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Existing models explaining the evolution of sexual dimorphism in the timing of emergence (SDT) in Lepidoptera assume equal mortality rates for males and females. The limiting assumption of equal mortality rates has the consequence that these models are only able to explain the evolution of emergence of males before females, i.e. protandry-the more common temporal sequence of emergence in Lepidoptera. The models fail, however, in providing adaptive explanations for the evolution of protogyny, where females emerge before males, but protogyny is not rare in insects. The assumption of equal mortality rates seems too restrictive for many insects, such as butterflies. To investigate the influence of unequal mortality rates on the evolution of SDT, we present a generalised version of a previously published model where we relax this assumption. We find that longer life-expectancy of females compared to males can indeed favour the evolution of protogyny as a fitness enhancing strategy. Moreover, the encounter rate between females and males and the sex-ratio are two important factors that also influence the evolution of optimal SDT. If considered independently for females and males the predicted strategies can be shown to be evolutionarily stable (ESS). Under the assumption of equal mortality rates the difference between the females' and males' ESS remains typically very small. However, female and male ESS may be quite dissimilar if mortality rates are different. This creates the potential for an 'evolutionary conflict' between females and males. Bagworm moths (Lepidoptera: Psychidae) provide an exemplary case where life-history attributes are such that protogyny should indeed be the optimal emergence strategy from the males' and females' perspectives: (i) Female longevity is considerably larger than that of males, (ii) encounter rates between females and males are presumably low, and (iii) females mate only once. Protogyny is indeed the general mating strategy found in the bagworm family.
Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling
(2015)
Tsai, Yu-Chen ; Grimm, Stefan ; Chao, Ju-Lan ; Wang, Shih-Chin ; Hofmeyer, Kerstin ; Shen, Jie ; Eichinger, Fred ; Michalopoulou, Theoni ; Yao, Chi-Kuang ; Chang, Chih-Hsuan ; Lin, Shih-Han ; Sun, Y. Henry ; Pflugfelder, Gert O.
Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg) is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb) is expressed in a similar pattern and is regulated by Wg. Omb mediates part of Wg activity in blocking eye development. Omb exerts its function primarily by blocking cell proliferation. These effects occur predominantly in the ventral margin. Our results suggest that the primary effect of Omb is the blocking of Jak/STAT signaling by repressing transcription of upd which encodes the Jak receptor ligand Unpaired.
How allopolyploids are able not only to cope but profit from their condition is a question that remains elusive, but is of great importance within the context of successful allopolyploid evolution. One outstanding example of successful allopolyploidy is the endemic Iberian cyprinid Squalius alburnoides. Previously, based on the evaluation of a few genes, it was reported that the transcription levels between diploid and triploid S. alburnoides were similar. If this phenomenon occurs on a full genomic scale, a wide functional "diploidization'' could be related to the success of these polyploids. We generated RNA-seq data from whole juvenile fish and from adult livers, to perform the first comparative quantitative transcriptomic analysis between diploid and triploid individuals of a vertebrate allopolyploid. Together with an assay to estimate relative expression per cell, it was possible to infer the relative sizes of transcriptomes. This showed that diploid and triploid S. alburnoides hybrids have similar liver transcriptome sizes. This in turn made it valid to directly compare the S. alburnoides RNA-seq transcript data sets and obtain a profile of dosage responses across the S. alburnoides transcriptome. We found that 64% of transcripts in juveniles' samples and 44% in liver samples differed less than twofold between diploid and triploid hybrids (similar expression). Yet, respectively 29% and 15% of transcripts presented accurate dosage compensation (PAA/PA expression ratio of 1 instead of 1.5). Therefore, an exact functional diploidization of the triploid genome does not occur, but a significant down regulation of gene expression in triploids was observed. However, for those genes with similar expression levels between diploids and triploids, expression is not globally strictly proportional to gene dosage nor is it set to a perfect diploid level. This quantitative expression flexibility may be a strong contributor to overcome the genomic shock, and be an immediate evolutionary advantage of allopolyploids.
Converging evidence from controlled experiments suggests that the mere processing of a number and its attributes such as value or parity might affect free choice decisions between different actions. For example the spatial numerical associations of response codes (SNARC) effect indicates the magnitude of a digit to be associated with a spatial representation and might therefore affect spatial response choices (i.e., decisions between a "left" and a "right" option). At the same time, other (linguistic) features of a number such as parity are embedded into space and might likewise prime left or right responses through feature words [odd or even, respectively; markedness association of response codes (MARC) effect]. In this experiment we aimed at documenting such influences in a natural setting. We therefore assessed number space and parity space association effects by exposing participants to a fair distribution task in a card playing scenario. Participants drew cards, read out loud their number values, and announced their response choice, i.e., dealing it to a left vs. right player, indicated by Playmobil characters. Not only did participants prefer to deal more cards to the right player, the card's digits also affected response choices and led to a slightly but systematically unfair distribution, supported by a regular SNARC effect and counteracted by a reversed MARC effect. The experiment demonstrates the impact of SNARC- and MARC-like biases in free choice behavior through verbal and visual numerical information processing even in a setting with high external validity.
Schütz, Burkhard ; Jurastow, Innokentij ; Bader, Sandra ; Ringer, Cornelia ; Engelhardt, Jakob von ; Chubanov, Vladimir ; Gudermann, Thomas ; Diener, Martin ; Kummer, Wolfgang ; Krasteva-Christ, Gabriela ; Weihe, Eberhard
The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline acetyltransferase (ChAT)-positive brush cells with taste cell-like traits. With the aid of two transgenic mouse lines that express green fluorescent protein (EGFP) under the control of the ChAT promoter (EGFP\(^{ChAT}\)) and by using in situ hybridization and immunohistochemistry we found that EGFP\(^{ChAT}\) cells were clustered in the epithelium lining the gastric groove. EGFP\(^{ChAT}\) cells were numerous in the gall bladder and bile duct, and found scattered as solitary cells along the small and large intestine. While all EGFP\(^{ChAT}\) cells were also ChAT-positive, expression of the high-affinity choline transporter (ChT1) was never detected. Except for the proximal colon, EGFP\(^{ChAT}\) cells also lacked detectable expression of the vesicular acetylcholine transporter (VAChT). EGFP\(^{ChAT}\) cells were found to be separate from enteroendocrine cells, however they were all immunoreactive for cytokeratin 18 (CK18), transient receptor potential melastatin-like subtype 5 channel (TRPM5), and for cyclooxygenases 1 (COX1) and 2 (COX2). The ex vivo stimulation of colonic EGFP\(^{ChAT}\) cells with the bitter substance denatonium resulted in a strong increase in intracellular calcium, while in other epithelial cells such an increase was significantly weaker and also timely delayed. Subsequent stimulation with cycloheximide was ineffective in both cell populations. Given their chemical coding and chemosensory properties, EGFP\(^{ChAT}\) brush cells thus may have integrative functions and participate in induction of protective reflexes and inflammatory events by utilizing ACh and prostaglandins for paracrine signaling.
Williams, Richard D. ; Chagtai, Tasnim ; Alcaide-German, Marisa ; Apps, John ; Wegert, Jenny ; Popov, Sergey ; Vujanic, Gordan ; Van Tinteren, Harm ; Van den Heuvel-Eibrink, Marry M ; Kool, Marcel ; De Kraker, Jan ; Gisselsson, David ; Graf, Norbert ; Gessler, Manfred ; Pritchard-Jones, Kathy
Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequencing, together with methylation and expression profiling, we show that MYCN is targeted by other mechanisms, including a recurrent somatic mutation, P44L, and specific DNA hypomethylation events associated with MYCN overexpression in tumours with high risk histologies. We describe parallel evolution of genomic copy number gain and point mutation of MYCN in the contralateral tumours of a remarkable bilateral case in which independent contralateral mutations of TP53 also evolve over time. We report a second bilateral case in which MYCN gain is a germline aberration. Our results suggest a significant role for MYCN dysregulation in the molecular biology of Wilms tumour. We conclude that MYCN gain is prognostically significant, and suggest that the novel P44L somatic variant is likely to be an activating mutation.
Blanco, Ignacio ; Kuchenbaecker, Karoline ; Cuadras, Daniel ; Wang, Xianshu ; Barrowdale, Daniel ; Ruiz de Garibay, Gorka ; Librado, Pablo ; Sanchez-Gracia, Alejandro ; Rozas, Julio ; Bonifaci, Núria ; McGuffog, Lesley ; Pankratz, Vernon S. ; Islam, Abul ; Mateo, Francesca ; Berenguer, Antoni ; Petit, Anna ; Català, Isabel ; Brunet, Joan ; Feliubadaló, Lidia ; Tornero, Eva ; Benítez, Javier ; Osorio, Ana ; Ramón y Cajal, Teresa ; Nevanlinna, Heli ; Aittomäki, Kristina ; Arun, Banu K. ; Toland, Amanda E. ; Karlan, Beth Y. ; Walsh, Christine ; Lester, Jenny ; Greene, Mark H. ; Mai, Phuong L. ; Nussbaum, Robert L. ; Andrulis, Irene L. ; Domchek, Susan M. ; Nathanson, Katherine L. ; Rebbeck, Timothy R. ; Barkardottir, Rosa B. ; Jakubowska, Anna ; Lubinski, Jan ; Durda, Katarzyna ; Jaworska-Bieniek, Katarzyna ; Claes, Kathleen ; Van Maerken, Tom ; Díez, Orland ; Hansen, Thomas V. ; Jønson, Lars ; Gerdes, Anne-Marie ; Ejlertsen, Bent ; De la Hoya, Miguel ; Caldés, Trinidad ; Dunning, Alison M. ; Oliver, Clare ; Fineberg, Elena ; Cook, Margaret ; Peock, Susan ; McCann, Emma ; Murray, Alex ; Jacobs, Chris ; Pichert, Gabriella ; Lalloo, Fiona ; Chu, Carol ; Dorkins, Huw ; Paterson, Joan ; Ong, Kai-Ren ; Teixeira, Manuel R. ; Hogervorst, Frans B. L. ; Van der Hout, Annemarie H. ; Seynaeve, Caroline ; Van der Luijt, Rob B. ; Ligtenberg, Marjolijn J. L. ; Devilee, Peter ; Wijnen, Juul T. ; Rookus, Matti A. ; Meijers-Heijboer, Hanne E. J. ; Blok, Marinus J. ; Van den Ouweland, Ans M. W. ; Aalfs, Cora M. ; Rodriguez, Gustavo C. ; Phillips, Kelly-Anne A. ; Piedmonte, Marion ; Nerenstone, Stacy R. ; Bae-Jump, Victoria L. ; O'Malley, David M. ; Schmutzler, Rita K. ; Wappenschmidt, Barbara ; Rhiem, Kerstin ; Engel, Christoph ; Meindl, Alfons ; Ditsch, Nina ; Arnold, Norbert ; Plendl, Hansjoerg J. ; Niederacher, Dieter ; Sutter, Christian ; Wang-Gohrke, Shan ; Steinemann, Doris ; Preisler-Adams, Sabine ; Kast, Karin ; Varon-Mateeva, Raymonda ; Gehrig, Andrea ; Bojesen, Anders ; Pedersen, Inge Sokilde ; Sunde, Lone ; Birk Jensen, Uffe ; Thomassen, Mads ; Kruse, Torben A. ; Foretova, Lenka ; Peterlongo, Paolo ; Bernard, Loris ; Peissel, Bernard ; Scuvera, Giulietta ; Manoukian, Siranoush ; Radice, Paolo ; Ottini, Laura ; Montagna, Marco ; Agata, Simona ; Maugard, Christine ; Simard, Jacques ; Soucy, Penny ; Berger, Andreas ; Fink-Retter, Anneliese ; Singer, Christian F. ; Rappaport, Christine ; Geschwantler-Kaulich, Daphne ; Tea, Muy-Kheng ; Pfeiler, Georg ; John, Esther M. ; Miron, Alex ; Neuhausen, Susan L. ; Terry, Mary Beth ; Chung, Wendy K. ; Daly, Mary B. ; Goldgar, David E. ; Janavicius, Ramunas ; Dorfling, Cecilia M. ; Van Rensburg, Elisabeth J. ; Fostira, Florentia ; Konstantopoulou, Irene ; Garber, Judy ; Godwin, Andrew K. ; Olah, Edith ; Narod, Steven A. ; Rennert, Gad ; Paluch, Shani Shimon ; Laitman, Yael ; Friedman, Eitan ; Liljegren, Annelie ; Rantala, Johanna ; Stenmark-Askmalm, Marie ; Loman, Niklas ; Imyanitov, Evgeny N. ; Hamann, Ute ; Spurdle, Amanda B. ; Healey, Sue ; Weitzel, Jeffrey N. ; Herzog, Josef ; Margileth, David ; Gorrini, Chiara ; Esteller, Manel ; Gómez, Antonio ; Sayols, Sergi ; Vidal, Enrique ; Heyn, Holger ; Stoppa-Lyonnet, Dominique ; Léoné, Melanie ; Barjhoux, Laure ; Fassy-Colcombet, Marion ; Pauw, Antoine de ; Lasset, Christine ; Fert Ferrer, Sandra ; Castera, Laurent ; Berthet, Pascaline ; Cornelis, François ; Bignon, Yves-Jean ; Damiola, Francesca ; Mazoyer, Sylvie ; Sinilnikova, Olga M. ; Maxwell, Christopher A. ; Vijai, Joseph ; Robson, Mark ; Kauff, Noah ; Corines, Marina J. ; Villano, Danylko ; Cunningham, Julie ; Lee, Adam ; Lindor, Noralane ; Lázaro, Conxi ; Easton, Douglas F. ; Offit, Kenneth ; Chenevix-Trench, Georgia ; Couch, Fergus J. ; Antoniou, Antonis C. ; Pujana, Miguel Angel
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10\(^{-4}\) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p\(_{interaction}\) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
The Urban Heat Island (UHI) is the phenomenon of altered increased temperatures in urban areas compared to their rural surroundings. UHIs grow and intensify under extreme hot periods, such as during heat waves, which can affect human health and also increase the demand for energy for cooling. This study applies remote sensing and land use/land cover (LULC) data to assess the cooling effect of varying urban vegetation cover, especially during extreme warm periods, in the city of Munich, Germany. To compute the relationship between Land Surface Temperature (LST) and Land Use Land Cover (LULC), MODIS eight-day interval LST data for the months of June, July and August from 2002 to 2012 and the Corine Land Cover (CLC) database were used. Due to similarities in the behavior of surface temperature of different CLCs, some classes were reclassified and combined to form two major, rather simplified, homogenized classes: one of built-up area and one of urban vegetation. The homogenized map was merged with the MODIS eight-day interval LST data to compute the relationship between them. The results revealed that (i) the cooling effect accrued from urban vegetation tended to be non-linear; and (ii) a remarkable and stronger cooling effect in terms of LST was identified in regions where the proportion of vegetation cover was between seventy and almost eighty percent per square kilometer. The results also demonstrated that LST within urban vegetation was affected by the temperature of the surrounding built-up and that during the well-known European 2003 heat wave, suburb areas were cooler from the core of the urbanized region. This study concluded that the optimum green space for obtaining the lowest temperature is a non-linear trend. This could support urban planning strategies to facilitate appropriate applications to mitigate heat-stress in urban area.
Sigma factor SigB is crucial to mediate Staphylococcus aureus adaptation during chronic infections
(2015)
Tuchscherr, Lorena ; Bischoff, Markus ; Lattar, Santiago M. ; Noto Llana, Mariangeles ; Pförtner, Henrike ; Niemann, Silke ; Geraci, Jennifer ; Van de Vyver, Hélène ; Fraunholz, Martin J. ; Cheung, Ambrose L. ; Herrmann, Mathias ; Völker, Uwe ; Sordelli, Daniel O. ; Peters, Georg ; Loeffler, Bettina
Staphylococcus aureus is a major human pathogen that causes a range of infections from acute invasive to chronic and difficult-to-treat. Infection strategies associated with persisting S. aureus infections are bacterial host cell invasion and the bacterial ability to dynamically change phenotypes from the aggressive wild-type to small colony variants (SCVs), which are adapted for intracellular long-term persistence. The underlying mechanisms of the bacterial switching and adaptation mechanisms appear to be very dynamic, but are largely unknown. Here, we analyzed the role and the crosstalk of the global S. aureus regulators agr, sarA and SigB by generating single, double and triple mutants, and testing them with proteome analysis and in different in vitro and in vivo infection models. We were able to demonstrate that SigB is the crucial factor for adaptation in chronic infections. During acute infection, the bacteria require the simultaneous action of the agr and sarA loci to defend against invading immune cells by causing inflammation and cytotoxicity and to escape from phagosomes in their host cells that enable them to settle an infection at high bacterial density. To persist intracellularly the bacteria subsequently need to silence agr and sarA. Indeed agr and sarA deletion mutants expressed a much lower number of virulence factors and could persist at high numbers intracellularly. SigB plays a crucial function to promote bacterial intracellular persistence. In fact, \(\Delta\)sigB-mutants did not generate SCVs and were completely cleared by the host cells within a few days. In this study we identified SigB as an essential factor that enables the bacteria to switch from the highly aggressive phenotype that settles an acute infection to a silent SCV-phenotype that allows for long-term intracellular persistence. Consequently, the SigB-operon represents a possible target to develop preventive and therapeutic strategies against chronic and therapy-refractory infections.
Energy Transfer Between Squaraine Polymer Sections: From helix to zig-zag and All the Way Back
(2015)
Lambert, Christoph ; Völker, Sebastian F. ; Koch, Federico ; Schmiedel, Alexander ; Holzapfel, Marco ; Humeniuk, Alexander ; Röhr, Merle I. S. ; Mitric, Roland ; Brixner, Tobias
Joint experimental and theoretical study of the absorption spectra of squaraine polymers in solution provide evidence that two different conformations are present in solution: a helix and a zig-zag structure. This unique situation allows investigating ultrafast energy transfer processes between different structural segments within a single polymer chain in solution. The understanding of the underlying dynamics is of fundamental importance for the development of novel materials for light-harvesting and optoelectronic applications. We combine here femtosecond transient absorption spectroscopy with time-resolved 2D electronic spectroscopy showing that ultrafast energy transfer within the squaraine polymer chains proceeds from initially excited helix segments to zig-zag segments or vice versa, depending on the solvent as well as on the excitation wavenumber. These observations contrast other conjugated polymers such as MEH-PPV where much slower intrachain energy transfer was reported. The reason for the very fast energy transfer in squaraine polymers is most likely a close matching of the density of states between donor and acceptor polymer segments because of very small reorganization energy in these cyanine-like chromophores.