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Chirkov, Maksym ; Stiller, Gabriele ; Laeng, Alexandra ; Kellmann, Sylvia ; Clarmann, Thomas von ; Boone, Chris D. ; Elkins, James William ; Engel, Andreas ; Glatthor, Norbert ; Grabowski, Udo ; Harth, Christina M. ; Kiefer, Michael ; Kolonjari, Felicia ; Krummel, Paul B. ; Linden, Andrea ; Lunder, Chris Rene ; Miller, Benjamin R. ; Montzka, Stephen A. ; Mühle, Jens ; O'Doherty, Simon ; Orphal, Johannes ; Prinn, Ronald G. ; Toon, Geoffrey C. ; Vollmer, Martin K. ; Walker, Kaley A. ; Weiss, Ray F. ; Wiegele, Andreas ; Young, Dickon
We report on HCFC-22 data acquired by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) in the reduced spectral resolution nominal observation mode. The data cover the period from January 2005 to April 2012 and the altitude range from the upper troposphere (above cloud top altitude) to about 50 km. The profile retrieval was performed by constrained nonlinear least squares fitting of modelled spectra to the measured limb spectral radiances. The spectral ν4-band at 816.5 ± 13 cm−1 was used for the retrieval. A Tikhonov-type smoothing constraint was applied to stabilise the retrieval. In the lower stratosphere, we find a global volume mixing ratio of HCFC-22 of about 185 pptv in January 2005. The rate of linear growth in the lower latitudes lower stratosphere was about 6 to 7 pptv year−1 in the period 2005–2012. The profiles obtained were compared with ACE-FTS satellite data v3.5, as well as with MkIV balloon profiles and cryosampler balloon measurements. Between 13 and 22 km, average agreement within −3 to +5 pptv (MIPAS – ACE) with ACE-FTS v3.5 profiles is demonstrated. Agreement with MkIV solar occultation balloon-borne measurements is within 10–20 pptv below 30 km and worse above, while in situ cryosampler balloon measurements are systematically lower over their full altitude range by 15–50 pptv below 24 km and less than 10 pptv above 28 km. MIPAS HCFC-22 time series below 10 km altitude are shown to agree mostly well to corresponding time series of near-surface abundances from the NOAA/ESRL and AGAGE networks, although a more pronounced seasonal cycle is obvious in the satellite data. This is attributed to tropopause altitude fluctuations and subsidence of polar winter stratospheric air into the troposphere. A parametric model consisting of constant, linear, quasi-biennial oscillation (QBO) and several sine and cosine terms with different periods has been fitted to the temporal variation of stratospheric HCFC-22 for all 10°-latitude/1-to-2-km-altitude bins. The relative linear variation was always positive, with relative increases of 40–70 % decade−1 in the tropics and global lower stratosphere, and up to 120 % decade−1 in the upper stratosphere of the northern polar region and the southern extratropical hemisphere. Asian HCFC-22 emissions have become the major source of global upper tropospheric HCFC-22. In the upper troposphere, monsoon air, rich in HCFC-22, is instantaneously mixed into the tropics. In the middle stratosphere, between 20 and 30 km, the observed trend is inconsistent with the trend at the surface (corrected for the age of stratospheric air), hinting at circulation changes. There exists a stronger positive trend in HCFC-22 in the Southern Hemisphere and a more muted positive trend in the Northern Hemisphere, implying a potential change in the stratospheric circulation over the observation period.
Chirkov, Maksym ; Stiller, Gabriele ; Laeng, Alexandra ; Kellmann, Sylvia ; Clarmann, Thomas von ; Boone, Chris D. ; Elkins, James William ; Engel, Andreas ; Glatthor, Norbert ; Grabowski, Udo ; Harth, Christina M. ; Kiefer, Michael ; Kolonjari, Felicia ; Krummel, Paul B. ; Linden, Andrea ; Lunder, Chris Rene ; Miller, Benjamin R. ; Montzka, Stephen A. ; Mühle, Jens ; O'Doherty, Simon ; Orphal, Johannes ; Prinn, Ronald G. ; Toon, Geoffrey C. ; Vollmer, Martin K. ; Walker, Kaley A. ; Weiss, Ray F. ; Wiegele, Andreas ; Young, Dickon
We report on HCFC-22 data acquired by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) in reduced spectral resolution nominal mode in the period from January 2005 to April 2012 from version 5.02 level-1b spectral data and covering an altitude range from the upper troposphere (above cloud top altitude) to about 50 km. The profile retrieval was performed by constrained nonlinear least squares fitting of measured limb spectral radiances to modelled spectra. The spectral v4-band at 816.5 ± 13 cm-1 was used for the retrieval. A Tikhonov-type smoothing constraint was applied to stabilise the retrieval. In the lower stratosphere, we find a global volume mixing ratio of HCFC-22 of about 185 pptv in January 2005. The linear growth rate in the lower latitudes lower stratosphere was about 6 to 7 pptv yr-1 in the period 2005–2012. The obtained profiles were compared with ACE-FTS satellite data v3.5, as well as with MkIV balloon profiles and in situ cryosampler balloon measurements. Between 13 and 22 km, average agreement within -3 to +5 pptv (MIPAS–ACE) with ACE-FTS v3.5 pro files is demonstrated. Agreement with MkIV solar occultation balloon-borne measurements is within 10–20 pptv below 30 km and worse above, while in situ cryosampler balloon measurements are systematically lower over their full altitude range by 15– 50 pptv below 24 km and less than 10 pptv above 28 km. Obtained MIPAS HCFC-22 time series below 10 km altitude are shown to agree mostly well to corresponding time series of near-surface abundances from NOAA/ESRL and AGAGE networks, although a more pronounced seasonal cycle is obvious in the satellite data, probably due to tropopause altitude fluctuations and subsidence of polar winter stratospheric air into the troposphere. A parametric model consisting of constant, linear, quasi-biennial oscillation (QBO) and several sine and cosine terms with different periods has been fitted to the temporal variation of stratospheric HCFC-22 for all 10° latitude/1 to 2 km altitude bins. The relative linear variation was always positive, with relative increases of 40–70%decade-1 in the tropics and global lower stratosphere, and up to 120%decade-1 in the upper stratosphere of the northern polar region and the southern extratropical hemisphere. In the middle stratosphere between 20 and 30 km, the observed trend is not consistent with the age of stratospheric air-corrected trend at ground, but stronger positive at the Southern Hemisphere and less strong increasing in the Northern Hemisphere, hinting towards changes in the stratospheric circulation over the observation period.
'Perhaps the sodomites should be written out of Dante's "Inferno"', Jarman wrote in his journal on 1 August 1990: 'I'll offer myself as the ghostwriter.' What does he mean by 'ghostwriter' here? How queer is this odd speech-act? What is he offering to do to the homophobic landscape of the "Inferno", that forbiddingly sealed textual prison, with his Hollywood pitchman's casual bid to 'write out' the sodomites as if they were a slight embarrassment to the divine justice system? Is he speaking in jest as a writer of gay satires and sacrilegious memoirs, or in deadly earnest as an activist who had renounced the middle-class pretensions and frivolities of the pre-AIDS gay world? [...] Jarman counters the trope of homosexual theft visually with the triumphant figure of Man with Snake. The Dantesque merging of snake and thief is replaced by an erotic dance in which the gilded youth raises his phallic partner above his head and seductively kisses it on the mouth. Whereas Dante would have us notice the grotesque parody of the Trinity played out in the seventh bolgia - with the unchanging Puccio as God the Father, the two-natured Agnello-Cianfa as Christ, and the fume-veiled Buoso receiving his forked tongue from the serpent Francesco in a demonic replay of the gift of tongues from the Spirit - Jarman clears away all overdetermined theological meanings to revel in the purely aesthetic impact of the phallic dancer. All the ghosts from Dante's snakepit are conjured away in the film and replaced with the solid presence of a single gorgeously spotlit male body. Ghostwriting Dante, for Jarman, meant more than a mere appropriation of homoerotic scenes from the "Inferno" into his screenplay. It meant a complete reimagining of their aesthetic significance within the filmscape of his Dantean transformations.
Frantz, Laurent A. F. ; Haile, James ; Lin, Audrey T. ; Scheu, Amelie ; Geörg, Christina ; Benecke, Norbert ; Alexander, Michelle ; Linderholm, Anna ; Mullin, Victoria E. ; Daly, Kevin G. ; Battista, Vincent M. ; Price, Max ; Gron, Kurt J. ; Alexandri, Panoraia ; Arbogast, Rose-Marie ; Arbuckle, Benjamin ; Bălăşescu, Adrian ; Barnett, Ross ; Bartosiewicz, László ; Baryshnikov, Gennady ; Bonsall, Clive ; Borić, Dušan ; Boroneanţ, Adina ; Bulatović, Jelena ; Çakırlar, Canan ; Carretero, José-Miguel ; Chapman, John ; Church, Mike ; Crooijmans, Richard ; DeCupere, Bea ; Detry, Cleia ; Dimitrijević, Vesna ; Dumitraşcu, Valentin ; Du Plessis, Louis ; Edwards, Ceiridwen ; Erek, Cevdet Merih ; Erim Özdoğan, Aslı ; Ervynck, Anton ; Fulgione, Domenico ; Gligor, Mihai ; Götherström, Anders ; Gourichon, Lionel ; Groenen, Martien A. M. ; Helmer, Daniel ; Hongo, Hitomi ; Horwitz, Liora Kolska ; Irving-Pease, Evan K. ; Lebrasseur, Ophélie ; Lesur, Joséphine ; Malone, Caroline ; Manaserya, Ninna ; Marciniak, Arkadiusz ; Martlew, Holley ; Mashkour, Marjan ; Matthews, Roger ; Motuzaitė Matuzevičiūtė, Giedrė ; Maziar, Sepideh ; Meijaard, Erik ; McGovern, Tom ; Megens, Hendrik-Jan ; Miller, Rebecca ; Mohaseb, Azadeh Fatemeh ; Orschiedt, Jörg ; Orton, David ; Papathanasiou, Anastasia ; Parker Pearson, Michael ; Pinhasi, Ron ; Radmanović, Darko ; Ricaut, François-Xavier ; Richards, Mike ; Sabin, Richard ; Sarti, Lucia ; Schier, Wolfram ; Sheikhi, Shiva ; Stephan, Elisabeth ; Stewart, John R. ; Stoddart, Simon ; Tagliacozzo, Antonio ; Tasić, Nenad N. ; Trantalidou, Katerina ; Tresset, Anne ; Valdiosera, Cristina ; Hurk, Youri van den ; Poucke, Sophie van ; Vigne, Jean-Denis ; Yanevich, Alexander ; Zeeb-Lanz, Andrea ; Triantafyllidis, Alexandros ; Gilbert, M. Thomas P. ; Schibler, Jörg ; Rowley-Conwy, Peter ; Zeder, Melinda ; Peters, Joris ; Cucchi, Thomas ; Bradley, Daniel G. ; Dobney, Keith ; Burger, Joachim ; Evin, Allowen ; Girdland-Flink, Linus ; Larson, Greger
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Casey, Jillian P. ; Magalhães, Tiago R. ; Conroy, Judith M. ; Regan, Regina ; Shah, Naisha ; Anney, Richard ; Shields, Denis C. ; Abrahams, Brett S. ; Almeida, Joana ; Bacchelli, Elena ; Bailey, Anthony J. ; Baird, Gillian ; Battaglia, Agatino ; Berney, Tom ; Bolshakova, Nadia ; Bolton, Patrick F. ; Bourgeron, Thomas ; Brennan, Sean ; Cali, Phil ; Correia, Catarina ; Corsello, Christina ; Coutanche, Marc ; Dawson, Geraldine ; Jonge, Maretha de ; Delorme, Richard ; Duketis, Eftichia ; Duque, Frederico ; Estes, Annette ; Farrar, Penny ; Fernandez, Bridget A. ; Folstein, Susan E. ; Foley, Suzanne ; Fombonne, Eric ; Freitag, Christine M. ; Gilbert, John ; Gillberg, Christopher ; Glessner, Joseph T. ; Green, Jonathan ; Guter, Stephen J. ; Hakonarson, Hakon ; Holt, Richard ; Hughes, Gillian ; Hus, Vanessa ; Igliozzi, Roberta ; Kim, Cecilia ; Klauck, Sabine M. ; Kolevzon, Alexander ; Lamb, Janine A. ; Leboyer, Marion ; Le Couteur, Ann ; Leventhal, Bennett L. ; Lord, Catherine ; Lund, Sabata C. ; Maestrini, Elena ; Mantoulan, Carine ; Marshall, Christian R. ; McConachie, Helen ; McDougle, Christopher J. ; McGrath, Jane ; McMahon, William M. ; Merikangas, Alison ; Miller, Judith ; Minopoli, Fiorella ; Mirza, Ghazala K. ; Munson, Jeff ; Nelson, Stanley F. ; Nygren, Gudrun ; Oliveira, Guiomar ; Pagnamenta, Alistair T. ; Papanikolaou, Katerina ; Parr, Jeremy R. ; Parrini, Barbara ; Pickles, Andrew ; Pinto, Dalila ; Piven, Joseph ; Posey, David J. ; Poustka, Annemarie ; Poustka, Fritz ; Ragoussis, Jiannis ; Roge, Bernadette ; Rutter, Michael L. ; Sequeira, Ana F. ; Soorya, Latha ; Sousa, Inês ; Sykes, Nuala ; Stoppioni, Vera ; Tancredi, Raffaella ; Tauber, Maïté ; Thompson, Ann P. ; Thomson, Susanne ; Tsiantis, John ; Engeland, Herman van ; Vincent, John B. ; Volkmar, Fred ; Vorstman, Jacob A. S. ; Wallace, Simon ; Wang, Kai ; Wassink, Thomas H. ; White, Kathy ; Wing, Kirsty ; Wittemeyer, Kerstin ; Yaspan, Brian L. ; Zwaigenbaum, Lonnie ; Betancur, Catalina ; Buxbaum, Joseph D. ; Cantor, Rita M. ; Cook, Edwin H. ; Coon, Hilary ; Cuccaro, Michael L. ; Geschwind, Daniel H. ; Haines, Jonathan L. ; Hallmayer, Joachim ; Monaco, Anthony P. ; Nurnberger, John I. ; Pericak-Vance, Margaret Ann ; Schellenberg, Gerard D. ; Scherer, Stephen W. ; Sutcliffe, James S. ; Szatmari, Peter ; Vieland, Veronica J. ; Wijsman, Ellen M. ; Green, Andrew ; Gill, Michael ; Gallagher, Louise ; Vicente, Astrid M. ; Ennis, Sean
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Anney, Richard ; Klei, Lambertus ; Pinto, Dalila ; Almeida, Joana ; Bacchelli, Elena ; Baird, Gillian ; Bolshakova, Nadia ; Bölte, Sven ; Bolton, Patrick F. ; Bourgeron, Thomas ; Brennan, Sean ; Brian, Jessica ; Casey, Jillian ; Conroy, Judith ; Correia, Catarina ; Corsello, Christina ; Crawford, Emily L. ; Jonge, Maretha de ; Delorme, Richard ; Duketis, Eftichia ; Duque, Frederico ; Estes, Annette ; Farrar, Penny ; Fernandez, Bridget A. ; Folstein, Susan E. ; Fombonne, Eric ; Gilbert, John ; Gillberg, Christopher ; Glessner, Joseph T. ; Green, Andrew ; Green, Jonathan ; Guter, Stephen J. ; Heron, Elizabeth A. ; Holt, Richard ; Howe, Jennifer L. ; Hughes, Gillian ; Hus, Vanessa ; Igliozzi, Roberta ; Jacob, Suma ; Kenny, Graham P. ; Kim, Cecilia ; Kolevzon, Alexander ; Kustanovich, Vlad ; Lajonchere, Clara M. ; Lamb, Janine A. ; Law-Smith, Miriam ; Leboyer, Marion ; Le Couteur, Ann ; Leventhal, Bennett L. ; Liu, Xiao-Qing ; Lombard, Frances ; Lord, Catherine ; Lotspeich, Linda ; Lotspeich, Linda ; Lund, Sabata C. ; Magalhães, Tiago R. ; Mantoulan, Carine ; McDougle, Christopher J. ; Melhem, Nadine M. ; Merikangas, Alison ; Minshew, Nancy J. ; Mirza, Ghazala K. ; Munson, Jeff ; Noakes, Carolyn ; Nygren, Gudrun ; Papanikolaou, Katerina ; Pagnamenta, Alistair T. ; Parrini, Barbara ; Paton, Tara ; Paton, Tara ; Pickles, Andrew ; Posey, David J. ; Poustka, Fritz ; Ragoussis, Jiannis ; Regan, Regina ; Roberts, Wendy ; Roeder, Kathryn ; Roge, Bernadette ; Rutter, Michael L. ; Schlitt, Sabine ; Shah, Naisha ; Sheffield, Val C. ; Soorya, Latha ; Sousa, Inês ; Stoppioni, Vera ; Sykes, Nuala ; Tancredi, Raffaella ; Thompson, Ann P. ; Thomson, Susanne ; Tryfon, Ana ; Tsiantis, John ; Engeland, Herman van ; Vincent, John B. ; Volkmar, Fred ; Vorstman, JAS ; Wallace, Simon ; Wing, Kirsty ; Wittemeyer, Kerstin ; Wood, Shawn ; Zurawiecki, Danielle ; Zwaigenbaum, Lonnie ; Bailey, Anthony J. ; Battaglia, Agatino ; Cantor, Rita M. ; Coon, Hilary ; Cuccaro, Michael L. ; Dawson, Geraldine ; Ennis, Sean ; Freitag, Christine M. ; Geschwind, Daniel H. ; Haines, Jonathan L. ; Klauck, Sabine M. ; McMahon, William M. ; Maestrini, Elena ; Miller, Judith ; Monaco, Anthony P. ; Nelson, Stanley F. ; Nurnberger, John I. ; Oliveira, Guiomar ; Parr, Jeremy R. ; Pericak-Vance, Margaret Ann ; Piven, Joseph ; Schellenberg, Gerard D. ; Scherer, Stephen W. ; Vicente, Astrid M. ; Wassink, Thomas H. ; Wijsman, Ellen M. ; Betancur, Catalina ; Buxbaum, Joseph D. ; Cook, Edwin H. ; Gallagher, Louise ; Gill, Michael ; Hallmayer, Joachim ; Paterson, Andrew D. ; Sutcliffe, James S. ; Szatmari, Peter ; Vieland, Veronica J. ; Hakonarson, Hakon ; Devlin, Bernie
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Anney, Richard ; Klei, Lambertus ; Pinto, Dalila ; Regan, Regina ; Conroy, Judith ; Magalhães, Tiago R. ; Correia, Catarina ; Abrahams, Brett S. ; Sykes, Nuala ; Pagnamenta, Alistair T. ; Almeida, Joana ; Bacchelli, Elena ; Bailey, Anthony J. ; Baird, Gillian ; Battaglia, Agatino ; Berney, Tom ; Bolshakova, Nadia ; Bölte, Sven ; Bolton, Patrick F. ; Bourgeron, Thomas ; Brennan, Sean ; Brian, Jessica ; Carson, Andrew R. ; Casallo, Guillermo ; Casey, Jillian ; Chu, Su H. ; Cochrane, Lynne ; Corsello, Christina ; Crawford, Emily L. ; Crossett, Andrew ; Dawson, Geraldine ; Jonge, Maretha de ; Delorme, Richard ; Drmic, Irene ; Duketis, Eftichia ; Duque, Frederico ; Estes, Annette ; Farrar, Penny ; Fernandez, Bridget A. ; Folstein, Susan E. ; Fombonne, Eric ; Freitag, Christine M. ; Gilbert, John ; Gillberg, Christopher ; Glessner, Joseph T. ; Goldberg, Jeremy ; Green, Jonathan ; Guter, Stephen J. ; Hakonarson, Hakon ; Heron, Elizabeth A. ; Hill, Matthew ; Holt, Richard ; Howe, Jennifer L. ; Hughes, Gillian ; Hus, Vanessa ; Igliozzi, Roberta ; Kim, Cecilia ; Klauck, Sabine M. ; Kolevzon, Alexander ; Korvatska, Olena ; Kustanovich, Vlad ; Lajonchere, Clara M. ; Lamb, Janine A. ; Laskawiec, Magdalena ; Leboyer, Marion ; Le Couteur, Ann ; Leventhal, Bennett L. ; Lionel, Anath C. ; Liu, Xiao-Qing ; Lord, Catherine ; Lotspeich, Linda ; Lund, Sabata C. ; Maestrini, Elena ; Mahoney, William ; Mantoulan, Carine ; Marshall, Christian R. ; McConachie, Helen ; McDougle, Christopher J. ; McGrath, Jane ; McMahon, William M. ; Melhem, Nadine M. ; Merikangas, Alison ; Migita, Ohsuke ; Minshew, Nancy J. ; Mirza, Ghazala K. ; Munson, Jeff ; Nelson, Stanley F. ; Noakes, Carolyn ; Noor, Abdul ; Nygren, Gudrun ; Oliveira, Guiomar ; Papanikolaou, Katerina ; Parr, Jeremy R. ; Parrini, Barbara ; Paton, Tara ; Pickles, Andrew ; Piven, Joseph ; Posey, David J. ; Poustka, Annemarie ; Poustka, Fritz ; Prasad, Aparna ; Ragoussis, Jiannis ; Renshaw, Katy ; Rickaby, Jessica ; Roberts, Wendy ; Roeder, Kathryn ; Roge, Bernadette ; Rutter, Michael L. ; Bierut, Laura Jean ; Rice, John P. ; Salt, Jeff ; Sansom, Katherine ; Sato, Daisuke ; Segurado, Ricardo ; Senman, Lili ; Shah, Naisha ; Sheffield, Val C. ; Soorya, Latha ; Sousa, Inês ; Stoppioni, Vera ; Strawbridge, Christina ; Tancredi, Raffaella ; Tansey, Katherine ; Thiruvahindrapduram, Bhooma ; Thompson, Ann P. ; Thomson, Susanne ; Tryfon, Ana ; Tsiantis, John ; Engeland, Herman van ; Vincent, John B. ; Volkmar, Fred ; Wallace, Simon ; Wang, Kai ; Wang, Zhouzhi ; Wassink, Thomas H. ; Wing, Kirsty ; Wittemeyer, Kerstin ; Wood, Shawn ; Yaspan, Brian L. ; Zurawiecki, Danielle ; Zwaigenbaum, Lonnie ; Betancur, Catalina ; Buxbaum, Joseph D. ; Cantor, Rita M. ; Cook, Edwin H. ; Coon, Hilary ; Cuccaro, Michael L. ; Gallagher, Louise ; Geschwind, Daniel H. ; Gill, Michael ; Haines, Jonathan L. ; Miller, Judith ; Monaco, Anthony P. ; Nurnberger, John I. ; Paterson, Andrew D. ; Pericak-Vance, Margaret Ann ; Schellenberg, Gerard D. ; Scherer, Stephen W. ; Sutcliffe, James S. ; Szatmari, Peter ; Vicente, Astrid M. ; Vieland, Veronica J. ; Wijsman, Ellen M. ; Devlin, Bernie ; Ennis, Sean ; Hallmayer, Joachim
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Matthews, Deborah L. ; Miller, Jacqueline Y. ; Warren, Andrew D. ; Toomey, James K. ; Portell, Roger W. ; Lott, Terry A. ; Grishin, Nick V.
We review the genus Cyclargus Nabokov (Lepidoptera: Lycaenidae) based on detailed comparative analyses of wing patterns, genitalia, and mitochondrial COI DNA barcode sequences, and suggest that Cyclargus is composed of four species: C. thomasi (Clench), C. woodruffi (W. Comstock and Huntington), C. ammon (Lucas), and C. dominica (Möschler). The following new subjective synonyms are proposed: C. erembis Nabokov syn. n. and C. kathleena K. Johnson and Matusik syn. n. are C. thomasi noeli (W. Comstock and Huntington); C. sorpresus K. Johnson and Matusik syn. n. and C. shuturn K. Johnson and Bálint syn. n. are C. ammon; and Cyclargus oualiri Brevignon syn. n. is C. woodruffi. Additionally, we report the discovery of C. thomasi noeli in Cuba (where this taxon was previously confused with C. ammon), report C. ammon from Hispaniola for the first time, and document the widespread sympatry of C. thomasi and C. ammon in the northern Caribbean (including south Florida, Cuba, Cayman Islands, Hispaniola, Lucayan Archipelago). Finally, we provide a provisional synonymic list of Cyclargus taxa, which may serve as a taxonomic framework to assist efforts to conserve the Miami blue (C. thomasi bethunebakeri (W. Comstock and Huntington)), a taxon listed as "Endangered" under the Endangered Species Act in the United States.
Boos, Frederike ; Oo, James A. ; Warwick, Timothy ; Günther, Stefan ; Ponce, Judit Izquierdo ; Buchmann, Giulia Karolin ; Li, Tianfu ; Seredinski, Sandra ; Haydar, Shaza ; Kashefiolasl, Sepide ; Baker, Andrew H. ; Boon, Reinier ; Schulz, Marcel Holger ; Miller, Francis J. ; Brandes, Ralf ; Leisegang, Matthias
Long non-coding RNAs (lncRNAs) can act as regulatory RNAs which, by altering the expression of target genes, impact on the cellular phenotype and cardiovascular disease development. Endothelial lncRNAs and their vascular functions are largely undefined. Deep RNA-Seq and FANTOM5 CAGE analysis revealed the lncRNA LINC00607 to be highly enriched in human endothelial cells. LINC00607 was induced in response to hypoxia, arteriosclerosis regression in non-human primates and also in response to propranolol used to induce regression of human arteriovenous malformations. siRNA knockdown or CRISPR/Cas9 knockout of LINC00607 attenuated VEGF-A-induced angiogenic sprouting. LINC00607 knockout in endothelial cells also integrated less into newly formed vascular networks in an in vivo assay in SCID mice. Overexpression of LINC00607 in CRISPR knockout cells restored normal endothelial function. RNA- and ATAC-Seq after LINC00607 knockout revealed changes in the transcription of endothelial gene sets linked to the endothelial phenotype and in chromatin accessibility around ERG-binding sites. Mechanistically, LINC00607 interacted with the SWI/SNF chromatin remodeling protein BRG1. CRISPR/Cas9-mediated knockout of BRG1 in HUVEC followed by CUT&RUN revealed that BRG1 is required to secure a stable chromatin state, mainly on ERG-binding sites. In conclusion, LINC00607 is an endothelial-enriched lncRNA that maintains ERG target gene transcription by interacting with the chromatin remodeler BRG1.
Adler, Clemens ; Ahammed, Zubayer ; Allgower, C. ; Amonett, J. ; Anderson, B.D. ; Anderson, M. ; Averichev, Georgy S. ; Balewski, J. ; Barannikova, O. ; Barnby, L.S. ; Baudot, J. ; Bekele, S. ; Belaga, V.V. ; Bellwied, Rene ; Berger, J. ; Bichsel, H. ; Billmeier, A. ; Bland, L.C. ; Blyth, C.O. ; Bonner, B.E. ; Boucham, A. ; Brandin, A. ; Bravar, A. ; Cadman, R.V. ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Cardenas, A. ; Carroll, J. ; Castillo Castellanos, Javier Ernesto ; Castro, M. ; Cebra, D. ; Chaloupka, Petr ; Chattopadhyay, S. ; Chen, Y. ; Chernenko, S.P. ; Cherney, M. ; Chikanian, A. ; Choi, B. ; Christie, William ; Coffin, J.P. ; Cormier, T.M. ; Cramer, J.G. ; Crawford, H.J. ; Deng, W.S. ; Derevschikov, A.A. ; Didenko, L. ; Dietel, Thomas ; Draper, J.E. ; Dunin, V.B. ; Dunlop, J.C. ; Eckardt, V. ; Efimov, L.G. ; Emelianov, V. ; Engelage, J. ; Eppley, G. ; Erazmus, B. ; Fachini, P. ; Faine, V. ; Filimonov, K. ; Finch, E. ; Fisyak, Y. ; Flierl, D. ; Foley, K.J. ; Fu, J. ; Gagliardi, Carl A. ; Gagunashvili, N. ; Gans, J. ; Gaudichet, L. ; Germain, M. ; Geurts, F. ; Ghazikhanian, V. ; Grachov, O. ; Grigoriev, Vladislav A. ; Guedon, M. ; Gushin, E. ; Hallman, T.J. ; Hardtke, D. ; Harris, J.W. ; Henry, T.W. ; Heppelmann, S. ; Herston, T. ; Hippolyte, Boris ; Hirsch, A. ; Hjort, E. ; Hoffmann, Gerald W. ; Horsley, M. ; Huang, H.Z. ; Humanic, Thomas J. ; Igo, G. ; Ishihara, A. ; Ivanshin, Yu.I. ; Jacobs, P. ; Jacobs, W.W. ; Janik, M. ; Johnson, I. ; Jones, Peter Graham ; Judd, Eleanor G. ; Kaneta, M. ; Kaplan, M. ; Keane, Declan ; Kiryluk, J. ; Kisiel, A. ; Klay, J. ; Klein, S.R. ; Klyachko, A. ; Konstantinov, A.S. ; Kopytine, M. ; Kotchenda, L. ; Kovalenko, A.D. ; Kramer, M. ; Kravtsov, P. ; Krueger, Keith William ; Kuhn, C. ; Kulikov, A.I. ; Kunde, G.J. ; Kunz, C.L. ; Kutuev, R.Kh. ; Kuznetsov, A.A. ; Lakehal-Ayat, L. ; Lamont, Matthew A. C. ; Landgraf, J.M. ; Lange, S. ; Lansdell, C.P. ; Lasiuk, B. ; Laue, F. ; Lebedev, A. ; Lednický, R. ; Leontiev, V.M. ; LeVine, M.J. ; Li, Q. ; Lindenbaum, S.J. ; Lisa, Michael A. ; Liu, F. ; Liu, L. ; Liu, Z. ; Liu, Q.J. ; Ljubicic, T. ; Llope, W.J. ; LoCurto, G. ; Long, H. ; Longacre, R.S. ; Lopez-Noriega, M. ; Love, W.A. ; Ludlam, T. ; Lynn, D. ; Ma, J. ; Majka, R. ; Margetis, Spyridon ; Markert, Christina ; Martin, L. ; Marx, J. ; Matis, Howard S. ; Matulenko, Yu.A. ; McShane, T.S. ; Meissner, F. ; Melnick, Yu. ; Meschanin, A. ; Messer, M. ; Miller, M.L. ; Milosevich, Z. ; Minaev, N.G. ; Mitchell, J. ; Moiseenko, V.A. ; Moore, C.F. ; Morozov, V. ; de Moura, M.M. ; Munhoz, M.G. ; Nelson, J.M. ; Nevski, P. ; Nikitin, V.A. ; Nogach, L.V. ; Norman, B. ; Nurushev, S.B. ; Odyniec, G. ; Ogawa, A. ; Okorokov, Vitaly A. ; Oldenburg, M. ; Olson, D. ; Paic, Guy ; Pandey, S.U. ; Panebratsev, Y. ; Panitkin, S.Y. ; Pavlinov, A.I. ; Pawlak, T. ; Perevoztchikov, V. ; Peryt, W. ; Petrov, V.A. ; Planinic, M. ; Pluta, J. ; Porile, N. ; Porter, J. ; Poskanzer, A.M. ; Potrebenikova, E. ; Prindle, D. ; Pruneau, C. ; Putschke, Jörn H. ; Rai, G. ; Rakness, G. ; Ravel, O. ; Ray, R.L. ; Razin, S.V. ; Reichhold, D. ; Reid, Jeffrey G. ; Retiere, F. ; Ridiger, A. ; Ritter, H.G. ; Roberts, J.B. ; Rogachevski, O.V. ; Romero, J.L. ; Rose, A. ; Roy, C. ; Rykov, V. ; Sakrejda, I. ; Salur, Sevil ; Sandweiss, J. ; Saulys, A.C. ; Savin, I. ; Schambach, Joachim ; Scharenberg, R.P. ; Schmitz, N. ; Schroeder, L.S. ; Schüttauf, A. ; Schweda, Kai ; Seger, J. ; Seliverstov, D. ; Seyboth, P. ; Shahaliev, E. ; Shestermanov, K.E. ; Shimanskii, S.S. ; Shvetcov, V.S. ; Skoro, G. ; Smirnov, Nikolai ; Snellings, Raimond ; Sorensen, P. ; Sowinski, J. ; Spinka, Harold. M. ; Srivastava, B. ; Stephenson, E.J. ; Stock, Reinhard ; Stolpovsky, A. ; Strikhanov, M. ; Stringfellow, B. ; Struck, C. ; Suaide, Alexandre Alarcon do Passo ; Sugarbaker, E. ; Suire, Christophe Pierre ; Šumbera, Michal ; Surrow, Bernd ; Symons, T.J.M. ; Szanto de Toledo, A. ; Szarwas, P. ; Tai, A. ; Takahashi, Jun ; Tang, A.H. ; Thomas, James H. ; Thompson, M. ; Tikhomirov, V. ; Tokarev, M. ; Tonjes, M.B. ; Trainor, T.A. ; Trentalange, Stephen ; Tribble, Robert E. ; Trofimov, V. ; Tsai, Oleg D. ; Ullrich, Thomas ; Underwood, D.G. ; Van Buren, G. ; VanderMolen, A.M. ; Vasilevski, I.M. ; Vasiliev, A.N. ; Vigdor, S.E. ; Voloshin, S.A. ; Wang, Fuqiang ; Ward, H. ; Watson, J.W. ; Wells, R. ; Westfall, Gary D. ; Whitten, C. ; Wieman, H. ; Willson, R. ; Wissink, S.W. ; Witt, Richard ; Wood, J. ; Xu, N. ; Xu, Z. ; Yakutin, A.E. ; Yamamoto, E. ; Yang, J. ; Yepes, P. ; Yurevich, V.I. ; Zanevski, Y.V. ; Zborovský, I. ; Zhang, H. ; Zhang, W.M. ; Zoulkarneev, R. ; Zubarev, A.N.
Mid-rapidity transverse mass spectra and multiplicity densities of charged and neutral kaons are reported for Au + Au collisions at √sNN = 130 GeV at RHIC. The spectra are exponential in transverse mass, with an inverse slope of about 280 MeV in central collisions. The multiplicity densities for these particles scale with the negative hadron pseudo-rapidity density. The charged kaon to pion ratios are K+/π− = 0.161± 0.002(stat) ± 0.024(syst) and K−/π− = 0.146± 0.002(stat) ± 0.022(syst) for the most central collisions. The K+/π− ratio is lower than the same ratio observed at the SPS while the K−/π− is higher than the SPS result. The ratios are enhanced by about 50% relative to p + p and p¯ + p collision data at similar energies.