment. We report clinical findings for two new individuals with a submicroscopic deletion of FOXP2: a boy with severe apraxia of speech and his currently moderately affected mother. A 1.57 Mb deletion on chromosome 7q31 was detected by array Comparative Genomic Hybridization (aCGH). In addition to FOXP2, the patients’ deletion involves two other genes, MDFIC and PPP1R3A, neither of which has been associated with speech or language disorders. Thus, findings for these two family members provide informative phenotypic information on FOXP2 haploinsufficiency. Evaluation by a clinical geneticist indicated no major congenital anomalies or dysmorphic features. Evaluations by a clinical psychologist and occupational therapist indicated cognitive-linguistic processing and sensorimotor control deficits, but did not support a diagnosis of autism spectrum disorder. Evaluation by clinical and research speech pathologists confirmed that both patients’ speech deficits met contemporary criteria for apraxia of speech. Notably, the patients were not able to laugh, cough, or sneeze spontaneously, replicating findings reported for two other FOXP2 cases and a potential diagnostic sign of nonsyndromic apraxia of speech. Speech severity findings for the boy were not consistent with the hypothesis that loss of maternal FOXP2 should be relatively benign. Better understanding of the behavioral phenotype of FOXP2 disruptions will aid identification of patients, toward an eventual understanding of the pathophysiology of syndromic and nonsyndromic apraxia of speech. PMID:22106036

  11. Extinction events can accelerate evolution.

    PubMed

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific in the long term.

  12. Extinction Events Can Accelerate Evolution

    PubMed Central

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific in the long term. PMID:26266804

  13. FOXP2 variation modulates functional hemispheric asymmetries for speech perception.

    PubMed

    Ocklenburg, Sebastian; Arning, Larissa; Gerding, Wanda M; Epplen, Jörg T; Güntürkün, Onur; Beste, Christian

    2013-09-01

    Left-hemispheric language dominance is a well-known characteristic of the human language system, but the molecular mechanisms underlying this crucial feature of vocal communication are still far from being understood. The forkhead box P2 gene FOXP2, which has been related to speech development, constitutes an interesting candidate gene in this regard. Therefore, the present study was aimed at investigating effects of variation in FOXP2 on individual language dominance. To this end, we used a dichotic listening and a visual half-field task in a sample of 456 healthy adults. The FOXP2 SNPs rs2396753 and rs12533005 were found to be significantly associated with the distribution of correct answers on the dichotic listening task. These results show that variation in FOXP2 may contribute to the inter-individual variability in hemispheric asymmetries for speech perception.

  14. FOXP2 as a molecular window into speech and language.

    PubMed

    Fisher, Simon E; Scharff, Constance

    2009-04-01

    Rare mutations of the FOXP2 transcription factor gene cause a monogenic syndrome characterized by impaired speech development and linguistic deficits. Recent genomic investigations indicate that its downstream neural targets make broader impacts on common language impairments, bridging clinically distinct disorders. Moreover, the striking conservation of both FoxP2 sequence and neural expression in different vertebrates facilitates the use of animal models to study ancestral pathways that have been recruited towards human speech and language. Intriguingly, reduced FoxP2 dosage yields abnormal synaptic plasticity and impaired motor-skill learning in mice, and disrupts vocal learning in songbirds. Converging data indicate that Foxp2 is important for modulating the plasticity of relevant neural circuits. This body of research represents the first functional genetic forays into neural mechanisms contributing to human spoken language.

  15. Genetics Home Reference: FOXP2-related speech and language disorder

    MedlinePlus

    ... before and after birth. It acts as a transcription factor, which means that it helps control the ... FOXP2 gene. Because forkhead box P2 is a transcription factor, these changes affect the activity of other ...

  16. Phenotype of FOXP2 haploinsufficiency in a mother and son.

    PubMed

    Rice, Gregory M; Raca, Gordana; Jakielski, Kathy J; Laffin, Jennifer J; Iyama-Kurtycz, Christina M; Hartley, Sigan L; Sprague, Rae E; Heintzelman, Anne T; Shriberg, Lawrence D

    2012-01-01

    Disruptions in FOXP2, a transcription factor, are the only known monogenic cause of speech and language impairment. We report on clinical findings for two new individuals with a submicroscopic deletion of FOXP2: a boy with severe apraxia of speech and his currently moderately affected mother. A 1.57 Mb deletion on chromosome 7q31 was detected by array comparative genomic hybridization (aCGH). In addition to FOXP2, the patients' deletion involves two other genes, MDFIC and PPP1R3A, neither of which has been associated with speech or language disorders. Thus, findings for these two family members provide informative phenotypic information on FOXP2 haploinsufficiency. Evaluation by a clinical geneticist indicated no major congenital anomalies or dysmorphic features. Evaluations by a clinical psychologist and occupational therapist indicated cognitive-linguistic processing and sensorimotor control deficits, but did not support a diagnosis of autism spectrum disorder. Evaluation by clinical and research speech pathologists confirmed that both patients' speech deficits met contemporary criteria for apraxia of speech. Notably, the patients were not able to laugh, cough, or sneeze spontaneously, replicating findings reported for two other FOXP2 cases and a potential diagnostic sign of nonsyndromic apraxia of speech. Speech severity findings for the boy were not consistent with the hypothesis that loss of maternal FOXP2 should be relatively benign. Better understanding of the behavioral phenotype of FOXP2 disruptions will aid identification of patients, toward an eventual understanding of the pathophysiology of syndromic and nonsyndromic apraxia of speech.

  17. Foxp2 mutations impair auditory-motor association learning.

    PubMed

    Kurt, Simone; Fisher, Simon E; Ehret, Günter

    2012-01-01

    Heterozygous mutations of the human FOXP2 transcription factor gene cause the best-described examples of monogenic speech and language disorders. Acquisition of proficient spoken language involves auditory-guided vocal learning, a specialized form of sensory-motor association learning. The impact of etiological Foxp2 mutations on learning of auditory-motor associations in mammals has not been determined yet. Here, we directly assess this type of learning using a newly developed conditioned avoidance paradigm in a shuttle-box for mice. We show striking deficits in mice heterozygous for either of two different Foxp2 mutations previously implicated in human speech disorders. Both mutations cause delays in acquiring new motor skills. The magnitude of impairments in association learning, however, depends on the nature of the mutation. Mice with a missense mutation in the DNA-binding domain are able to learn, but at a much slower rate than wild type animals, while mice carrying an early nonsense mutation learn very little. These results are consistent with expression of Foxp2 in distributed circuits of the cortex, striatum and cerebellum that are known to play key roles in acquisition of motor skills and sensory-motor association learning, and suggest differing in vivo effects for distinct variants of the Foxp2 protein. Given the importance of such networks for the acquisition of human spoken language, and the fact that similar mutations in human FOXP2 cause problems with speech development, this work opens up a new perspective on the use of mouse models for understanding pathways underlying speech and language disorders.

  18. FOXP2 promotes the nuclear translocation of POT1, but FOXP2(R553H), mutation related to speech-language disorder, partially prevents it

    SciTech Connect

    Tanabe, Yuko; Fujita, Eriko; Momoi, Takashi

    2011-07-08

    Highlights: {yields} We isolated protection of telomeres 1 (POT1) as a FOXP2-associated protein by a yeast two-hybrid. {yields} FOXP2 associated and co-localized with POT1 in the nuclei. {yields} FOXP2(R553H) also co-localized with POT1 in both the cytoplasm and nuclei. {yields} FOXP2(R553H) partially prevented the nuclear translocation of POT1. {yields} FOXP2(R553H) mutation may be associated with the pathogenesis of speech-language disorder. -- Abstract: FOXP2 is a forkhead box-containing transcription factor with several recognizable sequence motifs. However, little is known about the FOXP2-associated proteins except for C-terminal binding protein (CtBP). In the present study, we attempted to isolate the FOXP2-associated protein with a yeast two-hybrid system using the C-terminal region, including the forkhead domain, as a bait probe, and identified protection of telomeres 1 (POT1) as a FOXP2-associated protein. Immunoprecipitation assay confirmed the association with FOXP2 and POT1. POT1 alone localized in the cytoplasm but co-localized with FOXP2 and the forkhead domain of FOXP2 in nuclei. However, both FOXP2 with mutated nuclear localization signals and (R553H) mutated forkhead, which is associated with speech-language disorder, prevented the nuclear translocation of POT1. These results suggest that FOXP2 is a binding partner for the nuclear translocation of POT1. As loss of POT1 function induces the cell arrest, the impaired nuclear translocation of POT1 in the developing neuronal cells may be associated with the pathogenesis of speech-language disorder with FOXP2(R553H) mutation.

  19. Specific expression of FOXP2 in cerebellum improves ultrasonic vocalization in heterozygous but not in homozygous Foxp2 (R552H) knock-in pups.

    PubMed

    Fujita-Jimbo, Eriko; Momoi, Takashi

    2014-04-30

    The R553H mutation has been found in the FOXP2 gene of patients with speech-language disorder. Foxp2(R552H) knock-in (KI) mice exhibit poor dendritic development of Purkinje cells in the cerebellum and impaired ultrasonic vocalization (USV), which is related to human speech and language; compared with wild-type mice, heterozygous Foxp2(R552H)-KI pups exhibit the reduced number of whistle-type USVs and the increased short-type ones, while homozygous pups exhibit only click-type USVs but no whistle-type or short-type ones. To make clear the relationship between the role of Foxp2 in the cerebellum and whistle-type USVs activity, we prepared transgenic (Tg) mice specifically expressing human FOXP2-myc in cerebellum (Pcp2-FOXP2-myc-Tg mice) by using purkinje cell protein-2 (Pcp2) promoter. FOXP2-myc expression in the cerebellum increased the relative numbers of whistle-type USVs in the heterozygous Foxp2(R552H)-KI pups and recovered their USVs but did not in the homozygous ones. Foxp2 in the cerebellum may pertain to the brain network engaged in whistle-type USVs activities including modification, but not their production. There may be common molecular contribution of Purkinje cells to human FOXP2-mediated speech-language and mouse Foxp2-mediated USVs.

  20. Motor Learning: The FoxP2 Puzzle Piece

    PubMed Central

    Teramitsu, Ikuko; White, Stephanie A.

    2009-01-01

    Mutation of the DNA-binding region of the FOXP2 protein causes an inherited language disorder. A recent study provides the first data on mice with this mutation, which exhibit deficits in motor-skill learning and abnormal properties of neural circuits that contribute to these skills. PMID:18430631

  1. The Key Regulator for Language and Speech Development, FOXP2, is a Novel Substrate for SUMOylation.

    PubMed

    Meredith, Leslie J; Wang, Chiung-Min; Nascimento, Leticia; Liu, Runhua; Wang, Lizhong; Yang, Wei-Hsiung

    2016-02-01

    Transcription factor forkhead box protein P2 (FOXP2) plays an essential role in the development of language and speech. However, the transcriptional activity of FOXP2 regulated by the post-translational modifications remains unknown. Here, we demonstrated that FOXP2 is clearly defined as a SUMO target protein at the cellular levels as FOXP2 is covalently modified by both SUMO1 and SUMO3. Furthermore, SUMOylation of FOXP2 was significantly decreased by SENP2 (a specific SUMOylation protease). We further showed that FOXP2 is selectively SUMOylated in vivo on a phylogenetically conserved lysine 674 but the SUMOylation does not alter subcellular localization and stability of FOXP2. Interestingly, we observed that human etiological FOXP2 R553H mutation robustly reduces its SUMOylation potential as compared to wild-type FOXP2. In addition, the acidic residues downstream the core SUMO motif on FOXP2 are required for its full SUMOylation capacity. Finally, our functional analysis using reporter gene assays showed that SUMOylation may modulate transcriptional activity of FOXP2 in regulating downstream target genes (DISC1, SRPX2, and MiR200c). Altogether, we provide the first evidence that FOXP2 is a substrate for SUMOylation and SUMOylation of FOXP2 plays a functional role in regulating its transcriptional activity.

  2. FOXP2 promotes the nuclear translocation of POT1, but FOXP2(R553H), mutation related to speech-language disorder, partially prevents it.

    PubMed

    Tanabe, Yuko; Fujita, Eriko; Momoi, Takashi

    2011-07-08

    FOXP2 is a forkhead box-containing transcription factor with several recognizable sequence motifs. However, little is known about the FOXP2-associated proteins except for C-terminal binding protein (CtBP). In the present study, we attempted to isolate the FOXP2-associated protein with a yeast two-hybrid system using the C-terminal region, including the forkhead domain, as a bait probe, and identified protection of telomeres 1 (POT1) as a FOXP2-associated protein. Immunoprecipitation assay confirmed the association with FOXP2 and POT1. POT1 alone localized in the cytoplasm but co-localized with FOXP2 and the forkhead domain of FOXP2 in nuclei. However, both FOXP2 with mutated nuclear localization signals and (R553H) mutated forkhead, which is associated with speech-language disorder, prevented the nuclear translocation of POT1. These results suggest that FOXP2 is a binding partner for the nuclear translocation of POT1. As loss of POT1 function induces the cell arrest, the impaired nuclear translocation of POT1 in the developing neuronal cells may be associated with the pathogenesis of speech-language disorder with FOXP2(R553H) mutation.

  3. FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways

    PubMed Central

    Devanna, Paolo; Middelbeek, Jeroen; Vernes, Sonja C.

    2014-01-01

    FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells. PMID:25309332

  4. Linkage disequilibrium extends across putative selected sites in FOXP2.

    PubMed

    Ptak, Susan E; Enard, Wolfgang; Wiebe, Victor; Hellmann, Ines; Krause, Johannes; Lachmann, Michael; Pääbo, Svante

    2009-10-01

    Polymorphism data in humans suggest that the gene encoding the transcription factor FOXP2, which influences speech and language development, has been subject to a selective sweep within the last 260,000 years. It has been proposed that one or both of two substitutions that occurred on the human evolutionary lineage and changed amino acids were the targets for selection. In apparent contradiction to this is the observation that these substitutions are present in Neandertals who diverged from humans maybe 300,000-400,000 years ago. We have collected polymorphism data upstream and downstream of the substitutions. Contrary to what is expected, following a selective sweep, we find that the haplotypes extend across the two sites. We discuss possible explanations for these observations. One of them is that the selective sweep reflected in FOXP2 polymorphism data was not associated with the two amino acid substitutions.

  5. The timing of selection at the human FOXP2 gene.

    PubMed

    Coop, Graham; Bullaughey, Kevin; Luca, Francesca; Przeworski, Molly

    2008-07-01

    Krause J, Lalueza-Fox C, Orlando L, et al. recently examined patterns of genetic variation at FOXP2 in 2 Neanderthals. This gene is of particular interest because it is involved in speech and language and was previously shown to harbor the signature of recent positive selection. The authors found the same 2 amino acid substitutions in Neanderthals as in modern humans. Assuming that these sites were the targets of selection and no interbreeding between the 2 groups, they concluded that selection at FOXP2 occurred before the populations split, over 300 thousand years ago. Here, we show that the data are unlikely under this scenario but may instead be consistent with low rates of gene flow between modern humans and Neanderthals. We also collect additional data and introduce a modeling framework to estimate levels of modern human contamination of the Neanderthal samples. We find that, depending on the assumptions, additional control experiments may be needed to rule out contamination at FOXP2.

  6. The Timing of Selection at the Human FOXP2 Gene

    PubMed Central

    Bullaughey, Kevin; Luca, Francesca; Przeworski, Molly

    2008-01-01

    Krause J, Lalueza-Fox C, Orlando L, et al. recently examined patterns of genetic variation at FOXP2 in 2 Neanderthals. This gene is of particular interest because it is involved in speech and language and was previously shown to harbor the signature of recent positive selection. The authors found the same 2 amino acid substitutions in Neanderthals as in modern humans. Assuming that these sites were the targets of selection and no interbreeding between the 2 groups, they concluded that selection at FOXP2 occurred before the populations split, over 300 thousand years ago. Here, we show that the data are unlikely under this scenario but may instead be consistent with low rates of gene flow between modern humans and Neanderthals. We also collect additional data and introduce a modeling framework to estimate levels of modern human contamination of the Neanderthal samples. We find that, depending on the assumptions, additional control experiments may be needed to rule out contamination at FOXP2. PMID:18413354

  7. Antagonistic coevolution accelerates molecular evolution

    PubMed Central

    Paterson, Steve; Vogwill, Tom; Buckling, Angus; Benmayor, Rebecca; Spiers, Andrew J.; Thomson, Nicholas R.; Quail, Mike; Smith, Frances; Walker, Danielle; Libberton, Ben; Fenton, Andrew; Hall, Neil; Brockhurst, Michael A.

    2013-01-01

    The Red Queen hypothesis proposes that coevolution of interacting species (such as hosts and parasites) should drive molecular evolution through continual natural selection for adaptation and counter-adaptation1–3. Although the divergence observed at some host-resistance4–6 and parasite-infectivity7–9 genes is consistent with this, the long time periods typically required to study coevolution have so far prevented any direct empirical test. Here we show, using experimental populations of the bacterium Pseudomonas fluorescens SBW25 and its viral parasite, phage Φ2 (refs 10, 11), that the rate of molecular evolution in the phage was far higher when both bacterium and phage coevolved with each other than when phage evolved against a constant host genotype. Coevolution also resulted in far greater genetic divergence between replicate populations, which was correlated with the range of hosts that coevolved phage were able to infect. Consistent with this, the most rapidly evolving phage genes under coevolution were those involved in host infection. These results demonstrate, at both the genomic and phenotypic level, that antagonistic coevolution is a cause of rapid and divergent evolution, and is likely to be a major driver of evolutionary change within species. PMID:20182425

  8. FOXP2 and the neuroanatomy of speech and language.

    PubMed

    Vargha-Khadem, Faraneh; Gadian, David G; Copp, Andrew; Mishkin, Mortimer

    2005-02-01

    That speech and language are innate capacities of the human brain has long been widely accepted, but only recently has an entry point into the genetic basis of these remarkable faculties been found. The discovery of a mutation in FOXP2 in a family with a speech and language disorder has enabled neuroscientists to trace the neural expression of this gene during embryological development, track the effects of this gene mutation on brain structure and function, and so begin to decipher that part of our neural inheritance that culminates in articulate speech.

  9. Birdsong Decreases Protein Levels of FoxP2, a Molecule Required for Human Speech

    PubMed Central

    Miller, Julie E.; Spiteri, Elizabeth; Condro, Michael C.; Dosumu-Johnson, Ryan T.; Geschwind, Daniel H.; White, Stephanie A.

    2008-01-01

    Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability. PMID:18701760

  10. Birdsong decreases protein levels of FoxP2, a molecule required for human speech.

    PubMed

    Miller, Julie E; Spiteri, Elizabeth; Condro, Michael C; Dosumu-Johnson, Ryan T; Geschwind, Daniel H; White, Stephanie A

    2008-10-01

    Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.

  11. Intracellular distribution of a speech/language disorder associated FOXP2 mutant.

    PubMed

    Mizutani, Akifumi; Matsuzaki, Ayumi; Momoi, Mariko Y; Fujita, Eriko; Tanabe, Yuko; Momoi, Takashi

    2007-02-23

    Although a mutation (R553H) in the forkhead box (FOX)P2 gene is associated with speech/language disorder, little is known about the function of FOXP2 or its relevance to this disorder. In the present study, we identify the forkhead nuclear localization domains that contribute to the cellular distribution of FOXP2. Nuclear localization of FOXP2 depended on two distally separated nuclear localization signals in the forkhead domain. A truncated version of FOXP2 lacking the leu-zip, Zn2+ finger, and forkhead domains that was observed in another patient with speech abnormalities demonstrated an aggregated cytoplasmic localization. Furthermore, FOXP2 (R553H) mainly exhibited a cytoplasmic localization despite retaining interactions with nuclear transport proteins (importin alpha and beta). Interestingly, wild type FOXP2 promoted the transport of FOXP2 (R553H) into the nucleus. Mutant and wild type FOXP2 heterodimers in the nucleus or FOXP2 R553H in the cytoplasm may underlie the pathogenesis of the autosomal dominant speech/language disorder.

  12. Intracellular distribution of a speech/language disorder associated FOXP2 mutant

    SciTech Connect

    Mizutani, Akifumi; Matsuzaki, Ayumi; Momoi, Mariko Y. . E-mail: mymomoi@jichi.ac.jp; Fujita, Eriko; Tanabe, Yuko; Momoi, Takashi

    2007-02-23

    Although a mutation (R553H) in the forkhead box (FOX)P2 gene is associated with speech/language disorder, little is known about the function of FOXP2 or its relevance to this disorder. In the present study, we identify the forkhead nuclear localization domains that contribute to the cellular distribution of FOXP2. Nuclear localization of FOXP2 depended on two distally separated nuclear localization signals in the forkhead domain. A truncated version of FOXP2 lacking the leu-zip, Zn{sup 2+} finger, and forkhead domains that was observed in another patient with speech abnormalities demonstrated an aggregated cytoplasmic localization. Furthermore, FOXP2 (R553H) mainly exhibited a cytoplasmic localization despite retaining interactions with nuclear transport proteins (importin {alpha} and {beta}). Interestingly, wild type FOXP2 promoted the transport of FOXP2 (R553H) into the nucleus. Mutant and wild type FOXP2 heterodimers in the nucleus or FOXP2 R553H in the cytoplasm may underlie the pathogenesis of the autosomal dominant speech/language disorder.

  13. Convergent repression of Foxp2 3'UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons.

    PubMed

    Clovis, Yoanne M; Enard, Wolfgang; Marinaro, Federica; Huttner, Wieland B; De Pietri Tonelli, Davide

    2012-09-01

    MicroRNAs (miRNAs) are rapidly emerging as a new layer of regulation of mammalian brain development. However, most of the miRNA target genes remain unidentified. Here, we explore gene expression profiling upon miRNA depletion and in vivo target validation as a strategy to identify novel miRNA targets in embryonic mouse neocortex. By this means, we find that Foxp2, a transcription factor associated with speech and language development and evolution, is a novel miRNA target. In particular, we find that miR-9 and miR-132 are able to repress ectopic expression of Foxp2 protein by targeting its 3' untranslated region (3'UTR) in vivo. Interestingly, ectopic expression of Foxp2 in cortical projection neurons (a scenario that mimics the absence of miRNA-mediated silencing of Foxp2 expression) delays neurite outgrowth in vitro and impairs their radial migration in embryonic mouse neocortex in vivo. Our results uncover a new layer of control of Foxp2 expression that may be required for proper neuronal maturation.

  14. Endophenotypes of FOXP2: dysfunction within the human articulatory network.

    PubMed

    Liégeois, F; Morgan, A T; Connelly, A; Vargha-Khadem, F

    2011-07-01

    The identification of the first gene involved in a speech-language disorder was made possible through the study of a British multi-generational family (the "KE family") in whom half the members have an inherited speech-language disorder caused by a FOXP2 mutation. Neuroimaging investigations in the affected members of the KE family have revealed structural and functional abnormalities in a wide cortical-subcortical network. Functional imaging studies have confirmed dysfunction of this network by revealing abnormal activation in several areas including Broca's area and the putamen during language-related tasks, such as word repetition and generation. Repeating nonsense words is particularly challenging for the affected members of the family, as well as in other individuals suffering from idiopathic developmental specific language impairments; yet, thus far the neural correlates of the nonword repetition task have not been examined in individuals with developmental speech and language disorders. Here, four affected members of the KE family and four unrelated age-matched healthy participants repeated nonsense words aloud during functional MRI scanning. Relative to control participants, repetition in the affected members was severely impaired, and brain activation was significantly reduced in the premotor, supplementary and primary motor cortices, as well as in the cerebellum and basal ganglia. We suggest that nonword repetition is the optimal endophenotype for FOXP2 disruption in humans because this task recruits brain regions involved in the imitation and vocal learning of novel sequences of speech sounds.

  15. Molecular cloning and developmental expression of foxP2 in zebrafish.

    PubMed

    Bonkowsky, Joshua L; Chien, Chi-Bin

    2005-11-01

    Forkhead domain transcription factors are a large gene family with multiple roles in development. FOXP2, a recently identified member of this family, has been shown to be critical for normal development of language in humans, but little is known of its broader function during nervous system development. We report here the cloning of foxP2, the zebrafish ortholog of FOXP2. Zebrafish FoxP2 is highly conserved in its zinc-finger and forkhead domains, but lacks the large glutamine repeat characteristic of its orthologs. In examining the spatial and temporal distribution of foxP2 during development, we find that it is specifically expressed in many domains of the nervous system, including the telencephalon, diencephalon, cerebellum, hindbrain, tectum, retinal ganglion cells, and spinal cord. Thus, in addition to specific roles in language development, foxP2 likely has a more general conserved role in nervous system development.

  16. Foxp2 Controls Synaptic Wiring of Corticostriatal Circuits and Vocal Communication by Opposing Mef2C

    PubMed Central

    Chen, Yi-Chuan; Kuo, Hsiao-Ying; Bornschein, Ulrich; Takahashi, Hiroshi; Chen, Shih-Yun; Lu, Kuan-Ming; Yang, Hao-Yu; Chen, Gui-May; Lin, Jing-Ruei; Lee, Yi-Hsin; Chou, Yun-Chia; Cheng, Sin-Jhong; Chien, Cheng-Ting; Enard, Wolfgang; Hevers, Wulf; Pääbo, Svante; Graybiel, Ann M.; Liu, Fu-Chin

    2016-01-01

    Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder (ASD), in which language function can be severely affected. We demonstrate that in the striatum, the gene, Foxp2, negatively interacts with the synapse suppressor, Mef2C. We present causal evidence that Mef2C inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2C suppresses corticostriatal synapse formation and striatal spinogenesis, but can, itself, be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2C, and both intrastriatal and global decrease of Mef2C rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders. PMID:27595386

  17. Expression of FoxP2 during zebrafish development and in the adult brain.

    PubMed

    Shah, Rina; Medina-Martinez, Olga; Chu, Li-Fang; Samaco, Rodney C; Jamrich, Milan

    2006-01-01

    Fox (forkhead) genes encode transcription factors that play important roles in the regulation of embryonic patterning as well as in tissue specific gene expression. Mutations in the human FOXP2 gene cause abnormal speech development. Here we report the structure and expression pattern of zebrafish FoxP2. In zebrafish, this gene is first expressed at the 20-somite stage in the presumptive telencephalon. At this stage there is a significant overlap of FoxP2 expression with the expression of the emx homeobox genes. However, in contrast to emx1, FoxP2 is not expressed in the pineal gland or in the pronephric duct. After 72 hours of development, the expression of zebrafish FoxP2 becomes more complex in the brain. The developing optic tectum becomes the major area of FoxP2 expression. In the adult brain, the highest concentrations of the FoxP2 transcript can be observed in the optic tectum. In the cerebellum, only the caudal lobes show high levels of Foxp2 expression. These regions correspond to the vestibulocerebellum of mammals. Several other regions of the brain also show high levels of Foxp2 expression.

  18. Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia.

    PubMed

    Feuk, Lars; Kalervo, Aino; Lipsanen-Nyman, Marita; Skaug, Jennifer; Nakabayashi, Kazuhiko; Finucane, Brenda; Hartung, Danielle; Innes, Micheil; Kerem, Batsheva; Nowaczyk, Malgorzata J; Rivlin, Joseph; Roberts, Wendy; Senman, Lili; Summers, Anne; Szatmari, Peter; Wong, Virginia; Vincent, John B; Zeesman, Susan; Osborne, Lucy R; Cardy, Janis Oram; Kere, Juha; Scherer, Stephen W; Hannula-Jouppi, Katariina

    2006-11-01

    Mutations in FOXP2 cause developmental verbal dyspraxia (DVD), but only a few cases have been described. We characterize 13 patients with DVD--5 with hemizygous paternal deletions spanning the FOXP2 gene, 1 with a translocation interrupting FOXP2, and the remaining 7 with maternal uniparental disomy of chromosome 7 (UPD7), who were also given a diagnosis of Silver-Russell Syndrome (SRS). Of these individuals with DVD, all 12 for whom parental DNA was available showed absence of a paternal copy of FOXP2. Five other individuals with deletions of paternally inherited FOXP2 but with incomplete clinical information or phenotypes too complex to properly assess are also described. Four of the patients with DVD also meet criteria for autism spectrum disorder. Individuals with paternal UPD7 or with partial maternal UPD7 or deletion starting downstream of FOXP2 do not have DVD. Using quantitative real-time polymerase chain reaction, we show the maternally inherited FOXP2 to be comparatively underexpressed. Our results indicate that absence of paternal FOXP2 is the cause of DVD in patients with SRS with maternal UPD7. The data also point to a role for differential parent-of-origin expression of FOXP2 in human speech development.

  19. Distributed Representations Accelerate Evolution of Adaptive Behaviours

    PubMed Central

    Stone, James V

    2007-01-01

    Animals with rudimentary innate abilities require substantial learning to transform those abilities into useful skills, where a skill can be considered as a set of sensory–motor associations. Using linear neural network models, it is proved that if skills are stored as distributed representations, then within-lifetime learning of part of a skill can induce automatic learning of the remaining parts of that skill. More importantly, it is shown that this “free-lunch” learning (FLL) is responsible for accelerated evolution of skills, when compared with networks which either 1) cannot benefit from FLL or 2) cannot learn. Specifically, it is shown that FLL accelerates the appearance of adaptive behaviour, both in its innate form and as FLL-induced behaviour, and that FLL can accelerate the rate at which learned behaviours become innate. PMID:17676948

  20. The evolutionary history of genes involved in spoken and written language: beyond FOXP2.

    PubMed

    Mozzi, Alessandra; Forni, Diego; Clerici, Mario; Pozzoli, Uberto; Mascheretti, Sara; Guerini, Franca R; Riva, Stefania; Bresolin, Nereo; Cagliani, Rachele; Sironi, Manuela

    2016-02-25

    Humans possess a communication system based on spoken and written language. Other animals can learn vocalization by imitation, but this is not equivalent to human language. Many genes were described to be implicated in language impairment (LI) and developmental dyslexia (DD), but their evolutionary history has not been thoroughly analyzed. Herein we analyzed the evolution of ten genes involved in DD and LI. Results show that the evolutionary history of LI genes for mammals and aves was comparable in vocal-learner species and non-learners. For the human lineage, several sites showing evidence of positive selection were identified in KIAA0319 and were already present in Neanderthals and Denisovans, suggesting that any phenotypic change they entailed was shared with archaic hominins. Conversely, in FOXP2, ROBO1, ROBO2, and CNTNAP2 non-coding changes rose to high frequency after the separation from archaic hominins. These variants are promising candidates for association studies in LI and DD.

  1. The evolutionary history of genes involved in spoken and written language: beyond FOXP2

    PubMed Central

    Mozzi, Alessandra; Forni, Diego; Clerici, Mario; Pozzoli, Uberto; Mascheretti, Sara; Guerini, Franca R.; Riva, Stefania; Bresolin, Nereo; Cagliani, Rachele; Sironi, Manuela

    2016-01-01

    Humans possess a communication system based on spoken and written language. Other animals can learn vocalization by imitation, but this is not equivalent to human language. Many genes were described to be implicated in language impairment (LI) and developmental dyslexia (DD), but their evolutionary history has not been thoroughly analyzed. Herein we analyzed the evolution of ten genes involved in DD and LI. Results show that the evolutionary history of LI genes for mammals and aves was comparable in vocal-learner species and non-learners. For the human lineage, several sites showing evidence of positive selection were identified in KIAA0319 and were already present in Neanderthals and Denisovans, suggesting that any phenotypic change they entailed was shared with archaic hominins. Conversely, in FOXP2, ROBO1, ROBO2, and CNTNAP2 non-coding changes rose to high frequency after the separation from archaic hominins. These variants are promising candidates for association studies in LI and DD. PMID:26912479

  2. The DISC1 promoter: characterization and regulation by FOXP2.

    PubMed

    Walker, Rosie M; Hill, Alison E; Newman, Alice C; Hamilton, Gillian; Torrance, Helen S; Anderson, Susan M; Ogawa, Fumiaki; Derizioti, Pelagia; Nicod, Jérôme; Vernes, Sonja C; Fisher, Simon E; Thomson, Pippa A; Porteous, David J; Evans, Kathryn L

    2012-07-01

    Disrupted in schizophrenia 1 (DISC1) is a leading candidate susceptibility gene for schizophrenia, bipolar disorder and recurrent major depression, which has been implicated in other psychiatric illnesses of neurodevelopmental origin, including autism. DISC1 was initially identified at the breakpoint of a balanced chromosomal translocation, t(1;11) (q42.1;14.3), in a family with a high incidence of psychiatric illness. Carriers of the translocation show a 50% reduction in DISC1 protein levels, suggesting altered DISC1 expression as a pathogenic mechanism in psychiatric illness. Altered DISC1 expression in the post-mortem brains of individuals with psychiatric illness and the frequent implication of non-coding regions of the gene by association analysis further support this assertion. Here, we provide the first characterization of the DISC1 promoter region. Using dual luciferase assays, we demonstrate that a region -300 to -177 bp relative to the transcription start site (TSS) contributes positively to DISC1 promoter activity, while a region -982 to -301 bp relative to the TSS confers a repressive effect. We further demonstrate inhibition of DISC1 promoter activity and protein expression by forkhead-box P2 (FOXP2), a transcription factor implicated in speech and language function. This inhibition is diminished by two distinct FOXP2 point mutations, R553H and R328X, which were previously found in families affected by developmental verbal dyspraxia. Our work identifies an intriguing mechanistic link between neurodevelopmental disorders that have traditionally been viewed as diagnostically distinct but which do share varying degrees of phenotypic overlap.

  3. FOXP2: novel exons, splice variants, and CAG repeat length stability.

    PubMed

    Bruce, Heather A; Margolis, Russell L

    2002-08-01

    FOXP2 is a transcription factor containing a polyglutamine tract, a zinc-finger motif, and a forkhead DNA-binding domain. The FOXP2 gene is located on 7q31. A missense mutation in the forkhead domain (exon 14) and a balanced reciprocal translocation t(5;7)(q22;q31.2) with a breakpoint between exons 3b and 4 have recently been associated with a speech and language disorder (SPCH1). The role of FOXP2 in this neurodevelopmental disorder suggests that mutations in FOXP2 could cause other neuropsychiatric disorders. To begin investigation of this possibility, we examined the genomic structure and CAG/CAA repeat region of FOXP2. We detected little polymorphism and no expansions in the FOXP2 CAG/CAA repeat in 142 individuals with progressive movement disorders. We found evidence of alternate splice variants and six previously undetected exons: three 5' untranslated exons (s1, s2, s3), two additional untranslated exons (2a and 2b) between exons 2 and 3, a translated exon (4a) between exons 4 and 5, and a longer version of exon 10 (10+) that contains an alternate stop codon and produces a truncated protein (FOXP2-S). Our results suggest that FOXP2 spans at least 603 kb of genomic DNA, more than twice the previously defined region, and provide evidence of a promoter region flanking exon s1. This demonstration of additional FOXP2 exons and splice variants should facilitate understanding of FOXP2 function and the search for additional FOXP2 mutations.

  4. Temporal expression and mitochondrial localization of a Foxp2 isoform lacking the forkhead domain in developing Purkinje cells.

    PubMed

    Tanabe, Yuko; Fujiwara, Yuji; Matsuzaki, Ayumi; Fujita, Eriko; Kasahara, Tadashi; Yuasa, Shigeki; Momoi, Takashi

    2012-07-01

    FOXP2, a forkhead box-containing transcription factor, forms homo- or hetero-dimers with FOXP family members and localizes to the nucleus, while FOXP2(R553H), which contains a mutation related to speech/language disorders, features reduced DNA binding activity and both cytoplasmic and nuclear localization. In addition to being a loss-of-function mutation, it is possible that FOXP2(R553H) also may act as a gain-of-function mutation to inhibit the functions of FOXP2 isoforms including FOXP2Ex10+ lacking forkhead domain. Foxp2(R552H) knock-in mouse pups exhibit impaired ultrasonic vocalization and poor dendritic development in Purkinje cells. However, expressions of Foxp2 isoforms in the developing Purkinje are unclear. The appearance of 'apical cytoplasmic swelling' (mitochondria-rich regions that are the source of budding processes) correlates with dendritic development of Purkinje cells. In the present study, we focused on Foxp2 isoforms localizing to the apical cytoplasmic swelling and identified two isoforms lacking forkhead domain: Foxp2Ex12+ and Foxp2Ex15. They partly localized to the membrane fraction that includes mitochondria. Foxp2Ex12+ mainly localized to the apical cytoplasmic swelling in early developing Purkinje cells at the stellate stage (P2-P4). Mitochondrial localization of Foxp2Ex12+ in Purkinje cells was confirmed by immune-electron microscopic analysis. Foxp2Ex12+ may play a role in dendritic development in Purkinje cells.

  5. Accelerated Evolution in the Death Galaxy

    NASA Astrophysics Data System (ADS)

    Austin, Robert; Tung, Chih-Kuan; Gong, Xiu-Quing; Lambert, Guillaume; Liao, David

    2010-03-01

    We recall 4 main guiding principles of evolution: 1) instability of defections, 2) stress induced non-random mutations, 3) genetic heterogeneity, and 4) fragmented populations. Our previous preliminary experiments have been relatively simple 1-D stress experiments. We are proceeding with 2-D experiments whose design is guided by these principles. Our new experiment we have dubbed the Death Galaxy because of it's use of these design principles. The ``galaxy'' name comes from the fact that the structure is designed as an interconnected array of micro-ecologies, these micro-ecologies are similar to the stars that comprise an astronomical galaxy, and provide the fragmented small populations. A gradient of the antibiotic Cipro is introduced across the galaxy, and we will present results which show how bacterial evolution resulting in resistance to Cipro is accelerated by the physics principles underlying the device.

  6. Regulation of MET by FOXP2, genes implicated in higher cognitive dysfunction and autism risk.

    PubMed

    Mukamel, Zohar; Konopka, Genevieve; Wexler, Eric; Osborn, Gregory E; Dong, Hongmei; Bergman, Mica Y; Levitt, Pat; Geschwind, Daniel H

    2011-08-10

    Autism spectrum disorder (ASD) is a highly heritable, behaviorally defined, heterogeneous disorder of unknown pathogenesis. Several genetic risk genes have been identified, including the gene encoding the receptor tyrosine kinase MET, which regulates neuronal differentiation and growth. An ASD-associated polymorphism disrupts MET gene transcription, and there are reduced levels of MET protein expression in the mature temporal cortex of subjects with ASD. To address the possible neurodevelopmental contribution of MET to ASD pathogenesis, we examined the expression and transcriptional regulation of MET by a transcription factor, FOXP2, which is implicated in regulation of cognition and language, two functions altered in ASD. MET mRNA expression in the midgestation human fetal cerebral cortex is strikingly restricted, localized to portions of the temporal and occipital lobes. Within the cortical plate of the temporal lobe, the pattern of MET expression is highly complementary to the expression pattern of FOXP2, suggesting the latter may play a role in repression of gene expression. Consistent with this, MET and FOXP2 also are reciprocally expressed by differentiating normal human neuronal progenitor cells (NHNPs) in vitro, leading us to assess whether FOXP2 transcriptionally regulates MET. Indeed, FOXP2 binds directly to the 5' regulatory region of MET, and overexpression of FOXP2 results in transcriptional repression of MET. The expression of MET in restricted human neocortical regions, and its regulation in part by FOXP2, is consistent with genetic evidence for MET contributing to ASD risk.

  7. Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits.

    PubMed

    MacDermot, Kay D; Bonora, Elena; Sykes, Nuala; Coupe, Anne-Marie; Lai, Cecilia S L; Vernes, Sonja C; Vargha-Khadem, Faraneh; McKenzie, Fiona; Smith, Robert L; Monaco, Anthony P; Fisher, Simon E

    2005-06-01

    FOXP2, the first gene to have been implicated in a developmental communication disorder, offers a unique entry point into neuromolecular mechanisms influencing human speech and language acquisition. In multiple members of the well-studied KE family, a heterozygous missense mutation in FOXP2 causes problems in sequencing muscle movements required for articulating speech (developmental verbal dyspraxia), accompanied by wider deficits in linguistic and grammatical processing. Chromosomal rearrangements involving this locus have also been identified. Analyses of FOXP2 coding sequence in typical forms of specific language impairment (SLI), autism, and dyslexia have not uncovered any etiological variants. However, no previous study has performed mutation screening of children with a primary diagnosis of verbal dyspraxia, the most overt feature of the disorder in affected members of the KE family. Here, we report investigations of the entire coding region of FOXP2, including alternatively spliced exons, in 49 probands affected with verbal dyspraxia. We detected variants that alter FOXP2 protein sequence in three probands. One such variant is a heterozygous nonsense mutation that yields a dramatically truncated protein product and cosegregates with speech and language difficulties in the proband, his affected sibling, and their mother. Our discovery of the first nonsense mutation in FOXP2 now opens the door for detailed investigations of neurodevelopment in people carrying different etiological variants of the gene. This endeavor will be crucial for gaining insight into the role of FOXP2 in human cognition.

  8. Host immune responses accelerate pathogen evolution

    PubMed Central

    Trivedi, Pankaj; Wang, Nian

    2014-01-01

    Pathogens face a hostile and often novel environment when infecting a new host, and adaptation is likely to be an important determinant of the success in colonization and establishment. We hypothesized that resistant hosts will impose stronger selection on pathogens than susceptible hosts, which should accelerate pathogen evolution through selection biased toward effector genes. To test this hypothesis, we conducted an experimental evolution study on Xanthomonas citri subsp. citri (Xcc) in a susceptible plant species and a resistant plant species. We performed 55 rounds of repeated reinoculation of Xcc through susceptible host grapefruit (isolates G1, G2, G3) and resistant host kumquat (isolates K1, K2, K3). Consequently, only K1 and K3 isolates lost their ability to elicit a hypersensitive response (HR) in kumquat. Illumina sequencing of the parental and descendant strains P, G1, G2, G3, K1, K2 and K3 revealed that fixed mutations were biased toward type three secretion system effectors in isolates K1 and K3. Parallel evolution was observed in the K1 and K3 strains, suggesting that the mutations result from selection rather than by random drift. Our results support our hypothesis and suggest that repeated infection of resistant hosts by pathogens should be prevented to avoid selecting for adaptive pathogens. PMID:24304673

  9. The language-related transcription factor FOXP2 is post-translationally modified with small ubiquitin-like modifiers.

    PubMed

    Estruch, Sara B; Graham, Sarah A; Deriziotis, Pelagia; Fisher, Simon E

    2016-02-12

    Mutations affecting the transcription factor FOXP2 cause a rare form of severe speech and language disorder. Although it is clear that sufficient FOXP2 expression is crucial for normal brain development, little is known about how this transcription factor is regulated. To investigate post-translational mechanisms for FOXP2 regulation, we searched for protein interaction partners of FOXP2, and identified members of the PIAS family as novel FOXP2 interactors. PIAS proteins mediate post-translational modification of a range of target proteins with small ubiquitin-like modifiers (SUMOs). We found that FOXP2 can be modified with all three human SUMO proteins and that PIAS1 promotes this process. An aetiological FOXP2 mutation found in a family with speech and language disorder markedly reduced FOXP2 SUMOylation. We demonstrate that FOXP2 is SUMOylated at a single major site, which is conserved in all FOXP2 vertebrate orthologues and in the paralogues FOXP1 and FOXP4. Abolishing this site did not lead to detectable changes in FOXP2 subcellular localization, stability, dimerization or transcriptional repression in cellular assays, but the conservation of this site suggests a potential role for SUMOylation in regulating FOXP2 activity in vivo.

  10. The language-related transcription factor FOXP2 is post-translationally modified with small ubiquitin-like modifiers

    PubMed Central

    Estruch, Sara B.; Graham, Sarah A.; Deriziotis, Pelagia; Fisher, Simon E.

    2016-01-01

    Mutations affecting the transcription factor FOXP2 cause a rare form of severe speech and language disorder. Although it is clear that sufficient FOXP2 expression is crucial for normal brain development, little is known about how this transcription factor is regulated. To investigate post-translational mechanisms for FOXP2 regulation, we searched for protein interaction partners of FOXP2, and identified members of the PIAS family as novel FOXP2 interactors. PIAS proteins mediate post-translational modification of a range of target proteins with small ubiquitin-like modifiers (SUMOs). We found that FOXP2 can be modified with all three human SUMO proteins and that PIAS1 promotes this process. An aetiological FOXP2 mutation found in a family with speech and language disorder markedly reduced FOXP2 SUMOylation. We demonstrate that FOXP2 is SUMOylated at a single major site, which is conserved in all FOXP2 vertebrate orthologues and in the paralogues FOXP1 and FOXP4. Abolishing this site did not lead to detectable changes in FOXP2 subcellular localization, stability, dimerization or transcriptional repression in cellular assays, but the conservation of this site suggests a potential role for SUMOylation in regulating FOXP2 activity in vivo. PMID:26867680

  11. Aberrant expression of the neuronal transcription factor FOXP2 in neoplastic plasma cells.

    PubMed

    Campbell, Andrew J; Lyne, Linden; Brown, Philip J; Launchbury, Rosalind J; Bignone, Paola; Chi, Jianxiang; Roncador, Giovanna; Lawrie, Charles H; Gatter, Kevin C; Kusec, Rajko; Banham, Alison H

    2010-04-01

    FOXP2 mutation causes a severe inherited speech and language defect, while the related transcription factors FOXP1, FOXP3 and FOXP4 are implicated in cancer. FOXP2 mRNA and protein expression were characterised in normal human tissues, haematological cell lines and multiple myeloma (MM) patients' samples. FOXP2 mRNA and protein were absent in mononuclear cells from different anatomical sites, lineages and stages of differentiation. However, FOXP2 mRNA and protein was detected in several lymphoma (8/20) and all MM-derived cell lines (n = 4). FOXP2 mRNA was expressed in bone marrow samples from 96% of MM patients (24/25), 66.7% of patients with the pre-neoplastic plasma cell proliferation monoclonal gammopathy of undetermined significance (MGUS) (6/9), but not in reactive plasma cells. The frequency of FOXP2 protein expression in CD138(+) plasma cells was significantly higher in MGUS (P = 0.0005; mean 46.4%) and MM patients (P < or = 0.0001; mean 57.3%) than in reactive marrows (mean 2.5%). FOXP2 (>10% nuclear positivity) was detectable in 90.2% of MM (55/61) and 90.9% of MGUS (10/11) patients, showing more frequent expression than CD56 and labelling 75% of CD56-negative MM (9/12). FOXP2 represents the first transcription factor whose expression consistently differentiates normal and abnormal plasma cells and FOXP2 target genes are implicated in MM pathogenesis.

  12. Recent acceleration of human adaptive evolution

    PubMed Central

    Hawks, John; Wang, Eric T.; Cochran, Gregory M.; Harpending, Henry C.; Moyzis, Robert K.

    2007-01-01

    Genomic surveys in humans identify a large amount of recent positive selection. Using the 3.9-million HapMap SNP dataset, we found that selection has accelerated greatly during the last 40,000 years. We tested the null hypothesis that the observed age distribution of recent positively selected linkage blocks is consistent with a constant rate of adaptive substitution during human evolution. We show that a constant rate high enough to explain the number of recently selected variants would predict (i) site heterozygosity at least 10-fold lower than is observed in humans, (ii) a strong relationship of heterozygosity and local recombination rate, which is not observed in humans, (iii) an implausibly high number of adaptive substitutions between humans and chimpanzees, and (iv) nearly 100 times the observed number of high-frequency linkage disequilibrium blocks. Larger populations generate more new selected mutations, and we show the consistency of the observed data with the historical pattern of human population growth. We consider human demographic growth to be linked with past changes in human cultures and ecologies. Both processes have contributed to the extraordinarily rapid recent genetic evolution of our species. PMID:18087044

  13. Enhanced procedural learning of speech sound categories in a genetic variant of FOXP2.

    PubMed

    Chandrasekaran, Bharath; Yi, Han-Gyol; Blanco, Nathaniel J; McGeary, John E; Maddox, W Todd

    2015-05-20

    A mutation of the forkhead box protein P2 (FOXP2) gene is associated with severe deficits in human speech and language acquisition. In rodents, the humanized form of FOXP2 promotes faster switching from declarative to procedural learning strategies when the two learning systems compete. Here, we examined a polymorphism of FOXP2 (rs6980093) in humans (214 adults; 111 females) for associations with non-native speech category learning success. Neurocomputational modeling results showed that individuals with the GG genotype shifted faster to procedural learning strategies, which are optimal for the task. These findings support an adaptive role for the FOXP2 gene in modulating the function of neural learning systems that have a direct bearing on human speech category learning.

  14. The speech and language FOXP2 gene modulates the phenotype of frontotemporal lobar degeneration.

    PubMed

    Padovani, Alessandro; Cosseddu, Maura; Premi, Enrico; Archetti, Silvana; Papetti, Alice; Agosti, Chiara; Bigni, Barbara; Cerini, Carlo; Paghera, Barbara; Bellelli, Giuseppe; Borroni, Barbara

    2010-01-01

    The FOXP2 gene is mutated in a severe monogenic form of speech and language deficits, but no study on the influence of genetic variations within FOXP2 in neurological disorders characterized by language impairment is available yet. In the present study, we investigated the impact of common FOXP2 polymorphisms with regard to frontotemporal lobar degeneration (FTLD). Two-hundred ten FTLD patients underwent clinical and a wide standardized neuropsychological examination as well as brain imaging. In all patients, and in 200 age-matched healthy controls, four FOXP2 polymorphisms were evaluated, namely rs2396753, rs1456031, rs17137124 and rs1852469. SPECT images were analyzed by Statistical Parametric Mapping (SPM5). No significant differences of the four FOXP2 polymorphisms in genotype distribution and allele frequency between FTLD and controls were observed. A significant and specific association between rs1456031 TT and rs17137124 TT genotypes and verbal fluency scores was reported. The two polymorphisms showed an addictive effect. When the analysis was computed on the number of observations over time, and 391 assessments considered, comparable results were obtained. FTLD patients carrying at-risk polymorphisms showed greater hypoperfusion in the frontal areas, namely the left inferior frontal gyrus, and putamen, compared to the non-carriers (p < 0.005). Genetic variations within FOXP2 do not represent a genetic risk to FTLD per se, but modulate FTLD presentation when disease is overt, affecting language performances and leading to hypoperfusion in language-associated brain areas.

  15. Salivary FOXP2 expression and oral feeding success in premature infants

    PubMed Central

    Zimmerman, Emily; Maki, Monika; Maron, Jill

    2016-01-01

    The objective of the study is to determine whether salivary FOXP2 gene expression levels at the initiation of oral feeding attempts are predictive of oral feeding success in the premature newborn. In this prospective study, saliva samples from 21 premature infants (13 males; birth gestational age [GA]: 30–34 wk) were collected around the initiation of oral feeding trials. Total RNA was extracted and underwent reverse transcription-quantitative polymerase chain reaction amplification for FOXP2. Oral feeding success was denoted by the days required to attain full oral feeds. A linear regression model, controlling for sex, birth GA, and weight at salivary collection, revealed that FOXP2 expression was significantly associated with oral feeding success (P = 0.002). The higher the expression level of FOXP2, the shorter the duration to feed. Salivary FOXP2 expression levels are significantly associated with oral feeding success in the preterm infant. FOXP2 may serve as a novel and informative biomarker to noninvasively assess infant feeding skills to reduce morbidities and length of stay. PMID:27148579

  16. FoxP2 is a parvocellular-specific transcription factor in the visual thalamus of monkeys and ferrets.

    PubMed

    Iwai, Lena; Ohashi, Yohei; van der List, Deborah; Usrey, William Martin; Miyashita, Yasushi; Kawasaki, Hiroshi

    2013-09-01

    Although the parallel visual pathways are a fundamental basis of visual processing, our knowledge of their molecular properties is still limited. Here, we uncovered a parvocellular-specific molecule in the dorsal lateral geniculate nucleus (dLGN) of higher mammals. We found that FoxP2 transcription factor was specifically expressed in X cells of the adult ferret dLGN. Interestingly, FoxP2 was also specifically expressed in parvocellular layers 3-6 of the dLGN of adult old world monkeys, providing new evidence for a homology between X cells in the ferret dLGN and parvocellular cells in the monkey dLGN. Furthermore, this expression pattern was established as early as gestation day 140 in the embryonic monkey dLGN, suggesting that parvocellular specification has already occurred when the cytoarchitectonic dLGN layers are formed. Our results should help in gaining a fundamental understanding of the development, evolution, and function of the parallel visual pathways, which are especially prominent in higher mammals.

  17. FoxP2 is a Parvocellular-Specific Transcription Factor in the Visual Thalamus of Monkeys and Ferrets

    PubMed Central

    Iwai, Lena; Ohashi, Yohei; van der List, Deborah; Usrey, William Martin; Miyashita, Yasushi; Kawasaki, Hiroshi

    2013-01-01

    Although the parallel visual pathways are a fundamental basis of visual processing, our knowledge of their molecular properties is still limited. Here, we uncovered a parvocellular-specific molecule in the dorsal lateral geniculate nucleus (dLGN) of higher mammals. We found that FoxP2 transcription factor was specifically expressed in X cells of the adult ferret dLGN. Interestingly, FoxP2 was also specifically expressed in parvocellular layers 3–6 of the dLGN of adult old world monkeys, providing new evidence for a homology between X cells in the ferret dLGN and parvocellular cells in the monkey dLGN. Furthermore, this expression pattern was established as early as gestation day 140 in the embryonic monkey dLGN, suggesting that parvocellular specification has already occurred when the cytoarchitectonic dLGN layers are formed. Our results should help in gaining a fundamental understanding of the development, evolution, and function of the parallel visual pathways, which are especially prominent in higher mammals. PMID:22791804

  18. The structure of innate vocalizations in Foxp2-deficient mouse pups.

    PubMed

    Gaub, S; Groszer, M; Fisher, S E; Ehret, G

    2010-06-01

    Heterozygous mutations of the human FOXP2 gene are implicated in a severe speech and language disorder. Aetiological mutations of murine Foxp2 yield abnormal synaptic plasticity and impaired motor-skill learning in mutant mice, while knockdown of the avian orthologue in songbirds interferes with auditory-guided vocal learning. Here, we investigate influences of two distinct Foxp2 point mutations on vocalizations of 4-day-old mouse pups (Mus musculus). The R552H missense mutation is identical to that causing speech and language deficits in a large well-studied human family, while the S321X nonsense mutation represents a null allele that does not produce Foxp2 protein. We ask whether vocalizations, based solely on innate mechanisms of production, are affected by these alternative Foxp2 mutations. Sound recordings were taken in two different situations: isolation and distress, eliciting a range of call types, including broadband vocalizations of varying noise content, ultrasonic whistles and clicks. Sound production rates and several acoustic parameters showed that, despite absence of functional Foxp2, homozygous mutants could vocalize all types of sounds in a normal temporal pattern, but only at comparably low intensities. We suggest that altered vocal output of these homozygotes may be secondary to developmental delays and somatic weakness. Heterozygous mutants did not differ from wild-types in any of the measures that we studied (R552H ) or in only a few (S321X ), which were in the range of differences routinely observed for different mouse strains. Thus, Foxp2 is not essential for the innate production of emotional vocalizations with largely normal acoustic properties by mouse pups.

  19. FOXP2 gene deletion and infant feeding difficulties: a case report

    PubMed Central

    Zimmerman, Emily; Maron, Jill L.

    2016-01-01

    Forkhead box protein P2 (FOXP2) is a well-studied gene known to play an essential role in normal speech development. Deletions in the gene have been shown to result in developmental speech disorders and regulatory disruption of downstream gene targets associated with common forms of language impairments. Despite similarities in motor planning and execution between speech development and oral feeding competence, there have been no reports to date linking deletions within the FOXP2 gene to oral feeding impairments in the newborn. The patient was a nondysmorphic, appropriately and symmetrically grown male infant born at 35-wk gestational age. He had a prolonged neonatal intensive care unit stay because of persistent oral feeding incoordination requiring gastrostomy tube placement. Cardiac and neurological imagings were within normal limits. A microarray analysis found an ∼9-kb loss within chromosome band 7q3.1 that contains exon 2 of FOXP2, demonstrating a single copy of this region instead of the normal two copies per diploid gene. This case study expands our current understanding of the role FOXP2 exerts on motor planning and coordination necessary for both oral feeding success and speech–language development. This case report has important consequences for future diagnosis and treatment for infants with FOXP2 deletions, mutations, and varying levels of gene expression. PMID:27148578

  20. Transcriptional regulation by FOXP1, FOXP2, and FOXP4 dimerization.

    PubMed

    Sin, Cora; Li, Hongyan; Crawford, Dorota A

    2015-02-01

    FOXP1, FOXP2, and FOXP4 are three members of the FOXP gene subfamily of transcription factors involved in the development of the central nervous system. Previous studies have shown that the transcriptional activity of FOXP1/2/4 is regulated by homo- and heterodimerization. However, their transcriptional gene targets in the developing brain are still largely unknown. FOXP2 regulates the expression of many genes important in embryonic development, including WNT and Notch signaling pathways. In this study, we investigate whether dimerization of FOXP1/2/4 leads to differential expression of ten known FOXP2 target genes (CER1, SFRP4, WISP2, PRICKLE1, NCOR2, SNW1, NEUROD2, PAX3, EFNB3, and SLIT1). FOXP1/2/4 open-reading frames were stably transfected into HEK293 cells, and the expression level of these FOXP2 target genes was quantified using real-time polymerase chain reaction. Our results revealed that the specific combination of FOXP1/2/4 dimers regulates transcription of various FOXP2 target genes involved in early neuronal development.

  1. Small intragenic deletion in FOXP2 associated with childhood apraxia of speech and dysarthria.

    PubMed

    Turner, Samantha J; Hildebrand, Michael S; Block, Susan; Damiano, John; Fahey, Michael; Reilly, Sheena; Bahlo, Melanie; Scheffer, Ingrid E; Morgan, Angela T

    2013-09-01

    Relatively little is known about the neurobiological basis of speech disorders although genetic determinants are increasingly recognized. The first gene for primary speech disorder was FOXP2, identified in a large, informative family with verbal and oral dyspraxia. Subsequently, many de novo and familial cases with a severe speech disorder associated with FOXP2 mutations have been reported. These mutations include sequencing alterations, translocations, uniparental disomy, and genomic copy number variants. We studied eight probands with speech disorder and their families. Family members were phenotyped using a comprehensive assessment of speech, oral motor function, language, literacy skills, and cognition. Coding regions of FOXP2 were screened to identify novel variants. Segregation of the variant was determined in the probands' families. Variants were identified in two probands. One child with severe motor speech disorder had a small de novo intragenic FOXP2 deletion. His phenotype included features of childhood apraxia of speech and dysarthria, oral motor dyspraxia, receptive and expressive language disorder, and literacy difficulties. The other variant was found in a family in two of three family members with stuttering, and also in the mother with oral motor impairment. This variant was considered a benign polymorphism as it was predicted to be non-pathogenic with in silico tools and found in database controls. This is the first report of a small intragenic deletion of FOXP2 that is likely to be the cause of severe motor speech disorder associated with language and literacy problems.

  2. Association between the FOXP2 gene and autistic disorder in Chinese population.

    PubMed

    Gong, Xiaohong; Jia, Meixiang; Ruan, Yan; Shuang, Mei; Liu, Jing; Wu, Suping; Guo, Yanqing; Yang, Jianzhong; Ling, Yansu; Yang, Xiaoling; Zhang, Dai

    2004-05-15

    Several genomewide screens indicated that chromosome 7q was linked to autistic disorder. FOXP2, located on 7q31, is a putative transcription factor containing a polyglutamine tract and a forkhead DNA binding domain. It is one member of the forkhead family who are known to be key regulators of embryogenesis. A point mutation at a highly conserved residue within the forkhead domain co-segregated with affected status in the KE family who was a unique three generation pedigree with a severe speech and language disorder and FOXP2 was directly disrupted by a translocation in an individual who had similar deficits as those of the KE family. Several studies have investigated the role of FOXP2 polymorphisms in autism and none of them found positive association. We performed a family-based association study of three single nucleotide polymorphisms (SNPs) of FOXP2 in 181 Chinese Han trios using the analyses of transmission/disequilibrium test (TDT) and haplotype. We found a significant association between autistic disorder and one SNP, as well as with specific haplotypes formed by this SNP with two other SNPs we investigated. Our findings suggest that the FOXP2 gene may be involved in the pathogenesis of autism in Chinese population.

  3. The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders.

    PubMed

    Bacon, Claire; Rappold, Gudrun A

    2012-11-01

    Rare disruptions of FOXP2 have been strongly implicated in deficits in language development. Research over the past decade has suggested a role in the formation of underlying neural circuits required for speech. Until recently no evidence existed to suggest that the closely related FOXP1 gene played a role in neurodevelopmental processes. However, in the last few years, novel rare disruptions in FOXP1 have been reported in multiple cases of cognitive dysfunction, including intellectual disability and autism spectrum disorder, together with language impairment. As FOXP1 and FOXP2 form heterodimers for transcriptional regulation, one may assume that they co-operate in common neurodevelopmental pathways through the co-regulation of common targets. Here we compare the phenotypic consequences of FOXP1 and FOXP2 impairment, drawing on well-known studies from the past as well as recent exciting findings and consider what these tell us regarding the functions of these two genes in neural development.

  4. FoxP2 protein levels regulate cell morphology changes and migration patterns in the vertebrate developing telencephalon.

    PubMed

    Garcia-Calero, Elena; Botella-Lopez, Arancha; Bahamonde, Olga; Perez-Balaguer, Ariadna; Martinez, Salvador

    2016-07-01

    In the mammalian telencephalon, part of the progenitor cells transition from multipolar to bipolar morphology as they invade the mantle zone. This associates with changing patterns of radial migration. However, the molecules implicated in these morphology transitions are not well known. In the present work, we analyzed the function of FoxP2 protein in this process during telencephalic development in vertebrates. We analyzed the expression of FoxP2 protein and its relation with cell morphology and migratory patterns in mouse and chicken developing striatum. We observed FoxP2 protein expressed in a gradient from the subventricular zone to the mantle layer in mice embryos. In the FoxP2 low domain cells showed multipolar migration. In the striatal mantle layer where FoxP2 protein expression is higher, cells showed locomoting migration and bipolar morphology. In contrast, FoxP2 showed a high and homogenous expression pattern in chicken striatum, thus bipolar morphology predominated. Elevation of FoxP2 in the striatal subventricular zone by in utero electroporation promoted bipolar morphology and impaired multipolar radial migration. In mouse cerebral cortex we obtained similar results. FoxP2 promotes transition from multipolar to bipolar morphology by means of gradiental expression in mouse striatum and cortex. Together these results indicate a role of FoxP2 differential expression in cell morphology control of the vertebrate telencephalon.

  5. FOXP2, APOE, and PRNP: new modulators in primary progressive aphasia.

    PubMed

    Premi, Enrico; Pilotto, Andrea; Alberici, Antonella; Papetti, Alice; Archetti, Silvana; Seripa, Davide; Daniele, Antonio; Masullo, Carlo; Garibotto, Valentina; Paghera, Barbara; Caobelli, Federico; Padovani, Alessandro; Borroni, Barbara

    2012-01-01

    Primary progressive aphasia (PPA) is a heterogeneous disorder characterized by progressive language impairment. Polymorphisms within forkhead box P2 gene (FOXP2) gene have been associated with speech and language impairment. Apolipoprotein E (APOE) genotype and PRNP 129 codon status have been demonstrated to increase the risk of PPA, but with contrasting results. In the present study, we have evaluated the impact of FOXP2, APOE and PRNP genetic variations as risk factors and/or disease-modulators in PPA. 94 PPA patients and 200 age-matched healthy controls were considered and FOXP2 polymorphisms (rs1456031, rs17137124), APOE genotype, and PRNP codon 129 polymorphism analyzed. In 34 PPA patients, SPECT imaging data were analyzed by Statistical Parametric Mapping (SPM8). Genetic distributions and allele frequencies of FOXP2 and PRNP polymorphisms did not differ between groups while APOE ε4 was more represented in PPA as compared to controls. PPA patients carrying at-risk FOXP2 polymorphisms (rs1456031 and/or rs17137124) showed greater hypoperfusion in the frontal areas, namely the left inferior frontal gyrus and the right cingulated gyrus compared to non-carriers (p < 0.005). PPA patients carrying at least one ε4 allele had greater hypoperfusion in orbitofrontal regions (superior frontal gyrus and orbital gyrus) as compared to non-carriers ε4 (p < 0.005). PRNP codon 129 homozigosity correlated with left frontotemporal hypoperfusion (p < 0.005). Genetic variations within FOXP2, APOE, and PRNP modulate PPA disease, leading to a specific regional hypoperfusion according to different molecular pathways. APOE ε4 is overrepresented in PPA, thus likely acting as genetic risk factor on disease development.

  6. The evolution of high energy accelerators

    SciTech Connect

    Courant, E.D.

    1989-10-01

    In this lecture I would like to trace how high energy particle accelerators have grown from tools used for esoteric small-scale experiments to gigantic projects being hotly debated in Congress as well as in the scientific community.

  7. Early Milestones in the Evolution of Accelerators

    NASA Astrophysics Data System (ADS)

    Courant, E. D.

    About 80 years ago Rutherford [1] expressed the hope that particles could be accelerated to energies exceeding those occurring in radioactivity, enabling the study of nuclei and their constituents. Physicists and engineers have more than met this challenge, and today the LHC (Large Hadron Collider) at CERN, Geneva is about to accelerate protons to 7 trillion (7 × 1012) eV. Here we describe some of the crucial steps that have gotten us there.

  8. The evolution of high energy accelerators

    SciTech Connect

    Courant, E.D.

    1994-08-01

    Accelerators have been devised and built for two reasons: In the first place, by physicists who needed high energy particles in order to have a means to explore the interactions between particles that probe the fundamental elementary forces of nature. And conversely, sometimes accelerator builders produce new machines for higher energy than ever before just because it can be done, and then challenge potential users to make new discoveries with the new means at hand. These two approaches or motivations have gone hand in hand. This lecture traces how high energy particle accelerators have grown from tools used for esoteric small-scale experiments to the gigantic projects of today. So far all the really high-energy machines built and planned in the world--except the SLC--have been ring accelerators and storage rings using the strong-focusing method. But this method has not removed the energy limit, it has only pushed it higher. It would seem unlikely that one can go beyond the Large Hadron Collider (LHC)--but in fact a workshop was held in Sicily in November 1991, concerned with the question of extrapolating to 100 TeV. Other acceleration and beam-forming methods are now being discussed--collective fields, laser acceleration, wake-field accelerators etc., all aimed primarily at making linear colliders possible and more attractive than with present radiofrequency methods. So far it is not entirely clear which of these schemes will dominate particle physics in the future--maybe something that has not been thought of as yet.

  9. Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex.

    PubMed

    Roll, Patrice; Vernes, Sonja C; Bruneau, Nadine; Cillario, Jennifer; Ponsole-Lenfant, Magali; Massacrier, Annick; Rudolf, Gabrielle; Khalife, Manal; Hirsch, Edouard; Fisher, Simon E; Szepetowski, Pierre

    2010-12-15

    It is a challenge to identify the molecular networks contributing to the neural basis of human speech. Mutations in transcription factor FOXP2 cause difficulties mastering fluent speech (developmental verbal dyspraxia, DVD), whereas mutations of sushi-repeat protein SRPX2 lead to epilepsy of the rolandic (sylvian) speech areas, with DVD or with bilateral perisylvian polymicrogyria. Pathophysiological mechanisms driven by SRPX2 involve modified interaction with the plasminogen activator receptor (uPAR). Independent chromatin-immunoprecipitation microarray screening has identified the uPAR gene promoter as a potential target site bound by FOXP2. Here, we directly tested for the existence of a transcriptional regulatory network between human FOXP2 and the SRPX2/uPAR complex. In silico searches followed by gel retardation assays identified specific efficient FOXP2-binding sites in each of the promoter regions of SRPX2 and uPAR. In FOXP2-transfected cells, significant decreases were observed in the amounts of both SRPX2 (43.6%) and uPAR (38.6%) native transcripts. Luciferase reporter assays demonstrated that FOXP2 expression yielded a marked inhibition of SRPX2 (80.2%) and uPAR (77.5%) promoter activity. A mutant FOXP2 that causes DVD (p.R553H) failed to bind to SRPX2 and uPAR target sites and showed impaired down-regulation of SRPX2 and uPAR promoter activity. In a patient with polymicrogyria of the left rolandic operculum, a novel FOXP2 mutation (p.M406T) was found in the leucine-zipper (dimerization) domain. p.M406T partially impaired the FOXP2 regulation of SRPX2 promoter activity, whereas that of the uPAR promoter remained unchanged. Together with recently described FOXP2-CNTNAP2 and SRPX2/uPAR links, the FOXP2-SRPX2/uPAR network provides exciting insights into molecular pathways underlying speech-related disorders.

  10. Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain.

    PubMed

    Ferland, Russell J; Cherry, Timothy J; Preware, Patricia O; Morrisey, Edward E; Walsh, Christopher A

    2003-05-26

    Foxp2 and Foxp1 are recently identified members of the Fox family of winged-helix/forkhead transcription factor genes. A recent study has found that mutations in human FOXP2 produce a severe language disorder. Since Foxp2 appears to be important in language, we wanted to explore the expression of this gene and a homologous gene, Foxp1, in the developing brain. In the present study, we investigated the time course and localization of Foxp2 and Foxp1 mRNA and protein expression in the developing and adult mouse using in situ hybridization and immunohistochemistry. Foxp2 and Foxp1 are expressed as early as E12.5 and persist into adulthood. Foxp2 and Foxp1 were most highly expressed in the developing and mature basal ganglia. Expression of Foxp2 was also observed in the cerebral cortex (layer 6), cerebellum (Purkinje neurons), and thalamus. Foxp1 expression was observed in the cerebral cortex (layers 3-5), hippocampus (CA1), and thalamus. Very little ventricular zone expression was observed for Foxp2 and Foxp1 and the expression of both of these genes occurred following neuronal migration, suggesting a role for these genes in postmigratory neuronal differentiation. Furthermore, we demonstrated the expression of FOXP2 in human fetal brain by RT-PCR, in the perisylvian area of the left and right cerebral hemispheres, as well as in the frontal and occipital cortices. Overall, the widespread expression of Foxp2 in the developing brain makes it difficult to draw specific conclusions about which areas of Foxp2 expression are critical to human language function.

  11. A Key Evolutionary Mutation Enhances DNA Binding of the FOXP2 Forkhead Domain.

    PubMed

    Morris, Gavin; Fanucchi, Sylvia

    2016-04-05

    Forkhead box (FOX) transcription factors share a conserved forkhead DNA binding domain (FHD) and are key role players in the development of many eukaryotic species. Their involvement in various congenital disorders and cancers makes them clinically relevant targets for novel therapeutic strategies. Among them, the FOXP subfamily of multidomain transcriptional repressors is unique in its ability to form DNA binding homo and heterodimers. The truncated FOXP2 FHD, in the absence of the leucine zipper, exists in equilibrium between monomeric and domain-swapped dimeric states in vitro. As a consequence, determining the DNA binding properties of the FOXP2 FHD becomes inherently difficult. In this work, two FOXP2 FHD hinge loop mutants have been generated to successfully prevent both the formation (A539P) and the dissociation (F541C) of the homodimers. This allows for the separation of the two species for downstream DNA binding studies. Comparison of DNA binding of the different species using electrophoretic mobility shift assay, fluorescence anisotropy and isothermal titration calorimetry indicates that the wild-type FOXP2 FHD binds DNA as a monomer. However, comparison of the DNA-binding energetics of the monomer and wild-type FHD, reveals that there is a difference in the mechanism of binding between the two species. We conclude that the naturally occurring reverse mutation (P539A) seen in the FOXP subfamily increases DNA binding affinity and may increase the potential for nonspecific binding compared to other FOX family members.

  12. A recent evolutionary change affects a regulatory element in the human FOXP2 gene.

    PubMed

    Maricic, Tomislav; Günther, Viola; Georgiev, Oleg; Gehre, Sabine; Curlin, Marija; Schreiweis, Christiane; Naumann, Ronald; Burbano, Hernán A; Meyer, Matthias; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Gajovic, Srecko; Kelso, Janet; Enard, Wolfgang; Schaffner, Walter; Pääbo, Svante

    2013-04-01

    The FOXP2 gene is required for normal development of speech and language. By isolating and sequencing FOXP2 genomic DNA fragments from a 49,000-year-old Iberian Neandertal and 50 present-day humans, we have identified substitutions in the gene shared by all or nearly all present-day humans but absent or polymorphic in Neandertals. One such substitution is localized in intron 8 and affects a binding site for the transcription factor POU3F2, which is highly conserved among vertebrates. We find that the derived allele of this site is less efficient than the ancestral allele in activating transcription from a reporter construct. The derived allele also binds less POU3F2 dimers than POU3F2 monomers compared with the ancestral allele. Because the substitution in the POU3F2 binding site is likely to alter the regulation of FOXP2 expression, and because it is localized in a region of the gene associated with a previously described signal of positive selection, it is a plausible candidate for having caused a recent selective sweep in the FOXP2 gene.

  13. Mosaic 7q31 deletion involving FOXP2 gene associated with language impairment.

    PubMed

    Palka, Chiara; Alfonsi, Melissa; Mohn, Angelika; Cerbo, Renato; Guanciali Franchi, Paolo; Fantasia, Donatella; Morizio, Elisena; Stuppia, Liborio; Calabrese, Giuseppe; Zori, Roberto; Chiarelli, Francesco; Palka, Giandomenico

    2012-01-01

    We report on a 10-year-old patient with childhood apraxia of speech (CAS) and mild dysmorphic features. Although multiple karyotypes were reported as normal, a bacterial artificial chromosome array comparative genomic hybridization revealed the presence of a de novo 14.8-Mb mosaic deletion of chromosome 7q31. The deleted region involved several genes, including FOXP2, which has been associated with CAS. Interestingly, the deletion reported here was observed in about 50% of cells, which is the first case of mosaicism in a 7q31 deletion. Despite the presence of the deletion in only 50% of cells, the phenotype of the patient was not milder than other published cases. To date, 6 cases with a deletion of 9.1-20 Mb involving the FOXP2 gene have been reported, suggesting a new contiguous gene deletion syndrome characterized mainly by CAS caused by haploinsufficiency of the genes encompassed in the 7q critical region. This report suggests that children found with a deletion involving the FOXP2 region should be evaluated for CAS and that analysis of the FOXP2 gene including array comparative genomic hybridization should be considered in selected patients with CAS. Mosaic deletions in this area may also be considered as causative of CAS.

  14. Neanderthals did speak, but FOXP2 doesn't prove it.

    PubMed

    Johansson, Sverker

    2014-12-01

    Ackermann et al. treat both genetic and paleoanthropological data too superficially to support their conclusions. The case of FOXP2 and Neanderthals is a prime example, which I will comment on in some detail; the issues are much more complex than they appear in Ackermann et al.

  15. Structure of the forkhead domain of FOXP2 bound to DNA.

    PubMed

    Stroud, James C; Wu, Yongqing; Bates, Darren L; Han, Aidong; Nowick, Katja; Paabo, Svante; Tong, Harry; Chen, Lin

    2006-01-01

    FOXP (FOXP1-4) is a newly defined subfamily of the forkhead box (FOX) transcription factors. A mutation in the FOXP2 forkhead domain cosegregates with a severe speech disorder, whereas several mutations in the FOXP3 forkhead domain are linked to the IPEX syndrome in human and a similar autoimmune phenotype in mice. Here we report a 1.9 A crystal structure of the forkhead domain of human FOXP2 bound to DNA. This structure allows us to revise the previously proposed DNA recognition mechanism and provide a unifying model of DNA binding for the FOX family of proteins. Our studies also reveal that the FOXP2 forkhead domain can form a domain-swapped dimer, made possible by a strategic substitution of a highly conserved proline in conventional FOX proteins with alanine in the P subfamily. Disease-causing mutations in FOXP2 and FOXP3 map either to the DNA binding surface or the domain-swapping dimer interface, functionally corroborating the crystal structure.

  16. Common Genetic Variants in FOXP2 Are Not Associated with Individual Differences in Language Development.

    PubMed

    Mueller, Kathryn L; Murray, Jeffrey C; Michaelson, Jacob J; Christiansen, Morten H; Reilly, Sheena; Tomblin, J Bruce

    2016-01-01

    Much of our current knowledge regarding the association of FOXP2 with speech and language development comes from singleton and small family studies where a small number of rare variants have been identified. However, neither genome-wide nor gene-specific studies have provided evidence that common polymorphisms in the gene contribute to individual differences in language development in the general population. One explanation for this inconsistency is that previous studies have been limited to relatively small samples of individuals with low language abilities, using low density gene coverage. The current study examined the association between common variants in FOXP2 and a quantitative measure of language ability in a population-based cohort of European decent (n = 812). No significant associations were found for a panel of 13 SNPs that covered the coding region of FOXP2 and extended into the promoter region. Power analyses indicated we should have been able to detect a QTL variance of 0.02 for an associated allele with MAF of 0.2 or greater with 80% power. This suggests that, if a common variant associated with language ability in this gene does exist, it is likely of small effect. Our findings lead us to conclude that while genetic variants in FOXP2 may be significant for rare forms of language impairment, they do not contribute appreciably to individual variation in the normal range as found in the general population.

  17. Genetic variation in FOXP2 alters grey matter concentrations in schizophrenia patients.

    PubMed

    Španiel, Filip; Horáček, Jiří; Tintěra, Jaroslav; Ibrahim, Ibrahim; Novák, Tomáš; Čermák, Jan; Klírová, Monika; Höschl, Cyril

    2011-04-15

    FOXP2, the first gene known to be involved in the development of speech and language, can be considered to be, a priori, a candidate gene in schizophrenia, given the mounting evidence that the underlying core deficit in this disease could be a failure of structures relevant to normal language processing. To investigate the potential link between grey matter concentration (GMC) changes in patients with schizophrenia and the FOXP2 rs2396753 polymorphism previously reported to be associated with hallucinations in schizophrenia, we analysed high-resolution anatomical magnetic resonance images of 40 genotyped patients with schizophrenia and 36 healthy controls, using optimised voxel-based morphometry (VBM). Here we show that the common SNP rs2396753 (C>A) gene variant of the FOXP2 gene has significant effects on GMC in patients with schizophrenia, within regions of the brain known to be affected by this disease. Our data suggest that GMC reductions in schizophrenia may be driven by C allele carriers of the FOXP2 gene variant.

  18. Common Genetic Variants in FOXP2 Are Not Associated with Individual Differences in Language Development

    PubMed Central

    Mueller, Kathryn L.; Murray, Jeffrey C.; Michaelson, Jacob J.; Christiansen, Morten H.; Reilly, Sheena; Tomblin, J. Bruce

    2016-01-01

    Much of our current knowledge regarding the association of FOXP2 with speech and language development comes from singleton and small family studies where a small number of rare variants have been identified. However, neither genome-wide nor gene-specific studies have provided evidence that common polymorphisms in the gene contribute to individual differences in language development in the general population. One explanation for this inconsistency is that previous studies have been limited to relatively small samples of individuals with low language abilities, using low density gene coverage. The current study examined the association between common variants in FOXP2 and a quantitative measure of language ability in a population-based cohort of European decent (n = 812). No significant associations were found for a panel of 13 SNPs that covered the coding region of FOXP2 and extended into the promoter region. Power analyses indicated we should have been able to detect a QTL variance of 0.02 for an associated allele with MAF of 0.2 or greater with 80% power. This suggests that, if a common variant associated with language ability in this gene does exist, it is likely of small effect. Our findings lead us to conclude that while genetic variants in FOXP2 may be significant for rare forms of language impairment, they do not contribute appreciably to individual variation in the normal range as found in the general population. PMID:27064276

  19. FoxP2 expression defines dorsolateral pontine neurons activated by sodium deprivation*

    PubMed Central

    Geerling, Joel C; Stein, Matthew K; Miller, Rebecca L; Shin, Jung-Won; Gray, Paul A; Loewy, Arthur D

    2010-01-01

    Two specific groups of neurons in the dorsolateral pons are activated by dietary sodium deprivation. These two groups are the pre-locus coeruleus (pre-LC) and the inner subdivision of the external lateral parabrachial nucleus (PBel-inner). In each site, after rats are fed an extremely low-sodium diet for over a week, neurons increase their expression of an activity-induced transcription factor, c-Fos. Here, we confirm this observation and extend it by demonstrating that these two groups of neurons express a common marker gene, the constitutively-expressed transcription factor Forkhead box protein 2 (FoxP2). That is, virtually all of the c-Fos activated neurons in both regions also express FoxP2. The expression of FoxP2 by both these groups of neurons suggests that they are developmentally-related subsets derived from the same basic population. Given that FoxP2, unlike c-Fos, is expressed independent of sodium deprivation, this marker may be useful in future studies of the pre-LC and PBel-inner. The molecular definition of these neurons, which project to circuits in the forebrain that influence visceral, appetitive, and hedonic functions, may allow direct experimental exploration of the functional role of these circuits using genetic tools. PMID:21108936

  20. FOXP2 Is Not a Major Susceptibility Gene for Autism or Specific Language Impairment

    PubMed Central

    Newbury, D. F.; Bonora, E.; Lamb, J. A.; Fisher, S. E.; Lai, C. S. L.; Baird, G.; Jannoun, L.; Slonims, V.; Stott, C. M.; Merricks, M. J.; Bolton, P. F.; Bailey, A. J.; Monaco, A. P.

    2002-01-01

    The FOXP2 gene, located on human 7q31 (at the SPCH1 locus), encodes a transcription factor containing a polyglutamine tract and a forkhead domain. FOXP2 is mutated in a severe monogenic form of speech and language impairment, segregating within a single large pedigree, and is also disrupted by a translocation in an isolated case. Several studies of autistic disorder have demonstrated linkage to a similar region of 7q (the AUTS1 locus), leading to the proposal that a single genetic factor on 7q31 contributes to both autism and language disorders. In the present study, we directly evaluate the impact of the FOXP2 gene with regard to both complex language impairments and autism, through use of association and mutation screening analyses. We conclude that coding-region variants in FOXP2 do not underlie the AUTS1 linkage and that the gene is unlikely to play a role in autism or more common forms of language impairment. PMID:11894222

  1. Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird basal ganglia nucleus Area X.

    PubMed

    Haesler, Sebastian; Rochefort, Christelle; Georgi, Benjamin; Licznerski, Pawel; Osten, Pavel; Scharff, Constance

    2007-12-01

    The gene encoding the forkhead box transcription factor, FOXP2, is essential for developing the full articulatory power of human language. Mutations of FOXP2 cause developmental verbal dyspraxia (DVD), a speech and language disorder that compromises the fluent production of words and the correct use and comprehension of grammar. FOXP2 patients have structural and functional abnormalities in the striatum of the basal ganglia, which also express high levels of FOXP2. Since human speech and learned vocalizations in songbirds bear behavioral and neural parallels, songbirds provide a genuine model for investigating the basic principles of speech and its pathologies. In zebra finch Area X, a basal ganglia structure necessary for song learning, FoxP2 expression increases during the time when song learning occurs. Here, we used lentivirus-mediated RNA interference (RNAi) to reduce FoxP2 levels in Area X during song development. Knockdown of FoxP2 resulted in an incomplete and inaccurate imitation of tutor song. Inaccurate vocal imitation was already evident early during song ontogeny and persisted into adulthood. The acoustic structure and the duration of adult song syllables were abnormally variable, similar to word production in children with DVD. Our findings provide the first example of a functional gene analysis in songbirds and suggest that normal auditory-guided vocal motor learning requires FoxP2.

  2. Assessing the effects of common variation in the FOXP2 gene on human brain structure

    PubMed Central

    Hoogman, Martine; Guadalupe, Tulio; Zwiers, Marcel P.; Klarenbeek, Patricia; Francks, Clyde; Fisher, Simon E.

    2014-01-01

    The FOXP2 transcription factor is one of the most well-known genes to have been implicated in developmental speech and language disorders. Rare mutations disrupting the function of this gene have been described in different families and cases. In a large three-generation family carrying a missense mutation, neuroimaging studies revealed significant effects on brain structure and function, most notably in the inferior frontal gyrus, caudate nucleus, and cerebellum. After the identification of rare disruptive FOXP2 variants impacting on brain structure, several reports proposed that common variants at this locus may also have detectable effects on the brain, extending beyond disorder into normal phenotypic variation. These neuroimaging genetics studies used groups of between 14 and 96 participants. The current study assessed effects of common FOXP2 variants on neuroanatomy using voxel-based morphometry (VBM) and volumetric techniques in a sample of >1300 people from the general population. In a first targeted stage we analyzed single nucleotide polymorphisms (SNPs) claimed to have effects in prior smaller studies (rs2253478, rs12533005, rs2396753, rs6980093, rs7784315, rs17137124, rs10230558, rs7782412, rs1456031), beginning with regions proposed in the relevant papers, then assessing impact across the entire brain. In the second gene-wide stage, we tested all common FOXP2 variation, focusing on volumetry of those regions most strongly implicated from analyses of rare disruptive mutations. Despite using a sample that is more than 10 times that used for prior studies of common FOXP2 variation, we found no evidence for effects of SNPs on variability in neuroanatomy in the general population. Thus, the impact of this gene on brain structure may be largely limited to extreme cases of rare disruptive alleles. Alternatively, effects of common variants at this gene exist but are too subtle to be detected with standard volumetric techniques. PMID:25013396

  3. Identification of the transcriptional targets of FOXP2, a gene linked to speech and language, in developing human brain.

    PubMed

    Spiteri, Elizabeth; Konopka, Genevieve; Coppola, Giovanni; Bomar, Jamee; Oldham, Michael; Ou, Jing; Vernes, Sonja C; Fisher, Simon E; Ren, Bing; Geschwind, Daniel H

    2007-12-01

    Mutations in FOXP2, a member of the forkhead family of transcription factor genes, are the only known cause of developmental speech and language disorders in humans. To date, there are no known targets of human FOXP2 in the nervous system. The identification of FOXP2 targets in the developing human brain, therefore, provides a unique tool with which to explore the development of human language and speech. Here, we define FOXP2 targets in human basal ganglia (BG) and inferior frontal cortex (IFC) by use of chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) and validate the functional regulation of targets in vitro. ChIP-chip identified 285 FOXP2 targets in fetal human brain; statistically significant overlap of targets in BG and IFC indicates a core set of 34 transcriptional targets of FOXP2. We identified targets specific to IFC or BG that were not observed in lung, suggesting important regional and tissue differences in FOXP2 activity. Many target genes are known to play critical roles in specific aspects of central nervous system patterning or development, such as neurite outgrowth, as well as plasticity. Subsets of the FOXP2 transcriptional targets are either under positive selection in humans or differentially expressed between human and chimpanzee brain. This is the first ChIP-chip study to use human brain tissue, making the FOXP2-target genes identified in these studies important to understanding the pathways regulating speech and language in the developing human brain. These data provide the first insight into the functional network of genes directly regulated by FOXP2 in human brain and by evolutionary comparisons, highlighting genes likely to be involved in the development of human higher-order cognitive processes.

  4. The status and evolution of plasma Wakefield particle accelerators.

    PubMed

    Joshi, C; Mori, W B

    2006-03-15

    The status and evolution of the electron beam-driven Plasma Wakefield Acceleration scheme is described. In particular, the effects of the radial electric field of the wake on the drive beam such as multiple envelope oscillations, hosing instability and emission of betatron radiation are described. Using ultra-short electron bunches, high-density plasmas can be produced by field ionization by the electric field of the bunch itself. Wakes excited in such plasmas have accelerated electrons in the back of the drive beam to greater that 4 G eV in just 10 cm in experiments carried out at the Stanford Linear Accelerator Centre.

  5. FOXP2 expression during brain development coincides with adult sites of pathology in a severe speech and language disorder.

    PubMed

    Lai, Cecilia S L; Gerrelli, Dianne; Monaco, Anthony P; Fisher, Simon E; Copp, Andrew J

    2003-11-01

    Disruption of FOXP2, a gene encoding a forkhead-domain transcription factor, causes a severe developmental disorder of verbal communication, involving profound articulation deficits, accompanied by linguistic and grammatical impairments. Investigation of the neural basis of this disorder has been limited previously to neuroimaging of affected children and adults. The discovery of the gene responsible, FOXP2, offers a unique opportunity to explore the relevant neural mechanisms from a molecular perspective. In the present study, we have determined the detailed spatial and temporal expression pattern of FOXP2 mRNA in the developing brain of mouse and human. We find expression in several structures including the cortical plate, basal ganglia, thalamus, inferior olives and cerebellum. These data support a role for FOXP2 in the development of corticostriatal and olivocerebellar circuits involved in motor control. We find intriguing concordance between regions of early expression and later sites of pathology suggested by neuroimaging. Moreover, the homologous pattern of FOXP2/Foxp2 expression in human and mouse argues for a role for this gene in development of motor-related circuits throughout mammalian species. Overall, this study provides support for the hypothesis that impairments in sequencing of movement and procedural learning might be central to the FOXP2-related speech and language disorder.

  6. Selective quantification of human DNA by real-time PCR of FOXP2.

    PubMed

    Soejima, Mikiko; Hiroshige, Kenichi; Yoshimoto, Joji; Koda, Yoshiro

    2012-07-01

    We established a simple quantitative PCR procedure with high specificity and sensitivity using TaqMan probes targeting the FOXP2 sequence. This assay distinguished human and nonhuman, including primates, samples with the exception of mouse, turtle, lizard, and fishes. However, the specific amplification of mouse, lizard, and turtle fragments of FOXP2 could be confirmed by electrophoresis after real-time PCR. Because the C(T) values obtained for human DNA were not affected by contaminating animal DNA at concentrations up to 30 times that of human DNA, we were able to estimate the concentration of human DNA in mixed specimens. This assay provides a reliable and useful method for routine quantification of human-specific DNA in forensic practice.

  7. Singing mice, songbirds, and more: models for FOXP2 function and dysfunction in human speech and language.

    PubMed

    White, Stephanie A; Fisher, Simon E; Geschwind, Daniel H; Scharff, Constance; Holy, Timothy E

    2006-10-11

    In 2001, a point mutation in the forkhead box P2 (FOXP2) coding sequence was identified as the basis of an inherited speech and language disorder suffered by members of the family known as "KE." This mini-symposium review focuses on recent findings and research-in-progress, primarily from five laboratories. Each aims at capitalizing on the FOXP2 discovery to build a neurobiological bridge between molecule and phenotype. Below, we describe genetic through behavioral techniques used currently to investigate FoxP2 in birds, rodents, and humans for discovery of the neural bases of vocal learning and language.

  8. Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex

    PubMed Central

    Roll, Patrice; Vernes, Sonja C.; Bruneau, Nadine; Cillario, Jennifer; Ponsole-Lenfant, Magali; Massacrier, Annick; Rudolf, Gabrielle; Khalife, Manal; Hirsch, Edouard; Fisher, Simon E.; Szepetowski, Pierre

    2010-01-01

    It is a challenge to identify the molecular networks contributing to the neural basis of human speech. Mutations in transcription factor FOXP2 cause difficulties mastering fluent speech (developmental verbal dyspraxia, DVD), whereas mutations of sushi-repeat protein SRPX2 lead to epilepsy of the rolandic (sylvian) speech areas, with DVD or with bilateral perisylvian polymicrogyria. Pathophysiological mechanisms driven by SRPX2 involve modified interaction with the plasminogen activator receptor (uPAR). Independent chromatin-immunoprecipitation microarray screening has identified the uPAR gene promoter as a potential target site bound by FOXP2. Here, we directly tested for the existence of a transcriptional regulatory network between human FOXP2 and the SRPX2/uPAR complex. In silico searches followed by gel retardation assays identified specific efficient FOXP2-binding sites in each of the promoter regions of SRPX2 and uPAR. In FOXP2-transfected cells, significant decreases were observed in the amounts of both SRPX2 (43.6%) and uPAR (38.6%) native transcripts. Luciferase reporter assays demonstrated that FOXP2 expression yielded a marked inhibition of SRPX2 (80.2%) and uPAR (77.5%) promoter activity. A mutant FOXP2 that causes DVD (p.R553H) failed to bind to SRPX2 and uPAR target sites and showed impaired down-regulation of SRPX2 and uPAR promoter activity. In a patient with polymicrogyria of the left rolandic operculum, a novel FOXP2 mutation (p.M406T) was found in the leucine-zipper (dimerization) domain. p.M406T partially impaired the FOXP2 regulation of SRPX2 promoter activity, whereas that of the uPAR promoter remained unchanged. Together with recently described FOXP2-CNTNAP2 and SRPX2/uPAR links, the FOXP2-SRPX2/uPAR network provides exciting insights into molecular pathways underlying speech-related disorders. PMID:20858596

  9. Absence of causative mutations and presence of autism-related allele in FOXP2 in Japanese autistic patients.

    PubMed

    Li, Hong; Yamagata, Takanori; Mori, Masato; Momoi, Mariko Y

    2005-04-01

    We analyzed the FOXP2 gene, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, for a possible causative mutation in autism. FOXP2 was reported to be mutated in patients with a severe speech and language disorder. FOXP2 was located on chromosome 7q31, which is one of the loci involved in autism. Autism and specific language impairment share some of their clinical phenotypes. In addition, FOXP2 was expressed abundantly in the brain. We screened all of the exons of FOXP2 for causative mutations in 53 Japanese autistic patients using denaturing high-performance liquid chromatography and direct sequencing. A delCAA in exon 5 causing one glutamine deletion in the first polyglutamine tract was detected in four patients and in 2 of 50 control individuals. The frequency of the TT allele with the G to T base change in intron 15 was significantly high in the autistic population. The other base changes included one silent base change (A569G) in exon 5 and three in introns. Our results may suggest a relationship between autism and the FOXP2 gene or a gene located nearby.

  10. Young and intense: FoxP2 immunoreactivity in Area X varies with age, song stereotypy, and singing in male zebra finches.

    PubMed

    Thompson, Christopher K; Schwabe, Fabian; Schoof, Alexander; Mendoza, Ezequiel; Gampe, Jutta; Rochefort, Christelle; Scharff, Constance

    2013-01-01

    FOXP2 is a transcription factor functionally relevant for learned vocalizations in humans and songbirds. In songbirds, FoxP2 mRNA expression in the medium spiny neurons of the basal ganglia song nucleus Area X is developmentally regulated and varies with singing conditions in different social contexts. How individual neurons in Area X change FoxP2 expression across development and in social contexts is not known, however. Here we address this critical gap in our understanding of FoxP2 as a link between neuronal networks and behavior. We used a statistically unbiased analysis of FoxP2-immunoreactivity (FoxP2-IR) on a neuron-by-neuron basis and found a bimodal distribution of FoxP2-IR neurons in Area X: weakly-stained and intensely-stained. The density of intensely-stained FoxP2-IR neurons was 10 times higher in juveniles than in adults, exponentially decreased with age, and was negatively correlated with adult song stability. Three-week old neurons labeled with BrdU were more than five times as likely to be intensely-stained than weakly-stained. The density of FoxP2-IR putative migratory neurons with fusiform-shaped nuclei substantially decreased as birds aged. The density of intensely-stained FoxP2-IR neurons was not affected by singing whereas the density of weakly-stained FoxP2-IR neurons was. Together, these data indicate that young Area X medium spiny neurons express FoxP2 at high levels and decrease expression as they become integrated into existing neural circuits. Once integrated, levels of FoxP2 expression correlate with singing behavior. Together, these findings raise the possibility that FoxP2 levels may orchestrate song learning and song stereotypy in adults by a common mechanism.

  11. Young and intense: FoxP2 immunoreactivity in Area X varies with age, song stereotypy, and singing in male zebra finches

    PubMed Central

    Thompson, Christopher K.; Schwabe, Fabian; Schoof, Alexander; Mendoza, Ezequiel; Gampe, Jutta; Rochefort, Christelle; Scharff, Constance

    2013-01-01

    FOXP2 is a transcription factor functionally relevant for learned vocalizations in humans and songbirds. In songbirds, FoxP2 mRNA expression in the medium spiny neurons of the basal ganglia song nucleus Area X is developmentally regulated and varies with singing conditions in different social contexts. How individual neurons in Area X change FoxP2 expression across development and in social contexts is not known, however. Here we address this critical gap in our understanding of FoxP2 as a link between neuronal networks and behavior. We used a statistically unbiased analysis of FoxP2-immunoreactivity (FoxP2-IR) on a neuron-by-neuron basis and found a bimodal distribution of FoxP2-IR neurons in Area X: weakly-stained and intensely-stained. The density of intensely-stained FoxP2-IR neurons was 10 times higher in juveniles than in adults, exponentially decreased with age, and was negatively correlated with adult song stability. Three-week old neurons labeled with BrdU were more than five times as likely to be intensely-stained than weakly-stained. The density of FoxP2-IR putative migratory neurons with fusiform-shaped nuclei substantially decreased as birds aged. The density of intensely-stained FoxP2-IR neurons was not affected by singing whereas the density of weakly-stained FoxP2-IR neurons was. Together, these data indicate that young Area X medium spiny neurons express FoxP2 at high levels and decrease expression as they become integrated into existing neural circuits. Once integrated, levels of FoxP2 expression correlate with singing behavior. Together, these findings raise the possibility that FoxP2 levels may orchestrate song learning and song stereotypy in adults by a common mechanism. PMID:23450800

  12. Rapid evolution accelerates plant population spread in fragmented experimental landscapes.

    PubMed

    Williams, Jennifer L; Kendall, Bruce E; Levine, Jonathan M

    2016-07-29

    Predicting the speed of biological invasions and native species migrations requires an understanding of the ecological and evolutionary dynamics of spreading populations. Theory predicts that evolution can accelerate species' spread velocity, but how landscape patchiness--an important control over traits under selection--influences this process is unknown. We manipulated the response to selection in populations of a model plant species spreading through replicated experimental landscapes of varying patchiness. After six generations of change, evolving populations spread 11% farther than nonevolving populations in continuously favorable landscapes and 200% farther in the most fragmented landscapes. The greater effect of evolution on spread in patchier landscapes was consistent with the evolution of dispersal and competitive ability. Accounting for evolutionary change may be critical when predicting the velocity of range expansions. Copyright © 2016, American Association for the Advancement of Science.

  13. Non-Markovian time evolution of an accelerated qubit

    NASA Astrophysics Data System (ADS)

    Moustos, Dimitris; Anastopoulos, Charis

    2017-01-01

    We present a new method for evaluating the response of a moving qubit detector interacting with a scalar field in Minkowski spacetime. We treat the detector as an open quantum system, but we do not invoke the Markov approximation. The evolution equations for the qubit density matrix are valid at all times, for all qubit trajectories, and they incorporate non-Markovian effects. We analyze in detail the case of uniform acceleration, providing a detailed characterization of all regimes where non-Markovian effects are significant. We argue that the most stable characterization of acceleration temperature refers to the late time behavior of the detector because interaction with the field vacuum brings the qubit to a thermal state at the Unruh temperature. In contrast, the early-time transition rate, that is invoked in most discussions of acceleration temperature, does not exhibit a thermal behavior when non-Markovian effects are taken into account. Finally, we note that the non-Markovian evolution derived here also applies to the mathematically equivalent problem of a static qubit interacting with a thermal field bath.

  14. Laser pulse evolution and electron acceleration in plasmas

    NASA Astrophysics Data System (ADS)

    Esarey, Eric

    2000-04-01

    Laser-driven plasma-based accelerators(For a review see, E. Esarey et al., IEEE Trans. Plasma Sci. 24, 252 (1996).) require the propagation of intense laser pulses over long distances in plasmas, the generation of large amplitude wakefields, and the injection and acceleration of electrons. This talk will discuss the nonlinear propagation of short laser pulses in plasmas, with or without channels. Non-paraxial effects will be analyzed and simulated, including finite pulse duration, finite group velocity, and dispersion(E. Esarey et al., Phys. Rev. Lett., submitted.). These effects on the evolution of the forward Raman and self-modulation instabilities, that lead the generation of wakefields, will be examined. Also discussed are methods for self-trapping and injecting electrons into the wakefield. Application to ongoing experiments at LBNL(W.P. Leemans et al., Phys. Plasma 5, 1615 (1998); in preparation.) will be discussed.

  15. Interaction between MAOA and FOXP2 in association with autism and verbal communication in a Korean population.

    PubMed

    Park, YoungJoon; Won, SeongSik; Nam, Min; Chung, Joo-Ho; Kwack, KyuBum

    2014-12-01

    Expression levels of monoamine oxidase A (MAOA), the enzyme that related to monoamine neurotransmitters metabolism such as serotonin, are related to schizophrenia and autism spectrum disorder. Forkhead box protein P2 (FOXP2), a transcription factor, is associated with abnormal language development and is expressed in several areas of the central nervous system in response to serotonin. For this reason, we undertook interaction analysis between MAOA and FOXP2 in autism spectrum disorder, including testing the verbal communication score of the childhood autism rating scale. In interaction analysis, the FOXP2-TCGC (rs12531289-rs1350135-rs10230087-rs2061183) diplotype and MAOA-TCG (rs6323-rs1801291-rs3027407) haplotype were significantly associated with autism spectrum disorder in males. However, when the interaction term was omitted, neither MAOA nor FOXP2 was associated with autism spectrum disorder or verbal communication. These results indicate that language and speech ability is affected by an interaction between FOXP2 and MAOA, but not by either gene separately. © The Author(s) 2013.

  16. Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction.

    PubMed

    Teramitsu, Ikuko; Kudo, Lili C; London, Sarah E; Geschwind, Daniel H; White, Stephanie A

    2004-03-31

    Humans and songbirds are two of the rare animal groups that modify their innate vocalizations. The identification of FOXP2 as the monogenetic locus of a human speech disorder exhibited by members of the family referred to as KE enables the first examination of whether molecular mechanisms for vocal learning are shared between humans and songbirds. Here, in situ hybridization analyses for FoxP1 and FoxP2 in a songbird reveal a corticostriatal expression pattern congruent with the abnormalities in brain structures of affected KE family members. The overlap in FoxP1 and FoxP2 expression observed in the songbird suggests that combinatorial regulation by these molecules during neural development and within vocal control structures may occur. In support of this idea, we find that FOXP1 and FOXP2 expression patterns in human fetal brain are strikingly similar to those in the songbird, including localization to subcortical structures that function in sensorimotor integration and the control of skilled, coordinated movement. The specific colocalization of FoxP1 and FoxP2 found in several structures in the bird and human brain predicts that mutations in FOXP1 could also be related to speech disorders.

  17. Foxp2 mediates sex differences in ultrasonic vocalization by rat pups and directs order of maternal retrieval.

    PubMed

    Bowers, J Michael; Perez-Pouchoulen, Miguel; Edwards, N Shalon; McCarthy, Margaret M

    2013-02-20

    The FOXP2 gene is central to acquisition of speech and language in humans and vocal production in birds and mammals. Rodents communicate via ultrasonic vocalizations (USVs) and newborn pups emit distress USVs when separated from their dam, thereby facilitating their retrieval. We observed that isolated male rat pups emitted substantially more USV calls and these were characterized by a significantly lower frequency and amplitude compared with female rat pups. Moreover, the dam was more likely to first retrieve male pups back to the nest, then females. The amount of Foxp2 protein was significantly higher in multiple regions of the developing male brain compared with females and a reduction of brain Foxp2 by siRNA eliminated the sex differences in USVs and altered the order of pup retrieval. Our results implicate Foxp2 as a component of the neurobiological basis of sex differences in vocal communication in mammals. We extended these observations to humans, a species reported to have gender differences in language acquisition, and found the amount of FOXP2 protein in the left hemisphere cortex of 4-year-old boys was significantly lower than in age-matched girls.

  18. Foxp2 mediates sex differences in ultrasonic vocalization by rat pups and directs order of maternal retrieval

    PubMed Central

    Bowers, J. Michael; Perez-Pouchoulen, Miguel; Edwards, N. Shalon; McCarthy, Margaret M.

    2013-01-01

    The FOXP2 gene is central to acquisition of speech and language in humans and vocal production in birds and mammals. Rodents communicate via ultrasonic vocalizations (USVs) and newborn pups emit distress USVs when separated from their dam, thereby facilitating their retrieval. We observed that isolated male rat pups emitted substantially more USV calls and these were characterized by a significantly lower frequency and amplitude compared to female rat pups. Moreover, the dam was more likely to first retrieve male pups back to the nest, then females. The amount of Foxp2 protein was significantly higher in multiple regions of the developing male brain compared to females and, a reduction of brain Foxp2 by siRNA eliminated the sex differences in USVs and altered the order of pup retrieval. Our results implicate Foxp2 as a component of the neurobiological basis of sex differences in vocal communication in mammals. We extended these observations to humans, a species reported to have gender differences in language acquisition, and found the amount of FOXP2 protein in the left hemisphere cortex of 4-year-old boys was significantly lower than in age-matched girls. PMID:23426656

  19. The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21WAF1/CIP1 in 143B Osteosarcoma Cell Growth Arrest.

    PubMed

    Gascoyne, Duncan M; Spearman, Hayley; Lyne, Linden; Puliyadi, Rathi; Perez-Alcantara, Marta; Coulton, Les; Fisher, Simon E; Croucher, Peter I; Banham, Alison H

    2015-01-01

    Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21WAF1/CIP1. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21WAF1/CIP1 activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1). Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology.

  20. Accelerated Evolution of Enhancer Hotspots in the Mammal Ancestor.

    PubMed

    Holloway, Alisha K; Bruneau, Benoit G; Sukonnik, Tatyana; Rubenstein, John L; Pollard, Katherine S

    2016-04-01

    Mammals have evolved remarkably different sensory, reproductive, metabolic, and skeletal systems. To explore the genetic basis for these differences, we developed a comparative genomics approach to scan whole-genome multiple sequence alignments to identify regions that evolved rapidly in an ancestral lineage but are conserved within extant species. This pattern suggests that ancestral changes in function were maintained in descendants. After applying this test to therian mammals, we identified 4,797 accelerated regions, many of which are noncoding and located near developmental transcription factors. We then used mouse transgenic reporter assays to test if noncoding accelerated regions are enhancers and to determine how therian-specific substitutions affect their activity in vivo. We discovered enhancers with expression specific to the therian version in brain regions involved in the hormonal control of milk ejection, uterine contractions, blood pressure, temperature, and visual processing. This work underscores the idea that changes in developmental gene expression are important for mammalian evolution, and it pinpoints candidate genes for unique aspects of mammalian biology. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Shrinkage of X cells in the lateral geniculate nucleus after monocular deprivation revealed by FoxP2 labeling.

    PubMed

    Duffy, Kevin R; Holman, Kaitlyn D; Mitchell, Donald E

    2014-05-01

    The parallel processing of visual features by distinct neuron populations is a central characteristic of the mammalian visual system. In the A laminae of the cat dorsal lateral geniculate nucleus (dLGN), parallel processing streams originate from two principal neuron types, called X and Y cells. Disruption of visual experience early in life by monocular deprivation has been shown to alter the structure and function of Y cells, but the extent to which deprivation influences X cells remains less clear. A transcription factor, FoxP2, has recently been shown to selectively label X cells in the ferret dLGN and thus provides an opportunity to examine whether monocular deprivation alters the soma size of X cells. In this study, FoxP2 labeling was examined in the dLGN of normal and monocularly deprived cats. The characteristics of neurons labeled for FoxP2 were consistent with FoxP2 being a marker for X cells in the cat dLGN. Monocular deprivation for either a short (7 days) or long (7 weeks) duration did not alter the density of FoxP2-positive neurons between nondeprived and deprived dLGN layers. However, for each deprived animal examined, measurement of the cross-sectional area of FoxP2-positive neurons (X cells) revealed that within deprived layers, X cells were smaller by approximately 20% after 7 days of deprivation, and by approximately 28% after 7 weeks of deprivation. The observed alteration to the cross-sectional area of X cells indicates that perturbation of this major pathway contributes to the functional impairments that develop from monocular deprivation.

  2. Differential FoxP2 and FoxP1 expression in a vocal learning nucleus of the developing budgerigar.

    PubMed

    Whitney, Osceola; Voyles, Tawni; Hara, Erina; Chen, Qianqian; White, Stephanie A; Wright, Timothy F

    2015-07-01

    The forkhead domain FOXP2 and FOXP1 transcription factors are implicated in several cognitive disorders with language deficits, notably autism, and thus play a central role in learned vocal motor behavior in humans. Although a similar role for FoxP2 and FoxP1 is proposed for other vertebrate species, including songbirds, the neurodevelopmental expression of these genes are unknown in a species with lifelong vocal learning abilities. Like humans, budgerigars (Melopsittacus undulatus) learn new vocalizations throughout their entire lifetime. Like songbirds, budgerigars have distinct brain nuclei for vocal learning, which include the magnocellular nucleus of the medial striatum (MMSt), a basal ganglia region that is considered developmentally and functionally analogous to Area X in songbirds. Here, we used in situ hybridization and immunohistochemistry to investigate FoxP2 and FoxP1 expression in the MMSt of juvenile and adult budgerigars. We found FoxP2 mRNA and protein expression levels in the MMSt that were lower than the surrounding striatum throughout development and adulthood. In contrast, FoxP1 mRNA and protein had an elevated MMSt/striatum expression ratio as birds matured, regardless of their sex. These results show that life-long vocal plasticity in budgerigars is associated with persistent low-level FoxP2 expression in the budgerigar MMSt, and suggests the possibility that FoxP1 plays an organizational role in the neurodevelopment of vocal motor circuitry. Thus, developmental regulation of the FoxP2 and FoxP1 genes in the basal ganglia appears essential for vocal mimicry in a range of species that possess this relatively rare trait.

  3. Differential FoxP2 and FoxP1 expression in a vocal learning nucleus of the developing budgerigar

    PubMed Central

    Whitney, Osceola; Voyles, Tawni; Hara, Erina; Chen, Qianqian; White, Stephanie A.; Wright, Timothy F.

    2014-01-01

    The forkhead domain FOXP2 and FOXP1 transcription factors are implicated in several cognitive disorders with language deficits, notably autism, and thus play a central role in learned vocal motor behavior in humans. Although a similar role for FoxP2 and FoxP1 is proposed for other vertebrate species, including songbirds, the neurodevelopmental expression of these genes are unknown in a species with lifelong vocal learning abilities. Like humans, budgerigars (Melopsittacus undulatus) learn new vocalizations throughout their entire lifetime. Like songbirds, budgerigars have distinct brain nuclei for vocal learning, which include the magnocellular nucleus of the medial striatum (MMSt), a basal ganglia region that is considered developmentally and functionally analogous to Area X in songbirds. Here we used in situ hybridization and immunohistochemistry to investigate FoxP2 and FoxP1 expression in the MMSt of juvenile and adult budgerigars. We found FoxP2 mRNA and protein expression levels in the MMSt that were lower than the surrounding striatum throughout development and adulthood. In contrast, FoxP1 mRNA and protein had an elevated MMSt/striatum expression ratio as birds matured, regardless of their sex. These results show that life-long vocal plasticity in budgerigars is associated with persistent low-level FoxP2 expression in the budgerigar MMSt, and suggests the possibility that FoxP1 plays an organizational role in the neurodevelopment of vocal motor circuitry. Thus, developmental regulation of the FoxP2 and FoxP1 genes in the basal ganglia appears essential for vocal mimicry in a range of species that possess this relatively rare trait. PMID:25407828

  4. Accelerated evolution of constraint elements for hematophagic adaptation in mosquitoes

    PubMed Central

    WANG, Ming-Shan; ADEOLA, Adeniyi C.; LI, Yan; ZHANG, Ya-Ping; WU, Dong-Dong

    2015-01-01

    Comparative genomics is a powerful approach that comprehensively interprets the genome. Herein, we performed whole genome comparative analysis of 16 Diptera genomes, including four mosquitoes and 12 Drosophilae. We found more than 540 000 constraint elements (CEs) in the Diptera genome, with the majority found in the intergenic, coding and intronic regions. Accelerated elements (AEs) identified in mosquitoes were mostly in the protein-coding regions (>93%), which differs from vertebrates in genomic distribution. Some genes functionally enriched in blood digestion, body temperature regulation and insecticide resistance showed rapid evolution not only in the lineage of the recent common ancestor of mosquitoes (RCAM), but also in some mosquito lineages. This may be associated with lineage-specific traits and/or adaptations in comparison with other insects. Our findings revealed that although universally fast evolution acted on biological systems in RCAM, such as hematophagy, same adaptations also appear to have occurred through distinct degrees of evolution in different mosquito species, enabling them to be successful blood feeders in different environments. PMID:26646568

  5. Accelerated evolution of constraint elements for hematophagic adaptation in mosquitoes.

    PubMed

    Wang, Ming-Shan; Adeola, Adeniyi C; Li, Yan; Zhang, Ya-Ping; Wu, Dong-Dong

    2015-11-18

    Comparative genomics is a powerful approach that comprehensively interprets the genome. Herein, we performed whole genome comparative analysis of 16 Diptera genomes, including four mosquitoes and 12 Drosophilae. We found more than 540 000 constraint elements (CEs) in the Diptera genome, with the majority found in the intergenic, coding and intronic regions. Accelerated elements (AEs) identified in mosquitoes were mostly in the protein-coding regions (>93%), which differs from vertebrates in genomic distribution. Some genes functionally enriched in blood digestion, body temperature regulation and insecticide resistance showed rapid evolution not only in the lineage of the recent common ancestor of mosquitoes (RCAM), but also in some mosquito lineages. This may be associated with lineage-specific traits and/or adaptations in comparison with other insects. Our findings revealed that although universally fast evolution acted on biological systems in RCAM, such as hematophagy, same adaptations also appear to have occurred through distinct degrees of evolution in different mosquito species, enabling them to be successful blood feeders in different environments.

  6. DNA and RNA editing of retrotransposons accelerate mammalian genome evolution.

    PubMed

    Knisbacher, Binyamin A; Levanon, Erez Y

    2015-04-01

    Genome evolution is commonly viewed as a gradual process that is driven by random mutations that accumulate over time. However, DNA- and RNA-editing enzymes have been identified that can accelerate evolution by actively modifying the genomically encoded information. The apolipoprotein B mRNA editing enzymes, catalytic polypeptide-like (APOBECs) are potent restriction factors that can inhibit retroelements by cytosine-to-uridine editing of retroelement DNA after reverse transcription. In some cases, a retroelement may successfully integrate into the genome despite being hypermutated. Such events introduce unique sequences into the genome and are thus a source of genomic innovation. adenosine deaminases that act on RNA (ADARs) catalyze adenosine-to-inosine editing in double-stranded RNA, commonly formed by oppositely oriented retroelements. The RNA editing confers plasticity to the transcriptome by generating many transcript variants from a single genomic locus. If the editing produces a beneficial variant, the genome may maintain the locus that produces the RNA-edited transcript for its novel function. Here, we discuss how these two powerful editing mechanisms, which both target inserted retroelements, facilitate expedited genome evolution.

  7. [FOXP2 and the molecular biology of language: new evidence. I. Phenotypic aspects and animal models].

    PubMed

    Benítez-Burraco, A

    FOXP2 is the first gene linked to a hereditary variant of specific language impairment and seems to code for a transcriptional repressor that intervenes in the regulation of development and the functioning of certain thalamic-cortical-striatal circuits. In the last three years significant progress has been made in the analysis of the structural and functional properties of the gene. The most notable advances have been made in the genotypic and phenotypic characterisation of new alterations in its sequencing in human beings; the determination in vivo of the functional properties of the mutated proteins generated from said variants; the cloning and characterisation of new orthologues of the gene; the generation of the first knockout and knockdown organisms for it; and a more precise molecular characterisation of the biological role played by the orthologues corresponding to species that are also capable of learning the articulatory patterns of the vocalisations they use to communicate. The latest clinical evidence and that obtained from analysing animal models generated to date appear to suggest the presence of a 'sensory-motor disorder' as the central deficit behind the different phenotypes associated to the different mutations of the gene in the human species, the functionality of the gene FOXP2 during development of the embryo and during the adult phase, its involvement in the development and functioning of the thalamic-cortical-striatal circuits associated to motor planning, sequential behaviour and procedural learning, and significant old age, in developmental terms, of a part of the neuroanatomical substrate that is involved in processing linguistic stimuli in our species.

  8. The plateau zokors' learning and memory ability is related to the high expression levels of foxP2 in the brain.

    PubMed

    Ma, Ben-Yuan; Wei, Lian; Sun, Sheng-Zhen; Wang, Duo-Wei; Wei, Deng-Bang

    2014-04-25

    Plateau zokor (Myospalax baileyi) is a subterranean mammal. Plateau zokor has high learning and memory ability, and can determine the location of blocking obstacles in their tunnels. Forkhead box p2 (FOXP2) is a transcription factor implicated in the neural control of orofacial coordination and sensory-motor integration, particularly with respect to learning, memory and vocalization. To explore the association of foxP2 with the high learning and memory ability of plateau zokor, the cDNA of foxP2 of plateau zokor was sequenced; by using plateau pika as control, the expression levels of foxP2 mRNA and FOXP2 protein in brain of plateau zokor were determined by real-time PCR and Western blot, respectively; and the location of FOXP2 protein in the brain of plateau zokor was determined by immunohistochemistry. The result showed that the cDNA sequence of plateau zokor foxP2 was similar to that of other mammals and the amino acid sequences showed a relatively high degree of conservation, with the exception of two particular amino acid substitutions [a Gln (Q)-to-His (H) change at position 231 and a Ser (S)-to-Ile (I) change at position 235]. Higher expression levels of foxP2 mRNA (3-fold higher) and FOXP2 protein (>2-fold higher) were detected in plateau zokor brain relative to plateau pika brain. In plateau zokor brain, FOXP2 protein was highly expressed in the cerebral cortex, thalamus and the striatum (a basal ganglia brain region). The results suggest that the high learning and memory ability of plateau zokor is related to the high expression levels of foxP2 in the brain.

  9. Accelerated Evolution of Enhancer Hotspots in the Mammal Ancestor

    PubMed Central

    Holloway, Alisha K.; Bruneau, Benoit G.; Sukonnik, Tatyana; Rubenstein, John L.; Pollard, Katherine S.

    2016-01-01

    Mammals have evolved remarkably different sensory, reproductive, metabolic, and skeletal systems. To explore the genetic basis for these differences, we developed a comparative genomics approach to scan whole-genome multiple sequence alignments to identify regions that evolved rapidly in an ancestral lineage but are conserved within extant species. This pattern suggests that ancestral changes in function were maintained in descendants. After applying this test to therian mammals, we identified 4,797 accelerated regions, many of which are noncoding and located near developmental transcription factors. We then used mouse transgenic reporter assays to test if noncoding accelerated regions are enhancers and to determine how therian-specific substitutions affect their activity in vivo. We discovered enhancers with expression specific to the therian version in brain regions involved in the hormonal control of milk ejection, uterine contractions, blood pressure, temperature, and visual processing. This work underscores the idea that changes in developmental gene expression are important for mammalian evolution, and it pinpoints candidate genes for unique aspects of mammalian biology. PMID:26715627

  10. Language Features in a Mother and Daughter of a Chromosome 7;13 Translocation Involving "FOXP2"

    ERIC Educational Resources Information Center

    Tomblin, J. Bruce; O'Brien, Marlea; Shriberg, Lawrence D.; Williams, Charles; Murray, Jeff; Patil, Shivanand; Bjork, Jonathan; Anderson, Steve; Ballard, Kirrie

    2009-01-01

    Purpose: The aims of this study were (a) to locate the breakpoints of a balanced translocation (7;13) within a mother (B) and daughter (T); (b) to describe the language and cognitive skills of B and T; and (c) to compare this profile with affected family members of the KE family who have a mutation within "FOXP2." Method: The breakpoint locations…

  11. Language Features in a Mother and Daughter of a Chromosome 7;13 Translocation Involving "FOXP2"

    ERIC Educational Resources Information Center

    Tomblin, J. Bruce; O'Brien, Marlea; Shriberg, Lawrence D.; Williams, Charles; Murray, Jeff; Patil, Shivanand; Bjork, Jonathan; Anderson, Steve; Ballard, Kirrie

    2009-01-01

    Purpose: The aims of this study were (a) to locate the breakpoints of a balanced translocation (7;13) within a mother (B) and daughter (T); (b) to describe the language and cognitive skills of B and T; and (c) to compare this profile with affected family members of the KE family who have a mutation within "FOXP2." Method: The breakpoint locations…

  12. Speech, Prosody, and Voice Characteristics of a Mother and Daughter with a 7;13 Translocation Affecting "FOXP2"

    ERIC Educational Resources Information Center

    Shriberg, Lawrence D.; Ballard, Kirrie J.; Tomblin, J. Bruce; Duffy, Joseph R.; Odell, Katharine H.; Williams, Charles A.

    2006-01-01

    Purpose: The primary goal of this case study was to describe the speech, prosody, and voice characteristics of a mother and daughter with a breakpoint in a balanced 7;13 chromosomal translocation that disrupted the transcription gene, "FOXP2" (cf. J. B. Tomblin et al., 2005). As with affected members of the widely cited KE family, whose…

  13. Speech, Prosody, and Voice Characteristics of a Mother and Daughter with a 7;13 Translocation Affecting "FOXP2"

    ERIC Educational Resources Information Center

    Shriberg, Lawrence D.; Ballard, Kirrie J.; Tomblin, J. Bruce; Duffy, Joseph R.; Odell, Katharine H.; Williams, Charles A.

    2006-01-01

    Purpose: The primary goal of this case study was to describe the speech, prosody, and voice characteristics of a mother and daughter with a breakpoint in a balanced 7;13 chromosomal translocation that disrupted the transcription gene, "FOXP2" (cf. J. B. Tomblin et al., 2005). As with affected members of the widely cited KE family, whose…

  14. Accelerated and Adaptive Evolution of Yeast Sexual Adhesins

    PubMed Central

    Xie, Xianfa; Qiu, Wei-Gang; Lipke, Peter N.

    2011-01-01

    There is a recent emergence of interest in the genes involved in gametic recognition as drivers of reproductive isolation. The recent population genomic sequencing of two species of sexually primitive yeasts (Liti G, Carter DM, Moses AM, Warringer J, Parts L, James SA, Davey RP, Roberts IN, Burt A, Koufopanou V et al. [23 co-authors]. 2009. Population genomics of domestic and wild yeasts. Nature 458:337–341.) has provided data for systematic study of the roles these genes play in the early evolution of sex and speciation. Here, we discovered that among genes encoding cell surface proteins, the sexual adhesin genes have evolved significantly more rapidly than others, both within and between Saccharomyces cerevisiae and its closest relative S. paradoxus. This result was supported by analyses using the PAML pairwise model, a modified McDonald–Kreitman test, and the PAML branch model. Moreover, using a combination of a new statistic of neutrality, an information theory–based measure of evolutionary variability, and functional characterization of amino acid changes, we found that a higher proportion of amino acid changes are fixed in the sexual adhesins than in other proteins and a greater proportion of the fixed amino acid changes either between the two species or the two subgroups of S. paradoxus are functionally dissimilar or radically different. These results suggest that the accelerated evolution of sexual adhesin genes may facilitate speciation, or incipient speciation, and promote sexual selection in general. PMID:21633112

  15. A study of the role of the FOXP2 and CNTNAP2 genes in persistent developmental stuttering.

    PubMed

    Han, Tae-Un; Park, John; Domingues, Carlos F; Moretti-Ferreira, Danilo; Paris, Emily; Sainz, Eduardo; Gutierrez, Joanne; Drayna, Dennis

    2014-09-01

    A number of speech disorders including stuttering have been shown to have important genetic contributions, as indicated by high heritability estimates from twin and other studies. We studied the potential contribution to stuttering from variants in the FOXP2 gene, which have previously been associated with developmental verbal dyspraxia, and from variants in the CNTNAP2 gene, which have been associated with specific language impairment (SLI). DNA sequence analysis of these two genes in a group of 602 unrelated cases, all with familial persistent developmental stuttering, revealed no excess of potentially deleterious coding sequence variants in the cases compared to a matched group of 487 well characterized neurologically normal controls. This was compared to the distribution of variants in the GNPTAB, GNPTG, and NAGPA genes which have previously been associated with persistent stuttering. Using an expanded subject data set, we again found that NAGPA showed significantly different mutation frequencies in North Americans of European descent (p=0.0091) and a significant difference existed in the mutation frequency of GNPTAB in Brazilians (p=0.00050). No significant differences in mutation frequency in the FOXP2 and CNTNAP2 genes were observed between cases and controls. To examine the pattern of expression of these five genes in the human brain, real time quantitative reverse transcription PCR was performed on RNA purified from 27 different human brain regions. The expression patterns of FOXP2 and CNTNAP2 were generally different from those of GNPTAB, GNPTG and NAPGA in terms of relatively lower expression in the cerebellum. This study provides an improved estimate of the contribution of mutations in GNPTAB, GNPTG and NAGPA to persistent stuttering, and suggests that variants in FOXP2 and CNTNAP2 are not involved in the genesis of familial persistent stuttering. This, together with the different brain expression patterns of GNPTAB, GNPTG, and NAGPA compared to that of

  16. A study of the role of the FOXP2 and CNTNAP2 genes in persistent developmental stuttering

    PubMed Central

    Han, Tae-Un; Park, John; Domingues, Carlos F.; Moretti-Ferreira, Danilo; Paris, Emily; Sainz, Eduardo; Guiterrez, Joanne; Drayna, Dennis

    2014-01-01

    A number of speech disorders including stuttering have been shown to have important genetic contributions, as indicated by high heritability estimates from twin and other studies. We studied the potential contribution to stuttering from variants in the FOXP2 gene, which have previously been associated with developmental verbal dyspraxia, and from variants in the CNTNAP2 gene, which have been associated with specific language impairment (SLI). DNA sequence analysis of these two genes in a group of 602 unrelated cases, all with familial persistent developmental stuttering, revealed no excess of potentially deleterious coding sequence variants in the cases compared to a matched group of 487 well characterized neurologically normal controls. This was compared to the distribution of variants in the GNPTAB, GNPTG, and NAGPA genes which have previously been associated with persistent stuttering. Using an expanded subject data set, we again found that NAGPA showed significantly different mutation frequencies in North Americans of European descent (p = 0.0091) and a significant difference existed in the mutation frequency of GNPTAB in Brazilians (p = 0.00050). No significant differences in mutation frequency in the FOXP2 and CNTNAP2 genes were observed between cases and controls. To examine the pattern of expression of these five genes in human brain, real time quantitative reverse transcription PCR was performed on RNA purified from 27 different human brain regions. The expression patterns of FOXP2 and CNTNAP2 were generally different from those of GNPTAB, GNPTG and NAPGA in terms of relatively lower expression in cerebellum. This study provides an improved estimate of the contribution of mutations in the GNPTAB, GNPTG and NAGPA to persistent stuttering, and suggests that variants in the FOXP2 and CNTNAP2 are not involved in the genesis of familial persistent stuttering. This, together with the different brain expression patterns of GNPTAB, GNPTG, and NAGPA compared to

  17. Language impairment in a case of a complex chromosomal rearrangement with a breakpoint downstream of FOXP2.

    PubMed

    Moralli, Daniela; Nudel, Ron; Chan, May T M; Green, Catherine M; Volpi, Emanuela V; Benítez-Burraco, Antonio; Newbury, Dianne F; García-Bellido, Paloma

    2015-01-01

    We report on a young female, who presents with a severe speech and language disorder and a balanced de novo complex chromosomal rearrangement, likely to have resulted from a chromosome 7 pericentromeric inversion, followed by a chromosome 7 and 11 translocation. Using molecular cytogenetics, we mapped the four breakpoints to 7p21.1-15.3 (chromosome position: 20,954,043-21,001,537, hg19), 7q31 (chromosome position: 114,528,369-114,556,605, hg19), 7q21.3 (chromosome position: 93,884,065-93,933,453, hg19) and 11p12 (chromosome position: 38,601,145-38,621,572, hg19). These regions contain only non-coding transcripts (ENSG00000232790 on 7p21.1 and TCONS_00013886, TCONS_00013887, TCONS_00014353, TCONS_00013888 on 7q21) indicating that no coding sequences are directly disrupted. The breakpoint on 7q31 mapped 200 kb downstream of FOXP2, a well-known language gene. No splice site or non-synonymous coding variants were found in the FOXP2 coding sequence. We were unable to detect any changes in the expression level of FOXP2 in fibroblast cells derived from the proband, although this may be the result of the low expression level of FOXP2 in these cells. We conclude that the phenotype observed in this patient either arises from a subtle change in FOXP2 regulation due to the disruption of a downstream element controlling its expression, or from the direct disruption of non-coding RNAs.

  18. FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures

    PubMed Central

    Wong, Kah Keng; Gascoyne, Duncan M.; Soilleux, Elizabeth J.; Lyne, Linden; Spearman, Hayley; Roncador, Giovanna; Pedersen, Lars M.; Møller, Michael B.; Green, Tina M.; Banham, Alison H.

    2016-01-01

    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL. PMID:27224915

  19. Foxp2 inhibits Nkx2.1-mediated transcription of SP-C via interactions with the Nkx2.1 homeodomain.

    PubMed

    Zhou, Beiyun; Zhong, Qian; Minoo, Parviz; Li, Changgong; Ann, David K; Frenkel, Baruch; Morrisey, Edward E; Crandall, Edward D; Borok, Zea

    2008-06-01

    The transcription factor (TF) Foxp2 has been shown to partially repress surfactant protein C (SP-C) transcription, presumably through interaction of an independent repressor domain with a conserved Foxp2 consensus site in the SP-C promoter. We explored the role of interactions between Foxp2 and the homeodomain TF Nkx2.1 that may contribute to the marked reduction in SP-C expression accompanying phenotypic transition of alveolar epithelial type II (AT2) to type I (AT1) cells. Foxp2 dose-dependently inhibited Nkx2.1-mediated activation of SP-C in MLE-15 cells. While electrophoretic mobility shift assays and chromatin immunoprecipitations revealed an interaction between Foxp2 and the conserved consensus motif in the SP-C promoter, Nkx2.1-mediated activation of the 318-bp proximal SP-C promoter (which lacks a Foxp2 consensus) was attenuated by increasing amounts of Foxp2. Co-immunoprecipitation and mammalian two-hybrid assays confirmed a physical interaction between Nkx2.1 and Foxp2 mediated through the Nkx2.1 homeodomain. Formation of an Nkx2.1 complex with an SP-C oligonucleotide was inhibited dose-dependently by recombinant Foxp2. These findings demonstrate that direct interaction between Foxp2 and Nkx2.1 inhibits Nkx2.1 DNA-binding and transcriptional activity and suggest a mechanism for down-regulation of SP-C (and probably other AT2 cell genes) during transition of AT2 cells to an AT1 cell phenotype.

  20. FoxP2 expression in the cerebellum and inferior olive: development of the transverse stripe-shaped expression pattern in the mouse cerebellar cortex.

    PubMed

    Fujita, Hirofumi; Sugihara, Izumi

    2012-02-15

    Many molecules are expressed heterogeneously in subpopulations of cerebellar Purkinje cells (PCs) and inferior olive (IO) neurons during development or in adulthood. These expression patterns are often organized in longitudinal stripes in the cerebellar cortex, which may be related to functional compartmentalization. FoxP2, a transcription factor, is expressed in PCs and IO neurons, but the details of its expression pattern remain unclear. Here we examined FoxP2 expression patterns systematically by immunostaining serial sections of the hindbrain from embryonic day 14.5 to adulthood in mice. FoxP2 was highly expressed in virtually all PCs at and before postnatal day 6 (P6), except for those in the flocculus and small parts of the nodulus (vermal lobule X), where FoxP2 expression was moderate or absent. After P6, FoxP2 expression gradually diminished in PCs in some areas. In adults, FoxP2 was expressed, less intensely than in earlier stages, in subsets of PCs that were mostly arranged transversely along the folial apices. In contrast, FoxP2 was expressed intensely in most IO neurons during development and in adulthood. FoxP2 was also expressed in a small population of neurons in the cerebellar nuclei. FoxP2 expression in adult rats and chicks was generally comparable to that in adult mice, suggesting evolutionary conservation of the expression pattern. Thus, the FoxP2 expression pattern reflects new transverse compartmentalization in the adult cerebellar cortex, although its functional significance remains unclear.

  1. FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures.

    PubMed

    Wong, Kah Keng; Gascoyne, Duncan M; Soilleux, Elizabeth J; Lyne, Linden; Spearman, Hayley; Roncador, Giovanna; Pedersen, Lars M; Møller, Michael B; Green, Tina M; Banham, Alison H

    2016-08-16

    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL.

  2. Effect of pH on the Structure and DNA Binding of the FOXP2 Forkhead Domain.

    PubMed

    Blane, Ashleigh; Fanucchi, Sylvia

    2015-06-30

    Forkhead box P2 (FOXP2) is a transcription factor expressed in cardiovascular, intestinal, and neural tissues during embryonic development and is implicated in language development. FOXP2 like other FOX proteins contains a DNA binding domain known as the forkhead domain (FHD). The FHD interacts with DNA by inserting helix 3 into the major groove. One of these DNA-protein interactions is a direct hydrogen bond that is formed with His554. FOXP2 is localized in the nuclear compartment that has a pH of 7.5. Histidine contains an imidazole side chain in which the amino group typically has a pKa of ~6.5. It seems possible that pH fluctuations around 6.5 may result in changes in the protonation state of His554 and thus the ability of the FOXP2 FHD to bind DNA. To investigate the effect of pH on the FHD, both the structure and the binding affinity were studied in the pH range of 5-9. This was done in the presence and absence of DNA. The structure was assessed using size exclusion chromatography, far-UV circular dichroism, and intrinsic and extrinsic fluorescence. The results indicated that while pH did not affect the secondary structure in the presence or absence of DNA, the tertiary structure was pH sensitive and the protein was less compact at low pH. Furthermore, the presence of DNA caused the protein to become more compact at low pH and also had the potential to increase the dimerization propensity. Fluorescence anisotropy was used to investigate the effect of pH on the FOXP2 FHD DNA binding affinity. It was found that pH had a direct effect on binding affinity. This was attributed to the altered hydrogen bonding patterns upon protonation or deprotonation of His554. These results could implicate pH as a means of regulating transcription by the FOXP2 FHD, which may also have repercussions for the behavior of this protein in cancer cells.

  3. Expression of FOXP2 in the developing monkey forebrain: comparison with the expression of the genes FOXP1, PBX3, and MEIS2.

    PubMed

    Takahashi, Kaoru; Liu, Fu-Chin; Oishi, Takao; Mori, Takuma; Higo, Noriyuki; Hayashi, Motoharu; Hirokawa, Katsuiku; Takahashi, Hiroshi

    2008-07-10

    By using the developing monkey brain as a model for human development, we investigated the expression pattern of the FOXP2 gene, a member of the FOX family of transcription factors in the developing monkey brain, and compared its expression pattern with transcription factors PBX3, MEIS2, and FOXP1. We observed FOXP2 mRNA expression in several brain structures, including the striatum, the islands of Calleja and other basal forebrain regions, the cerebral cortex, and the thalamus. FOXP2 mRNA was preferentially expressed in striosomal compartments during striatal development. The striosomal expression was transient and developmentally down-regulated in a topographical order. Specifically, during the perinatal state, striosomal FOXP2 expression was detected in both the caudate nucleus and the putamen, although expression was more prominent in the caudate nucleus than in the putamen. Striosomal FOXP2 expression declined during the postnatal period, first in the putamen and later in the caudate nucleus. During the same period, we also detected PBX3 mRNA in the striosomal compartment of the developing monkey striatum. FOXP2, as well as PBX3 and MEIS2, was expressed in the islands of Calleja and other cell clusters of the basal forebrain. FOXP2, in combination with PBX3 and MEIS2, may play a pivotal role in the development of striosomal neurons of the striatum and the islands of Calleja.

  4. Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review.

    PubMed

    Lennon, P A; Cooper, M L; Peiffer, D A; Gunderson, K L; Patel, A; Peters, Sarika; Cheung, S W; Bacino, C A

    2007-04-15

    We report on a young male with moderate mental retardation, dysmorphic features, and language delay who is deleted for 7q31.1-7q31.31. His full karyotype is 46,XY,der(7)del(7)(q31.1q31.31)ins(10;7)(q24.3;q31.1q31.31)mat. This child had language impairment, including developmental verbal dyspraxia, but did not meet criteria for autism according to standardized ADOS testing. Our patient's deletion, which is the smallest reported deletion including FOXP2, adds to the body of evidence that supports the role of FOXP2 in speech and language impairment, but not in autism. A reported association between autism and deletions of WNT2, a gene also deleted in our patient, is likewise not supported by our case. Previously, fine mapping with microsatellites markers within in a large three-generation family, in which half the members had severe specific language impairment, aided the localization of the SPCH1 locus to 7q31 within markers D7S2459 (107.1 Mb) and D7S643 (120.5 Mb). Additionally, chromosome rearrangement of 7q31 and mutational analyses have supported the growing evidence that FOXP2, a gene within the SPCH1 region, is involved with speech and language development. It is unclear however whether the AUTS1 (autistic spectrum 1) locus, highly linked to 7q31, overlaps with the SPCH1 and FOXP2.

  5. [FOXP2: from the specific disorder to the molecular biology of language. I. Aetiological, neuroanatomical, neurophysiological and molecular aspects].

    PubMed

    Benítez-Burraco, A

    The task of cloning the genes whose products are involved in the organisation and functioning of the nerve centres that enable language tasks to be executed must necessarily start with the identification and the cognitive, linguistic, neuroanatomical and neurophysiological analysis of individuals with hereditary (specific) language impairment (SLI). The first of these genes to be characterised in this way--a gene called FOXP2--codes for a regulating factor that acts as a transcriptional repressor in the central nervous system. It is expressed in neuronal populations mainly situated in the basal ganglia, but also in the cortex, cerebellum and the thalamus, which are presumably involved in the development and/or functioning of the thalamic-cortical-striatal circuits associated with motor planning and learning. The protein FOXP2 shows several structural patterns that, when altered in other proteins, also give rise to different disorders in the central nervous system. The pattern of expression of the gene is preserved phylogenetically, although this does not happen in the case of the pattern of mRNA maturation. In individuals with a mutated version of FOXP2, morphological and functional anomalies are detected in those areas in which the gene is expressed. These abnormalities can be correlated satisfactorily with the phenotypic characteristics of the disorder, which are at the same time of both a motor and linguistic nature. The fact that other variations of SLI are not linked to the FOXP2 gene raises the need for further research into the genetic bases of the disorder, while also suggesting that it would be advisable to reassess the phenotypic scope of the variant associated to the mutation of this gene.

  6. Simple and sensitive method for identification of human DNA by allele-specific polymerase chain reaction of FOXP2.

    PubMed

    Hiroshige, Kenichi; Soejima, Mikiko; Nishioka, Tomoki; Kamimura, Shigeo; Koda, Yoshiro

    2009-07-01

    The forkhead box P2 (FOXP2) gene is specifically involved in speech and language development in humans. The sequence is well conserved among many vertebrate species but has accumulated amino acid changes in the human lineage. The aim of this study was to develop a simple method to discriminate between human and nonhuman vertebrate DNA in forensic specimens by amplification of a human-specific genomic region. In the present study, we designed an allele-specific polymerase chain reaction (PCR) using primers to amplify smaller than 70-bp regions of FOXP2 to identify DNA as being of human or nonhuman, including ape, origin. PCR amplification was also successfully performed using fluorescence-labeled primers, and this method allows a single PCR reaction with a genomic DNA sample as small as 0.01 ng. This system also identified the presence of human DNA in two blood stains stored for 20 and 38 years. The results suggested the potential usefulness of FOXP2 as an identifier of human DNA in forensic samples.

  7. Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2.

    PubMed

    Zeesman, Susan; Nowaczyk, Małgorzata J M; Teshima, Ikuko; Roberts, Wendy; Cardy, Janis Oram; Brian, Jessica; Senman, Lili; Feuk, Lars; Osborne, Lucy R; Scherer, Stephen W

    2006-03-01

    We report detailed clinical, cytogenetic, and molecular findings in a girl with a deletion of chromosome 7q31-q32. This child has a severe communication disorder with evidence of oromotor dyspraxia, dysmorphic features, and mild developmental delay. She is unable to cough, sneeze, or laugh spontaneously. Her deletion is on the paternally inherited chromosome and includes the FOXP2 gene, which has recently been associated with speech and language impairment and a similar form of oromotor dyspraxia in at least three other published cases. We hypothesize that our patient's communication disorder and oromotor deficiency are due to haploinsufficiency for FOXP2 and that her dysmorphism and developmental delay are a consequence of the absence of the other genes involved in the microdeletion. We propose that this patient, together with others reported in the literature, may define a new contiguous gene deletion syndrome encompassing the 7q31-FOXP2 region. Cytogenetic and molecular analysis of this region should be considered for other individuals displaying similar characteristics.

  8. MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis.

    PubMed

    Cuiffo, Benjamin G; Campagne, Antoine; Bell, George W; Lembo, Antonio; Orso, Francesca; Lien, Evan C; Bhasin, Manoj K; Raimo, Monica; Hanson, Summer E; Marusyk, Andriy; El-Ashry, Dorraya; Hematti, Peiman; Polyak, Kornelia; Mechta-Grigoriou, Fatima; Mariani, Odette; Volinia, Stefano; Vincent-Salomon, Anne; Taverna, Daniela; Karnoub, Antoine E

    2014-12-04

    Mesenchymal stem/stromal cells (MSCs) are progenitor cells shown to participate in breast tumor stroma formation and to promote metastasis. Despite expanding knowledge of their contributions to breast malignancy, the underlying molecular responses of breast cancer cells (BCCs) to MSC influences remain incompletely understood. Here, we show that MSCs cause aberrant expression of microRNAs, which, led by microRNA-199a, provide BCCs with enhanced cancer stem cell (CSC) properties. We demonstrate that such MSC-deregulated microRNAs constitute a network that converges on and represses the expression of FOXP2, a forkhead transcription factor tightly associated with speech and language development. FOXP2 knockdown in BCCs was sufficient in promoting CSC propagation, tumor initiation, and metastasis. Importantly, elevated microRNA-199a and depressed FOXP2 expression levels are prominent features of malignant clinical breast cancer and are associated significantly with poor survival. Our results identify molecular determinants of cancer progression of potential utility in the prognosis and therapy of breast cancer.

  9. A Foxp2 Mutation Implicated in Human Speech Deficits Alters Sequencing of Ultrasonic Vocalizations in Adult Male Mice

    PubMed Central

    Chabout, Jonathan; Sarkar, Abhra; Patel, Sheel R.; Radden, Taylor; Dunson, David B.; Fisher, Simon E.; Jarvis, Erich D.

    2016-01-01

    Development of proficient spoken language skills is disrupted by mutations of the FOXP2 transcription factor. A heterozygous missense mutation in the KE family causes speech apraxia, involving difficulty producing words with complex learned sequences of syllables. Manipulations in songbirds have helped to elucidate the role of this gene in vocal learning, but findings in non-human mammals have been limited or inconclusive. Here, we performed a systematic study of ultrasonic vocalizations (USVs) of adult male mice carrying the KE family mutation. Using novel statistical tools, we found that Foxp2 heterozygous mice did not have detectable changes in USV syllable acoustic structure, but produced shorter sequences and did not shift to more complex syntax in social contexts where wildtype animals did. Heterozygous mice also displayed a shift in the position of their rudimentary laryngeal motor cortex (LMC) layer-5 neurons. Our findings indicate that although mouse USVs are mostly innate, the underlying contributions of FoxP2 to sequencing of vocalizations are conserved with humans. PMID:27812326

  10. Turbulence Evolution and Shock Acceleration of Solar Energetic Particles

    NASA Technical Reports Server (NTRS)

    Chee, Ng K.

    2007-01-01

    We model the effects of self-excitation/damping and shock transmission of Alfven waves on solar-energetic-particle (SEP) acceleration at a coronal-mass-ejection (CME) driven parallel shock. SEP-excited outward upstream waves speedily bootstrap acceleration. Shock transmission further raises the SEP-excited wave intensities at high wavenumbers but lowers them at low wavenumbers through wavenumber shift. Downstream, SEP excitation of inward waves and damping of outward waves tend to slow acceleration. Nevertheless, > 2000 km/s parallel shocks at approx. 3.5 solar radii can accelerate SEPs to 100 MeV in < 5 minutes.

  11. SRF acceleration for heavy ions: ATLAS decadal operation and evolution

    NASA Astrophysics Data System (ADS)

    Ostroumov, P. N.; Pardo, R. C.

    2017-04-01

    This review paper presents the history and status of superconducting RF at the Argonne Tandem Linac Accelerator System (ATLAS) which is a Department of Energy (DOE) National User Facility for research in nuclear physics with accelerated stable and radioactive ion beams.

  12. High-throughput analysis of promoter occupancy reveals direct neural targets of FOXP2, a gene mutated in speech and language disorders.

    PubMed

    Vernes, Sonja C; Spiteri, Elizabeth; Nicod, Jérôme; Groszer, Matthias; Taylor, Jennifer M; Davies, Kay E; Geschwind, Daniel H; Fisher, Simon E

    2007-12-01

    We previously discovered that mutations of the human FOXP2 gene cause a monogenic communication disorder, primarily characterized by difficulties in learning to make coordinated sequences of articulatory gestures that underlie speech. Affected people have deficits in expressive and receptive linguistic processing and display structural and/or functional abnormalities in cortical and subcortical brain regions. FOXP2 provides a unique window into neural processes involved in speech and language. In particular, its role as a transcription factor gene offers powerful functional genomic routes for dissecting critical neurogenetic mechanisms. Here, we employ chromatin immunoprecipitation coupled with promoter microarrays (ChIP-chip) to successfully identify genomic sites that are directly bound by FOXP2 protein in native chromatin of human neuron-like cells. We focus on a subset of downstream targets identified by this approach, showing that altered FOXP2 levels yield significant changes in expression in our cell-based models and that FOXP2 binds in a specific manner to consensus sites within the relevant promoters. Moreover, we demonstrate significant quantitative differences in target expression in embryonic brains of mutant mice, mediated by specific in vivo Foxp2-chromatin interactions. This work represents the first identification and in vivo verification of neural targets regulated by FOXP2. Our data indicate that FOXP2 has dual functionality, acting to either repress or activate gene expression at occupied promoters. The identified targets suggest roles in modulating synaptic plasticity, neurodevelopment, neurotransmission, and axon guidance and represent novel entry points into in vivo pathways that may be disturbed in speech and language disorders.

  13. Angular-momentum evolution in laser-plasma accelerators.

    PubMed

    Thaury, C; Guillaume, E; Corde, S; Lehe, R; Le Bouteiller, M; Ta Phuoc, K; Davoine, X; Rax, J M; Rousse, A; Malka, V

    2013-09-27

    The transverse properties of an electron beam are characterized by two quantities, the emittance which indicates the electron beam extent in the phase space and the angular momentum which allows for nonplanar electron trajectories. Whereas the emittance of electron beams produced in a laser-plasma accelerator has been measured in several experiments, their angular momentum has been scarcely studied. It was demonstrated that electrons in a laser-plasma accelerator carry some angular momentum, but its origin was not established. Here we identify one source of angular-momentum growth and we present experimental results showing that the angular-momentum content evolves during the acceleration.

  14. Accelerated GPU simulation of compressible flow by the discontinuous evolution Galerkin method

    NASA Astrophysics Data System (ADS)

    Block, B. J.; Lukáčová-Medvid'ová, M.; Virnau, P.; Yelash, L.

    2012-08-01

    The aim of the present paper is to report on our recent results for GPU accelerated simulations of compressible flows. For numerical simulation the adaptive discontinuous Galerkin method with the multidimensional bicharacteristic based evolution Galerkin operator has been used. For time discretization we have applied the explicit third order Runge-Kutta method. Evaluation of the genuinely multidimensional evolution operator has been accelerated using the GPU implementation. We have obtained a speedup up to 30 (in comparison to a single CPU core) for the calculation of the evolution Galerkin operator on a typical discretization mesh consisting of 16384 mesh cells.

  15. Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome.

    PubMed

    Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

    2016-10-01

    Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species

    PubMed Central

    Chen, Qianqian; Heston, Jonathan B.; Burkett, Zachary D.; White, Stephanie A.

    2013-01-01

    SUMMARY Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song. PMID:24006346

  17. Accelerated evolution of morph-biased genes in pea aphids.

    PubMed

    Purandare, Swapna R; Bickel, Ryan D; Jaquiery, Julie; Rispe, Claude; Brisson, Jennifer A

    2014-08-01

    Phenotypic plasticity, the production of alternative phenotypes (or morphs) from the same genotype due to environmental factors, results in some genes being expressed in a morph-biased manner. Theoretically, these morph-biased genes experience relaxed selection, the consequence of which is the buildup of slightly deleterious mutations at these genes. Over time, this is expected to result in increased protein divergence at these genes between species and a signature of relaxed purifying selection within species. Here we test these theoretical expectations using morph-biased genes in the pea aphid, a species that produces multiple morphs via polyphenism. We find that morph-biased genes exhibit faster rates of evolution (in terms of dN/dS) relative to unbiased genes and that divergence generally increases with increasing morph bias. Further, genes with expression biased toward rarer morphs (sexual females and males) show faster rates of evolution than genes expressed in the more common morph (asexual females), demonstrating that the amount of time a gene spends being expressed in a morph is associated with its rate of evolution. And finally, we show that genes expressed in the rarer morphs experience decreased purifying selection relative to unbiased genes, suggesting that it is a relaxation of purifying selection that contributes to their faster rates of evolution. Our results provide an important empirical look at the impact of phenotypic plasticity on gene evolution.

  18. Accelerated Evolution of Morph-Biased Genes in Pea Aphids

    PubMed Central

    Purandare, Swapna R.; Bickel, Ryan D.; Jaquiery, Julie; Rispe, Claude; Brisson, Jennifer A.

    2014-01-01

    Phenotypic plasticity, the production of alternative phenotypes (or morphs) from the same genotype due to environmental factors, results in some genes being expressed in a morph-biased manner. Theoretically, these morph-biased genes experience relaxed selection, the consequence of which is the buildup of slightly deleterious mutations at these genes. Over time, this is expected to result in increased protein divergence at these genes between species and a signature of relaxed purifying selection within species. Here we test these theoretical expectations using morph-biased genes in the pea aphid, a species that produces multiple morphs via polyphenism. We find that morph-biased genes exhibit faster rates of evolution (in terms of dN/dS) relative to unbiased genes and that divergence generally increases with increasing morph bias. Further, genes with expression biased toward rarer morphs (sexual females and males) show faster rates of evolution than genes expressed in the more common morph (asexual females), demonstrating that the amount of time a gene spends being expressed in a morph is associated with its rate of evolution. And finally, we show that genes expressed in the rarer morphs experience decreased purifying selection relative to unbiased genes, suggesting that it is a relaxation of purifying selection that contributes to their faster rates of evolution. Our results provide an important empirical look at the impact of phenotypic plasticity on gene evolution. PMID:24770714

  19. Niche divergence accelerates evolution in Asian endemic Procapra gazelles

    PubMed Central

    Hu, Junhua; Jiang, Zhigang; Chen, Jing; Qiao, Huijie

    2015-01-01

    Ecological niche divergence and adaptation to new environments are thought to play important roles in driving speciation. Whether recently evolved species show evidence for niche divergence or conservation is vital towards understanding the role of ecology in the process of speciation. The genus Procapra is an ancient, monophyletic lineage endemic to Asia that contains three extant species (P. gutturosa, P. przewalskii and P. picticaudata). These species mainly inhabit the Qinghai-Tibetan and Mongolian Plateaus, and today have primarily allopatric distributions. We applied a series of geographic information system–based analyses to test for environmental variation and niche divergence among these three species. We found substantial evidence for niche divergence in species’ bioclimatic preferences, which supports the hypothesis that niche divergence accelerates diversification in Procapra. Our results provide important insight into the evolutionary history of ungulates in Asia and help to elucidate how environmental changes accelerate lineage diversification. PMID:25951051

  20. The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2.

    PubMed

    Nazaryan, Lusine; Stefanou, Eunice G; Hansen, Claus; Kosyakova, Nadezda; Bak, Mads; Sharkey, Freddie H; Mantziou, Theodora; Papanastasiou, Anastasios D; Velissariou, Voula; Liehr, Thomas; Syrrou, Maria; Tommerup, Niels

    2014-03-01

    Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes.

  1. The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

    PubMed Central

    Nazaryan, Lusine; Stefanou, Eunice G; Hansen, Claus; Kosyakova, Nadezda; Bak, Mads; Sharkey, Freddie H; Mantziou, Theodora; Papanastasiou, Anastasios D; Velissariou, Voula; Liehr, Thomas; Syrrou, Maria; Tommerup, Niels

    2014-01-01

    Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes. PMID:23860044

  2. Morphological change in machines accelerates the evolution of robust behavior

    PubMed Central

    Bongard, Josh

    2011-01-01

    Most animals exhibit significant neurological and morphological change throughout their lifetime. No robots to date, however, grow new morphological structure while behaving. This is due to technological limitations but also because it is unclear that morphological change provides a benefit to the acquisition of robust behavior in machines. Here I show that in evolving populations of simulated robots, if robots grow from anguilliform into legged robots during their lifetime in the early stages of evolution, and the anguilliform body plan is gradually lost during later stages of evolution, gaits are evolved for the final, legged form of the robot more rapidly—and the evolved gaits are more robust—compared to evolving populations of legged robots that do not transition through the anguilliform body plan. This suggests that morphological change, as well as the evolution of development, are two important processes that improve the automatic generation of robust behaviors for machines. It also provides an experimental platform for investigating the relationship between the evolution of development and robust behavior in biological organisms. PMID:21220304

  3. Accelerated Adaptive Evolution on a Newly Formed X Chromosome

    PubMed Central

    Bachtrog, Doris; Jensen, Jeffrey D; Zhang, Zhi

    2009-01-01

    Sex chromosomes originated from ordinary autosomes, and their evolution is characterized by continuous gene loss from the ancestral Y chromosome. Here, we document a new feature of sex chromosome evolution: bursts of adaptive fixations on a newly formed X chromosome. Taking advantage of the recently formed neo-X chromosome of Drosophila miranda, we compare patterns of DNA sequence variation at genes located on the neo-X to genes on the ancestral X chromosome. This contrast allows us to draw inferences of selection on a newly formed X chromosome relative to background levels of adaptation in the genome while controlling for demographic effects. Chromosome-wide synonymous diversity on the neo-X is reduced 2-fold relative to the ancestral X, as expected under recent and recurrent directional selection. Several statistical tests employing various features of the data consistently identify 10%–15% of neo-X genes as targets of recent adaptive evolution but only 1%–3% of genes on the ancestral X. In addition, both the rate of adaptation and the fitness effects of adaptive substitutions are estimated to be roughly an order of magnitude higher for neo-X genes relative to genes on the ancestral X. Thus, newly formed X chromosomes are not passive players in the evolutionary process of sex chromosome differentiation, but respond adaptively to both their sex-biased transmission and to Y chromosome degeneration, possibly through demasculinization of their gene content and the evolution of dosage compensation. PMID:19402745

  4. Programming cells by multiplex genome engineering and accelerated evolution

    PubMed Central

    Carr, Peter A.; Sun, Zachary Z.; Xu, George; Forest, Craig R.; Church, George M.

    2015-01-01

    The breadth of genomic diversity found among organisms in nature allows populations to adapt to diverse environments1,2. However, genomic diversity is difficult to generate in the laboratory and new phenotypes do not easily arise on practical timescales3. Although in vitro and directed evolution methods4–9 have created genetic variants with usefully altered phenotypes, these methods are limited to laborious and serial manipulation of single genes and are not used for parallel and continuous directed evolution of gene networks or genomes. Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-d-xylulose-5-phosphate (DXP) biosynthesis pathway in Escherichia coli to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day. We isolated variants with more than fivefold increase in lycopene production within 3 days, a significant improvement over existing metabolic engineering techniques. Our multiplex approach embraces engineering in the context of evolution by expediting the design and evolution of organisms with new and improved properties. PMID:19633652

  5. Transcriptomic insights into human brain evolution: acceleration, neutrality, heterochrony.

    PubMed

    Somel, Mehmet; Rohlfs, Rori; Liu, Xiling

    2014-12-01

    Primate brain transcriptome comparisons within the last 12 years have yielded interesting but contradictory observations on how the transcriptome evolves, and its adaptive role in human cognitive evolution. Since the human-chimpanzee common ancestor, the human prefrontal cortex transcriptome seems to have evolved more than that of the chimpanzee. But at the same time, most expression differences among species, especially those observed in adults, appear as consequences of neutral evolution at cis-regulatory sites. Adaptive expression changes in the human brain may be rare events involving timing shifts, or heterochrony, in specific neurodevelopmental processes. Disentangling adaptive and neutral expression changes, and associating these with human-specific features of the brain require improved methods, comparisons across more species, and further work on comparative development.

  6. Contactin‑associated protein‑like 2 expression in SH‑SY5Y cells is upregulated by a FOXP2 mutant with a shortened poly‑glutamine tract.

    PubMed

    Zhao, Yunjing; Liu, Xiaoliang; Sun, Hongwei; Wang, Yueping; Yang, Wenzhu; Ma, Hongwei

    2015-12-01

    The forkhead box protein P2 (FOXP2) gene encodes an important transcription factor that contains a polyglutamine (poly‑Q) tract and a forkhead DNA binding domain. It has been observed that FOXP2 is associated with speech sound disorder (SSD), and mutations that decrease the length of the poly‑Q tract were identified in the FOXP2 gene of SSD patients. However, the exact role of poly‑Q reduction is not well understood. In the present study, constructs expressing wild‑type and poly‑Q reduction mutants of FOXP2 were generated by polymerase chain reaction (PCR) using lentiviral vectors and transfected into the SH‑SY5Y neuronal cell line. Quantitative reverse transcription (qRT)‑PCR and western blotting indicated that infected cells stably expressed high levels of FOXP2. Using this cell model, the impact of FOXP2 on the expression of contactin‑associated protein‑like 2 (CNTNAP2) were investigated, and CNTNAP2 mRNA expression levels were observed to be significantly higher in cells expressing poly‑Q‑reduced FOXP2. In addition, the expression level of CASPR2, a mammalian homolog of Drosophila Neurexin IV, was increased in cells expressing the FOXP2 mutant. Demonstration of regulation by FOXP2 indicates that CNTNAP2 may also be involved in SSD.

  7. Effects of sex and seasonality on the song control system and FoxP2 protein expression in black-capped chickadees (Poecile atricapillus).

    PubMed

    Phillmore, Leslie S; MacGillivray, Heather L; Wilson, K Ryan; Martin, Stephanie

    2015-02-01

    Plasticity in behavior is mirrored by corresponding plasticity in the brain in many songbird species. In some species, song system nuclei (Phillmore et al. [2006]: J Neurobiol 66:1002-1010) are larger in birds in breeding condition than birds in nonbreeding condition, possibly due to increased vocal output in spring. FOXP2, a transcription factor associated with language expression and comprehension in humans and song learning in songbirds, also shows plasticity. FoxP2 expression in songbird Area X, a region important for sensorimotor integration, is related to developmental and adult vocal plasticity (Teramitsu et al. [2010]: J Neurosci 24:3152-3163, Chen et al. [2013], J Exp Biol 216:3682-3692). In this study, we examined whether sex and breeding condition affects both song control system volume (HVC, X) and FoxP2 protein expression in black-capped chickadees (Poecile atricapillus). HVC volume was larger in males in breeding condition than males in nonbreeding condition, but there were no sex differences. In contrast, Area X volume was larger in males than females, regardless of breeding condition, likely reflecting that male and female chickadees produce learned chick-a-dee calls year round, but output of the learned song increases in breeding males. FoxP2 protein levels did not differ between sexes or breeding condition when calculated as a ratio of labeled cells in Area X to labeled cells in the surrounding striato-pallium, however, absolute density of FoxP2 in both regions was higher in males than in females. This may indicate that chickadees maintain a level of FoxP2 necessary for plasticity year-round, but males have greater potential for plasticity compared to females.

  8. Accelerated gene evolution through replication-transcription conflicts.

    PubMed

    Paul, Sandip; Million-Weaver, Samuel; Chattopadhyay, Sujay; Sokurenko, Evgeni; Merrikh, Houra

    2013-03-28

    Several mechanisms that increase the rate of mutagenesis across the entire genome have been identified; however, how the rate of evolution might be promoted in individual genes is unclear. Most genes in bacteria are encoded on the leading strand of replication. This presumably avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand. Here we identify the ubiquitous (core) genes in Bacillus subtilis and determine that 17% of them are on the lagging strand. We find a higher rate of point mutations in the core genes on the lagging strand compared with those on the leading strand, with this difference being primarily in the amino-acid-changing (nonsynonymous) mutations. We determine that, overall, the genes under strong negative selection against amino-acid-changing mutations tend to be on the leading strand, co-oriented with replication. In contrast, on the basis of the rate of convergent mutations, genes under positive selection for amino-acid-changing mutations are more commonly found on the lagging strand, indicating faster adaptive evolution in many genes in the head-on orientation. Increased gene length and gene expression amounts are positively correlated with the rate of accumulation of nonsynonymous mutations in the head-on genes, suggesting that the conflict between replication and transcription could be a driving force behind these mutations. Indeed, using reversion assays, we show that the difference in the rate of mutagenesis of genes in the two orientations is transcription dependent. Altogether, our findings indicate that head-on replication-transcription conflicts are more mutagenic than co-directional conflicts and that these encounters can significantly increase adaptive structural variation in the coded proteins. We propose that bacteria, and potentially other organisms, promote faster evolution of specific genes through orientation

  9. Tropics accelerate the evolution of hybrid male sterility in Drosophila.

    PubMed

    Yukilevich, Roman

    2013-06-01

    Understanding the evolutionary mechanisms that facilitate speciation and explain global patterns of species diversity has remained a challenge for decades. The most general pattern of species biodiversity is the latitudinal gradient, whereby species richness increases toward the tropics. Although such a global pattern probably has a multitude of causes, recent attention has focused on the hypothesis that speciation and the evolution of reproductive isolation occur faster in the tropics. Here, I tested this prediction using a dataset on premating and postzygotic isolation between recently diverged Drosophila species. Results showed that while the evolution of premating isolation was not greater between tropical Drosophila relative to nontropical species, postzygotic isolation evolved faster in the tropics. In particular, hybrid male sterility was much greater among tropical Drosophila compared to nontropical species pairs of similar genetic age. Several testable explanations for the novel pattern are discussed, including greater role for sterility-inducing bacterial endosymbionts in the tropics and more intense sperm-sperm competition or sperm-egg sexual conflict in the tropics. The results imply that processes of speciation in the tropics may evolve at different rates or may even be somewhat different from those at higher latitudes.

  10. Instability evolution in shock-accelerated inclined heavy gas cylinder

    NASA Astrophysics Data System (ADS)

    Olmstead, Dell; Wayne, Patrick; Vorobieff, Peter; Davis, Daniel; Truman, C. Randall

    2014-11-01

    A heavy gas cylinder interacts with a normal or oblique shockwave at Mach numbers M ranging from 1.13 to 2.0. The angle between the shock front and cylinder axis is varied between 0 and 30°, while the Atwood numbers A range from 0.25 (SF6-N2 mix) to 0.67 (pure SF6). The evolution of the column is imaged in two perpendicular planes with Planar Laser Induced Fluorescence (PLIF). For oblique shock interactions, the nature of the flow is fully three-dimensional, with several instabilities developing in separate directions. In the plane that captures a cross-section of the column, Richtmyer-Meshkov instability (RMI) leads to formation of a pair of counter-rotating vortex columns. A uniform scaling appears to govern the primary instability growth in this plane across the M and A ranges, when the length scale is normalized by a product of the minimum streamwise scale after shock compression and M0.5. In the vertical plane through the column, Kelvin-Helmholtz vortices form with regular spacing along the column. The dominant wavelength of the structures in the vertical plane also appears to scale with the minimum compressed streamwise length. This research is supported by the US DOE National Nuclear Security Administration (NNSA) Grant DE-NA0002220.

  11. Simplified models for the evolution of supernova remnants including particle acceleration

    NASA Astrophysics Data System (ADS)

    Drury, L. O'C.; Markiewicz, W. J.; Voelk, H. J.

    1989-11-01

    A system of coupled ordinary differential equations is presented which models the dynamical evolution of a supernova remnant including the acceleration of the Galactic cosmic rays. In contrast to earlier two-fluid models the closure parameters needed for a hydrodynamic approximation of the cosmic ray 'gas' are not taken as prescribed constants but are estimated dynamically within the model. Diffusive coupling between the outer shock and the remnant interior is introduced; this is shown to be an important moderator of the acceleration as is heating of the thermal plasma by Alfven wave dissipation. For reasonable estimates of the suprathermal particle injection rate into the acceleration process, of the diffusion coefficient appropriate to the accelerated particles, of the coupling between interior and shock, and of wave heating, solutions are found which appear consistent both with observations of young remnants and the idea that the bulk of the Galactic cosmic rays are produced in supernova remnants.

  12. Replication of CNTNAP2 association with nonword repetition and support for FOXP2 association with timed reading and motor activities in a dyslexia family sample.

    PubMed

    Peter, Beate; Raskind, Wendy H; Matsushita, Mark; Lisowski, Mark; Vu, Tiffany; Berninger, Virginia W; Wijsman, Ellen M; Brkanac, Zoran

    2011-03-01

    Two functionally related genes, FOXP2 and CNTNAP2, influence language abilities in families with rare syndromic and common nonsyndromic forms of impaired language, respectively. We investigated whether these genes are associated with component phenotypes of dyslexia and measures of sequential motor ability. Quantitative transmission disequilibrium testing (QTDT) and linear association modeling were used to evaluate associations with measures of phonological memory (nonword repetition, NWR), expressive language (sentence repetition), reading (real word reading efficiency, RWRE; word attack, WATT), and timed sequential motor activities (rapid alternating place of articulation, RAPA; finger succession in the dominant hand, FS-D) in 188 family trios with a child with dyslexia. Consistent with a prior study of language impairment, QTDT in dyslexia showed evidence of CNTNAP2 single nucleotide polymorphism (SNP) association with NWR. For FOXP2, we provide the first evidence for SNP association with component phenotypes of dyslexia, specifically NWR and RWRE but not WATT. In addition, FOXP2 SNP associations with both RAPA and FS-D were observed. Our results confirm the role of CNTNAP2 in NWR in a dyslexia sample and motivate new questions about the effects of FOXP2 in neurodevelopmental disorders.

  13. Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.

    PubMed

    Toma, Claudio; Hervás, Amaia; Torrico, Bàrbara; Balmaña, Noemí; Salgado, Marta; Maristany, Marta; Vilella, Elisabet; Martínez-Leal, Rafael; Planelles, Ma Inmaculada; Cuscó, Ivon; del Campo, Miguel; Pérez-Jurado, Luis A; Caballero-Andaluz, Rafaela; de Diego-Otero, Yolanda; Pérez-Costillas, Lucía; Ramos-Quiroga, Josep A; Ribasés, Marta; Bayés, Mònica; Cormand, Bru

    2013-04-01

    Impairment of language abilities is a common feature in autistic individuals. Heterozygous mutations in the Forkhead Box P2 (FOXP2) gene lead to a severe spoken language disorder. Recently, several studies have pinpointed the involvement of common variants of the Contactin-Associated Protein-Like 2 (CNTNAP2) gene, whose transcription is regulated by the product of FOXP2, in several disorders characterized by language impairments such as autism, specific language impairment (SLI), and selective mutism (SM). In the present study, common variants of the FOXP2 and the CNTNAP2 genes were analyzed through a case-control association study in 322 Spanish autistic patients and 524 controls. The results of this study suggest that common variants of FOXP2 are unlikely to contribute to autism susceptibility, in agreement with previous findings. Furthermore, we failed to replicate in our sample a previous association finding of two single nucleotide polymorphisms (rs2710102 and rs7794745) in the CNTNAP2 gene with autism. No evidence for the association of these genes with language traits was observed in our analysis.

  14. Neural FoxP2 and FoxP1 expression in the budgerigar, an avian species with adult vocal learning

    PubMed Central

    Hara, Erina; Perez, Jemima M.; Whitney, Osceola; Chen, Qianqian; White, Stephanie A.; Wright, Timothy F.

    2015-01-01

    Vocal learning underlies acquisition of both language in humans and vocal signals in some avian taxa. These bird groups and humans exhibit convergent developmental phases and associated brain pathways for vocal communication. The transcription factor FoxP2 plays critical roles in vocal learning in humans and songbirds. Another member of the forkhead box gene family, FoxP1 also shows high expression in brain areas involved in vocal learning and production. Here, we investigate FoxP2 and FoxP1 mRNA and protein in adult male budgerigars (Melopsittacus undulatus), a parrot species that exhibits vocal learning as both juveniles and adults. To examine these molecules in adult vocal learners, we compared their expression patterns in the budgerigar striatal nucleus involved in vocal learning, magnocellular nucleus of the medial striatum (MMSt), across birds with different vocal states, such as vocalizing to a female (directed), vocalizing alone (undirected), and non-vocalizing. We found that both FoxP2 mRNA and protein expressions were consistently lower in MMSt than in the adjacent striatum regardless of the vocal states, whereas previous work has shown that songbirds exhibit downregulation in the homologous region, Area X, only after singing alone. In contrast, FoxP1 levels were high in MMSt compared to the adjacent striatum in all groups. Taken together these results strengthen the general hypothesis that FoxP2 and FoxP1 have specialized expression in vocal nuclei across a range of taxa, and suggest that the adult vocal plasticity seen in budgerigars may be a product of persistent down-regulation of FoxP2 in MMSt. PMID:25601574

  15. Neural FoxP2 and FoxP1 expression in the budgerigar, an avian species with adult vocal learning.

    PubMed

    Hara, Erina; Perez, Jemima M; Whitney, Osceola; Chen, Qianqian; White, Stephanie A; Wright, Timothy F

    2015-04-15

    Vocal learning underlies acquisition of both language in humans and vocal signals in some avian taxa. These bird groups and humans exhibit convergent developmental phases and associated brain pathways for vocal communication. The transcription factor FoxP2 plays critical roles in vocal learning in humans and songbirds. Another member of the forkhead box gene family, FoxP1 also shows high expression in brain areas involved in vocal learning and production. Here, we investigate FoxP2 and FoxP1 mRNA and protein in adult male budgerigars (Melopsittacus undulatus), a parrot species that exhibits vocal learning as both juveniles and adults. To examine these molecules in adult vocal learners, we compared their expression patterns in the budgerigar striatal nucleus involved in vocal learning, magnocellular nucleus of the medial striatum (MMSt), across birds with different vocal states, such as vocalizing to a female (directed), vocalizing alone (undirected), and non-vocalizing. We found that both FoxP2 mRNA and protein expressions were consistently lower in MMSt than in the adjacent striatum regardless of the vocal states, whereas previous work has shown that songbirds exhibit down-regulation in the homologous region, Area X, only after singing alone. In contrast, FoxP1 levels were high in MMSt compared to the adjacent striatum in all groups. Taken together these results strengthen the general hypothesis that FoxP2 and FoxP1 have specialized expression in vocal nuclei across a range of taxa, and suggest that the adult vocal plasticity seen in budgerigars may be a product of persistent down-regulation of FoxP2 in MMSt.

  16. [FOXP2 and the molecular biology of language: new evidence. II. Molecular aspects and implications for the ontogenesis and phylogeny of language].

    PubMed

    Benítez-Burraco, A

    FOXP2 is the first gene linked to a hereditary variant of specific language impairment and seems to code for a transcriptional repressor that intervenes in the regulation of the development and the functioning of certain thalamic-cortical-striatal circuits. In the last three years, significant progress has been made in the determination of the structural and functional properties of the gene. These advances essentially have to do with the precise analysis of the most important structural motifs of the protein that it codes for and the main parameters that determine its interaction with DNA. They also concern the determination of the functional and behavioural properties in vivo of the main isoforms of the FOXP2 protein, the exact determination of the pattern of expression of new orthologues of the gene, and the identification of the different target genes for factor FOXP2. This new evidence suggests that protein FOXP2 protein has a high degree of versatility in vivo when it comes to binding to DNA; that its different isoforms are biologically functional; and that the FOXP2 gene is functional during embryonic development and during the adult phase. It also suggests that it is involved in the development and/or functioning of the thalamic-cortical-striatal circuits associated to motor planning, sequential behaviour and procedural learning (a significant saving in developmental terms of the regulatory mechanism in which the gene is involved), as well as the accuracy of the models of linguistic processing that consider language to be, to a large extent, the result of an interaction between certain cortical and subcortical structures.

  17. Wakefield evolution and electron acceleration in interaction of frequency-chirped laser pulse with inhomogeneous plasma

    NASA Astrophysics Data System (ADS)

    Rezaei-Pandari, M.; Niknam, A. R.; Massudi, R.; Jahangiri, F.; Hassaninejad, H.; Khorashadizadeh, S. M.

    2017-02-01

    The nonlinear interaction of an ultra-short intense frequency-chirped laser pulse with an underdense plasma is studied. The effects of plasma inhomogeneity and laser parameters such as chirp, pulse duration, and intensity on plasma density and wakefield evolutions, and electron acceleration are examined. It is found that a properly chirped laser pulse could induce a stronger laser wakefield in an inhomogeneous plasma and result in higher electron acceleration energy. It is also shown that the wakefield amplitude is enhanced by increasing the slope of density in the inhomogeneous plasma.

  18. miR-9 and miR-140-5p Target FoxP2 and Are Regulated as a Function of the Social Context of Singing Behavior in Zebra Finches

    PubMed Central

    Shi, Zhimin; Luo, Guanzheng; Fu, Lijuan; Fang, Zhide; Wang, XiuJie

    2013-01-01

    Mutations in the FOXP2 gene cause speech and language impairments, accompanied by structural and functional abnormalities in brain regions underlying speech-related sensory-motor processing, including the striatum and cerebellum. The sequence and expression patterns of FOXP2 are highly conserved among higher vertebrates. In the zebra finch brain, FoxP2 is expressed in Area X, a striatal nucleus required for vocal learning, and reduced FoxP2 expression impairs dendritic development and vocal learning. The FoxP2 gene encodes a transcription factor that controls the expression of many downstream genes. However, how FOXP2 gene expression is regulated is not clearly understood. miRNAs regulate gene expression post-transcriptionally by targeting the 3′-untranslated regions (UTRs) of mRNAs, leading to translational suppression or mRNA degradation. In this study, we identified miR-9 and miR-140-5p as potential regulators of the FoxP2 gene. We show that both miR-9 and miR-140-5p target specific sequences in the FoxP2 3′-UTR and downregulate FoxP2 protein and mRNA expression in vitro. We also show that the expression of miR-9 and miR-140-5p in Area X of the zebra finch brain is regulated during song development in juvenile zebra finches. We further show that in adult zebra finches the expression of miR-9 and miR-140-5p in Area X is regulated as a function of the social context of song behavior in males singing undirected songs. Our findings reveal a post-transcriptional mechanism that regulates FoxP2 expression and suggest that social vocal behavior can influence the basal ganglia circuit controlling vocal learning via a miRNA-FoxP2 gene regulatory network. PMID:24133256

  19. Mimosoid legume plastome evolution: IR expansion, tandem repeat expansions, and accelerated rate of evolution in clpP

    PubMed Central

    Dugas, Diana V.; Hernandez, David; Koenen, Erik J.M.; Schwarz, Erika; Straub, Shannon; Hughes, Colin E.; Jansen, Robert K.; Nageswara-Rao, Madhugiri; Staats, Martijn; Trujillo, Joshua T.; Hajrah, Nahid H.; Alharbi, Njud S.; Al-Malki, Abdulrahman L.; Sabir, Jamal S. M.; Bailey, C. Donovan

    2015-01-01

    The Leguminosae has emerged as a model for studying angiosperm plastome evolution because of its striking diversity of structural rearrangements and sequence variation. However, most of what is known about legume plastomes comes from few genera representing a subset of lineages in subfamily Papilionoideae. We investigate plastome evolution in subfamily Mimosoideae based on two newly sequenced plastomes (Inga and Leucaena) and two recently published plastomes (Acacia and Prosopis), and discuss the results in the context of other legume and rosid plastid genomes. Mimosoid plastomes have a typical angiosperm gene content and general organization as well as a generally slow rate of protein coding gene evolution, but they are the largest known among legumes. The increased length results from tandem repeat expansions and an unusual 13 kb IR-SSC boundary shift in Acacia and Inga. Mimosoid plastomes harbor additional interesting features, including loss of clpP intron1 in Inga, accelerated rates of evolution in clpP for Acacia and Inga, and dN/dS ratios consistent with neutral and positive selection for several genes. These new plastomes and results provide important resources for legume comparative genomics, plant breeding, and plastid genetic engineering, while shedding further light on the complexity of plastome evolution in legumes and angiosperms. PMID:26592928

  20. Mimosoid legume plastome evolution: IR expansion, tandem repeat expansions, and accelerated rate of evolution in clpP.

    PubMed

    Dugas, Diana V; Hernandez, David; Koenen, Erik J M; Schwarz, Erika; Straub, Shannon; Hughes, Colin E; Jansen, Robert K; Nageswara-Rao, Madhugiri; Staats, Martijn; Trujillo, Joshua T; Hajrah, Nahid H; Alharbi, Njud S; Al-Malki, Abdulrahman L; Sabir, Jamal S M; Bailey, C Donovan

    2015-11-23

    The Leguminosae has emerged as a model for studying angiosperm plastome evolution because of its striking diversity of structural rearrangements and sequence variation. However, most of what is known about legume plastomes comes from few genera representing a subset of lineages in subfamily Papilionoideae. We investigate plastome evolution in subfamily Mimosoideae based on two newly sequenced plastomes (Inga and Leucaena) and two recently published plastomes (Acacia and Prosopis), and discuss the results in the context of other legume and rosid plastid genomes. Mimosoid plastomes have a typical angiosperm gene content and general organization as well as a generally slow rate of protein coding gene evolution, but they are the largest known among legumes. The increased length results from tandem repeat expansions and an unusual 13 kb IR-SSC boundary shift in Acacia and Inga. Mimosoid plastomes harbor additional interesting features, including loss of clpP intron1 in Inga, accelerated rates of evolution in clpP for Acacia and Inga, and dN/dS ratios consistent with neutral and positive selection for several genes. These new plastomes and results provide important resources for legume comparative genomics, plant breeding, and plastid genetic engineering, while shedding further light on the complexity of plastome evolution in legumes and angiosperms.

  1. Does vocal learning accelerate acoustic diversification? Evolution of contact calls in Neotropical parrots.

    PubMed

    Medina-García, A; Araya-Salas, M; Wright, T F

    2015-10-01

    Learning has been traditionally thought to accelerate the evolutionary change of behavioural traits. We evaluated the evolutionary rate of learned vocalizations and the interplay of morphology and ecology in the evolution of these signals. We examined contact calls of 51 species of Neotropical parrots from the tribe Arini. Parrots are ideal subjects due to their wide range of body sizes and habitats, and their open-ended vocal learning that allows them to modify their calls throughout life. We estimated the evolutionary rate of acoustic parameters of parrot contact calls and compared them to those of morphological traits and habitat. We also evaluated the effect of body mass, bill length, vegetation density and species interactions on acoustic parameters of contact calls while controlling for phylogeny. Evolutionary rates of acoustic parameters did not differ from those of our predictor variables except for spectral entropy, which had a significantly slower rate of evolution. We found support for correlated evolution of call duration, and fundamental and peak frequencies with body mass, and of fundamental frequency with bill length. The degree of sympatry between species did not have a significant effect on acoustic parameters. Our results suggest that parrot contact calls, which are learned acoustic signals, show evolutionary rates similar to those of morphological traits. This is the first study to our knowledge to provide evidence that change through cultural evolution does not necessarily accelerate the evolutionary rate of traits acquired through life-long vocal learning.

  2. Evolution of dispersal and life history interact to drive accelerating spread of an invasive species.

    PubMed

    Perkins, T Alex; Phillips, Benjamin L; Baskett, Marissa L; Hastings, Alan

    2013-08-01

    Populations on the edge of an expanding range are subject to unique evolutionary pressures acting on their life-history and dispersal traits. Empirical evidence and theory suggest that traits there can evolve rapidly enough to interact with ecological dynamics, potentially giving rise to accelerating spread. Nevertheless, which of several evolutionary mechanisms drive this interaction between evolution and spread remains an open question. We propose an integrated theoretical framework for partitioning the contributions of different evolutionary mechanisms to accelerating spread, and we apply this model to invasive cane toads in northern Australia. In doing so, we identify a previously unrecognised evolutionary process that involves an interaction between life-history and dispersal evolution during range shift. In roughly equal parts, life-history evolution, dispersal evolution and their interaction led to a doubling of distance spread by cane toads in our model, highlighting the potential importance of multiple evolutionary processes in the dynamics of range expansion. © 2013 John Wiley & Sons Ltd/CNRS.

  3. Accelerated evolution after gene duplication: a time-dependent process affecting just one copy.

    PubMed

    Pegueroles, Cinta; Laurie, Steve; Albà, M Mar

    2013-08-01

    Gene duplication is widely regarded as a major mechanism modeling genome evolution and function. However, the mechanisms that drive the evolution of the two, initially redundant, gene copies are still ill defined. Many gene duplicates experience evolutionary rate acceleration, but the relative contribution of positive selection and random drift to the retention and subsequent evolution of gene duplicates, and for how long the molecular clock may be distorted by these processes, remains unclear. Focusing on rodent genes that duplicated before and after the mouse and rat split, we find significantly increased sequence divergence after duplication in only one of the copies, which in nearly all cases corresponds to the novel daughter copy, independent of the mechanism of duplication. We observe that the evolutionary rate of the accelerated copy, measured as the ratio of nonsynonymous to synonymous substitutions, is on average 5-fold higher in the period spanning 4-12 My after the duplication than it was before the duplication. This increase can be explained, at least in part, by the action of positive selection according to the results of the maximum likelihood-based branch-site test. Subsequently, the rate decelerates until purifying selection completely returns to preduplication levels. Reversion to the original rates has already been accomplished 40.5 My after the duplication event, corresponding to a genetic distance of about 0.28 synonymous substitutions per site. Differences in tissue gene expression patterns parallel those of substitution rates, reinforcing the role of neofunctionalization in explaining the evolution of young gene duplicates.

  4. Mutational Pathway Determines Whether Drug Gradients Accelerate Evolution of Drug-Resistant Cells

    NASA Astrophysics Data System (ADS)

    Greulich, Philip; Waclaw, Bartłomiej; Allen, Rosalind J.

    2012-08-01

    Drug gradients are believed to play an important role in the evolution of bacteria resistant to antibiotics and tumors resistant to anticancer drugs. We use a statistical physics model to study the evolution of a population of malignant cells exposed to drug gradients, where drug resistance emerges via a mutational pathway involving multiple mutations. We show that a nonuniform drug distribution has the potential to accelerate the emergence of resistance when the mutational pathway involves a long sequence of mutants with increasing resistance, but if the pathway is short or crosses a fitness valley, the evolution of resistance may actually be slowed down by drug gradients. These predictions can be verified experimentally, and may help to improve strategies for combating the emergence of resistance.

  5. Refuting the hypothesis that the acquisition of germ plasm accelerates animal evolution

    PubMed Central

    Whittle, Carrie A.; Extavour, Cassandra G.

    2016-01-01

    Primordial germ cells (PGCs) give rise to the germ line in animals. PGCs are specified during embryogenesis either by an ancestral mechanism of cell–cell signalling (induction) or by a derived mechanism of maternally provided germ plasm (preformation). Recently, a hypothesis was set forth purporting that germ plasm liberates selective constraint and accelerates an organism's protein sequence evolution, especially for genes from early developmental stages, thereby leading to animal species radiations; empirical validation has been claimed in vertebrates. Here we present findings from global rates of protein evolution in vertebrates and invertebrates refuting this hypothesis. Contrary to assertions of the hypothesis, we find no effect of preformation on protein sequence evolution, the evolutionary rates of early-stage developmental genes, or on species diversification. We conclude that the hypothesis is mechanistically implausible, and our multi-faceted analysis shows no empirical support for any of its predictions. PMID:27577604

  6. Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions.

    PubMed

    Pinel, Philippe; Fauchereau, Fabien; Moreno, Antonio; Barbot, Alexis; Lathrop, Mark; Zelenika, Diana; Le Bihan, Denis; Poline, Jean-Baptiste; Bourgeron, Thomas; Dehaene, Stanislas

    2012-01-18

    Recent advances have been made in the genetics of two human communication skills: speaking and reading. Mutations of the FOXP2 gene cause a severe form of language impairment and orofacial dyspraxia, while single-nucleotide polymorphisms (SNPs) located within a KIAA0319/TTRAP/THEM2 gene cluster and affecting the KIAA0319 gene expression are associated with reading disability. Neuroimaging studies of clinical populations point to partially distinct cerebral bases for language and reading impairments. However, alteration of FOXP2 and KIAA0319/TTRAP/THEM2 polymorphisms on typically developed language networks has never been explored. Here, we genotyped and scanned 94 healthy subjects using fMRI during a reading task. We studied the correlation of genetic polymorphisms with interindividual variability in brain activation and functional asymmetry in frontal and temporal cortices. In FOXP2, SNPs rs6980093 and rs7799109 were associated with variations of activation in the left frontal cortex. In the KIAA0319/TTRAP/THEM2 locus, rs17243157 was associated with asymmetry in functional activation of the superior temporal sulcus (STS). Interestingly, healthy subjects bearing the KIAA0319/TTRAP/THEM2 variants previously identified as enhancing the risk of dyslexia showed a reduced left-hemispheric asymmetry of the STS. Our results confirm that both FOXP2 and KIAA0319/TTRAP/THEM2 genes play an important role in human language development, but probably through different cerebral pathways. The observed cortical effects mirror previous fMRI results in developmental language and reading disorders, and suggest that a continuum may exist between these pathologies and normal interindividual variability.

  7. Temporal evolution of the electric field accelerating electrons away from the auroral ionosphere.

    PubMed

    Marklund, G T; Ivchenko, N; Karlsson, T; Fazakerley, A; Dunlop, M; Lindqvist, P A; Buchert, S; Owen, C; Taylor, M; Vaivalds, A; Carter, P; André, M; Balogh, A

    2001-12-13

    The bright night-time aurorae that are visible to the unaided eye are caused by electrons accelerated towards Earth by an upward-pointing electric field. On adjacent geomagnetic field lines the reverse process occurs: a downward-pointing electric field accelerates electrons away from Earth. Such magnetic-field-aligned electric fields in the collisionless plasma above the auroral ionosphere have been predicted, but how they could be maintained is still a matter for debate. The spatial and temporal behaviour of the electric fields-a knowledge of which is crucial to an understanding of their nature-cannot be resolved uniquely by single satellite measurements. Here we report on the first observations by a formation of identically instrumented satellites crossing a beam of upward-accelerated electrons. The structure of the electric potential accelerating the beam grew in magnitude and width for about 200 s, accompanied by a widening of the downward-current sheet, with the total current remaining constant. The 200-s timescale suggests that the evacuation of the electrons from the ionosphere contributes to the formation of the downward-pointing magnetic-field-aligned electric fields. This evolution implies a growing load in the downward leg of the current circuit, which may affect the visible discrete aurorae.

  8. Frequent changes in expression profile and accelerated sequence evolution of duplicated imprinted genes in arabidopsis.

    PubMed

    Qiu, Yichun; Liu, Shao-Lun; Adams, Keith L

    2014-07-01

    Eukaryotic genomes have large numbers of duplicated genes that can evolve new functions or expression patterns by changes in coding and regulatory sequences, referred to as neofunctionalization. In flowering plants, some duplicated genes are imprinted in the endosperm, where only one allele is expressed depending on its parental origin. We found that 125 imprinted genes in Arabidopsis arose from gene duplication events during the evolution of the Brassicales. Analyses of 46 gene pairs duplicated by an ancient whole-genome duplication (alpha WGD) indicated that many imprinted genes show an accelerated rate of amino acid changes compared with their paralogs. Analyses of microarray expression data from 63 organ types and developmental stages indicated that many imprinted genes have expression patterns restricted to flowers and/or seeds in contrast to their broadly expressed paralogs. Assays of expression in orthologs from outgroup species revealed that some imprinted genes have acquired an organ-specific expression pattern restricted to flowers and/or seeds. The changes in expression pattern and the accelerated sequence evolution in the imprinted genes suggest that some of them may have undergone neofunctionalization. The imprinted genes MPC, HOMEODOMAIN GLABROUS6 (HDG6), and HDG3 are particularly interesting cases that have different functions from their paralogs. This study indicates that a large number of imprinted genes in Arabidopsis are evolutionarily recent duplicates and that many of them show changes in expression profiles and accelerated sequence evolution. Acquisition of imprinting is a mode of duplicate gene divergence in plants that is more common than previously thought.

  9. Fos-activation of FoxP2 and Lmx1b neurons in the parabrachial nucleus evoked by hypotension and hypertension in conscious rats

    PubMed Central

    Miller, Rebecca L.; Knuepfer, Mark M.; Wang, Michelle H.; Denny, George O.; Gray, Paul A.; Loewy, Arthur D.

    2012-01-01

    The parabrachial nucleus (PB) is a brainstem cell group that receives a strong input from the nucleus tractus solitarius regarding the physiological status of the internal organs and sends efferent projections throughout the forebrain. Since the neuroanatomical organization of the PB remains unclear, our first step was to use specific antibodies against two neural lineage transcription factors: Forkhead box protein2 (FoxP2) and LIM homeodomain transcription factor 1 beta (Lmx1b) to define the PB in adult rats. This allowed us to construct a cytoarchitectonic PB map based on the distribution of neurons that constitutively express these two transcription factors. Second, the in situ hybridization method combined with immunohistochemistry demonstrated that mRNA for glutamate vesicular transporter Vglut2 (Slc17a6) was present in most of the Lmx1b+ and FoxP2+ parabrachial neurons, indicating these neurons use glutamate as a transmitter. Third, conscious rats were maintained in a hypotensive or hypertensive state for two hours, and then, their brainstems were prepared by the standard c-Fos method which is a measure of neuronal activity. Both hypotension and hypertension resulted in c-Fos activation of Lmx1b+ neurons in the external lateral-outer subdivision of the PB (PBel-outer). Hypotension, but not hypertension, caused c-Fos activity in the FoxP2+ neurons of the central lateral PB (PBcl) subnucleus. The Kölliker-Fuse nucleus as well as the lateral crescent PB and rostralmost part of the PBcl contain neurons that co-express FoxP2+ and Lmx1b+, but none of these were activated after blood pressure changes. Salt-sensitive FoxP2 neurons in the pre-locus coeruleus and PBel-inner were not c-Fos activated following blood pressure changes. In summary, the present study shows that the PBel-outer and PBcl subnuclei originate from two different neural progenitors, contain glutamatergic neurons, and are affected by blood pressure changes, with the PBel-outer reacting to both hypo- and hypertension, and the PBcl signaling only hypotensive changes. PMID:22641087

  10. Adaptive radiation of venomous marine snail lineages and the accelerated evolution of venom peptide genes

    PubMed Central

    Olivera, Baldomero M.; Watkins, Maren; Bandyopadhyay, Pradip; Imperial, Julita S.; de la Cotera, Edgar P. Heimer; Aguilar, Manuel B.; Vera, Estuardo López; Concepcion, Gisela P.; Lluisma, Arturo

    2012-01-01

    An impressive biodiversity (>10,000 species) of marine snails (suborder Toxoglossa or superfamily Conoidea) have complex venoms, containing ca. 100 biologically active, disulfide-rich peptides. In the genus Conus, the most intensively investigated toxoglossan lineage (~500 species), a small set of venom gene superfamilies undergo rapid sequence hyperdiversification within their mature toxin regions. Each major lineage of Toxoglossa has its own distinct set of venom gene superfamilies. Two recently identified venom gene superfamilies are expressed in the large Turridae clade, but not in Conus. Thus, as major venomous molluscan clades expand, a small set of lineage specific venom gene superfamilies undergo accelerated evolution. The juxtaposition of extremely conserved signal sequences with hypervariable mature peptide regions is unprecedented and raises the possibility that in these gene superfamilies, the signal sequences are conserved as a result of an essential role they play in enabling rapid sequence evolution of the region of the gene that encodes the active toxin. PMID:22954218

  11. Evolution of eusociality and the soldier caste in termites: Influence of intraspecific competition and accelerated inheritance

    PubMed Central

    Thorne, Barbara L.; Breisch, Nancy L.; Muscedere, Mario L.

    2003-01-01

    We present new hypotheses and report experimental evidence for powerful selective forces impelling the evolution of both eusociality and the soldier caste in termites. Termite ancestors likely had a nesting and developmental life history similar to that of the living family Termopsidae, in which foraging does not occur outside the host wood, and nonsoldier helpers retain lifelong options for differentiation into reproductives. A local neighborhood of families that live exclusively within a limited resource results in interactions between conspecific colonies, high mortality of founding reproductives, and opportunities for accelerated inheritance of the nest and population by offspring that differentiate into nondispersing neotenic reproductives. In addition, fertile reproductive soldiers, a type of neotenic previously considered rare and docile, frequently develop in this intraspecific competitive context. They can be highly aggressive in subsequent interactions, supporting the hypothesis that intercolonial battles influenced the evolution of modern sterile termite soldier weaponry and behaviors. PMID:14555764

  12. Acceleration and evolution of a hollow electron beam in wakefields driven by a Laguerre-Gaussian laser pulse

    SciTech Connect

    Zhang, Guo-Bo; Chen, Min E-mail: yanyunma@126.com; Luo, Ji; Zeng, Ming; Yu, Lu-Le; Weng, Su-Ming; Schroeder, C. B.; Esarey, E.; Li, Fei-Yu; Ma, Yan-Yun E-mail: yanyunma@126.com; Yu, Tong-Pu; Sheng, Zheng-Ming

    2016-03-15

    We show that a ring-shaped hollow electron beam can be injected and accelerated by using a Laguerre-Gaussian laser pulse and ionization-induced injection in a laser wakefield accelerator. The acceleration and evolution of such a hollow, relativistic electron beam are investigated through three-dimensional particle-in-cell simulations. We find that both the ring size and the beam thickness oscillate during the acceleration. The beam azimuthal shape is angularly dependent and evolves during the acceleration. The beam ellipticity changes resulting from the electron angular momenta obtained from the drive laser pulse and the focusing forces from the wakefield. The dependence of beam ring radius on the laser-plasma parameters (e.g., laser intensity, focal size, and plasma density) is studied. Such a hollow electron beam may have potential applications for accelerating and collimating positively charged particles.

  13. Crossover accelerates evolution in GAs with a Babel-like fitness landscape: mathematical analyses.

    PubMed

    Suzuki, H; Iwasa, Y

    1999-01-01

    The effectiveness of crossover in accelerating evolution in genetic algorithms (GAs) is studied with a haploid finite population of bit sequences. A Babel-like fitness landscape is assumed. There is a single bit sequence (schema) that is significantly more advantageous than all the others. We study the time until domination of the advantageous schema (Τ&subd;). Evolution proceeds with appearance, spread, and domination of the advantageous schema. The most important process determining Τ&subd; is the appearance (creation) of the advantageous schema. Crossover helps this creation process and enhances the rate of evolution. To study this effect, we first establish an analytical method to estimate Τ&subd; with or without crossover. Then, we conduct a numerical analysis using the frequency vector representation of the population with the recurrence relations formulated after GA operations. Finally, we carry out direct computer simulations with simple GAs operating on a population of binary strings directly prepared in the computer memory to examine the performance of the two analytical methods. It is shown that Τ&subd; is reduced greatly by crossover with a mildly high rate when the mutation rate is adjusted to a moderate value and that an advantageous schema has a fairly larger order (the number of bits). From these observations, we can determine implementation criteria for GAs, which are useful when we are applying GAs to engineering problems having a conspicuously discontinuous fitness landscape.

  14. Comprehensive transcriptome analysis reveals accelerated genic evolution in a Tibet fish, Gymnodiptychus pachycheilus.

    PubMed

    Yang, Liandong; Wang, Ying; Zhang, Zhaolei; He, Shunping

    2014-12-26

    Elucidating the genetic mechanisms of organismal adaptation to the Tibetan Plateau at a genomic scale can provide insights into the process of adaptive evolution. Many highland species have been investigated and various candidate genes that may be responsible for highland adaptation have been identified. However, we know little about the genomic basis of adaptation to Tibet in fishes. Here, we performed transcriptome sequencing of a schizothoracine fish (Gymnodiptychus pachycheilus) and used it to identify potential genetic mechanisms of highland adaptation. We obtained totally 66,105 assembled unigenes, of which 7,232 were assigned as putative one-to-one orthologs in zebrafish. Comparative gene annotations from several species indicated that at least 350 genes lost and 41 gained since the divergence between G. pachycheilus and zebrafish. An analysis of 6,324 orthologs among zebrafish, fugu, medaka, and spotted gar identified consistent evidence for genome-wide accelerated evolution in G. pachycheilus and only the terminal branch of G. pachycheilus had an elevated Ka/Ks ratio than the ancestral branch. Many functional categories related to hypoxia and energy metabolism exhibited rapid evolution in G. pachycheilus relative to zebrafish. Genes showing signature of rapid evolution and positive selection in the G. pachycheilus lineage were also enriched in functions associated with energy metabolism and hypoxia. The first genomic resources for fish in the Tibetan Plateau and evolutionary analyses provided some novel insights into highland adaptation in fishes and served as a foundation for future studies aiming to identify candidate genes underlying the genetic bases of adaptation to Tibet in fishes.

  15. Accelerated evolution and coevolution drove the evolutionary history of AGPase sub-units during angiosperm radiation

    PubMed Central

    Corbi, Jonathan; Dutheil, Julien Y.; Damerval, Catherine; Tenaillon, Maud I.; Manicacci, Domenica

    2012-01-01

    Background and Aims ADP-glucose pyrophosphorylase (AGPase) is a key enzyme of starch biosynthesis. In the green plant lineage, it is composed of two large (LSU) and two small (SSU) sub-units encoded by paralogous genes, as a consequence of several rounds of duplication. First, our aim was to detect specific patterns of molecular evolution following duplication events and the divergence between monocotyledons and dicotyledons. Secondly, we investigated coevolution between amino acids both within and between sub-units. Methods A phylogeny of each AGPase sub-unit was built using all gymnosperm and angiosperm sequences available in databases. Accelerated evolution along specific branches was tested using the ratio of the non-synonymous to the synonymous substitution rate. Coevolution between amino acids was investigated taking into account compensatory changes between co-substitutions. Key Results We showed that SSU paralogues evolved under high functional constraints during angiosperm radiation, with a significant level of coevolution between amino acids that participate in SSU major functions. In contrast, in the LSU paralogues, we identified residues under positive selection (1) following the first LSU duplication that gave rise to two paralogues mainly expressed in angiosperm source and sink tissues, respectively; and (2) following the emergence of grass-specific paralogues expressed in the endosperm. Finally, we found coevolution between residues that belong to the interaction domains of both sub-units. Conclusions Our results support the view that coevolution among amino acid residues, especially those lying in the interaction domain of each sub-unit, played an important role in AGPase evolution. First, within SSU, coevolution allowed compensating mutations in a highly constrained context. Secondly, the LSU paralogues probably acquired tissue-specific expression and regulatory properties via the coevolution between sub-unit interacting domains. Finally, the

  16. Accelerated evolution and coevolution drove the evolutionary history of AGPase sub-units during angiosperm radiation.

    PubMed

    Corbi, Jonathan; Dutheil, Julien Y; Damerval, Catherine; Tenaillon, Maud I; Manicacci, Domenica

    2012-03-01

    ADP-glucose pyrophosphorylase (AGPase) is a key enzyme of starch biosynthesis. In the green plant lineage, it is composed of two large (LSU) and two small (SSU) sub-units encoded by paralogous genes, as a consequence of several rounds of duplication. First, our aim was to detect specific patterns of molecular evolution following duplication events and the divergence between monocotyledons and dicotyledons. Secondly, we investigated coevolution between amino acids both within and between sub-units. A phylogeny of each AGPase sub-unit was built using all gymnosperm and angiosperm sequences available in databases. Accelerated evolution along specific branches was tested using the ratio of the non-synonymous to the synonymous substitution rate. Coevolution between amino acids was investigated taking into account compensatory changes between co-substitutions. We showed that SSU paralogues evolved under high functional constraints during angiosperm radiation, with a significant level of coevolution between amino acids that participate in SSU major functions. In contrast, in the LSU paralogues, we identified residues under positive selection (1) following the first LSU duplication that gave rise to two paralogues mainly expressed in angiosperm source and sink tissues, respectively; and (2) following the emergence of grass-specific paralogues expressed in the endosperm. Finally, we found coevolution between residues that belong to the interaction domains of both sub-units. Our results support the view that coevolution among amino acid residues, especially those lying in the interaction domain of each sub-unit, played an important role in AGPase evolution. First, within SSU, coevolution allowed compensating mutations in a highly constrained context. Secondly, the LSU paralogues probably acquired tissue-specific expression and regulatory properties via the coevolution between sub-unit interacting domains. Finally, the pattern we observed during LSU evolution is consistent

  17. Comprehensive Transcriptome Analysis Reveals Accelerated Genic Evolution in a Tibet Fish, Gymnodiptychus pachycheilus

    PubMed Central

    Yang, Liandong; Wang, Ying; Zhang, Zhaolei; He, Shunping

    2015-01-01

    Elucidating the genetic mechanisms of organismal adaptation to the Tibetan Plateau at a genomic scale can provide insights into the process of adaptive evolution. Many highland species have been investigated and various candidate genes that may be responsible for highland adaptation have been identified. However, we know little about the genomic basis of adaptation to Tibet in fishes. Here, we performed transcriptome sequencing of a schizothoracine fish (Gymnodiptychus pachycheilus) and used it to identify potential genetic mechanisms of highland adaptation. We obtained totally 66,105 assembled unigenes, of which 7,232 were assigned as putative one-to-one orthologs in zebrafish. Comparative gene annotations from several species indicated that at least 350 genes lost and 41 gained since the divergence between G. pachycheilus and zebrafish. An analysis of 6,324 orthologs among zebrafish, fugu, medaka, and spotted gar identified consistent evidence for genome-wide accelerated evolution in G. pachycheilus and only the terminal branch of G. pachycheilus had an elevated Ka/Ks ratio than the ancestral branch. Many functional categories related to hypoxia and energy metabolism exhibited rapid evolution in G. pachycheilus relative to zebrafish. Genes showing signature of rapid evolution and positive selection in the G. pachycheilus lineage were also enriched in functions associated with energy metabolism and hypoxia. The first genomic resources for fish in the Tibetan Plateau and evolutionary analyses provided some novel insights into highland adaptation in fishes and served as a foundation for future studies aiming to identify candidate genes underlying the genetic bases of adaptation to Tibet in fishes. PMID:25543049

  18. Molecular co-catalyst accelerating hole transfer for enhanced photocatalytic H2 evolution

    NASA Astrophysics Data System (ADS)

    Bi, Wentuan; Li, Xiaogang; Zhang, Lei; Jin, Tao; Zhang, Lidong; Zhang, Qun; Luo, Yi; Wu, Changzheng; Xie, Yi

    2015-10-01

    In artificial photocatalysis, sluggish kinetics of hole transfer and the resulting high-charge recombination rate have been the Achilles' heel of photocatalytic conversion efficiency. Here we demonstrate water-soluble molecules as co-catalysts to accelerate hole transfer for improved photocatalytic H2 evolution activity. Trifluoroacetic acid (TFA), by virtue of its reversible redox couple TFA./TFA-, serves as a homogeneous co-catalyst that not only maximizes the contact areas between co-catalysts and reactants but also greatly promotes hole transfer. Thus K4Nb6O17 nanosheet catalysts achieve drastically increased photocatalytic H2 production rate in the presence of TFA, up to 32 times with respect to the blank experiment. The molecular co-catalyst represents a new, simple and highly effective approach to suppress recombination of photogenerated charges, and has provided fertile new ground for creating high-efficiency photosynthesis systems, avoiding use of noble-metal co-catalysts.

  19. TALENs-Assisted Multiplex Editing for Accelerated Genome Evolution To Improve Yeast Phenotypes.

    PubMed

    Zhang, Guoqiang; Lin, Yuping; Qi, Xianni; Li, Lin; Wang, Qinhong; Ma, Yanhe

    2015-10-16

    Genome editing is an important tool for building novel genotypes with a desired phenotype. However, the fundamental challenge is to rapidly generate desired alterations on a genome-wide scale. Here, we report TALENs (transcription activator-like effector nucleases)-assisted multiplex editing (TAME), based on the interaction of designed TALENs with the DNA sequences between the critical TATA and GC boxes, for generating multiple targeted genomic modifications. Through iterative cycles of TAME to induce abundant semirational indels coupled with efficient screening using a reporter, the targeted fluorescent trait can be continuously and rapidly improved by accumulating multiplex beneficial genetic modifications in the evolving yeast genome. To further evaluate its efficiency, we also demonstrate the application of TAME for significantly improving ethanol tolerance of yeast in a short amount of time. Therefore, TAME is a broadly generalizable platform for accelerated genome evolution to rapidly improve yeast phenotypes.

  20. Molecular co-catalyst accelerating hole transfer for enhanced photocatalytic H2 evolution

    PubMed Central

    Bi, Wentuan; Li, Xiaogang; Zhang, Lei; Jin, Tao; Zhang, Lidong; Zhang, Qun; Luo, Yi; Wu, Changzheng; Xie, Yi

    2015-01-01

    In artificial photocatalysis, sluggish kinetics of hole transfer and the resulting high-charge recombination rate have been the Achilles' heel of photocatalytic conversion efficiency. Here we demonstrate water-soluble molecules as co-catalysts to accelerate hole transfer for improved photocatalytic H2 evolution activity. Trifluoroacetic acid (TFA), by virtue of its reversible redox couple TFA·/TFA−, serves as a homogeneous co-catalyst that not only maximizes the contact areas between co-catalysts and reactants but also greatly promotes hole transfer. Thus K4Nb6O17 nanosheet catalysts achieve drastically increased photocatalytic H2 production rate in the presence of TFA, up to 32 times with respect to the blank experiment. The molecular co-catalyst represents a new, simple and highly effective approach to suppress recombination of photogenerated charges, and has provided fertile new ground for creating high-efficiency photosynthesis systems, avoiding use of noble-metal co-catalysts. PMID:26486863

  1. From inflation to recent cosmic acceleration: the fermionic Elko field driving the evolution of the universe

    NASA Astrophysics Data System (ADS)

    Pereira, S. H.; Guimarães, T. M.

    2017-09-01

    In this paper we construct the complete evolution of the universe driven by the mass dimension one dark spinor called Elko, starting with inflation, passing by the matter dominated era and finishing with the recent accelerated expansion. The dynamic of the fermionic Elko field with a symmetry breaking type potential can reproduce all phases of the universe in a natural and elegant way. The dynamical equations in general case and slow roll conditions in the limit Hll mpl are also presented for the Elko system. Numerical analysis for the number of e-foldings during inflation, energy density after inflation and for present time and also the actual size of the universe are in good agreement with the standard model of cosmology. An interpretation of the inflationary phase as a result of Pauli exclusion principle is also possible if the Elko field is treated as an average value of its quantum analogue.

  2. Mid-Infrared Evidence for Accelerated Evolution in Compact Group Galaxies

    NASA Astrophysics Data System (ADS)

    Walker, L. M.; Johnson, K. E.; Gallagher, S. C.; Hibbard, J. E.; Hornschemeier, A. E.; Charlton, J. C.; Jarrett, T. H.

    2010-06-01

    We find evidence for accelerated evolution in compact group galaxies from the distribution in mid-infrared colorspace of 42 galaxies from 12 Hickson Compact Groups (HCGs) compared to the distributions of several other samples including the LVL+SINGS galaxies, interacting galaxies, and galaxies from the Coma Cluster. We find that the HCG galaxies are not uniformly distributed in colorspace, as well as quantitative evidence for a gap. Galaxies in the infall region of the Coma cluster also exhibit a non-uniform distribution and a less well defined gap, which may reflect a similarity with the compact group environment. Neither the Coma Center or interacting samples show evidence of a gap, leading us to speculate that the gap is unique to the environment of high galaxy density where gas has not been fully processed or stripped.

  3. Mid-Infrared Evidence for Accelerated Evolution in Compact Group Galaxies

    NASA Astrophysics Data System (ADS)

    Walker, Lisa May; Johnson, K. E.; Gallagher, S. C.; Hibbard, J. E.; Hornschemeier, A. E.; Charlton, J. C.; Jarrett, T. H.

    2010-01-01

    We find evidence for accelerated evolution in compact group galaxies from the mid-infrared distribution in colorspace of 42 galaxies from 12 Hickson Compact Groups (HCGs) and the distributions of several comparison samples including the LVL+SINGS galaxies, interacting galaxies, and galaxies from the Coma Cluster. We find that the HCG galaxies are not uniformly distributed in colorspace, as well as quantitative evidence for a gap. Galaxies in the infall region of the Coma cluster also exhibit a non-uniform distribution and a less well defined gap, which may reflect a similarity with the compact group environment. None of the other samples we studied show evidence of a gap, leading us to speculate that it is unique to the environment present in compact groups and clusters; one of high density where gas has not been fully processed or stripped.

  4. Identification of the Imprinted KLF14 Transcription Factor Undergoing Human-Specific Accelerated Evolution

    PubMed Central

    Parker-Katiraee, Layla; Carson, Andrew R; Yamada, Takahiro; Arnaud, Philippe; Feil, Robert; Abu-Amero, Sayeda N; Moore, Gudrun E; Kaneda, Masahiro; Perry, George H; Stone, Anne C; Lee, Charles; Meguro-Horike, Makiko; Sasaki, Hiroyuki; Kobayashi, Keiko; Nakabayashi, Kazuhiko; Scherer, Stephen W

    2007-01-01

    Imprinted genes are expressed in a parent-of-origin manner and are located in clusters throughout the genome. Aberrations in the expression of imprinted genes on human Chromosome 7 have been suggested to play a role in the etiologies of Russell-Silver Syndrome and autism. We describe the imprinting of KLF14, an intronless member of the Krüppel-like family of transcription factors located at Chromosome 7q32. We show that it has monoallelic maternal expression in all embryonic and extra-embryonic tissues studied, in both human and mouse. We examine epigenetic modifications in the KLF14 CpG island in both species and find this region to be hypomethylated. In addition, we perform chromatin immunoprecipitation and find that the murine Klf14 CpG island lacks allele-specific histone modifications. Despite the absence of these defining features, our analysis of Klf14 in offspring from DNA methyltransferase 3a conditional knockout mice reveals that the gene's expression is dependent upon a maternally methylated region. Due to the intronless nature of Klf14 and its homology to Klf16, we suggest that the gene is an ancient retrotransposed copy of Klf16. By sequence analysis of numerous species, we place the timing of this event after the divergence of Marsupialia, yet prior to the divergence of the Xenarthra superclade. We identify a large number of sequence variants in KLF14 and, using several measures of diversity, we determine that there is greater variability in the human lineage with a significantly increased number of nonsynonymous changes, suggesting human-specific accelerated evolution. Thus, KLF14 may be the first example of an imprinted transcript undergoing accelerated evolution in the human lineage. PMID:17480121

  5. Identification of the imprinted KLF14 transcription factor undergoing human-specific accelerated evolution.

    PubMed

    Parker-Katiraee, Layla; Carson, Andrew R; Yamada, Takahiro; Arnaud, Philippe; Feil, Robert; Abu-Amero, Sayeda N; Moore, Gudrun E; Kaneda, Masahiro; Perry, George H; Stone, Anne C; Lee, Charles; Meguro-Horike, Makiko; Sasaki, Hiroyuki; Kobayashi, Keiko; Nakabayashi, Kazuhiko; Scherer, Stephen W

    2007-05-04

    Imprinted genes are expressed in a parent-of-origin manner and are located in clusters throughout the genome. Aberrations in the expression of imprinted genes on human Chromosome 7 have been suggested to play a role in the etiologies of Russell-Silver Syndrome and autism. We describe the imprinting of KLF14, an intronless member of the Krüppel-like family of transcription factors located at Chromosome 7q32. We show that it has monoallelic maternal expression in all embryonic and extra-embryonic tissues studied, in both human and mouse. We examine epigenetic modifications in the KLF14 CpG island in both species and find this region to be hypomethylated. In addition, we perform chromatin immunoprecipitation and find that the murine Klf14 CpG island lacks allele-specific histone modifications. Despite the absence of these defining features, our analysis of Klf14 in offspring from DNA methyltransferase 3a conditional knockout mice reveals that the gene's expression is dependent upon a maternally methylated region. Due to the intronless nature of Klf14 and its homology to Klf16, we suggest that the gene is an ancient retrotransposed copy of Klf16. By sequence analysis of numerous species, we place the timing of this event after the divergence of Marsupialia, yet prior to the divergence of the Xenarthra superclade. We identify a large number of sequence variants in KLF14 and, using several measures of diversity, we determine that there is greater variability in the human lineage with a significantly increased number of nonsynonymous changes, suggesting human-specific accelerated evolution. Thus, KLF14 may be the first example of an imprinted transcript undergoing accelerated evolution in the human lineage.

  6. Transient Hypermutagenesis Accelerates the Evolution of Legume Endosymbionts following Horizontal Gene Transfer

    PubMed Central

    Remigi, Philippe; Capela, Delphine; Clerissi, Camille; Tasse, Léna; Torchet, Rachel; Bouchez, Olivier; Batut, Jacques; Cruveiller, Stéphane; Rocha, Eduardo P. C.; Masson-Boivin, Catherine

    2014-01-01

    Horizontal gene transfer (HGT) is an important mode of adaptation and diversification of prokaryotes and eukaryotes and a major event underlying the emergence of bacterial pathogens and mutualists. Yet it remains unclear how complex phenotypic traits such as the ability to fix nitrogen with legumes have successfully spread over large phylogenetic distances. Here we show, using experimental evolution coupled with whole genome sequencing, that co-transfer of imuABC error-prone DNA polymerase genes with key symbiotic genes accelerates the evolution of a soil bacterium into a legume symbiont. Following introduction of the symbiotic plasmid of Cupriavidus taiwanensis, the Mimosa symbiont, into pathogenic Ralstonia solanacearum we challenged transconjugants to become Mimosa symbionts through serial plant-bacteria co-cultures. We demonstrate that a mutagenesis imuABC cassette encoded on the C. taiwanensis symbiotic plasmid triggered a transient hypermutability stage in R. solanacearum transconjugants that occurred before the cells entered the plant. The generated burst in genetic diversity accelerated symbiotic adaptation of the recipient genome under plant selection pressure, presumably by improving the exploration of the fitness landscape. Finally, we show that plasmid imuABC cassettes are over-represented in rhizobial lineages harboring symbiotic plasmids. Our findings shed light on a mechanism that may have facilitated the dissemination of symbiotic competency among α- and β-proteobacteria in natura and provide evidence for the positive role of environment-induced mutagenesis in the acquisition of a complex lifestyle trait. We speculate that co-transfer of complex phenotypic traits with mutagenesis determinants might frequently enhance the ecological success of HGT. PMID:25181317

  7. Domain loss facilitates accelerated evolution and neofunctionalization of duplicate snake venom metalloproteinase toxin genes.

    PubMed

    Casewell, Nicholas R; Wagstaff, Simon C; Harrison, Robert A; Renjifo, Camila; Wüster, Wolfgang

    2011-09-01

    Gene duplication is a key mechanism for the adaptive evolution and neofunctionalization of gene families. Large multigene families often exhibit complex evolutionary histories as a result of frequent gene duplication acting in concordance with positive selection pressures. Alterations in the domain structure of genes, causing changes in the molecular scaffold of proteins, can also result in a complex evolutionary history and has been observed in functionally diverse multigene toxin families. Here, we investigate the role alterations in domain structure have on the tempo of evolution and neofunctionalization of multigene families using the snake venom metalloproteinases (SVMPs) as a model system. Our results reveal that the evolutionary history of viperid (Serpentes: Viperidae) SVMPs is repeatedly punctuated by domain loss, with the single loss of the cysteine-rich domain, facilitating the formation of P-II class SVMPs, occurring prior to the convergent loss of the disintegrin domain to form multiple P-I SVMP structures. Notably, the majority of phylogenetic branches where domain loss was inferred to have occurred exhibited highly significant evidence of positive selection in surface-exposed amino acid residues, resulting in the neofunctionalization of P-II and P-I SVMP classes. These results provide a valuable insight into the mechanisms by which complex gene families evolve and detail how the loss of domain structures can catalyze the accelerated evolution of novel gene paralogues. The ensuing generation of differing molecular scaffolds encoded by the same multigene family facilitates gene neofunctionalization while presenting an evolutionary advantage through the retention of multiple genes capable of encoding functionally distinct proteins.

  8. Is the Size Evolution of Massive Galaxies Accelerated in Cluster Environments?

    NASA Astrophysics Data System (ADS)

    Wilson, Gillian

    2013-10-01

    At z 1.6 the main progenitors of present-day massive clusters are undergoing rapid collapse, and have the highest rates of galaxy merging and assembly. Recent observational studies have hinted at accelerated galaxy evolution in dense environments at this epoch, including increased merger rates and rapid growth in galaxy size relative to the field. We propose WFC3 G102 spectroscopy and F125W {Broad J} imaging of a sample of four massive spectroscopically-confirmed clusters at z = 1.6. Our primary scientific goal is to leverage the CANDELS Wide Legacy dataset to carry out a head-to-head comparison of the sizes of cluster members relative to the field {as a function of stellar mass and Sersic index}, and quantify the role of environment in the observed rapid evolution in galaxy sizes since z = 2. These clusters are four of the highest significance overdensities in the 50 square degree SWIRE fields, and will evolve over time to have present-day masses similar to Coma. They were detected using IRAC [3.6]-[4.5] color, which identifies galaxy overdensities regardless of optically red or blue color. A heroic ground-based spectroscopic campaign has resulted in 44 spectroscopically-confirmed members. However this sample is heavily biased toward star-forming {SF} galaxies, and WFC3 spectroscopy is essential to definitively determine cluster membership for 200 members, without bias with respect to quiescent or SF type. The F125W {rest-frame V-band} imaging is necessary to measure the sizes and morphologies of cluster members. 17-passband broadband imaging spanning UV, optical, near-IR, Spitzer IR and Herschel far-IR is already in hand.

  9. MID-INFRARED EVIDENCE FOR ACCELERATED EVOLUTION IN COMPACT GROUP GALAXIES

    SciTech Connect

    Walker, Lisa May; Johnson, Kelsey E.; Gallagher, Sarah C.; Hibbard, John E.; Hornschemeier, Ann E.; Tzanavaris, Panayiotis; Charlton, Jane C.; Jarrett, Thomas H.

    2010-11-15

    Compact galaxy groups are at the extremes of the group environment, with high number densities and low velocity dispersions that likely affect member galaxy evolution. To explore the impact of this environment in detail, we examine the distribution in the mid-infrared (MIR) 3.6-8.0 {mu}m color space of 42 galaxies from 12 Hickson compact groups (HCGs) in comparison with several control samples, including the LVL+SINGS galaxies, interacting galaxies, and galaxies from the Coma Cluster. We find that the HCG galaxies are strongly bimodal, with statistically significant evidence for a gap in their distribution. In contrast, none of the other samples show such a marked gap, and only galaxies in the Coma infall region have a distribution that is statistically consistent with the HCGs in this parameter space. To further investigate the cause of the HCG gap, we compare the galaxy morphologies of the HCG and LVL+SINGS galaxies, and also probe the specific star formation rate (SSFR) of the HCG galaxies. While galaxy morphology in HCG galaxies is strongly linked to position with MIR color space, the more fundamental property appears to be the SSFR, or star formation rate normalized by stellar mass. We conclude that the unusual MIR color distribution of HCG galaxies is a direct product of their environment, which is most similar to that of the Coma infall region. In both cases, galaxy densities are high, but gas has not been fully processed or stripped. We speculate that the compact group environment fosters accelerated evolution of galaxies from star-forming and neutral gas-rich to quiescent and neutral gas-poor, leaving few members in the MIR gap at any time.

  10. Mid-infrared Evidence for Accelerated Evolution in Compact Group Galaxies

    NASA Astrophysics Data System (ADS)

    Walker, Lisa May; Johnson, Kelsey E.; Gallagher, Sarah C.; Hibbard, John E.; Hornschemeier, Ann E.; Tzanavaris, Panayiotis; Charlton, Jane C.; Jarrett, Thomas H.

    2010-11-01

    Compact galaxy groups are at the extremes of the group environment, with high number densities and low velocity dispersions that likely affect member galaxy evolution. To explore the impact of this environment in detail, we examine the distribution in the mid-infrared (MIR) 3.6-8.0 μm color space of 42 galaxies from 12 Hickson compact groups (HCGs) in comparison with several control samples, including the LVL+SINGS galaxies, interacting galaxies, and galaxies from the Coma Cluster. We find that the HCG galaxies are strongly bimodal, with statistically significant evidence for a gap in their distribution. In contrast, none of the other samples show such a marked gap, and only galaxies in the Coma infall region have a distribution that is statistically consistent with the HCGs in this parameter space. To further investigate the cause of the HCG gap, we compare the galaxy morphologies of the HCG and LVL+SINGS galaxies, and also probe the specific star formation rate (SSFR) of the HCG galaxies. While galaxy morphology in HCG galaxies is strongly linked to position with MIR color space, the more fundamental property appears to be the SSFR, or star formation rate normalized by stellar mass. We conclude that the unusual MIR color distribution of HCG galaxies is a direct product of their environment, which is most similar to that of the Coma infall region. In both cases, galaxy densities are high, but gas has not been fully processed or stripped. We speculate that the compact group environment fosters accelerated evolution of galaxies from star-forming and neutral gas-rich to quiescent and neutral gas-poor, leaving few members in the MIR gap at any time.

  11. Alternative splicing modulated by genetic variants demonstrates accelerated evolution regulated by highly conserved proteins

    PubMed Central

    Hsiao, Yun-Hua Esther; Bahn, Jae Hoon; Lin, Xianzhi; Chan, Tak-Ming; Wang, Rena; Xiao, Xinshu

    2016-01-01

    Identification of functional genetic variants and elucidation of their regulatory mechanisms represent significant challenges of the post-genomic era. A poorly understood topic is the involvement of genetic variants in mediating post-transcriptional RNA processing, including alternative splicing. Thus far, little is known about the genomic, evolutionary, and regulatory features of genetically modulated alternative splicing (GMAS). Here, we systematically identified intronic tag variants for genetic modulation of alternative splicing using RNA-seq data specific to cellular compartments. Combined with our previous method that identifies exonic tags for GMAS, this study yielded 622 GMAS exons. We observed that GMAS events are highly cell type independent, indicating that splicing-altering genetic variants could have widespread function across cell types. Interestingly, GMAS genes, exons, and single-nucleotide variants (SNVs) all demonstrated positive selection or accelerated evolution in primates. We predicted that GMAS SNVs often alter binding of splicing factors, with SRSF1 affecting the most GMAS events and demonstrating global allelic binding bias. However, in contrast to their GMAS targets, the predicted splicing factors are more conserved than expected, suggesting that cis-regulatory variation is the major driving force of splicing evolution. Moreover, GMAS-related splicing factors had stronger consensus motifs than expected, consistent with their susceptibility to SNV disruption. Intriguingly, GMAS SNVs in general do not alter the strongest consensus position of the splicing factor motif, except the more than 100 GMAS SNVs in linkage disequilibrium with polymorphisms reported by genome-wide association studies. Our study reports many GMAS events and enables a better understanding of the evolutionary and regulatory features of this phenomenon. PMID:26888265

  12. Accelerated molecular evolution in Microtus (Rodentia) as assessed via complete mitochondrial genome sequences.

    PubMed

    Triant, Deborah A; Dewoody, J Andrew

    2006-01-01

    Microtus is one of the most taxonomically diverse mammalian genera, including over 60 extant species. These rodents have evolved rapidly, as the genus originated less than 2 million years ago. If these numbers are taken at face value, then an average of 30 microtine speciation events have occurred every million years. One explanation for the rapid rate of cladogenesis in Microtus could be the karyotypic differentiation exhibited across the genus: diploid numbers range from 17 to 64. Despite the striking chromosomal variability within Microtus, phenotypic variation is unremarkable. To determine whether nucleotide substitution rates are also elevated in voles, we sequenced the entire mitochondrial DNA (mtDNA) genome of the Eurasian sibling vole (Microtus rossiaemeridionalis). We compared this genome to another previously sequenced vole mtDNA genome (Microtus kikuchii) and performed pairwise sequence comparisons with the mtDNA genomes of ten additional mammalian genera. We found that microtine mtDNA genomes are evolving more rapidly than any other mammalian lineage we sampled, as gauged by the rate of nucleotide substitution across the entire mtDNA genome as well as at each individual protein-coding gene. Additionally, we compared substitution rates within the cytochrome b gene to seven other rodent genera and found that Microtus mtDNA is evolving fastest. The root cause of accelerated evolution in Microtus remains uncertain, but merits further investigation.

  13. Metabolic acceleration and the evolution of human brain size and life history.

    PubMed

    Pontzer, Herman; Brown, Mary H; Raichlen, David A; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Thompson, Melissa Emery; Shumaker, Robert W; Ross, Stephen R

    2016-05-19

    Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

  14. Evolution of the solar wind acceleration region during 1990-1994

    NASA Technical Reports Server (NTRS)

    Tokumaru, M.; Kondo, T.; Takaba, H.; Mori, H.; Tanaka, T.

    1995-01-01

    The single-station measurements of interplanetary scintillation (IPS) at 2 and 8 GHz have been made at the Kashima Space Research Center of the Communications Research Laboratory in the period from 1990 to 1994. These IPS data are used to study the radial distribution of solar wind velocity and density fluctuations near the sun (i.e. 10-70 Rs), and the long-term variation in these properties. The IPS co-spectrum technique is applied here to estimate the solar wind velocity. Derived velocities show that the solar wind gains a speed significantly in the radial range from 10 to 30 Rs (solar radii). which is much farther than the source surface of the thermally driven solar wind model. From the scintillation index analysis. it is found that the radial fall of density fluctuations is well described by the power-law function. A series of IPS observations reveals that a pronounced change in velocity and turbulence level for this radial range occurs at the polar region of the sun during 1990-1994. That is, the high speed wind and the reduced turbulence region develop there as the solar activity declines. On the other hand, little long-term variation is observed for the solar wind acceleration region at a low latitude. From the comparison with He 1O83 nm observations. it is demonstrated that the change of the solar wind structure is closely linked with the evolution of the coronal hole on the solar surface.

  15. Metabolic acceleration and the evolution of human brain size and life history

    PubMed Central

    Pontzer, Herman; Brown, Mary H.; Raichlen, David A.; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R.; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E.; Lambert, Estelle V.; Thompson, Melissa Emery; Shumaker, Robert W.; Ross, Stephen R.

    2016-01-01

    Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity1. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day−1) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day−1, respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day−1), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history. PMID:27144364

  16. Evolution in Fast Forward: a Potential Role for Mutators in Accelerating Staphylococcus aureus Pathoadaptation

    PubMed Central

    Canfield, Gregory S.; Schwingel, Johanna M.; Foley, Matthew H.; Vore, Kelly L.; Boonanantanasarn, Kanitsak; Gill, Ann L.; Sutton, Mark D.

    2013-01-01

    Pathogen evolution and subsequent phenotypic heterogeneity during chronic infection are proposed to enhance Staphylococcus aureus survival during human infection. We tested this theory by genetically and phenotypically characterizing strains with mutations constructed in the mismatch repair (MMR) and oxidized guanine (GO) system, termed mutators, which exhibit increased spontaneous-mutation frequencies. Analysis of these mutators revealed not only strain-dependent increases in the spontaneous-mutation frequency but also shifts in mutational type and hot spots consistent with loss of GO or MMR functions. Although the GO and MMR systems are relied upon in some bacterial species to prevent reactive oxygen species-induced DNA damage, no deficit in hydrogen peroxide sensitivity was found when either of these DNA repair pathways was lost in S. aureus. To gain insight into the contribution of increased mutation supply to S. aureus pathoadaptation, we measured the rate of α-hemolysin and staphyloxanthin inactivation during serial passage. Detection of increased rates of α-hemolysin and staphyloxanthin inactivation in GO and MMR mutants suggests that these strains are capable of modifying virulence phenotypes implicated in mediating infection. Accelerated derivation of altered virulence phenotypes, combined with the absence of increased ROS sensitivity, highlights the potential of mutators to drive pathoadaptation in the host and serve as catalysts for persistent infections. PMID:23204459

  17. Differential Gene Expression in the Developing Lateral Geniculate Nucleus and Medial Geniculate Nucleus Reveals Novel Roles for Zic4 and Foxp2 in Visual and Auditory Pathway Development

    PubMed Central

    Horng, Sam; Kreiman, Gabriel; Ellsworth, Charlene; Page, Damon; Blank, Marissa; Millen, Kathleen; Sur, Mriganka

    2010-01-01

    Primary sensory nuclei of the thalamus process and relay parallel channels of sensory input into the cortex. The developmental processes by which these nuclei acquire distinct functional roles are not well understood. To identify novel groups of genes with a potential role in differentiating two adjacent sensory nuclei, we performed a microarray screen comparing perinatal gene expression in the principal auditory relay nucleus, the medial geniculate nucleus (MGN), and principal visual relay nucleus, the lateral geniculate nucleus (LGN). We discovered and confirmed groups of highly ranked, differentially expressed genes with qRT-PCR and in situ hybridization. A functional role for Zic4, a transcription factor highly enriched in the LGN, was investigated using Zic4-null mice, which were found to have changes in topographic patterning of retinogeniculate projections. Foxp2, a transcriptional repressor expressed strongly in the MGN, was found to be positively regulated by activity in the MGN. These findings identify roles for two differentially expressed genes, Zic4 and Foxp2, in visual and auditory pathway development. Finally, to test whether modality-specific patterns of gene expression are influenced by extrinsic patterns of input, we performed an additional microarray screen comparing the normal MGN to “rewired” MGN, in which normal auditory afferents are ablated and novel retinal inputs innervate the MGN. Data from this screen indicate that rewired MGN acquires some patterns of gene expression that are present in the developing LGN, including an upregulation of Zic4 expression, as well as novel patterns of expression which may represent unique processes of cross-modal plasticity. PMID:19864579

  18. Rapid courtship evolution in grouse (Tetraonidae): contrasting patterns of acceleration between the Eurasian and North American polygynous clades

    PubMed Central

    Spaulding, Allen

    2007-01-01

    Sexual selection is thought to be a powerful diversifying force, based on large ornamental differences between sexually dimorphic species. This assumes that unornamented phenotypes represent evolution without sexual selection. If sexual selection is more powerful than other forms of selection, then two effects would be: rapid divergence of sexually selected traits and a correlation between these divergence rates and variance in mating success in the ornamented sex. I tested for these effects in grouse (Tetraonidae). For three species pairs, within and among polygynous clades, male courtship characters had significantly greater divergence than other characters. This was most pronounced for two species in Tympanuchus. In the Eurasian polygynous clade, relative courtship divergence gradually increased with nucleotide divergence, suggesting a less dramatic acceleration. Increase in relative courtship divergence was associated with mating systems having higher variance in male mating success. These results suggest that sexual selection has accelerated courtship evolution among grouse, although the microevolutionary details appear to vary among clades. PMID:17284413

  19. Massive Thermal Acceleration of the Emergence of Primordial Chemistry, the Incidence of Spontaneous Mutation, and the Evolution of Enzymes*

    PubMed Central

    Wolfenden, Richard

    2014-01-01

    Kelvin considered it unlikely that sufficient time had elapsed on the earth for life to have reached its present level of complexity. In the warm surroundings in which life first appeared, however, elevated temperatures would have reduced the kinetic barriers to reaction. Recent experiments disclose the profound extent to which very slow reactions are accelerated by elevated temperatures, collapsing the time that would have been required for early events in primordial chemistry before the advent of enzymes. If a primitive enzyme, like model catalysts and most modern enzymes, accelerated a reaction by lowering its enthalpy of activation, then the rate enhancement that it produced would have increased automatically as the environment cooled, quite apart from any improvements in catalytic activity that arose from mutation and natural selection. The chemical events responsible for spontaneous mutation are also highly sensitive to temperature, furnishing an independent mechanism for accelerating evolution. PMID:25210030

  20. Massive thermal acceleration of the emergence of primordial chemistry, the incidence of spontaneous mutation, and the evolution of enzymes.

    PubMed

    Wolfenden, Richard

    2014-10-31

    Kelvin considered it unlikely that sufficient time had elapsed on the earth for life to have reached its present level of complexity. In the warm surroundings in which life first appeared, however, elevated temperatures would have reduced the kinetic barriers to reaction. Recent experiments disclose the profound extent to which very slow reactions are accelerated by elevated temperatures, collapsing the time that would have been required for early events in primordial chemistry before the advent of enzymes. If a primitive enzyme, like model catalysts and most modern enzymes, accelerated a reaction by lowering its enthalpy of activation, then the rate enhancement that it produced would have increased automatically as the environment cooled, quite apart from any improvements in catalytic activity that arose from mutation and natural selection. The chemical events responsible for spontaneous mutation are also highly sensitive to temperature, furnishing an independent mechanism for accelerating evolution.

  1. Role of accelerated segment switch in exons to alter targeting (ASSET) in the molecular evolution of snake venom proteins

    PubMed Central

    Doley, Robin; Mackessy, Stephen P; Kini, R Manjunatha

    2009-01-01

    Background Snake venom toxins evolve more rapidly than other proteins through accelerated changes in the protein coding regions. Previously we have shown that accelerated segment switch in exons to alter targeting (ASSET) might play an important role in its functional evolution of viperid three-finger toxins. In this phenomenon, short sequences in exons are radically changed to unrelated sequences and hence affect the folding and functional properties of the toxins. Results Here we analyzed other snake venom protein families to elucidate the role of ASSET in their functional evolution. ASSET appears to be involved in the functional evolution of three-finger toxins to a greater extent than in several other venom protein families. ASSET leads to replacement of some of the critical amino acid residues that affect the biological function in three-finger toxins as well as change the conformation of the loop that is involved in binding to specific target sites. Conclusion ASSET could lead to novel functions in snake venom proteins. Among snake venom serine proteases, ASSET contributes to changes in three surface segments. One of these segments near the substrate binding region is known to affect substrate specificity, and its exchange may have significant implications for differences in isoform catalytic activity on specific target protein substrates. ASSET therefore plays an important role in functional diversification of snake venom proteins, in addition to accelerated point mutations in the protein coding regions. Accelerated point mutations lead to fine-tuning of target specificity, whereas ASSET leads to large-scale replacement of multiple functionally important residues, resulting in change or gain of functions. PMID:19563684

  2. Efficient numerical modelling of the emittance evolution of beams with finite energy spread in plasma wakefield accelerators

    NASA Astrophysics Data System (ADS)

    Mehrling, T. J.; Robson, R. E.; Erbe, J.-H.; Osterhoff, J.

    2016-09-01

    This paper introduces a semi-analytic numerical approach (SANA) for the rapid computation of the transverse emittance of beams with finite energy spread in plasma wakefield accelerators in the blowout regime. The SANA method is used to model the beam emittance evolution when injected into and extracted from realistic plasma profiles. Results are compared to particle-in-cell simulations, establishing the accuracy and efficiency of the procedure. In addition, it is demonstrated that the tapering of vacuum-to-plasma and plasma-to-vacuum transitions is a viable method for the mitigation of emittance growth of beams during their injection and extraction from and into plasma cells.

  3. Evolution of high-repetition-rate induction accelerators through advancements in switching

    NASA Astrophysics Data System (ADS)

    Kirbie, H. C.; Caporaso, G. J.; Newton, M. A.; Yu, S. S.

    1992-08-01

    Future applications of linear and recirculating induction accelerators include microwave sources for plasma heating and linear colliders, industrial manufacturing processes, and heavy ion fusion. These applications require pulsed sources capable of sustained operation at high pulse-repetition rates. Powering these new accelerators places severe switching demands on the source, demands that often can not be met withcommercially-available technology. Consequently, several new accelerator switching schemes have been developed at Lawrence Livermore National Laboratory (LLNL). Our transition from spark-gap technology to magnetic switching has merged the formerly independent roles of source and cell into a single system and reshaped our design methods to emphasize high efficiency. Treatment of the accelerator as a system has also enabled us to optimize new accelerator designs based on cost considerations. Presently, we are developing a technology for driving a heavy-ion induction recirculator at pulse rates exceeding 100 kHz. In this case, the switching method is all solid state and the source and cell have evolved into a unified device.

  4. Accelerated body size evolution during cold climatic periods in the Cenozoic.

    PubMed

    Clavel, Julien; Morlon, Hélène

    2017-04-03

    How ecological and morphological diversity accumulates over geological time is much debated. Adaptive radiation theory has been successful in testing the effects of biotic interactions on the rapid divergence of phenotypes within a clade, but this theory ignores abiotic effects. The role of abiotic drivers on the tempo of phenotypic evolution has been tested only in a few lineages or small clades from the fossil record. Here, we develop a phylogenetic comparative framework for testing if and how clade-wide rates of phenotypic evolution vary with abiotic drivers. We apply this approach to comprehensive bird and mammal phylogenies, body size data for 9,465 extant species, and global average temperature trends over the Cenozoic. Across birds and mammals, we find that the rate of body size evolution is primarily driven by past climate. Unexpectedly, evolutionary rates are inferred to be higher during periods of cold rather than warm climates in most groups, suggesting that temperature influences evolutionary rates by modifying selective pressures rather than through its effect on energy availability and metabolism. The effect of climate on the rate of body size evolution seems to be a general feature of endotherm evolution, regardless of wide differences in species' ecology and evolutionary history. These results suggest that climatic changes played a major role in shaping species' evolution in the past and could also play a major role in shaping their evolution in the future.

  5. The evolution of tooling, techniques, and quality control for accelerator dipole magnet cables

    SciTech Connect

    Scanlan, R.M.

    1992-08-01

    The present generation of particle accelerators are utilizing the flattened, compacted, single layer cable design introduced nearly 20 years ago at Rutherford Laboratory. However, the requirements for current density, filament size, dimensional control long lengths, and low current degradation are much more stringent for the present accelerators compared with the earlier Tevatron and HERA accelerators. Also, in order to achieve higher field strengths with efficient use of superconductor, the new designs require wider cables with more strands. These requirements have stimulated an active research effort which has led to significant improvements in critical current density and conductor manufacturing. In addition they have stimulated the development of new cabling techniques, improved tooling, and better measurement techniques. The need to produce over 20 million meters of cable has led to the development of high speed cabling machines and on-line quality assurance measurements. These new developments will be discussed, and areas still requiring improvement will be identified.

  6. A geodynamic model of subduction evolution to explain Australian plate acceleration and deceleration during the latest Cretaceous-Early Cenozoic

    NASA Astrophysics Data System (ADS)

    Schellart, Wouter P.

    2017-04-01

    The northern margin of the Australian plate, in the region of present-day New Guinea, was characterized by a large north dipping subduction zone consuming a marginal basin during the latest Cretaceous (Maastrichtian) and Early Cenozoic. Observational data imply that the subduction zone was active at 71-50 Ma, and suggest that it was responsible for plate acceleration from 1 to 7 cm/yr between 66 and 59 Ma, and plate deceleration from 7 to 0 cm/yr between 52 and 49 Ma. A numerical model of buoyancy-driven subduction is presented to simulate the latest Cretaceous-Early Cenozoic geodynamic setting of the New Guinea region and to test if the rates of plate acceleration and deceleration can be ascribed to the progressive evolution of a subducting slab, from an initial transient subduction phase to the terminal stage of subduction involving slab detachment. The geodynamic model can reproduce the first-order plate velocity evolution of the Australian plate and demonstrates that plate velocity increases and decreases of the order of 5 cm/yr, due to transient early and terminal subduction phases, respectively, can occur over periods lasting only a few Myr.

  7. A Redox Shuttle Accelerates O2 Evolution of Photocatalysts Formed In Situ under Visible Light.

    PubMed

    Li, Jia-Xin; Ye, Chen; Li, Xu-Bing; Li, Zhi-Jun; Gao, Xue-Wang; Chen, Bin; Tung, Chen-Ho; Wu, Li-Zhu

    2017-02-20

    A redox shuttle strategy is demonstrated to be a promising approach to accelerate hole removal for efficient O2 production with mesoporous graphitic carbon nitride, WO3 , BiVO4 , NiTi-LDH, and Ag3 PO4 water-oxidation catalysts under visible-light irradiation.

  8. Acceleration and transport of anomalous cosmic rays: Investigating the spectral evolution at Voyager 1 beyond the termination shock

    NASA Astrophysics Data System (ADS)

    Senanayake, Udara K.

    Interstellar neutral atoms entering the heliosphere could become ionized by photo-ionization or charge exchange with solar-wind ions. These newly created ions are picked up by the solar wind and carried to the termination shock (TS) where they are believed to be accelerated by the diffusive shock acceleration process to high energies (˜1-100 MeV n-1). The accelerated ions are known as anomalous cosmic rays (ACRs). When NASA's space probe, Voyager 1 crossed the TS in 2004, the measured ACR spectra did not match the theoretical prediction of a continuous power law, and the source of the high-energy ACRs was not observed. However, over the next few years, in the declining phase of the solar cycle, the spectra began to evolve into the expected power-law profile. The model developed here is based on the suggestion that ACRs are still accelerated at the shock, but away from the Voyager crossing points. First, we study ACR acceleration using a three-dimensional, non-spherical model of the heliosphere that is axisymmetric with respect to the interstellar flow direction. A semi-analytic model of the plasma and magnetic field backgrounds is developed to permit an investigation over a wide range of parameters under controlled conditions. The model is applied to helium ACRs, whose phase-space trajectories are stochastically integrated backward in time until a pre-specified, low-energy boundary of 0.5 MeV n-1, is reached. Next, we propose that the solar cycle had an important effect on the evolving of the spectra in the heliosheath. To investigate this, a magnetohydrodynamic background model with stationary solar-wind inner boundary conditions was used to model the transport of helium and oxygen ions. In addition, we developed a charge consistent stochastic model to simulate multiply charged oxygen ACRs. It is shown that the spectral evolution of ACRs in the heliosheath at Voyager 1 could be explained by combining intermediate-energy particles arriving from the heliotail

  9. Accelerated evolution of 3'avian FOXE1 genes, and thyroid and feather specific expression of chicken FoxE1.

    PubMed

    Yaklichkin, Sergey Yu; Darnell, Diana K; Pier, Maricela V; Antin, Parker B; Hannenhalli, Sridhar

    2011-10-15

    The forkhead transcription factor gene E1 (FOXE1) plays an important role in regulation of thyroid development, palate formation and hair morphogenesis in mammals. However, avian FOXE1 genes have not been characterized and as such, codon evolution of FOXE1 orthologs in a broader evolutionary context of mammals and birds is not known. In this study we identified the avian FOXE1 gene in chicken, turkey and zebra finch, all of which consist of a single exon. Chicken and zebra finch FOXE1 are uniquely located on the sex-determining Z chromosome. In situ hybridization shows that chicken FOXE1 is specifically expressed in the developing thyroid. Its expression is initiated at the placode stage and is maintained during the stages of vesicle formation and follicle primordia. Based on this expression pattern, we propose that avian FOXE1 may be involved in regulating the evagination and morphogenesis of thyroid. Chicken FOXE1 is also expressed in growing feathers. Sequence analysis identified two microdeletions in the avian FOXE1 genes, corresponding to the loss of a transferable repression domain and an engrailed homology motif 1 (Eh1) C-terminal to the forkhead domain. The avian FOXE1 proteins exhibit a significant sequence divergence of the C-terminus compared to those of amphibian and mammalian FOXE1. The codon evolution analysis (dN/dS) of FOXE1 shows a significantly increased dN/dS ratio in the avian lineages, consistent with either a relaxed purifying selection or positive selection on a few residues in avian FOXE1 evolution. Further site specific analysis indicates that while relaxed purifying selection is likely to be a predominant cause of accelerated evolution at the 3'-region of avian FOXE1, a few residues might have evolved under positive selection. We have identified three avian FOXE1 genes based on synteny and sequence similarity as well as characterized the expression pattern of the chicken FOXE1 gene during development. Our evolutionary analyses suggest that

  10. Cytonuclear interactions and relaxed selection accelerate sequence evolution in organelle ribosomes.

    PubMed

    Sloan, Daniel B; Triant, Deborah A; Wu, Martin; Taylor, Douglas R

    2014-03-01

    Many mitochondrial and plastid protein complexes contain subunits that are encoded in different genomes. In animals, nuclear-encoded mitochondrial proteins often exhibit rapid sequence evolution, which has been hypothesized to result from selection for mutations that compensate for changes in interacting subunits encoded in mutation-prone animal mitochondrial DNA. To test this hypothesis, we analyzed nuclear genes encoding cytosolic and organelle ribosomal proteins in flowering plants. The model angiosperm genus Arabidopsis exhibits low organelle mutation rates, typical of most plants. Nevertheless, we found that (nuclear-encoded) subunits of organelle ribosomes in Arabidopsis have higher amino acid sequence polymorphism and divergence than their counterparts in cytosolic ribosomes, suggesting that organelle ribosomes experience relaxed functional constraint. However, the observed difference between organelle and cytosolic ribosomes was smaller than in animals and could be partially attributed to rapid evolution in N-terminal organelle-targeting peptides that are not involved in ribosome function. To test the role of organelle mutation more directly, we used transcriptomic data from an angiosperm genus (Silene) with highly variable rates of organelle genome evolution. We found that Silene species with unusually fast-evolving mitochondrial and plastid DNA exhibited increased amino acid sequence divergence in ribosomal proteins targeted to the organelles but not in those that function in cytosolic ribosomes. Overall, these findings support the hypothesis that rapid organelle genome evolution has selected for compensatory mutations in nuclear-encoded proteins. We conclude that coevolution between interacting subunits encoded in different genomic compartments within the eukaryotic cell is an important determinant of variation in rates of protein sequence evolution.

  11. Adaptive Mistranslation Accelerates the Evolution of Fluconazole Resistance and Induces Major Genomic and Gene Expression Alterations in Candida albicans.

    PubMed

    Weil, Tobias; Santamaría, Rodrigo; Lee, Wanseon; Rung, Johan; Tocci, Noemi; Abbey, Darren; Bezerra, Ana R; Carreto, Laura; Moura, Gabriela R; Bayés, Mónica; Gut, Ivo G; Csikasz-Nagy, Attila; Cavalieri, Duccio; Berman, Judith; Santos, Manuel A S

    2017-01-01

    Regulated erroneous protein translation (adaptive mistranslation) increases proteome diversity and produces advantageous phenotypic variability in the human pathogen Candida albicans. It also increases fitness in the presence of fluconazole, but the underlying molecular mechanism is not understood. To address this question, we evolved hypermistranslating and wild-type strains in the absence and presence of fluconazole and compared their fluconazole tolerance and resistance trajectories during evolution. The data show that mistranslation increases tolerance and accelerates the acquisition of resistance to fluconazole. Genome sequencing, array-based comparative genome analysis, and gene expression profiling revealed that during the course of evolution in fluconazole, the range of mutational and gene deregulation differences was distinctively different and broader in the hypermistranslating strain, including multiple chromosome duplications, partial chromosome deletions, and polyploidy. Especially, the increased accumulation of loss-of-heterozygosity events, aneuploidy, translational and cell surface modifications, and differences in drug efflux seem to mediate more rapid drug resistance acquisition under mistranslation. Our observations support a pivotal role for adaptive mistranslation in the evolution of drug resistance in C. albicans. IMPORTANCE Infectious diseases caused by drug-resistant fungi are an increasing threat to public health because of the high mortality rates and high costs associated with treatment. Thus, understanding of the molecular mechanisms of drug resistance is of crucial interest for the medical community. Here we investigated the role of regulated protein mistranslation, a characteristic mechanism used by C. albicans to diversify its proteome, in the evolution of fluconazole resistance. Such codon ambiguity is usually considered highly deleterious, yet recent studies found that mistranslation can boost adaptation in stressful environments

  12. Isolation of Hox Cluster Genes from Insects Reveals an Accelerated Sequence Evolution Rate

    PubMed Central

    Hadrys, Heike; Simon, Sabrina; Kaune, Barbara; Schmitt, Oliver; Schöner, Anja; Jakob, Wolfgang; Schierwater, Bernd

    2012-01-01

    Among gene families it is the Hox genes and among metazoan animals it is the insects (Hexapoda) that have attracted particular attention for studying the evolution of development. Surprisingly though, no Hox genes have been isolated from 26 out of 35 insect orders yet, and the existing sequences derive mainly from only two orders (61% from Hymenoptera and 22% from Diptera). We have designed insect specific primers and isolated 37 new partial homeobox sequences of Hox cluster genes (lab, pb, Hox3, ftz, Antp, Scr, abd-a, Abd-B, Dfd, and Ubx) from six insect orders, which are crucial to insect phylogenetics. These new gene sequences provide a first step towards comparative Hox gene studies in insects. Furthermore, comparative distance analyses of homeobox sequences reveal a correlation between gene divergence rate and species radiation success with insects showing the highest rate of homeobox sequence evolution. PMID:22685537

  13. Tolerance of whole-genome doubling propagates chromosomal instability and accelerates cancer genome evolution.

    PubMed

    Dewhurst, Sally M; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Grönroos, Eva; Endesfelder, David; Joshi, Tejal; Mouradov, Dmitri; Gibbs, Peter; Ward, Robyn L; Hawkins, Nicholas J; Szallasi, Zoltan; Sieber, Oliver M; Swanton, Charles

    2014-02-01

    The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells that survive genome doubling demonstrate increased tolerance to chromosome aberrations. Tetraploid cells do not exhibit increased frequencies of structural or numerical CIN per chromosome. However, the tolerant phenotype in tetraploid cells, coupled with a doubling of chromosome aberrations per cell, allows chromosome abnormalities to evolve specifically in tetraploids, recapitulating chromosomal changes in genomically complex colorectal tumors. Finally, a genome-doubling event is independently predictive of poor relapse-free survival in early-stage disease in two independent cohorts in multivariate analyses [discovery data: hazard ratio (HR), 4.70, 95% confidence interval (CI), 1.04-21.37; validation data: HR, 1.59, 95% CI, 1.05-2.42]. These data highlight an important role for the tolerance of genome doubling in driving cancer genome evolution. Our work sheds light on the importance of whole-genome–doubling events in colorectal cancer evolution. We show that tetraploid cells undergo rapid genomic changes and recapitulate the genetic alterations seen in chromosomally unstable tumors. Furthermore, we demonstrate that a genome-doubling event is prognostic of poor relapse-free survival in this disease type. 2014 AACR

  14. Effect of Austenite Deformation on the Microstructure Evolution and Grain Refinement Under Accelerated Cooling Conditions

    NASA Astrophysics Data System (ADS)

    Zhao, H.; Palmiere, E. J.

    2017-07-01

    Although there has been much research regarding the effect of austenite deformation on accelerated cooled microstructures in microalloyed steels, there is still a lack of accurate data on boundary densities and effective grain sizes. Previous results observed from optical micrographs are not accurate enough, because, for displacive transformation products, a substantial part of the boundaries have disorientation angles below 15 deg. Therefore, in this research, a niobium microalloyed steel was used and electron backscattering diffraction mappings were performed on all of the transformed microstructures to obtain accurate results on boundary densities and grain refinement. It was found that with strain rising from 0 to 0.5, a transition from bainitic ferrite to acicular ferrite occurs and the effective grain size reduces from 5.7 to 3.1 μm. When further increasing strain from 0.5 to 0.7, dynamic recrystallization was triggered and postdynamic softening occurred during the accelerated cooling, leading to an inhomogeneous and coarse transformed microstructure. In the entire strain range, the density changes of boundaries with different disorientation angles are distinct, due to different boundary formation mechanisms. Finally, the controversial influence of austenite deformation on effective grain size of low-temperature transformation products was argued to be related to the differences in transformation conditions and final microstructures.

  15. Future evolution and finite-time singularities in F(R) gravity unifying inflation and cosmic acceleration

    SciTech Connect

    Nojiri, Shin'ichi; Odintsov, Sergei D.

    2008-08-15

    We study the future evolution of quintessence/phantom-dominated epoch in modified F(R) gravity which unifies the early-time inflation with late-time acceleration and which is consistent with observational tests. Using the reconstruction technique it is demonstrated that there are models where any known (big rip, II, III, or IV type) singularity may classically occur. From another side, in Einstein frame (scalar-tensor description) only IV type singularity occurs. Near the singularity the classical description breaks up, and it is demonstrated that quantum effects act against the singularity and may prevent its appearance. The realistic F(R) gravity which is future singularity free is proposed. We point out that additional modification of any F(R) gravity by the terms relevant at the early universe is possible, in such a way that future singularity does not occur even classically.

  16. Nonlinear evolution of Buneman instability and its implication for electron acceleration in high Mach number collisionless perpendicular shocks

    SciTech Connect

    Amano, Takanobu; Hoshino, Masahiro

    2009-10-15

    Nonlinear evolution of the Buneman instability and its application to electron acceleration in collisionless shocks are discussed. Two-dimensional particle-in-cell simulations show that the saturation level of the instability is reduced from one-dimensional simulation results. It is demonstrated that the reduced saturation level is due to the resonant wave-particle interactions with large amplitude obliquely propagating waves. A new estimate for the saturation level is given by considering the interactions with oblique modes. The effects of the large amplitude oblique modes on electron shock surfing acceleration that is mainly controlled by the Buneman instability are also investigated. Two-dimensional particle-in-cell simulations of the shock transition region are performed by adopting a local model with the periodic boundary condition. The results indicate that the presence of oblique modes introduces a stochastic behavior to the trajectories of energetic electrons. The maximum energy is limited by the finite lifetime of the instability in the present periodic model. However, this will not be the case in the realistic shock transition region. The application to realistic shocks with Mach numbers typical of supernova remnants is also discussed.

  17. Nonlinear evolution of Buneman instability and its implication for electron acceleration in high Mach number collisionless perpendicular shocks

    NASA Astrophysics Data System (ADS)

    Amano, Takanobu; Hoshino, Masahiro

    2009-10-01

    Nonlinear evolution of the Buneman instability and its application to electron acceleration in collisionless shocks are discussed. Two-dimensional particle-in-cell simulations show that the saturation level of the instability is reduced from one-dimensional simulation results. It is demonstrated that the reduced saturation level is due to the resonant wave-particle interactions with large amplitude obliquely propagating waves. A new estimate for the saturation level is given by considering the interactions with oblique modes. The effects of the large amplitude oblique modes on electron shock surfing acceleration that is mainly controlled by the Buneman instability are also investigated. Two-dimensional particle-in-cell simulations of the shock transition region are performed by adopting a local model with the periodic boundary condition. The results indicate that the presence of oblique modes introduces a stochastic behavior to the trajectories of energetic electrons. The maximum energy is limited by the finite lifetime of the instability in the present periodic model. However, this will not be the case in the realistic shock transition region. The application to realistic shocks with Mach numbers typical of supernova remnants is also discussed.

  18. Community-level education accelerates the cultural evolution of fertility decline.

    PubMed

    Colleran, Heidi; Jasienska, Grazyna; Nenko, Ilona; Galbarczyk, Andrzej; Mace, Ruth

    2014-03-22

    Explaining why fertility declines as populations modernize is a profound theoretical challenge. It remains unclear whether the fundamental drivers are economic or cultural in nature. Cultural evolutionary theory suggests that community-level characteristics, for example average education, can alter how low-fertility preferences are transmitted and adopted. These assumptions have not been empirically tested. Here, we show that community-level education accelerates fertility decline in a way that is neither predicted by individual characteristics, nor by the level of economic modernization in a population. In 22 high-fertility communities in Poland, fertility converged on a smaller family size as average education in the community increased-indeed community-level education had a larger impact on fertility decline than did individual education. This convergence was not driven by educational levels being more homogeneous, but by less educated women having fewer children than expected, and more highly educated social networks, when living among more highly educated neighbours. The average level of education in a community may influence the social partners women interact with, both within and beyond their immediate social environments, altering the reproductive norms they are exposed to. Given a critical mass of highly educated women, less educated neighbours may adopt their reproductive behaviour, accelerating the pace of demographic transition. Individual characteristics alone cannot capture these dynamics and studies relying solely on them may systematically underestimate the importance of cultural transmission in driving fertility declines. Our results are inconsistent with a purely individualistic, rational-actor model of fertility decline and suggest that optimization of reproduction is partly driven by cultural dynamics beyond the individual.

  19. Community-level education accelerates the cultural evolution of fertility decline

    PubMed Central

    Colleran, Heidi; Jasienska, Grazyna; Nenko, Ilona; Galbarczyk, Andrzej; Mace, Ruth

    2014-01-01

    Explaining why fertility declines as populations modernize is a profound theoretical challenge. It remains unclear whether the fundamental drivers are economic or cultural in nature. Cultural evolutionary theory suggests that community-level characteristics, for example average education, can alter how low-fertility preferences are transmitted and adopted. These assumptions have not been empirically tested. Here, we show that community-level education accelerates fertility decline in a way that is neither predicted by individual characteristics, nor by the level of economic modernization in a population. In 22 high-fertility communities in Poland, fertility converged on a smaller family size as average education in the community increased—indeed community-level education had a larger impact on fertility decline than did individual education. This convergence was not driven by educational levels being more homogeneous, but by less educated women having fewer children than expected, and more highly educated social networks, when living among more highly educated neighbours. The average level of education in a community may influence the social partners women interact with, both within and beyond their immediate social environments, altering the reproductive norms they are exposed to. Given a critical mass of highly educated women, less educated neighbours may adopt their reproductive behaviour, accelerating the pace of demographic transition. Individual characteristics alone cannot capture these dynamics and studies relying solely on them may systematically underestimate the importance of cultural transmission in driving fertility declines. Our results are inconsistent with a purely individualistic, rational-actor model of fertility decline and suggest that optimization of reproduction is partly driven by cultural dynamics beyond the individual. PMID:24500166

  20. Accelerating Markov chain Monte Carlo simulation by differential evolution with self-adaptive randomized subspace sampling

    SciTech Connect

    Vrugt, Jasper A; Hyman, James M; Robinson, Bruce A; Higdon, Dave; Ter Braak, Cajo J F; Diks, Cees G H

    2008-01-01

    Markov chain Monte Carlo (MCMC) methods have found widespread use in many fields of study to estimate the average properties of complex systems, and for posterior inference in a Bayesian framework. Existing theory and experiments prove convergence of well constructed MCMC schemes to the appropriate limiting distribution under a variety of different conditions. In practice, however this convergence is often observed to be disturbingly slow. This is frequently caused by an inappropriate selection of the proposal distribution used to generate trial moves in the Markov Chain. Here we show that significant improvements to the efficiency of MCMC simulation can be made by using a self-adaptive Differential Evolution learning strategy within a population-based evolutionary framework. This scheme, entitled DiffeRential Evolution Adaptive Metropolis or DREAM, runs multiple different chains simultaneously for global exploration, and automatically tunes the scale and orientation of the proposal distribution in randomized subspaces during the search. Ergodicity of the algorithm is proved, and various examples involving nonlinearity, high-dimensionality, and multimodality show that DREAM is generally superior to other adaptive MCMC sampling approaches. The DREAM scheme significantly enhances the applicability of MCMC simulation to complex, multi-modal search problems.

  1. Accelerated evolution of developmentally biased genes in the tetraphenic ant Cardiocondyla obscurior.

    PubMed

    Schrader, Lukas; Helanterä, Heikki; Oettler, Jan

    2016-12-20

    Plastic gene expression underlies phenotypic plasticity and plastically expressed genes evolve under different selection regimes compared to ubiquitously expressed genes. Social insects are well-suited models to elucidate the evolutionary dynamics of plastic genes for their genetically and environmentally induced discrete polymorphisms. Here, we study the evolution of plastically expressed genes in the ant Cardiocondyla obscurior - a species that produces two discrete male morphs in addition to the typical female polymorphism of workers and queens. Based on individual-level gene expression data from 28 early third instar larvae, we test whether the same evolutionary dynamics that pertain to plastically expressed genes in adults also pertain to genes with plastic expression during development. In order to quantify plasticity of gene expression over multiple contrasts, we develop a novel geometric measure. For genes expressed during development, we show that plasticity of expression is positively correlated with evolutionary rates. We furthermore find a strong correlation between expression plasticity and expression variation within morphs, suggesting a close link between active and passive plasticity of gene expression. Our results support the notion of relaxed selection and neutral processes as important drivers in the evolution of adaptive plasticity.

  2. Comprehensive analysis of animal TALE homeobox genes: new conserved motifs and cases of accelerated evolution.

    PubMed

    Mukherjee, Krishanu; Bürglin, Thomas R

    2007-08-01

    TALE homeodomain proteins are an ancient subgroup within the group of homeodomain transcription factors that play important roles in animal, plant, and fungal development. We have extracted the full complement of TALE superclass homeobox genes from the genome projects of seven protostomes, seven deuterostomes, and Nematostella. This was supplemented with TALE homeobox genes from additional species and phylogenetic analyses were carried out with 276 sequences. We found 20 homeobox genes and 4 pseudogenes in humans, 21 genes in mouse, 8 genes in Drosophila, and 5 genes plus one truncated gene in Caenorhabditis elegans. Apart from the previously identified TALE classes MEIS, PBC, IRO, and TGIF, a novel class is identified, termed MOHAWK (MKX). Further, we show that the MEIS class can be divided into two families, PREP and MEIS. Prep genes have previously only been described in vertebrates but are lacking in Drosophila. Here we identify orthologues in other insect taxa as well as in the cnidarian Nematostella. In C. elegans, a divergent Prep protein has lost the homeodomain. Full-length multiple sequence alignment of the protostome and deuterostome sequences allowed us to identify several novel conserved motifs within the MKX, TGIF, and MEIS classes. Phylogenetic analyses revealed fast-evolving PBC class genes; in particular, some X-linked PBC genes in nematodes are subject to rapid evolution. In addition, several instances of gene loss were identified. In conclusion, our comprehensive analysis provides a defining framework for the classification of animal TALE homeobox genes and the understanding of their evolution.

  3. Tolerance whole of genome doubling propagates chromosomal instability and accelerates cancer genome evolution

    PubMed Central

    Burrell, Rebecca A; Rowan, Andrew J; Grönroos, Eva; Endesfelder, David; Joshi, Tejal; Mouradov, Dmitri; Gibbs, Peter; Ward, Robyn L.; Hawkins, Nicholas J.; Szallasi, Zoltan; Sieber, Oliver M.; Swanton, Charles

    2015-01-01

    The contribution of whole genome doubling to chromosomal instability (CIN) and tumour evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells that survive genome doubling demonstrate increased tolerance to chromosome aberrations. Tetraploid cells do not exhibit increased frequencies of structural or numerical CIN per chromosome. However, the tolerant phenotype in tetraploid cells, coupled with a doubling of chromosome aberrations per cell, allows chromosome abnormalities to evolve specifically in tetraploids, recapitulating chromosomal changes in genomically complex colorectal tumours. Finally, a genome-doubling event is independently predictive of poor relapse-free survival in early stage disease in two independent cohorts in multivariate analyses (discovery data: HR=4.70, 95% CI 1.04-21.37, validation data: HR=1.59, 95% CI 1.05-2.42). These data highlight an important role for the tolerance of genome doubling in driving cancer genome evolution. PMID:24436049

  4. Abrupt plate acceleration through oblique rifting: Geodynamic aspects of Gulf of California evolution

    NASA Astrophysics Data System (ADS)

    Brune, S.

    2016-12-01

    The Gulf of California formed by oblique divergence across the Pacific-North America plate boundary. This presentation combines numerical forward modeling and plate tectonic reconstructions in order to address 2 important aspects of rift dynamics: (1) Plate motions during continental rifting are decisively controlled by the non-linear decay of rift strength. This conclusion is based on a recent plate-kinematic analysis of post-Pangea rift systems (Central Atlantic, South Atlantic, Iberia/Newfoundland, Australia/Antarctica, North Atlantic, South China Sea). In all cases, continental rifting starts with a slow phase followed by an abrupt acceleration within a few My introducing a fast rift phase. Numerical forward modeling with force boundary conditions shows that the two-phase velocity behavior and the rapid speed-up during rifting are intrinsic features of continental rupture that can be robustly inferred for different crust and mantle rheologies. (2) Rift strength depends on the obliquity of the rift system: the force required to maintain a given rift velocity can be computed from simple analytical and more realistic numerical models alike, and both modeling approaches demonstrate that less force is required to perpetuate oblique extension. The reason is that plastic yielding requires a smaller plate boundary force when extension is oblique to the rift trend. Comparing strike slip and pure extension end-member scenarios, it can be shown that about 50% less force is required to deform the lithosphere under strike-slip. This result implies that rift systems involving significant obliquity are mechanically preferred. These two aspects shed new light on the underlying geodynamic causes of Gulf of California rift history. Continental extension is thought to have started in Late Eocene/Oligocene times as part of the southern Basin and Range Province and evolved in a protracted history at low extension rate (≤15 mm/yr). However, with a direction change in Baja

  5. Positive selection drives accelerated evolution of mosquito salivary genes associated with blood-feeding

    PubMed Central

    Arcà, Bruno; Struchiner, Cláudio J.; Pham, Van M.; Sferra, Gabriella; Lombardo, Fabrizio; Pombi, Marco; Ribeiro, José M. C.

    2013-01-01

    Saliva of bloodsucking animals contains dozens to hundreds of proteins that counteract their hosts’ hemostasis, inflammation, and immunity. It was previously observed that salivary proteins involved in hematophagy are much more divergent in their primary sequence than those of housekeeping function, when comparisons were made between closely related organisms. While this pattern of evolution could result from relaxed selection or drift, it could alternatively be the result of positive selection driven by the intense pressure of the host immune system. We investigated the polymorphism of five different genes associated with blood feeding in the mosquito Anopheles gambiae and obtained evidence in four genes for sites with signatures of positive selection. These results add salivary gland genes from bloodsucking arthropods to the small list of genes driven by positive selection. PMID:24237399

  6. Accelerated evolution of the Prdm9 speciation gene across diverse metazoan taxa.

    PubMed

    Oliver, Peter L; Goodstadt, Leo; Bayes, Joshua J; Birtle, Zoë; Roach, Kevin C; Phadnis, Nitin; Beatson, Scott A; Lunter, Gerton; Malik, Harmit S; Ponting, Chris P

    2009-12-01

    The onset of prezygotic and postzygotic barriers to gene flow between populations is a hallmark of speciation. One of the earliest postzygotic isolating barriers to arise between incipient species is the sterility of the heterogametic sex in interspecies' hybrids. Four genes that underlie hybrid sterility have been identified in animals: Odysseus, JYalpha, and Overdrive in Drosophila and Prdm9 (Meisetz) in mice. Mouse Prdm9 encodes a protein with a KRAB motif, a histone methyltransferase domain and several zinc fingers. The difference of a single zinc finger distinguishes Prdm9 alleles that cause hybrid sterility from those that do not. We find that concerted evolution and positive selection have rapidly altered the number and sequence of Prdm9 zinc fingers across 13 rodent genomes. The patterns of positive selection in Prdm9 zinc fingers imply that rapid evolution has acted on the interface between the Prdm9 protein and the DNA sequences to which it binds. Similar patterns are apparent for Prdm9 zinc fingers for diverse metazoans, including primates. Indeed, allelic variation at the DNA-binding positions of human PRDM9 zinc fingers show significant association with decreased risk of infertility. Prdm9 thus plays a role in determining male sterility both between species (mouse) and within species (human). The recurrent episodes of positive selection acting on Prdm9 suggest that the DNA sequences to which it binds must also be evolving rapidly. Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis. We propose a hypothetical model in which incompatibilities between Prdm9-binding specificity and satellite DNAs provide the molecular basis for Prdm9-mediated hybrid sterility. We suggest that Prdm9 should be investigated as a candidate gene in other instances of hybrid sterility in metazoans.

  7. Accelerated evolution of mitochondrial but not nuclear genomes of Hymenoptera: new evidence from crabronid wasps.

    PubMed

    Kaltenpoth, Martin; Showers Corneli, Patrice; Dunn, Diane M; Weiss, Robert B; Strohm, Erhard; Seger, Jon

    2012-01-01

    Mitochondrial genes in animals are especially useful as molecular markers for the reconstruction of phylogenies among closely related taxa, due to the generally high substitution rates. Several insect orders, notably Hymenoptera and Phthiraptera, show exceptionally high rates of mitochondrial molecular evolution, which has been attributed to the parasitic lifestyle of current or ancestral members of these taxa. Parasitism has been hypothesized to entail frequent population bottlenecks that increase rates of molecular evolution by reducing the efficiency of purifying selection. This effect should result in elevated substitution rates of both nuclear and mitochondrial genes, but to date no extensive comparative study has tested this hypothesis in insects. Here we report the mitochondrial genome of a crabronid wasp, the European beewolf (Philanthus triangulum, Hymenoptera, Crabronidae), and we use it to compare evolutionary rates among the four largest holometabolous insect orders (Coleoptera, Diptera, Hymenoptera, Lepidoptera) based on phylogenies reconstructed with whole mitochondrial genomes as well as four single-copy nuclear genes (18S rRNA, arginine kinase, wingless, phosphoenolpyruvate carboxykinase). The mt-genome of P. triangulum is 16,029 bp in size with a mean A+T content of 83.6%, and it encodes the 37 genes typically found in arthropod mt genomes (13 protein-coding, 22 tRNA, and two rRNA genes). Five translocations of tRNA genes were discovered relative to the putative ancestral genome arrangement in insects, and the unusual start codon TTG was predicted for cox2. Phylogenetic analyses revealed significantly longer branches leading to the apocritan Hymenoptera as well as the Orussoidea, to a lesser extent the Cephoidea, and, possibly, the Tenthredinoidea than any of the other holometabolous insect orders for all mitochondrial but none of the four nuclear genes tested. Thus, our results suggest that the ancestral parasitic lifestyle of Apocrita is unlikely

  8. Evolution on neutral networks accelerates the ticking rate of the molecular clock

    PubMed Central

    Manrubia, Susanna; Cuesta, José A.

    2015-01-01

    Large sets of genotypes give rise to the same phenotype, because phenotypic expression is highly redundant. Accordingly, a population can accept mutations without altering its phenotype, as long as the genotype mutates into another one on the same set. By linking every pair of genotypes that are mutually accessible through mutation, genotypes organize themselves into neutral networks (NNs). These networks are known to be heterogeneous and assortative, and these properties affect the evolutionary dynamics of the population. By studying the dynamics of populations on NNs with arbitrary topology, we analyse the effect of assortativity, of NN (phenotype) fitness and of network size. We find that the probability that the population leaves the network is smaller the longer the time spent on it. This progressive ‘phenotypic entrapment’ entails a systematic increase in the overdispersion of the process with time and an acceleration in the fixation rate of neutral mutations. We also quantify the variation of these effects with the size of the phenotype and with its fitness relative to that of neighbouring alternatives. PMID:25392402

  9. Accelerated Evolution of Conserved Noncoding Sequences in theHuman Genome

    SciTech Connect

    Prambhakar, Shyam; Noonan, James P.; Paabo, Svante; Rubin, EdwardM.

    2006-07-06

    Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detect"cryptic" functional elements, which are too weakly conserved amongmammals to distinguish from nonfunctional DNA. To address this problem,we explored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.

  10. A porous proton-relaying metal-organic framework material that accelerates electrochemical hydrogen evolution

    SciTech Connect

    Hod, Idan; Deria, Pravas; Bury, Wojciech; Mondloch, Joseph E.; Kung, Chung-Wei; So, Monica; Sampson, Matthew D.; Peters, Aaron W.; Kubiak, Cliff P.; Farha, Omar K.; Hupp, Joseph T.

    2015-09-14

    The availability of efficient hydrogen evolution reaction (HER) catalysts is of high importance for solar fuel technologies aimed at reducing future carbon emissions. Even though Pt electrodes are excellent HER electrocatalysts, commercialization of large-scale hydrogen production technology requires finding an equally efficient, low-cost, earth-abundant alternative. Here, high porosity, metal-organic framework (MOF) films have been used as scaffolds for the deposition of a Ni-S electrocatalyst. Compared with an MOF-free Ni-S, the resulting hybrid materials exhibit significantly enhanced performance for HER from aqueous acid, decreasing the kinetic overpotential by more than 200 mV at a benchmark current density of 10 mA cm−2. In conclusion, although the initial aim was to improve electrocatalytic activity by greatly boosting the active area of the Ni-S catalyst, the performance enhancements instead were found to arise primarily from the ability of the proton-conductive MOF to favourably modify the immediate chemical environment of the sulfide-based catalyst.

  11. A porous proton-relaying metal-organic framework material that accelerates electrochemical hydrogen evolution

    DOE PAGES

    Hod, Idan; Deria, Pravas; Bury, Wojciech; ...

    2015-09-14

    The availability of efficient hydrogen evolution reaction (HER) catalysts is of high importance for solar fuel technologies aimed at reducing future carbon emissions. Even though Pt electrodes are excellent HER electrocatalysts, commercialization of large-scale hydrogen production technology requires finding an equally efficient, low-cost, earth-abundant alternative. Here, high porosity, metal-organic framework (MOF) films have been used as scaffolds for the deposition of a Ni-S electrocatalyst. Compared with an MOF-free Ni-S, the resulting hybrid materials exhibit significantly enhanced performance for HER from aqueous acid, decreasing the kinetic overpotential by more than 200 mV at a benchmark current density of 10 mA cm−2. In conclusion, althoughmore » the initial aim was to improve electrocatalytic activity by greatly boosting the active area of the Ni-S catalyst, the performance enhancements instead were found to arise primarily from the ability of the proton-conductive MOF to favourably modify the immediate chemical environment of the sulfide-based catalyst.« less

  12. A porous proton-relaying metal-organic framework material that accelerates electrochemical hydrogen evolution

    PubMed Central

    Hod, Idan; Deria, Pravas; Bury, Wojciech; Mondloch, Joseph E.; Kung, Chung-Wei; So, Monica; Sampson, Matthew D.; Peters, Aaron W.; Kubiak, Cliff P.; Farha, Omar K.; Hupp, Joseph T.

    2015-01-01

    The availability of efficient hydrogen evolution reaction (HER) catalysts is of high importance for solar fuel technologies aimed at reducing future carbon emissions. Even though Pt electrodes are excellent HER electrocatalysts, commercialization of large-scale hydrogen production technology requires finding an equally efficient, low-cost, earth-abundant alternative. Here, high porosity, metal-organic framework (MOF) films have been used as scaffolds for the deposition of a Ni-S electrocatalyst. Compared with an MOF-free Ni-S, the resulting hybrid materials exhibit significantly enhanced performance for HER from aqueous acid, decreasing the kinetic overpotential by more than 200 mV at a benchmark current density of 10 mA cm−2. Although the initial aim was to improve electrocatalytic activity by greatly boosting the active area of the Ni-S catalyst, the performance enhancements instead were found to arise primarily from the ability of the proton-conductive MOF to favourably modify the immediate chemical environment of the sulfide-based catalyst. PMID:26365764

  13. On the evolution of spherical gas interfaces accelerated by a planar shock wave

    NASA Astrophysics Data System (ADS)

    Zhai, Zhigang; Si, Ting; Luo, Xisheng; Yang, Jiming

    2011-08-01

    The interaction of a planar shock wave with a spherical gas interface (SF6 or helium) surrounded by air is studied experimentally and numerically. By means of the high-speed schlieren photography with high time resolutions and the numerical method VAS2D, the detailed flow field structures including the evolution of interfaces and the development of wave patterns are obtained. The sequences of schlieren frames of SF6 show that the refracted shock wave converges inside the volume and causes the shock focusing within the bubble interface, resulting in an outward jet. The SF6 jet is different from the krypton jet studied because of the difference in their acoustic impedances. The pressure perturbation plays an important role in the jet formation. Quantitative data of the evolving interface length, height, and vortex spacing as well as the displacements of the interface and the jet are acquired and compared. The generation and distribution of vorticity are also analyzed numerically and are found to be the dominant factors for the interface deformation and the resulting turbulent mixing. Furthermore, the velocities of the interfaces and shock waves obtained from the x-t diagrams in the experimental and numerical photographs are compared with those predicted from one-dimensional gasdynamics. In this way, the air contaminations of both gases are re-evaluated and it is shown that the contamination by air inside the helium bubble is significant while it has just small influence in the SF6 case, which confirms the findings in literatures.

  14. Postcopulatory sexual selection is associated with accelerated evolution of sperm morphology.

    PubMed

    Rowe, Melissah; Albrecht, Tomáš; Cramer, Emily R A; Johnsen, Arild; Laskemoen, Terje; Weir, Jason T; Lifjeld, Jan T

    2015-04-01

    Rapid diversification of sexual traits is frequently attributed to sexual selection, though explicit tests of this hypothesis remain limited. Spermatozoa exhibit remarkable variability in size and shape, and studies report a correlation between sperm morphology (sperm length and shape) and sperm competition risk or female reproductive tract morphology. However, whether postcopulatory processes (e.g., sperm competition and cryptic female choice) influence the speed of evolutionary diversification in sperm form is unknown. Using passerine birds, we quantified evolutionary rates of sperm length divergence among lineages (i.e., species pairs) and determined whether these rates varied with the level of sperm competition (estimated as relative testes mass). We found that relative testes mass was significantly and positively associated with more rapid phenotypic divergence in sperm midpiece and flagellum lengths, as well as total sperm length. In contrast, there was no association between relative testes mass and rates of evolutionary divergence in sperm head size, and models suggested that head length is evolutionarily constrained. Our results are the first to show an association between the strength of sperm competition and the speed of sperm evolution, and suggest that postcopulatory sexual selection promotes rapid evolutionary diversification of sperm morphology. © 2015 The Author(s).

  15. A porous proton-relaying metal-organic framework material that accelerates electrochemical hydrogen evolution.

    PubMed

    Hod, Idan; Deria, Pravas; Bury, Wojciech; Mondloch, Joseph E; Kung, Chung-Wei; So, Monica; Sampson, Matthew D; Peters, Aaron W; Kubiak, Cliff P; Farha, Omar K; Hupp, Joseph T

    2015-09-14

    The availability of efficient hydrogen evolution reaction (HER) catalysts is of high importance for solar fuel technologies aimed at reducing future carbon emissions. Even though Pt electrodes are excellent HER electrocatalysts, commercialization of large-scale hydrogen production technology requires finding an equally efficient, low-cost, earth-abundant alternative. Here, high porosity, metal-organic framework (MOF) films have been used as scaffolds for the deposition of a Ni-S electrocatalyst. Compared with an MOF-free Ni-S, the resulting hybrid materials exhibit significantly enhanced performance for HER from aqueous acid, decreasing the kinetic overpotential by more than 200 mV at a benchmark current density of 10 mA cm(-2). Although the initial aim was to improve electrocatalytic activity by greatly boosting the active area of the Ni-S catalyst, the performance enhancements instead were found to arise primarily from the ability of the proton-conductive MOF to favourably modify the immediate chemical environment of the sulfide-based catalyst.

  16. A porous proton-relaying metal-organic framework material that accelerates electrochemical hydrogen evolution

    NASA Astrophysics Data System (ADS)

    Hod, Idan; Deria, Pravas; Bury, Wojciech; Mondloch, Joseph E.; Kung, Chung-Wei; So, Monica; Sampson, Matthew D.; Peters, Aaron W.; Kubiak, Cliff P.; Farha, Omar K.; Hupp, Joseph T.

    2015-09-01

    The availability of efficient hydrogen evolution reaction (HER) catalysts is of high importance for solar fuel technologies aimed at reducing future carbon emissions. Even though Pt electrodes are excellent HER electrocatalysts, commercialization of large-scale hydrogen production technology requires finding an equally efficient, low-cost, earth-abundant alternative. Here, high porosity, metal-organic framework (MOF) films have been used as scaffolds for the deposition of a Ni-S electrocatalyst. Compared with an MOF-free Ni-S, the resulting hybrid materials exhibit significantly enhanced performance for HER from aqueous acid, decreasing the kinetic overpotential by more than 200 mV at a benchmark current density of 10 mA cm-2. Although the initial aim was to improve electrocatalytic activity by greatly boosting the active area of the Ni-S catalyst, the performance enhancements instead were found to arise primarily from the ability of the proton-conductive MOF to favourably modify the immediate chemical environment of the sulfide-based catalyst.

  17. Flow Visualization and Measurements of the Mixing Evolution of a Shock-Accelerated Gas Curtain

    SciTech Connect

    Prestridge, K.; Vorobieff, P.V.; Rightley, P.M.; Benjamin, R.F

    1999-07-19

    We describe a highly-detailed experimental characterization of the impulsively driven Rayleigh-Taylor instability, called the Richtmyer-Meshkov instability. This instability is produced by flowing a diffuse, vertical curtain of heavy gas (SF{sub 6}) into the test section of an air-filled horizontally oriented shock tube. The instability evolves after the passage of a Mach 1.2 shock past the curtain, and the development of the curtain is visualized by seeding the SF{sub 6} with small (d{approximately}0.5 and micro;m) glycol droplets using a modified theatrical fog generator. Because the event lasts only 1 ms and the initial conditions vary from test to test, rapid and complete data acquisition is required in order to characterize the initial and dynamic conditions for each experimental shot. Through the use of a custom-built pulsed Nd: YAG laser, we are able to image the flowfield at seven different times. We acquire a double-pulsed image of the flow with the use of a second pulsed Nd:YAG, which is used to determine the instantaneous velocity field using Particle Image Velocimetry (PIV). During a single experiment, high resolution images of the initial conditions and dynamic conditions are acquired using three CCD cameras. Issues of the fidelity of the flow seeding technique and the reliability of the PIV technique will be addressed. We have successfully provided interesting data through analysis of the images alone, and we are hoping that PIV information will be able to add further physical insight to the evolution of the RM instability and the transition to turbulence.

  18. Evaluation of whether accelerated protein evolution in chordates has occurred before, after, or simultaneously with gene duplication.

    PubMed

    Johnston, Catrióna R; O'Dushlaine, Colm; Fitzpatrick, David A; Edwards, Richard J; Shields, Denis C

    2007-01-01

    Gene duplication and loss are predicted to be at least of the order of the substitution rate and are key contributors to the development of novel gene function and overall genome evolution. Although it has been established that proteins evolve more rapidly after gene duplication, we were interested in testing to what extent this reflects causation or association. Therefore, we investigated the rate of evolution prior to gene duplication in chordates. Two patterns emerged; firstly, branches, which are both preceded by a duplication and followed by a duplication, display an elevated rate of amino acid replacement. This is reflected in the ratio of nonsynonymous to synonymous substitution (mean nonsynonymous to synonymous nucleotide substitution rate ratio [Ka:Ks]) of 0.44 compared with branches preceded by and followed by a speciation (mean Ka:Ks of 0.23). The observed patterns suggest that there can be simultaneous alteration in the selection pressures on both gene duplication and amino acid replacement, which may be consistent with co-occurring increases in positive selection, or alternatively with concurrent relaxation of purifying selection. The pattern is largely, but perhaps not completely, explained by the existence of certain families that have elevated rates of both gene duplication and amino acid replacement. Secondly, we observed accelerated amino acid replacement prior to duplication (mean Ka:Ks for postspeciation preduplication branches was 0.27). In some cases, this could reflect adaptive changes in protein function precipitating a gene duplication event. In conclusion, the circumstances surrounding the birth of new proteins may frequently involve a simultaneous change in selection pressures on both gene-copy number and amino acid replacement. More precise modeling of the relative importance of preduplication, postduplication, and simultaneous amino acid replacement will require larger and denser genomic data sets from multiple species, allowing

  19. Mosaic evolution of neural development in anurans: acceleration of spinal cord development in the direct developing frog Eleutherodactylus coqui.

    PubMed

    Schlosser, Gerhard

    2003-02-01

    Previous studies have shown that spinal cord development in direct developing frogs of the genus Eleutherodactylus, which have evolutionarily lost the tadpole stage, differs from that in biphasically developing anurans (with the larval and the adult stage separated by metamorphosis). The present study of spinal cord development in Eleutherodactylus coqui provides additional information about neurogenesis, neuronal differentiation and growth analyzed by immunostaining for proliferating cell nuclear antigen (PCNA), in situ hybridization for NeuroD, and morphometric measurements in various developmental stages. Furthermore, spinal cord development in the frogs Discoglossus pictus, Xenopus laevis, and Physalaemus pustulosus, which belong to different anuran families but all exhibit biphasic development, was similarly analyzed. This comparative analysis allows inference of the ancestral anuran pattern of spinal cord development and how it has been modified during the evolution of Eleutherodactylus. All biphasically developing frogs analyzed share a similar pattern of spinal cord development, suggesting that this is ancestral for anurans: after neural tube closure, levels of proliferation and neurogenesis in the spinal cord were low throughout embryogenesis until they were upregulated drastically at early larval stages followed by development of the lateral motor columns. In contrast, no such quiescent embryonic period exists in E. coqui, where rapid growth, high levels of proliferation and neurogenesis, and early formation of lateral motor columns occur shortly after neural tube closure, while other parts of the central nervous system develop more slowly. Thus, spinal cord development has been accelerated during the evolution of Eleutherodactylus relative to the development of other parts of the central nervous system, probably related to the precocious development of limbs in this lineage.

  20. Recent acceleration of ice loss in the Northern Patagonia Icefield based on an updated decennial evolution

    NASA Astrophysics Data System (ADS)

    López, P.; Casassa, G.

    2011-12-01

    Ice elevation changes of the Northern Patagonia Icefield (NPI) were analyzed by comparing three Digital Elevation Models (DEM) corresponding to 1975 (constructed based on topographic maps), the SRTM DEM of 2000 yr and a SPOT 5 DEM of 2005. In addition, the glacier length fluctuations and the surface area evolution between 2001 and 2011 of 25 glaciers of the NPI were studied: the information extracted from the Landsat ETM+ satellite image of 11 March 2001 was compared to the measurements performed based on the Landsat ETM+ satellite image of 19 February 2011. From a global point of view, the majority of the studied glaciers thinned, retreated and lost surface between 2001 and 2011, only few glaciers (Leones, Nef, Pared Sur and Soler) located on the eastern side of the NPI have been stable. Glaciers located on the western side of the NPI suffered a stronger wasting compared to the glaciers located on the eastern side. Overall, over the ablation areas of the NPI (below 1150 m a.s.l.) a more rapid thinning of 2.6 m yr-1 occurred between 2000 and 2005 yr compared to the period 1975-2000, in which a mean thinning of 1.7 m yr-1 was measured for the same zones of the NPI. For the whole period (1975-2005) the most important thinning of the ablation areas has been estimated for HPN-1 Glacier (4.4 m yr-1) followed by Benito (3.4 m yr-1), Fraenkel (2.4 m yr-1), Gualas (2.1 m yr-1) and Acodado glaciers, all of them located on the western side of the NPI. Between 2001 and 2011, a noteworthy retreat of 1.9 km was experienced by Gualas Glacier and by Reichert Glacier with 1.6 km, both located on the north-western side of the NPI. On the south-western side of the NPI, during the same decennia, Steffen Glacier experienced a remarkable retreat of 1.6 km as well. During the 2001-2011 period, Steffen Glacier more than doubled its rate of retreat (compared to the 1979-2001 period) and experienced the disintegration of its main front as well as a lateral tongue that retreated 3.1 km. The

  1. Activation-induced cytidine deaminase accelerates clonal evolution in BCR-ABL1-driven B cell lineage acute lymphoblastic leukemia

    PubMed Central

    Gruber, Tanja Andrea; Chang, Mi Sook; Sposto, Richard; Müschen, Markus

    2010-01-01

    Activation-Induced Cytidine Deaminase (AID) is required for somatic hypermutation and immunoglobulin (Ig) class switch recombination in germinal center B cells. Occasionally, AID can target non-Ig genes and thereby promote GC B cell lymphomagenesis. We recently demonstrated that the oncogenic BCR-ABL1 kinase induces aberrant expression of AID in pre-B acute lymphoblastic leukemia (ALL) and lymphoid CML blast crisis. To elucidate the biological significance of aberrant AID expression, we studied loss of AID function in a murine model of BCR-ABL1 ALL. Mice transplanted with BCR-ABL1-transduced AID-/- bone marrow had prolonged survival as compared to mice transplanted with leukemia cells generated from AID+/+ bone marrow. Consistent with a causative role of AID in genetic instability, AID-/- leukemia had a lower frequency of amplifications, deletions and a lower frequency of mutations in non-Ig genes including Pax5 and Rhoh as compared to AID+/+ leukemias. AID-/- and AID+/+ ALL cells showed a markedly distinct gene expression pattern and AID-/- ALL cells failed to downregulate a number of tumor suppressor genes including Rhoh, Cdkn1a (p21), and Blnk (SLP65). We conclude that AID accelerates clonal evolution in BCR-ABL1 ALL by enhancing genetic instability, aberrant somatic hypermutation, and by negative regulation of tumor suppressor genes. PMID:20876806

  2. Evolution of the microstructure of unmodified and polymer modified asphalt binders with aging in an accelerated weathering tester.

    PubMed

    Menapace, Ilaria; Masad, Eyad

    2016-09-01

    This paper presents findings on the evolution of the surface microstructure of two asphalt binders, one unmodified and one polymer modified, directly exposed to aging agents with increasing durations. The aging is performed using an accelerated weathering tester, where ultraviolet radiation, oxygen and an increased temperature are applied to the asphalt binder surface. Ultraviolet and dark cycles, which simulated the succession of day and night, alternated during the aging process, and also the temperature varied, which corresponded to typical summer day and night temperatures registered in the state of Qatar. Direct aging of an exposed binder surface is more effective in showing microstructural modifications than previously applied protocols, which involved the heat treatment of binders previously aged with standardized methods. With the new protocol, any molecular rearrangements in the binder surface after aging induced by the heat treatment is prevented. Optical photos show the rippling and degradation of the binder surface due to aging. Microstructure images obtained by means of atomic force microscopy show gradual alteration of the surface due to aging. The original relatively flat microstructure was substituted with a profoundly different microstructure, which significantly protrudes from the surface, and is characterized by various shapes, such as rods, round structures and finally 'flower' or 'leaf' structures.

  3. Evolution.

    ERIC Educational Resources Information Center

    Mayr, Ernst

    1978-01-01

    Traces the history of evolution theory from Lamarck and Darwin to the present. Discusses natural selection in detail. Suggests that, besides biological evolution, there is also a cultural evolution which is more rapid than the former. (MA)

  4. Evolution.

    ERIC Educational Resources Information Center

    Mayr, Ernst

    1978-01-01

    Traces the history of evolution theory from Lamarck and Darwin to the present. Discusses natural selection in detail. Suggests that, besides biological evolution, there is also a cultural evolution which is more rapid than the former. (MA)

  5. A High Performance Platform Based on cDNA Display for Efficient Synthesis of Protein Fusions and Accelerated Directed Evolution.

    PubMed

    Naimuddin, Mohammed; Kubo, Tai

    2016-02-08

    We describe a high performance platform based on cDNA display technology by developing a new modified puromycin linker-oligonucleotide. The linker consists of four major characteristics: a "ligation site" for hybridization and ligation of mRNA by T4 RNA ligase, a "puromycin arm" for covalent linkage of the protein, a "polyadenosine site" for a longer puromycin arm and purification of protein fusions (optional) using oligo-dT matrices, and a "reverse transcription site" for the formation of stable cDNA protein fusions whose cDNA is covalently linked to its encoded protein. The linker was synthesized by a novel branching strategy and provided >8-fold higher yield than previous linkers. This linker enables rapid and highly efficient ligation of mRNA (>90%) and synthesis of protein fusions (∼ 50-95%) in various cell-free expression systems. Overall, this new cDNA display method provides 10-200 fold higher end-usage fusions than previous methods and benefits higher diversity libraries crucial for directed protein/peptide evolution. With the increased efficiency, this system was able to reduce the time for one selection cycle to <8 h and is potentially amenable to high-throughput systems. We demonstrate the efficiency of this system for higher throughput selections of various biomolecular interactions and achieved 30-40-fold enrichment per selection cycle. Furthermore, a 4-fold higher enrichment of Flag-tag was obtained from a doped mixture compared with that of the previous cDNA display method. A three-finger protein library was evolved to isolate superior nanomolar range binding candidates for vascular endothelial growth factor. This method is expected to provide a beneficial impact to accelerated drug discovery and proteome analysis.

  6. Evidence of Accelerated Evolution and Ectodermal-Specific Expression of Presumptive BDS Toxin cDNAs from Anemonia viridis

    PubMed Central

    Nicosia, Aldo; Maggio, Teresa; Mazzola, Salvatore; Cuttitta, Angela

    2013-01-01

    Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging to the β-defensin fold family and were initially described for their antihypertensive and antiviral activities. BDS-1 and BDS-2 are 43 amino acid peptides characterised by three disulfide bonds that act as neurotoxins affecting Kv3.1, Kv3.2 and Kv3.4 channel gating kinetics. In addition, BDS-1 inactivates the Nav1.7 and Nav1.3 channels. The development of a large dataset of A. viridis expressed sequence tags (ESTs) and the identification of 13 putative BDS-like cDNA sequences has attracted interest, especially as scientific and diagnostic tools. A comparison of BDS cDNA sequences showed that the untranslated regions are more conserved than the protein-coding regions. Moreover, the KA/KS ratios calculated for all pairwise comparisons showed values greater than 1, suggesting mechanisms of accelerated evolution. The structures of the BDS homologs were predicted by molecular modelling. All toxins possess similar 3D structures that consist of a triple-stranded antiparallel β-sheet and an additional small antiparallel β-sheet located downstream of the cleavage/maturation site; however, the orientation of the triple-stranded β-sheet appears to differ among the toxins. To characterise the spatial expression profile of the putative BDS cDNA sequences, tissue-specific cDNA libraries, enriched for BDS transcripts, were constructed. In addition, the proper amplification of ectodermal or endodermal markers ensured the tissue specificity of each library. Sequencing randomly selected clones from each library revealed ectodermal-specific expression of ten BDS transcripts, while transcripts of BDS-8, BDS-13, BDS-14 and BDS-15 failed to be retrieved, likely due to under-representation in our

  7. Evidence of accelerated evolution and ectodermal-specific expression of presumptive BDS toxin cDNAs from Anemonia viridis.

    PubMed

    Nicosia, Aldo; Maggio, Teresa; Mazzola, Salvatore; Cuttitta, Angela

    2013-10-30

    Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging to the β-defensin fold family and were initially described for their antihypertensive and antiviral activities. BDS-1 and BDS-2 are 43 amino acid peptides characterised by three disulfide bonds that act as neurotoxins affecting Kv3.1, Kv3.2 and Kv3.4 channel gating kinetics. In addition, BDS-1 inactivates the Nav1.7 and Nav1.3 channels. The development of a large dataset of A. viridis expressed sequence tags (ESTs) and the identification of 13 putative BDS-like cDNA sequences has attracted interest, especially as scientific and diagnostic tools. A comparison of BDS cDNA sequences showed that the untranslated regions are more conserved than the protein-coding regions. Moreover, the KA/KS ratios calculated for all pairwise comparisons showed values greater than 1, suggesting mechanisms of accelerated evolution. The structures of the BDS homologs were predicted by molecular modelling. All toxins possess similar 3D structures that consist of a triple-stranded antiparallel β-sheet and an additional small antiparallel β-sheet located downstream of the cleavage/maturation site; however, the orientation of the triple-stranded β-sheet appears to differ among the toxins. To characterise the spatial expression profile of the putative BDS cDNA sequences, tissue-specific cDNA libraries, enriched for BDS transcripts, were constructed. In addition, the proper amplification of ectodermal or endodermal markers ensured the tissue specificity of each library. Sequencing randomly selected clones from each library revealed ectodermal-specific expression of ten BDS transcripts, while transcripts of BDS-8, BDS-13, BDS-14 and BDS-15 failed to be retrieved, likely due to under-representation in our

  8. Acceleration modules in linear induction accelerators

    NASA Astrophysics Data System (ADS)

    Wang, Shao-Heng; Deng, Jian-Jun

    2014-05-01

    The Linear Induction Accelerator (LIA) is a unique type of accelerator that is capable of accelerating kilo-Ampere charged particle current to tens of MeV energy. The present development of LIA in MHz bursting mode and the successful application into a synchrotron have broadened LIA's usage scope. Although the transformer model is widely used to explain the acceleration mechanism of LIAs, it is not appropriate to consider the induction electric field as the field which accelerates charged particles for many modern LIAs. We have examined the transition of the magnetic cores' functions during the LIA acceleration modules' evolution, distinguished transformer type and transmission line type LIA acceleration modules, and re-considered several related issues based on transmission line type LIA acceleration module. This clarified understanding should help in the further development and design of LIA acceleration modules.

  9. Epoch-based likelihood models reveal no evidence for accelerated evolution of viviparity in squamate reptiles in response to cenozoic climate change.

    PubMed

    King, Benedict; Lee, Michael S Y

    2015-09-01

    A broad scale analysis of the evolution of viviparity across nearly 4,000 species of squamates revealed that origins increase in frequency toward the present, raising the question of whether rates of change have accelerated. We here use simulations to show that the increased frequency is within the range expected given that the number of squamate lineages also increases with time. Novel, epoch-based methods implemented in BEAST (which allow rates of discrete character evolution to vary across time-slices) also give congruent results, with recent epochs having very similar rates to older epochs. Thus, contrary to expectations, there was no accelerated burst of origins of viviparity in response to global cooling during the Cenozoic or glacial cycles during the Plio-Pleistocene. However, if one accepts the conventional view that viviparity is more likely to evolve than to be lost, and also the evidence here that viviparity has evolved with similar regularity throughout the last 200 Ma, then the absence of large, ancient clades of viviparous squamates (analogs to therian mammals) requires explanation. Viviparous squamate lineages might be more prone to extinction than are oviparous lineages, due to their prevalance at high elevations and latitudes and thus greater susceptibility to climate fluctuations. If so, the directional bias in character evolution would be offset by the bias in extinction rates. © 2015 Wiley Periodicals, Inc.

  10. Accelerators, Colliders, and Snakes

    NASA Astrophysics Data System (ADS)

    Courant, Ernest D.

    2003-12-01

    The author traces his involvement in the evolution of particle accelerators over the past 50 years. He participated in building the first billion-volt accelerator, the Brookhaven Cosmotron, which led to the introduction of the "strong-focusing" method that has in turn led to the very large accelerators and colliders of the present day. The problems of acceleration of spin-polarized protons are also addressed, with discussions of depolarizing resonances and "Siberian snakes" as a technique for mitigating these resonances.

  11. The Evolution of the single-mode Rayleigh-Taylor instability under the influence of time-dependent accelerations

    NASA Astrophysics Data System (ADS)

    Ramaprabhu, Praveen; Karkhanis, Varad; Banerjee, Rahul; Varshochi, Hilda; Khan, Manoranjan; Lawrie, Andrew; Variable g RT Collaboration

    2015-11-01

    From detailed numerical simulations of the single-mode Rayleigh-Taylor (RT) instability driven by time-varying acceleration histories, we report on several findings of relevance to the performance of Inertial Confinement Fusion capsules. The incompressible, Direct Numerical Simulations (DNS) were performed in two- and three-dimensions, and over a range of density ratios of the fluid combinations (characterized by the Atwood number). We have investigated several acceleration histories, including acceleration profiles g(t) of the general form tn, with n > -2. For the 2D flow, results from numerical simulations are compared with a potential flow model developed and reported as part of this work. When the simulations are extended to three dimensions, bubble and spike growth rates are in agreement with an extension to the drag buoyancy model with modifications for time-dependent acceleration histories. We have come up with simple analytic solutions to the Drag Buoyancy model for variable g flows, and compared the solution with the 2D and 3D DNS results. This work was supported in part by the (U.S.) Department of Energy (DOE) under Contract No. DE-AC52-06NA2-5396.

  12. Evolution of the single-mode Rayleigh-Taylor instability under the influence of time-dependent accelerations.

    PubMed

    Ramaprabhu, P; Karkhanis, V; Banerjee, R; Varshochi, H; Khan, M; Lawrie, A G W

    2016-01-01

    From nonlinear models and direct numerical simulations we report on several findings of relevance to the single-mode Rayleigh-Taylor (RT) instability driven by time-varying acceleration histories. The incompressible, direct numerical simulations (DNSs) were performed in two (2D) and three dimensions (3D), and at a range of density ratios of the fluid combinations (characterized by the Atwood number). We investigated several acceleration histories, including acceleration profiles of the general form g(t)∼t^{n}, with n≥0 and acceleration histories reminiscent of the linear electric motor experiments. For the 2D flow, results from numerical simulations compare well with a 2D potential flow model and solutions to a drag-buoyancy model reported as part of this work. When the simulations are extended to three dimensions, bubble and spike growth rates are in agreement with the so-called level 2 and level 3 models of Mikaelian [K. O. Mikaelian, Phys. Rev. E 79, 065303(R) (2009)10.1103/PhysRevE.79.065303], and with corresponding 3D drag-buoyancy model solutions derived in this article. Our generalization of the RT problem to study variable g(t) affords us the opportunity to investigate the appropriate scaling for bubble and spike amplitudes under these conditions. We consider two candidates, the displacement Z and width s^{2}, but find the appropriate scaling is dependent on the density ratios between the fluids-at low density ratios, bubble and spike amplitudes are explained by both s^{2} and Z, while at large density differences the displacement collapses the spike data. Finally, for all the acceleration profiles studied here, spikes enter a free-fall regime at lower Atwood numbers than predicted by all the models.

  13. Evolution of the single-mode Rayleigh-Taylor instability under the influence of time-dependent accelerations

    NASA Astrophysics Data System (ADS)

    Ramaprabhu, P.; Karkhanis, V.; Banerjee, R.; Varshochi, H.; Khan, M.; Lawrie, A. G. W.

    2016-01-01

    From nonlinear models and direct numerical simulations we report on several findings of relevance to the single-mode Rayleigh-Taylor (RT) instability driven by time-varying acceleration histories. The incompressible, direct numerical simulations (DNSs) were performed in two (2D) and three dimensions (3D), and at a range of density ratios of the fluid combinations (characterized by the Atwood number). We investigated several acceleration histories, including acceleration profiles of the general form g (t ) ˜tn , with n ≥0 and acceleration histories reminiscent of the linear electric motor experiments. For the 2D flow, results from numerical simulations compare well with a 2D potential flow model and solutions to a drag-buoyancy model reported as part of this work. When the simulations are extended to three dimensions, bubble and spike growth rates are in agreement with the so-called level 2 and level 3 models of Mikaelian [K. O. Mikaelian, Phys. Rev. E 79, 065303(R) (2009), 10.1103/PhysRevE.79.065303], and with corresponding 3D drag-buoyancy model solutions derived in this article. Our generalization of the RT problem to study variable g (t ) affords us the opportunity to investigate the appropriate scaling for bubble and spike amplitudes under these conditions. We consider two candidates, the displacement Z and width s2, but find the appropriate scaling is dependent on the density ratios between the fluids—at low density ratios, bubble and spike amplitudes are explained by both s2 and Z , while at large density differences the displacement collapses the spike data. Finally, for all the acceleration profiles studied here, spikes enter a free-fall regime at lower Atwood numbers than predicted by all the models.

  14. Evolutionary dynamics of Rh2 opsins in birds demonstrate an episode of accelerated evolution in the New World warblers (Setophaga)

    PubMed Central

    Price, Trevor D.

    2015-01-01

    Low rates of sequence evolution associated with purifying selection can be interrupted by episodic changes in selective regimes. Visual pigments are a unique system in which we can investigate the functional consequences of genetic changes, therefore connecting genotype to phenotype in the context of natural and sexual selection pressures. We study the RH2 and RH1 visual pigments (opsins) across 22 bird species belonging to two ecologically convergent clades, the New World warblers (Parulidae) and Old World warblers (Phylloscopidae), and evaluate rates of evolution in these clades along with data from 21 additional species. We demonstrate generally slow evolution of these opsins: both Rh1 and Rh2 are highly conserved across Old World and New World warblers. However, Rh2 underwent a burst of evolution within the New World genus Setophaga, where it accumulated substitutions at 6 amino acid sites across the species we studied. Evolutionary analyses revealed a significant increase in dN/dS in Setophaga, implying relatively strong selective pressures to overcome long-standing purifying selection. We studied the effects of each substitution on spectral tuning and found they do not cause large spectral shifts. Thus substitutions may reflect other aspects of opsin function, such as those affecting photosensitivity and/or dark-light adaptation. Although it is unclear what these alterations mean for color perception, we suggest that rapid evolution is linked to sexual selection, given the exceptional plumage colour diversification in Setophaga. PMID:25827331

  15. Evolutionary dynamics of Rh2 opsins in birds demonstrate an episode of accelerated evolution in the New World warblers (Setophaga).

    PubMed

    Bloch, Natasha I; Price, Trevor D; Chang, Belinda S W

    2015-05-01

    Low rates of sequence evolution associated with purifying selection can be interrupted by episodic changes in selective regimes. Visual pigments are a unique system in which we can investigate the functional consequences of genetic changes, therefore connecting genotype to phenotype in the context of natural and sexual selection pressures. We study the RH2 and RH1 visual pigments (opsins) across 22 bird species belonging to two ecologically convergent clades, the New World warblers (Parulidae) and Old World warblers (Phylloscopidae) and evaluate rates of evolution in these clades along with data from 21 additional species. We demonstrate generally slow evolution of these opsins: both Rh1 and Rh2 are highly conserved across Old World and New World warblers. However, Rh2 underwent a burst of evolution within the New World genus Setophaga, where it accumulated substitutions at 6 amino acid sites across the species we studied. Evolutionary analyses revealed a significant increase in dN /dS in Setophaga, implying relatively strong selective pressures to overcome long-standing purifying selection. We studied the effects of each substitution on spectral tuning and found they do not cause large spectral shifts. Thus, substitutions may reflect other aspects of opsin function, such as those affecting photosensitivity and/or dark-light adaptation. Although it is unclear what these alterations mean for colour perception, we suggest that rapid evolution is linked to sexual selection, given the exceptional plumage colour diversification in Setophaga. © 2015 John Wiley & Sons Ltd.

  16. Origin and evolution of viruses: escaped DNA/RNA sequences as evolutionary accelerators and natural biological weapons.

    PubMed

    Bubanovic, Ivan; Najman, Stevo; Andjelkovic, Zlatibor

    2005-01-01

    Knowledge of the origin and evolution of viruses could provide a better understanding of a number of phenomena in the field of evolution such as the origin and development of multi-cellular organisms, the rapid diversification of species over the last 600-700 million years and the lack of transitional forms in the evolution of species ("missing links") etc. One of the possible effects of escaped DNA/RNA sequences or viruses on the evolution of multi-cellular organisms, especially vertebrates, could be the phenomenon of horizontal transmission and dissemination of genes. Interestingly, if so, this effect could be considered as a model of primeval and natural genetic engineering. Other possible links between the evolution of multi-cellular organisms and viruses are connected with the fact that viruses represent the source of different forms of selective pressure such as epidemics of infectious diseases, autoimmunity, malignant alteration, reproductive efficiency, etc. At the same time, these two models of "long-term evolutionary relations" could represent "key factors" in the evolution between viruses and multi-cellular organisms. The capability of a genome to produce and emit DNA/RNA sequences or de novo created viruses which can be a vector of genes horizontal transmission and/or cause selective pressure on concurrent or predator species gives a new characteristic to viruses--the possibility of their acting as natural biological weapons. Finally, possibly evolutionary advantages of this genome capability could be one of explanations for the phenomena such as genome instability and its ability to emit DNA/RNA sequences and/or de novo created viruses, as well as evolutionary conservation of this unique phenomena.

  17. Evolution of structure and properties of VVER-1000 RPV steels under accelerated irradiation up to beyond design fluences

    NASA Astrophysics Data System (ADS)

    Gurovich, B.; Kuleshova, E.; Shtrombakh, Ya.; Fedotova, S.; Maltsev, D.; Frolov, A.; Zabusov, O.; Erak, D.; Zhurko, D.

    2015-01-01

    In this paper comprehensive studies of structure and properties of VVER-1000 RPV steels after the accelerated irradiation to fluences corresponding to extended lifetime up to 60 years or more as well as comparative studies of materials irradiated with different fluxes were carried out. The significant flux effect is confirmed for the weld metal (nickel concentration ⩾1.35%) which is mainly due to development of reversible temper brittleness. The rate of radiation embrittlement of VVER-1000 RPV steels under operation up to 60 years and more (based on the results of accelerated irradiation considering flux effect for weld metal) is expected not to differ significantly from the observed rate under irradiation within surveillance specimens.

  18. Accelerated rates of protein evolution in barley grain and pistil biased genes might be legacy of domestication.

    PubMed

    Shi, Tao; Dimitrov, Ivan; Zhang, Yinling; Tax, Frans E; Yi, Jing; Gou, Xiaoping; Li, Jia

    2015-10-01

    Traits related to grain and reproductive organs in grass crops have been under continuous directional selection during domestication. Barley is one of the oldest domesticated crops in human history. Thus genes associated with the grain and reproductive organs in barley may show evidence of dramatic evolutionary change. To understand how artificial selection contributes to protein evolution of biased genes in different barley organs, we used Digital Gene Expression analysis of six barley organs (grain, pistil, anther, leaf, stem and root) to identify genes with biased expression in specific organs. Pairwise comparisons of orthologs between barley and Brachypodium distachyon, as well as between highland and lowland barley cultivars mutually indicated that grain and pistil biased genes show relatively higher protein evolutionary rates compared with the median of all orthologs and other organ biased genes. Lineage-specific protein evolutionary rates estimation showed similar patterns with elevated protein evolution in barley grain and pistil biased genes, yet protein sequences generally evolve much faster in the lowland barley cultivar. Further functional annotations revealed that some of these grain and pistil biased genes with rapid protein evolution are related to nutrient biosynthesis and cell cycle/division. Our analyses provide insights into how domestication differentially shaped the evolution of genes specific to different organs of a crop species, and implications for future functional studies of domestication genes.

  19. Evolution

    NASA Astrophysics Data System (ADS)

    Peter, Ulmschneider

    When we are looking for intelligent life outside the Earth, there is a fundamental question: Assuming that life has formed on an extraterrestrial planet, will it also develop toward intelligence? As this is hotly debated, we will now describe the development of life on Earth in more detail in order to show that there are good reasons why evolution should culminate in intelligent beings.

  20. Rapid evolution of the plastid translational apparatus in a nonphotosynthetic plant: loss or accelerated sequence evolution of tRNA and ribosomal protein genes.

    PubMed

    Wolfe, K H; Morden, C W; Ems, S C; Palmer, J D

    1992-10-01

    The vestigial plastid genome of Epifagus virginiana (beechdrops), a nonphotosynthetic parasitic flowering plant, is functional but lacks six ribosomal protein and 13 tRNA genes found in the chloroplast DNAs of photosynthetic flowering plants. Import of nuclear gene products is hypothesized to compensate for many of these losses. Codon usage and amino acid usage patterns in Epifagus plastic genes have not been affected by the tRNA gene losses, though a small shift in the base composition of the whole genome (toward A+T-richness) is apparent. The ribosomal protein and tRNA genes that remain have had a high rate of molecular evolution, perhaps due to relaxation of constraints on the translational apparatus. Despite the compactness and extensive gene loss, one translational gene (infA, encoding initiation factor 1) that is a pseudogene in tobacco has been maintained intact in Epifagus.

  1. Comparative Analysis of Syntenic Genes in Grass Genomes Reveals Accelerated Rates of Gene Structure and Coding Sequence Evolution in Polyploid Wheat1[W][OA

    PubMed Central

    Akhunov, Eduard D.; Sehgal, Sunish; Liang, Hanquan; Wang, Shichen; Akhunova, Alina R.; Kaur, Gaganpreet; Li, Wanlong; Forrest, Kerrie L.; See, Deven; Šimková, Hana; Ma, Yaqin; Hayden, Matthew J.; Luo, Mingcheng; Faris, Justin D.; Doležel, Jaroslav; Gill, Bikram S.

    2013-01-01

    Cycles of whole-genome duplication (WGD) and diploidization are hallmarks of eukaryotic genome evolution and speciation. Polyploid wheat (Triticum aestivum) has had a massive increase in genome size largely due to recent WGDs. How these processes may impact the dynamics of gene evolution was studied by comparing the patterns of gene structure changes, alternative splicing (AS), and codon substitution rates among wheat and model grass genomes. In orthologous gene sets, significantly more acquired and lost exonic sequences were detected in wheat than in model grasses. In wheat, 35% of these gene structure rearrangements resulted in frame-shift mutations and premature termination codons. An increased codon mutation rate in the wheat lineage compared with Brachypodium distachyon was found for 17% of orthologs. The discovery of premature termination codons in 38% of expressed genes was consistent with ongoing pseudogenization of the wheat genome. The rates of AS within the individual wheat subgenomes (21%–25%) were similar to diploid plants. However, we uncovered a high level of AS pattern divergence between the duplicated homeologous copies of genes. Our results are consistent with the accelerated accumulation of AS isoforms, nonsynonymous mutations, and gene structure rearrangements in the wheat lineage, likely due to genetic redundancy created by WGDs. Whereas these processes mostly contribute to the degeneration of a duplicated genome and its diploidization, they have the potential to facilitate the origin of new functional variations, which, upon selection in the evolutionary lineage, may play an important role in the origin of novel traits. PMID:23124323

  2. E Pluribus Unum: 50 Years of Research, Millions of Viruses, and One Goal—Tailored Acceleration of AAV Evolution

    PubMed Central

    Grimm, Dirk; Zolotukhin, Sergei

    2015-01-01

    Fifty years ago, a Science paper by Atchison et al. reported a newly discovered virus that would soon become known as adeno-associated virus (AAV) and that would subsequently emerge as one of the most versatile and most auspicious vectors for human gene therapy. A large part of its attraction stems from the ease with which the viral capsid can be engineered for particle retargeting to cell types of choice, evasion from neutralizing antibodies or other desirable properties. Particularly powerful and in the focus of the current review are high-throughput methods aimed at expanding the repertoire of AAV vectors by means of directed molecular evolution, such as random mutagenesis, DNA family shuffling, in silico reconstruction of ancestral capsids, or peptide display. Here, unlike the wealth of prior reviews on this topic, we especially emphasize and critically discuss the practical aspects of the different procedures that affect the ultimate outcome, including diversification protocols, combinatorial library complexity, and selection strategies. Our overall aim is to provide general guidance that should help users at any level, from novice to expert, to safely navigate through the rugged space of directed AAV evolution while avoiding the pitfalls that are associated with these challenging but promising technologies. PMID:26388463

  3. EXPANDED SEARCH FOR z {approx} 10 GALAXIES FROM HUDF09, ERS, AND CANDELS DATA: EVIDENCE FOR ACCELERATED EVOLUTION AT z > 8?

    SciTech Connect

    Oesch, P. A.; Illingworth, G. D.; Gonzalez, V.; Magee, D.; Trenti, M.; Carollo, C. M.; Van Dokkum, P. G.

    2012-02-01

    We search for z {approx} 10 galaxies over {approx}160 arcmin{sup 2} of Wide-Field Camera 3 (WFC3)/IR data in the Chandra Deep Field South, using the public HUDF09, Early Release Science, and CANDELS surveys, that reach to 5{sigma} depths ranging from 26.9 to 29.4 in H{sub 160} AB mag. z {approx}> 9.5 galaxy candidates are identified via J{sub 125} - H{sub 160} > 1.2 colors and non-detections in any band blueward of J{sub 125}. Spitzer Infrared Array Camera (IRAC) photometry is key for separating the genuine high-z candidates from intermediate-redshift (z {approx} 2-4) galaxies with evolved or heavily dust obscured stellar populations. After removing 16 sources of intermediate brightness (H{sub 160} {approx} 24-26 mag) with strong IRAC detections, we only find one plausible z {approx} 10 galaxy candidate in the whole data set, previously reported in Bouwens et al.. The newer data cover a 3 Multiplication-Sign larger area and provide much stronger constraints on the evolution of the UV luminosity function (LF). If the evolution of the z {approx} 4-8 LFs is extrapolated to z {approx} 10, six z {approx} 10 galaxies are expected in our data. The detection of only one source suggests that the UV LF evolves at an accelerated rate before z {approx} 8. The luminosity density is found to increase by more than an order of magnitude in only 170 Myr from z {approx} 10 to z {approx} 8. This increase is {>=}4 Multiplication-Sign larger than expected from the lower redshift extrapolation of the UV LF. We are thus likely witnessing the first rapid buildup of galaxies in the heart of cosmic reionization. Future deep Hubble Space Telescope WFC3/IR data, reaching to well beyond 29 mag, can enable a more robust quantification of the accelerated evolution around z {approx} 10.

  4. Human brain evolution: from gene discovery to phenotype discovery.

    PubMed

    Preuss, Todd M

    2012-06-26

    The rise of comparative genomics and related technologies has added important new dimensions to the study of human evolution. Our knowledge of the genes that underwent expression changes or were targets of positive selection in human evolution is rapidly increasing, as is our knowledge of gene duplications, translocations, and deletions. It is now clear that the genetic differences between humans and chimpanzees are far more extensive than previously thought; their genomes are not 98% or 99% identical. Despite the rapid growth in our understanding of the evolution of the human genome, our understanding of the relationship between genetic changes and phenotypic changes is tenuous. This is true even for the most intensively studied gene, FOXP2, which underwent positive selection in the human terminal lineage and is thought to have played an important role in the evolution of human speech and language. In part, the difficulty of connecting genes to phenotypes reflects our generally poor knowledge of human phenotypic specializations, as well as the difficulty of interpreting the consequences of genetic changes in species that are not amenable to invasive research. On the positive side, investigations of FOXP2, along with genomewide surveys of gene-expression changes and selection-driven sequence changes, offer the opportunity for "phenotype discovery," providing clues to human phenotypic specializations that were previously unsuspected. What is more, at least some of the specializations that have been proposed are amenable to testing with noninvasive experimental techniques appropriate for the study of humans and apes.

  5. Extreme mtDNA divergences in a terrestrial slug (Gastropoda, Pulmonata, Arionidae): accelerated evolution, allopatric divergence and secondary contact.

    PubMed

    Pinceel, J; Jordaens, K; Backeljau, T

    2005-09-01

    Extremely high levels of intraspecific mtDNA differences in pulmonate gastropods have been reported repeatedly and several hypotheses to explain them have been postulated. We studied the phylogeny and phylogeography of 51 populations (n = 843) of the highly polymorphic terrestrial slug Arion subfuscus (Draparnaud, 1805) across its native distribution range in Western Europe. By combining the analysis of single stranded conformation polymorphisms (SSCP) and nucleotide sequencing, we obtained individual sequence data for a fragment of the mitochondrial 16S rDNA and a fragment of the nuclear ITS1. Additionally, five polymorphic allozyme loci were scored. Based on the 16S rDNA phylogeny, five monophyletic haplotype groups with sequence divergences of 9-21% were found. Despite this deep mitochondrial divergence, the haplotype groups were not monophyletic for the nuclear ITS1 fragment and haplotype group-specific allozyme alleles were not found. Although there is evidence for an accelerated mtDNA clock, the divergence among the haplotype groups is older than the Pleistocene and their current allopatric ranges probably reflect allopatric divergence and glacial survival in separate refugia from which different post-glacial colonization routes were established. A range-overlap of two mtDNA groups (S1 and S2, 21% sequence divergence) stretched from Central France and Belgium up to the North of the British Isles. The nuclear data suggest that this secondary contact resulted in hybridization between the allopatrically diverged groups. Therefore, it seems that, at least for two of the groups, the deep mtDNA divergence was only partially accompanied by the formation of reproductive isolation.

  6. Evolution of the subglacial hydrologic system beneath the rapidly decaying Cordilleran Ice Sheet caused by ice-dammed lake drainage: implications for meltwater-induced ice acceleration

    NASA Astrophysics Data System (ADS)

    Burke, Matthew J.; Brennand, Tracy A.; Perkins, Andrew J.

    2012-09-01

    A positive correlation between ice-dammed lake drainage and ice acceleration at Antarctic Ice Sheets (AIS) and land-terminating sections of the Greenland Ice Sheet (GrIS) has been implicated in enhanced ice sheet decay. However, the paucity of direct measurements at the ice sheet bed restricts our understanding of subglacial drainage system evolution in response to transient water inputs. We present evidence that two meltwater corridors on the former bed of the thin (˜600 m at Last Glacial Maximum over the interior Plateaus of British Columbia) and rapidly decaying Cordilleran Ice Sheet (CIS) were generated subglacially in response to the drainage of an ice-dammed lake and operated as canals (tunnel channels). Geomorphological, ground-penetrating radar (GPR) and electrical resistivity tomography (ERT) data reveal a simple event sequence that includes initial propagation of a broad (at least 2.5 km wide) floodwave (inefficient drainage) from an ice-dammed lake, over relatively short (3-24 km) zones at the corridor heads that collapsed into efficient canals (large (up to 0.25-2.5 km wide) channels incised down into the sediment bed and up into the ice) downglacier. Canal formation on the southern Fraser Plateau involved synchronous (along the full canal length) system development, including elements of headward erosion and plunge pool formation. Our data suggest that ice-dammed lake drainage beneath a rapidly decaying thin ice mass that has an efficient antecedent drainage network is not conducive to large-scale ice acceleration. These data may aid better assessment of the role of ice-dammed lake drainage on the dynamics of former, as well as contemporary, ice sheets.

  7. Microstructural Evolution of SAC305 Solder Joints in Wafer Level Chip-Scale Packaging (WLCSP) with Continuous and Interrupted Accelerated Thermal Cycling

    NASA Astrophysics Data System (ADS)

    Zhou, Quan; Zhou, Bite; Lee, Tae-Kyu; Bieler, Thomas

    2016-06-01

    Four high-strain design wafer level chip scale packages were given accelerated thermal cycling with a 10°C/min ramp rate and 10 min hold times between 0°C and 100°C to examine the effects of continuous and interrupted thermal cycling on the number of cycles to failure. The interruptions given two of the samples were the result of periodic examinations using electron backscattered pattern mapping, leading to room temperature aging of 30 days-2.5 years after increments of about 100 cycles at several stages of the cycling history. The continuous thermal cycling resulted in solder joints with a much larger degree of recrystallization, whereas the interrupted thermal cycling tests led to much less recrystallization, which was more localized near the package side, and the crack was more localized near the interface and had less branching. The failure mode for both conditions was still the same, with cracks nucleating along the high angle grain boundaries formed during recrystallization. In conditions where there were few recrystallized grains, recovery led to formation of subgrains that strengthened the solder, and the higher strength led to a larger driving force for crack growth through the solder, leading to failure after less than half of the cycles in the continuous accelerated thermal cycling condition. This work shows that there is a critical point where sufficient strain energy accumulation will trigger recrystallization, but this point depends on the rate of strain accumulation in each cycle and various recovery processes, which further depends on local crystal orientations, stress state evolution, and specific activated slip and twinning systems.

  8. Accelerated evolution of CES7, a gene encoding a novel major urinary protein in the cat family.

    PubMed

    Li, Gang; Janecka, Jan E; Murphy, William J

    2011-02-01

    Cauxin is a novel urinary protein recently identified in the domestic cat that regulates the excretion of felinine, a pheromone precursor involved in sociochemical communication and territorial marking of domestic and wild felids. Understanding the evolutionary history of cauxin may therefore illuminate molecular adaptations involved in the evolution of pheromone-based communication, recognition, and mate selection in wild animals. We sequenced the gene encoding cauxin, CES7, in 22 species representing all major felid lineages, and multiple outgroups and showed that it has undergone rapid evolutionary change preceding and during the diversification of the cat family. A comparison between feline cauxin and orthologous carboxylesterases from other mammalian lineages revealed evidence of strong positive Darwinian selection within and between several cat lineages, enriched at functionally important sites of the protein. The higher rate of radical amino acid replacements in small felids, coupled with the lack of felinine and extremely low levels of cauxin in the urine of the great cats (Panthera), correlates with functional divergence of this gene in Panthera, and its putative loss in the snow leopard. Expression studies found evidence for several alternatively spliced transcripts in testis and brain, suggesting additional roles in male reproductive fitness and behavior. Our work presents the first report of strong positive natural selection acting on a major urinary protein of nonrodent mammals, providing evidence for parallel selection pressure on the regulation of pheromones in different mammalian lineages, despite the use of different metabolic pathways. Our results imply that natural selection may drive rapid changes in the regulation of pheromones in urine among the different cat species, which in turn may influence social behavior, such as territorial marking and conspecific recognition, therefore serving as an important mechanism for the radiation of this group

  9. Hydrodynamical and radio evolution of young supernova remnant G1.9+0.3 based on the model of diffusive shock acceleration

    NASA Astrophysics Data System (ADS)

    Pavlović, M. Z.

    2017-06-01

    The radio evolution of, so far the youngest known, Galactic supernova remnant (SNR) G1.9+0.3 is investigated by using three-dimensional (3D) hydrodynamic modelling and non-linear kinetic theory of cosmic ray (CR) acceleration in SNRs. We include consistent numerical treatment of magnetic field amplification (MFA) due to resonant streaming instability. Under the assumption that SNR G1.9+0.3 is the result of a Type Ia supernova explosion located near the Galactic Centre, using widely accepted values for explosion energy 1051 erg and ejecta mass 1.4 M⊙, the non-thermal continuum radio emission is calculated. The main purpose of this paper is to explain radio flux brightening measured over recent decades and also predict its future temporal evolution. We estimate that the SNR is now ˜120 yr old, expanding in an ambient density of 0.02 cm-3, and explain its steep radio spectral index only by means of efficient non-linear diffusive shock acceleration (NLDSA). We also make comparison between simulations and observations of this young SNR, in order to test the models and assumptions suggested. Our model prediction of a radio flux density increase of ˜1.8 per cent yr-1 during the past two decades agrees well with the measured values. We synthesize the synchrotron spectrum from radio to X-ray and it fits well the Very Large Array, Molonglo Observatory Synthesis Telescope, Effelsberg, Chandra and NuSTAR measurements. We also propose a simplified evolutionary model of the SNR in gamma rays and suggest it may be a promising target for gamma-ray observations at TeV energies with the future generation of instruments like Cherenkov Telescope Array. SNR G1.9+0.3 is the only known Galactic SNR with the increasing flux density and we present here the prediction that the flux density will start to decrease approximately 500 yr from now. We conclude that this is a general property of SNRs in the free expansion phase.

  10. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  11. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  12. Particle acceleration in flares

    NASA Technical Reports Server (NTRS)

    Benz, Arnold O.; Kosugi, Takeo; Aschwanden, Markus J.; Benka, Steve G.; Chupp, Edward L.; Enome, Shinzo; Garcia, Howard; Holman, Gordon D.; Kurt, Victoria G.; Sakao, Taro

    1994-01-01

    Particle acceleration is intrinsic to the primary energy release in the impulsive phase of solar flares, and we cannot understand flares without understanding acceleration. New observations in soft and hard X-rays, gamma-rays and coherent radio emissions are presented, suggesting flare fragmentation in time and space. X-ray and radio measurements exhibit at least five different time scales in flares. In addition, some new observations of delayed acceleration signatures are also presented. The theory of acceleration by parallel electric fields is used to model the spectral shape and evolution of hard X-rays. The possibility of the appearance of double layers is further investigated.

  13. Particle acceleration in flares

    NASA Technical Reports Server (NTRS)

    Benz, Arnold O.; Kosugi, Takeo; Aschwanden, Markus J.; Benka, Steve G.; Chupp, Edward L.; Enome, Shinzo; Garcia, Howard; Holman, Gordon D.; Kurt, Victoria G.; Sakao, Taro

    1994-01-01

    Particle acceleration is intrinsic to the primary energy release in the impulsive phase of solar flares, and we cannot understand flares without understanding acceleration. New observations in soft and hard X-rays, gamma-rays and coherent radio emissions are presented, suggesting flare fragmentation in time and space. X-ray and radio measurements exhibit at least five different time scales in flares. In addition, some new observations of delayed acceleration signatures are also presented. The theory of acceleration by parallel electric fields is used to model the spectral shape and evolution of hard X-rays. The possibility of the appearance of double layers is further investigated.

  14. Shift from slow- to fast-water habitats accelerates lineage and phenotype evolution in a clade of Neotropical suckermouth catfishes (Loricariidae: Hypoptopomatinae).

    PubMed

    Roxo, Fábio F; Lujan, Nathan K; Tagliacollo, Victor A; Waltz, Brandon T; Silva, Gabriel S C; Oliveira, Claudio; Albert, James S

    2017-01-01

    Identifying habitat characteristics that accelerate organismal evolution is essential to understanding both the origins of life on Earth and the ecosystem properties that are most critical to maintaining life into the future. Searching for these characteristics on a large scale has only recently become possible via advances in phylogenetic reconstruction, time-calibration, and comparative analyses. In this study, we combine these tools with habitat and phenotype data for 105 species in a clade of Neotropical suckermouth catfishes commonly known as cascudinhos. Our goal was to determine whether riverine mesohabitats defined by different flow rates (i.e., pools vs. rapids) and substrates (plants vs. rocks) have affected rates of cascudinho cladogenesis and morphological diversification. In contrast to predictions based on general theory related to life in fast-flowing, rocky riverine habitats, Neoplecostomini lineages associated with these habitats exhibited increased body size, head shape diversity, and lineage and phenotype diversification rates. These findings are consistent with a growing understanding of river rapids as incubators of biological diversification and specialization. They also highlight the urgent need to conserve rapids habitats throughout the major rivers of the world.

  15. The Non-linear Evolution of Whistler-mode Waves at the Dayside Magnetopause and Its Relation to Magnetic Reconnection and Particle Acceleration

    NASA Astrophysics Data System (ADS)

    Wilder, F. D.; Ergun, R.; Goodrich, K.; Newman, D. L.; Goldman, M. V.; Schwartz, S. J.; Jaynes, A. N.; Holmes, J.; Sturner, A. P.; Eriksson, S.; Burch, J. L.; Torbert, R. B.; Phan, T.; Argall, M. R.; Le Contel, O.; Khotyaintsev, Y. V.; Lindqvist, P. A.; Giles, B. L.; Gershman, D. J.; Strangeway, R. J.; Russell, C. T.; Leonard, T. W.

    2016-12-01

    Whistler-mode waves have been observed at the subsolar magnetopause in association with magnetic reconnection, including near the electron diffusion region (EDR) and near the separatrices. Observations by the Magnetospheric Multiscale (MMS) mission have shown oblique whistler-mode waves at the electron edge of the reconnection layer that are coincident with time-domain structures such as double layers and electrostatic solitary waves, as well as intense Langmuir oscillations. Additionally, large amplitude non-linear parallel oscillations often coincide with these waves, and may be the result of interactions between the whistler-mode waves and electron-acoustic waves, similar to what has been observed in the radiation belts. We present results of an investigation by MMS into the non-linear evolution of these whistlers and their effects on the local plasma population. Preliminary results suggest that the waves are less common near EDR candidates than on the separatrices and that, via non-linear parallel electric fields, they contribute to direct acceleration of electrons.

  16. Shift from slow- to fast-water habitats accelerates lineage and phenotype evolution in a clade of Neotropical suckermouth catfishes (Loricariidae: Hypoptopomatinae)

    PubMed Central

    Roxo, Fábio F.; Lujan, Nathan K.; Tagliacollo, Victor A.; Waltz, Brandon T.; Silva, Gabriel S. C.; Oliveira, Claudio; Albert, James S.

    2017-01-01

    Identifying habitat characteristics that accelerate organismal evolution is essential to understanding both the origins of life on Earth and the ecosystem properties that are most critical to maintaining life into the future. Searching for these characteristics on a large scale has only recently become possible via advances in phylogenetic reconstruction, time-calibration, and comparative analyses. In this study, we combine these tools with habitat and phenotype data for 105 species in a clade of Neotropical suckermouth catfishes commonly known as cascudinhos. Our goal was to determine whether riverine mesohabitats defined by different flow rates (i.e., pools vs. rapids) and substrates (plants vs. rocks) have affected rates of cascudinho cladogenesis and morphological diversification. In contrast to predictions based on general theory related to life in fast-flowing, rocky riverine habitats, Neoplecostomini lineages associated with these habitats exhibited increased body size, head shape diversity, and lineage and phenotype diversification rates. These findings are consistent with a growing understanding of river rapids as incubators of biological diversification and specialization. They also highlight the urgent need to conserve rapids habitats throughout the major rivers of the world. PMID:28591189

  17. Temporospatial evolution and removal mechanisms of As(V) and Se(VI) in ZVI column with H2O2 as corrosion accelerator.

    PubMed

    Yang, Zhe; Shan, Chao; Zhang, Weiming; Jiang, Zhao; Guan, Xiaohong; Pan, Bingcai

    2016-12-01

    Enhanced removal of As(V) and Se(VI) by zero valent iron (ZVI) has been recently revealed by using H2O2 as the corrosion accelerator, however, the detailed performance of such enhanced removal in ZVI column as well as the underlying mechanism is still unclear. In this study, the temporospatial evolution of As(V) and Se(VI) along a self-designed ZVI/H2O2 column in down-flow mode was systematically investigated. The variations of concerned aqueous parameters (pH, ORP, H2O2, Fe(2+), As, and Se) were monitored at different positions along the column throughout the experiments. Results showed the corrosion degree of ZVI decreased with the depth of the column, as confirmed by SEM and XRD analyses of the solid samples from different layers. The retention of As and Se also decreased along the column, suggesting the uptake of As(V) and Se(VI) was highly dependent upon the ZVI corrosion evolution. In the initial stage, the influent H2O2 was mostly consumed by ZVI in the top layer. With the continuous corrosion of ZVI, the breakthrough of H2O2 would activate the ZVI at lower positions, resulting in the reactive zone continuously shifting downward along the column. The reduction of As(V) and Se(VI) to aqueous As(III) and Se(IV) was significantly inhibited at the positions in the presence of H2O2, whereas favorably enhanced in the presence of abundant Fe(2+). The retention of As(III) in the lower part of the column was observed while that of Se(IV) was negligible, as related to the different effects of pH on the adsorption of As(III) and Se(IV). In addition, the evolution of different oxidation states of As and Se retained in the column were identified by XPS, further demonstrating the comprehensive mechanisms of As(V)/Se(VI) removal involving reduction and adsorption in the ZVI/H2O2 column. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  19. Can Accelerators Accelerate Learning?

    SciTech Connect

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-10

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ)[1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  20. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  1. CEBAF Accelerator Achievements

    NASA Astrophysics Data System (ADS)

    Chao, Y. C.; Drury, M.; Hovater, C.; Hutton, A.; Krafft, G. A.; Poelker, M.; Reece, C.; Tiefenback, M.

    2011-05-01

    In the past decade, nuclear physics users of Jefferson Lab's Continuous Electron Beam Accelerator Facility (CEBAF) have benefited from accelerator physics advances and machine improvements. As of early 2011, CEBAF operates routinely at 6 GeV, with a 12 GeV upgrade underway. This article reports highlights of CEBAF's scientific and technological evolution in the areas of cryomodule refurbishment, RF control, polarized source development, beam transport for parity experiments, magnets and hysteresis handling, beam breakup, and helium refrigerator operational optimization.

  2. Accelerated Evolution of the Lyα Luminosity Function at z >~ 7 Revealed by the Subaru Ultra-deep Survey for Lyα Emitters at z = 7.3

    NASA Astrophysics Data System (ADS)

    Konno, Akira; Ouchi, Masami; Ono, Yoshiaki; Shimasaku, Kazuhiro; Shibuya, Takatoshi; Furusawa, Hisanori; Nakajima, Kimihiko; Naito, Yoshiaki; Momose, Rieko; Yuma, Suraphong; Iye, Masanori

    2014-12-01

    We present the ultra-deep Subaru narrowband imaging survey for Lyα emitters (LAEs) at z = 7.3 in the Subaru/XMM-Newton Deep Survey (SXDS) and Cosmic Evolution Survey (COSMOS) fields (~0.5 deg2) with a total integration time of 106 hr. Exploiting our new sharp bandwidth filter, NB101, installed on the Suprime-Cam, we have reached L(Lyα) = 2.4 × 1042 erg s-1 (5σ) for z = 7.3 LAEs, about four times deeper than previous Subaru z >~ 7 studies, which allows us to reliably investigate the evolution of the Lyα luminosity function (LF) for the first time down to the luminosity limit same as those of Subaru z = 3.1-6.6 LAE samples. Surprisingly, we only find three and four LAEs in the SXDS and COSMOS fields, respectively, while one expects a total of ~65 LAEs by our survey in the case of no Lyα LF evolution from z = 6.6 to 7.3. We identify a decrease of the Lyα LF from z = 6.6 to 7.3 at the >90% confidence level from our z = 7.3 Lyα LF with the best-fit Schechter parameters of L*{Lyα } = 2.7+8.0-1.2 × 1042 {erg} {s}-1 and φ * = 3.7+17.6-3.3 × 10-4 {Mpc}-3 for a fixed α = -1.5. Moreover, the evolution of the Lyα LF is clearly accelerated at z > 6.6 beyond the measurement uncertainties including cosmic variance. Because no such accelerated evolution of the UV-continuum LF or the cosmic star formation rate (SFR) is found at z ~ 7, but suggested only at z > 8, this accelerated Lyα LF evolution is explained by physical mechanisms different from a pure SFR decrease but related to the Lyα production and escape in the process of cosmic reionization. Because a simple accelerating increase of intergalactic medium neutral hydrogen absorbing Lyα cannot be reconciled with Thomson scattering of optical depth measurements from WMAP and Planck, our findings may support new physical pictures suggested by recent theoretical studies, such as the existence of HI clumpy clouds within cosmic ionized bubbles that are selectively absorbing Lyα and the large ionizing photon escape

  3. Role of synoptic- and meso-scales on the evolution of the boundary-layer wind profile over a coastal region: the near-coast diurnal acceleration

    NASA Astrophysics Data System (ADS)

    Jiménez, Pedro A.; de Arellano, Jordi Vilà-Guerau; Dudhia, Jimy; Bosveld, Fred C.

    2016-02-01

    The contributions of synoptic- and meso-scales to the boundary layer wind profile evolution in a coastal environment are examined. The analysis is based on observations of the wind profile within the first 200 m of the atmosphere continuously recorded during a 10 year period (2001-2010) at the 213-m meteorological tower at the Cabauw Experimental Site for Atmospheric Research (CESAR, The Netherlands). The analysis is supported by a numerical experiment based on the Weather Research and Forecasting (WRF) model performed at high horizontal resolution of 2 km and spanning the complete observational period (10 years). Results indicate that WRF is able to reproduce the inter-annual wind variability but with a tendency to be too geostrophic. At seasonal scales, we find a differentiated behavior between Winter and Summer seasons with the Spring and Autumn transition periods more similar to the Summer and Winter modes, respectively. The winter momentum budget shows a weak intradiurnal variability. The synoptic scale controls the shape of the near surface wind profile that is characterized by weaker and more ageostrophic winds near the surface than at higher altitudes within the planetary boundary layer (PBL) as a result of the frictional turning. In turn, during summer, mesoscale circulations associated with the differential heating of land and sea become important. As a result, the PBL winds show a stronger intradiurnal component that is characterized by an oscillation of the near surface winds around the geostrophic direction with the maximum departure in the afternoon. Although also driven by thermal land-sea differences, this mesoscale component is not associated with the classical concept of a sea-breeze front. It originates from the thermal expansion of the boundary layer over land and primarily differs from the sea-breeze in its propagation speed resulting in a wind rotation far ahead of any coastal front. We refer to it as the near-coast diurnal acceleration (NCDA

  4. Future accelerators (?)

    SciTech Connect

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  5. Comparative analysis of syntenic genes in grass genomes reveals accelerated rates of gene structure and coding sequence evolution in polyploid wheat

    USDA-ARS?s Scientific Manuscript database

    Cycles of whole genome duplication (WGD) and diploidization are hallmarks of eukaryotic genome evolution and speciation. Polyploid wheat (Triticum aestivum) has had a massive increase in genome size largely due to recent WGDs. How these processes may impact the dynamics of gene evolution was studied...

  6. Acceleration of Field-Scale Bioreduction of U(VI) in a Shallow Alluvial Aquifer: Temporal and Spatial Evolution of Biogeochemistry

    SciTech Connect

    Long, Phil

    2005-04-20

    Uranium mill tailings sites provide access to uranium-contaminated groundwater at sites that are shallow and low hazard, making it possible to address the following scientific objectives: (1) Determine the dominant electron accepting processes at field sites with long-term metal/rad contamination; (2) Define the biogeochemical transformations that may be important to either natural or accelerated bioremediation under field conditions; and (3) Examine the potential for using biostimulation (electron donor addition) to accelerate reduction of U(VI) to U(IV) at the field scale.

  7. Accelerators for research and applications

    SciTech Connect

    Alonso, J.R.

    1990-06-01

    The newest particle accelerators are almost always built for extending the frontiers of research, at the cutting edge of science and technology. Once these machines are operating and these technologies mature, new applications are always found, many of which touch our lives in profound ways. The evolution of accelerator technologies will be discussed, with descriptions of accelerator types and characteristics. The wide range of applications of accelerators will be discussed, in fields such as nuclear science, medicine, astrophysics and space-sciences, power generation, airport security, materials processing and microcircuit fabrication. 13 figs.

  8. Accelerated evolution of the Lyα luminosity function at z ≳ 7 revealed by the Subaru ultra-deep survey for Lyα emitters at z = 7.3

    SciTech Connect

    Konno, Akira; Ouchi, Masami; Ono, Yoshiaki; Shibuya, Takatoshi; Naito, Yoshiaki; Momose, Rieko; Yuma, Suraphong; Shimasaku, Kazuhiro; Nakajima, Kimihiko; Furusawa, Hisanori; Iye, Masanori

    2014-12-10

    We present the ultra-deep Subaru narrowband imaging survey for Lyα emitters (LAEs) at z = 7.3 in the Subaru/XMM-Newton Deep Survey (SXDS) and Cosmic Evolution Survey (COSMOS) fields (∼0.5 deg{sup 2}) with a total integration time of 106 hr. Exploiting our new sharp bandwidth filter, NB101, installed on the Suprime-Cam, we have reached L(Lyα) = 2.4 × 10{sup 42} erg s{sup –1} (5σ) for z = 7.3 LAEs, about four times deeper than previous Subaru z ≳ 7 studies, which allows us to reliably investigate the evolution of the Lyα luminosity function (LF) for the first time down to the luminosity limit same as those of Subaru z = 3.1-6.6 LAE samples. Surprisingly, we only find three and four LAEs in the SXDS and COSMOS fields, respectively, while one expects a total of ∼65 LAEs by our survey in the case of no Lyα LF evolution from z = 6.6 to 7.3. We identify a decrease of the Lyα LF from z = 6.6 to 7.3 at the >90% confidence level from our z = 7.3 Lyα LF with the best-fit Schechter parameters of L{sub Lyα}{sup ∗}=2.7{sub −1.2}{sup +8.0}×10{sup 42} erg s{sup −1} and ϕ{sup ∗}=3.7{sub −3.3}{sup +17.6}×10{sup −4} Mpc{sup −3} for a fixed α = –1.5. Moreover, the evolution of the Lyα LF is clearly accelerated at z > 6.6 beyond the measurement uncertainties including cosmic variance. Because no such accelerated evolution of the UV-continuum LF or the cosmic star formation rate (SFR) is found at z ∼ 7, but suggested only at z > 8, this accelerated Lyα LF evolution is explained by physical mechanisms different from a pure SFR decrease but related to the Lyα production and escape in the process of cosmic reionization. Because a simple accelerating increase of intergalactic medium neutral hydrogen absorbing Lyα cannot be reconciled with Thomson scattering of optical depth measurements from WMAP and Planck, our findings may support new physical pictures suggested by recent theoretical studies, such as the existence of HI clumpy clouds within

  9. Radical Acceleration

    ERIC Educational Resources Information Center

    Gross, Miraca U. M.; Van Vliet, Helen E.

    2005-01-01

    Research has found that teachers' objections to accelerating gifted students are mainly based on a fear that acceleration will lead to social or emotional damage. Ironically, it is the academic and emotional maturity which characterizes intellectually gifted students, coupled with their high levels of academic achievement, which makes them such…

  10. RECIRCULATING ACCELERATION

    SciTech Connect

    BERG,J.S.; GARREN,A.A.; JOHNSTONE,C.

    2000-04-07

    This paper compares various types of recirculating accelerators, outlining the advantages and disadvantages of various approaches. The accelerators are characterized according to the types of arcs they use: whether there is a single arc for the entire recirculator or there are multiple arcs, and whether the arc(s) are isochronous or non-isochronous.

  11. LINEAR ACCELERATOR

    DOEpatents

    Colgate, S.A.

    1958-05-27

    An improvement is presented in linear accelerators for charged particles with respect to the stable focusing of the particle beam. The improvement consists of providing a radial electric field transverse to the accelerating electric fields and angularly introducing the beam of particles in the field. The results of the foregoing is to achieve a beam which spirals about the axis of the acceleration path. The combination of the electric fields and angular motion of the particles cooperate to provide a stable and focused particle beam.

  12. Wakefield accelerators

    SciTech Connect

    Simpson, J.D.

    1990-01-01

    The search for new methods to accelerate particle beams to high energy using high gradients has resulted in a number of candidate schemes. One of these, wakefield acceleration, has been the subject of considerable R D in recent years. This effort has resulted in successful proof of principle experiments and in increased understanding of many of the practical aspects of the technique. Some wakefield basics plus the status of existing and proposed experimental work is discussed, along with speculations on the future of wake field acceleration. 10 refs., 6 figs.

  13. The evolution of accelerated, partial breast irradiation as a potential treatment option for women with newly diagnosed breast cancer considering breast conservation.

    PubMed

    Dirbas, Frederick M; Jeffrey, Stefanie S; Goffinet, Don R

    2004-12-01

    Breast conservation therapy (BCT) is a safe, effective alternative to mastectomy for many women with newly diagnosed breast cancer. This approach involves local excision of the malignancy with tumor-free margins, followed by 5-7 weeks of external beam whole breast (WB) radiotherapy (XRT) to minimize the risk of an in-breast tumor recurrence (IBTR). Though clearly beneficial, the extended course of almost daily postoperative radiotherapy interrupts normal activities and lengthens care. Additional options are now available that shorten the radiotherapy treatment time to 1-5 days (accelerated) and focus an increased dose of radiation on just the breast tissue around the excision cavity (partial breast). Recent trials with accelerated, partial breast irradiation (APBI) have shown promise as a potential replacement to the longer, whole breast treatments for select women with early-stage breast cancer. Current APBI approaches include interstitial brachytherapy, intracavitary (balloon) brachytherapy, and accelerated external beam (3-D conformal) radiotherapy, all of which normally complete treatment over 5 days, while intraoperative radiotherapy (IORT) condenses the entire treatment into a single dose delivered immediately after tumor excision. Each approach has benefits and limitations. This study covers over 2 decades of clinical trials exploring APBI, discusses treatment variables that appear necessary for successful implementation of this new form of radiotherapy, compares and contrasts the various APBI approaches, and summarizes current and planned randomized trials that will shape if and how APBI is introduced into routine clinical care. Some of the more important outcome variables from these trials will be local toxicity, local and regional recurrence, and overall survival. If APBI options are ultimately demonstrated to be as safe and effective as current whole breast radiotherapy approaches, breast conservation may become an even more appealing choice, and the

  14. ION ACCELERATOR

    DOEpatents

    Bell, J.S.

    1959-09-15

    An arrangement for the drift tubes in a linear accelerator is described whereby each drift tube acts to shield the particles from the influence of the accelerating field and focuses the particles passing through the tube. In one embodiment the drift tube is splii longitudinally into quadrants supported along the axis of the accelerator by webs from a yoke, the quadrants. webs, and yoke being of magnetic material. A magnetic focusing action is produced by energizing a winding on each web to set up a magnetic field between adjacent quadrants. In the other embodiment the quadrants are electrically insulated from each other and have opposite polarity voltages on adjacent quadrants to provide an electric focusing fleld for the particles, with the quadrants spaced sufficienily close enough to shield the particles within the tube from the accelerating electric field.

  15. Acceleration switch

    DOEpatents

    Abbin, J.P. Jr.; Devaney, H.F.; Hake, L.W.

    1979-08-29

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  16. Acceleration switch

    DOEpatents

    Abbin, Jr., Joseph P.; Devaney, Howard F.; Hake, Lewis W.

    1982-08-17

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  17. LINEAR ACCELERATOR

    DOEpatents

    Christofilos, N.C.; Polk, I.J.

    1959-02-17

    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  18. Accelerating the dissolution of enteric coatings in the upper small intestine: evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release.

    PubMed

    Varum, Felipe J O; Merchant, Hamid A; Goyanes, Alvaro; Assi, Pardis; Zboranová, Veronika; Basit, Abdul W

    2014-07-01

    Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2 h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ System, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5 mg/cm(2) of partially neutralized EUDRAGIT(®) L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT(®) L 30 D-55 was applied at 5mg/cm(2). For comparison purposes, a standard single layer of EUDRAGIT(®) L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1 M HCl for 2 h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT(®) L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75 min in buffer, whereas release from the EUDRAGIT(®) L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages during the development of dosage forms designed to release the drug in the upper small intestine. Copyright © 2014. Published by Elsevier B.V.

  19. Superconducting Magnets for Particle Accelerators

    DOE PAGES

    Bottura, Luca; Gourlay, Stephen A.; Yamamoto, Akira; ...

    2015-11-10

    In this study, we summarize the evolution and contributions of superconducting magnets to particle accelerators as chronicled over the last 50 years of Particle Accelerator Conferences (PAC, NA-PAC and IPAC). We begin with an historical overview based primarily on PAC Proceedings augmented with references to key milestones in the development of superconducting magnets for particle accelerators. We then provide some illustrative examples of applications that have occurred over the past 50 years, focusing on those that have either been realized in practice or provided technical development for other projects, with discussion of possible future applications.

  20. Superconducting Magnets for Particle Accelerators

    NASA Astrophysics Data System (ADS)

    Bottura, Luca; Gourlay, Stephen A.; Yamamoto, Akira; Zlobin, Alexander V.

    2016-04-01

    In this paper we summarize the evolution and contributions of superconducting magnets to particle accelerators as chronicled over the last 50 years of Particle Accelerator Conferences (PAC, NA-PAC and IPAC). We begin with an historical overview based primarily on PAC Proceedings augmented with references to key milestones in the development of superconducting magnets for particle accelerators. We then provide some illustrative examples of applications that have occurred over the past 50 years, focusing on those that have either been realized in practice or provided technical development for other projects, with discussion of possible future applications.

  1. STOCHASTIC ACCELERATION AND THE EVOLUTION OF SPECTRAL DISTRIBUTIONS IN SYNCHRO-SELF-COMPTON SOURCES: A SELF-CONSISTENT MODELING OF BLAZARS' FLARES

    SciTech Connect

    Tramacere, A.; Taylor, A. M.; Massaro, E.

    2011-10-01

    The broadband spectral distributions of non-thermal sources, such as those of several known blazars, are well described by a log-parabolic fit. The second-degree term in these fits measures the curvature in the spectrum. In this paper, we investigate whether the curvature parameter observed in the spectra of the synchrotron emission can be used as a fingerprint of stochastic acceleration. As a first approach, we use the multiplicative central limit theorem to show how fluctuations in the energy gain result in the broadening of the spectral shape, introducing a curvature into the energy distribution. Then, by means of a Monte Carlo description, we investigate how the curvature produced in the electron distribution is linked to the diffusion in momentum space. To get a more generic description of the problem we turn to the diffusion equation in momentum space. We first study some 'standard' scenarios, in order to understand the conditions that make the curvature in the spectra significant, and the relevance of cooling during the acceleration process. We try to quantify the correlation between the curvature and the diffusive process in the pre-equilibrium stage, and investigate how the transition between the Klein-Nishina and the Thomson regimes, in inverse Compton cooling, determine the curvature in the distribution at equilibrium. We apply these results to some observed trends, such as the anticorrelation between the peak energy and the curvature term observed in the spectra of Mrk 421, and a sample of BL Lac objects whose synchrotron emission peaks at X-ray energies.

  2. Ultrasonic vocalizations in mouse models for speech and socio-cognitive disorders: insights into the evolution of vocal communication

    PubMed Central

    Fischer, J; Hammerschmidt, K

    2011-01-01

    Comparative analyses used to reconstruct the evolution of traits associated with the human language faculty, including its socio-cognitive underpinnings, highlight the importance of evolutionary constraints limiting vocal learning in non-human primates. After a brief overview of this field of research and the neural basis of primate vocalizations, we review studies that have addressed the genetic basis of usage and structure of ultrasonic communication in mice, with a focus on the gene FOXP2 involved in specific language impairments and neuroligin genes (NL-3 and NL-4) involved in autism spectrum disorders. Knockout of FoxP2 leads to reduced vocal behavior and eventually premature death. Introducing the human variant of FoxP2 protein into mice, in contrast, results in shifts in frequency and modulation of pup ultrasonic vocalizations. Knockout of NL-3 and NL-4 in mice diminishes social behavior and vocalizations. Although such studies may provide insights into the molecular and neural basis of social and communicative behavior, the structure of mouse vocalizations is largely innate, limiting the suitability of the mouse model to study human speech, a learned mode of production. Although knockout or replacement of single genes has perceptible effects on behavior, these genes are part of larger networks whose functions remain poorly understood. In humans, for instance, deficiencies in NL-4 can lead to a broad spectrum of disorders, suggesting that further factors (experiential and/or genetic) contribute to the variation in clinical symptoms. The precise nature as well as the interaction of these factors is yet to be determined. PMID:20579107

  3. Accelerated evolution of fetuin family proteins in Protobothrops flavoviridis (habu snake) serum and the discovery of an L1-like genomic element in the intronic sequence of a fetuin-encoding gene.

    PubMed

    Tanaka, Yasuyoshi; Oyama, Sachiko; Hori, Shin-ichi; Ushio, Koya; Shioi, Narumi; Terada, Shigeyuki; Deshimaru, Masanobu

    2013-01-01

    Habu serum factor (HSF) and HSF-like protein (HLP) are fetuin family proteins isolated from Protobothrops flavoviridis (habu snake) serum with different physiological activities. A comparison of their cDNAs and intronic sequences revealed that nucleotide substitutions were primarily in protein-coding regions, and the substitution patterns indicated accelerated evolution of these proteins. Genomic DNA fragment analysis, including intron 1, revealed a 6.6-kb insertion homologous to the full-length mammalian LINE1 (L1) retrotransposable element (PfL1) only in the HLP gene. This segment retains an open reading frame (ORF) that encodes a reverse transcriptase (RT)-like protein (PfRT). We further found that a large number of homologous segments have dispersed in the habu snake genome, although we could not determine the enzymatic activities of their products. Moreover, an analysis of habu snake liver RNA indicated active transcription of the PfRT genes, suggesting that high levels of RT activity in this snake have driven the evolution of unique phenotypes of venom enzymes and serum inhibitors of them.

  4. Acceleration Studies

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.

    1993-01-01

    Work to support the NASA MSFC Acceleration Characterization and Analysis Project (ACAP) was performed. Four tasks (analysis development, analysis research, analysis documentation, and acceleration analysis) were addressed by parallel projects. Work concentrated on preparation for and implementation of near real-time SAMS data analysis during the USMP-1 mission. User support documents and case specific software documentation and tutorials were developed. Information and results were presented to microgravity users. ACAP computer facilities need to be fully implemented and networked, data resources must be cataloged and accessible, future microgravity missions must be coordinated, and continued Orbiter characterization is necessary.

  5. Accelerated Achievement

    ERIC Educational Resources Information Center

    Ford, William J.

    2010-01-01

    This article focuses on the accelerated associate degree program at Ivy Tech Community College (Indiana) in which low-income students will receive an associate degree in one year. The three-year pilot program is funded by a $2.3 million grant from the Lumina Foundation for Education in Indianapolis and a $270,000 grant from the Indiana Commission…

  6. Particle acceleration

    NASA Technical Reports Server (NTRS)

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  7. ACCELERATION INTEGRATOR

    DOEpatents

    Pope, K.E.

    1958-01-01

    This patent relates to an improved acceleration integrator and more particularly to apparatus of this nature which is gyrostabilized. The device may be used to sense the attainment by an airborne vehicle of a predetermined velocitv or distance along a given vector path. In its broad aspects, the acceleration integrator utilizes a magnetized element rotatable driven by a synchronous motor and having a cylin drical flux gap and a restrained eddy- current drag cap deposed to move into the gap. The angular velocity imparted to the rotatable cap shaft is transmitted in a positive manner to the magnetized element through a servo feedback loop. The resultant angular velocity of tae cap is proportional to the acceleration of the housing in this manner and means may be used to measure the velocity and operate switches at a pre-set magnitude. To make the above-described dcvice sensitive to acceleration in only one direction the magnetized element forms the spinning inertia element of a free gyroscope, and the outer housing functions as a gimbal of a gyroscope.

  8. Plasma accelerator

    DOEpatents

    Wang, Zhehui; Barnes, Cris W.

    2002-01-01

    There has been invented an apparatus for acceleration of a plasma having coaxially positioned, constant diameter, cylindrical electrodes which are modified to converge (for a positive polarity inner electrode and a negatively charged outer electrode) at the plasma output end of the annulus between the electrodes to achieve improved particle flux per unit of power.

  9. Accelerated Achievement

    ERIC Educational Resources Information Center

    Ford, William J.

    2010-01-01

    This article focuses on the accelerated associate degree program at Ivy Tech Community College (Indiana) in which low-income students will receive an associate degree in one year. The three-year pilot program is funded by a $2.3 million grant from the Lumina Foundation for Education in Indianapolis and a $270,000 grant from the Indiana Commission…

  10. Phylum-wide analysis of SSU rDNA reveals deep phylogenetic relationships among nematodes and accelerated evolution toward crown Clades.

    PubMed

    Holterman, Martijn; van der Wurff, Andre; van den Elsen, Sven; van Megen, Hanny; Bongers, Tom; Holovachov, Oleksandr; Bakker, Jaap; Helder, Johannes

    2006-09-01

    Inference of evolutionary relationships between nematodes is severely hampered by their conserved morphology, the high frequency of homoplasy, and the scarcity of phylum-wide molecular data. To study the origin of nematode radiation and to unravel the phylogenetic relationships between distantly related species, 339 nearly full-length small-subunit rDNA sequences were analyzed from a diverse range of nematodes. Bayesian inference revealed a backbone comprising 12 consecutive dichotomies that subdivided the phylum Nematoda into 12 clades. The most basal clade is dominated by the subclass Enoplia, and members of the order Triplonchida occupy positions most close to the common ancestor of the nematodes. Crown Clades 8-12, a group formerly indicated as "Secernentea" that includes Caenorhabditis elegans and virtually all major plant and animal parasites, show significantly higher nucleotide substitution rates than the more basal Clades 1-7. Accelerated substitution rates are associated with parasitic lifestyles (Clades 8 and 12) or short generation times (Clades 9-11). The relatively high substitution rates in the distal clades resulted in numerous autapomorphies that allow in most cases DNA barcode-based species identification. Teratocephalus, a genus comprising terrestrial bacterivores, was shown to be most close to the starting point of Secernentean radiation. Notably, fungal feeding nematodes were exclusively found basal to or as sister taxon next to the 3 groups of plant parasitic nematodes, namely, Trichodoridae, Longidoridae, and Tylenchomorpha. The exclusive common presence of fungivorous and plant parasitic nematodes supports a long-standing hypothesis that states that plant parasitic nematodes arose from fungivorous ancestors.

  11. Influence of volcanic activity on the population genetic structure of Hawaiian Tetragnatha spiders: Fragmentation, rapid population growth and the potential for accelerated evolution

    USGS Publications Warehouse

    Vandergast, A.G.; Gillespie, R.G.; Roderick, G.K.

    2004-01-01

    Volcanic activity on the island of Hawaii results in a cyclical pattern of habitat destruction and fragmentation by lava, followed by habitat regeneration on newly formed substrates. While this pattern has been hypothesized to promote the diversification of Hawaiian lineages, there have been few attempts to link geological processes to measurable changes in population structure. We investigated the genetic structure of three species of Hawaiian spiders in forests fragmented by a 150-year-old lava flow on Mauna Loa Volcano, island of Hawaii: Tetragnatha quasimodo (forest and lava flow generalist), T. anuenue and T. brevignatha (forest specialists). To estimate fragmentation effects on population subdivision in each species, we examined variation in mitochondrial and nuclear genomes (DNA sequences and allozymes, respectively). Population subdivision was higher for forest specialists than for the generalist in fragments separated by lava. Patterns of mtDNA sequence evolution also revealed that forest specialists have undergone rapid expansion, while the generalist has experienced more gradual population growth. Results confirm that patterns of neutral genetic variation reflect patterns of volcanic activity in some Tetragnatha species. Our study further suggests that population subdivision and expansion can occur across small spatial and temporal scales, which may facilitate the rapid spread of new character states, leading to speciation as hypothesized by H. L. Carson 30 years ago.

  12. Acting in Light of the Future: How Do Future-Oriented Cultural Practices Evolve and How Can We Accelerate Their Evolution?

    PubMed Central

    Biglan, Anthony; Barnes-Holmes, Yvonne

    2015-01-01

    Despite extensive knowledge of how to prevent or ameliorate serious diseases, natural disasters, environmental degradation, and a wide range of other problems, we often fail to take action that that would prevent or mitigate these problematic outcomes. In short, although we may have sound scientific knowledge about threats to future wellbeing, we appear to have limited insight into how to benefit from this knowledge. With this paper, we argue that our current scientific understanding of how to act in light of the future is limited, but we offer a theoretical analysis of future-oriented behavior at both individual and organizational levels. Specifically, the paper draws on a functional contextualist account of human language and cognition, Relational Frame Theory (RFT), and its integrated therapeutic approach, Acceptance and Commitment Therapy (ACT), and extends this framework to analyzing the evolution of the practices of groups and organizations. This framework can provide an understanding of how human behavior may be modified in the present to serve improving human wellbeing in the future at individual, organizational, and even national levels. PMID:26693140

  13. Acting in Light of the Future: How Do Future-Oriented Cultural Practices Evolve and How Can We Accelerate Their Evolution?

    PubMed

    Biglan, Anthony; Barnes-Holmes, Yvonne

    2015-07-01

    Despite extensive knowledge of how to prevent or ameliorate serious diseases, natural disasters, environmental degradation, and a wide range of other problems, we often fail to take action that that would prevent or mitigate these problematic outcomes. In short, although we may have sound scientific knowledge about threats to future wellbeing, we appear to have limited insight into how to benefit from this knowledge. With this paper, we argue that our current scientific understanding of how to act in light of the future is limited, but we offer a theoretical analysis of future-oriented behavior at both individual and organizational levels. Specifically, the paper draws on a functional contextualist account of human language and cognition, Relational Frame Theory (RFT), and its integrated therapeutic approach, Acceptance and Commitment Therapy (ACT), and extends this framework to analyzing the evolution of the practices of groups and organizations. This framework can provide an understanding of how human behavior may be modified in the present to serve improving human wellbeing in the future at individual, organizational, and even national levels.

  14. The acceleration intermediate phase (NiS and Ni3S2) evolution by nanocrystallization in Li/NiS2 thermal batteries with high specific capacity

    NASA Astrophysics Data System (ADS)

    Jin, Chuanyu; Zhou, Lingping; Fu, Licai; Zhu, Jiajun; Li, Deyi; Yang, Wulin

    2017-06-01

    The intermediate phase of NiS2 is thought to be a bottleneck currently to improve the overall performance of Li/NiS2 thermal batteries because of its low conductivity and close formation enthalpy between NiS2 and the intermediate phase (NiS, Ni3S2, etc). For improving the discharge performances of Li/NiS2 thermal batteries, the nano NiS2 with an average size of 85 ± 5 nm is designated as a cathode material. The electrochemical measurements show that the specific capacity of nano NiS2 cathode is higher than micro NiS2. The nano NiS2 cathode exhibits excellent electrochemical performances with high specific capacities of 794 and 654 mAh g-1 at current density of 0.1 and 0.5 A cm-2 under a cut-off voltage of 0.5 V, respectively. These results show that the rapid intermediate phase evolution from the nanocrystallization can obviously enhance use efficiency of NiS2 and improve discharge performances of thermal batteries.

  15. Influence of volcanic activity on the population genetic structure of Hawaiian Tetragnatha spiders: fragmentation, rapid population growth and the potential for accelerated evolution.

    PubMed

    Vandergast, Amy G; Gillespie, Rosemary G; Roderick, George K

    2004-07-01

    Volcanic activity on the island of Hawaii results in a cyclical pattern of habitat destruction and fragmentation by lava, followed by habitat regeneration on newly formed substrates. While this pattern has been hypothesized to promote the diversification of Hawaiian lineages, there have been few attempts to link geological processes to measurable changes in population structure. We investigated the genetic structure of three species of Hawaiian spiders in forests fragmented by a 150-year-old lava flow on Mauna Loa Volcano, island of Hawaii: Tetragnatha quasimodo (forest and lava flow generalist), T. anuenue and T. brevignatha (forest specialists). To estimate fragmentation effects on population subdivision in each species, we examined variation in mitochondrial and nuclear genomes (DNA sequences and allozymes, respectively). Population subdivision was higher for forest specialists than for the generalist in fragments separated by lava. Patterns of mtDNA sequence evolution also revealed that forest specialists have undergone rapid expansion, while the generalist has experienced more gradual population growth. Results confirm that patterns of neutral genetic variation reflect patterns of volcanic activity in some Tetragnatha species. Our study further suggests that population subdivision and expansion can occur across small spatial and temporal scales, which may facilitate the rapid spread of new character states, leading to speciation as hypothesized by H. L. Carson 30 years ago.

  16. Particle Accelerators in China

    NASA Astrophysics Data System (ADS)

    Zhang, Chuang; Fang, Shouxian

    As the special machines that can accelerate charged particle beams to high energy by using electromagnetic fields, particle accelerators have been widely applied in scientific research and various areas of society. The development of particle accelerators in China started in the early 1950s. After a brief review of the history of accelerators, this article describes in the following sections: particle colliders, heavy-ion accelerators, high-intensity proton accelerators, accelerator-based light sources, pulsed power accelerators, small scale accelerators, accelerators for applications, accelerator technology development and advanced accelerator concepts. The prospects of particle accelerators in China are also presented.

  17. Coastal response to accelerated sea-level rise (>4 mm/yr) based on early-mid Holocene coastal evolution in the northwestern Gulf of Mexico

    NASA Astrophysics Data System (ADS)

    Anderson, J. B.; Rodriguez, A. B.; Simms, A.

    2009-12-01

    indicate that coastal inundation models, which focus on the magnitude of sea-level rise, greatly underestimate the impact of accelerated sea-level rise that will likely occur by the end of this century.

  18. Compact accelerator

    DOEpatents

    Caporaso, George J.; Sampayan, Stephen E.; Kirbie, Hugh C.

    2007-02-06

    A compact linear accelerator having at least one strip-shaped Blumlein module which guides a propagating wavefront between first and second ends and controls the output pulse at the second end. Each Blumlein module has first, second, and third planar conductor strips, with a first dielectric strip between the first and second conductor strips, and a second dielectric strip between the second and third conductor strips. Additionally, the compact linear accelerator includes a high voltage power supply connected to charge the second conductor strip to a high potential, and a switch for switching the high potential in the second conductor strip to at least one of the first and third conductor strips so as to initiate a propagating reverse polarity wavefront(s) in the corresponding dielectric strip(s).

  19. MUON ACCELERATION

    SciTech Connect

    BERG,S.J.

    2003-11-18

    One of the major motivations driving recent interest in FFAGs is their use for the cost-effective acceleration of muons. This paper summarizes the progress in this area that was achieved leading up to and at the FFAG workshop at KEK from July 7-12, 2003. Much of the relevant background and references are also given here, to give a context to the progress we have made.

  20. BICEP's acceleration

    SciTech Connect

    Contaldi, Carlo R.

    2014-10-01

    The recent Bicep2 [1] detection of, what is claimed to be primordial B-modes, opens up the possibility of constraining not only the energy scale of inflation but also the detailed acceleration history that occurred during inflation. In turn this can be used to determine the shape of the inflaton potential V(φ) for the first time — if a single, scalar inflaton is assumed to be driving the acceleration. We carry out a Monte Carlo exploration of inflationary trajectories given the current data. Using this method we obtain a posterior distribution of possible acceleration profiles ε(N) as a function of e-fold N and derived posterior distributions of the primordial power spectrum P(k) and potential V(φ). We find that the Bicep2 result, in combination with Planck measurements of total intensity Cosmic Microwave Background (CMB) anisotropies, induces a significant feature in the scalar primordial spectrum at scales k∼ 10{sup -3} Mpc {sup -1}. This is in agreement with a previous detection of a suppression in the scalar power [2].

  1. Laser acceleration

    NASA Astrophysics Data System (ADS)

    Tajima, T.; Nakajima, K.; Mourou, G.

    2017-02-01

    The fundamental idea of Laser Wakefield Acceleration (LWFA) is reviewed. An ultrafast intense laser pulse drives coherent wakefield with a relativistic amplitude robustly supported by the plasma. While the large amplitude of wakefields involves collective resonant oscillations of the eigenmode of the entire plasma electrons, the wake phase velocity ˜ c and ultrafastness of the laser pulse introduce the wake stability and rigidity. A large number of worldwide experiments show a rapid progress of this concept realization toward both the high-energy accelerator prospect and broad applications. The strong interest in this has been spurring and stimulating novel laser technologies, including the Chirped Pulse Amplification, the Thin Film Compression, the Coherent Amplification Network, and the Relativistic Mirror Compression. These in turn have created a conglomerate of novel science and technology with LWFA to form a new genre of high field science with many parameters of merit in this field increasing exponentially lately. This science has triggered a number of worldwide research centers and initiatives. Associated physics of ion acceleration, X-ray generation, and astrophysical processes of ultrahigh energy cosmic rays are reviewed. Applications such as X-ray free electron laser, cancer therapy, and radioisotope production etc. are considered. A new avenue of LWFA using nanomaterials is also emerging.

  2. Fate of an accelerating universe

    SciTech Connect

    Gu, J.-A.; Hwang, W-Y. P.

    2006-01-15

    The presently accelerating universe may keep accelerating forever, eventually run into the event horizon problem, and thus be in conflict with the superstring idea. On the other hand, the current accelerating phase as well as the fate of the universe may be swayed by a negative cosmological constant, which dictates a big crunch. Based on the current observational data, in this paper we investigate how large the magnitude of a negative cosmological constant is allowed to be. In addition, for distinguishing the sign of the cosmological constant via observations, we point out that a measure of the evolution of the dark energy equation-of-state may be a good discriminator. Hopefully future observations will provide much more detailed information about dark energy and thereby indicate the sign of the cosmological constant as well as the fate of the presently accelerating universe.

  3. Advanced concepts for acceleration

    SciTech Connect

    Keefe, D.

    1986-07-01

    Selected examples of advanced accelerator concepts are reviewed. Such plasma accelerators as plasma beat wave accelerator, plasma wake field accelerator, and plasma grating accelerator are discussed particularly as examples of concepts for accelerating relativistic electrons or positrons. Also covered are the pulsed electron-beam, pulsed laser accelerator, inverse Cherenkov accelerator, inverse free-electron laser, switched radial-line accelerators, and two-beam accelerator. Advanced concepts for ion acceleration discussed include the electron ring accelerator, excitation of waves on intense electron beams, and two-wave combinations. (LEW)

  4. Accelerators and the Accelerator Community

    SciTech Connect

    Malamud, Ernest; Sessler, Andrew

    2008-06-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  5. Laser wakefield acceleration of polarized electron beams

    NASA Astrophysics Data System (ADS)

    Pugacheva, D. V.; Andreev, N. E.; Cros, B.

    2016-11-01

    The acceleration of highly polarized electron beams are widely used in state-of-the-art high-energy physics experiments. In this work, a model for investigation of polarization dynamics of electron beams in the laser-plasma accelerator depending on the initial energy of electrons was developed and tested. To obtain the evolution of the trajectory and momentum of the electron for modeling its acceleration the wakefield structure was determined. The spin precession of the beam electron was described by Thomas-Bargman-Michel-Telegdi equations. The evolution of the electron beam polarization was investigated for zero-emittance beams with zero-energy spread.

  6. Impact accelerations

    NASA Technical Reports Server (NTRS)

    Vongierke, H. E.; Brinkley, J. W.

    1975-01-01

    The degree to which impact acceleration is an important factor in space flight environments depends primarily upon the technology of capsule landing deceleration and the weight permissible for the associated hardware: parachutes or deceleration rockets, inflatable air bags, or other impact attenuation systems. The problem most specific to space medicine is the potential change of impact tolerance due to reduced bone mass and muscle strength caused by prolonged weightlessness and physical inactivity. Impact hazards, tolerance limits, and human impact tolerance related to space missions are described.

  7. Centralized digital control of accelerators

    SciTech Connect

    Melen, R.E.

    1983-09-01

    In contrasting the title of this paper with a second paper to be presented at this conference entitled Distributed Digital Control of Accelerators, a potential reader might be led to believe that this paper will focus on systems whose computing intelligence is centered in one or more computers in a centralized location. Instead, this paper will describe the architectural evolution of SLAC's computer based accelerator control systems with respect to the distribution of their intelligence. However, the use of the word centralized in the title is appropriate because these systems are based on the use of centralized large and computationally powerful processors that are typically supported by networks of smaller distributed processors.

  8. Accelerator system and method of accelerating particles

    NASA Technical Reports Server (NTRS)

    Wirz, Richard E. (Inventor)

    2010-01-01

    An accelerator system and method that utilize dust as the primary mass flux for generating thrust are provided. The accelerator system can include an accelerator capable of operating in a self-neutralizing mode and having a discharge chamber and at least one ionizer capable of charging dust particles. The system can also include a dust particle feeder that is capable of introducing the dust particles into the accelerator. By applying a pulsed positive and negative charge voltage to the accelerator, the charged dust particles can be accelerated thereby generating thrust and neutralizing the accelerator system.

  9. Accelerated probabilistic inference of RNA structure evolution

    PubMed Central

    Holmes, Ian

    2005-01-01

    Background Pairwise stochastic context-free grammars (Pair SCFGs) are powerful tools for evolutionary analysis of RNA, including simultaneous RNA sequence alignment and secondary structure prediction, but the associated algorithms are intensive in both CPU and memory usage. The same problem is faced by other RNA alignment-and-folding algorithms based on Sankoff's 1985 algorithm. It is therefore desirable to constrain such algorithms, by pre-processing the sequences and using this first pass to limit the range of structures and/or alignments that can be considered. Results We demonstrate how flexible classes of constraint can be imposed, greatly reducing the computational costs while maintaining a high quality of structural homology prediction. Any score-attributed context-free grammar (e.g. energy-based scoring schemes, or conditionally normalized Pair SCFGs) is amenable to this treatment. It is now possible to combine independent structural and alignment constraints of unprecedented general flexibility in Pair SCFG alignment algorithms. We outline several applications to the bioinformatics of RNA sequence and structure, including Waterman-Eggert N-best alignments and progressive multiple alignment. We evaluate the performance of the algorithm on test examples from the RFAM database. Conclusion A program, Stemloc, that implements these algorithms for efficient RNA sequence alignment and structure prediction is available under the GNU General Public License. PMID:15790387

  10. Evolution of coiled tubing drilling technology accelerates

    SciTech Connect

    Simmons, J.; Adam, B.

    1993-09-01

    This paper reviews the status of coiled tubing technology in oil and gas drilling operations. The paper starts with a description of current coiled tubing technology and provides a cost comparison between conventional and coiled tubing drilling. The results show that offshore operations are already competitive while onshore operations will still lag behind conventional drilling methods. A list of known coiled tubing drilling operations is provided which gives the current borehole diameters and depths associated with this technology. The paper then goes on to provide the advantages and disadvantages of the technology. The advantages include improved well control, a continuous drillstring, reduced mobilization costs, simplified logging and measurement-while drilling measurements, and less tripping required. The disadvantages include high friction with the borehole wall, downhole motors required, limited drillhole size, and fatigued or damaged sections of the tubing cannot be removed. Finally, a review of the reliability of this technology is provided.

  11. Speeding up evolution

    NASA Astrophysics Data System (ADS)

    Hoff, Wouter

    Proteins and cells offer great opportunities for green chemistry and renewable energy. However, few of these possible applications have been put into practice because of details that turn out to be major barriers to cost-efficient implementation and that prove difficult to solve by genetic engineering. A better understanding of molecular evolution promises a novel approach to addressing these important challenges. While major advances have been made, major gaps remain in understanding the evolution of proteins. Different approaches to accelerating molecular evolution into targeted directions will be discussed, including recent progress on evolution in non-homogeneous environments.

  12. Progress on plasma accelerators

    SciTech Connect

    Chen, P.

    1986-05-01

    Several plasma accelerator concepts are reviewed, with emphasis on the Plasma Beat Wave Accelerator (PBWA) and the Plasma Wake Field Accelerator (PWFA). Various accelerator physics issues regarding these schemes are discussed, and numerical examples on laboratory scale experiments are given. The efficiency of plasma accelerators is then revealed with suggestions on improvements. Sources that cause emittance growth are discussed briefly.

  13. Methods of geometrical integration in accelerator physics

    NASA Astrophysics Data System (ADS)

    Andrianov, S. N.

    2016-12-01

    In the paper we consider a method of geometric integration for a long evolution of the particle beam in cyclic accelerators, based on the matrix representation of the operator of particles evolution. This method allows us to calculate the corresponding beam evolution in terms of two-dimensional matrices including for nonlinear effects. The ideology of the geometric integration introduces in appropriate computational algorithms amendments which are necessary for preserving the qualitative properties of maps presented in the form of the truncated series generated by the operator of evolution. This formalism extends both on polarized and intense beams. Examples of practical applications are described.

  14. Electron acceleration via magnetic island coalescence

    NASA Astrophysics Data System (ADS)

    Shinohara, I.; Yumura, T.; Tanaka, K. G.; Fujimoto, M.

    2009-06-01

    Electron acceleration via fast magnetic island coalescence that happens as quick magnetic reconnection triggering (QMRT) proceeds has been studied. We have carried out a three-dimensional full kinetic simulation of the Harris current sheet with a large enough simulation run for two magnetic islands coalescence. Due to the strong inductive electric field associated with the non-linear evolution of the lower-hybrid-drift instability and the magnetic island coalescence process observed in the non-linear stage of the collisionless tearing mode, electrons are significantly accelerated at around the neutral sheet and the subsequent X-line. The accelerated meandering electrons generated by the non-linear evolution of the lower-hybrid-drift instability are resulted in QMRT, and QMRT leads to fast magnetic island coalescence. As a whole, the reconnection triggering and its transition to large-scale structure work as an effective electron accelerator.

  15. Community Petascale Project for Accelerator Science and Simulation: Advancing Computational Science for Future Accelerators and Accelerator Technologies

    SciTech Connect

    Spentzouris, P.; Cary, J.; McInnes, L.C.; Mori, W.; Ng, C.; Ng, E.; Ryne, R.; /LBL, Berkeley

    2011-11-14

    The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessary accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R&D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors. ComPASS is in the first year of executing its plan to develop the next-generation HPC accelerator modeling tools. ComPASS aims to develop an integrated simulation environment that will utilize existing and new accelerator physics modules with petascale capabilities, by employing modern computing and solver technologies. The ComPASS vision is to deliver to accelerator scientists a virtual accelerator and virtual prototyping modeling environment, with the necessary multiphysics, multiscale capabilities. The plan for this development includes delivering accelerator modeling applications appropriate for each stage of the ComPASS software evolution. Such applications are already being used to address challenging problems in accelerator design and optimization. The ComPASS organization

  16. ACCELERATION AND THE GIFTED.

    ERIC Educational Resources Information Center

    GIBSON, ARTHUR R.; STEPHANS, THOMAS M.

    ACCELERATION OF PUPILS AND SUBJECTS IS CONSIDERED A MEANS OF EDUCATING THE ACADEMICALLY GIFTED STUDENT. FIVE INTRODUCTORY ARTICLES PROVIDE A FRAMEWORK FOR THINKING ABOUT ACCELERATION. FIVE PROJECT REPORTS OF ACCELERATED PROGRAMS IN OHIO ARE INCLUDED. ACCELERATION IS NOW BEING REGARDED MORE FAVORABLY THAN FORMERLY, BECAUSE METHODS HAVE BEEN…

  17. Future accelerator technology

    SciTech Connect

    Sessler, A.M.

    1986-05-01

    A general discussion is presented of the acceleration of particles. Upon this foundation is built a categorization scheme into which all accelerators can be placed. Special attention is devoted to accelerators which employ a wake-field mechanism and a restricting theorem is examined. It is shown how the theorem may be circumvented. Comments are made on various acceleration schemes.

  18. ACCELERATION AND THE GIFTED.

    ERIC Educational Resources Information Center

    GIBSON, ARTHUR R.; STEPHANS, THOMAS M.

    ACCELERATION OF PUPILS AND SUBJECTS IS CONSIDERED A MEANS OF EDUCATING THE ACADEMICALLY GIFTED STUDENT. FIVE INTRODUCTORY ARTICLES PROVIDE A FRAMEWORK FOR THINKING ABOUT ACCELERATION. FIVE PROJECT REPORTS OF ACCELERATED PROGRAMS IN OHIO ARE INCLUDED. ACCELERATION IS NOW BEING REGARDED MORE FAVORABLY THAN FORMERLY, BECAUSE METHODS HAVE BEEN…

  19. Laser driven ion accelerator

    DOEpatents

    Tajima, Toshiki

    2005-06-14

    A system and method of accelerating ions in an accelerator to optimize the energy produced by a light source. Several parameters may be controlled in constructing a target used in the accelerator system to adjust performance of the accelerator system. These parameters include the material, thickness, geometry and surface of the target.

  20. Laser driven ion accelerator

    DOEpatents

    Tajima, Toshiki

    2006-04-18

    A system and method of accelerating ions in an accelerator to optimize the energy produced by a light source. Several parameters may be controlled in constructing a target used in the accelerator system to adjust performance of the accelerator system. These parameters include the material, thickness, geometry and surface of the target.

  1. Piezoelectric particle accelerator

    DOEpatents

    Kemp, Mark A.; Jongewaard, Erik N.; Haase, Andrew A.; Franzi, Matthew

    2017-08-29

    A particle accelerator is provided that includes a piezoelectric accelerator element, where the piezoelectric accelerator element includes a hollow cylindrical shape, and an input transducer, where the input transducer is disposed to provide an input signal to the piezoelectric accelerator element, where the input signal induces a mechanical excitation of the piezoelectric accelerator element, where the mechanical excitation is capable of generating a piezoelectric electric field proximal to an axis of the cylindrical shape, where the piezoelectric accelerator is configured to accelerate a charged particle longitudinally along the axis of the cylindrical shape according to the piezoelectric electric field.

  2. The direction of acceleration

    NASA Astrophysics Data System (ADS)

    Wilhelm, Thomas; Burde, Jan-Philipp; Lück, Stephan

    2015-11-01

    Acceleration is a physical quantity that is difficult to understand and hence its complexity is often erroneously simplified. Many students think of acceleration as equivalent to velocity, a ˜ v. For others, acceleration is a scalar quantity, which describes the change in speed Δ|v| or Δ|v|/Δt (as opposed to the change in velocity). The main difficulty with the concept of acceleration therefore lies in developing a correct understanding of its direction. The free iOS app AccelVisu supports students in acquiring a correct conception of acceleration by showing acceleration arrows directly at moving objects.

  3. Operational radiation protection in high-energy physics accelerators: implementation of ALARA in design and operation of accelerators.

    PubMed

    Fassò, A; Rokni, S

    2009-11-01

    This paper considers the historical evolution of the concept of optimisation of radiation exposures, as commonly expressed by the acronym ALARA, and discusses its application to various aspects of radiation protection at high-energy accelerators.

  4. Accelerating momentum for change!

    PubMed

    Wenzel, S; Panetta, J

    1995-05-01

    As we develop strategies to compete globally, we are challenged with integrating our resources to execute these strategies effectively. Many companies are in the midst of dramatic shifts in corporate cultures, giving more responsibility to employees while raising expectations for their performance. The extent of these changes is far reaching and brings significant challenges to both employees and corporations. This article is a continuation of the evolution (over five years) of a corrective action/continuous improvement process implemented at Exide Electronics. It discusses organizational structures, including steering committees, corrective action teams, task teams, and work cells. Specific expectations, goals, and results of the teams are presented, along with ground rules for functioning within the organization. After structuring the organization and coordinating the resources effectively, the next challenge is accelerating momentum for change. The presentation also discusses the evolutionary process required to make a culture focused on change, including ongoing communication and feedback, constant evaluation and direction of the process, and measuring and paying for performance.

  5. Cyclotrons and FFAG Accelerators as Drivers for ADS

    DOE PAGES

    Calabretta, Luciano; Méot, François

    2015-01-01

    Our review summarizes projects and studies on circular accelerators proposed for driving subcritical reactors. The early isochronous cyclotron cascades, proposed about 20 years ago, and the evolution of these layouts up to the most recent solutions or designs based on cyclotrons and fixed field alternating gradient accelerators, are reported. Additionally, the newest ideas and their prospects for development are discussed.

  6. Cyclotrons and FFAG Accelerators as Drivers for ADS

    SciTech Connect

    Calabretta, Luciano; Méot, François

    2015-01-01

    Our review summarizes projects and studies on circular accelerators proposed for driving subcritical reactors. The early isochronous cyclotron cascades, proposed about 20 years ago, and the evolution of these layouts up to the most recent solutions or designs based on cyclotrons and fixed field alternating gradient accelerators, are reported. Additionally, the newest ideas and their prospects for development are discussed.

  7. Investigations of the plasma and structure based accelerators

    SciTech Connect

    Shvets, Gennady

    2012-08-30

    The objective of our research during the reported period was three-fold: (a) theoretical investigation of novel mechanisms of injection into laser wake field accelerators; (b) theoretical investigation of single-shot frequency domain diagnostics of relativistic plasma wakes, specifically in the context of spatio-temporal evolution of the plasma bubble;(c) experimental and theoretical investigation of laser-driven accelerating structure, specifically in the context of the Surface Wave Accelerator Based on SiC (SWABSIC).

  8. The Modern Temperature-Accelerated Dynamics Approach.

    PubMed

    Zamora, Richard J; Uberuaga, Blas P; Perez, Danny; Voter, Arthur F

    2016-06-07

    Accelerated molecular dynamics (AMD) is a class of MD-based methods used to simulate atomistic systems in which the metastable state-to-state evolution is slow compared with thermal vibrations. Temperature-accelerated dynamics (TAD) is a particularly efficient AMD procedure in which the predicted evolution is hastened by elevating the temperature of the system and then recovering the correct state-to-state dynamics at the temperature of interest. TAD has been used to study various materials applications, often revealing surprising behavior beyond the reach of direct MD. This success has inspired several algorithmic performance enhancements, as well as the analysis of its mathematical framework. Recently, these enhancements have leveraged parallel programming techniques to enhance both the spatial and temporal scaling of the traditional approach. We review the ongoing evolution of the modern TAD method and introduce the latest development: speculatively parallel TAD.

  9. The modern temperature-accelerated dynamics approach

    DOE PAGES

    Zamora, Richard J.; Uberuaga, Blas P.; Perez, Danny; ...

    2016-06-01

    Accelerated molecular dynamics (AMD) is a class of MD-based methods used to simulate atomistic systems in which the metastable state-to-state evolution is slow compared with thermal vibrations. Temperature-accelerated dynamics (TAD) is a particularly efficient AMD procedure in which the predicted evolution is hastened by elevating the temperature of the system and then recovering the correct state-to-state dynamics at the temperature of interest. TAD has been used to study various materials applications, often revealing surprising behavior beyond the reach of direct MD. This success has inspired several algorithmic performance enhancements, as well as the analysis of its mathematical framework. Recently, thesemore » enhancements have leveraged parallel programming techniques to enhance both the spatial and temporal scaling of the traditional approach. Here, we review the ongoing evolution of the modern TAD method and introduce the latest development: speculatively parallel TAD.« less

  10. The modern temperature-accelerated dynamics approach

    SciTech Connect

    Zamora, Richard J.; Uberuaga, Blas P.; Perez, Danny; Voter, Arthur F.

    2016-06-01

    Accelerated molecular dynamics (AMD) is a class of MD-based methods used to simulate atomistic systems in which the metastable state-to-state evolution is slow compared with thermal vibrations. Temperature-accelerated dynamics (TAD) is a particularly efficient AMD procedure in which the predicted evolution is hastened by elevating the temperature of the system and then recovering the correct state-to-state dynamics at the temperature of interest. TAD has been used to study various materials applications, often revealing surprising behavior beyond the reach of direct MD. This success has inspired several algorithmic performance enhancements, as well as the analysis of its mathematical framework. Recently, these enhancements have leveraged parallel programming techniques to enhance both the spatial and temporal scaling of the traditional approach. Here, we review the ongoing evolution of the modern TAD method and introduce the latest development: speculatively parallel TAD.

  11. The modern temperature-accelerated dynamics approach

    SciTech Connect

    Zamora, Richard J.; Uberuaga, Blas P.; Perez, Danny; Voter, Arthur F.

    2016-06-01

    Accelerated molecular dynamics (AMD) is a class of MD-based methods used to simulate atomistic systems in which the metastable state-to-state evolution is slow compared with thermal vibrations. Temperature-accelerated dynamics (TAD) is a particularly efficient AMD procedure in which the predicted evolution is hastened by elevating the temperature of the system and then recovering the correct state-to-state dynamics at the temperature of interest. TAD has been used to study various materials applications, often revealing surprising behavior beyond the reach of direct MD. This success has inspired several algorithmic performance enhancements, as well as the analysis of its mathematical framework. Recently, these enhancements have leveraged parallel programming techniques to enhance both the spatial and temporal scaling of the traditional approach. Here, we review the ongoing evolution of the modern TAD method and introduce the latest development: speculatively parallel TAD.

  12. Peak acceleration limiter

    NASA Technical Reports Server (NTRS)

    Chapman, C. P.

    1972-01-01

    Device is described that limits accelerations by shutting off shaker table power very rapidly in acceleration tests. Absolute value of accelerometer signal is used to trigger electronic switch which terminates test and sounds alarm.

  13. Improved plasma accelerator

    NASA Technical Reports Server (NTRS)

    Cheng, D. Y.

    1971-01-01

    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  14. Linear Accelerator (LINAC)

    MedlinePlus

    ... equipment? How is safety ensured? What is this equipment used for? A linear accelerator (LINAC) is the ... Therapy (SBRT) . top of page How does the equipment work? The linear accelerator uses microwave technology (similar ...

  15. Accelerating Particles with Plasma

    SciTech Connect

    Litos, Michael; Hogan, Mark

    2014-11-05

    Researchers at SLAC explain how they use plasma wakefields to accelerate bunches of electrons to very high energies over only a short distance. Their experiments offer a possible path for the future of particle accelerators.

  16. Linear Accelerator (LINAC)

    MedlinePlus

    ... equipment? How is safety ensured? What is this equipment used for? A linear accelerator (LINAC) is the ... Therapy (SBRT) . top of page How does the equipment work? The linear accelerator uses microwave technology (similar ...

  17. Accelerating Particles with Plasma

    ScienceCinema

    Litos, Michael; Hogan, Mark

    2016-07-12

    Researchers at SLAC explain how they use plasma wakefields to accelerate bunches of electrons to very high energies over only a short distance. Their experiments offer a possible path for the future of particle accelerators.

  18. Accelerator Technology Division

    NASA Astrophysics Data System (ADS)

    1992-04-01

    In fiscal year (FY) 1991, the Accelerator Technology (AT) division continued fulfilling its mission to pursue accelerator science and technology and to develop new accelerator concepts for application to research, defense, energy, industry, and other areas of national interest. This report discusses the following programs: The Ground Test Accelerator Program; APLE Free-Electron Laser Program; Accelerator Transmutation of Waste; JAERI, OMEGA Project, and Intense Neutron Source for Materials Testing; Advanced Free-Electron Laser Initiative; Superconducting Super Collider; The High-Power Microwave Program; (Phi) Factory Collaboration; Neutral Particle Beam Power System Highlights; Accelerator Physics and Special Projects; Magnetic Optics and Beam Diagnostics; Accelerator Design and Engineering; Radio-Frequency Technology; Free-Electron Laser Technology; Accelerator Controls and Automation; Very High-Power Microwave Sources and Effects; and GTA Installation, Commissioning, and Operations.

  19. Acceleration: It's Elementary

    ERIC Educational Resources Information Center

    Willis, Mariam

    2012-01-01

    Acceleration is one tool for providing high-ability students the opportunity to learn something new every day. Some people talk about acceleration as taking a student out of step. In actuality, what one is doing is putting a student in step with the right curriculum. Whole-grade acceleration, also called grade-skipping, usually happens between…

  20. Accelerated test design

    NASA Technical Reports Server (NTRS)

    Mcdermott, P. P.

    1980-01-01

    The design of an accelerated life test program for electric batteries is discussed. A number of observations and suggestions on the procedures and objectives for conducting an accelerated life test program are presented. Equations based on nonlinear regression analysis for predicting the accelerated life test parameters are discussed.

  1. Angular Acceleration without Torque?

    ERIC Educational Resources Information Center

    Kaufman, Richard D.

    2012-01-01

    Hardly. Just as Robert Johns qualitatively describes angular acceleration by an internal force in his article "Acceleration Without Force?" here we will extend the discussion to consider angular acceleration by an internal torque. As we will see, this internal torque is due to an internal force acting at a distance from an instantaneous center.

  2. Acceleration: It's Elementary

    ERIC Educational Resources Information Center

    Willis, Mariam

    2012-01-01

    Acceleration is one tool for providing high-ability students the opportunity to learn something new every day. Some people talk about acceleration as taking a student out of step. In actuality, what one is doing is putting a student in step with the right curriculum. Whole-grade acceleration, also called grade-skipping, usually happens between…

  3. Far field acceleration

    SciTech Connect

    Fernow, R.C.

    1995-07-01

    Far fields are propagating electromagnetic waves far from their source, boundary surfaces, and free charges. The general principles governing the acceleration of charged particles by far fields are reviewed. A survey of proposed field configurations is given. The two most important schemes, Inverse Cerenkov acceleration and Inverse free electron laser acceleration, are discussed in detail.

  4. Angular Acceleration without Torque?

    ERIC Educational Resources Information Center

    Kaufman, Richard D.

    2012-01-01

    Hardly. Just as Robert Johns qualitatively describes angular acceleration by an internal force in his article "Acceleration Without Force?" here we will extend the discussion to consider angular acceleration by an internal torque. As we will see, this internal torque is due to an internal force acting at a distance from an instantaneous center.

  5. Particle Acceleration and Emission in Relativistic Jets

    NASA Technical Reports Server (NTRS)

    Nishikawa, K.; Hardee, P. E.; Richardson, G. A.; Preece, R. D.; Sol, H.; Fishman, G. J.

    2003-01-01

    Shock wave acceleration is an ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., the Buneman instability, two-streaming instability, and the Weibel instability) created in the shocks are responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic jet front propagating through an ambient plasma with and without initial magnetic fields. We find only small differences in the results between no ambient and weak ambient magnetic fields. Simulations show that the Weibel instability created in the collisionless shock front accelerates particles perpendicular and parallel to the jet propagation direction. While some Fermi acceleration may occur at the jet front, the majority of electron acceleration takes place behind the jet front and cannot be characterized as Fermi acceleration. The simulation results show that this instability is responsible for generating and amplifying highly nonuniform, small-scale magnetic fields, which contribute to the electron's transverse deflection behind the jet head. The 'jitter' radiation from deflected electrons has different properties than synchrotron radiation which is calculated in a uniform magnetic field. This jitter radiation may be important to understanding the complex time evolution and/or spectral structure in gamma-ray bursts, relativistic jets, and supernova remnants.

  6. Compact Plasma Accelerator

    NASA Technical Reports Server (NTRS)

    Foster, John E.

    2004-01-01

    A plasma accelerator has been conceived for both material-processing and spacecraft-propulsion applications. This accelerator generates and accelerates ions within a very small volume. Because of its compactness, this accelerator could be nearly ideal for primary or station-keeping propulsion for spacecraft having masses between 1 and 20 kg. Because this accelerator is designed to generate beams of ions having energies between 50 and 200 eV, it could also be used for surface modification or activation of thin films.

  7. Acceleration of black hole universe

    NASA Astrophysics Data System (ADS)

    Zhang, T. X.; Frederick, C.

    2014-01-01

    Recently, Zhang slightly modified the standard big bang theory and developed a new cosmological model called black hole universe, which is consistent with Mach's principle, governed by Einstein's general theory of relativity, and able to explain all observations of the universe. Previous studies accounted for the origin, structure, evolution, expansion, and cosmic microwave background radiation of the black hole universe, which grew from a star-like black hole with several solar masses through a supermassive black hole with billions of solar masses to the present state with hundred billion-trillions of solar masses by accreting ambient matter and merging with other black holes. This paper investigates acceleration of the black hole universe and provides an alternative explanation for the redshift and luminosity distance measurements of type Ia supernovae. The results indicate that the black hole universe accelerates its expansion when it accretes the ambient matter in an increasing rate. In other words, i.e., when the second-order derivative of the mass of the black hole universe with respect to the time is positive . For a constant deceleration parameter , we can perfectly explain the type Ia supernova measurements with the reduced chi-square to be very close to unity, χ red˜1.0012. The expansion and acceleration of black hole universe are driven by external energy.

  8. Fiber Accelerating Structures

    SciTech Connect

    Hammond, Andrew P.; /Reed Coll. /SLAC

    2010-08-25

    One of the options for future particle accelerators are photonic band gap (PBG) fiber accelerators. PBG fibers are specially designed optical fibers that use lasers to excite an electric field that is used to accelerate electrons. To improve PBG accelerators, the basic parameters of the fiber were tested to maximize defect size and acceleration. Using the program CUDOS, several accelerating modes were found that maximized these parameters for several wavelengths. The design of multiple defects, similar to having closely bound fibers, was studied to find possible coupling or the change of modes. The amount of coupling was found to be dependent on distance separated. For certain distances accelerating coupled modes were found and examined. In addition, several non-periodic fiber structures were examined using CUDOS. The non-periodic fibers produced several interesting results and promised more modes given time to study them in more detail.

  9. High brightness electron accelerator

    DOEpatents

    Sheffield, Richard L.; Carlsten, Bruce E.; Young, Lloyd M.

    1994-01-01

    A compact high brightness linear accelerator is provided for use, e.g., in a free electron laser. The accelerator has a first plurality of acclerating cavities having end walls with four coupling slots for accelerating electrons to high velocities in the absence of quadrupole fields. A second plurality of cavities receives the high velocity electrons for further acceleration, where each of the second cavities has end walls with two coupling slots for acceleration in the absence of dipole fields. The accelerator also includes a first cavity with an extended length to provide for phase matching the electron beam along the accelerating cavities. A solenoid is provided about the photocathode that emits the electons, where the solenoid is configured to provide a substantially uniform magnetic field over the photocathode surface to minimize emittance of the electons as the electrons enter the first cavity.

  10. High brightness electron accelerator

    SciTech Connect

    Sheffield, R.L.; Carlsten, B.E.; Young, L.M.

    1992-12-31

    A compact high brightness linear accelerator is provided for use, e.g., in a free electron laser. The accelerator has a first plurality of acclerating cavities having end walls with four coupling slots for accelerating electrons to high velocities in the absence of quadrupole fields. A second plurality of cavities receives the high velocity electrons for further acceleration, where each of the second cavities has end walls with two coupling slots for acceleration in the absence of dipole fields. The accelerator also includes a first cavity with an extended length to provide for phase matching the electron beam along the accelerating cavities. A solenoid is provided about the photocathode that emits the electrons, where the solenoid is configured to provide a substantially uniform magnetic field over the photocathode surface to minimize emittance of the electrons as the electrons enter the first cavity.

  11. Acceleration in astrophysics

    SciTech Connect

    Colgate, S.A.

    1993-12-31

    The origin of cosmic rays and applicable laboratory experiments are discussed. Some of the problems of shock acceleration for the production of cosmic rays are discussed in the context of astrophysical conditions. These are: The presumed unique explanation of the power law spectrum is shown instead to be a universal property of all lossy accelerators; the extraordinary isotropy of cosmic rays and the limited diffusion distances implied by supernova induced shock acceleration requires a more frequent and space-filling source than supernovae; the near perfect adiabaticity of strong hydromagnetic turbulence necessary for reflecting the accelerated particles each doubling in energy roughly 10{sup 5} to {sup 6} scatterings with negligible energy loss seems most unlikely; the evidence for acceleration due to quasi-parallel heliosphere shocks is weak. There is small evidence for the expected strong hydromagnetic turbulence, and instead, only a small number of particles accelerate after only a few shock traversals; the acceleration of electrons in the same collisionless shock that accelerates ions is difficult to reconcile with the theoretical picture of strong hydromagnetic turbulence that reflects the ions. The hydromagnetic turbulence will appear adiabatic to the electrons at their much higher Larmor frequency and so the electrons should not be scattered incoherently as they must be for acceleration. Therefore the electrons must be accelerated by a different mechanism. This is unsatisfactory, because wherever electrons are accelerated these sites, observed in radio emission, may accelerate ions more favorably. The acceleration is coherent provided the reconnection is coherent, in which case the total flux, as for example of collimated radio sources, predicts single charge accelerated energies much greater than observed.

  12. An introduction to acceleration mechanisms

    SciTech Connect

    Palmer, R.B.

    1987-05-01

    This paper discusses the acceleration of charged particles by electromagnetic fields, i.e., by fields that are produced by the motion of other charged particles driven by some power source. The mechanisms that are discussed include: Ponderamotive Forces, Acceleration, Plasma Beat Wave Acceleration, Inverse Free Electron Laser Acceleration, Inverse Cerenkov Acceleration, Gravity Acceleration, 2D Linac Acceleration and Conventional Iris Loaded Linac Structure Acceleration. (LSP)

  13. Accelerated universes from type IIA compactifications

    SciTech Connect

    Blåbäck, Johan; Danielsson, Ulf; Dibitetto, Giuseppe E-mail: ulf.danielsson@physics.uu.se

    2014-03-01

    We study slow-roll accelerating cosmologies arising from geometric compactifications of type IIA string theory on T{sup 6}/(Z{sub 2}  ×  Z{sub 2}). With the aid of a genetic algorithm, we are able to find quasi-de Sitter backgrounds with both slow-roll parameters of order 0.1. Furthermore, we study their evolution by numerically solving the corresponding time-dependent equations of motion, and we show that they actually display a few e-folds of accelerated expansion. Finally, we comment on their perturbative reliability.

  14. Schooling in Times of Acceleration

    ERIC Educational Resources Information Center

    Buddeberg, Magdalena; Hornberg, Sabine

    2017-01-01

    Modern societies are characterised by forms of acceleration, which influence social processes. Sociologist Hartmut Rosa has systematised temporal structures by focusing on three categories of social acceleration: technical acceleration, acceleration of social change, and acceleration of the pace of life. All three processes of acceleration are…

  15. Schooling in Times of Acceleration

    ERIC Educational Resources Information Center

    Buddeberg, Magdalena; Hornberg, Sabine

    2017-01-01

    Modern societies are characterised by forms of acceleration, which influence social processes. Sociologist Hartmut Rosa has systematised temporal structures by focusing on three categories of social acceleration: technical acceleration, acceleration of social change, and acceleration of the pace of life. All three processes of acceleration are…

  16. Rayleigh-Taylor instability with complex acceleration history.

    PubMed

    Dimonte, Guy; Ramaprabhu, Praveen; Andrews, Malcolm

    2007-10-01

    Experiments and numerical simulations are performed on the Rayleigh-Taylor instability with a complex acceleration history g(t) consisting of consecutive periods of acceleration, deceleration, and acceleration. The dominant bubbles and spikes that grow in the initial unstable phase are found to be shredded by the trailing structures during the stable deceleration phase. This reduces their diameter at the front and increases the atomic mixing such that the growth during the final unstable acceleration is retarded. The simulations are able to describe the bubble evolution only if broadband initial perturbations are assumed. Such a complex g(t) is useful for validating mix models.

  17. Leaky Fermi accelerators.

    PubMed

    Shah, Kushal; Gelfreich, Vassili; Rom-Kedar, Vered; Turaev, Dmitry

    2015-06-01

    A Fermi accelerator is a billiard with oscillating walls. A leaky accelerator interacts with an environment of an ideal gas at equilibrium by exchange of particles through a small hole on its boundary. Such interaction may heat the gas: we estimate the net energy flow through the hole under the assumption that the particles inside the billiard do not collide with each other and remain in the accelerator for a sufficiently long time. The heat production is found to depend strongly on the type of Fermi accelerator. An ergodic accelerator, i.e., one that has a single ergodic component, produces a weaker energy flow than a multicomponent accelerator. Specifically, in the ergodic case the energy gain is independent of the hole size, whereas in the multicomponent case the energy flow may be significantly increased by shrinking the hole size.

  18. The Dielectric Wall Accelerator

    SciTech Connect

    Caporaso, George J.; Chen, Yu-Jiuan; Sampayan, Stephen E.

    2009-01-01

    The Dielectric Wall Accelerator (DWA), a class of induction accelerators, employs a novel insulating beam tube to impress a longitudinal electric field on a bunch of charged particles. The surface flashover characteristics of this tube may permit the attainment of accelerating gradients on the order of 100 MV/m for accelerating pulses on the order of a nanosecond in duration. A virtual traveling wave of excitation along the tube is produced at any desired speed by controlling the timing of pulse generating modules that supply a tangential electric field to the tube wall. Because of the ability to control the speed of this virtual wave, the accelerator is capable of handling any charge to mass ratio particle; hence it can be used for electrons, protons and any ion. The accelerator architectures, key technologies and development challenges will be described.

  19. Uniformly accelerated black holes

    NASA Astrophysics Data System (ADS)

    Letelier, Patricio S.; Oliveira, Samuel R.

    2001-09-01

    The static and stationary C metric are examined in a generic framework and their interpretations studied in some detail, especially those with two event horizons, one for the black hole and another for the acceleration. We find that (i) the spacetime of an accelerated static black hole is plagued by either conical singularities or a lack of smoothness and compactness of the black hole horizon, (ii) by using standard black hole thermodynamics we show that accelerated black holes have a higher Hawking temperature than Unruh temperature of the accelerated frame, and (iii) the usual upper bound on the product of the mass and acceleration parameters (<1/27) is just a coordinate artifact. The main results are extended to accelerated rotating black holes with no significant changes.

  20. Switched Matrix Accelerator

    SciTech Connect

    Whittum, David H

    2000-10-04

    We describe a new concept for a microwave circuit functioning as a charged-particle accelerator at mm-wavelengths, permitting an accelerating gradient higher than conventional passive circuits can withstand consistent with cyclic fatigue. The device provides acceleration for multiple bunches in parallel channels, and permits a short exposure time for the conducting surface of the accelerating cavities. Our analysis includes scalings based on a smooth transmission line model and a complementary treatment with a coupled-cavity simulation. We provide also an electromagnetic design for the accelerating structure, arriving at rough dimensions for a seven-cell accelerator matched to standard waveguide and suitable for bench tests at low power in air at 91.392. GHz. A critical element in the concept is a fast mm-wave switch suitable for operation at high-power, and we present the considerations for implementation in an H-plane tee. We discuss the use of diamond as the photoconductor switch medium.

  1. Optically pulsed electron accelerator

    DOEpatents

    Fraser, J.S.; Sheffield, R.L.

    1985-05-20

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radiofrequency-powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  2. Optically pulsed electron accelerator

    DOEpatents

    Fraser, John S.; Sheffield, Richard L.

    1987-01-01

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radio frequency powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  3. ACCELERATION RESPONSIVE SWITCH

    DOEpatents

    Chabrek, A.F.; Maxwell, R.L.

    1963-07-01

    An acceleration-responsive device with dual channel capabilities whereby a first circuit is actuated upon attainment of a predetermined maximum acceleration level and when the acceleration drops to a predetermined minimum acceleriltion level another circuit is actuated is described. A fluid-damped sensing mass slidably mounted in a relatively frictionless manner on a shaft through the intermediation of a ball bushing and biased by an adjustable compression spring provides inertially operated means for actuating the circuits. (AEC)

  4. The foxhole accelerating structure

    SciTech Connect

    Fernow, R.C.; Claus, J.

    1992-07-17

    This report examines some properties of a new type of open accelerating structure. It consists of a series of rectangular cavities, which we call foxholes, joined by a beam channel. The power for accelerating the particles comes from an external radiation source and enters the cavities through their open upper surfaces. Analytic and computer calculations are presented showing that the foxhole is a suitable structure for accelerating relativistic electrons.

  5. Particle acceleration by combined diffusive shock acceleration and downstream multiple magnetic island acceleration

    NASA Astrophysics Data System (ADS)

    Zank, G. P.; Hunana, P.; Mostafavi, P.; le Roux, J. A.; Li, Gang; Webb, G. M.; Khabarova, O.

    2015-09-01

    As a consequence of the evolutionary conditions [28; 29], shock waves can generate high levels of downstream vortical turbulence. Simulations [32-34] and observations [30; 31] support the idea that downstream magnetic islands (also called plasmoids or flux ropes) result from the interaction of shocks with upstream turbulence. Zank et al. [18] speculated that a combination of diffusive shock acceleration (DSA) and downstream reconnection-related effects associated with the dynamical evolution of a “sea of magnetic islands” would result in the energization of charged particles. Here, we utilize the transport theory [18; 19] for charged particles propagating diffusively in a turbulent region filled with contracting and reconnecting plasmoids and small-scale current sheets to investigate a combined DSA and downstream multiple magnetic island charged particle acceleration mechanism. We consider separately the effects of the anti-reconnection electric field that is a consequence of magnetic island merging [17], and magnetic island contraction [14]. For the merging plasmoid reconnection- induced electric field only, we find i) that the particle spectrum is a power law in particle speed, flatter than that derived from conventional DSA theory, and ii) that the solution is constant downstream of the shock. For downstream plasmoid contraction only, we find that i) the accelerated particle spectrum is a power law in particle speed, flatter than that derived from conventional DSA theory; ii) for a given energy, the particle intensity peaks downstream of the shock, and the peak location occurs further downstream of the shock with increasing particle energy, and iii) the particle intensity amplification for a particular particle energy, f(x, c/c0)/f(0, c/c0), is not 1, as predicted by DSA theory, but increases with increasing particle energy. These predictions can be tested against observations of electrons and ions accelerated at interplanetary shocks and the heliospheric

  6. Accelerator-based BNCT.

    PubMed

    Kreiner, A J; Baldo, M; Bergueiro, J R; Cartelli, D; Castell, W; Thatar Vento, V; Gomez Asoia, J; Mercuri, D; Padulo, J; Suarez Sandin, J C; Erhardt, J; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Igarzabal, M; Minsky, D M; Herrera, M S; Capoulat, M E; Gonzalez, S J; del Grosso, M F; Gagetti, L; Suarez Anzorena, M; Gun, M; Carranza, O

    2014-06-01

    The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases.

  7. Superconductivity and future accelerators

    SciTech Connect

    Danby, G.T.; Jackson, J.W.

    1983-08-01

    With the absence, thus far, of charged particle beam accelerators, particle accelerators employing accelerating cavities and deflecting magnets applying superconductivity are still being developed. This paper discusses hadron colliders which involve 20 TeV rings with 40 TeV CM energy with an emphasis to obtain maximum GeV/$, which may be crucial for serious consideration of funding. The accelerator design and operating features are discussed with an emphasis placed on the superconducting magnets. Material and labor costs are discussed. A diagram is given which illustrates magnet superconductor requirements, comparing Fe dominated 2.5T with air core cos theta magnets.

  8. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-01-01

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  9. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-09-02

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  10. High Gradient Accelerator Research

    SciTech Connect

    Temkin, Richard

    2016-07-12

    The goal of the MIT program of research on high gradient acceleration is the development of advanced acceleration concepts that lead to a practical and affordable next generation linear collider at the TeV energy level. Other applications, which are more near-term, include accelerators for materials processing; medicine; defense; mining; security; and inspection. The specific goals of the MIT program are: • Pioneering theoretical research on advanced structures for high gradient acceleration, including photonic structures and metamaterial structures; evaluation of the wakefields in these advanced structures • Experimental research to demonstrate the properties of advanced structures both in low-power microwave cold test and high-power, high-gradient test at megawatt power levels • Experimental research on microwave breakdown at high gradient including studies of breakdown phenomena induced by RF electric fields and RF magnetic fields; development of new diagnostics of the breakdown process • Theoretical research on the physics and engineering features of RF vacuum breakdown • Maintaining and improving the Haimson / MIT 17 GHz accelerator, the highest frequency operational accelerator in the world, a unique facility for accelerator research • Providing the Haimson / MIT 17 GHz accelerator facility as a facility for outside users • Active participation in the US DOE program of High Gradient Collaboration, including joint work with SLAC and with Los Alamos National Laboratory; participation of MIT students in research at the national laboratories • Training the next generation of Ph. D. students in the field of accelerator physics.

  11. FFAGS for rapid acceleration

    SciTech Connect

    Carol J. Johnstone and Shane Koscielniak

    2002-09-30

    When large transverse and longitudinal emittances are to be transported through a circular machine, extremely rapid acceleration holds the advantage that the beam becomes immune to nonlinear resonances because there is insufficient time for amplitudes to build up. Uncooled muon beams exhibit large emittances and require fast acceleration to avoid decay losses and would benefit from this style of acceleration. The approach here employs a fixed-field alternating gradient or FFAG magnet structure and a fixed frequency acceleration system. Acceptance is enhanced by the use only of linear lattice elements, and fixed-frequency rf enables the use of cavities with large shunt resistance and quality factor.

  12. Acceleration of polarized protons in circular accelerators

    SciTech Connect

    Courant, E.D.; Ruth, R.D.

    1980-09-12

    The theory of depolarization in circular accelerators is presented. The spin equation is first expressed in terms of the particle orbit and then converted to the equivalent spinor equation. The spinor equation is then solved for three different situations: (1) a beam on a flat top near a resonance, (2) uniform acceleration through an isolated resonance, and (3) a model of a fast resonance jump. Finally, the depolarization coefficient, epsilon, is calculated in terms of properties of the particle orbit and the results are applied to a calculation of depolarization in the AGS.

  13. Design of a plasma discharge circuit for particle wakefield acceleration

    NASA Astrophysics Data System (ADS)

    Anania, M. P.; Chiadroni, E.; Cianchi, A.; Di Giovenale, D.; Ferrario, M.; Flora, F.; Gallerano, G. P.; Ghigo, A.; Marocchino, A.; Massimo, F.; Mostacci, A.; Mezi, L.; Musumeci, P.; Serio, M.

    2014-03-01

    Plasma wakefield acceleration is the most promising acceleration technique known nowadays, able to provide very high accelerating fields (10-100 GV m-1), enabling acceleration of electrons to GeV energy in few centimetres. However, the quality of the electron bunches accelerated with this technique is still not comparable with that of conventional accelerators; radiofrequency-based accelerators, in fact, are limited in the accelerating field (10-100 MV m-1) requiring therefore kilometric distances to reach the GeV energies, but can provide very bright electron bunches. Combining high brightness electron bunches from conventional accelerators and high accelerating fields reachable with plasmas could be a good compromise allowing to further accelerate high brightness electron bunches coming from LINAC while preserving electron beam quality. Following the idea of plasma wave resonant excitation driven by a train of short bunches, we have started to study the requirements in terms of plasma for SPARC-LAB [1,2]. In particular, here we focus on the ionization process; we show a simplified model to study the evolution of plasma induced by discharge, very useful to design the discharge circuit able to fully ionize the gas and bring the plasma at the needed temperature and density.

  14. Scaling FFAG accelerator for muon acceleration

    SciTech Connect

    Lagrange, JB.; Planche, T.; Mori, Y.

    2011-10-06

    Recent developments in scaling fixed field alternating gradient (FFAG) accelerators have opened new ways for lattice design, with straight sections, and insertions like dispersion suppressors. Such principles and matching issues are detailed in this paper. An application of these new concepts is presented to overcome problems in the PRISM project.

  15. Scaling FFAG accelerator for muon acceleration

    NASA Astrophysics Data System (ADS)

    Lagrange, JB.; Planche, T.; Mori, Y.

    2011-10-01

    Recent developments in scaling fixed field alternating gradient (FFAG) accelerators have opened new ways for lattice design, with straight sections, and insertions like dispersion suppressors. Such principles and matching issues are detailed in this paper. An application of these new concepts is presented to overcome problems in the PRISM project.

  16. Angular velocities, angular accelerations, and coriolis accelerations

    NASA Technical Reports Server (NTRS)

    Graybiel, A.

    1975-01-01

    Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

  17. Angular velocities, angular accelerations, and coriolis accelerations

    NASA Technical Reports Server (NTRS)

    Graybiel, A.

    1975-01-01

    Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

  18. Accelerators (3/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  19. KEK digital accelerator

    NASA Astrophysics Data System (ADS)

    Iwashita, T.; Adachi, T.; Takayama, K.; Leo, K. W.; Arai, T.; Arakida, Y.; Hashimoto, M.; Kadokura, E.; Kawai, M.; Kawakubo, T.; Kubo, Tomio; Koyama, K.; Nakanishi, H.; Okazaki, K.; Okamura, K.; Someya, H.; Takagi, A.; Tokuchi, A.; Wake, M.

    2011-07-01

    The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA) is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR) ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  20. Microscale acceleration history discriminators

    DOEpatents

    Polosky, Marc A.; Plummer, David W.

    2002-01-01

    A new class of micromechanical acceleration history discriminators is claimed. These discriminators allow the precise differentiation of a wide range of acceleration-time histories, thereby allowing adaptive events to be triggered in response to the severity (or lack thereof) of an external environment. Such devices have applications in airbag activation, and other safety and surety applications.

  1. Accelerator Science: Why RF?

    SciTech Connect

    Lincoln, Don

    2016-12-21

    Particle accelerators can fire beams of subatomic particles at near the speed of light. The accelerating force is generated using radio frequency technology and a whole lot of interesting features. In this video, Fermilab’s Dr. Don Lincoln explains how it all works.

  2. Measuring Model Rocket Acceleration.

    ERIC Educational Resources Information Center

    Jenkins, Randy A.

    1993-01-01

    Presents an experiment that measures the acceleration and velocity of a model rocket. Lift-off information is transmitted to a computer that creates a graph of the velocity. Discusses the analysis of the computer-generated data and differences between calculated and experimental velocity and acceleration of several rocket types. (MDH)

  3. Induction linear accelerators

    NASA Astrophysics Data System (ADS)

    Birx, Daniel

    1992-03-01

    Among the family of particle accelerators, the Induction Linear Accelerator is the best suited for the acceleration of high current electron beams. Because the electromagnetic radiation used to accelerate the electron beam is not stored in the cavities but is supplied by transmission lines during the beam pulse it is possible to utilize very low Q (typically<10) structures and very large beam pipes. This combination increases the beam breakup limited maximum currents to of order kiloamperes. The micropulse lengths of these machines are measured in 10's of nanoseconds and duty factors as high as 10-4 have been achieved. Until recently the major problem with these machines has been associated with the pulse power drive. Beam currents of kiloamperes and accelerating potentials of megavolts require peak power drives of gigawatts since no energy is stored in the structure. The marriage of liner accelerator technology and nonlinear magnetic compressors has produced some unique capabilities. It now appears possible to produce electron beams with average currents measured in amperes, peak currents in kiloamperes and gradients exceeding 1 MeV/meter, with power efficiencies approaching 50%. The nonlinear magnetic compression technology has replaced the spark gap drivers used on earlier accelerators with state-of-the-art all-solid-state SCR commutated compression chains. The reliability of these machines is now approaching 1010 shot MTBF. In the following paper we will briefly review the historical development of induction linear accelerators and then discuss the design considerations.

  4. Measuring Model Rocket Acceleration.

    ERIC Educational Resources Information Center

    Jenkins, Randy A.

    1993-01-01

    Presents an experiment that measures the acceleration and velocity of a model rocket. Lift-off information is transmitted to a computer that creates a graph of the velocity. Discusses the analysis of the computer-generated data and differences between calculated and experimental velocity and acceleration of several rocket types. (MDH)

  5. Accelerators (4/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  6. Accelerators (5/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  7. Diagnostics for induction accelerators

    SciTech Connect

    Fessenden, T.J.

    1996-04-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at LLNL from the early 1960`s to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400 ns pulses. The Advanced Test Accelerator (ATA) built at Livermore`s Site 300 produced 10,000 Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and LBNL. This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high current, short pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail.

  8. Particle Acceleration in Jets

    NASA Technical Reports Server (NTRS)

    Nishikawa, Ken-Ichi

    2005-01-01

    Nonthermal radiation observed from astrophysical systems containing relativistic jets and shocks, e.g., active galactic nuclei (AGNs), gamma ray burst (GRBs), and Galactic microquasar systems usually have power-law emission spectra. Fermi acceleration is the mechanism usually assumed for the acceleration of particles in astrophysical environments.

  9. Accelerators Beyond The Tevatron?

    SciTech Connect

    Lach, Joseph; /Fermilab

    2010-07-01

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?

  10. Accelerators Beyond The Tevatron?

    SciTech Connect

    Lach, Joseph

    2010-07-29

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?.

  11. Particle Acceleration in Clusters of Galaxies

    NASA Astrophysics Data System (ADS)

    Takizawa, M.; Naito, Tsuguya; Ohno, Hiroshi; Shibata, Shinpei

    2003-07-01

    Clusters of galaxies have non-thermal high energy particles as well as the thermal intracluster medium in the intracluster space. One bit of direct evidence is the existence of non-thermal synchrotron radio halos and relics. However, it is still unclear how they are accelerated. Here, we consider two kinds of acceleration processes which likely work in the intracluster space and intro duce models based on them. One is shock acceleration associated with cluster mergers. We calculate evolution of non-thermal electrons during cluster merger based on N-b o dy + SPH simulations. Radio emission is localized near the shocks. This is qualitatively similar to radio relics. The other is resonant scattering of random Alfv´n waves. e We calculate steady state electron distribution functions when Alfv´n wave power e spectra are power-law. We successfully repro duce the Coma cluster radio halo spectrum.

  12. Accelerators, Beams And Physical Review Special Topics - Accelerators And Beams

    SciTech Connect

    Siemann, R.H.; /SLAC

    2011-10-24

    Accelerator science and technology have evolved as accelerators became larger and important to a broad range of science. Physical Review Special Topics - Accelerators and Beams was established to serve the accelerator community as a timely, widely circulated, international journal covering the full breadth of accelerators and beams. The history of the journal and the innovations associated with it are reviewed.

  13. The Atomki accelerator center

    NASA Astrophysics Data System (ADS)

    Vajda, I.; Fülöp, Zs.; Biri, S.

    2017-06-01

    Particle accelerators are the driving forces of nuclear physics laboratories and MTA Atomki, the Institute for Nuclear Research of the Hungarian Academy of Sciences is no exception. The Atomki Accelerator Center (AAC) incorporates several low-energy charged-particle accelerators, offering the possibility of choosing ions with various charge states, energies and beam intensities. Currently, the AAC has six main facilities: a cyclotron (K=20), two Van de Graaff accelerators (1 MV, 5 MV), an ECR ion source, an electromagnetic isotope separator and a 2 MV Tandetron installed in 2015. The accelerators, spanning a range of beam energies from 50 eV to 27 MeV, have been designed for a broad range of research projects and applications in various fields - mainly in nuclear and atomic physics, materials science, environmental research and archaeology. The structure of the laboratory with a short description of the most important topics, education and outreach activities are presented.

  14. Rapid evolution of genes involved in learning and energy metabolism for domestication of the laboratory rat.

    PubMed

    Zeng, Lin; Ming, Chen; Li, Yan; Su, Ling-Yan; Su, Yan-Hua; O Otecko, Newton; Liu, He-Qun; Wang, Ming-Shan; Yao, Yong-Gang; Li, Hai-Peng; Wu, Dong-Dong; Zhang, Ya-Ping

    2017-09-12

    The laboratory rat, widely used in biomedical research, is domesticated from wild brown rat. The origin and genetic mechanism underlying domestication of the laboratory rat remain largely elusive. In the present study, large scale genomes supported a single origin for the laboratory rat, possibly from a sister group to wild rats from Europe/Africa/Middle East. Genomic and transcriptomic analyses uncovered many artificially selected genes (e.g. FOXP2, B3GAT1, and CLOCK) involved in the nervous system. These genes associate with learning ability and regulation of circadian rhythm, which likely enabled the successful domestication of the laboratory rat. Particularly, many genes, including mitochondrial genes responsible for energy metabolism, displayed a substantially increased expression in the brain of laboratory rats compared to wild rats. Our findings demystify the origin and evolution of this model animal, and provide insight into the process of its domestication. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Space Acceleration Measurement Systems

    NASA Technical Reports Server (NTRS)

    Foster, William

    2000-01-01

    The Space Acceleration Measurement Systems (SAMS) Project develops and deploys the measurement systems for the Acceleration Measurement Program (AMP). At this time there are two types of measurement systems available, quasi-steady and vibratory. Orbital Acceleration Research Experiment (OARE) and Microgravity Acceleration Measurement System (MAMS) are the current quasi-steady systems available. OARE has flown numerous times supporting STS missions. MAMS has been delivered to Kennedy Space Center (KSC) for its deployment on the International Space Station (ISS). Vibratory measurements have been made and will be made by the Space Acceleration Measurement System (SAMS-I) Generation I, Space Acceleration Measurement System Generation II (SAMS-II), and Space Acceleration Measurement System Free Flyer or Generation III (SAMS-FF). SAMS-I supported 21 STS missions and has been retired. SAMS-II will be delivered to KSC to support ISS-6A launch (currently April 19, 2001). SAMS-FF has replaced SAMS-I in support of STS missions and has been deployed on sounding rockets, the KC-135 and ground facilities. SAMS-FF hardware shall be deployed on ISS in the future to provide a more compact solution.

  16. Large electrostatic accelerators

    SciTech Connect

    Jones, C.M.

    1984-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators.

  17. Nonlinear Particle Acceleration and Thermal Particles in GRB Afterglows

    NASA Astrophysics Data System (ADS)

    Warren, Donald C.; Ellison, Donald C.; Barkov, Maxim V.; Nagataki, Shigehiro

    2017-02-01

    The standard model for GRB afterglow emission treats the accelerated electron population as a simple power law, N(E)\\propto {E}-p for p≳ 2. However, in standard Fermi shock acceleration, a substantial fraction of the swept-up particles do not enter the acceleration process at all. Additionally, if acceleration is efficient, then the nonlinear back-reaction of accelerated particles on the shock structure modifies the shape of the nonthermal tail of the particle spectra. Both of these modifications to the standard synchrotron afterglow impact the luminosity, spectra, and temporal variation of the afterglow. To examine the effects of including thermal particles and nonlinear particle acceleration on afterglow emission, we follow a hydrodynamical model for an afterglow jet and simulate acceleration at numerous points during the evolution. When thermal particles are included, we find that the electron population is at no time well fitted by a single power law, though the highest-energy electrons are; if the acceleration is efficient, then the power-law region is even smaller. Our model predicts hard–soft–hard spectral evolution at X-ray energies, as well as an uncoupled X-ray and optical light curve. Additionally, we show that including emission from thermal particles has drastic effects (increases by factors of 100 and 30, respectively) on the observed flux at optical and GeV energies. This enhancement of GeV emission makes afterglow detections by future γ-ray observatories, such as CTA, very likely.

  18. Ion beam accelerator system

    NASA Technical Reports Server (NTRS)

    Aston, Graeme (Inventor)

    1984-01-01

    A system is described that combines geometrical and electrostatic focusing to provide high ion extraction efficiency and good focusing of an accelerated ion beam. The apparatus includes a pair of curved extraction grids (16, 18) with multiple pairs of aligned holes positioned to direct a group of beamlets (20) along converging paths. The extraction grids are closely spaced and maintained at a moderate potential to efficiently extract beamlets of ions and allow them to combine into a single beam (14). An accelerator electrode device (22) downstream from the extraction grids, is at a much lower potential than the grids to accelerate the combined beam.

  19. Ion beam accelerator system

    NASA Technical Reports Server (NTRS)

    Aston, G. (Inventor)

    1981-01-01

    A system is described that combines geometrical and electrostatic focusing to provide high ion extraction efficiency and good focusing of an accelerated ion beam. The apparatus includes a pair of curved extraction grids with multiple pairs of aligned holes positioned to direct a group of beamlets along converging paths. The extraction grids are closely spaced and maintained at a moderate potential to efficiently extract beamlets of ions and allow them to combine into a single beam. An accelerator electrode device downstream from the extraction grids is at a much lower potential than the grids to accelerate the combined beam. The application of the system to ion implantation is mentioned.

  20. Vacuum Beat Wave Accelerator

    NASA Astrophysics Data System (ADS)

    Moore, C. I.; Hafizi, B.; Ting, A.; Burris, H. R.; Sprangle, P.; Esarey, E.; Ganguly, A.; Hirshfield, J. L.

    1997-11-01

    The Vacuum Beat Wave Accelerator (VBWA) is a particle acceleration scheme which uses the non-linear ponderomotive beating of two different frequency laser beams to accelerate electrons. A proof-of-principle experiment to demonstrate the VBWA is underway at the Naval Research Laboratory (NRL). This experiment will use the beating of a 1054 nm and 527 nm laser pulse from the NRL T-cubed laser to generate the beat wave and a 4.5 MeV RF electron gun as the electron source. Simulation results and the experimental design will be presented. The suitability of using axicon or higher order Gaussian laser beams will also be discussed.

  1. CLASHING BEAM PARTICLE ACCELERATOR

    DOEpatents

    Burleigh, R.J.

    1961-04-11

    A charged-particle accelerator of the proton synchrotron class having means for simultaneously accelerating two separate contra-rotating particle beams within a single annular magnet structure is reported. The magnet provides two concentric circular field regions of opposite magnetic polarity with one field region being of slightly less diameter than the other. The accelerator includes a deflector means straddling the two particle orbits and acting to collide the two particle beams after each has been accelerated to a desired energy. The deflector has the further property of returning particles which do not undergo collision to the regular orbits whereby the particles recirculate with the possibility of colliding upon subsequent passages through the deflector.

  2. DIELECTRIC WALL ACCELERATOR TECHNOLOGY

    SciTech Connect

    Sampayan, S; Caporaso, G; Chen, Y; Harris, J; Hawkins, S; Holmes, C; Nelson, S; Poole, B; Rhodes, M; Sanders, D; Sullivan, J; Wang, L; Watson, J

    2007-10-18

    The dielectric wall accelerator (DWA) is a compact pulsed power device where the pulse forming lines, switching, and vacuum wall are integrated into a single compact geometry. For this effort, we initiated a extensive compact pulsed power development program and have pursued the study of switching (gas, oil, laser induced surface flashover and photoconductive), dielectrics (ceramics and nanoparticle composites), pulse forming line topologies (asymmetric and symmetric Blumleins and zero integral pulse forming lines), and multilayered vacuum insulator (HGI) technology. Finally, we fabricated an accelerator cell for test on ETAII (a 5.5 MeV, 2 kA, 70 ns pulsewidth electron beam accelerator). We review our past results and report on the progress of accelerator cell testing.

  3. Accelerator on a Chip

    SciTech Connect

    England, Joel

    2014-06-30

    SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

  4. Charged particle accelerator grating

    DOEpatents

    Palmer, R.B.

    1985-09-09

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator is described. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams onto the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  5. Principles of Induction Accelerators

    NASA Astrophysics Data System (ADS)

    Briggs*, Richard J.

    The basic concepts involved in induction accelerators are introduced in this chapter. The objective is to provide a foundation for the more detailed coverage of key technology elements and specific applications in the following chapters. A wide variety of induction accelerators are discussed in the following chapters, from the high current linear electron accelerator configurations that have been the main focus of the original developments, to circular configurations like the ion synchrotrons that are the subject of more recent research. The main focus in the present chapter is on the induction module containing the magnetic core that plays the role of a transformer in coupling the pulsed power from the modulator to the charged particle beam. This is the essential common element in all these induction accelerators, and an understanding of the basic processes involved in its operation is the main objective of this chapter. (See [1] for a useful and complementary presentation of the basic principles in induction linacs.)

  6. Wake field acceleration experiments

    SciTech Connect

    Simpson, J.D.

    1988-01-01

    Where and how will wake field acceleration devices find use for other than, possibly, accelerators for high energy physics. I don't know that this can be responsibly answered at this time. What I can do is describe some recent results from an ongoing experimental program at Argonne which support the idea that wake field techniques and devices are potentially important for future accelerators. Perhaps this will spawn expanded interest and even new ideas for the use of this new technology. The Argonne program, and in particular the Advanced Accelerator Test Facility (AATF), has been reported in several fairly recent papers and reports. But because this is a substantially new audience for the subject, I will include a brief review of the program and the facility before describing experiments. 10 refs., 7 figs.

  7. TESLA superconducting accelerating structures

    NASA Astrophysics Data System (ADS)

    Sekutowicz, J.

    2007-08-01

    Superconducting standing wave structures have been used for charged particle acceleration for almost 40 years. A brief introduction to this application with examples, test procedures and recently achieved results are discussed in this paper.

  8. HEAVY ION LINEAR ACCELERATOR

    DOEpatents

    Van Atta, C.M.; Beringer, R.; Smith, L.

    1959-01-01

    A linear accelerator of heavy ions is described. The basic contributions of the invention consist of a method and apparatus for obtaining high energy particles of an element with an increased charge-to-mass ratio. The method comprises the steps of ionizing the atoms of an element, accelerating the resultant ions to an energy substantially equal to one Mev per nucleon, stripping orbital electrons from the accelerated ions by passing the ions through a curtain of elemental vapor disposed transversely of the path of the ions to provide a second charge-to-mass ratio, and finally accelerating the resultant stripped ions to a final energy of at least ten Mev per nucleon.

  9. Accelerated immunotherapy schedules.

    PubMed

    Calabria, Christopher W

    2013-08-01

    Rush and cluster immunotherapy schedules are accelerated immunotherapy build-up schedules. A cluster immunotherapy schedule involves the patient receiving several allergen injections (generally 2-4) sequentially in a single day of treatment on nonconsecutive days. The maintenance dose is generally reached in 4-8 weeks. In rush immunotherapy protocols, higher doses are administered at 15- to 60-min intervals over a 1- to 3-day period until the maintenance dose is achieved. This review will serve as an update for accelerated immunotherapy schedules. The review will include recent investigations demonstrating the safety of cluster schedules in atopic dermatitis, pediatric patients, and inhalant allergen mixtures and an accelerated protocol utilizing an infusion pump for allergen delivery. There has also been further elucidation on the immunological changes which occur during accelerated immunotherapy. Finally, new studies analyzing systemic reaction risk factors are discussed.

  10. Accelerator on a Chip

    ScienceCinema

    England, Joel

    2016-07-12

    SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

  11. Dielectric assist accelerating structure

    NASA Astrophysics Data System (ADS)

    Satoh, D.; Yoshida, M.; Hayashizaki, N.

    2016-01-01

    A higher-order TM02 n mode accelerating structure is proposed based on a novel concept of dielectric loaded rf cavities. This accelerating structure consists of ultralow-loss dielectric cylinders and disks with irises which are periodically arranged in a metallic enclosure. Unlike conventional dielectric loaded accelerating structures, most of the rf power is stored in the vacuum space near the beam axis, leading to a significant reduction of the wall loss, much lower than that of conventional normal-conducting linac structures. This allows us to realize an extremely high quality factor and a very high shunt impedance at room temperature. A simulation of a 5 cell prototype design with an existing alumina ceramic indicates an unloaded quality factor of the accelerating mode over 120 000 and a shunt impedance exceeding 650 M Ω /m at room temperature.

  12. Vibration control in accelerators

    SciTech Connect

    Montag, C.

    2011-01-01

    In the vast majority of accelerator applications, ground vibration amplitudes are well below tolerable magnet jitter amplitudes. In these cases, it is necessary and sufficient to design a rigid magnet support structure that does not amplify ground vibration. Since accelerator beam lines are typically installed at an elevation of 1-2m above ground level, special care has to be taken in order to avoid designing a support structure that acts like an inverted pendulum with a low resonance frequency, resulting in untolerable lateral vibration amplitudes of the accelerator components when excited by either ambient ground motion or vibration sources within the accelerator itself, such as cooling water pumps or helium flow in superconducting magnets. In cases where ground motion amplitudes already exceed the required jiter tolerances, for instance in future linear colliders, passive vibration damping or active stabilization may be considered.

  13. Amps particle accelerator definition study

    NASA Technical Reports Server (NTRS)

    Sellen, J. M., Jr.

    1975-01-01

    The Particle Accelerator System of the AMPS (Atmospheric, Magnetospheric, and Plasmas in Space) payload is a series of charged particle accelerators to be flown with the Space Transportation System Shuttle on Spacelab missions. In the configuration presented, the total particle accelerator system consists of an energetic electron beam, an energetic ion accelerator, and both low voltage and high voltage plasma acceleration devices. The Orbiter is illustrated with such a particle accelerator system.

  14. Breakthrough: Fermilab Accelerator Technology

    ScienceCinema

    None

    2016-07-12

    There are more than 30,000 particle accelerators in operation around the world. At Fermilab, scientists are collaborating with other laboratories and industry to optimize the manufacturing processes for a new type of powerful accelerator that uses superconducting niobium cavities. Experimenting with unique polishing materials, a Fermilab team has now developed an efficient and environmentally friendly way of creating cavities that can propel particles with more than 30 million volts per meter.

  15. Rolamite acceleration sensor

    DOEpatents

    Abbin, Joseph P.; Briner, Clifton F.; Martin, Samuel B.

    1993-01-01

    A rolamite acceleration sensor which has a failsafe feature including a housing, a pair of rollers, a tension band wrapped in an S shaped fashion around the rollers, wherein the band has a force-generation cut out and a failsafe cut out or weak portion. The failsafe cut out or weak portion breaks when the sensor is subjected to an excessive acceleration so that the sensor fails in an open circuit (non-conducting) state permanently.

  16. Rolamite acceleration sensor

    DOEpatents

    Abbin, J.P.; Briner, C.F.; Martin, S.B.

    1993-12-21

    A rolamite acceleration sensor is described which has a failsafe feature including a housing, a pair of rollers, a tension band wrapped in an S shaped fashion around the rollers, wherein the band has a force-generation cut out and a failsafe cut out or weak portion. The failsafe cut out or weak portion breaks when the sensor is subjected to an excessive acceleration so that the sensor fails in an open circuit (non-conducting) state permanently. 6 figures.

  17. Accelerated Corrosion Testing

    DTIC Science & Technology

    1982-12-01

    conducted on high-strength 4340 steel and 7075-T6 aluminum alloy usina accelerating pollutants such as sulfur dinxide, nitrogen dioxide, surface salt...CONTROLLED 100 ATMOSPHERES APPiENDIX B - ACCELERATED ATMDSPHERIC-CORROSION TESTING 128 v I. LIST OF ILLUSTRATIONS Ficure Page 1 Schematic Diagram of Applied...Static-Load Crack-Growth Rate (from ref. 17). 26 12 Environmental-System Flow Diagram . 33 13 Compact-Tension Plane-Strain Fracture-Toughness Specimen

  18. Microgravity Acceleration Measurement System

    NASA Technical Reports Server (NTRS)

    Foster, William

    2009-01-01

    Microgravity Acceleration Measurement System (MAMS) is an ongoing study of the small forces (vibrations and accelerations) on the ISS that result from the operation of hardware, crew activities, as well as dockings and maneuvering. Results will be used to generalize the types of vibrations affecting vibration-sensitive experiments. Investigators seek to better understand the vibration environment on the space station to enable future research.

  19. Designing reliability into accelerators

    NASA Astrophysics Data System (ADS)

    Hutton, A.

    1992-07-01

    Future accelerators will have to provide a high degree of reliability. Quality must be designed in right from the beginning and must remain a central theme throughout the project. The problem is similar to the problems facing US industry today, and examples of the successful application of quality engineering will be given. Different aspects of an accelerator project will be addressed: Concept, Design, Motivation, Management Techniques, and Fault Diagnosis. The importance of creating and maintaining a coherent team will be stressed.

  20. Accelerator Experiments for Astrophysics

    SciTech Connect

    Ng, J

    2003-10-15

    Many recent discoveries in astrophysics involve phenomena that are highly complex. Carefully designed experiments, together with sophisticated computer simulations, are required to gain insights into the underlying physics. We show that particle accelerators are unique tools in this area of research, by providing precision calibration data and by creating extreme experimental conditions relevant for astrophysics. In this paper we discuss laboratory experiments that can be carried out at the Stanford Linear Accelerator Center and implications for astrophysics.

  1. Collective field accelerator

    DOEpatents

    Luce, John S.

    1978-01-01

    A collective field accelerator which operates with a vacuum diode and utilizes a grooved cathode and a dielectric anode that operates with a relativistic electron beam with a .nu./.gamma. of .about. 1, and a plurality of dielectric lenses having an axial magnetic field thereabout to focus the collectively accelerated electrons and ions which are ejected from the anode. The anode and lenses operate as unoptimized r-f cavities which modulate and focus the beam.

  2. Accelerators for America's Future

    NASA Astrophysics Data System (ADS)

    Bai, Mei

    2016-03-01

    Particle accelerator, a powerful tool to energize beams of charged particles to a desired speed and energy, has been the working horse for investigating the fundamental structure of matter and fundermental laws of nature. Most known examples are the 2-mile long Stanford Linear Accelerator at SLAC, the high energy proton and anti-proton collider Tevatron at FermiLab, and Large Hadron Collider that is currently under operation at CERN. During the less than a century development of accelerator science and technology that led to a dazzling list of discoveries, particle accelerators have also found various applications beyond particle and nuclear physics research, and become an indispensible part of the economy. Today, one can find a particle accelerator at almost every corner of our lives, ranging from the x-ray machine at the airport security to radiation diagnostic and therapy in hospitals. This presentation will give a brief introduction of the applications of this powerful tool in fundermental research as well as in industry. Challenges in accelerator science and technology will also be briefly presented

  3. APT accelerator technology

    SciTech Connect

    Schneider, J.D.

    1996-09-01

    Proposed accelerator production of tritium (APT) project requires an accelerator providing a cw proton beam of 100 mA at 1300 MeV. Since most of the technical risk of a high-current cw (continuous-wave, 100% DF) accelerator resides in the low-energy section, Los Alamos is building a 20 MeV duplicate of the accelerator front end to confirm design codes, beam performance, and demonstrate operaional reliability. We report on design details of this low-energy demonstration accelerator (LEDA) and discuss the integrated design of the full accelerator for the APT plant. LEDA`s proton injector is under test and has produced more than 130 mA at 75 keV. Fabrication is proceeding on a 6.7-KeV, 8-m long RFQ, and detailed design is underway on coupled-cavity drift-tube linac (CCDTL) structures. Detailed design and technology experiments are underway on medium-beta superconducting cavities to assess feasibility of replacing the conventional (room-temperature copper) high-energy linac with a linac made of niobium superconducting RF cavities.

  4. Photon acceleration in laser wakefield accelerators

    SciTech Connect

    Trines, R. M. G. M.

    2007-07-11

    If the index of a refraction of a dispersive medium, such as a plasma, changes in time, it can be used to change the frequency of light propagating through the medium. This effect is called photon acceleration. It has been predicted in both theory and simulations, and also been demonstrated experimentally for the case of moving ionization fronts in gases (the so-called ionization blueshift) as well as for laser-driven wakefields.Here, we present studies of photon acceleration in laser-driven plasma wakefields. The unique spectral characteristics of this process will be discussed, to distinguish it from e.g. photon acceleration by ionization fronts, frequency domain interferometry or self-phase modulation. The dynamics of the photons in laser-wakefield interaction are studied through both regular particle-in-cell and wave-kinetic simulations. The latter approach provides a powerful, versatile, and easy-to-use method to track the propagation of individual spectral components, providing new insight into the physics of laser-plasma interaction. Theory, simulations and experimental results will be brought together to provide a full understanding of the dynamics of a laser pulse in its own wakefield.Even though the wave-kinetic approach mentioned above has mainly been developed for the description of laser-plasma interaction, it can be applied to a much wider range of fast wave-slow wave interaction processes: Langmuir waves-ion acoustic waves, drift waves-zonal flow, Rossby waves-zonal flow, or even photons-gravitational waves. Several recent results in these areas will be shown, often with surprising results.

  5. Diffusive Shock Acceleration and Reconnection Acceleration Processes

    NASA Astrophysics Data System (ADS)

    Zank, G. P.; Hunana, P.; Mostafavi, P.; Le Roux, J. A.; Li, Gang; Webb, G. M.; Khabarova, O.; Cummings, A.; Stone, E.; Decker, R.

    2015-12-01

    Shock waves, as shown by simulations and observations, can generate high levels of downstream vortical turbulence, including magnetic islands. We consider a combination of diffusive shock acceleration (DSA) and downstream magnetic-island-reconnection-related processes as an energization mechanism for charged particles. Observations of electron and ion distributions downstream of interplanetary shocks and the heliospheric termination shock (HTS) are frequently inconsistent with the predictions of classical DSA. We utilize a recently developed transport theory for charged particles propagating diffusively in a turbulent region filled with contracting and reconnecting plasmoids and small-scale current sheets. Particle energization associated with the anti-reconnection electric field, a consequence of magnetic island merging, and magnetic island contraction, are considered. For the former only, we find that (i) the spectrum is a hard power law in particle speed, and (ii) the downstream solution is constant. For downstream plasmoid contraction only, (i) the accelerated spectrum is a hard power law in particle speed; (ii) the particle intensity for a given energy peaks downstream of the shock, and the distance to the peak location increases with increasing particle energy, and (iii) the particle intensity amplification for a particular particle energy, f(x,c/{c}0)/f(0,c/{c}0), is not 1, as predicted by DSA, but increases with increasing particle energy. The general solution combines both the reconnection-induced electric field and plasmoid contraction. The observed energetic particle intensity profile observed by Voyager 2 downstream of the HTS appears to support a particle acceleration mechanism that combines both DSA and magnetic-island-reconnection-related processes.

  6. Mass varying neutrinos, symmetry breaking, and cosmic acceleration

    NASA Astrophysics Data System (ADS)

    Sadjadi, H. Mohseni; Anari, V.

    2017-06-01

    We introduce a new proposal for the onset of cosmic acceleration based on mass varying neutrinos. When massive neutrinos become nonrelativistic, the Z2 symmetry breaks, and the quintessence potential becomes positive from its initially zero value. This positive potential behaves like a cosmological constant at the present era and drives the Universe's acceleration during the slow roll evolution of the quintessence. In contrast to Λ CDM model, the dark energy in our model is dynamical, and the acceleration is not persistent. Contrary to some of the previous models of dark energy with mass varying neutrinos, we do not use the adiabaticity condition, which leads to instability.

  7. Fully vectorial accelerating diffraction-free Helmholtz beams.

    PubMed

    Aleahmad, Parinaz; Miri, Mohammad-Ali; Mills, Matthew S; Kaminer, Ido; Segev, Mordechai; Christodoulides, Demetrios N

    2012-11-16

    We show that new families of diffraction-free nonparaxial accelerating optical beams can be generated by considering the symmetries of the underlying vectorial Helmholtz equation. Both two-dimensional transverse electric and magnetic accelerating wave fronts are possible, capable of moving along elliptic trajectories. Experimental results corroborate these predictions when these waves are launched from either the major or minor axis of the ellipse. In addition, three-dimensional spherical nondiffracting field configurations are presented along with their evolution dynamics. Finally, fully vectorial self-similar accelerating optical wave solutions are obtained via oblate-prolate spheroidal wave functions. In all occasions, these effects are illustrated via pertinent examples.

  8. Physics of Laser-driven plasma-based acceleration

    SciTech Connect

    Esarey, Eric; Schroeder, Carl B.

    2003-06-30

    The physics of plasma-based accelerators driven by short-pulse lasers is reviewed. This includes the laser wake-field accelerator, the plasma beat wave accelerator, the self-modulated laser wake-field accelerator, and plasma waves driven by multiple laser pulses. The properties of linear and nonlinear plasma waves are discussed, as well as electron acceleration in plasma waves. Methods for injecting and trapping plasma electrons in plasma waves are also discussed. Limits to the electron energy gain are summarized, including laser pulse direction, electron dephasing, laser pulse energy depletion, as well as beam loading limitations. The basic physics of laser pulse evolution in underdense plasmas is also reviewed. This includes the propagation, self-focusing, and guiding of laser pulses in uniform plasmas and plasmas with preformed density channels. Instabilities relevant to intense short-pulse laser-plasma interactions, such as Raman, self-modulation, and hose instabilities, are discussed. Recent experimental results are summarized.

  9. Advanced accelerator theory development

    SciTech Connect

    Sampayan, S.E.; Houck, T.L.; Poole, B.; Tishchenko, N.; Vitello, P.A.; Wang, I.

    1998-02-09

    A new accelerator technology, the dielectric wall accelerator (DWA), is potentially an ultra compact accelerator/pulsed power driver. This new accelerator relies on three new components: the ultra-high gradient insulator, the asymmetric Blumlein and low jitter switches. In this report, we focused our attention on the first two components of the DWA system the insulators and the asymmetric Blumlein. First, we sought to develop the necessary design tools to model and scale the behavior of the high gradient insulator. To perform this task we concentrated on modeling the discharge processes (i.e., initiation and creation of the surface discharge). In addition, because these high gradient structures exhibit favorable microwave properties in certain accelerator configurations, we performed experiments and calculations to determine the relevant electromagnetic properties. Second, we performed circuit modeling to understand energy coupling to dynamic loads by the asymmetric Blumlein. Further, we have experimentally observed a non-linear coupling effect in certain asymmetric Blumlein configurations. That is, as these structures are stacked into a complete module, the output voltage does not sum linearly and a lower than expected output voltage results. Although we solved this effect experimentally, we performed calculations to understand this effect more fully to allow better optimization of this DWA pulse-forming line system.

  10. Dielectric laser accelerators

    NASA Astrophysics Data System (ADS)

    England, R. Joel; Noble, Robert J.; Bane, Karl; Dowell, David H.; Ng, Cho-Kuen; Spencer, James E.; Tantawi, Sami; Wu, Ziran; Byer, Robert L.; Peralta, Edgar; Soong, Ken; Chang, Chia-Ming; Montazeri, Behnam; Wolf, Stephen J.; Cowan, Benjamin; Dawson, Jay; Gai, Wei; Hommelhoff, Peter; Huang, Yen-Chieh; Jing, Chunguang; McGuinness, Christopher; Palmer, Robert B.; Naranjo, Brian; Rosenzweig, James; Travish, Gil; Mizrahi, Amit; Schachter, Levi; Sears, Christopher; Werner, Gregory R.; Yoder, Rodney B.

    2014-10-01

    The use of infrared lasers to power optical-scale lithographically fabricated particle accelerators is a developing area of research that has garnered increasing interest in recent years. The physics and technology of this approach is reviewed, which is referred to as dielectric laser acceleration (DLA). In the DLA scheme operating at typical laser pulse lengths of 0.1 to 1 ps, the laser damage fluences for robust dielectric materials correspond to peak surface electric fields in the GV /m regime. The corresponding accelerating field enhancement represents a potential reduction in active length of the accelerator between 1 and 2 orders of magnitude. Power sources for DLA-based accelerators (lasers) are less costly than microwave sources (klystrons) for equivalent average power levels due to wider availability and private sector investment. Because of the high laser-to-particle coupling efficiency, required pulse energies are consistent with tabletop microJoule class lasers. Combined with the very high (MHz) repetition rates these lasers can provide, the DLA approach appears promising for a variety of applications, including future high-energy physics colliders, compact light sources, and portable medical scanners and radiative therapy machines.

  11. Electrostatic Plasma Accelerator (EPA)

    NASA Technical Reports Server (NTRS)

    Brophy, John R.; Aston, Graeme

    1989-01-01

    The Electrostatic Plasma Accelerator (EPA) is a thruster concept which promises specific impulse levels between low power arcjets and those of the ion engine while retaining the relative simplicity of the arcjet. The EPA thruster produces thrust through the electrostatic acceleration of a moderately dense plasma. No accelerating electrodes are used and the specific impulse is a direct function of the applied discharge voltage and the propellant atomic mass. The goal of the present program is to demonstrate feasibility of the EPA thruster concept through experimental and theoretical investigations of the EPA acceleration mechanism and discharge chamber performance. Experimental investigations will include operating the test bed ion (TBI) engine as an EPA thruster and parametrically varying the thruster geometry and operating conditions to quantify the electrostatic plasma acceleration effect. The theoretical investigations will include the development of a discharge chamber model which describes the relationships between the engine size, plasma properties, and overall performance. For the EPA thruster to be a viable propulsion concept, overall thruster efficiencies approaching 30% with specific impulses approaching 1000 s must be achieved.

  12. Laser Ion Acceleration Control

    NASA Astrophysics Data System (ADS)

    Kawata, Shigeo; Nagashima, T.; Izumiyama, T.; Sato, D.; Takano, M.; Barada, D.; Ma, Y. Y.; Gu, Y. J.; Kong, Q.; Wang, P. X.; Wang, W. M.

    2013-10-01

    An intense femtosecond pulsed laser is employed to accelerate ions. The issues in the laser ion accelerator include the energy efficiency from the laser to the ions, the ion beam collimation, the ion energy spectrum control, the ion beam bunching, the ion particle energy control, etc. In the study particle computer simulations were performed to solve the issues, and each component was designed to control the ion beam quality. When an intense laser illuminates a target, electrons in the target are accelerated and leave from the target; temporarily a strong electric field is formed between the high-energy electrons and the target ions, and the target ions are accelerated. The energy efficiency from the laser to ions was improved by using a solid target with a fine sub-wavelength structure or by a near critical density gas plasma. The ion beam collimation was realized by holes behind the solid target. The control of the ion energy spectrum and the ion particle energy, and the ion beam bunching were successfully realized by a multi-stage laser-target interaction. The present study proposed a novel concept for a future compact laser ion accelerator, based on each component study required to control the ion beam quality and parameters. Partly supported by JSPS, MEXT, CORE, Japan/US Cooperation program, ASHULA and ILE/Osaka University.

  13. Gyro-induced acceleration of magnetic reconnection

    SciTech Connect

    Comisso, L.; Grasso, D.; Waelbroeck, F. L.; Borgogno, D.

    2013-09-15

    The linear and nonlinear evolution of magnetic reconnection in collisionless high-temperature plasmas with a strong guide field is analyzed on the basis of a two-dimensional gyrofluid model. The linear growth rate of the reconnecting instability is compared to analytical calculations over the whole spectrum of linearly unstable wave numbers. In the strongly unstable regime (large Δ′), the nonlinear evolution of the reconnecting instability is found to undergo two distinctive acceleration phases separated by a stall phase in which the instantaneous growth rate decreases. The first acceleration phase is caused by the formation of strong electric fields close to the X-point due to ion gyration, while the second acceleration phase is driven by the development of an open Petschek-like configuration due to both ion and electron temperature effects. Furthermore, the maximum instantaneous growth rate is found to increase dramatically over its linear value for decreasing diffusion layers. This is a consequence of the fact that the peak instantaneous growth rate becomes weakly dependent on the microscopic plasma parameters if the diffusion region thickness is sufficiently smaller than the equilibrium magnetic field scale length. When this condition is satisfied, the peak reconnection rate asymptotes to a constant value.

  14. Plasma-based accelerator structures

    SciTech Connect

    Schroeder, Carl B.

    1999-12-01

    Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas.

  15. The History and Role of Accelerators in Radiation Oncology

    NASA Astrophysics Data System (ADS)

    Smith, Alfred

    2003-04-01

    Over one million people are diagnosed with cancer (excluding skin cancer) each year in the United States - about half of those patients will receive radiation as part of their treatment. Radiation Oncology is the field of medicine that specializes in the treatment of cancer with radiation. The evolution of Radiation Oncology, and its success as a cancer treatment modality, has generally paralleled developments in imaging and accelerator technologies. Accelerators, the topic of this paper, have proven to be highly reliable, safe and efficient sources of radiation for cancer treatment. Advances in accelerator technology, especially those that have provided higher energies and dose rates, and more localized (to the tumor volume) dose distributions, have enabled significant improvements in the outcomes of cancer treatments. The use of Cobalt 60 beams has greatly declined in the past decade. Radiation beams used in cancer treatment include x-rays, electrons, protons, negative pions, neutrons, and ions of helium, carbon, neon and silicon. X-rays and electrons, produced by linear electron accelerators, have been the most widely used. The history of medical accelerators can be traced from Roentgen's discovery of x-rays in 1895. The evolution of medical electron accelerators will be discussed and the use of x-ray tubes, electrostatic accelerators, betatrons, and linear accelerators will be described. Heavy particle cancer treatments began in 1955 using proton beams from the Berkeley 184-inch cyclotron. Accelerators that have been used for heavy particle therapy include the Berkeley Bevalac, Los Alamos Pion Facility, Fermi Laboratory, and various research and medical cyclotrons and synchrotrons. Heavy particle accelerators and their application for cancer treatment will be discussed.

  16. Uniform acceleration in general relativity

    NASA Astrophysics Data System (ADS)

    Friedman, Yaakov; Scarr, Tzvi

    2015-10-01

    We extend de la Fuente and Romero's (Gen Relativ Gravit 47:33, 2015) defining equation for uniform acceleration in a general curved spacetime from linear acceleration to the full Lorentz covariant uniform acceleration. In a flat spacetime background, we have explicit solutions. We use generalized Fermi-Walker transport to parallel transport the Frenet basis along the trajectory. In flat spacetime, we obtain velocity and acceleration transformations from a uniformly accelerated system to an inertial system. We obtain the time dilation between accelerated clocks. We apply our acceleration transformations to the motion of a charged particle in a constant electromagnetic field and recover the Lorentz-Abraham-Dirac equation.

  17. Cosmic Plasma Wakefield Acceleration

    SciTech Connect

    Chen, P

    2004-04-26

    Recently we proposed a new cosmic acceleration mechanism which was based on the wakefields excited by the Alfven shocks in a relativistically owing plasma. In this paper we include some omitted details, and show that there exists a threshold condition for transparency below which the accelerating particle is collision-free and suffers little energy loss in the plasma medium. The stochastic encounters of the random accelerating-decelerating phases results in a power-law energy spectrum: f({epsilon}) {proportional_to} 1/{epsilon}{sup 2}. As an example, we discuss the possible production of super-GZK ultra high energy cosmic rays (UHECR) in the atmosphere of gamma ray bursts. The estimated event rate in our model agrees with that from UHECR observations.

  18. Chaos in Accelerators

    SciTech Connect

    Chao, Alex

    1999-05-11

    Chaos is a general phenomenon in nonlinear dynamical systems. Accelerators--storage rings in particular--in which particles are stored for 10{sup 10} revolutions constitute a particularly intricate nonlinear dynamical system. (In comparison, the earth has revolved around the sun for only 10{sup 9} turns.) Storage rings therefore provide an ideal testing ground for chaos physics. In fact, it is the chaos phenomenon that imposes one of the key design criteria for these accelerators. One might arguably say that the demise of the Superconducting Super Collider project originated from a misjudgement in its chaos analysis at one point along its design path, leading to its first substantial cost escalation. This talk gives an elementary introduction to the study of chaos in accelerators.

  19. Perturbations for transient acceleration

    SciTech Connect

    Vargas, Cristofher Zuñiga; Zimdahl, Winfried; Hipólito-Ricaldi, Wiliam S. E-mail: hipolito@ceunes.ufes.br

    2012-04-01

    According to the standard ΛCDM model, the accelerated expansion of the Universe will go on forever. Motivated by recent observational results, we explore the possibility of a finite phase of acceleration which asymptotically approaches another period of decelerated expansion. Extending an earlier study on a corresponding homogeneous and isotropic dynamics, in which interactions between dark matter and dark energy are crucial, the present paper also investigates the dynamics of the matter perturbations both on the Newtonian and General Relativistic (GR) levels and quantifies the potential relevance of perturbations of the dark-energy component. In the background, the model is tested against the Supernova type Ia (SNIa) data of the Constitution set and on the perturbative level against growth rate data, among them those of the WiggleZ survey, and the data of the 2dFGRS project. Our results indicate that a transient phase of accelerated expansion is not excluded by current observations.

  20. Microelectromechanical acceleration-sensing apparatus

    DOEpatents

    Lee, Robb M.; Shul, Randy J.; Polosky, Marc A.; Hoke, Darren A.; Vernon, George E.

    2006-12-12

    An acceleration-sensing apparatus is disclosed which includes a moveable shuttle (i.e. a suspended mass) and a latch for capturing and holding the shuttle when an acceleration event is sensed above a predetermined threshold level. The acceleration-sensing apparatus provides a switch closure upon sensing the acceleration event and remains latched in place thereafter. Examples of the acceleration-sensing apparatus are provided which are responsive to an acceleration component in a single direction (i.e. a single-sided device) or to two oppositely-directed acceleration components (i.e. a dual-sided device). A two-stage acceleration-sensing apparatus is also disclosed which can sense two acceleration events separated in time. The acceleration-sensing apparatus of the present invention has applications, for example, in an automotive airbag deployment system.

  1. Diffusive Shock Acceleration

    NASA Astrophysics Data System (ADS)

    Baring, Matthew

    2003-04-01

    The process of diffusive acceleration of charged particles in shocked plasmas is widely invoked in astrophysics to account for the ubiquitous presence of signatures of non-thermal relativistic electrons and ions in the universe. This statistical energization mechanism, manifested in turbulent media, was first posited by Enrico Fermi in 1949 to explain the observed cosmic ray population, which exhibits an almost power-law distribution in rigidity. The absence of a momentum scale is a key characteristic of diffusive shock acceleration, and astrophysical systems generally only impose scales at the injection (low energy) and loss (high energy) ends of the particle spectrum. The existence of structure in the cosmic ray spectrum (the "knee") at around 3000 TeV has promoted contentions that there are at least two origins for cosmic rays, a galactic one supplying those up to the knee, and perhaps an extragalactic one that can explain even the ultra-high energy cosmic rays (UHECRs) seen at 1-300 EeV. Accounting for the UHECRs with familiar astrophysical sites of acceleration has historically proven difficult due to the need to assume high magnetic fields in order to reduce the shortest diffusive acceleration timescale, the ion gyroperiod, to meaningful values. Yet active galaxies and gamma-ray bursts remain strong and interesting candidate sources for UHECRs, turning the theoretical focus to relativistic shocks. This review summarizes properties of diffusive shock acceleration that are salient to the issue of UHECR generation. These include spectral indices, anisotropies, acceleration efficencies and timescales, as functions of the shock speed and mean field orientation, and also the degree of field turbulence. Astrophysical sites for UHECR production are also critiqued.

  2. [Evolution of human brain and intelligence].

    PubMed

    Lakatos, László; Janka, Zoltán

    2008-07-30

    The biological evolution, including human evolution is mainly driven by environmental changes. Accidental genetic modifications and their innovative results make the successful adaptation possible. As we know the human evolution started 7-8 million years ago in the African savannah, where upright position and bipedalism were significantly advantageous. The main drive of improving manual actions and tool making could be to obtain more food. Our ancestor got more meat due to more successful hunting, resulting in more caloric intake, more protein and essential fatty acid in the meal. The nervous system uses disproportionally high level of energy, so better quality of food was a basic condition for the evolution of huge human brain. The size of human brain was tripled during 3.5 million years, it increased from the average of 450 cm3 of Australopithecinae to the average of 1350 cm3 of Homo sapiens. A genetic change in the system controlling gene expression could happen about 200 000 years ago, which influenced the development of nervous system, the sensorimotor function and learning ability for motor processes. The appearance and stabilisation of FOXP2 gene structure as feature of modern man coincided with the first presence and quick spread of Homo sapiens on the whole Earth. This genetic modification made opportunity for human language, as the basis of abrupt evolution of human intelligence. The brain region being responsible for human language is the left planum temporale, which is much larger in left hemisphere. This shows the most typical human brain asymmetry. In this case the anatomical asymmetry means a clearly defined functional asymmetry as well, where the brain hemispheres act differently. The preference in using hands, the lateralised using of tools resulted in the brain asymmetry, which is the precondition of human language and intelligence. However, it cannot be held anymore, that only humans make tools, because our closest relatives, the chimpanzees are

  3. "Light sail" acceleration reexamined.

    PubMed

    Macchi, Andrea; Veghini, Silvia; Pegoraro, Francesco

    2009-08-21

    The dynamics of the acceleration of ultrathin foil targets by the radiation pressure of superintense, circularly polarized laser pulses is investigated by analytical modeling and particle-in-cell simulations. By addressing self-induced transparency and charge separation effects, it is shown that for "optimal" values of the foil thickness only a thin layer at the rear side is accelerated by radiation pressure. The simple "light sail" model gives a good estimate of the energy per nucleon, but overestimates the conversion efficiency of laser energy into monoenergetic ions.

  4. High intensity hadron accelerators

    SciTech Connect

    Teng, L.C.

    1989-05-01

    This rapporteur report consists mainly of two parts. Part I is an abridged review of the status of all High Intensity Hadron Accelerator projects in the world in semi-tabulated form for quick reference and comparison. Part II is a brief discussion of the salient features of the different technologies involved. The discussion is based mainly on my personal experiences and opinions, tempered, I hope, by the discussions I participated in in the various parallel sessions of the workshop. In addition, appended at the end is my evaluation and expression of the merits of high intensity hadron accelerators as research facilities for nuclear and particle physics.

  5. Jupiter's Auroras Acceleration Processes

    NASA Image and Video Library

    2017-09-06

    This image, created with data from Juno's Ultraviolet Imaging Spectrometer (UVS), marks the path of Juno's readings of Jupiter's auroras, highlighting the electron measurements that show the discovery of the so-called discrete auroral acceleration processes indicated by the "inverted Vs" in the lower panel (Figure 1). This signature points to powerful magnetic-field-aligned electric potentials that accelerate electrons toward the atmosphere to energies that are far greater than what drive the most intense aurora at Earth. Scientists are looking into why the same processes are not the main factor in Jupiter's most powerful auroras. https://photojournal.jpl.nasa.gov/catalog/PIA21937

  6. HIGH GRADIENT INDUCTION ACCELERATOR

    SciTech Connect

    Caporaso, G J; Sampayan, S; Chen, Y; Blackfield, D; Harris, J; Hawkins, S; Holmes, C; Krogh, M; Nelson, S; Nunnally, W; Paul, A; Poole, B; Rhodes, M; Sanders, D; Selenes, K; Sullivan, J; Wang, L; Watson, J

    2007-06-21

    A new type of compact induction accelerator is under development at the Lawrence Livermore National Laboratory that promises to increase the average accelerating gradient by at least an order of magnitude over that of existing induction machines. The machine is based on the use of high gradient vacuum insulators, advanced dielectric materials and switches and is stimulated by the desire for compact flash x-ray radiography sources. Research describing an extreme variant of this technology aimed at proton therapy for cancer will be described. Progress in applying this technology to several applications will be reviewed.

  7. 'Light Sail' Acceleration Reexamined

    SciTech Connect

    Macchi, Andrea; Veghini, Silvia; Pegoraro, Francesco

    2009-08-21

    The dynamics of the acceleration of ultrathin foil targets by the radiation pressure of superintense, circularly polarized laser pulses is investigated by analytical modeling and particle-in-cell simulations. By addressing self-induced transparency and charge separation effects, it is shown that for 'optimal' values of the foil thickness only a thin layer at the rear side is accelerated by radiation pressure. The simple 'light sail' model gives a good estimate of the energy per nucleon, but overestimates the conversion efficiency of laser energy into monoenergetic ions.

  8. The parental antagonism theory of language evolution: preliminary evidence for the proposal.

    PubMed

    Brown, William M

    2011-04-01

    Language--as with most communication systems--likely evolved by means of natural selection. Accounts for the genetical selection of language can usually be divided into two scenarios, either of which used in isolation of the other appear insufficient to explain the phenomena: (1) there are group benefits from communicating, and (2) there are individual benefits from being a better communicator. In contrast, it is hypothesized that language phenotypes emerged during a coevolutionary struggle between parental genomes via genomic imprinting, which is differential gene expression depending on parental origin of the genetic element. It is hypothesized that relatedness asymmetries differentially selected for patrigene-caused language phenotypes to extract resources from mother (early in development) and matrigene-caused language phenotypes to influence degree of cooperativeness among asymmetric kin (later in development). This paper reports that imprinted genes have a high frequency of involvement in language phenotypes (~36%), considering their presumed rarity in the human genome (~2%). For example, two well-studied genes associated with language impairments (FOXP2 and UBE3A) exhibit parent-of- origin effects. Specifically, FOXP2 is putatively paternally expressed, whereas UBE3A is a maternally expressed imprinted gene. It is also hypothesized that the more unique and cooperative aspects of human language emerged to the benefit of matrilineal inclusive fitness. Consistent with this perspective, it is reported here that the X-chromosome has higher involvement in loci that have associations with language than would be expected by chance. It is also reported, for the first time, that human and chimpanzee maternally expressed overlapping imprinted genes exhibit greater evolutionary divergence (in terms of the degree of overlapping transcripts) than paternally expressed overlapping imprinted genes. Finally, an analysis of global language patterns reveals that paternally but

  9. From the ultrasonic to the infrared: molecular evolution and the sensory biology of bats

    PubMed Central

    Jones, Gareth; Teeling, Emma C.; Rossiter, Stephen J.

    2013-01-01

    Great advances have been made recently in understanding the genetic basis of the sensory biology of bats. Research has focused on the molecular evolution of candidate sensory genes, genes with known functions [e.g., olfactory receptor (OR) genes] and genes identified from mutations associated with sensory deficits (e.g., blindness and deafness). For example, the FoxP2 gene, underpinning vocal behavior and sensorimotor coordination, has undergone diversification in bats, while several genes associated with audition show parallel amino acid substitutions in unrelated lineages of echolocating bats and, in some cases, in echolocating dolphins, representing a classic case of convergent molecular evolution. Vision genes encoding the photopigments rhodopsin and the long-wave sensitive opsin are functional in bats, while that encoding the short-wave sensitive opsin has lost functionality in rhinolophoid bats using high-duty cycle laryngeal echolocation, suggesting a sensory trade-off between investment in vision and echolocation. In terms of olfaction, bats appear to have a distinctive OR repertoire compared with other mammals, and a gene involved in signal transduction in the vomeronasal system has become non-functional in most bat species. Bitter taste receptors appear to have undergone a “birth-and death” evolution involving extensive gene duplication and loss, unlike genes coding for sweet and umami tastes that show conservation across most lineages but loss in vampire bats. Common vampire bats have also undergone adaptations for thermoperception, via alternative splicing resulting in the evolution of a novel heat-sensitive channel. The future for understanding the molecular basis of sensory biology is promising, with great potential for comparative genomic analyses, studies on gene regulation and expression, exploration of the role of alternative splicing in the generation of proteomic diversity, and linking genetic mechanisms to behavioral consequences. PMID

  10. From the ultrasonic to the infrared: molecular evolution and the sensory biology of bats.

    PubMed

    Jones, Gareth; Teeling, Emma C; Rossiter, Stephen J

    2013-01-01

    Great advances have been made recently in understanding the genetic basis of the sensory biology of bats. Research has focused on the molecular evolution of candidate sensory genes, genes with known functions [e.g., olfactory receptor (OR) genes] and genes identified from mutations associated with sensory deficits (e.g., blindness and deafness). For example, the FoxP2 gene, underpinning vocal behavior and sensorimotor coordination, has undergone diversification in bats, while several genes associated with audition show parallel amino acid substitutions in unrelated lineages of echolocating bats and, in some cases, in echolocating dolphins, representing a classic case of convergent molecular evolution. Vision genes encoding the photopigments rhodopsin and the long-wave sensitive opsin are functional in bats, while that encoding the short-wave sensitive opsin has lost functionality in rhinolophoid bats using high-duty cycle laryngeal echolocation, suggesting a sensory trade-off between investment in vision and echolocation. In terms of olfaction, bats appear to have a distinctive OR repertoire compared with other mammals, and a gene involved in signal transduction in the vomeronasal system has become non-functional in most bat species. Bitter taste receptors appear to have undergone a "birth-and death" evolution involving extensive gene duplication and loss, unlike genes coding for sweet and umami tastes that show conservation across most lineages but loss in vampire bats. Common vampire bats have also undergone adaptations for thermoperception, via alternative splicing resulting in the evolution of a novel heat-sensitive channel. The future for understanding the molecular basis of sensory biology is promising, with great potential for comparative genomic analyses, studies on gene regulation and expression, exploration of the role of alternative splicing in the generation of proteomic diversity, and linking genetic mechanisms to behavioral consequences.

  11. Brane assisted quintessential inflation with transient acceleration

    SciTech Connect

    Bento, M. C.; Santos, N. M. C.; Gonzalez Felipe, R.

    2008-06-15

    A simple model of quintessential inflation with the modified exponential potential e{sup -{alpha}}{sup {phi}}[A+({phi}-{phi}{sub 0}){sup 2}] is analyzed in the braneworld context. Considering reheating via instant preheating, it is shown that the evolution of the scalar field {phi} from inflation to the present epoch is consistent with the observational constraints in a wide region of the parameter space. The model exhibits transient acceleration at late times for 0.96 < or approx. A{alpha}{sup 2} < or approx. 1.26 and 271 < or approx. {phi}{sub 0}{alpha} < or approx. 273, while permanent acceleration is obtained for 2.3x10{sup -8} < or approx. A{alpha}{sup 2} < or approx. 0.98 and 255 < or approx. {phi}{sub 0}{alpha} < or approx. 273. The steep parameter {alpha} is constrained to be in the range 5.3 < or approx. {alpha} < or approx. 10.8.

  12. Combined generating-accelerating buncher for compact linear accelerators

    NASA Astrophysics Data System (ADS)

    Savin, E. A.; Matsievskiy, S. V.; Sobenin, N. P.; Sokolov, I. D.; Zavadtsev, A. A.

    2016-09-01

    Described in the previous article [1] method of the power extraction from the modulated electron beam has been applied to the compact standing wave electron linear accelerator feeding system, which doesnt require any connection waveguides between the power source and the accelerator itself [2]. Generating and accelerating bunches meet in the hybrid accelerating cell operating at TM020 mode, thus the accelerating module is placed on the axis of the generating module, which consists from the pulsed high voltage electron sources and electrons dumps. This combination makes the accelerator very compact in size which is very valuable for the modern applications such as portable inspection sources. Simulations and geometry cold tests are presented.

  13. Radioisotope Dating with Accelerators.

    ERIC Educational Resources Information Center

    Muller, Richard A.

    1979-01-01

    Explains a new method of detecting radioactive isotopes by counting their accelerated ions rather than the atoms that decay during the counting period. This method increases the sensitivity by several orders of magnitude, and allows one to find the ages of much older and smaller samples. (GA)

  14. Radioisotope Dating with Accelerators.

    ERIC Educational Resources Information Center

    Muller, Richard A.

    1979-01-01

    Explains a new method of detecting radioactive isotopes by counting their accelerated ions rather than the atoms that decay during the counting period. This method increases the sensitivity by several orders of magnitude, and allows one to find the ages of much older and smaller samples. (GA)

  15. Accelerated Management Development

    ERIC Educational Resources Information Center

    Munn, Kenn

    1974-01-01

    Western Electric's accelerated management development program for hand picked college graduate students consists of a high risk training project in which the management candidate accomplishes his task or is terminated. The success of such projects puts candidates in third level management in seven years or half the normal time. (DS)

  16. The neutrino electron accelerator

    SciTech Connect

    Shukla, P.K.; Stenflo, L.; Bingham, R.; Bethe, H.A.; Dawson, J.M.; Mendonca, J.T.

    1998-01-01

    It is shown that a wake of electron plasma oscillations can be created by the nonlinear ponderomotive force of an intense neutrino flux. The electrons trapped in the plasma wakefield will be accelerated to high energies. Such processes may be important in supernovas and pulsars. {copyright} {ital 1998 American Institute of Physics.}

  17. Prospects for Accelerator Technology

    NASA Astrophysics Data System (ADS)

    Todd, Alan

    2011-02-01

    Accelerator technology today is a greater than US$5 billion per annum business. Development of higher-performance technology with improved reliability that delivers reduced system size and life cycle cost is expected to significantly increase the total accelerator technology market and open up new application sales. Potential future directions are identified and pitfalls in new market penetration are considered. Both of the present big market segments, medical radiation therapy units and semiconductor ion implanters, are approaching the "maturity" phase of their product cycles, where incremental development rather than paradigm shifts is the norm, but they should continue to dominate commercial sales for some time. It is anticipated that large discovery-science accelerators will continue to provide a specialty market beset by the unpredictable cycles resulting from the scale of the projects themselves, coupled with external political and economic drivers. Although fraught with differing market entry difficulties, the security and environmental markets, together with new, as yet unrealized, industrial material processing applications, are expected to provide the bulk of future commercial accelerator technology growth.

  18. FPGA Verification Accelerator (FVAX)

    NASA Technical Reports Server (NTRS)

    Oh, Jane; Burke, Gary

    2008-01-01

    Is Verification Acceleration Possible? - Increasing the visibility of the internal nodes of the FPGA results in much faster debug time - Forcing internal signals directly allows a problem condition to be setup very quickly center dot Is this all? - No, this is part of a comprehensive effort to improve the JPL FPGA design and V&V process.

  19. Pulsed electromagnetic gas acceleration

    NASA Technical Reports Server (NTRS)

    Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

    1974-01-01

    Detailed measurements of the axial velocity profile and electromagnetic structure of a high power, quasi-steady MPD discharge are used to formulate a gasdynamic model of the acceleration process. Conceptually dividing the accelerated plasma into an inner flow and an outer flow, it is found that more than two-thirds of the total power in the plasma is deposited in the inner flow, accelerating it to an exhaust velocity of 12.5 km/sec. The outer flow, which is accelerated to a velocity of only 6.2 km/sec, appears to provide a current conduction path between the inner flow and the anode. Related cathode studies have shown that the critical current for the onset of terminal voltage fluctuations, which was recently shown to be a function of the cathode area, appears to reach an asymptote for cathodes of very large surface area. Detailed floating potential measurements show that the fluctuations are confined to the vicinity of the cathode and hence reflect a cathode emission process rather than a fundamental limit on MPD performance.

  20. Progress in radiocarbon dating with the Chalk River MP tandem accelerator

    SciTech Connect

    Andrews, H.R.; Ball, G.C.; Brown, R.M.; Davies, W.G.; Imahori, Y.; Milton, J.C.D.

    1980-01-01

    The evolution of a tandem accelerator /sup 14/C dating system at Chalk River is recounted. Background problems and sources of instability are discussed and solutions are described. Details of sample chemistry and source preparation are presented.