Spatial transposition gradients in visual working memory.

PubMed

Rerko, Laura; Oberauer, Klaus; Lin, Hsuan-Yu

2014-01-01

In list memory, access to individual items reflects limits of temporal distinctiveness. This is reflected in the finding that neighbouring list items tend to be confused most often. This article investigates the analogous effect of spatial proximity in a visual working-memory task. Items were presented in different locations varying in spatial distance. A retro-cue indicated the location of the item relevant for the subsequent memory test. In two recognition experiments, probes matching spatially close neighbours of the relevant item led to more false alarms than probes matching distant neighbours or non-neighbouring memory items. In two probed-recall experiments, one with simultaneous, the other with sequential memory item presentation, items closer to the cued location were more frequently chosen for recall than more distant items. These results reflect a spatial transposition gradient analogous to the temporal transposition gradient in serial recall and challenge fixed-capacity models of visual working memory (WM).

[Sex differences of spatial-temporal organization of biopotentials of the brain in adults and child 5-6 years old].

PubMed

Panasevich, E A; Tsitseroshin, M N

2011-01-01

Research of topical features of spatial structure of EEG distant relationships has been performed with correlation and coherent analyses of EEG for 26 children of 5-6 years old (12 boys and 14 girls) in comparison to the data at 33 adult subjects (15 men and 18 women). Men have much higher level of EEG intrahemispherical relations of posttemporal and frontal regions of the left hemisphere whereas women have the higher level prevalence of interhemispheric interactions, especially of bilateral-symmetrical arials of both hemispheres. Preschoolers have another character of sex differences in the system organization of inter-regional interactions of brain biopotentials than adults. In particularly the girls have exceeding of EEG distant relations in the same zones of left hemispheres, where at men such relations have exceeding in comparison with woman. The obtained data shows that the pronounced sexual dimorphism of inter-regional interactions of cortical biopotentials at adults and at children is formed, first of all, owing to of EEG distant relations topology differing in males and females subject. Investigation sex differences of spatial-temporal organization of biopotentials of the brain in children can promote forming of more hole and deep understanding of role of sex factor in development of human brain system activity.

Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

PubMed

Cheng, Skye Hung-Chun; Huang, Tzu-Ting; Cheng, Yu-Hao; Tan, Tee Benita Kiat; Horng, Chen-Fang; Wang, Yong Alison; Brian, Nicholas Shannon; Shih, Li-Sun; Yu, Ben-Long

2017-01-01

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%-98.8%) and 80.9% (74.6%-81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%-98.5%), and 90.9% (50.8%-98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100%) and 80.3% (70.7%-89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%-94.1%) and 73.6% (67.2%-79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

Outbreeding and lack of temporal genetic structure in a drone congregation of the neotropical stingless bee Scaptotrigona mexicana

PubMed Central

Mueller, Matthias Y; Moritz, Robin FA; Kraus, F Bernhard

2012-01-01

Drone aggregations are a widespread phenomenon in many stingless bee species (Meliponini), but the ultimate and proximate causes for their formation are still not well understood. One adaptive explanation for this phenomenon is the avoidance of inbreeding, which is especially detrimental for stingless bees due to the combined effects of the complementary sex-determining system and the small effective population size caused by eusociality and monandry. We analyzed the temporal genetic dynamics of a drone aggregation of the stingless bee Scaptotrigona mexicana with microsatellite markers over a time window of four weeks. We estimated the drones of the aggregation to originate from a total of 55 colonies using sibship re-construction. There was no detectable temporal genetic differentiation or sub-structuring in the aggregation. Most important, we could exclude all colonies in close proximity of the aggregation as origin of the drones in the aggregation, implicating that they originate from more distant colonies. We conclude that the diverse genetic composition and the distant origin of the drones of the S. mexicana drone congregation provides an effective mechanism to avoid mating among close relatives. PMID:22833802

Outbreeding and lack of temporal genetic structure in a drone congregation of the neotropical stingless bee Scaptotrigona mexicana.

PubMed

Mueller, Matthias Y; Moritz, Robin Fa; Kraus, F Bernhard

2012-06-01

Drone aggregations are a widespread phenomenon in many stingless bee species (Meliponini), but the ultimate and proximate causes for their formation are still not well understood. One adaptive explanation for this phenomenon is the avoidance of inbreeding, which is especially detrimental for stingless bees due to the combined effects of the complementary sex-determining system and the small effective population size caused by eusociality and monandry. We analyzed the temporal genetic dynamics of a drone aggregation of the stingless bee Scaptotrigona mexicana with microsatellite markers over a time window of four weeks. We estimated the drones of the aggregation to originate from a total of 55 colonies using sibship re-construction. There was no detectable temporal genetic differentiation or sub-structuring in the aggregation. Most important, we could exclude all colonies in close proximity of the aggregation as origin of the drones in the aggregation, implicating that they originate from more distant colonies. We conclude that the diverse genetic composition and the distant origin of the drones of the S. mexicana drone congregation provides an effective mechanism to avoid mating among close relatives.

In silico search for functionally similar proteins involved in meiosis and recombination in evolutionarily distant organisms.

PubMed

Bogdanov, Yuri F; Dadashev, Sergei Y; Grishaeva, Tatiana M

2003-01-01

Evolutionarily distant organisms have not only orthologs, but also nonhomologous proteins that build functionally similar subcellular structures. For instance, this is true with protein components of the synaptonemal complex (SC), a universal ultrastructure that ensures the successful pairing and recombination of homologous chromosomes during meiosis. We aimed at developing a method to search databases for genes that code for such nonhomologous but functionally analogous proteins. Advantage was taken of the ultrastructural parameters of SC and the conformation of SC proteins responsible for these. Proteins involved in SC central space are known to be similar in secondary structure. Using published data, we found a highly significant correlation between the width of the SC central space and the length of rod-shaped central domain of mammalian and yeast intermediate proteins forming transversal filaments in the SC central space. Basing on this, we suggested a method for searching genome databases of distant organisms for genes whose virtual proteins meet the above correlation requirement. Our recent finding of the Drosophila melanogaster CG17604 gene coding for synaptonemal complex transversal filament protein received experimental support from another lab. With the same strategy, we showed that the Arabidopsis thaliana and Caenorhabditis elegans genomes contain unique genes coding for such proteins.

Intracranial spectral amplitude dynamics of perceptual suppression in fronto-insular, occipito-temporal, and primary visual cortex

PubMed Central

Vidal, Juan R.; Perrone-Bertolotti, Marcela; Kahane, Philippe; Lachaux, Jean-Philippe

2015-01-01

If conscious perception requires global information integration across active distant brain networks, how does the loss of conscious perception affect neural processing in these distant networks? Pioneering studies on perceptual suppression (PS) described specific local neural network responses in primary visual cortex, thalamus and lateral prefrontal cortex of the macaque brain. Yet the neural effects of PS have rarely been studied with intracerebral recordings outside these cortices and simultaneously across distant brain areas. Here, we combined (1) a novel experimental paradigm in which we produced a similar perceptual disappearance and also re-appearance by using visual adaptation with transient contrast changes, with (2) electrophysiological observations from human intracranial electrodes sampling wide brain areas. We focused on broadband high-frequency (50–150 Hz, i.e., gamma) and low-frequency (8–24 Hz) neural activity amplitude modulations related to target visibility and invisibility. We report that low-frequency amplitude modulations reflected stimulus visibility in a larger ensemble of recording sites as compared to broadband gamma responses, across distinct brain regions including occipital, temporal and frontal cortices. Moreover, the dynamics of the broadband gamma response distinguished stimulus visibility from stimulus invisibility earlier in anterior insula and inferior frontal gyrus than in temporal regions, suggesting a possible role of fronto-insular cortices in top–down processing for conscious perception. Finally, we report that in primary visual cortex only low-frequency amplitude modulations correlated directly with perceptual status. Interestingly, in this sensory area broadband gamma was not modulated during PS but became positively modulated after 300 ms when stimuli were rendered visible again, suggesting that local networks could be ignited by top–down influences during conscious perception. PMID:25642199

Recently Deglaciated High-Altitude Soils of the Himalaya: Diverse Environments, Heterogenous Bacterial Communities and Long-Range Dust Inputs from the Upper Troposphere

PubMed Central

Stres, Blaz; Sul, Woo Jun; Murovec, Bostjan; Tiedje, James M.

2013-01-01

Background The Himalaya with its altitude and geographical position forms a barrier to atmospheric transport, which produces much aqueous-particle monsoon precipitation and makes it the largest continuous ice-covered area outside polar regions. There is a paucity of data on high-altitude microbial communities, their native environments and responses to environmental-spatial variables relative to seasonal and deglaciation events. Methodology/Principal Findings Soils were sampled along altitude transects from 5000 m to 6000 m to determine environmental, spatial and seasonal factors structuring bacterial communities characterized by 16 S rRNA gene deep sequencing. Dust traps and fresh-snow samples were used to assess dust abundance and viability, community structure and abundance of dust associated microbial communities. Significantly different habitats among the altitude-transect samples corresponded to both phylogenetically distant and closely-related communities at distances as short as 50 m showing high community spatial divergence. High within-group variability that was related to an order of magnitude higher dust deposition obscured seasonal and temporal rearrangements in microbial communities. Although dust particle and associated cell deposition rates were highly correlated, seasonal dust communities of bacteria were distinct and differed significantly from recipient soil communities. Analysis of closest relatives to dust OTUs, HYSPLIT back-calculation of airmass trajectories and small dust particle size (4–12 µm) suggested that the deposited dust and microbes came from distant continental, lacustrine and marine sources, e.g. Sahara, India, Caspian Sea and Tibetan plateau. Cyanobacteria represented less than 0.5% of microbial communities suggesting that the microbial communities benefitted from (co)deposited carbon which was reflected in the psychrotolerant nature of dust-particle associated bacteria. Conclusions/Significance The spatial, environmental and temporal complexity of the high-altitude soils of the Himalaya generates ongoing disturbance and colonization events that subject heterogeneous microniches to stochastic colonization by far away dust associated microbes and result in the observed spatially divergent bacterial communities. PMID:24086740

Turning I into me: Imagining your future self.

PubMed

Macrae, C Neil; Mitchell, Jason P; Tait, Kirsten A; McNamara, Diana L; Golubickis, Marius; Topalidis, Pavlos P; Christian, Brittany M

2015-12-01

A widely endorsed belief is that perceivers imagine their present selves using a different representational format than imagining their future selves (i.e., near future=first-person; distant future=third-person). But is this really the case? Responding to the paucity of work on this topic, here we considered how temporal distance influences the extent to which individuals direct their attention outward or inward during a brief imaginary episode. Using a non-verbal measure of visual perspective taking (i.e., letter-drawing task) our results confirmed the hypothesized relation between temporal distance and conceptions of the self. Whereas simulations of an event in the near future were dominated by a first-person representation of the self, this switched to a third-person depiction when the event was located in the distant future. Critically, this switch in vantage point was restricted to self-related simulations. The theoretical and practical implications of these findings are considered. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-wide introgression among distantly related Heliconius butterfly species.

PubMed

Zhang, Wei; Dasmahapatra, Kanchon K; Mallet, James; Moreira, Gilson R P; Kronforst, Marcus R

2016-02-27

Although hybridization is thought to be relatively rare in animals, the raw genetic material introduced via introgression may play an important role in fueling adaptation and adaptive radiation. The butterfly genus Heliconius is an excellent system to study hybridization and introgression but most studies have focused on closely related species such as H. cydno and H. melpomene. Here we characterize genome-wide patterns of introgression between H. besckei, the only species with a red and yellow banded 'postman' wing pattern in the tiger-striped silvaniform clade, and co-mimetic H. melpomene nanna. We find a pronounced signature of putative introgression from H. melpomene into H. besckei in the genomic region upstream of the gene optix, known to control red wing patterning, suggesting adaptive introgression of wing pattern mimicry between these two distantly related species. At least 39 additional genomic regions show signals of introgression as strong or stronger than this mimicry locus. Gene flow has been on-going, with evidence of gene exchange at multiple time points, and bidirectional, moving from the melpomene to the silvaniform clade and vice versa. The history of gene exchange has also been complex, with contributions from multiple silvaniform species in addition to H. besckei. We also detect a signature of ancient introgression of the entire Z chromosome between the silvaniform and melpomene/cydno clades. Our study provides a genome-wide portrait of introgression between distantly related butterfly species. We further propose a comprehensive and efficient workflow for gene flow identification in genomic data sets.

TIME STRUCTURE OF GAMMA-RAY SIGNALS GENERATED IN LINE-OF-SIGHT INTERACTIONS OF COSMIC RAYS FROM DISTANT BLAZARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prosekin, Anton; Aharonian, Felix; Essey, Warren

2012-10-01

Blazars are expected to produce both gamma rays and cosmic rays. Therefore, observed high-energy gamma rays from distant blazars may contain a significant contribution from secondary gamma rays produced along the line of sight by the interactions of cosmic-ray protons with background photons. Unlike the standard models of blazars that consider only the primary photons emitted at the source, models that include the cosmic-ray contribution predict that even {approx}10 TeV photons should be detectable from distant objects with redshifts as high as z {>=} 0.1. Secondary photons contribute to signals of point sources only if the intergalactic magnetic fields aremore » very small, B {approx}< 10{sup -14} G, and their detection can be used to set upper bounds on magnetic fields along the line of sight. Secondary gamma rays have distinct spectral and temporal features. We explore the temporal properties of such signals using a semi-analytical formalism and detailed numerical simulations, which account for all the relevant processes, including magnetic deflections. In particular, we elucidate the interplay of time delays coming from the proton deflections and from the electromagnetic cascade, and we find that, at multi-TeV energies, secondary gamma rays can show variability on timescales of years for B {approx} 10{sup -15} G.« less

Concreteness and Psychological Distance in Natural Language Use

PubMed Central

Snefjella, Bryor; Kuperman, Victor

2015-01-01

Existing evidence shows that more abstract mental representations are formed, and more abstract language is used, to characterize phenomena which are more distant from self. Yet the precise form of the functional relationship between distance and linguistic abstractness has been unknown. In four studies, we test whether more abstract language is used in textual references to more geographically distant cities (Study 1), times further into the past or future (Study 2), references to more socially distant people (Study 3), and references to a specific topic (Study 4). Using millions of linguistic productions from thousands of social media users, we determine that linguistic concreteness is a curvilinear function of the logarithm of distance and discuss psychological underpinnings of the mathematical properties of the relationship. We also demonstrate that gradient curvilinear effects of geographic and temporal distance on concreteness are near-identical, suggesting uniformity in representation of abstractness along multiple dimensions. PMID:26239108

Concreteness and Psychological Distance in Natural Language Use.

PubMed

Snefjella, Bryor; Kuperman, Victor

2015-09-01

Existing evidence shows that more abstract mental representations are formed and more abstract language is used to characterize phenomena that are more distant from the self. Yet the precise form of the functional relationship between distance and linguistic abstractness is unknown. In four studies, we tested whether more abstract language is used in textual references to more geographically distant cities (Study 1), time points further into the past or future (Study 2), references to more socially distant people (Study 3), and references to a specific topic (Study 4). Using millions of linguistic productions from thousands of social-media users, we determined that linguistic concreteness is a curvilinear function of the logarithm of distance, and we discuss psychological underpinnings of the mathematical properties of this relationship. We also demonstrated that gradient curvilinear effects of geographic and temporal distance on concreteness are nearly identical, which suggests uniformity in representation of abstractness along multiple dimensions. © The Author(s) 2015.

Horizontal transfer of a ß-1,6-glucanase gene from an ancestral species of fungal endophyte to a cool-season grass host.

PubMed

Shinozuka, Hiroshi; Hettiarachchige, Inoka K; Shinozuka, Maiko; Cogan, Noel O I; Spangenberg, German C; Cocks, Benjamin G; Forster, John W; Sawbridge, Timothy I

2017-08-22

Molecular characterisation has convincingly demonstrated some types of horizontal gene transfer in eukaryotes, but nuclear gene transfer between distantly related eukaryotic groups appears to have been rare. For angiosperms (flowering plants), nuclear gene transfer events identified to date have been confined to genes originating from prokaryotes or other plant species. In this report, evidence for ancient horizontal transfer of a fungal nuclear gene, encoding a ß-1,6-glucanase enzyme for fungal cell wall degradation, into an angiosperm lineage is presented for the first time. The gene was identified from de novo sequencing and assembly of the genome and transcriptome of perennial ryegrass, a cool-season grass species. Molecular analysis confirmed the presence of the complete gene in the genome of perennial ryegrass. No corresponding sequence was found in other plant species, apart from members of the Poeae sub-tribes Loliinae and Dactylidinae. Evidence suggests that a common ancestor of the two sub-tribes acquired the gene from a species ancestral to contemporary grass-associated fungal endophytes around 9-13 million years ago. This first report of horizontal transfer of a nuclear gene from a taxonomically distant eukaryote to modern flowering plants provides evidence for a novel adaptation mechanism in angiosperms.

Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.

PubMed

Sgroi, Dennis C; Sestak, Ivana; Cuzick, Jack; Zhang, Yi; Schnabel, Catherine A; Schroeder, Brock; Erlander, Mark G; Dunbier, Anita; Sidhu, Kally; Lopez-Knowles, Elena; Goss, Paul E; Dowsett, Mitch

2013-10-01

Biomarkers to improve the risk-benefit of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinically valuable. We compared the prognostic ability of the breast-cancer index (BCI) assay, 21-gene recurrence score (Oncotype DX), and an immunohistochemical prognostic model (IHC4) for both early and late recurrence in patients with oestrogen-receptor-positive, node-negative (N0) disease who took part in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial. In this prospective comparison study, we obtained archival tumour blocks from the TransATAC tissue bank from all postmenopausal patients with oestrogen-receptor-positive breast cancer from whom the 21-gene recurrence score and IHC4 values had already been derived. We did BCI analysis in matched samples with sufficient residual RNA using two BCI models-cubic (BCI-C) and linear (BCI-L)-using previously validated cutoffs. We assessed prognostic ability of BCI for distant recurrence over 10 years (the primary endpoint) and compared it with that of the 21-gene recurrence score and IHC4. We also tested the ability of the assays to predict early (0-5 years) and late (5-10 years) distant recurrence. To assess the ability of the biomarkers to predict recurrence beyond standard clinicopathological variables, we calculated the change in the likelihood-ratio χ(2) (LR-Δχ(2)) from Cox proportional hazards models. Suitable tissue was available from 665 patients with oestrogen-receptor-positive, N0 breast cancer for BCI analysis. The primary analysis showed significant differences in risk of distant recurrence over 10 years in the categorical BCI-C risk groups (p<0·0001) with 6·8% (95% CI 4·4-10·0) of patients in the low-risk group, 17·3% (12·0-24·7) in the intermediate group, and 22·2% (15·3-31·5) in the high-risk group having distant recurrence. The secondary analysis showed that BCI-L was a much stronger predictor for overall (0-10 year) distant recurrence compared with BCI-C (interquartile HR 2·30 [95% CI 1·62-3·27]; LR-Δχ(2)=22·69; p<0·0001). When compared with BCI-L, the 21-gene recurrence score was less predictive (HR 1·48 [95% CI 1·22-1·78]; LR-Δχ(2)=13·68; p=0·0002) and IHC4 was similar (HR 1·69 [95% CI 1·51-2·56]; LR-Δχ(2)=22·83; p<0·0001). All further analyses were done with the BCI-L model. In a multivariable analysis, all assays had significant prognostic ability for early distant recurrence (BCI-L HR 2·77 [95% CI 1·63-4·70], LR-Δχ(2)=15·42, p<0·0001; 21-gene recurrence score HR 1·80 [1·42-2·29], LR-Δχ(2)=18·48, p<0·0001; IHC4 HR 2·90 [2·01-4·18], LR-Δχ(2)=29·14, p<0·0001); however, only BCI-L was significant for late distant recurrence (BCI-L HR 1·95 [95% CI 1·22-3·14], LR-Δχ(2)=7·97, p=0·0048; 21-gene recurrence score HR 1·13 [0·82-1·56], LR-Δχ(2)=0·48, p=0·47; IHC4 HR 1·30 [0·88-1·94], LR-Δχ(2)=1·59, p=0·20). BCI-L was the only significant prognostic test for risk of both early and late distant recurrence and identified two risk populations for each timeframe. It could help to identify patients at high risk for late distant recurrence who might benefit from extended endocrine or other therapy. Avon Foundation, National Institutes of Health, Breast Cancer Foundation, US Department of Defense Breast Cancer Research Program, Susan G Komen for the Cure, Breakthrough Breast Cancer through the Mary-Jean Mitchell Green Foundation, AstraZeneca, Cancer Research UK, and the National Institute for Health Research Biomedical Research Centre at the Royal Marsden (London, UK). Copyright © 2013 Elsevier Ltd. All rights reserved.

mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family

PubMed Central

Chen, Hua-Wei; Chen, Xiu; Oh, Su-Wan; Marinissen, Maria J.; Gutkind, J. Silvio; Hou, Steven X.

2002-01-01

The JAK/STAT signal transduction pathway controls numerous events in Drosophila melanogaster development. Receptors for the pathway have yet to be identified. Here we have identified a Drosophila gene that shows embryonic mutant phenotypes identical to those in the hopscotch (hop)/JAK kinase and marelle (mrl)/Stat92e mutations. We named this gene master of marelle (mom). Genetic analyses place mom's function between upd (the ligand) and hop. We further show that cultured cells transfected with the mom gene bind UPD and activate the HOP/STAT92E signal transduction pathway. mom encodes a protein distantly related to the mammalian cytokine receptor family. These data show that mom functions as a receptor of the Drosophila JAK/STAT signal transduction pathway. PMID:11825879

Domestic dog origin of canine distemper virus in free-ranging wolves in Portugal as revealed by hemagglutinin gene characterization.

PubMed

Müller, Alexandra; Silva, Eliane; Santos, Nuno; Thompson, Gertrude

2011-07-01

Serologic evidence for canine distemper virus (CDV) has been described in grey wolves but, to our knowledge, virus strains circulating in wolves have not been characterized genetically. The emergence of CDV in several non-dog hosts has been associated with amino acid substitutions at sites 530 and 549 of the hemagglutinin (H) protein. We sequenced the H gene of wild-type canine distemper virus obtained from two free-ranging Iberian wolves (Canis lupus signatus) and from one domestic dog (Canis familiaris). More differences were found between the two wolf sequences than between one of the wolves (wolf 75) and the dog. The latter two had a very high nucleotide similarity resulting in identical H gene amino acid sequences. Possible explanations include geographic and especially temporal proximity of the CDV obtained from wolf 75 and the domestic dog, taken in 2007-2008, as opposed to that from wolf 3 taken more distantly in 1998. Analysis of the deduced amino acids of the viral hemagglutinin revealed a glycine (G) and a tyrosine (Y) at amino acid positions 530 and 549, respectively, of the partial signaling lymphocytic activation molecule (SLAM)-receptor binding region which is typically found in viral strains obtained from domestic dogs. This suggests that the CDV found in these wolves resulted from transmission events from local domestic dogs rather than from wildlife species.

Distant Determination of Bilirubin Distribution in Skin by Multi-Spectral Imaging

NASA Astrophysics Data System (ADS)

Saknite, I.; Jakovels, D.; Spigulis, J.

2011-01-01

For mapping the bilirubin distribution in bruised skin the multi-spectral imaging technique was employed, which made it possible to observe temporal changes of the bilirubin content in skin photo-types II and III. The obtained results confirm the clinical potential of this technique for skin bilirubin diagnostics.

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

PubMed

Paik, Soonmyung; Shak, Steven; Tang, Gong; Kim, Chungyeul; Baker, Joffre; Cronin, Maureen; Baehner, Frederick L; Walker, Michael G; Watson, Drew; Park, Taesung; Hiller, William; Fisher, Edwin R; Wickerham, D Lawrence; Bryant, John; Wolmark, Norman

2004-12-30

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer. Copyright 2004 Massachusetts Medical Society.

Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-diethylaminoethyl-dextran methyl methacrylate copolymer non-viral vector-p53.

PubMed

Baliaka, A; Zarogoulidis, P; Domvri, K; Hohenforst-Schmidt, W; Sakkas, A; Huang, H; Le Pivert, P; Koliakos, G; Koliakou, E; Kouzi-Koliakos, K; Tsakiridis, K; Chioti, A; Siotou, E; Cheva, A; Zarogoulidis, K; Sakkas, L

2014-02-01

Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis.

PubMed

McDonald, Oliver G; Li, Xin; Saunders, Tyler; Tryggvadottir, Rakel; Mentch, Samantha J; Warmoes, Marc O; Word, Anna E; Carrer, Alessandro; Salz, Tal H; Natsume, Sonoko; Stauffer, Kimberly M; Makohon-Moore, Alvin; Zhong, Yi; Wu, Hao; Wellen, Kathryn E; Locasale, Jason W; Iacobuzio-Donahue, Christine A; Feinberg, Andrew P

2017-03-01

During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis. Changes were targeted to thousands of large chromatin domains across the genome that collectively specified malignant traits, including euchromatin and large organized chromatin histone H3 lysine 9 (H3K9)-modified (LOCK) heterochromatin. Remarkably, distant metastases co-evolved a dependence on the oxidative branch of the pentose phosphate pathway (oxPPP), and oxPPP inhibition selectively reversed reprogrammed chromatin, malignant gene expression programs, and tumorigenesis. These findings suggest a model whereby linked metabolic-epigenetic programs are selected for enhanced tumorigenic fitness during the evolution of distant metastasis.

High E6 Gene Expression Predicts for Distant Metastasis and Poor Survival in Patients With HPV-Positive Oropharyngeal Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khwaja, Shariq S.; Baker, Callie; Haynes, Wesley

Purpose: Patients with human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC) have a favorable prognosis. As a result, de-escalation clinical trials are under way. However, approximately 10% of patients will experience distant recurrence even with standard-of-care treatment. Here, we sought to identify novel biomarkers to better risk-stratify HPV-positive patients with OPSCC. Methods and Materials: Gene expression profiling by RNA sequencing (RNA-seq) and quantitative polymerase chain reaction was performed on HPV-positive OPSCC primary tumor specimens from patients with and without distant metastasis (DM). Results: RNA-seq analysis of 39 HPV-positive OPSCC specimens revealed that patients with DM had 2-fold higher E6 genemore » expression levels than did patients without DM (P=.029). This observation was confirmed in a validation cohort comprising 93 patients with HPV-positive OPSCC. The mean normalized E6 expression level in the 17 recurring primary specimens was 13 ± 2 compared with 8 ± 1 in the remaining 76 nonrecurring primaries (P=.001). Receiver operating characteristic analysis established an E6 expression level of 7.3 as a cutoff for worse recurrence-free survival (RFS). Patients from this cohort with high E6 gene expression (E6-high) (n=51, 55%) had more cancer-related deaths (23% vs 2%, P<.001) and DM (26% vs 5%, P<.001) than did patients with low E6 gene expression (E6-low) (n=42, 45%). Kaplan-Meier survival analysis revealed that E6-high had worse RFS (95% vs 69%, P=.004) and cancer-specific survival (97% vs 79%, P=.007). E6-high maintained statistical significance in multivariate regression models balancing surgery, chemotherapy, nodal stage, and smoking status. Gene set enrichment analysis demonstrated that tumors with high E6 expression were associated with P53, epidermal growth factor receptor, activating transcription factor-2, and transforming growth factor-β signaling pathways. Conclusion: High E6 gene expression level identifies HPV-positive OPSCC patients with 5-fold greater risk of distant disease recurrence and worse cancer-specific survival. Validation in a multi-institutional prospective clinical trial is required to assess the utility of E6 gene expression as a clinically useful prognostic biomarker.« less

Microbial population index and community structure in saline-alkaline soil using gene targeted metagenomics.

PubMed

Keshri, Jitendra; Mishra, Avinash; Jha, Bhavanath

2013-03-30

Population indices of bacteria and archaea were investigated from saline-alkaline soil and a possible microbe-environment pattern was established using gene targeted metagenomics. Clone libraries were constructed using 16S rRNA and functional gene(s) involved in carbon fixation (cbbL), nitrogen fixation (nifH), ammonia oxidation (amoA) and sulfur metabolism (apsA). Molecular phylogeny revealed the dominance of Actinobacteria, Firmicutes and Proteobacteria along with archaeal members of Halobacteraceae. The library consisted of novel bacterial (20%) and archaeal (38%) genera showing ≤95% similarity to previously retrieved sequences. Phylogenetic analysis indicated ability of inhabitant to survive in stress condition. The 16S rRNA gene libraries contained novel gene sequences and were distantly homologous with cultured bacteria. Functional gene libraries were found unique and most of the clones were distantly related to Proteobacteria, while clones of nifH gene library also showed homology with Cyanobacteria and Firmicutes. Quantitative real-time PCR exhibited that bacterial abundance was two orders of magnitude higher than archaeal. The gene(s) quantification indicated the size of the functional guilds harboring relevant key genes. The study provides insights on microbial ecology and different metabolic interactions occurring in saline-alkaline soil, possessing phylogenetically diverse groups of bacteria and archaea, which may be explored further for gene cataloging and metabolic profiling. Copyright © 2012 Elsevier GmbH. All rights reserved.

Negotiation From a Near and Distant Time Perspective

PubMed Central

Henderson, Marlone D.; Trope, Yaacov; Carnevale, Peter J.

2011-01-01

Across 3 experiments, the authors examined the effects of temporal distance on negotiation behavior. They found that greater temporal distance from negotiation decreased preference for piecemeal, single-issue consideration over integrative, multi-issue consideration (Experiment 1). They also found that greater temporal distance from an event being negotiated increased interest in conceding on the lowest priority issue and decreased interest in conceding on the highest priority issue (Experiment 2). Lastly, they found increased temporal distance from an event being negotiated produced a greater proportion of multi-issue offers, a greater likelihood of conceding on the lowest priority issue in exchange for a concession on the highest priority issue, and greater individual and joint outcomes (Experiment 3). Implications for conflict resolution and construal level theory are discussed. PMID:17014295

Exploiting the full power of temporal gene expression profiling through a new statistical test: application to the analysis of muscular dystrophy data.

PubMed

Vinciotti, Veronica; Liu, Xiaohui; Turk, Rolf; de Meijer, Emile J; 't Hoen, Peter A C

2006-04-03

The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other. We validate the temporal Hotelling T2-test on muscular gene expression data from four mouse strains which were profiled at different ages: dystrophin-, beta-sarcoglycan and gamma-sarcoglycan deficient mice, and wild-type mice. The first three are animal models for different muscular dystrophies. Extensive biological validation shows that the method is capable of finding genes with temporal profiles significantly different across the four strains, as well as identifying potential biomarkers for each form of the disease. The added value of the temporal test compared to an identical test which does not make use of temporal ordering is demonstrated via a simulation study, and through confirmation of the expression profiles from selected genes by quantitative PCR experiments. The proposed method maximises the detection of the biologically interesting genes, whilst minimising false detections. The temporal Hotelling T2-test is capable of finding relatively small and robust sets of genes that display different temporal profiles between the conditions of interest. The test is simple, it can be used on gene expression data generated from any experimental design and for any number of conditions, and it allows fast interpretation of the temporal behaviour of genes. The R code is available from V.V. The microarray data have been submitted to GEO under series GSE1574 and GSE3523.

Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data

PubMed Central

Vinciotti, Veronica; Liu, Xiaohui; Turk, Rolf; de Meijer, Emile J; 't Hoen, Peter AC

2006-01-01

Background The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other. Results We validate the temporal Hotelling T2-test on muscular gene expression data from four mouse strains which were profiled at different ages: dystrophin-, beta-sarcoglycan and gamma-sarcoglycan deficient mice, and wild-type mice. The first three are animal models for different muscular dystrophies. Extensive biological validation shows that the method is capable of finding genes with temporal profiles significantly different across the four strains, as well as identifying potential biomarkers for each form of the disease. The added value of the temporal test compared to an identical test which does not make use of temporal ordering is demonstrated via a simulation study, and through confirmation of the expression profiles from selected genes by quantitative PCR experiments. The proposed method maximises the detection of the biologically interesting genes, whilst minimising false detections. Conclusion The temporal Hotelling T2-test is capable of finding relatively small and robust sets of genes that display different temporal profiles between the conditions of interest. The test is simple, it can be used on gene expression data generated from any experimental design and for any number of conditions, and it allows fast interpretation of the temporal behaviour of genes. The R code is available from V.V. The microarray data have been submitted to GEO under series GSE1574 and GSE3523. PMID:16584545

Nonclassicality of Temporal Correlations.

PubMed

Brierley, Stephen; Kosowski, Adrian; Markiewicz, Marcin; Paterek, Tomasz; Przysiężna, Anna

2015-09-18

The results of spacelike separated measurements are independent of distant measurement settings, a property one might call two-way no-signaling. In contrast, timelike separated measurements are only one-way no-signaling since the past is independent of the future but not vice versa. For this reason some temporal correlations that are formally identical to nonclassical spatial correlations can still be modeled classically. We propose a new formulation of Bell's theorem for temporal correlations; namely, we define nonclassical temporal correlations as the ones which cannot be simulated by propagating in time the classical information content of a quantum system given by the Holevo bound. We first show that temporal correlations between results of any projective quantum measurements on a qubit can be simulated classically. Then we present a sequence of general measurements on a single m-level quantum system that cannot be explained by propagating in time an m-level classical system and using classical computers with unlimited memory.

Do convergent developmental mechanisms underlie convergent phenotypes?

NASA Technical Reports Server (NTRS)

Wray, Gregory A.

2002-01-01

Convergence is a pervasive evolutionary process, affecting many aspects of phenotype and even genotype. Relatively little is known about convergence in developmental processes, however, nor about the degree to which convergence in development underlies convergence in anatomy. A switch in the ecology of sea urchins from feeding to nonfeeding larvae illustrates how convergence in development can be associated with convergence in anatomy. Comparisons to more distantly related taxa, however, suggest that this association may be limited to relatively close phylogenetic comparisons. Similarities in gene expression during development provide another window into the association between convergence in developmental processes and convergence in anatomy. Several well-studied transcription factors exhibit likely cases of convergent gene expression in distantly related animal phyla. Convergence in regulatory gene expression domains is probably more common than generally acknowledged, and can arise for several different reasons. Copyright 2002 S. Karger AG, Basel.

Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes

PubMed Central

2014-01-01

Background Sho-saiko-to (SST) (also known as so-shi-ho-tang or xiao-chai-hu-tang) has been widely prescribed for chronic liver diseases in traditional Oriental medicine. Despite the substantial amount of clinical evidence for SST, its molecular mechanism has not been clearly identified at a genome-wide level. Methods By using a microarray, we analyzed the temporal changes of messenger RNA (mRNA) and microRNA expression in primary mouse hepatocytes after SST treatment. The pattern of genes regulated by SST was identified by using time-series microarray analysis. The biological function of genes was measured by pathway analysis. For the identification of the exact targets of the microRNAs, a permutation-based correlation method was implemented in which the temporal expression of mRNAs and microRNAs were integrated. The similarity of the promoter structure between temporally regulated genes was measured by analyzing the transcription factor binding sites in the promoter region. Results The SST-regulated gene expression had two major patterns: (1) a temporally up-regulated pattern (463 genes) and (2) a temporally down-regulated pattern (177 genes). The integration of the genes and microRNA demonstrated that 155 genes could be the targets of microRNAs from the temporally up-regulated pattern and 19 genes could be the targets of microRNAs from the temporally down-regulated pattern. The temporally up-regulated pattern by SST was associated with signaling pathways such as the cell cycle pathway, whereas the temporally down-regulated pattern included drug metabolism-related pathways and immune-related pathways. All these pathways could be possibly associated with liver regenerative activity of SST. Genes targeted by microRNA were moreover associated with different biological pathways from the genes not targeted by microRNA. An analysis of promoter similarity indicated that co-expressed genes after SST treatment were clustered into subgroups, depending on the temporal expression patterns. Conclusions We are the first to identify that SST regulates temporal gene expression by way of microRNA. MicroRNA targets and non-microRNA targets moreover have different biological roles. This functional segregation by microRNA would be critical for the elucidation of the molecular activities of SST. PMID:24410935

Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes.

PubMed

Song, Kwang Hoon; Kim, Yun Hee; Kim, Bu-Yeo

2014-01-11

Sho-saiko-to (SST) (also known as so-shi-ho-tang or xiao-chai-hu-tang) has been widely prescribed for chronic liver diseases in traditional Oriental medicine. Despite the substantial amount of clinical evidence for SST, its molecular mechanism has not been clearly identified at a genome-wide level. By using a microarray, we analyzed the temporal changes of messenger RNA (mRNA) and microRNA expression in primary mouse hepatocytes after SST treatment. The pattern of genes regulated by SST was identified by using time-series microarray analysis. The biological function of genes was measured by pathway analysis. For the identification of the exact targets of the microRNAs, a permutation-based correlation method was implemented in which the temporal expression of mRNAs and microRNAs were integrated. The similarity of the promoter structure between temporally regulated genes was measured by analyzing the transcription factor binding sites in the promoter region. The SST-regulated gene expression had two major patterns: (1) a temporally up-regulated pattern (463 genes) and (2) a temporally down-regulated pattern (177 genes). The integration of the genes and microRNA demonstrated that 155 genes could be the targets of microRNAs from the temporally up-regulated pattern and 19 genes could be the targets of microRNAs from the temporally down-regulated pattern. The temporally up-regulated pattern by SST was associated with signaling pathways such as the cell cycle pathway, whereas the temporally down-regulated pattern included drug metabolism-related pathways and immune-related pathways. All these pathways could be possibly associated with liver regenerative activity of SST. Genes targeted by microRNA were moreover associated with different biological pathways from the genes not targeted by microRNA. An analysis of promoter similarity indicated that co-expressed genes after SST treatment were clustered into subgroups, depending on the temporal expression patterns. We are the first to identify that SST regulates temporal gene expression by way of microRNA. MicroRNA targets and non-microRNA targets moreover have different biological roles. This functional segregation by microRNA would be critical for the elucidation of the molecular activities of SST.

Psychological distance reduces literal imitation: Evidence from an imitation-learning paradigm.

PubMed

Hansen, Jochim; Alves, Hans; Trope, Yaacov

2016-03-01

The present experiments tested the hypothesis that observers engage in more literal imitation of a model when the model is psychologically near to (vs. distant from) the observer. Participants learned to fold a dog out of towels by watching a model performing this task. Temporal (Experiment 1) and spatial (Experiment 2) distance from the model were manipulated. As predicted, participants copied more of the model's specific movements when the model was near (vs. distant). Experiment 3 replicated this finding with a paper-folding task, suggesting that distance from a model also affects imitation of less complex tasks. Perceived task difficulty, motivation, and the quality of the end product were not affected by distance. We interpret the findings as reflecting different levels of construal of the model's performance: When the model is psychologically distant, social learners focus more on the model's goal and devise their own means for achieving the goal, and as a result show less literal imitation of the model. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The Location of the Bacterial Origin of Replication is Critical for Initial Ciproflaxcin Antibiotic Resistance

NASA Astrophysics Data System (ADS)

Bos, Julia; Nehring, Ralph; Cruz, Diane; Austin, Doug; Rosenberg, Susan; Austin, Robert

By using E. coli cells in which the unique origin of replication has been moved to a ectopic chromosome location distant from the native one, we probe how perturbation of gene order near the origin of replication impacts genome stability and survival under genomic attack. We find that when challenged with sub-inhibitory doses of ciprofloxacin, an antibiotic that generates replication fork stalling, cells with the ectopic origin show significant fitness loss. We show that genes functionally relevant to the cipro-induced stress response are largely located near the native origin, even in distantly related species. We show that while cipro induces increased copy number of genes proximal to the origin of replication as a direct consequence of replication fork stalling, gene copy number variation was reduced near the ectopic origin. Altered gene dosage in cells with an ectopic origin resulted in impaired replication fork repair and chromosome instability. We propose that gene distribution in the origin region acts as a fundamental first line of defense when the integrity of the genome is threatened and that genes proximal to the origin of replication serve as a mechanism of genetic innovation and a driving force of genome evolution in the presence of genotoxic antibiotics. Lewis Sigler Institute for Integrative Genomics and the Physics Department at Princeton University.

Insights into recent and ancient trends in the co-evolution of Earth and life as revealed by microbial genomics

NASA Astrophysics Data System (ADS)

Anderson, R. E.; Huber, J. A.; Parsons, C.; Stüeken, E.

2017-12-01

Since the origin of life over 4 billion years ago, life has fundamentally altered the habitability of Earth. Similarly, the environment molds the evolutionary trajectory of life itself through natural selection. Microbial genomes retain a "memory" of the co-evolution of life and Earth and can be analyzed to better understand trends and events in both the recent and distant past. To examine evolutionary trends in the more recent past, we have used metagenomics analyses to investigate which environmental factors play the strongest role in driving the evolution of microbes in deep-sea hydrothermal vents, which are thought to have been important habitats in the earliest stages of life's evolution. We have shown that microbial populations in a deep, basalt-hosted system appear to be under stronger purifying selection than populations inhabiting a cooler serpentinizing system less than 20 km away, suggesting that environmental context and geochemistry have an important impact on evolutionary rates and trends. We also found evidence that viruses play an important role in driving evolution in these habitats. Changing environmental conditions may also effect long-term evolutionary trends in Earth's distant past, as revealed by comparative genomics. By reconciling phylogenetic trees for microbial species with trees of metabolic genes, we can determine approximately when crucial metabolic genes began to spread across the tree of life through horizontal gene transfer. Using these methods, we conducted an analysis of the relative timing of the spread of genes related to the nitrogen cycle. Our results indicate that the rate of horizontal gene transfer for important genes related to denitrification increased after the Great Oxidation Event, concurrent with geochemical evidence for increasing availability of nitrate, suggesting that the oxygenation of the atmosphere and surface ocean may have been an important determining factor for the spread of denitrification genes across the tree of life. In contrast, genes related to nitrogen fixation display much more consistent rates of horizontal gene transfer throughout Earth's history. Studies that couple genomics approaches with geochemistry have the potential to reveal insights into the co-evolution of life and Earth both in the recent and distant past.

The future is now: prospective temporal self-appraisals among defensive pessimists and optimists.

PubMed

Sanna, Lawrence J; Chang, Edward C; Carter, Seth E; Small, Eulena M

2006-06-01

Three studies found that prospective temporal self-appraisals can be part of defensive pessimists' strategy; they felt closer to equally distant negative than positive futures. In Study 1, defensive pessimists felt closer to future failures and reported more negative affect than those considering success. In Study 2, when manipulated negative futures were close, defensive pessimists felt bad and performed well; results suggested that viewing negative futures as close may be part of their natural strategy. Study 3 found that prospective self-appraisals influenced performances through felt preparation. Optimists did not use prospective self-appraisals (Study 1) and their performances were unaffected by manipulated temporal distance (Studies 2 and 3). Discussion centers on prospective self-appraisals and multiple strategies of defensive pessimists.

Extracting microRNA-gene relations from biomedical literature using distant supervision

PubMed Central

Clarke, Luka A.; Couto, Francisco M.

2017-01-01

Many biomedical relation extraction approaches are based on supervised machine learning, requiring an annotated corpus. Distant supervision aims at training a classifier by combining a knowledge base with a corpus, reducing the amount of manual effort necessary. This is particularly useful for biomedicine because many databases and ontologies have been made available for many biological processes, while the availability of annotated corpora is still limited. We studied the extraction of microRNA-gene relations from text. MicroRNA regulation is an important biological process due to its close association with human diseases. The proposed method, IBRel, is based on distantly supervised multi-instance learning. We evaluated IBRel on three datasets, and the results were compared with a co-occurrence approach as well as a supervised machine learning algorithm. While supervised learning outperformed on two of those datasets, IBRel obtained an F-score 28.3 percentage points higher on the dataset for which there was no training set developed specifically. To demonstrate the applicability of IBRel, we used it to extract 27 miRNA-gene relations from recently published papers about cystic fibrosis. Our results demonstrate that our method can be successfully used to extract relations from literature about a biological process without an annotated corpus. The source code and data used in this study are available at https://github.com/AndreLamurias/IBRel. PMID:28263989

Extracting microRNA-gene relations from biomedical literature using distant supervision.

PubMed

Lamurias, Andre; Clarke, Luka A; Couto, Francisco M

2017-01-01

Many biomedical relation extraction approaches are based on supervised machine learning, requiring an annotated corpus. Distant supervision aims at training a classifier by combining a knowledge base with a corpus, reducing the amount of manual effort necessary. This is particularly useful for biomedicine because many databases and ontologies have been made available for many biological processes, while the availability of annotated corpora is still limited. We studied the extraction of microRNA-gene relations from text. MicroRNA regulation is an important biological process due to its close association with human diseases. The proposed method, IBRel, is based on distantly supervised multi-instance learning. We evaluated IBRel on three datasets, and the results were compared with a co-occurrence approach as well as a supervised machine learning algorithm. While supervised learning outperformed on two of those datasets, IBRel obtained an F-score 28.3 percentage points higher on the dataset for which there was no training set developed specifically. To demonstrate the applicability of IBRel, we used it to extract 27 miRNA-gene relations from recently published papers about cystic fibrosis. Our results demonstrate that our method can be successfully used to extract relations from literature about a biological process without an annotated corpus. The source code and data used in this study are available at https://github.com/AndreLamurias/IBRel.

Molecular evolution of candidate male reproductive genes in the brown algal model Ectocarpus.

PubMed

Lipinska, Agnieszka P; Van Damme, Els J M; De Clerck, Olivier

2016-01-05

Evolutionary studies of genes that mediate recognition between sperm and egg contribute to our understanding of reproductive isolation and speciation. Surface receptors involved in fertilization are targets of sexual selection, reinforcement, and other evolutionary forces including positive selection. This observation was made across different lineages of the eukaryotic tree from land plants to mammals, and is particularly evident in free-spawning animals. Here we use the brown algal model species Ectocarpus (Phaeophyceae) to investigate the evolution of candidate gamete recognition proteins in a distant major phylogenetic group of eukaryotes. Male gamete specific genes were identified by comparing transcriptome data covering different stages of the Ectocarpus life cycle and screened for characteristics expected from gamete recognition receptors. Selected genes were sequenced in a representative number of strains from distant geographical locations and varying stages of reproductive isolation, to search for signatures of adaptive evolution. One of the genes (Esi0130_0068) showed evidence of selective pressure. Interestingly, that gene displayed domain similarities to the receptor for egg jelly (REJ) protein involved in sperm-egg recognition in sea urchins. We have identified a male gamete specific gene with similarity to known gamete recognition receptors and signatures of adaptation. Altogether, this gene could contribute to gamete interaction during reproduction as well as reproductive isolation in Ectocarpus and is therefore a good candidate for further functional evaluation.

Breast cancers with EGFR and HER2 co-amplification favor distant metastasis and poor clinical outcome

PubMed Central

Guo, Peng; Pu, Tianjie; Chen, Shinan; Qiu, Yan; Zhong, Xiaorong; Zheng, Hong; Chen, Lina; Bu, Hong; Ye, Feng

2017-01-01

ErbB signaling serves essential roles in invasive ductal carcinoma (IDC). The aim of the present study was to assess gene amplification in ErbB family members in IDC with clinical implications. Quantitative polymerase chain reaction and fluorescence in situ hybridization were performed on formalin-fixed paraffin-embedded tumor samples for gene amplification detection. The clinical and histopathological characteristics, as well as the prognostic significance, were analyzed. Among the 119 IDC patients evaluated, epidermal growth factor receptor [EGFR; also known as human epidermal growth factor receptor (HER)1], HER2, HER3 and HER4 gene amplification was observed in 30 (25.2%), 44 (36.9%), 0 (0.0%) and 1 (0.8%) patients, respectively. EGFR amplification was associated with estrogen receptor status (P=0.028) and higher possibilities of recurrence (P=0.015) and distant metastasis (following initial surgery) (P=0.011). In survival analysis, EGFR amplification was also associated with disease-free survival (DFS) (P=0.001) and overall survival (OS) (P=0.003). HER2 amplification was associated with larger tumor size (P=0.006), later clinical stage (P=0.003) and distant metastasis (following initial surgery) (P=0.006). In survival analysis, HER2 amplification was also associated with DFS (P=0.011). Notably, the present study identified a group of patients in whom EGFR and HER2 were co-amplified. This group of patients appeared to have a higher possibility of metastasis (when diagnosed) (P=0.014) and distant metastasis (following initial surgery) (P<0.001). In survival analysis, these patients were noticed to be associated with DFS (P<0.001) and OS (P=0.002). With respect to treatment regimen, this was also true for the DFS association with chemotherapy (P<0.001), radiotherapy (P<0.001) and hormonal therapy (P=0.001). The present results suggest that EGFR and HER2 amplification favor distant metastasis following initial surgery and are significantly associated with poor clinical outcome in breast cancer patients. PMID:29181099

Introgressive Hybridization between Anciently Diverged Lineages of Silene (Caryophyllaceae)

PubMed Central

Petri, Anna; Pfeil, Bernard E.; Oxelman, Bengt

2013-01-01

Hybridization has played a major role during the evolution of angiosperms, mediating both gene flow between already distinct species and the formation of new species. Newly formed hybrids between distantly related taxa are often sterile. For this reason, interspecific crosses resulting in fertile hybrids have rarely been described to take place after more than a few million years after divergence. We describe here the traces of a reproductively successful hybrid between two ancestral species of Silene, diverged for about six million years prior to hybridization. No extant hybrids between the two parental lineages are currently known, but introgression of the RNA polymerase gene NRPA2 provides clear evidence of a temporary and fertile hybrid. Parsimony reconciliation between gene trees and the species tree, as well as consideration of clade ages, help exclude gene paralogy and lineage sorting as alternative hypotheses. This may represent one of the most extreme cases of divergence between species prior to introgressive hybridization discovered yet, notably at a homoploid level. Although species boundaries are generally believed to be stable after millions of years of divergence, we believe that this finding may indicate that gene flow between distantly related species is merely largely undetected at present. PMID:23861793

Microsporidian polar tube proteins: highly divergent but closely linked genes encode PTP1 and PTP2 in members of the evolutionarily distant Antonospora and Encephalitozoon groups.

PubMed

Polonais, Valérie; Prensier, Gérard; Méténier, Guy; Vivarès, Christian P; Delbac, Frédéric

2005-09-01

The spore polar tube is a unique organelle required for cell invasion by fungi-related microsporidian parasites. Two major polar tube proteins (PTP1 and PTP2) are encoded by two tandemly arranged genes in Encephalitozoon species. A look at Antonospora (Nosema) locustae contigs (http://jbpc.mbl.edu/Nosema/Contigs/) revealed significant conservation in the order and orientation of various genes, despite high sequence divergence features, when comparing with Encephalitozoon cuniculi complete genome. This syntenic relationship between distantly related Encephalitozoon and Antonospora genera has been successfully exploited to identify ptp1 and ptp2 genes in two insect-infecting species assigned to the Antonospora clade (A. locustae and Paranosema grylli). Targeting of respective proteins to the polar tube was demonstrated through immunolocalization experiments with antibodies raised against recombinant proteins. Both PTPs were extracted from spores with 100mM dithiothreitol. Evidence for PTP1 mannosylation was obtained in studied species, supporting a key role of PTP1 in interactions with host cell surface.

Diverse Forms of RPS9 Splicing Are Part of an Evolving Autoregulatory Circuit

PubMed Central

Plocik, Alex M.; Guthrie, Christine

2012-01-01

Ribosomal proteins are essential to life. While the functions of ribosomal protein-encoding genes (RPGs) are highly conserved, the evolution of their regulatory mechanisms is remarkably dynamic. In Saccharomyces cerevisiae, RPGs are unusual in that they are commonly present as two highly similar gene copies and in that they are over-represented among intron-containing genes. To investigate the role of introns in the regulation of RPG expression, we constructed 16 S. cerevisiae strains with precise deletions of RPG introns. We found that several yeast introns function to repress rather than to increase steady-state mRNA levels. Among these, the RPS9A and RPS9B introns were required for cross-regulation of the two paralogous gene copies, which is consistent with the duplication of an autoregulatory circuit. To test for similar intron function in animals, we performed an experimental test and comparative analyses for autoregulation among distantly related animal RPS9 orthologs. Overexpression of an exogenous RpS9 copy in Drosophila melanogaster S2 cells induced alternative splicing and degradation of the endogenous copy by nonsense-mediated decay (NMD). Also, analysis of expressed sequence tag data from distantly related animals, including Homo sapiens and Ciona intestinalis, revealed diverse alternatively-spliced RPS9 isoforms predicted to elicit NMD. We propose that multiple forms of splicing regulation among RPS9 orthologs from various eukaryotes operate analogously to translational repression of the alpha operon by S4, the distant prokaryotic ortholog. Thus, RPS9 orthologs appear to have independently evolved variations on a fundamental autoregulatory circuit. PMID:22479208

Regulation of CYBB Gene Expression in Human Phagocytes by a Distant Upstream NF-κB Binding Site.

PubMed

Frazão, Josias B; Thain, Alison; Zhu, Zhiqing; Luengo, Marcos; Condino-Neto, Antonio; Newburger, Peter E

2015-09-01

The human CYBB gene encodes the gp91-phox component of the phagocyte oxidase enzyme complex, which is responsible for generating superoxide and other downstream reactive oxygen species essential to microbial killing. In the present study, we have identified by sequence analysis a putative NF-κB binding site in a DNase I hypersensitive site, termed HS-II, located in the distant 5' flanking region of the CYBB gene. Electrophoretic mobility assays showed binding of the sequence element by recombinant NF-κB protein p50 and by proteins in nuclear extract from the HL-60 myeloid leukemia cell line corresponding to p50 and to p50/p65 heterodimers. Chromatin immunoprecipitation demonstrated NF-κB binding to the site in intact HL-60 cells. Chromosome conformation capture (3C) assays demonstrated physical interaction between the NF-κB binding site and the CYBB promoter region. Inhibition of NF-κB activity by salicylate reduced CYBB expression in peripheral blood neutrophils and differentiated U937 monocytic leukemia cells. U937 cells transfected with a mutant inhibitor of κB "super-repressor" showed markedly diminished CYBB expression. Luciferase reporter analysis of the NF-κB site linked to the CYBB 5' flanking promoter region revealed enhanced expression, augmented by treatment with interferon-γ. These studies indicate a role for this distant, 15 kb upstream, binding site in NF-κB regulation of the CYBB gene, an essential component of phagocyte-mediated host defense. © 2015 Wiley Periodicals, Inc.

Xanthomonas adaptation to common bean is associated with horizontal transfers of genes encoding TAL effectors.

PubMed

Ruh, Mylène; Briand, Martial; Bonneau, Sophie; Jacques, Marie-Agnès; Chen, Nicolas W G

2017-08-30

Common bacterial blight is a devastating bacterial disease of common bean (Phaseolus vulgaris) caused by Xanthomonas citri pv. fuscans and Xanthomonas phaseoli pv. phaseoli. These phylogenetically distant strains are able to cause similar symptoms on common bean, suggesting that they have acquired common genetic determinants of adaptation to common bean. Transcription Activator-Like (TAL) effectors are bacterial type III effectors that are able to induce the expression of host genes to promote infection or resistance. Their capacity to bind to a specific host DNA sequence suggests that they are potential candidates for host adaption. To study the diversity of tal genes from Xanthomonas strains responsible for common bacterial blight of bean, whole genome sequences of 17 strains representing the diversity of X. citri pv. fuscans and X. phaseoli pv. phaseoli were obtained by single molecule real time sequencing. Analysis of these genomes revealed the existence of four tal genes named tal23A, tal20F, tal18G and tal18H, respectively. While tal20F and tal18G were chromosomic, tal23A and tal18H were carried on plasmids and shared between phylogenetically distant strains, therefore suggesting recent horizontal transfers of these genes between X. citri pv. fuscans and X. phaseoli pv. phaseoli strains. Strikingly, tal23A was present in all strains studied, suggesting that it played an important role in adaptation to common bean. In silico predictions of TAL effectors targets in the common bean genome suggested that TAL effectors shared by X. citri pv. fuscans and X. phaseoli pv. phaseoli strains target the promoters of genes of similar functions. This could be a trace of convergent evolution among TAL effectors from different phylogenetic groups, and comforts the hypothesis that TAL effectors have been implied in the adaptation to common bean. Altogether, our results favour a model where plasmidic TAL effectors are able to contribute to host adaptation by being horizontally transferred between distant lineages.

Long-distance thermal temporal ghost imaging over optical fibers

NASA Astrophysics Data System (ADS)

Yao, Xin; Zhang, Wei; Li, Hao; You, Lixing; Wang, Zhen; Huang, Yidong

2018-02-01

A thermal ghost imaging scheme between two distant parties is proposed and experimentally demonstrated over long-distance optical fibers. In the scheme, the weak thermal light is split into two paths. Photons in one path are spatially diffused according to their frequencies by a spatial dispersion component, then illuminate the object and record its spatial transmission information. Photons in the other path are temporally diffused by a temporal dispersion component. By the coincidence measurement between photons of two paths, the object can be imaged in a way of ghost imaging, based on the frequency correlation between photons in the two paths. In the experiment, the weak thermal light source is prepared by the spontaneous four-wave mixing in a silicon waveguide. The temporal dispersion is introduced by single mode fibers of 50 km, which also could be looked as a fiber link. Experimental results show that this scheme can be realized over long-distance optical fibers.

Amnesia, rehearsal, and temporal distinctiveness models of recall.

PubMed

Brown, Gordon D A; Della Sala, Sergio; Foster, Jonathan K; Vousden, Janet I

2007-04-01

Classical amnesia involves selective memory impairment for temporally distant items in free recall (impaired primacy) together with relative preservation of memory for recency items. This abnormal serial position curve is traditionally taken as evidence for a distinction between different memory processes, with amnesia being associated with selectively impaired long-term memory. However recent accounts of normal serial position curves have emphasized the importance of rehearsal processes in giving rise to primacy effects and have suggested that a single temporal distinctiveness mechanism can account for both primacy and recency effects when rehearsal is considered. Here we explore the pattern of strategic rehearsal in a patient with very severe amnesia. When the patient's rehearsal pattern is taken into account, a temporal distinctiveness model can account for the serial position curve in both amnesic and control free recall. The results are taken as consistent with temporal distinctiveness models of free recall, and they motivate an emphasis on rehearsal patterns in understanding amnesic deficits in free recall.

Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

PubMed

Ryan, Veronica H; Primiani, Christopher T; Rao, Jagadeesh S; Ahn, Kwangmi; Rapoport, Stanley I; Blanchard, Helene

2014-01-01

The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

Mapping the Information Trace in Local Field Potentials by a Computational Method of Two-Dimensional Time-Shifting Synchronization Likelihood Based on Graphic Processing Unit Acceleration.

PubMed

Zhao, Zi-Fang; Li, Xue-Zhu; Wan, You

2017-12-01

The local field potential (LFP) is a signal reflecting the electrical activity of neurons surrounding the electrode tip. Synchronization between LFP signals provides important details about how neural networks are organized. Synchronization between two distant brain regions is hard to detect using linear synchronization algorithms like correlation and coherence. Synchronization likelihood (SL) is a non-linear synchronization-detecting algorithm widely used in studies of neural signals from two distant brain areas. One drawback of non-linear algorithms is the heavy computational burden. In the present study, we proposed a graphic processing unit (GPU)-accelerated implementation of an SL algorithm with optional 2-dimensional time-shifting. We tested the algorithm with both artificial data and raw LFP data. The results showed that this method revealed detailed information from original data with the synchronization values of two temporal axes, delay time and onset time, and thus can be used to reconstruct the temporal structure of a neural network. Our results suggest that this GPU-accelerated method can be extended to other algorithms for processing time-series signals (like EEG and fMRI) using similar recording techniques.

Dynamic CRM occupancy reflects a temporal map of developmental progression.

PubMed

Wilczyński, Bartek; Furlong, Eileen E M

2010-06-22

Development is driven by tightly coordinated spatio-temporal patterns of gene expression, which are initiated through the action of transcription factors (TFs) binding to cis-regulatory modules (CRMs). Although many studies have investigated how spatial patterns arise, precise temporal control of gene expression is less well understood. Here, we show that dynamic changes in the timing of CRM occupancy is a prevalent feature common to all TFs examined in a developmental ChIP time course to date. CRMs exhibit complex binding patterns that cannot be explained by the sequence motifs or expression of the TFs themselves. The temporal changes in TF binding are highly correlated with dynamic patterns of target gene expression, which in turn reflect transitions in cellular function during different stages of development. Thus, it is not only the timing of a TF's expression, but also its temporal occupancy in refined time windows, which determines temporal gene expression. Systematic measurement of dynamic CRM occupancy may therefore serve as a powerful method to decode dynamic changes in gene expression driving developmental progression.

Genes from scratch--the evolutionary fate of de novo genes.

PubMed

Schlötterer, Christian

2015-04-01

Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Distant influences of amygdala lesion on visual cortical activation during emotional face processing.

PubMed

Vuilleumier, Patrik; Richardson, Mark P; Armony, Jorge L; Driver, Jon; Dolan, Raymond J

2004-11-01

Emotional visual stimuli evoke enhanced responses in the visual cortex. To test whether this reflects modulatory influences from the amygdala on sensory processing, we used event-related functional magnetic resonance imaging (fMRI) in human patients with medial temporal lobe sclerosis. Twenty-six patients with lesions in the amygdala, the hippocampus or both, plus 13 matched healthy controls, were shown pictures of fearful or neutral faces in task-releant or task-irrelevant positions on the display. All subjects showed increased fusiform cortex activation when the faces were in task-relevant positions. Both healthy individuals and those with hippocampal damage showed increased activation in the fusiform and occipital cortex when they were shown fearful faces, but this was not the case for individuals with damage to the amygdala, even though visual areas were structurally intact. The distant influence of the amygdala was also evidenced by the parametric relationship between amygdala damage and the level of emotional activation in the fusiform cortex. Our data show that combining the fMRI and lesion approaches can help reveal the source of functional modulatory influences between distant but interconnected brain regions.

Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early-stage breast cancer: a cost-effectiveness evaluation in the German setting.

PubMed

Blohmer, J U; Rezai, M; Kümmel, S; Kühn, T; Warm, M; Friedrichs, K; Benkow, A; Valentine, W J; Eiermann, W

2013-01-01

The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany. A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually. The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care. Country-specific data on the risk of distant recurrence and quality-of-life were not available. Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current standard of care women with ER+, HER2- early-stage breast cancer.

TEMPORAL GENE INDUCTION PATTERNS IN SHEEPSHEAD MINNOWS EXPOSED TO 17-ESTRADIOL

EPA Science Inventory

Gene arrays provide a powerful method to examine changes in gene expression in fish due to chemical exposures in the environment. In this study, we expanded an existing gene array for sheepshead minnows (Cyprinodon variegatus) (SHM) and used it to examine temporal changes in gene...

Coexpression of α6β4 Integrin and Guanine Nucleotide Exchange Factor Net1 Identifies Node-Positive Breast Cancer Patients at High Risk for Distant Metastasis

PubMed Central

Gilcrease, Michael Z.; Kilpatrick, Shannan K.; Woodward, Wendy A.; Zhou, Xiao; Nicolas, Marlo M.; Corley, Lynda J.; Fuller, Gregory N.; Tucker, Susan L.; Diaz, Leslie K.; Buchholz, Thomas A.; Frost, Jeffrey A.

2009-01-01

Preclinical data indicate that α6β4 integrin signaling through Ras homolog gene family, member A, plays an important role in tumor cell motility. The objective of this study was to determine whether the combined expression of α6β4 integrin and neuroepithelioma transforming gene 1 (Net1), a guanine nucleotide exchange factor specific for Ras homolog gene family member A, is associated with adverse clinical outcome in breast cancer patients. Immunohistochemical expression of each protein was evaluated in a tumor tissue microarray prepared from the primary tumors of 94 node-positive patients with invasive breast carcinoma treated with total mastectomy and doxorubicin-based chemotherapy without radiation with a median follow-up of 12.5 years. Associations between staining results and multiple clinicopathologic variables were investigated. Although there was no significant association between α6β4 integrin or Net1 expression and clinical outcome when each marker was considered individually, coexpression of α6β4 and Net1 was associated with decreased distant metastasis–free survival (P = 0.030). In the subset of patients with hormone receptor–positive tumors, coexpression of α6β4 and Net1 was associated with a decrease in distant metastasis–free and overall survival (P < 0.001 and P = 0.006, respectively). Although an association between human epidermal growth factor receptor 2 expression and coexpression of α6β4 and Net1 (P = 0.008) was observed, coexpression of α6β4 and Net1 (hazard ratio, 1.63; P = 0.02) and lymphovascular invasion (hazard ratio, 2.35; P = 0.02) were the only factors independently associated with the development of distant metastasis in multivariate analysis. These findings suggest that coexpression of α6β4 integrin and Net1 could be a useful biomarker for aggressive disease in node-positive breast cancer patients. PMID:19124484

A Graphical Model of Smoking-Induced Global Instability in Lung Cancer.

PubMed

Wang, Yanbo; Qian, Weikang; Yuan, Bo

2018-01-01

Smoking is the major cause of lung cancer and the leading cause of cancer-related death in the world. The most current view about lung cancer is no longer limited to individual genes being mutated by any carcinogenic insults from smoking. Instead, tumorigenesis is a phenotype conferred by many systematic and global alterations, leading to extensive heterogeneity and variation for both the genotypes and phenotypes of individual cancer cells. Thus, strategically it is foremost important to develop a methodology to capture any consistent and global alterations presumably shared by most of the cancerous cells for a given population. This is particularly true that almost all of the data collected from solid cancers (including lung cancers) are usually distant apart over a large span of temporal or even spatial contexts. Here, we report a multiple non-Gaussian graphical model to reconstruct the gene interaction network using two previously published gene expression datasets. Our graphical model aims to selectively detect gross structural changes at the level of gene interaction networks. Our methodology is extensively validated, demonstrating good robustness, as well as the selectivity and specificity expected based on our biological insights. In summary, gene regulatory networks are still relatively stable during presumably the early stage of neoplastic transformation. But drastic structural differences can be found between lung cancer and its normal control, including the gain of functional modules for cellular proliferations such as EGFR and PDGFRA, as well as the lost of the important IL6 module, supporting their roles as potential drug targets. Interestingly, our method can also detect early modular changes, with the ALDH3A1 and its associated interactions being strongly implicated as a potential early marker, whose activations appear to alter LCN2 module as well as its interactions with the important TP53-MDM2 circuitry. Our strategy using the graphical model to reconstruct gene interaction work with biologically-inspired constraints exemplifies the importance and beauty of biology in developing any bio-computational approach.

An anti-silencer– and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development

PubMed Central

Hao, Bingtao; Naik, Abani Kanta; Watanabe, Akiko; Tanaka, Hirokazu; Chen, Liang; Richards, Hunter W.; Kondo, Motonari; Taniuchi, Ichiro; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi

2015-01-01

Rag1 and Rag2 gene expression in CD4+CD8+ double-positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unknown. Here, we show that the ASE physically interacts with the distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub. Moreover, we show that the ASE functions as a classical enhancer that can potently activate these promoters in the absence of the silencer or other locus elements. In thymocytes lacking the chromatin organizer SATB1, we identified a partial defect in Tcra gene rearrangement that was associated with reduced expression of Rag1 and Rag2 at the DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes. PMID:25847946

ChIP-seq Accurately Predicts Tissue-Specific Activity of Enhancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Visel, Axel; Blow, Matthew J.; Li, Zirong

2009-02-01

A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover since they are scattered amongst the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here, we performed chromatin immunoprecipitation with the enhancer-associated protein p300, followed by massively-parallel sequencing, to map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain, and limb tissue. Wemore » tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases revealed reproducible enhancer activity in those tissues predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities and suggest that such datasets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.« less

Genomic admixture tracks pulses of economic activity over 2,000 years in the Indian Ocean trading network.

PubMed

Brucato, Nicolas; Kusuma, Pradiptajati; Beaujard, Philippe; Sudoyo, Herawati; Cox, Murray P; Ricaut, François-Xavier

2017-06-07

The Indian Ocean has long been a hub of interacting human populations. Following land- and sea-based routes, trade drove cultural contacts between far-distant ethnic groups in Asia, India, the Middle East and Africa, creating one of the world's first proto-globalized environments. However, the extent to which population mixing was mediated by trade is poorly understood. Reconstructing admixture times from genomic data in 3,006 individuals from 187 regional populations reveals a close association between bouts of human migration and trade volumes during the last 2,000 years across the Indian Ocean trading system. Temporal oscillations in trading activity match phases of contraction and expansion in migration, with high water marks following the expansion of the Silk Roads in the 5 th century AD, the rise of maritime routes in the 11 th century and a drastic restructuring of the trade network following the arrival of Europeans in the 16 th century. The economic fluxes of the Indian Ocean trade network therefore directly shaped exchanges of genes, in addition to goods and concepts.

Leek yellow stripe virus isolates from Brazil form a distant clade based on the P1 gene

USDA-ARS?s Scientific Manuscript database

The complete genomic sequence of a garlic isolate of Leek yellow stripe virus from Brazil (LYSV-MG) has been determined, and phylogenetic comparisons made to LYSV isolates from other parts of the world. In addition, the nucleotide sequence of the 5'UTR and part of the P1 gene of multiple LYSV isolat...

Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping

PubMed Central

Schörg, Alexandra; Santambrogio, Sara; Platt, James L.; Schödel, Johannes; Lindenmeyer, Maja T.; Cohen, Clemens D.; Schrödter, Katrin; Mole, David R.; Wenger, Roland H.; Hoogewijs, David

2015-01-01

A crucial step in the cellular adaptation to oxygen deficiency is the binding of hypoxia-inducible factors (HIFs) to hypoxia response elements (HREs) of oxygen-regulated genes. Genome-wide HIF-1α/2α/β DNA-binding studies revealed that the majority of HREs reside distant to the promoter regions, but the function of these distal HREs has only been marginally studied in the genomic context. We used chromatin immunoprecipitation (ChIP), gene editing (TALEN) and chromosome conformation capture (3C) to localize and functionally characterize a 82 kb upstream HRE that solely drives oxygen-regulated expression of the newly identified HIF target gene PAG1. PAG1, a transmembrane adaptor protein involved in Src signalling, was hypoxically induced in various cell lines and mouse tissues. ChIP and reporter gene assays demonstrated that the −82 kb HRE regulates PAG1, but not an equally distant gene further upstream, by direct interaction with HIF. Ablation of the consensus HRE motif abolished the hypoxic induction of PAG1 but not general oxygen signalling. 3C assays revealed that the −82 kb HRE physically associates with the PAG1 promoter region, independent of HIF-DNA interaction. These results demonstrate a constitutive interaction between the −82 kb HRE and the PAG1 promoter, suggesting a physiologically important rapid response to hypoxia. PMID:26007655

First results from stellar occultations in the "GAIA era"

NASA Astrophysics Data System (ADS)

Benedetti-Rossi, G.; Vieira-Martins, R.; Sicardy, B.

2017-09-01

Stellar occultation is a powerful technique to study distant solar system bodies. It allows high angular resolution of the occulting body from the analysis of a light curve acquired with high temporal resolution with uncertainties comparable as probes. In the "GAIA era", stellar occultations is now able to obtain even more impressive results such as the presence of atmosphere, rings and topographic features.

DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks

PubMed Central

Gerstein, Mark

2016-01-01

Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem’s gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally–e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org) for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the “state” and “control” in the model refer to its own (internal) and another subsystem’s (external) gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model’s parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation) representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs), seeing the degree to which these can be accounted for by orthologous (internal) versus species-specific (external) TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with evolutionarily ancient functions (e.g. the ribosomal proteins), in contrast to those with more recently evolved functions (e.g., cell-cell communication). This suggests that despite striking morphological differences, some fundamental embryonic-developmental processes are still controlled by ancient regulatory systems. PMID:27760135

DREISS: Using State-Space Models to Infer the Dynamics of Gene Expression Driven by External and Internal Regulatory Networks.

PubMed

Wang, Daifeng; He, Fei; Maslov, Sergei; Gerstein, Mark

2016-10-01

Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem's gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally-e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution. We developed a computational method (DREISS, dreiss.gerteinlab.org) for analyzing the Dynamics of gene expression driven by Regulatory networks, both External and Internal based on State Space models. Given a subsystem, the "state" and "control" in the model refer to its own (internal) and another subsystem's (external) gene expression levels. The state at a given time is determined by the state and control at a previous time. Because typical time-series data do not have enough samples to fully estimate the model's parameters, DREISS uses dimensionality reduction, and identifies canonical temporal expression trajectories (e.g., degradation, growth and oscillation) representing the regulatory effects emanating from various subsystems. To demonstrate capabilities of DREISS, we study the regulatory effects of evolutionarily conserved vs. divergent TFs across distant species. In particular, we applied DREISS to the time-series gene expression datasets of C. elegans and D. melanogaster during their embryonic development. We analyzed the expression dynamics of the conserved, orthologous genes (orthologs), seeing the degree to which these can be accounted for by orthologous (internal) versus species-specific (external) TFs. We found that between two species, the orthologs have matched, internally driven expression patterns but very different externally driven ones. This is particularly true for genes with evolutionarily ancient functions (e.g. the ribosomal proteins), in contrast to those with more recently evolved functions (e.g., cell-cell communication). This suggests that despite striking morphological differences, some fundamental embryonic-developmental processes are still controlled by ancient regulatory systems.

Genome-Wide Temporal Expression Profiling in Caenorhabditis elegans Identifies a Core Gene Set Related to Long-Term Memory.

PubMed

Freytag, Virginie; Probst, Sabine; Hadziselimovic, Nils; Boglari, Csaba; Hauser, Yannick; Peter, Fabian; Gabor Fenyves, Bank; Milnik, Annette; Demougin, Philippe; Vukojevic, Vanja; de Quervain, Dominique J-F; Papassotiropoulos, Andreas; Stetak, Attila

2017-07-12

The identification of genes related to encoding, storage, and retrieval of memories is a major interest in neuroscience. In the current study, we analyzed the temporal gene expression changes in a neuronal mRNA pool during an olfactory long-term associative memory (LTAM) in Caenorhabditis elegans hermaphrodites. Here, we identified a core set of 712 (538 upregulated and 174 downregulated) genes that follows three distinct temporal peaks demonstrating multiple gene regulation waves in LTAM. Compared with the previously published positive LTAM gene set (Lakhina et al., 2015), 50% of the identified upregulated genes here overlap with the previous dataset, possibly representing stimulus-independent memory-related genes. On the other hand, the remaining genes were not previously identified in positive associative memory and may specifically regulate aversive LTAM. Our results suggest a multistep gene activation process during the formation and retrieval of long-term memory and define general memory-implicated genes as well as conditioning-type-dependent gene sets. SIGNIFICANCE STATEMENT The identification of genes regulating different steps of memory is of major interest in neuroscience. Identification of common memory genes across different learning paradigms and the temporal activation of the genes are poorly studied. Here, we investigated the temporal aspects of Caenorhabditis elegans gene expression changes using aversive olfactory associative long-term memory (LTAM) and identified three major gene activation waves. Like in previous studies, aversive LTAM is also CREB dependent, and CREB activity is necessary immediately after training. Finally, we define a list of memory paradigm-independent core gene sets as well as conditioning-dependent genes. Copyright © 2017 the authors 0270-6474/17/376661-12$15.00/0.

Characterization of maspardin, responsible for human Mast syndrome, in an insect species and analysis of its evolution in metazoans

NASA Astrophysics Data System (ADS)

Chertemps, Thomas; Montagné, Nicolas; Bozzolan, Françoise; Maria, Annick; Durand, Nicolas; Maïbèche-Coisne, Martine

2012-07-01

Mast syndrome is a complicated form of human hereditary spastic paraplegias, caused by a mutation in the gene acid cluster protein 33, which encodes a protein designated as "maspardin." Maspardin presents similarity to the α/β-hydrolase superfamily, but might lack enzymatic activity and rather be involved in protein-protein interactions. Association with the vesicles of the endosomal network also suggested that maspardin may be involved in the sorting and/or trafficking of molecules in the endosomal pathway, a crucial process for maintenance of neuron health. Despite a high conservation in living organisms, studies of maspardin in other animal species than mammals were lacking. In the cotton armyworm Spodoptera littoralis, an insect pest model, analysis of an expressed sequence tag collection from antenna, the olfactory organ, has allowed identifying a maspardin homolog ( SlMasp). We have investigated SlMasp tissue distribution and temporal expression by PCR and in situ hybridization techniques. Noteworthy, we found that maspardin was highly expressed in antennae and associated with the structures specialized in odorant detection. We have, in addition, identified maspardin sequences in numerous "nonmammalian" species and described here their phylogenetic analysis in the context of metazoan diversity. We observed a strong conservation of maspardin in metazoans, with surprisingly two independent losses of this gene in two relatively distant ecdysozoan taxa that include major model organisms, i.e., dipterans and nematodes.

Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy

PubMed Central

Miller-Delaney, Suzanne F.C.; Bryan, Kenneth; Das, Sudipto; McKiernan, Ross C.; Bray, Isabella M.; Reynolds, James P.; Gwinn, Ryder; Stallings, Raymond L.

2015-01-01

Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to DNA are attractive mechanisms to explain the sustained hyperexcitability of chronic epilepsy. Here, through methylation analysis of all annotated C-phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of temporal lobe epilepsy with or without hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive non-coding RNA in human temporal lobe epilepsy. A total of 146 protein-coding genes exhibited altered DNA methylation in temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in temporal lobe epilepsy with or without hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild hippocampal sclerosis). In addition to genes associated with neuronal, neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in temporal lobe epilepsy, but overall few genes previously associated with epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive microRNA were identified in temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain. PMID:25552301

Coordination of Gene Expression of Arachidonic and Docosahexaenoic Acid Cascade Enzymes during Human Brain Development and Aging

PubMed Central

Ryan, Veronica H.; Primiani, Christopher T.; Rao, Jagadeesh S.; Ahn, Kwangmi; Rapoport, Stanley I.; Blanchard, Helene

2014-01-01

Background The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. Hypothesis AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. Methods The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Results Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Conclusions Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease. PMID:24963629

SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in pulmonary squamous cell carcinoma.

PubMed

Chang, Dong; Ma, Kai; Gong, Min; Cui, Yong; Liu, Zhi-hua; Zhou, Xiao-ge; Zhou, Chuan-nong; Wang, Tian-you

2010-03-01

To investigate the role of stomatin-like protein 2 (SLP-2), a novel cancer-related gene, in pulmonary squamous cell carcinoma (PSCC) and its implications. Immunohistochemical detection of SLP-2 was performed on 96 cases of PSCC with a tissue microarray. SLP-2 was overexpressed in lung cancer compared with normal lung tissue (p <0.001). High-level SLP-2 expression was significantly correlated with distant metastasis (p = 0.025), decreased overall survival (p = 0.018) and disease-free survival (p = 0.017). SLP-2 overexpression was an independent prognostic factor in multivariate analysis using the Cox regression model (p <0.05). SLP-2 overexpression is associated with tumour distant metastasis and poor prognosis in PSCC. SLP-2 could be regarded as a new significant prognostic biomarker for patients with PSCC.

Gene modules associated with breast cancer distant metastasis-free survival in the PAM50 molecular subtypes.

PubMed

Liu, Rong; Zhang, Wei; Liu, Zhao-Qian; Zhou, Hong-Hao

2016-04-19

To identify PAM50 subtype-specific associations between distant metastasis-free survival (DMFS) in breast cancer (BC) patients and gene modules describing potentially targetable oncogenic pathways, a comprehensive analysis evaluating the prognostic efficacy of published gene signatures in 2027 BC patients from 13 studies was conducted. We calculated 21 gene modules and computed hazard ratios (HRs) for DMFS for one-unit increases in module score, with and without adjustment for clinical characteristics. By comparing gene expression to survival outcomes, we derived four subtype-specific prognostic signatures for BC. Univariate and multivariate analyses showed that in the luminal A subgroup, E2F3, PTEN and GGI gene module scores were associated with clinical outcome. In the luminal B tumors, RAS was associated with DMFS and in the basal-like tumors, ER was associated with DMFS. Our defined gene modules predicted high-risk patients in multivariate analyses for the basal-like (HR: 2.19, p=2.5×10-4), luminal A (HR: 3.03, p=7.2×10-5), luminal B (HR: 3.00, p=2.4×10-10) and HER2+ (HR: 5.49, p=9.7×10-10) subgroups. We found that different modules are associated with DMFS in different BC subtypes. The results of this study could help to identify new therapeutic strategies for specific molecular subgroups of BC, and could enhance efforts to improve patient-specific therapy options.

A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors.

PubMed

Filipits, Martin; Rudas, Margaretha; Jakesz, Raimund; Dubsky, Peter; Fitzal, Florian; Singer, Christian F; Dietze, Otto; Greil, Richard; Jelen, Andrea; Sevelda, Paul; Freibauer, Christa; Müller, Volkmar; Jänicke, Fritz; Schmidt, Marcus; Kölbl, Heinz; Rody, Achim; Kaufmann, Manfred; Schroth, Werner; Brauch, Hiltrud; Schwab, Matthias; Fritz, Peter; Weber, Karsten E; Feder, Inke S; Hennig, Guido; Kronenwett, Ralf; Gehrmann, Mathias; Gnant, Michael

2011-09-15

According to current guidelines, molecular tests predicting the outcome of breast cancer patients can be used to assist in making treatment decisions after consideration of conventional markers. We developed and validated a gene expression signature predicting the likelihood of distant recurrence in patients with estrogen receptor (ER)-positive, HER2-negative breast cancer treated with adjuvant endocrine therapy. RNA levels assessed by quantitative reverse transcriptase PCR in formalin-fixed, paraffin-embedded tumor tissue were used to calculate a risk score (Endopredict, EP) consisting of eight cancer-related and three reference genes. EP was combined with nodal status and tumor size into a comprehensive risk score, EPclin. Both prespecified risk scores including cutoff values to determine a risk group for each patient (low and high) were validated independently in patients from two large randomized phase III trials [Austrian Breast and Colorectal Cancer Study Group (ABCSG)-6: n = 378, ABCSG-8: n = 1,324]. In both validation cohorts, continuous EP was an independent predictor of distant recurrence in multivariate analysis (ABCSG-6: P = 0.010, ABCSG-8: P < 0.001). Combining Adjuvant!Online, quantitative ER, Ki67, and treatment with EP yielded a prognostic power significantly superior to the clinicopathologic factors alone [c-indices: 0.764 vs. 0.750, P = 0.024 (ABCSG-6) and 0.726 vs. 0.701, P = 0.003 (ABCSG-8)]. EPclin had c-indices of 0.788 and 0.732 and resulted in 10-year distant recurrence rates of 4% and 4% in EPclin low-risk and 28% and 22% in EPclin high-risk patients in ABCSG-6 (P < 0.001) and ABCSG-8 (P < 0.001), respectively. The multigene EP risk score provided additional prognostic information to the risk of distant recurrence of breast cancer patients, independent from clinicopathologic parameters. The EPclin score outperformed all conventional clinicopathologic risk factors. ©2011 AACR.

Breast Carcinoma with Oncotype DX Recurrence Score Lower Than 18: Rate of Distant Metastases in a Large Series with Clinical Follow-Up

PubMed Central

Wen, Hannah Y; Krystel-Whittemore, Melissa; Patil, Sujata; Pareja, Fresia; Bowser, Zenica L; Dickler, Maura N.; Norton, Larry; Morrow, Monica; Hudis, Clifford A.; Brogi, Edi

2016-01-01

Backgrounds A 21-gene expression assay (Oncotype DX™ Recurrence Score (“RS”)) that utilizes RT-PCR is used clinically in early-stage estrogen receptor-positive, HER2-negative breast carcinoma (ER+/HER2− BC) to determine both prognosis with tamoxifen therapy and the utility of adding adjuvant chemotherapy. Use of the assay is associated with reductions in overall chemotherapy usage. This study examined the treatments and outcomes in patients with low recurrence scores. Methods We reviewed the institutional database to identify patients with node-negative, ER+/HER2− BC and the 21-gene recurrence score results treated at our center between September 2008 and August 2013. Results We identified 1406 consecutive patients with node-negative ER+/HER2− BC and low RS [RS 0–10: n=510; RS 11–17: n=896]. The median age at BC diagnosis was 56 years; 63 (4%) patients were younger than 40 years. Overall, 1361 (97%) of patients received endocrine therapy and 170 (12%) received chemotherapy. The median follow-up time was 46 months. Six patients (0.4%) developed distant metastases (one patient with RS = 5, and five with RS of 11–17). In the RS 11–17 cohort, the absolute rate of distant metastasis among patients <40 years old was 7.1% (3/42), versus 0.2% (2/854) among patients ≥40 years. Conclusions Our data document a 0.4% rate of distant metastasis within 5 years of BC diagnosis among patients with node-negative ER+/HER2− BC of RS<18. Patients younger than 40 years at BC diagnosis were observed to have a higher rate of distant metastases. Analysis of data from other studies is necessary to further validate this observation. PMID:27526056

A High-Resolution Enhancer Atlas of the Developing Telencephalon

PubMed Central

Visel, Axel; Taher, Leila; Girgis, Hani; May, Dalit; Golonzhka, Olga; Hoch, Renee; McKinsey, Gabriel L.; Pattabiraman, Kartik; Silberberg, Shanni N.; Blow, Matthew J.; Hansen, David V.; Nord, Alex S.; Akiyama, Jennifer A.; Holt, Amy; Hosseini, Roya; Phouanenavong, Sengthavy; Plajzer-Frick, Ingrid; Shoukry, Malak; Afzal, Veena; Kaplan, Tommy; Kriegstein, Arnold R.; Rubin, Edward M.; Ovcharenko, Ivan; Pennacchio, Len A.; Rubenstein, John L. R.

2013-01-01

Summary The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. While many of the genes required for its development have been identified, the distant-acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified over 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web-based data collection comprising over 32,000 sections. We also used epigenomic analysis of human and mouse cortex tissue to directly compare the genome-wide enhancer architecture in these species. These data provide a primary resource for investigating gene regulatory mechanisms of telencephalon development and enable studies of the role of distant-acting enhancers in neurodevelopmental disorders. PMID:23375746

Recognition and identification of famous faces in patients with unilateral temporal lobe epilepsy.

PubMed

Seidenberg, Michael; Griffith, Randall; Sabsevitz, David; Moran, Maria; Haltiner, Alan; Bell, Brian; Swanson, Sara; Hammeke, Thomas; Hermann, Bruce

2002-01-01

We examined the performance of 21 patients with unilateral temporal lobe epilepsy (TLE) and hippocampal damage (10 lefts, and 11 rights) and 10 age-matched controls on the recognition and identification (name and occupation) of well-known faces. Famous face stimuli were selected from four time periods; 1970s, 1980s, 1990-1994, and 1995-1996. Differential patterns of performance were observed for the left and right TLE group across distinct face processing components. The left TLE group showed a selective impairment in naming famous faces while they performed similar to the controls in face recognition and semantic identification (i.e. occupation). In contrast, the right TLE group was impaired across all components of face memory; face recognition, semantic identification, and face naming. Face naming impairment in the left TLE group was characterized by a temporal gradient with better naming performance for famous faces from more distant time periods. Findings are discussed in terms of the role of the temporal lobe system for the acquisition, retention, and retrieval of face semantic networks, and the differential effects of lateralized temporal lobe lesions in this process.

Regional and temporal differences in gene expression of LH(BETA)T(AG) retinoblastoma tumors.

PubMed

Houston, Samuel K; Pina, Yolanda; Clarke, Jennifer; Koru-Sengul, Tulay; Scott, William K; Nathanson, Lubov; Schefler, Amy C; Murray, Timothy G

2011-07-23

The purpose of this study was to evaluate by microarray the hypothesis that LH(BETA)T(AG) retinoblastoma tumors exhibit regional and temporal variations in gene expression. LH(BETA)T(AG) mice aged 12, 16, and 20 weeks were euthanatized (n = 9). Specimens were taken from five tumor areas (apex, anterior lateral, center, base, and posterior lateral). Samples were hybridized to gene microarrays. The data were preprocessed and analyzed, and genes with a P < 0.01, according to the ANOVA models, and a log(2)-fold change >2.5 were considered to be differentially expressed. Differentially expressed genes were analyzed for overlap with known networks by using pathway analysis tools. There were significant temporal (P < 10(-8)) and regional differences in gene expression for LH(BETA)T(AG) retinoblastoma tumors. At P < 0.01 and log(2)-fold change >2.5, there were significant changes in gene expression of 190 genes apically, 84 genes anterolaterally, 126 genes posteriorly, 56 genes centrally, and 134 genes at the base. Differentially expressed genes overlapped with known networks, with significant involvement in regulation of cellular proliferation and growth, response to oxygen levels and hypoxia, regulation of cellular processes, cellular signaling cascades, and angiogenesis. There are significant temporal and regional variations in the LH(BETA)T(AG) retinoblastoma model. Differentially expressed genes overlap with key pathways that may play pivotal roles in murine retinoblastoma development. These findings suggest the mechanisms involved in tumor growth and progression in murine retinoblastoma tumors and identify pathways for analysis at a functional level, to determine significance in human retinoblastoma. Microarray analysis of LH(BETA)T(AG) retinal tumors showed significant regional and temporal variations in gene expression, including dysregulation of genes involved in hypoxic responses and angiogenesis.

The Ties that Bind (the Igh Locus).

PubMed

Krangel, Michael S

2016-05-01

Immunoglobulin heavy-chain locus V(D)J recombination requires a 3D chromatin organization which permits widely distributed variable (V) gene segments to contact distant diversity (D) and joining (J) gene segments. A recent study has identified key nodes in the locus interactome, paving the way for new molecular insights into how the locus is configured for recombination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulation of Chlamydia Gene Expression by Tandem Promoters with Different Temporal Patterns.

PubMed

Rosario, Christopher J; Tan, Ming

2016-01-15

Chlamydia is a genus of pathogenic bacteria with an unusual intracellular developmental cycle marked by temporal waves of gene expression. The three main temporal groups of chlamydial genes are proposed to be controlled by separate mechanisms of transcriptional regulation. However, we have noted genes with discrepancies, such as the early gene dnaK and the midcycle genes bioY and pgk, which have promoters controlled by the late transcriptional regulators EUO and σ(28). To resolve this issue, we analyzed the promoters of these three genes in vitro and in Chlamydia trachomatis bacteria grown in cell culture. Transcripts from the σ(28)-dependent promoter of each gene were detected only at late times in the intracellular infection, bolstering the role of σ(28) RNA polymerase in late gene expression. In each case, however, expression prior to late times was due to a second promoter that was transcribed by σ(66) RNA polymerase, which is the major form of chlamydial polymerase. These results demonstrate that chlamydial genes can be transcribed from tandem promoters with different temporal profiles, leading to a composite expression pattern that differs from the expression profile of a single promoter. In addition, tandem promoters allow a gene to be regulated by multiple mechanisms of transcriptional regulation, such as DNA supercoiling or late regulation by EUO and σ(28). We discuss how tandem promoters broaden the repertoire of temporal gene expression patterns in the chlamydial developmental cycle and can be used to fine-tune the expression of specific genes. Chlamydia is a pathogenic bacterium that is responsible for the majority of infectious disease cases reported to the CDC each year. It causes an intracellular infection that is characterized by coordinated expression of chlamydial genes in temporal waves. Chlamydial transcription has been shown to be regulated by DNA supercoiling, alternative forms of RNA polymerase, and transcription factors, but the number of transcription factors found in Chlamydia is far fewer than the number found in most bacteria. This report describes the use of tandem promoters that allow the temporal expression of a gene or operon to be controlled by more than one regulatory mechanism. This combinatorial strategy expands the range of expression patterns that are available to regulate chlamydial genes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Conditional clustering of temporal expression profiles

PubMed Central

Wang, Ling; Montano, Monty; Rarick, Matt; Sebastiani, Paola

2008-01-01

Background Many microarray experiments produce temporal profiles in different biological conditions but common cluster techniques are not able to analyze the data conditional on the biological conditions. Results This article presents a novel technique to cluster data from time course microarray experiments performed across several experimental conditions. Our algorithm uses polynomial models to describe the gene expression patterns over time, a full Bayesian approach with proper conjugate priors to make the algorithm invariant to linear transformations, and an iterative procedure to identify genes that have a common temporal expression profile across two or more experimental conditions, and genes that have a unique temporal profile in a specific condition. Conclusion We use simulated data to evaluate the effectiveness of this new algorithm in finding the correct number of clusters and in identifying genes with common and unique profiles. We also use the algorithm to characterize the response of human T cells to stimulations of antigen-receptor signaling gene expression temporal profiles measured in six different biological conditions and we identify common and unique genes. These studies suggest that the methodology proposed here is useful in identifying and distinguishing uniquely stimulated genes from commonly stimulated genes in response to variable stimuli. Software for using this clustering method is available from the project home page. PMID:18334028

CYP2D6 gene polymorphisms in Brazilian patients with breast cancer treated with adjuvant tamoxifen and its association with disease recurrence

PubMed Central

De Ameida Melo, Mariella; De Vasconcelos-Valença, Rodrigo José; Neto, Fidelis Manes; Borges, Rafael Soares; Costa-Silva, Danylo Rafhael; Da Conceição Barros-Oliveira, Maria; Borges, Umbelina Soares; Alencar, Airlane Pereira; Silva, Vladimir Costa; Da Silva, Benedito Borges

2016-01-01

At present, there is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms, in terms of recurrence and overall survival. Thus, the aim of the present study was to investigate the association of the CYP2D6 *4, *10 and *17 gene polymorphisms with breast cancer recurrence in a Brazilian population. The cohort comprised 40 receptor-positive breast cancer patients without recurrence and 40 with distant recurrence. A 3-ml sample of peripheral blood was collected from each patient to determine the presence of the *4, *10 and *17 single nucleotide polymorphisms of the CYP2D6 gene by quantitative polymerase chain reaction analysis. There was no statistically significant difference between the two groups regarding the polymorphism frequency (P=0.246). The results revealed that intermediate metabolizers occurred in 5% of patients without recurrence and in 15% of those with distant recurrence. Poor metabolizers occurred in only 1 patient (2.5%) per group, and there was no significant difference between the groups (P=0.789). The present study concluded that the CYP2D6 gene polymorphism in women with hormone-sensitive breast cancer treated with tamoxifen was not associated with disease recurrence. PMID:27882219

Horizontal acquisition of toxic alkaloid synthesis in a clade of plant associated fungi.

PubMed

Marcet-Houben, Marina; Gabaldón, Toni

2016-01-01

Clavicipitaceae is a fungal group that comprises species that closely interact with plants as pathogens, parasites or symbionts. A key factor in these interactions is the ability of these fungi to synthesize toxic alkaloid compounds that contribute to the protection of the plant host against herbivores. Some of these compounds such as ergot alkaloids are toxic to humans and have caused important epidemics throughout history. The gene clusters encoding the proteins responsible for the synthesis of ergot alkaloids and lolines in Clavicipitaceae have been elucidated. Notably, homologs to these gene clusters can be found in distantly related species such as Aspergillus fumigatus and Penicillium expansum, which diverged from Clavicipitaceae more than 400 million years ago. We here use a phylogenetic approach to analyze the evolution of these gene clusters. We found that the gene clusters conferring the ability to synthesize ergot alkaloids and loline emerged first in Eurotiomycetes and were then likely transferred horizontally to Clavicipitaceae. Horizontal gene transfer is known to play a role in shaping the distribution of secondary metabolism clusters across distantly related fungal species. We propose that HGT events have played an important role in the capability of Clavicipitaceae to produce two key secondary metabolites that have enhanced the ability of these species to protect their plant hosts, therefore favoring their interactions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

High prevalence of non-clonal imipenem-nonsusceptible Enterobacter spp. isolates in Korea and their association with porin down-regulation.

PubMed

Lee, Ji-Young; Hong, Yoon-Kyoung; Lee, Haejeong; Ko, Kwan Soo

2017-01-01

We investigated the prevalence and clonal distribution of imipenem-nonsusceptible Enterobacter clinical isolates from hospitals in Korea and the contributions of various mechanisms to imipenem nonsusceptibility. The in vitro antimicrobial susceptibility to imipenem of 357 non-duplicated Enterobacter isolates obtained from eight geographically distant tertiary care hospitals in Korea was evaluated. Imipenem-nonsusceptible Enterobacter isolates were genotyped. Additionally, β-lactamase genes were screened using PCR, and the expression of efflux pump and porin genes was investigated using quantitative RT-PCR. A total of 31 isolates (8.7%) were not susceptible to imipenem. Clonal diversity of 17 imipenem-nonsusceptible E. cloacae isolates was demonstrated by multilocus sequence typing. Fourteen imipenem-nonsusceptible E. aerogenes isolates were found to be distantly genetically related by an ERIC-PCR analysis. Expression levels of porin ompD and ompK35 genes were decreased in all imipenem-nonsusceptible E. cloacae and E. aerogenes isolates. However, only two isolates were found positive for bla IMP and bla VIM genes, and expression of the efflux pump gene, acrB, was not associated with reduced imipenem susceptibility. Imipenem resistance seems to have occurred independently in most of the imipenem-nonsusceptible isolates in this study, and decreased porin expression was found to be the main mechanism underlying this reduced susceptibility to imipenem. Copyright © 2016 Elsevier Inc. All rights reserved.

NF-κB-Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis.

PubMed

Rodrigues, Paulo; Patel, Saroor A; Harewood, Louise; Olan, Ioana; Vojtasova, Erika; Syafruddin, Saiful E; Zaini, M Nazhif; Richardson, Emma K; Burge, Johanna; Warren, Anne Y; Stewart, Grant D; Saeb-Parsy, Kourosh; Samarajiwa, Shamith A; Vanharanta, Sakari

2018-06-06

Metastases, the spread of cancer cells to distant organs, cause the majority of cancer-related deaths. Few metastasis-specific driver mutations have been identified, suggesting aberrant gene regulation as a source of metastatic traits. However, how metastatic gene expression programs arise is poorly understood. Here, using human-derived metastasis models of renal cancer, we identify transcriptional enhancers that promote metastatic carcinoma progression. Specific enhancers and enhancer clusters are activated in metastatic cancer cell populations, and the associated gene expression patterns are predictive of poor patient outcome in clinical samples. We find that the renal cancer metastasis-associated enhancer complement consists of multiple coactivated tissue-specific enhancer modules. Specifically, we identify and functionally characterize a coregulatory enhancer cluster, activated by the renal cancer driver HIF2A and an NF-κB-driven lymphoid element, as a mediator of metastasis in vivo We conclude that oncogenic pathways can acquire metastatic phenotypes through cross-lineage co-option of physiologic epigenetic enhancer states. SIGNIFICANCE: Renal cancer is associated with significant mortality due to metastasis. We show that in metastatic renal cancer, functionally important metastasis genes are activated via co-option of gene regulatory enhancer modules from distant developmental lineages, thus providing clues to the origins of metastatic cancer. Cancer Discov; 8(7); 1-16. ©2018 AACR. ©2018 American Association for Cancer Research.

Gene length as a biological timer to establish temporal transcriptional regulation

PubMed Central

Kirkconnell, Killeen S.; Magnuson, Brian; Paulsen, Michelle T.; Lu, Brian; Bedi, Karan; Ljungman, Mats

2017-01-01

ABSTRACT Transcriptional timing is inherently influenced by gene length, thus providing a mechanism for temporal regulation of gene expression. While gene size has been shown to be important for the expression timing of specific genes during early development, whether it plays a role in the timing of other global gene expression programs has not been extensively explored. Here, we investigate the role of gene length during the early transcriptional response of human fibroblasts to serum stimulation. Using the nascent sequencing techniques Bru-seq and BruUV-seq, we identified immediate genome-wide transcriptional changes following serum stimulation that were linked to rapid activation of enhancer elements. We identified 873 significantly induced and 209 significantly repressed genes. Variations in gene size allowed for a large group of genes to be simultaneously activated but produce full-length RNAs at different times. The median length of the group of serum-induced genes was significantly larger than the median length of all expressed genes, housekeeping genes, and serum-repressed genes. These gene length relationships were also observed in corresponding mouse orthologs, suggesting that relative gene size is evolutionarily conserved. The sizes of transcription factor and microRNA genes immediately induced after serum stimulation varied dramatically, setting up a cascade mechanism for temporal expression arising from a single activation event. The retention and expansion of large intronic sequences during evolution have likely played important roles in fine-tuning the temporal expression of target genes in various cellular response programs. PMID:28055303

Methods of Combinatorial Optimization to Reveal Factors Affecting Gene Length

PubMed Central

Bolshoy, Alexander; Tatarinova, Tatiana

2012-01-01

In this paper we present a novel method for genome ranking according to gene lengths. The main outcomes described in this paper are the following: the formulation of the genome ranking problem, presentation of relevant approaches to solve it, and the demonstration of preliminary results from prokaryotic genomes ordering. Using a subset of prokaryotic genomes, we attempted to uncover factors affecting gene length. We have demonstrated that hyperthermophilic species have shorter genes as compared with mesophilic organisms, which probably means that environmental factors affect gene length. Moreover, these preliminary results show that environmental factors group together in ranking evolutionary distant species. PMID:23300345

Destruction of a distal hypoxia response element abolishes trans-activation of the PAG1 gene mediated by HIF-independent chromatin looping.

PubMed

Schörg, Alexandra; Santambrogio, Sara; Platt, James L; Schödel, Johannes; Lindenmeyer, Maja T; Cohen, Clemens D; Schrödter, Katrin; Mole, David R; Wenger, Roland H; Hoogewijs, David

2015-07-13

A crucial step in the cellular adaptation to oxygen deficiency is the binding of hypoxia-inducible factors (HIFs) to hypoxia response elements (HREs) of oxygen-regulated genes. Genome-wide HIF-1α/2α/β DNA-binding studies revealed that the majority of HREs reside distant to the promoter regions, but the function of these distal HREs has only been marginally studied in the genomic context. We used chromatin immunoprecipitation (ChIP), gene editing (TALEN) and chromosome conformation capture (3C) to localize and functionally characterize a 82 kb upstream HRE that solely drives oxygen-regulated expression of the newly identified HIF target gene PAG1. PAG1, a transmembrane adaptor protein involved in Src signalling, was hypoxically induced in various cell lines and mouse tissues. ChIP and reporter gene assays demonstrated that the -82 kb HRE regulates PAG1, but not an equally distant gene further upstream, by direct interaction with HIF. Ablation of the consensus HRE motif abolished the hypoxic induction of PAG1 but not general oxygen signalling. 3C assays revealed that the -82 kb HRE physically associates with the PAG1 promoter region, independent of HIF-DNA interaction. These results demonstrate a constitutive interaction between the -82 kb HRE and the PAG1 promoter, suggesting a physiologically important rapid response to hypoxia. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

[The evolution of heat shock genes and expression patterns of heat shock proteins in the species from temperature contrasting habitats].

PubMed

Garbuz, D G; Evgen’ev, M B

2017-01-01

Heat shock genes are the most evolutionarily ancient among the systems responsible for adaptation of organisms to a harsh environment. The encoded proteins (heat shock proteins, Hsps) represent the most important factors of adaptation to adverse environmental conditions. They serve as molecular chaperones, providing protein folding and preventing aggregation of damaged cellular proteins. Structural analysis of the heat shock genes in individuals from both phylogenetically close and very distant taxa made it possible to reveal the basic trends of the heat shock gene organization in the context of adaptation to extreme conditions. Using different model objects and nonmodel species from natural populations, it was demonstrated that modulation of the Hsps expression during adaptation to different environmental conditions could be achieved by changing the number and structural organization of heat shock genes in the genome, as well as the structure of their promoters. It was demonstrated that thermotolerant species were usually characterized by elevated levels of Hsps under normal temperature or by the increase in the synthesis of these proteins in response to heat shock. Analysis of the heat shock genes in phylogenetically distant organisms is of great interest because, on one hand, it contributes to the understanding of the molecular mechanisms of evolution of adaptogenes and, on the other hand, sheds the light on the role of different Hsps families in the development of thermotolerance and the resistance to other stress factors.

What model organisms and interactomics can reveal about the genetics of human obesity.

PubMed

Williams, Michael J; Almén, Markus S; Fredriksson, Robert; Schiöth, Helgi B

2012-11-01

Genome-wide association studies have identified a number of genes associated with human body weight. While some of these genes are large fields within obesity research, such as MC4R, POMC, FTO and BDNF, the majority do not have a clearly defined functional role explaining why they may affect body weight. Here, we searched biological databases and discovered 33 additional genes associated with human obesity (CADM2, GIPR, GPCR5B, LRP1B, NEGR1, NRXN3, SH2B1, FANCL, GNPDA2, HMGCR, MAP2K5, NUDT3, PRKD1, QPCTL, TNNI3K, MTCH2, DNAJC27, SLC39A8, MTIF3, RPL27A, SEC16B, ETV5, HMGA1, TFAP2B, TUB, ZNF608, FAIM2, KCTD15, LINGO2, POC5, PTBP2, TMEM18, TMEM160). We find that the majority have orthologues in distant species, such as D. melanogaster and C. elegans, suggesting that they are important for the biology of most bilateral species. Intriguingly, signalling cascade genes and transcription factors are enriched among these obesity genes, and several of the genes show properties that could be useful for potential drug discovery. In this review, we demonstrate how information from several distant model species, interactomics and signalling pathway analysis represents an important way to better understand the functional diversity of the surprisingly high number of molecules that seem to be important for human obesity.

Coevolution of antibiotic production and counter-resistance in soil bacteria.

PubMed

Laskaris, Paris; Tolba, Sahar; Calvo-Bado, Leo; Wellington, Elizabeth M; Wellington, Liz

2010-03-01

We present evidence for the coexistence and coevolution of antibiotic resistance and biosynthesis genes in soil bacteria. The distribution of the streptomycin (strA) and viomycin (vph) resistance genes was examined in Streptomyces isolates. strA and vph were found either within a biosynthetic gene cluster or independently. Streptomyces griseus strains possessing the streptomycin cluster formed part of a clonal complex. All S. griseus strains possessing solely strA belonged to two clades; both were closely related to the streptomycin producers. Other more distantly related S. griseus strains did not contain strA. S. griseus strains with only vph also formed two clades, but they were more distantly related to the producers and to one another. The expression of the strA gene was constitutive in a resistance-only strain whereas streptomycin producers showed peak strA expression in late log phase that correlates with the switch on of streptomycin biosynthesis. While there is evidence that antibiotics have diverse roles in nature, our data clearly support the coevolution of resistance in the presence of antibiotic biosynthetic capability within closely related soil dwelling bacteria. This reinforces the view that, for some antibiotics at least, the primary role is one of antibiosis during competition in soil for resources.

Evolution of patchily distributed proteins shared between eukaryotes and prokaryotes: Dictyostelium as a case study.

PubMed

Andersson, Jan O

2011-04-01

Protein families are often patchily distributed in the tree of life; they are present in distantly related organisms, but absent in more closely related lineages. This could either be the result of lateral gene transfer between ancestors of organisms that encode them, or losses in the lineages that lack them. Here a novel approach is developed to study the evolution of patchily distributed proteins shared between prokaryotes and eukaryotes. Proteins encoded in the genome of cellular slime mold Dictyostelium discoideum and a restricted number of other lineages, including at least one prokaryote, were identified. Analyses of the phylogenetic distribution of 49 such patchily distributed protein families showed conflicts with organismal phylogenies; 25 are shared with the distantly related amoeboflagellate Naegleria (Excavata), whereas only two are present in the more closely related Entamoeba. Most protein families show unexpected topologies in phylogenetic analyses; eukaryotes are polyphyletic in 85% of the trees. These observations suggest that gene transfers have been an important mechanism for the distribution of patchily distributed proteins across all domains of life. Further studies of this exchangeable gene fraction are needed for a better understanding of the origin and evolution of eukaryotic genes and the diversification process of eukaryotes. Copyright © 2011 S. Karger AG, Basel.

Increased Brahma-related Gene 1 Expression Predicts Distant Metastasis and Shorter Survival in Patients with Invasive Ductal Carcinoma of the Breast.

PubMed

Do, Sung-Im; Yoon, Gun; Kim, Hyun-Soo; Kim, Kyungeun; Lee, Hyunjoo; Do, In-Gu; Kim, Dong-Hoon; Chae, Seoung Wan; Sohn, Jin Hee

2016-09-01

Previous studies have demonstrated aberrant Brahma-related gene 1 (BRG1) expression in various tumor types. Increased BRG1 expression has recently been shown to correlate with aggressive oncogenic behavior in many different types of human cancer. However, the role of BRG1 in breast cancer development and progression is not fully understood. We evaluated BRG1 expression in 224 patients with invasive ductal carcinoma (IDC) of the breast using tissue microarray samples and immunohistochemistry. We also investigated whether BRG1 expression status is associated with clinicopathological characteristics and outcomes of patients with IDC. Among the 224 patients with IDC, 37.5% (84/224) exhibited high BRG1 expression. IDC exhibited significantly higher BRG1 expression compared to ductal carcinoma in situ (p=0.009) and normal breast tissue (p=0.005). High BRG1 expression in IDC significantly correlated with higher histological grade (p=0.035) and presence of distant metastasis (p=0.002). Furthermore, high BRG1 expression was an independent factor for predicting distant metastasis (relative risk=4.079; p=0.007). In addition, high BRG1 expression predicted shorter overall (p=0.011) and recurrence-free (p=0.003) survival in patients with IDC. In particular, BRG1 had a significant prognostic value in predicting recurrence-free survival of patients with IDC with lymph node metastasis or stage III disease. BRG1 is involved in the progression and metastasis of breast cancer and can serve as a novel biomarker predictive of distant metastasis and patient outcomes. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Inter-phylum HGT has shaped the metabolism of many mesophilic and anaerobic bacteria.

PubMed

Caro-Quintero, Alejandro; Konstantinidis, Konstantinos T

2015-03-17

Genome sequencing has revealed that horizontal gene transfer (HGT) is a major evolutionary process in bacteria. Although it is generally assumed that closely related organisms engage in genetic exchange more frequently than distantly related ones, the frequency of HGT among distantly related organisms and the effect of ecological relatedness on the frequency has not been rigorously assessed. Here, we devised a novel bioinformatic pipeline, which minimized the effect of over-representation of specific taxa in the available databases and other limitations of homology-based approaches by analyzing genomes in standardized triplets, to quantify gene exchange between bacterial genomes representing different phyla. Our analysis revealed the existence of networks of genetic exchange between organisms with overlapping ecological niches, with mesophilic anaerobic organisms showing the highest frequency of exchange and engaging in HGT twice as frequently as their aerobic counterparts. Examination of individual cases suggested that inter-phylum HGT is more pronounced than previously thought, affecting up to ∼ 16% of the total genes and ∼ 35% of the metabolic genes in some genomes (conservative estimation). In contrast, ribosomal and other universal protein-coding genes were subjected to HGT at least 150 times less frequently than genes encoding the most promiscuous metabolic functions (for example, various dehydrogenases and ABC transport systems), suggesting that the species tree based on the former genes may be reliable. These results indicated that the metabolic diversity of microbial communities within most habitats has been largely assembled from preexisting genetic diversity through HGT and that HGT accounts for the functional redundancy among phyla.

Bayesian median regression for temporal gene expression data

NASA Astrophysics Data System (ADS)

Yu, Keming; Vinciotti, Veronica; Liu, Xiaohui; 't Hoen, Peter A. C.

2007-09-01

Most of the existing methods for the identification of biologically interesting genes in a temporal expression profiling dataset do not fully exploit the temporal ordering in the dataset and are based on normality assumptions for the gene expression. In this paper, we introduce a Bayesian median regression model to detect genes whose temporal profile is significantly different across a number of biological conditions. The regression model is defined by a polynomial function where both time and condition effects as well as interactions between the two are included. MCMC-based inference returns the posterior distribution of the polynomial coefficients. From this a simple Bayes factor test is proposed to test for significance. The estimation of the median rather than the mean, and within a Bayesian framework, increases the robustness of the method compared to a Hotelling T2-test previously suggested. This is shown on simulated data and on muscular dystrophy gene expression data.

Temporal and Spatial Regulation of Gene Expression during Asexual Development of Neurospora crassa

USDA-ARS?s Scientific Manuscript database

In this study we profiled spatial and temporal transcriptional changes during asexual sporulation in the filamentous fungus Neurospora crassa. Aerial tissue was separated from the mycelium to allow detection of genes specific to each tissue. We identified 2641 genes that were differentially expresse...

A molecular study of microbe transfer between distant environments.

PubMed

Hooper, Sean D; Raes, Jeroen; Foerstner, Konrad U; Harrington, Eoghan D; Dalevi, Daniel; Bork, Peer

2008-07-09

Environments and their organic content are generally not static and isolated, but in a constant state of exchange and interaction with each other. Through physical or biological processes, organisms, especially microbes, may be transferred between environments whose characteristics may be quite different. The transferred microbes may not survive in their new environment, but their DNA will be deposited. In this study, we compare two environmental sequencing projects to find molecular evidence of transfer of microbes over vast geographical distances. By studying synonymous nucleotide composition, oligomer frequency and orthology between predicted genes in metagenomics data from two environments, terrestrial and aquatic, and by correlating with phylogenetic mappings, we find that both environments are likely to contain trace amounts of microbes which have been far removed from their original habitat. We also suggest a bias in direction from soil to sea, which is consistent with the cycles of planetary wind and water. Our findings support the Baas-Becking hypothesis formulated in 1934, which states that due to dispersion and population sizes, microbes are likely to be found in widely disparate environments. Furthermore, the availability of genetic material from distant environments is a possible font of novel gene functions for lateral gene transfer.

A Molecular Study of Microbe Transfer between Distant Environments

PubMed Central

Hooper, Sean D.; Raes, Jeroen; Foerstner, Konrad U.; Harrington, Eoghan D.; Dalevi, Daniel; Bork, Peer

2008-01-01

Background Environments and their organic content are generally not static and isolated, but in a constant state of exchange and interaction with each other. Through physical or biological processes, organisms, especially microbes, may be transferred between environments whose characteristics may be quite different. The transferred microbes may not survive in their new environment, but their DNA will be deposited. In this study, we compare two environmental sequencing projects to find molecular evidence of transfer of microbes over vast geographical distances. Methodology By studying synonymous nucleotide composition, oligomer frequency and orthology between predicted genes in metagenomics data from two environments, terrestrial and aquatic, and by correlating with phylogenetic mappings, we find that both environments are likely to contain trace amounts of microbes which have been far removed from their original habitat. We also suggest a bias in direction from soil to sea, which is consistent with the cycles of planetary wind and water. Conclusions Our findings support the Baas-Becking hypothesis formulated in 1934, which states that due to dispersion and population sizes, microbes are likely to be found in widely disparate environments. Furthermore, the availability of genetic material from distant environments is a possible font of novel gene functions for lateral gene transfer. PMID:18612393

Rapid and tunable method to temporally control gene editing based on conditional Cas9 stabilization. | Office of Cancer Genomics

Cancer.gov

The CRISPR/Cas9 system is a powerful tool for studying gene function. Here, we describe a method that allows temporal control of CRISPR/Cas9 activity based on conditional Cas9 destabilization. We demonstrate that fusing an FKBP12-derived destabilizing domain to Cas9 (DD-Cas9) enables conditional Cas9 expression and temporal control of gene editing in the presence of an FKBP12 synthetic ligand. This system can be easily adapted to co-express, from the same promoter, DD-Cas9 with any other gene of interest without co-modulation of the latter.

COI (cytochrome oxidase-I) sequence based studies of Carangid fishes from Kakinada coast, India.

PubMed

Persis, M; Chandra Sekhar Reddy, A; Rao, L M; Khedkar, G D; Ravinder, K; Nasruddin, K

2009-09-01

Mitochondrial DNA, cytochrome oxidase-1 gene sequences were analyzed for species identification and phylogenetic relationship among the very high food value and commercially important Indian carangid fish species. Sequence analysis of COI gene very clearly indicated that all the 28 fish species fell into five distinct groups, which are genetically distant from each other and exhibited identical phylogenetic reservation. All the COI gene sequences from 28 fishes provide sufficient phylogenetic information and evolutionary relationship to distinguish the carangid species unambiguously. This study proves the utility of mtDNA COI gene sequence based approach in identifying fish species at a faster pace.

A high-resolution enhancer atlas of the developing telencephalon.

PubMed

Visel, Axel; Taher, Leila; Girgis, Hani; May, Dalit; Golonzhka, Olga; Hoch, Renee V; McKinsey, Gabriel L; Pattabiraman, Kartik; Silberberg, Shanni N; Blow, Matthew J; Hansen, David V; Nord, Alex S; Akiyama, Jennifer A; Holt, Amy; Hosseini, Roya; Phouanenavong, Sengthavy; Plajzer-Frick, Ingrid; Shoukry, Malak; Afzal, Veena; Kaplan, Tommy; Kriegstein, Arnold R; Rubin, Edward M; Ovcharenko, Ivan; Pennacchio, Len A; Rubenstein, John L R

2013-02-14

The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. Though many of the genes required for its development have been identified, the distant-acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here, we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified more than 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web-based data collection comprising more than 32,000 sections. We also used epigenomic analysis of human and mouse cortex tissue to directly compare the genome-wide enhancer architecture in these species. These data provide a primary resource for investigating gene regulatory mechanisms of telencephalon development and enable studies of the role of distant-acting enhancers in neurodevelopmental disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Nucleosome-free DNA regions differentially affect distant communication in chromatin

PubMed Central

Nizovtseva, Ekaterina V.; Clauvelin, Nicolas; Todolli, Stefjord; Kulaeva, Olga I.; Wengrzynek, Scott

2017-01-01

Abstract Communication between distantly spaced genomic regions is one of the key features of gene regulation in eukaryotes. Chromatin per se can stimulate efficient enhancer-promoter communication (EPC); however, the role of chromatin structure and dynamics in this process remains poorly understood. Here we show that nucleosome spacing and the presence of nucleosome-free DNA regions can modulate chromatin structure/dynamics and, in turn, affect the rate of EPC in vitro and in silico. Increasing the length of internucleosomal linker DNA from 25 to 60 bp results in more efficient EPC. The presence of longer nucleosome-free DNA regions can positively or negatively affect the rate of EPC, depending upon the length and location of the DNA region within the chromatin fiber. Thus the presence of histone-free DNA regions can differentially affect the efficiency of EPC, suggesting that gene regulation over a distance could be modulated by changes in the length of internucleosomal DNA spacers. PMID:27940560

Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions: clinical experience and literature review.

PubMed

He, Jian; Chen, Xiancheng; Gan, Weidong; Zhu, Bin; Fan, Xiangshan; Guo, Hongqian; Jia, Ruipeng

2015-01-01

To analyze the clinicopathological features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 RCC) in our institution. We screened 983 RCC specimens. TFE3 immunohistochemical staining and FISH assay confirmed 22 Xp11.2 RCCs out of 65 suspicious cases. Clinicopathological and treatment outcomes of 22 patients were retrospectively analyzed. In total, 22 patients included 13 females and nine males with a mean age of 27 years. Ten patients showed gross hematuria. Treatments included surgeries, immunotherapy and molecular-targeted therapy. Seven cases were at stage III/IV and four cases had tumor thrombosis or distant metastasis. During a median follow-up of 34 months, 19 patients were alive while three died of distant metastasis. Xp11.2 RCC is rare and FISH proved a useful diagnostic tool. Surgical resection achieved favorable outcome for early disease. Adult patients at advanced stage had poorer outcomes even with postoperative adjuvant therapy.

Genomic characterization of a fructophilic bee symbiont Lactobacillus kunkeei reveals its niche-specific adaptation.

PubMed

Maeno, Shintaro; Tanizawa, Yasuhiro; Kanesaki, Yu; Kubota, Eri; Kumar, Himanshu; Dicks, Leon; Salminen, Seppo; Nakagawa, Junichi; Arita, Masanori; Endo, Akihito

2016-12-01

Lactobacillus kunkeei is classified as a sole obligate fructophilic lactic acid bacterium that is found in fructose-rich niches, including the guts of honeybees. The species is differentiated from other lactobacilli based on its poor growth with glucose, enhanced growth in the presence of oxygen and other electron acceptors, and production of high concentrations of acetate from the metabolism of glucose. These characteristics are similar to phylogenetically distant Fructobacillus spp. In the present study, the genomic structure of L. kunkeei was characterized by using 16 different strains, and it had significantly less genes and smaller genomes when compared with other lactobacilli. Functional gene classification revealed that L. kunkeei had lost genes specifically involved in carbohydrate transport and metabolism. The species also lacked most of the genes for respiration, although growth was enhanced in the presence of oxygen. The adhE gene of L. kunkeei, encoding a bifunctional alcohol dehydrogenase (ADH)/aldehyde dehydrogenase (ALDH) protein, lacked the part encoding the ADH domain, which is reported here for the first time in lactic acid bacteria. The deletion resulted in the lack of ADH activity, implying a requirement for electron acceptors in glucose assimilation. These results clearly indicated that L. kunkeei had undergone a specific reductive evolution in order to adapt to fructose-rich environments. The reduction characteristics were similar to those of Fructobacillus spp., but distinct from other lactobacilli with small genomes, such as Lactobacillus gasseri and Lactobacillus vaginalis. Fructose-richness thus induced an environment-specific gene reduction in phylogenetically distant microorganisms. Copyright © 2016 Elsevier GmbH. All rights reserved.

Encoding of Spatio-Temporal Input Characteristics by a CA1 Pyramidal Neuron Model

PubMed Central

Pissadaki, Eleftheria Kyriaki; Sidiropoulou, Kyriaki; Reczko, Martin; Poirazi, Panayiota

2010-01-01

The in vivo activity of CA1 pyramidal neurons alternates between regular spiking and bursting, but how these changes affect information processing remains unclear. Using a detailed CA1 pyramidal neuron model, we investigate how timing and spatial arrangement variations in synaptic inputs to the distal and proximal dendritic layers influence the information content of model responses. We find that the temporal delay between activation of the two layers acts as a switch between excitability modes: short delays induce bursting while long delays decrease firing. For long delays, the average firing frequency of the model response discriminates spatially clustered from diffused inputs to the distal dendritic tree. For short delays, the onset latency and inter-spike-interval succession of model responses can accurately classify input signals as temporally close or distant and spatially clustered or diffused across different stimulation protocols. These findings suggest that a CA1 pyramidal neuron may be capable of encoding and transmitting presynaptic spatiotemporal information about the activity of the entorhinal cortex-hippocampal network to higher brain regions via the selective use of either a temporal or a rate code. PMID:21187899

ENHANCED BETA-CATENIN EXPRESSION IS ASSOCIATED WITH THE RECURRENCE OF PAPILLARY THYROID CARCINOMA.

PubMed

Kordestani, Zeinab; Sanjari, Mojgan; Safavi, Moeinadin; Mashrouteh, Mahdieh; Asadikaram, Gholamreza; FekriSoofiAbadi, Maryam; Mirzazadeh, Ali

2018-03-02

A direct role of Catenin beta-1(βcat) in the proliferation of human thyroid tumor cells has been identified. This study aimed to determine if there is an association between βcat gene expression and the staging, recurrence, metastasis, and disease free survival of papillary thyroid cancer. A retrospective cohort study was conducted using data from available information in the medical records and paraffin blocks of 81 of 400 patients referred to the endocrine clinic over a 10-year period. Real-time polymerase chain reaction (PCR) was used to evaluate βcat gene expression. Disease-free survival was assessed using Kaplan-Meier method. The ten-year survival rate in these patients was 98.25% and disease-free survival was 48.1%. Cumulative dose of radioactive iodine that patients received was significantly and positively correlated with βcat gene expression (r = -0.2, p value=0.03).Also, in patients with recurrence, βcat gene expression was higher and statistically significant (5 fold increase p=0.002). Patients in more advanced stage and those with recurrence /distant metastasis had higher βcat gene expression .We found that the patients had a better survival (lower recurrence) if they had a lower βcat gene expression. (SD = 0.142-0.052) (Mantel-Cox test, P =0.002). We concluded that βcat gene expression was positively correlated with recurrence, distant metastasis and TNM stage. PTC = Papillary thyroid carcinoma; βcat = Catenin beta-1; FTC = Follicular thyroid cancer; TCF/LEF-1 = T-cell factor / lymphoid enhancer factor1; IHC = immunohistochemical; TG = Thyroglobulin; AUC = Area under the ROC curve; APC = Adenomatosis polyposis coli.

Automating gene library synthesis by structure-based combinatorial protein engineering: examples from plant sesquiterpene synthases.

PubMed

Dokarry, Melissa; Laurendon, Caroline; O'Maille, Paul E

2012-01-01

Structure-based combinatorial protein engineering (SCOPE) is a homology-independent recombination method to create multiple crossover gene libraries by assembling defined combinations of structural elements ranging from single mutations to domains of protein structure. SCOPE was originally inspired by DNA shuffling, which mimics recombination during meiosis, where mutations from parental genes are "shuffled" to create novel combinations in the resulting progeny. DNA shuffling utilizes sequence identity between parental genes to mediate template-switching events (the annealing and extension of one parental gene fragment on another) in PCR reassembly reactions to generate crossovers and hence recombination between parental genes. In light of the conservation of protein structure and degeneracy of sequence, SCOPE was developed to enable the "shuffling" of distantly related genes with no requirement for sequence identity. The central principle involves the use of oligonucleotides to encode for crossover regions to choreograph template-switching events during PCR assembly of gene fragments to create chimeric genes. This approach was initially developed to create libraries of hybrid DNA polymerases from distantly related parents, and later developed to create a combinatorial mutant library of sesquiterpene synthases to explore the catalytic landscapes underlying the functional divergence of related enzymes. This chapter presents a simplified protocol of SCOPE that can be integrated with different mutagenesis techniques and is suitable for automation by liquid-handling robots. Two examples are presented to illustrate the application of SCOPE to create gene libraries using plant sesquiterpene synthases as the model system. In the first example, we outline how to create an active-site library as a series of complex mixtures of diverse mutants. In the second example, we outline how to create a focused library as an array of individual clones to distil minimal combinations of functionally important mutations. Through these examples, the principles of the technique are illustrated and the suitability of automating various aspects of the procedure for given applications are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

PubMed

Mählmann, K; Hamza, E; Marti, E; Dolf, G; Klukowska, J; Gerber, V; Koch, C

2014-12-01

Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Origin of African Physacanthus (Acanthaceae) via wide hybridization.

PubMed

Tripp, Erin A; Fatimah, Siti; Darbyshire, Iain; McDade, Lucinda A

2013-01-01

Gene flow between closely related species is a frequent phenomenon that is known to play important roles in organismal evolution. Less clear, however, is the importance of hybridization between distant relatives. We present molecular and morphological evidence that support origin of the plant genus Physacanthus via "wide hybridization" between members of two distantly related lineages in the large family Acanthaceae. These two lineages are well characterized by very different morphologies yet, remarkably, Physacanthus shares features of both. Chloroplast sequences from six loci indicate that all three species of Physacanthus contain haplotypes from both lineages, suggesting that heteroplasmy likely predated speciation in the genus. Although heteroplasmy is thought to be unstable and thus transient, multiple haplotypes have been maintained through time in Physacanthus. The most likely scenario to explain these data is that Physacanthus originated via an ancient hybridization event that involved phylogenetically distant parents. This wide hybridization has resulted in the establishment of an independently evolving clade of flowering plants.

Origin of African Physacanthus (Acanthaceae) via Wide Hybridization

PubMed Central

Tripp, Erin A.; Fatimah, Siti; Darbyshire, Iain; McDade, Lucinda A.

2013-01-01

Gene flow between closely related species is a frequent phenomenon that is known to play important roles in organismal evolution. Less clear, however, is the importance of hybridization between distant relatives. We present molecular and morphological evidence that support origin of the plant genus Physacanthus via “wide hybridization” between members of two distantly related lineages in the large family Acanthaceae. These two lineages are well characterized by very different morphologies yet, remarkably, Physacanthus shares features of both. Chloroplast sequences from six loci indicate that all three species of Physacanthus contain haplotypes from both lineages, suggesting that heteroplasmy likely predated speciation in the genus. Although heteroplasmy is thought to be unstable and thus transient, multiple haplotypes have been maintained through time in Physacanthus. The most likely scenario to explain these data is that Physacanthus originated via an ancient hybridization event that involved phylogenetically distant parents. This wide hybridization has resulted in the establishment of an independently evolving clade of flowering plants. PMID:23383261

Temporal Changes Rather than Long-Term Repeated Burning Predominately Control the Shift in the Abundance of Soil Denitrifying Community in an Australian Sclerophyll Forest.

PubMed

Liu, Xian; Chen, C R; Hughes, J M; Wang, W J; Lewis, Tom

2017-01-01

To understand the temporal dynamics of soil bacterial denitrifying community in response to long-term prescribed burning and its resilience and recovery following a fire, a wet sclerophyll forest study site under two treatments (2 yearly burning (2YB) and no burning (NB)) and with 40-year-old burning history was used. Similar temporal patterns in the abundance of total (16S rRNA) and denitrifying (narG, nirK, nirS, nosZ) bacteria between two burning treatments revealed strong temporal influences. The magnitude of burning impacts on the abundance of 16S rRNA and denitrification genes was smaller compared with the impact of sampling time, but significant burning and temporal impacts were recorded for all (P < 0.001)-except for the nirS gene. Impacts of prescribed fire on the abundance of soil denitrifying community could be observed immediately after fire, and this impact diminished over a 24-month period prior to the next prescribed burning event. In conclusion, temporal changes govern the fluctuations of the abundance of soil denitrifying genes over the sampling period and the denitrifying community can recover after fire, suggesting that this community is resilient to the effects of prescribed burning. A combination of biotic and abiotic factors may account for the different temporal dynamics of denitrification gene abundance.

Comparative methods for the analysis of gene-expression evolution: an example using yeast functional genomic data.

PubMed

Oakley, Todd H; Gu, Zhenglong; Abouheif, Ehab; Patel, Nipam H; Li, Wen-Hsiung

2005-01-01

Understanding the evolution of gene function is a primary challenge of modern evolutionary biology. Despite an expanding database from genomic and developmental studies, we are lacking quantitative methods for analyzing the evolution of some important measures of gene function, such as gene-expression patterns. Here, we introduce phylogenetic comparative methods to compare different models of gene-expression evolution in a maximum-likelihood framework. We find that expression of duplicated genes has evolved according to a nonphylogenetic model, where closely related genes are no more likely than more distantly related genes to share common expression patterns. These results are consistent with previous studies that found rapid evolution of gene expression during the history of yeast. The comparative methods presented here are general enough to test a wide range of evolutionary hypotheses using genomic-scale data from any organism.

Object-location training elicits an overlapping but temporally distinct transcriptional profile from contextual fear conditioning.

PubMed

Poplawski, Shane G; Schoch, Hannah; Wimmer, Mathieu; Hawk, Joshua D; Walsh, Jennifer L; Giese, Karl P; Abel, Ted

2014-12-01

Hippocampus-dependent learning is known to induce changes in gene expression, but information on gene expression differences between different learning paradigms that require the hippocampus is limited. The bulk of studies investigating RNA expression after learning use the contextual fear conditioning task, which couples a novel environment with a footshock. Although contextual fear conditioning has been useful in discovering gene targets, gene expression after spatial memory tasks has received less attention. In this study, we used the object-location memory task and studied gene expression at two time points after learning in a high-throughput manner using a microfluidic qPCR approach. We found that expression of the classic immediate-early genes changes after object-location training in a fashion similar to that observed after contextual fear conditioning. However, the temporal dynamics of gene expression are different between the two tasks, with object-location memory producing gene expression changes that last at least 2 hours. Our findings indicate that different training paradigms may give rise to distinct temporal dynamics of gene expression after learning. Copyright © 2014 Elsevier Inc. All rights reserved.

Object-Location Training Elicits an Overlapping but Temporally Distinct Transcriptional Profile from Contextual Fear Conditioning

PubMed Central

Wimmer, Mathieu; Hawk, Joshua D.; Walsh, Jennifer L.; Giese, Karl P.; Abel, Ted

2014-01-01

Hippocampus-dependent learning is known to induce changes in gene expression, but information on gene expression differences between different learning paradigms that require the hippocampus is limited. The bulk of studies investigating RNA expression after learning use the contextual fear conditioning task, which couples a novel environment with a footshock. Although contextual fear conditioning has been useful in discovering gene targets, gene expression after spatial memory tasks has received less attention. In this study, we used the object-location memory task and studied gene expression at two time points after learning in a high-throughput manner using a microfluidic qPCR approach. We found that expression of the classic immediate-early genes changes after object-location training in a fashion similar to that observed after contextual fear conditioning. However, the temporal dynamics of gene expression are different between the two tasks, with object-location memory producing gene expression changes that last at least 2 hours. Our findings indicate that different training paradigms may give rise to distinct temporal dynamics of gene expression after learning. PMID:25242102

From the analysis of verbal data to the analysis of organizations: organizing as a dialogical process.

PubMed

Lorino, Philippe

2014-12-01

The analysis of conversational turn-taking and its implications on time (the speaker cannot completely anticipate the future effects of her/his speech) and sociality (the speech is co-produced by the various speakers rather than by the speaking individual) can provide a useful basis to analyze complex organizing processes and collective action: the actor cannot completely anticipate the future effects of her/his acts and the act is co-produced by multiple actors. This translation from verbal to broader classes of interaction stresses the performativity of speeches, the importance of the situation, the role of semiotic mediations to make temporally and spatially distant "ghosts" present in the dialog, and the dissymmetrical relationship between successive conversational turns, due to temporal irreversibility.

Conserved Noncoding Elements in the Most Distant Genera of Cephalochordates: The Goldilocks Principle

PubMed Central

Yue, Jia-Xing; Kozmikova, Iryna; Ono, Hiroki; Nossa, Carlos W.; Kozmik, Zbynek; Putnam, Nicholas H.; Yu, Jr-Kai; Holland, Linda Z.

2016-01-01

Cephalochordates, the sister group of vertebrates + tunicates, are evolving particularly slowly. Therefore, genome comparisons between two congeners of Branchiostoma revealed so many conserved noncoding elements (CNEs), that it was not clear how many are functional regulatory elements. To more effectively identify CNEs with potential regulatory functions, we compared noncoding sequences of genomes of the most phylogenetically distant cephalochordate genera, Asymmetron and Branchiostoma, which diverged approximately 120–160 million years ago. We found 113,070 noncoding elements conserved between the two species, amounting to 3.3% of the genome. The genomic distribution, target gene ontology, and enriched motifs of these CNEs all suggest that many of them are probably cis-regulatory elements. More than 90% of previously verified amphioxus regulatory elements were re-captured in this study. A search of the cephalochordate CNEs around 50 developmental genes in several vertebrate genomes revealed eight CNEs conserved between cephalochordates and vertebrates, indicating sequence conservation over >500 million years of divergence. The function of five CNEs was tested in reporter assays in zebrafish, and one was also tested in amphioxus. All five CNEs proved to be tissue-specific enhancers. Taken together, these findings indicate that even though Branchiostoma and Asymmetron are distantly related, as they are evolving slowly, comparisons between them are likely optimal for identifying most of their tissue-specific cis-regulatory elements laying the foundation for functional characterizations and a better understanding of the evolution of developmental regulation in cephalochordates. PMID:27412606

Hormone-dependent control of developmental timing through regulation of chromatin accessibility

PubMed Central

Uyehara, Christopher M.; Nystrom, Spencer L.; Niederhuber, Matthew J.; Leatham-Jensen, Mary; Ma, Yiqin; Buttitta, Laura A.

2017-01-01

Specification of tissue identity during development requires precise coordination of gene expression in both space and time. Spatially, master regulatory transcription factors are required to control tissue-specific gene expression programs. However, the mechanisms controlling how tissue-specific gene expression changes over time are less well understood. Here, we show that hormone-induced transcription factors control temporal gene expression by regulating the accessibility of DNA regulatory elements. Using the Drosophila wing, we demonstrate that temporal changes in gene expression are accompanied by genome-wide changes in chromatin accessibility at temporal-specific enhancers. We also uncover a temporal cascade of transcription factors following a pulse of the steroid hormone ecdysone such that different times in wing development can be defined by distinct combinations of hormone-induced transcription factors. Finally, we show that the ecdysone-induced transcription factor E93 controls temporal identity by directly regulating chromatin accessibility across the genome. Notably, we found that E93 controls enhancer activity through three different modalities, including promoting accessibility of late-acting enhancers and decreasing accessibility of early-acting enhancers. Together, this work supports a model in which an extrinsic signal triggers an intrinsic transcription factor cascade that drives development forward in time through regulation of chromatin accessibility. PMID:28536147

Identification of an intact ParaHox cluster with temporal colinearity but altered spatial colinearity in the hemichordate Ptychodera flava

PubMed Central

2013-01-01

Background ParaHox and Hox genes are thought to have evolved from a common ancestral ProtoHox cluster or from tandem duplication prior to the divergence of cnidarians and bilaterians. Similar to Hox clusters, chordate ParaHox genes including Gsx, Xlox, and Cdx, are clustered and their expression exhibits temporal and spatial colinearity. In non-chordate animals, however, studies on the genomic organization of ParaHox genes are limited to only a few animal taxa. Hemichordates, such as the Enteropneust acorn worms, have been used to gain insights into the origins of chordate characters. In this study, we investigated the genomic organization and expression of ParaHox genes in the indirect developing hemichordate acorn worm Ptychodera flava. Results We found that P. flava contains an intact ParaHox cluster with a similar arrangement to that of chordates. The temporal expression order of the P. flava ParaHox genes is the same as that of the chordate ParaHox genes. During embryogenesis, the spatial expression pattern of PfCdx in the posterior endoderm represents a conserved feature similar to the expression of its orthologs in other animals. On the other hand, PfXlox and PfGsx show a novel expression pattern in the blastopore. Nevertheless, during metamorphosis, PfXlox and PfCdx are expressed in the endoderm in a spatially staggered pattern similar to the situation in chordates. Conclusions Our study shows that P. flava ParaHox genes, despite forming an intact cluster, exhibit temporal colinearity but lose spatial colinearity during embryogenesis. During metamorphosis, partial spatial colinearity is retained in the transforming larva. These results strongly suggest that intact ParaHox gene clustering was retained in the deuterostome ancestor and is correlated with temporal colinearity. PMID:23802544

The genome of wine yeast Dekkera bruxellensis provides a tool to explore its food-related properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Piskur, Jure; Ling, Zhihao; Marcet-Houben, Marina

2012-03-14

The yeast Dekkera/Brettanomyces bruxellensis can cause enormous economic losses in wine industry due to production of phenolic off-flavor compounds. D. bruxellensis is a distant relative of baker's yeast Saccharomyces cerevisiae. Nevertheless, these two yeasts are often found in the same habitats and share several food-related traits, such as production of high ethanol levels and ability to grow without oxygen. In some food products, like lambic beer, D. bruxellensis can importantly contribute to flavor development. We determined the 13.4 Mb genome sequence of the D. bruxellensis strain Y879 (CBS2499) and deduced the genetic background of several ?food-relevant? properties and evolutionary historymore » of this yeast. Surprisingly, we find that this yeast is phylogenetically distant to other food-related yeasts and most related to Pichia (Komagataella) pastoris, which is an aerobic poor ethanol producer. We further show that the D. bruxellensis genome does not contain an excess of lineage specific duplicated genes nor a horizontally transferred URA1 gene, two crucial events that promoted the evolution of the food relevant traits in the S. cerevisiae lineage. However, D. bruxellensis has several independently duplicated ADH and ADH-like genes, which are likely responsible for metabolism of alcohols, including ethanol, and also a range of aromatic compounds.« less

Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma.

PubMed

Finocchiaro, L M E; Glikin, G C

2008-02-01

We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life.

Arm-specific dynamics of chromosome evolution in malaria mosquitoes

PubMed Central

2011-01-01

Background The malaria mosquito species of subgenus Cellia have rich inversion polymorphisms that correlate with environmental variables. Polymorphic inversions tend to cluster on the chromosomal arms 2R and 2L but not on X, 3R and 3L in Anopheles gambiae and homologous arms in other species. However, it is unknown whether polymorphic inversions on homologous chromosomal arms of distantly related species from subgenus Cellia nonrandomly share similar sets of genes. It is also unclear if the evolutionary breakage of inversion-poor chromosomal arms is under constraints. Results To gain a better understanding of the arm-specific differences in the rates of genome rearrangements, we compared gene orders and established syntenic relationships among Anopheles gambiae, Anopheles funestus, and Anopheles stephensi. We provided evidence that polymorphic inversions on the 2R arms in these three species nonrandomly captured similar sets of genes. This nonrandom distribution of genes was not only a result of preservation of ancestral gene order but also an outcome of extensive reshuffling of gene orders that created new combinations of homologous genes within independently originated polymorphic inversions. The statistical analysis of distribution of conserved gene orders demonstrated that the autosomal arms differ in their tolerance to generating evolutionary breakpoints. The fastest evolving 2R autosomal arm was enriched with gene blocks conserved between only a pair of species. In contrast, all identified syntenic blocks were preserved on the slowly evolving 3R arm of An. gambiae and on the homologous arms of An. funestus and An. stephensi. Conclusions Our results suggest that natural selection favors specific gene combinations within polymorphic inversions when distant species are exposed to similar environmental pressures. This knowledge could be useful for the discovery of genes responsible for an association of inversion polymorphisms with phenotypic variations in multiple species. Our data support the chromosomal arm specificity in rates of gene order disruption during mosquito evolution. We conclude that the distribution of breakpoint regions is evolutionary conserved on slowly evolving arms and tends to be lineage-specific on rapidly evolving arms. PMID:21473772

Temporal windows in visual processing: "prestimulus brain state" and "poststimulus phase reset" segregate visual transients on different temporal scales.

PubMed

Wutz, Andreas; Weisz, Nathan; Braun, Christoph; Melcher, David

2014-01-22

Dynamic vision requires both stability of the current perceptual representation and sensitivity to the accumulation of sensory evidence over time. Here we study the electrophysiological signatures of this intricate balance between temporal segregation and integration in vision. Within a forward masking paradigm with short and long stimulus onset asynchronies (SOA), we manipulated the temporal overlap of the visual persistence of two successive transients. Human observers enumerated the items presented in the second target display as a measure of the informational capacity read-out from this partly temporally integrated visual percept. We observed higher β-power immediately before mask display onset in incorrect trials, in which enumeration failed due to stronger integration of mask and target visual information. This effect was timescale specific, distinguishing between segregation and integration of visual transients that were distant in time (long SOA). Conversely, for short SOA trials, mask onset evoked a stronger visual response when mask and targets were correctly segregated in time. Examination of the target-related response profile revealed the importance of an evoked α-phase reset for the segregation of those rapid visual transients. Investigating this precise mapping of the temporal relationships of visual signals onto electrophysiological responses highlights how the stream of visual information is carved up into discrete temporal windows that mediate between segregated and integrated percepts. Fragmenting the stream of visual information provides a means to stabilize perceptual events within one instant in time.

Anthropological Contributions to the Search for Extraterrestrial Intelligence

NASA Astrophysics Data System (ADS)

Vakoch, D. A.

2009-12-01

Three recent annual conferences of the American Anthropological Association (AAA) have included symposia on the Search for Extraterrestrial Intelligence (SETI). This paper reviews these symposia, which dealt with themes associated with the overarching AAA conference themes for each year: in 2004, the SETI session addressed Anthropology, Archaeology, and Interstellar Communication: Science and the Knowledge of Distant Worlds; in 2005, it dealt with Historical Perspectives on Anthropology and SETI; and in 2006, the session examined Culture, Anthropology, and SETI. Among the topics considered in these symposia were analogues for contact with extraterrestrial intelligence (ETI), examining anthropologists’ experience in the field encountering other cultures-past and present. Similarly, the methodologies of archaeologists provide analogies for making contact with temporally distant civilizations, based on reconstructions from fragmentary information. Case studies helped make such analogies concrete in the symposia. The challenges of comprehending intelligences with different mental worlds was explored through a study of the meetings of Neanderthals and Homo sapiens, for example, while the decryption of Mayan hieroglyphics provided lessons on understanding others of own species.

Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex.

PubMed

Alvarado, Sebastian; Tajerian, Maral; Millecamps, Magali; Suderman, Mathew; Stone, Laura S; Szyf, Moshe

2013-04-18

Peripheral nerve injury can have long-term consequences including pain-related manifestations, such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. Changes in brain structure and cortical function associated with many chronic pain conditions have been reported in the prefrontal cortex (PFC). The PFC is implicated in pain-related co-morbidities such as depression, anxiety and impaired emotional decision-making ability. We recently reported that this region is subject to significant epigenetic reprogramming following peripheral nerve injury, and normalization of pain-related structural, functional and epigenetic abnormalities in the PFC are all associated with effective pain reduction. In this study, we used the Spared Nerve Injury (SNI) model of neuropathic pain to test the hypothesis that peripheral nerve injury triggers persistent long-lasting changes in gene expression in the PFC, which alter functional gene networks, thus providing a possible explanation for chronic pain associated behaviors. SNI or sham surgery where performed in male CD1 mice at three months of age. Six months after injury, we performed transcriptome-wide sequencing (RNAseq), which revealed 1147 differentially regulated transcripts in the PFC in nerve-injured vs. control mice. Changes in gene expression occurred across a number of functional gene clusters encoding cardinal biological processes as revealed by Ingenuity Pathway Analysis. Significantly altered biological processes included neurological disease, skeletal muscular disorders, behavior, and psychological disorders. Several of the changes detected by RNAseq were validated by RT-QPCR and included transcripts with known roles in chronic pain and/or neuronal plasticity including the NMDA receptor (glutamate receptor, ionotropic, NMDA; grin1), neurite outgrowth (roundabout 3; robo3), gliosis (glial fibrillary acidic protein; gfap), vesicular release (synaptotagmin 2; syt2), and neuronal excitability (voltage-gated sodium channel, type I; scn1a). This study used an unbiased approach to document long-term alterations in gene expression in the brain following peripheral nerve injury. We propose that these changes are maintained as a memory of an insult that is temporally and spatially distant from the initial injury.

How young trees cope with removal of whole or parts of shoots: an analysis of local and distant responses to pruning in 1-year-old apple (Malus xdomestica; Rosaceae) trees.

PubMed

Fumey, Damien; Lauri, Pierre-Éric; Guédon, Yann; Godin, Christophe; Costes, Evelyne

2011-11-01

Manipulation of tree architecture by pruning provides an experimental context to analyze architectural plasticity resulting from competition between developing organs. The objective of this study was to quantify the effects of the removal of all or part of shoots through pruning on the redistribution of growth and flowering at spatial and temporal levels. Two types of pruning cuts were applied: (1) heading cuts of either the main stem or laterals and (2) thinning cuts (i.e., complete removal) of laterals. These two types of cuts were applied in summer and winter on 1-yr-old cultivars of Fuji and Braeburn apple trees. Tree topology and geometry were described over 3 years, and responses were analyzed for both local and distant scales. Heading cuts induced quasi-deterministic local responses on pruned axes, whereas responses to thinning cuts were more variable. For the main stem and laterals, responses over greater spatial and temporal scales were highlighted with (1) stronger growth the year after summer pruning and (2) modification of branching and flowering along the unpruned parts after winter pruning. Pruning typically induced growth redistribution toward traumatic reiterations and enhanced growth of the remaining unpruned axes with a concomitant decrease of flowering and cambial growth. Although results could be interpreted in relation to the root-shoot balance, tree responses appeared highly cultivar-specific.

Assessing the clinical outcome of Vim radiosurgery with voxel-based morphometry: visual areas are linked with tremor arrest!

PubMed

Tuleasca, Constantin; Witjas, Tatiana; Najdenovska, Elena; Verger, Antoine; Girard, Nadine; Champoudry, Jerome; Thiran, Jean-Philippe; Van de Ville, Dimitri; Cuadra, Meritxell Bach; Levivier, Marc; Guedj, Eric; Régis, Jean

2017-11-01

Radiosurgery (RS) is an alternative to open standard stereotactic procedures (deep-brain stimulation or radiofrequency thalamotomy) for drug-resistant essential tremor (ET), aiming at the same target (ventro-intermediate nucleus, Vim). We investigated the Vim RS outcome using voxel-based morphometry by evaluating the interaction between clinical response and time. Thirty-eight patients with right-sided ET benefited from left unilateral Vim RS. Targeting was performed using 130 Gy and a single 4-mm collimator. Neurological and neuroimaging assessment was completed at baseline and 1 year. Clinical responders were considered those with at least 50% improvement in tremor score on the treated hand (TSTH). Interaction between clinical response and time showed the left temporal pole and occipital cortex (Brodmann area 19, including V4, V5 and the parahippocampal place area) as statistically significant. A decrease in gray matter density (GMD) 1 year after Vim RS correlated with higher TSTH improvement (Spearman = 0.01) for both anatomical areas. Higher baseline GMD within the left temporal pole correlated with better TSTH improvement (Spearman = 0.004). Statistically significant structural changes in the relationship to clinical response after Vim RS are present in remote areas, advocating a distant neurobiological effect. The former regions are mainly involved in locomotor monitoring toward the local and distant environment, suggesting the recruiting requirement in targeting of the specific visuomotor networks.

Distinctive Expansion of Gene Families Associated with Virulence Functions in the Genomes of Grapevine Trunk Pathogens

USDA-ARS?s Scientific Manuscript database

Trunk diseases are responsible for important economic losses in all viticulture production systems. They are caused by distantly-related fungi that form chronic wood infections. Variation in wood-decay abilities and production of phytotoxic compounds are thought to contribute to differences in the d...

CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design

PubMed Central

Rose, Timothy M.; Henikoff, Jorja G.; Henikoff, Steven

2003-01-01

We have developed a new primer design strategy for PCR amplification of distantly related gene sequences based on consensus-degenerate hybrid oligonucleotide primers (CODEHOPs). An interactive program has been written to design CODEHOP PCR primers from conserved blocks of amino acids within multiply-aligned protein sequences. Each CODEHOP consists of a pool of related primers containing all possible nucleotide sequences encoding 3–4 highly conserved amino acids within a 3′ degenerate core. A longer 5′ non-degenerate clamp region contains the most probable nucleotide predicted for each flanking codon. CODEHOPs are used in PCR amplification to isolate distantly related sequences encoding the conserved amino acid sequence. The primer design software and the CODEHOP PCR strategy have been utilized for the identification and characterization of new gene orthologs and paralogs in different plant, animal and bacterial species. In addition, this approach has been successful in identifying new pathogen species. The CODEHOP designer (http://blocks.fhcrc.org/codehop.html) is linked to BlockMaker and the Multiple Alignment Processor within the Blocks Database World Wide Web (http://blocks.fhcrc.org). PMID:12824413

A Mechanism for Reducing Delay Discounting by Altering Temporal Attention

PubMed Central

Radu, Peter T; Yi, Richard; Bickel, Warren K; Gross, James J; McClure, Samuel M

2011-01-01

Rewards that are not immediately available are discounted compared to rewards that are immediately available. The more a person discounts a delayed reward, the more likely that person is to have a range of behavioral problems, including clinical disorders. This latter observation has motivated the search for interventions that reduce discounting. One surprisingly simple method to reduce discounting is an “explicit-zero” reframing that states default or null outcomes. Reframing a classical discounting choice as “something now but nothing later” versus “nothing now but more later” decreases discount rates. However, it is not clear how this “explicit-zero” framing intervention works. The present studies delineate and test two possible mechanisms to explain the phenomenon. One mechanism proposes that the explicit-zero framing creates the impression of an improving sequence, thereby enhancing the present value of the delayed reward. A second possible mechanism posits an increase in attention allocation to temporally distant reward representations. In four experiments, we distinguish between these two hypothesized mechanisms and conclude that the temporal attention hypothesis is superior for explaining our results. We propose a model of temporal attention whereby framing affects intertemporal preferences by modifying present bias. PMID:22084496

An exceptional horizontal gene transfer in plastids: gene replacement by a distant bacterial paralog and evidence that haptophyte and cryptophyte plastids are sisters

PubMed Central

Rice, Danny W; Palmer, Jeffrey D

2006-01-01

Background Horizontal gene transfer (HGT) to the plant mitochondrial genome has recently been shown to occur at a surprisingly high rate; however, little evidence has been found for HGT to the plastid genome, despite extensive sequencing. In this study, we analyzed all genes from sequenced plastid genomes to unearth any neglected cases of HGT and to obtain a measure of the overall extent of HGT to the plastid. Results Although several genes gave strongly supported conflicting trees under certain conditions, we are confident of HGT in only a single case beyond the rubisco HGT already reported. Most of the conflicts involved near neighbors connected by long branches (e.g. red algae and their secondary hosts), where phylogenetic methods are prone to mislead. However, three genes – clpP, ycf2, and rpl36 – provided strong support for taxa moving far from their organismal position. Further taxon sampling of clpP and ycf2 resulted in rejection of HGT due to long-branch attraction and a serious error in the published plastid genome sequence of Oenothera elata, respectively. A single new case, a bacterial rpl36 gene transferred into the ancestor of the cryptophyte and haptophyte plastids, appears to be a true HGT event. Interestingly, this rpl36 gene is a distantly related paralog of the rpl36 type found in other plastids and most eubacteria. Moreover, the transferred gene has physically replaced the native rpl36 gene, yet flanking genes and intergenic regions show no sign of HGT. This suggests that gene replacement somehow occurred by recombination at the very ends of rpl36, without the level and length of similarity normally expected to support recombination. Conclusion The rpl36 HGT discovered in this study is of considerable interest in terms of both molecular mechanism and phylogeny. The plastid acquisition of a bacterial rpl36 gene via HGT provides the first strong evidence for a sister-group relationship between haptophyte and cryptophyte plastids to the exclusion of heterokont and alveolate plastids. Moreover, the bacterial gene has replaced the native plastid rpl36 gene by an uncertain mechanism that appears inconsistent with existing models for the recombinational basis of gene conversion. PMID:16956407

Evolution of vertebrate sex chromosomes and dosage compensation.

PubMed

Graves, Jennifer A Marshall

2016-01-01

Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

Anatomical study of the superficial temporal branches of the auriculotemporal nerve: Application to surgery and other invasive treatments to the temporal region.

PubMed

Iwanaga, Joe; Watanabe, Koichi; Saga, Tsuyoshi; Fisahn, Christian; Oskouian, Rod J; Tubbs, R Shane

2017-03-01

The auriculotemporal nerve (ATN) is one of the branches of the mandibular division of the trigeminal nerve, which gives rise to many branches to the retromandibular and temporal regions. Of these, the superficial temporal branch can occasionally be the cause of migraine headaches and auriculotemporal neuralgia. The purpose of this study was to elucidate the anatomy of the superficial temporal branch, which has never been described in detail. A total of 14 sides of cadaveric heads were used for this study. The number of superficial temporal branch was counted, and the horizontal and vertical distances from the middle of the tragus to the branching point were measured. Three of 14 sides had two main trunks, and 11 sides had one main trunk. Each of the duplicated ATN had already branches into two main trunks as they left the retromandibular space. The number of superficial temporal branches ranged from two to seven. The vertical and horizontal distances from the middle of the tragus to the branching point of the superficial temporal branch ranged from 6.19 to 25.65 mm and from 3.45 to 11.88 mm, respectively. The communicating branches occasionally formed a loop or so-called "ansa," and a double ansa was identified in one case. These data can provide surgeons a better view of the course of these distant branches, so that skin incisions can be better planned. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Evolution of the Iga Heavy Chain Gene in the Genus Mus

PubMed Central

Osborne, B. A.; Golde, T. E.; Schwartz, R. L.; Rudikoff, S.

1988-01-01

To examine questions of immunoglobulin gene evolution, the IgA α heavy chain gene from Mus pahari, an evolutionarily distant relative to Mus musculus domesticus, was cloned and sequenced. The sequence, when compared to the IgA gene of BALB/c or human, demonstrated that the IgA gene is evolving in a mosaic fashion with the hinge region accumulating mutations most rapidly and the third domain at a considerably lower frequency. In spite of this pronounced accumulation of mutations, the hinge region appears to maintain the conformation of a random coil. A marked propensity to accumulate replacement over silent site changes in the coding regions was noted, as was a definite codon bias. The possibility that these two phenomena are interrelated is discussed. PMID:2842228

Ancestral synteny shared between distantly-related plant species from the asterid (Coffea canephora and Solanum Sp.) and rosid (Vitis vinifera) clades

PubMed Central

2012-01-01

Background Coffee trees (Rubiaceae) and tomato (Solanaceae) belong to the Asterid clade, while grapevine (Vitaceae) belongs to the Rosid clade. Coffee and tomato separated from grapevine 125 million years ago, while coffee and tomato diverged 83-89 million years ago. These long periods of divergent evolution should have permitted the genomes to reorganize significantly. So far, very few comparative mappings have been performed between very distantly related species belonging to different clades. We report the first multiple comparison between species from Asterid and Rosid clades, to examine both macro-and microsynteny relationships. Results Thanks to a set of 867 COSII markers, macrosynteny was detected between coffee, tomato and grapevine. While coffee and tomato genomes share 318 orthologous markers and 27 conserved syntenic segments (CSSs), coffee and grapevine also share a similar number of syntenic markers and CSSs: 299 and 29 respectively. Despite large genome macrostructure reorganization, several large chromosome segments showed outstanding macrosynteny shedding new insights into chromosome evolution between Asterids and Rosids. We also analyzed a sequence of 174 kb containing the ovate gene, conserved in a syntenic block between coffee, tomato and grapevine that showed a high-level of microstructure conservation. A higher level of conservation was observed between coffee and grapevine, both woody and long life-cycle plants, than between coffee and tomato. Out of 16 coffee genes of this syntenic segment, 7 and 14 showed complete synteny between coffee and tomato or grapevine, respectively. Conclusions These results show that significant conservation is found between distantly related species from the Asterid (Coffea canephora and Solanum sp.) and Rosid (Vitis vinifera) clades, at the genome macrostructure and microstructure levels. At the ovate locus, conservation did not decline in relation to increasing phylogenetic distance, suggesting that the time factor alone does not explain divergences. Our results are considerably useful for syntenic studies between supposedly remote species for the isolation of important genes for agronomy. PMID:22433423

Abstract Mindsets Increase Believability of Spatially Distant Online Messages

PubMed Central

Sungur, Hande; Hartmann, Tilo; van Koningsbruggen, Guido M.

2016-01-01

Growing evidence from online credibility research reveals that online users rely on heuristic processes to evaluate the credibility of online information. The current paper, which is based on the construal level theory (CLT), proposes that congruency between the psychological distance of a stimulus and the way it is mentally construed can act as a heuristic for believability. According to CLT, psychologically close (e.g., spatially, temporally, socially) stimuli are represented concretely whereas psychologically distant stimuli are represented abstractly. The level of mental construals and the psychological distance of information have been shown to influence people’s truth judgments in offline contexts. This study tests whether congruency between the construal level of people’s mindsets (abstract vs. concrete) and the psychological distance implied in an online message (far vs. close) enhances message believability. By partially confirming CLT predictions, we found that believability of an online news item about a distant location increased when people maintained an abstract mindset rather than a concrete one. The effect of a concrete mindset on believability was not significant for the close psychological distance condition. Our findings provide initial evidence that congruency between the construal level of people’s mindsets and psychological distance cues in online messages can act as a heuristic for believability. We discuss the potential of applying the CLT framework to the growing literature on online cognitive heuristics in the area of online information credibility. PMID:27468272

The prospect of gene therapy for prostate cancer: update on theory and status.

PubMed

Koeneman, K S; Hsieh, J T

2001-09-01

Molecularly based novel therapeutic agents are needed to address the problem of locally recurrent, or metastatic, advanced hormone-refractory prostate cancer. Recent basic science advances in mechanisms of gene expression, vector delivery, and targeting have rendered clinically relevant gene therapy to the prostatic fossa and distant sites feasible in the near future. Current research and clinical investigative efforts involving methods for more effective vector delivery and targeting, with enhanced gene expression to selected (specific) sites, are reviewed. These areas of research involve tissue-specific promoters, transgene exploration, vector design and delivery, and selective vector targeting. The 'vectorology' involved mainly addresses selective tissue homing with ligands, mechanisms of innate immune system evasion for durable transgene expression, and the possibility of repeat administration.

Masking release due to linguistic and phonetic dissimilarity between the target and masker speech

PubMed Central

Calandruccio, Lauren; Brouwer, Susanne; Van Engen, Kristin J.; Dhar, Sumitrajit; Bradlow, Ann R.

2013-01-01

Purpose To investigate masking release for speech maskers for linguistically and phonetically close (English and Dutch) and distant (English and Mandarin) language pairs. Method Twenty monolingual speakers of English with normal-audiometric thresholds participated. Data are reported for an English sentence recognition task in English, Dutch and Mandarin competing speech maskers (Experiment I) and noise maskers (Experiment II) that were matched either to the long-term-average-speech spectra or to the temporal modulations of the speech maskers from Experiment I. Results Results indicated that listener performance increased as the target-to-masker linguistic distance increased (English-in-English < English-in-Dutch < English-in-Mandarin). Conclusions Spectral differences between maskers can account for some, but not all, of the variation in performance between maskers; however, temporal differences did not seem to play a significant role. PMID:23800811

Mesoscale variations in acoustic signals induced by atmospheric gravity waves.

PubMed

Chunchuzov, Igor; Kulichkov, Sergey; Perepelkin, Vitaly; Ziemann, Astrid; Arnold, Klaus; Kniffka, Anke

2009-02-01

The results of acoustic tomographic monitoring of the coherent structures in the lower atmosphere and the effects of these structures on acoustic signal parameters are analyzed in the present study. From the measurements of acoustic travel time fluctuations (periods 1 min-1 h) with distant receivers, the temporal fluctuations of the effective sound speed and wind speed are retrieved along different ray paths connecting an acoustic pulse source and several receivers. By using a coherence analysis of the fluctuations near spatially distanced ray turning points, the internal wave-associated fluctuations are filtered and their spatial characteristics (coherences, horizontal phase velocities, and spatial scales) are estimated. The capability of acoustic tomography in estimating wind shear near ground is shown. A possible mechanism describing the temporal modulation of the near-ground wind field by ducted internal waves in the troposphere is proposed.

Discovery of prognostic biomarkers for predicting lung cancer metastasis using microarray and survival data.

PubMed

Huang, Hui-Ling; Wu, Yu-Chung; Su, Li-Jen; Huang, Yun-Ju; Charoenkwan, Phasit; Chen, Wen-Liang; Lee, Hua-Chin; Chu, William Cheng-Chung; Ho, Shinn-Ying

2015-02-21

Few studies have investigated prognostic biomarkers of distant metastases of lung cancer. One of the central difficulties in identifying biomarkers from microarray data is the availability of only a small number of samples, which results overtraining. Recently obtained evidence reveals that epithelial-mesenchymal transition (EMT) of tumor cells causes metastasis, which is detrimental to patients' survival. This work proposes a novel optimization approach to discovering EMT-related prognostic biomarkers to predict the distant metastasis of lung cancer using both microarray and survival data. This weighted objective function maximizes both the accuracy of prediction of distant metastasis and the area between the disease-free survival curves of the non-distant and distant metastases. Seventy-eight patients with lung cancer and a follow-up time of 120 months are used to identify a set of gene markers and an independent cohort of 26 patients is used to evaluate the identified biomarkers. The medical records of the 78 patients show a significant difference between the disease-free survival times of the 37 non-distant- and the 41 distant-metastasis patients. The experimental results thus obtained are as follows. 1) The use of disease-free survival curves can compensate for the shortcoming of insufficient samples and greatly increase the test accuracy by 11.10%; and 2) the support vector machine with a set of 17 transcripts, such as CCL16 and CDKN2AIP, can yield a leave-one-out cross-validation accuracy of 93.59%, a test accuracy of 76.92%, a large disease-free survival area of 74.81%, and a mean survival prediction error of 3.99 months. The identified putative biomarkers are examined using related studies and signaling pathways to reveal the potential effectiveness of the biomarkers in prospective confirmatory studies. The proposed new optimization approach to identifying prognostic biomarkers by combining multiple sources of data (microarray and survival) can facilitate the accurate selection of biomarkers that are most relevant to the disease while solving the problem of insufficient samples.

Temporal changes in soil bacterial and archaeal communities with different fertilizers in tea orchards.

PubMed

Wang, Hua; Yang, Shao-hui; Yang, Jing-ping; Lv, Ya-min; Zhao, Xing; Pang, Ji-liang

2014-11-01

It is important to understand the effects of temporal changes in microbial communities in the acidic soils of tea orchards with different fertilizers. A field experiment involving organic fertilizer (OF), chemical fertilizer (CF), and unfertilized control (CK) treatments was arranged to analyze the temporal changes in the bacterial and archaeal communities at bimonthly intervals based on the 16S ribosomal RNA (rRNA) gene using terminal restriction fragment length polymorphism (T-RFLP) profiling. The abundances of total bacteria, total archaea, and selected functional genes (bacterial and archaeal amoA, bacterial narG, nirK, nirS, and nosZ) were determined by quantitative polymerase chain reaction (qPCR). The results indicate that the structures of bacterial and archaeal communities varied significantly with time and fertilization based on changes in the relative abundance of dominant T-RFs. The abundancy of the detected genes changed with time. The total bacteria, total archaea, and archaeal amoA were less abundant in July. The bacterial amoA and denitrifying genes were less abundant in September, except the nirK gene. The OF treatment increased the abundance of the observed genes, while the CF treatment had little influence on them. The soil temperature significantly affected the bacterial and archaeal community structures. The soil moisture was significantly correlated with the abundance of denitrifying genes. Of the soil chemical properties, soil organic carbon was the most important factor and was significantly correlated with the abundance of the detected genes, except the nirK gene. Overall, this study demonstrated the effects of both temporal alteration and organic fertilizer on the structures of microbial communities and the abundance of genes involved in the nitrogen cycle.

Temporal changes in soil bacterial and archaeal communities with different fertilizers in tea orchards* #

PubMed Central

Wang, Hua; Yang, Shao-hui; Yang, Jing-ping; Lv, Ya-min; Zhao, Xing; Pang, Ji-liang

2014-01-01

It is important to understand the effects of temporal changes in microbial communities in the acidic soils of tea orchards with different fertilizers. A field experiment involving organic fertilizer (OF), chemical fertilizer (CF), and unfertilized control (CK) treatments was arranged to analyze the temporal changes in the bacterial and archaeal communities at bimonthly intervals based on the 16S ribosomal RNA (rRNA) gene using terminal restriction fragment length polymorphism (T-RFLP) profiling. The abundances of total bacteria, total archaea, and selected functional genes (bacterial and archaeal amoA, bacterial narG, nirK, nirS, and nosZ) were determined by quantitative polymerase chain reaction (qPCR). The results indicate that the structures of bacterial and archaeal communities varied significantly with time and fertilization based on changes in the relative abundance of dominant T-RFs. The abundancy of the detected genes changed with time. The total bacteria, total archaea, and archaeal amoA were less abundant in July. The bacterial amoA and denitrifying genes were less abundant in September, except the nirK gene. The OF treatment increased the abundance of the observed genes, while the CF treatment had little influence on them. The soil temperature significantly affected the bacterial and archaeal community structures. The soil moisture was significantly correlated with the abundance of denitrifying genes. Of the soil chemical properties, soil organic carbon was the most important factor and was significantly correlated with the abundance of the detected genes, except the nirK gene. Overall, this study demonstrated the effects of both temporal alteration and organic fertilizer on the structures of microbial communities and the abundance of genes involved in the nitrogen cycle. PMID:25367788

Balancing selection on the number of repeats in the ribosomal intergenic spacer present in naturally occurring yellow perch (Perca flavescens) populations.

PubMed

Bélanger-Lépine, Frédérique; Leung, Christelle; Glémet, Hélène; Angers, Bernard

2018-01-01

The ribosomal intergenic spacer (IGS), responsible for the rate of transcription of rRNA genes, is associated with the growth and fecundity of individuals. A previous study of IGS length variants in a yellow perch (Perca flavescens) population revealed the presence of two predominant alleles differing by 1 kb due to variation in the number of repeat units. This study aims to assess whether length variation of IGS is the result of selection in natural populations. Length variation of IGS and 11 neutral microsatellite loci were assessed in geographically distant yellow perch populations. Most populations displayed the very same IGS alleles; they did not differ in frequencies among populations and the F ST was not significantly different from zero. In contrast, diversity at microsatellite loci was high and differed among populations (F ST = 0.18). Selection test based on F ST identified IGS as a significant outlier from neutral expectations for population differentiation. Heterozygote excess was also detected in one specific cohort, suggesting temporal variation in the selection regime. While the exact mechanism remains to be specified, together the results of this study support the contention that balancing selection is acting to maintain two distinct IGS alleles in natural fish populations.

Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

PubMed

Paik, Soonmyung; Tang, Gong; Shak, Steven; Kim, Chungyeul; Baker, Joffre; Kim, Wanseop; Cronin, Maureen; Baehner, Frederick L; Watson, Drew; Bryant, John; Costantino, Joseph P; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

2006-08-10

The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

Comparative genome analysis of non-toxigenic non-O1 versus toxigenic O1 Vibrio cholerae

PubMed Central

Mukherjee, Munmun; Kakarla, Prathusha; Kumar, Sanath; Gonzalez, Esmeralda; Floyd, Jared T.; Inupakutika, Madhuri; Devireddy, Amith Reddy; Tirrell, Selena R.; Bruns, Merissa; He, Guixin; Lindquist, Ingrid E.; Sundararajan, Anitha; Schilkey, Faye D.; Mudge, Joann; Varela, Manuel F.

2015-01-01

Pathogenic strains of Vibrio cholerae are responsible for endemic and pandemic outbreaks of the disease cholera. The complete toxigenic mechanisms underlying virulence in Vibrio strains are poorly understood. The hypothesis of this work was that virulent versus non-virulent strains of V. cholerae harbor distinctive genomic elements that encode virulence. The purpose of this study was to elucidate genomic differences between the O1 serotypes and non-O1 V. cholerae PS15, a non-toxigenic strain, in order to identify novel genes potentially responsible for virulence. In this study, we compared the whole genome of the non-O1 PS15 strain to the whole genomes of toxigenic serotypes at the phylogenetic level, and found that the PS15 genome was distantly related to those of toxigenic V. cholerae. Thus we focused on a detailed gene comparison between PS15 and the distantly related O1 V. cholerae N16961. Based on sequence alignment we tentatively assigned chromosome numbers 1 and 2 to elements within the genome of non-O1 V. cholerae PS15. Further, we found that PS15 and O1 V. cholerae N16961 shared 98% identity and 766 genes, but of the genes present in N16961 that were missing in the non-O1 V. cholerae PS15 genome, 56 were predicted to encode not only for virulence–related genes (colonization, antimicrobial resistance, and regulation of persister cells) but also genes involved in the metabolic biosynthesis of lipids, nucleosides and sulfur compounds. Additionally, we found 113 genes unique to PS15 that were predicted to encode other properties related to virulence, disease, defense, membrane transport, and DNA metabolism. Here, we identified distinctive and novel genomic elements between O1 and non-O1 V. cholerae genomes as potential virulence factors and, thus, targets for future therapeutics. Modulation of such novel targets may eventually enhance eradication efforts of endemic and pandemic disease cholera in afflicted nations. PMID:25722857

Comparative genome analysis of non-toxigenic non-O1 versus toxigenic O1 Vibrio cholerae.

PubMed

Mukherjee, Munmun; Kakarla, Prathusha; Kumar, Sanath; Gonzalez, Esmeralda; Floyd, Jared T; Inupakutika, Madhuri; Devireddy, Amith Reddy; Tirrell, Selena R; Bruns, Merissa; He, Guixin; Lindquist, Ingrid E; Sundararajan, Anitha; Schilkey, Faye D; Mudge, Joann; Varela, Manuel F

Pathogenic strains of Vibrio cholerae are responsible for endemic and pandemic outbreaks of the disease cholera. The complete toxigenic mechanisms underlying virulence in Vibrio strains are poorly understood. The hypothesis of this work was that virulent versus non-virulent strains of V. cholerae harbor distinctive genomic elements that encode virulence. The purpose of this study was to elucidate genomic differences between the O1 serotypes and non-O1 V. cholerae PS15, a non-toxigenic strain, in order to identify novel genes potentially responsible for virulence. In this study, we compared the whole genome of the non-O1 PS15 strain to the whole genomes of toxigenic serotypes at the phylogenetic level, and found that the PS15 genome was distantly related to those of toxigenic V. cholerae . Thus we focused on a detailed gene comparison between PS15 and the distantly related O1 V. cholerae N16961. Based on sequence alignment we tentatively assigned chromosome numbers 1 and 2 to elements within the genome of non-O1 V. cholerae PS15. Further, we found that PS15 and O1 V. cholerae N16961 shared 98% identity and 766 genes, but of the genes present in N16961 that were missing in the non-O1 V. cholerae PS15 genome, 56 were predicted to encode not only for virulence-related genes (colonization, antimicrobial resistance, and regulation of persister cells) but also genes involved in the metabolic biosynthesis of lipids, nucleosides and sulfur compounds. Additionally, we found 113 genes unique to PS15 that were predicted to encode other properties related to virulence, disease, defense, membrane transport, and DNA metabolism. Here, we identified distinctive and novel genomic elements between O1 and non-O1 V. cholerae genomes as potential virulence factors and, thus, targets for future therapeutics. Modulation of such novel targets may eventually enhance eradication efforts of endemic and pandemic disease cholera in afflicted nations.

Prevalence and genetic heterogeneity of porcine group C rotaviruses in nursing and weaned piglets in Ohio, USA and identification of a potential new VP4 genotype.

PubMed

Amimo, J O; Vlasova, A N; Saif, L J

2013-05-31

Swine fecal samples collected from seven farms were screened for group C rotaviruses (RVCs) using a reverse transcription-polymerase chain reaction assay. A total of 380 samples were tested and 19.5% were positive. Of the 128 samples collected in 2012, 23.5% from nursing piglets and 8.5% from weaned piglets were RVC positive, with a higher RVC frequency in diarrheic (28.4%) than in non-diarrheic (6.6%) piglets. Two strains (RVC/Pig-wt/USA/RV0104/2011/G3PX and RVC/Pig-wt/USA/RV0143/2012/G6Px) from two different farms were characterized genetically to gain information on virus diversity based on full length sequences of the inner capsid VP6, enterotoxin NSP4 and the outer capsid VP7 and VP4 (partial for RV0104) genes. The VP6 gene of the two strains showed high (99%) nucleotide identity to one another, 84-91% identity to other porcine RVCstrains and 81-82% identity to human and bovine RVC strains. The NSP4 gene analysis revealed that RVC/Pig-wt/USA/RV0104/2011/G3PX and RVC/Pig-wt/USA/RV0143/2012/G6Px strains were not closely related to each other (87% identity), but shared higher identity with prototype RVC/Pig-wt/USA/Cowden/1980/G1Px strain (93% and 89%, respectively) and were more distantly related to human strains (72-76% identity). The VP7 gene analysis indicated that the two strains were distantly related to one another (72% identity). RVC/Pig-wt/USA/RV0143/2012/G6Px was most closely related to porcine RVC G6 strains (82-86% identity), whereas RVC/Pig-wt/USA/RV0104/2011/G3PX was most closely related to porcine HF (G3) strain (94% identity). Analysis of the full length nucleotide sequence of the VP4 gene revealed that RVC/Pig-wt/USA/RV0143/2012/G6Px was distantly related to porcine (75%), bovine (74%) and human (70%) strains. The deduced amino acid identities (69.5-75.6%) of VP4 between RVC/Pig-wt/USA/RV0143/2012/G6Px and other RVCs were low; hence, we propose that this strain comprises a new VP4 genotype. Our results indicate high genetic heterogeneity in RVCs genes and the concurrent co-circulation of different genotypes at the same time. Our findings are useful for the development of more accurate diagnostic tools, for basic research to understand gene function and to provide information for RVC diversity germane to vaccine development. Copyright © 2013 Elsevier B.V. All rights reserved.

Exploring the limits to energy scaling and distant-target delivery of high-intensity midinfrared pulses

NASA Astrophysics Data System (ADS)

Panagiotopoulos, Paris; Kolesik, Miroslav; Moloney, Jerome V.

2016-09-01

We numerically investigate the scaling behavior of midinfrared filaments at extremely high input energies. It is shown that, given sufficient power, kilometer-scale, low-loss atmospheric filamentation is attainable by prechirping the pulse. Fully resolved four-dimensional (x y z t ) simulations show that, while in a spatially imperfect beam the modulation instability can lead to multiple hot-spot formation, the individual filaments are still stabilized by the recently proposed mechanism that relies on the temporal walk-off of short-wavelength radiation.

Computer constructed imagery of distant plasma interaction boundaries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grenstadt, E.W.; Schurr, H.D.; Tsugawa, R.K.

1982-01-01

Computer constructed sketches of plasma boundaries arising from the interaction between the solar wind and the magnetosphere can serve as both didactic and research tools. In particular, the structure of the earth's bow shock can be represented as a nonuniform surfce according to the instantaneous orientation of the IMF, and temporal changes in structural distribution can be modeled as a sequence of sketches based on observed sequences of spacecraft-based measurements. Viewed rapidly, such a sequence of sketches can be the basis for representation of plasma processes by computer animation.

Genome-wide identification of lineage-specific genes in Arabidopsis, Oryza and Populus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xiaohan; Jawdy, Sara; Tschaplinski, Timothy J

2009-01-01

Protein sequences were compared among Arabidopsis, Oryza and Populus to identify differential gene (DG) sets that are in one but not the other two genomes. The DG sets were screened against a plant transcript database, the NR protein database and six newly-sequenced genomes (Carica, Glycine, Medicago, Sorghum, Vitis and Zea) to identify a set of species-specific genes (SS). Gene expression, protein motif and intron number were examined. 192, 641 and 109 SS genes were identified in Arabidopsis, Oryza and Populus, respectively. Some SS genes were preferentially expressed in flowers, roots, xylem and cambium or up-regulated by stress. Six conserved motifsmore » in Arabidopsis and Oryza SS proteins were found in other distant lineages. The SS gene sets were enriched with intronless genes. The results reflect functional and/or anatomical differences between monocots and eudicots or between herbaceous and woody plants. The Populus-specific genes are candidates for carbon sequestration and biofuel research.« less

Degradation of Benzene by Pseudomonas veronii 1YdBTEX2 and 1YB2 Is Catalyzed by Enzymes Encoded in Distinct Catabolism Gene Clusters.

PubMed

de Lima-Morales, Daiana; Chaves-Moreno, Diego; Wos-Oxley, Melissa L; Jáuregui, Ruy; Vilchez-Vargas, Ramiro; Pieper, Dietmar H

2016-01-01

Pseudomonas veronii 1YdBTEX2, a benzene and toluene degrader, and Pseudomonas veronii 1YB2, a benzene degrader, have previously been shown to be key players in a benzene-contaminated site. These strains harbor unique catabolic pathways for the degradation of benzene comprising a gene cluster encoding an isopropylbenzene dioxygenase where genes encoding downstream enzymes were interrupted by stop codons. Extradiol dioxygenases were recruited from gene clusters comprising genes encoding a 2-hydroxymuconic semialdehyde dehydrogenase necessary for benzene degradation but typically absent from isopropylbenzene dioxygenase-encoding gene clusters. The benzene dihydrodiol dehydrogenase-encoding gene was not clustered with any other aromatic degradation genes, and the encoded protein was only distantly related to dehydrogenases of aromatic degradation pathways. The involvement of the different gene clusters in the degradation pathways was suggested by real-time quantitative reverse transcription PCR. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Characterization of a microcystin and detection of microcystin synthetase genes from a Brazilian isolate of Nostoc.

PubMed

Genuário, Diego Bonaldo; Silva-Stenico, Maria Estela; Welker, Martin; Beraldo Moraes, Luiz Alberto; Fiore, Marli Fátima

2010-04-01

A nostocalean nitrogen-fixing cyanobacterium isolated from an eutrophic freshwater reservoir located in Piracicaba, São Paulo, Brazil, was evaluated for the production of hepatotoxic cyclic heptapeptides, microcystins. Morphologically this new cyanobacterium strain appears closest to Nostoc, however, in the phylogenetic analysis of 16S rRNA gene it falls into a highly stable cluster distantly only related to the typical Nostoc cluster. Extracts of Nostoc sp. CENA88 cultured cells, investigated using ELISA assay, gave positive results and the microcystin profile revealed by ESI-Q-TOF/MS/MS analysis confirmed the production of [Dha(7)]MCYST-YR. Further, Nostoc sp. CENA88 genomic DNA was analyzed by PCR for sequences of mcyD, mcyE and mcyG genes of microcystin synthetase (mcy) cluster. The result revealed the presence of mcyD, mcyE and mcyG genes with similarities to those from mcy of Nostoc sp. strains 152 and IO-102-I and other cyanobacterial genera. The phylogenetic tree based on concatenated McyG, McyD and McyE amino acids clustered the sequences according to cyanobacterial genera, with exception of the Nostoc sp. CENA88 sequence, which was placed in a clade distantly related from other Nostoc strains, as previously observed also in the 16S rRNA phylogenetic analysis. The present study describes for the first time a Brazilian Nostoc microcystin producer and also the occurrence of demethyl MCYST-YR variant in this genus. The sequenced Nostoc genes involved in the microcystin synthesis can contribute to a better understanding of the toxigenicity and evolution of this cyanotoxin. Copyright 2009 Elsevier Ltd. All rights reserved.

Comparative genomics of geographically distant Fusarium fujikuroi isolates revealed two distinct pathotypes correlating with secondary metabolite profiles

PubMed Central

Arndt, Birgit; Kalinina, Svetlana A.; Houterman, Petra M.; Ahn, Il-Pyung; Tonti, Stefano; Sieber, Christian M. K.

2017-01-01

Fusarium fujikuroi causes bakanae (“foolish seedling”) disease of rice which is characterized by hyper-elongation of seedlings resulting from production of gibberellic acids (GAs) by the fungus. This plant pathogen is also known for production of harmful mycotoxins, such as fusarins, fusaric acid, apicidin F and beauvericin. Recently, we generated the first de novo genome sequence of F. fujikuroi strain IMI 58289 combined with extensive transcriptional, epigenetic, proteomic and chemical product analyses. GA production was shown to provide a selective advantage during infection of the preferred host plant rice. Here, we provide genome sequences of eight additional F. fujikuroi isolates from distant geographic regions. The isolates differ in the size of chromosomes, most likely due to variability of subtelomeric regions, the type of asexual spores (microconidia and/or macroconidia), and the number and expression of secondary metabolite gene clusters. Whilst most of the isolates caused the typical bakanae symptoms, one isolate, B14, caused stunting and early withering of infected seedlings. In contrast to the other isolates, B14 produced no GAs but high amounts of fumonisins during infection on rice. Furthermore, it differed from the other isolates by the presence of three additional polyketide synthase (PKS) genes (PKS40, PKS43, PKS51) and the absence of the F. fujikuroi-specific apicidin F (NRPS31) gene cluster. Analysis of additional field isolates confirmed the strong correlation between the pathotype (bakanae or stunting/withering), and the ability to produce either GAs or fumonisins. Deletion of the fumonisin and fusaric acid-specific PKS genes in B14 reduced the stunting/withering symptoms, whereas deletion of the PKS51 gene resulted in elevated symptom development. Phylogenetic analyses revealed two subclades of F. fujikuroi strains according to their pathotype and secondary metabolite profiles. PMID:29073267

Lateral Transfer of a Lectin-Like Antifreeze Protein Gene in Fishes

PubMed Central

Graham, Laurie A.; Lougheed, Stephen C.; Ewart, K. Vanya; Davies, Peter L.

2008-01-01

Fishes living in icy seawater are usually protected from freezing by endogenous antifreeze proteins (AFPs) that bind to ice crystals and stop them from growing. The scattered distribution of five highly diverse AFP types across phylogenetically disparate fish species is puzzling. The appearance of radically different AFPs in closely related species has been attributed to the rapid, independent evolution of these proteins in response to natural selection caused by sea level glaciations within the last 20 million years. In at least one instance the same type of simple repetitive AFP has independently originated in two distant species by convergent evolution. But, the isolated occurrence of three very similar type II AFPs in three distantly related species (herring, smelt and sea raven) cannot be explained by this mechanism. These globular, lectin-like AFPs have a unique disulfide-bonding pattern, and share up to 85% identity in their amino acid sequences, with regions of even higher identity in their genes. A thorough search of current databases failed to find a homolog in any other species with greater than 40% amino acid sequence identity. Consistent with this result, genomic Southern blots showed the lectin-like AFP gene was absent from all other fish species tested. The remarkable conservation of both intron and exon sequences, the lack of correlation between evolutionary distance and mutation rate, and the pattern of silent vs non-silent codon changes make it unlikely that the gene for this AFP pre-existed but was lost from most branches of the teleost radiation. We propose instead that lateral gene transfer has resulted in the occurrence of the type II AFPs in herring, smelt and sea raven and allowed these species to survive in an otherwise lethal niche. PMID:18612417

Distinctive expansion of gene families associated with plant cell wall degradation, secondary metabolism, and nutrient uptake in the genomes of grapevine trunk pathogens

USDA-ARS?s Scientific Manuscript database

Trunk diseases threaten the longevity and productivity of grapevines in all viticulture production systems. They are caused by distantly-related fungi that form chronic wood infections, but variation in wood-decay abilities and production of phytotoxic compounds are thought to contribute to their un...

A genetic screen for bioluminescence genes in the fungus Armillaria mellea, through the use of Agrobacterium tumefaciens-mediated random insertional mutagenesis

USDA-ARS?s Scientific Manuscript database

Bioluminescence is reported from 71 saprobic species of fungi from four, distant lineages in the order Agaricales. Analyses of the fungal luminescent chemistry shows that all four lineages share a functionally conserved substrate and luciferase, indicating that the bioluminescent pathway is likely c...

Iterative local Gaussian clustering for expressed genes identification linked to malignancy of human colorectal carcinoma

PubMed Central

Wasito, Ito; Hashim, Siti Zaiton M; Sukmaningrum, Sri

2007-01-01

Gene expression profiling plays an important role in the identification of biological and clinical properties of human solid tumors such as colorectal carcinoma. Profiling is required to reveal underlying molecular features for diagnostic and therapeutic purposes. A non-parametric density-estimation-based approach called iterative local Gaussian clustering (ILGC), was used to identify clusters of expressed genes. We used experimental data from a previous study by Muro and others consisting of 1,536 genes in 100 colorectal cancer and 11 normal tissues. In this dataset, the ILGC finds three clusters, two large and one small gene clusters, similar to their results which used Gaussian mixture clustering. The correlation of each cluster of genes and clinical properties of malignancy of human colorectal cancer was analysed for the existence of tumor or normal, the existence of distant metastasis and the existence of lymph node metastasis. PMID:18305825

Iterative local Gaussian clustering for expressed genes identification linked to malignancy of human colorectal carcinoma.

PubMed

Wasito, Ito; Hashim, Siti Zaiton M; Sukmaningrum, Sri

2007-12-30

Gene expression profiling plays an important role in the identification of biological and clinical properties of human solid tumors such as colorectal carcinoma. Profiling is required to reveal underlying molecular features for diagnostic and therapeutic purposes. A non-parametric density-estimation-based approach called iterative local Gaussian clustering (ILGC), was used to identify clusters of expressed genes. We used experimental data from a previous study by Muro and others consisting of 1,536 genes in 100 colorectal cancer and 11 normal tissues. In this dataset, the ILGC finds three clusters, two large and one small gene clusters, similar to their results which used Gaussian mixture clustering. The correlation of each cluster of genes and clinical properties of malignancy of human colorectal cancer was analysed for the existence of tumor or normal, the existence of distant metastasis and the existence of lymph node metastasis.

Complete mitochondrial genome of the invasive brown alga Sargassum muticum (Sargassaceae, Phaeophyceae).

PubMed

Liu, Feng; Pang, Shaojun

2016-01-01

Sargassum muticum (Yendo) Fensholt is an invasive canopy-forming brown alga, expanding its presence from Northeast Asia to North America and Europe. The complete mitochondrial genome of S. muticum is characterized as a circular molecule of 34,720 bp. The overall AT content of S. muticum mitogenome is 63.41%. This mitogenome contains 65 genes typically found in brown algae, including 3 ribosomal RNA genes, 25 transfer RNA genes, 35 protein-coding genes, and 2 conserved open reading frames (ORFs). The gene order of mitogenome for S. muticum is identical to that for Sargassum horneri, Fucus vesiculosus and Desmarestia viridis. Phylogenetic analyses based on 35 protein-coding genes reveal that S. muticum has a close evolutionary relationship with S. horneri and a distant relationship with Dictyota dichotoma, supporting current taxonomic systems. The present investigation provides new molecular data for studies of S. muticum population diversity as well as comparative genomics in the Phaeophyceae.

The genome of wine yeast Dekkera bruxellensis provides a tool to explore its food-related properties.

PubMed

Piškur, Jure; Ling, Zhihao; Marcet-Houben, Marina; Ishchuk, Olena P; Aerts, Andrea; LaButti, Kurt; Copeland, Alex; Lindquist, Erika; Barry, Kerrie; Compagno, Concetta; Bisson, Linda; Grigoriev, Igor V; Gabaldón, Toni; Phister, Trevor

2012-07-02

The yeast Dekkera/Brettanomyces bruxellensis can cause enormous economic losses in wine industry due to production of phenolic off-flavor compounds. D. bruxellensis is a distant relative of baker's yeast Saccharomyces cerevisiae. Nevertheless, these two yeasts are often found in the same habitats and share several food-related traits, such as production of high ethanol levels and ability to grow without oxygen. In some food products, like lambic beer, D. bruxellensis can importantly contribute to flavor development. We determined the 13.4 Mb genome sequence of the D. bruxellensis strain Y879 (CBS2499) and deduced the genetic background of several "food-relevant" properties and evolutionary history of this yeast. Surprisingly, we find that this yeast is phylogenetically distant to other food-related yeasts and most related to Pichia (Komagataella) pastoris, which is an aerobic poor ethanol producer. We further show that the D. bruxellensis genome does not contain an excess of lineage specific duplicated genes nor a horizontally transferred URA1 gene, two crucial events that promoted the evolution of the food relevant traits in the S. cerevisiae lineage. However, D. bruxellensis has several independently duplicated ADH and ADH-like genes, which are likely responsible for metabolism of alcohols, including ethanol, and also a range of aromatic compounds. Copyright © 2012 Elsevier B.V. All rights reserved.

Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy.

PubMed

Gerami, Pedram; Cook, Robert W; Russell, Maria C; Wilkinson, Jeff; Amaria, Rodabe N; Gonzalez, Rene; Lyle, Stephen; Jackson, Gilchrist L; Greisinger, Anthony J; Johnson, Clare E; Oelschlager, Kristen M; Stone, John F; Maetzold, Derek J; Ferris, Laura K; Wayne, Jeffrey D; Cooper, Chelsea; Obregon, Roxana; Delman, Keith A; Lawson, David

2015-05-01

A gene expression profile (GEP) test able to accurately identify risk of metastasis for patients with cutaneous melanoma has been clinically validated. We aimed for assessment of the prognostic accuracy of GEP and sentinel lymph node biopsy (SLNB) tests, independently and in combination, in a multicenter cohort of 217 patients. Reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the expression of 31 genes from primary melanoma tumors, and SLNB outcome was determined from clinical data. Prognostic accuracy of each test was determined using Kaplan-Meier and Cox regression analysis of disease-free, distant metastasis-free, and overall survivals. GEP outcome was a more significant and better predictor of each end point in univariate and multivariate regression analysis, compared with SLNB (P < .0001 for all). In combination with SLNB, GEP improved prognostication. For patients with a GEP high-risk outcome and a negative SLNB result, Kaplan-Meier 5-year disease-free, distant metastasis-free, and overall survivals were 35%, 49%, and 54%, respectively. Within the SLNB-negative cohort of patients, overall risk of metastatic events was higher (∼30%) than commonly found in the general population of patients with melanoma. In this study cohort, GEP was an objective tool that accurately predicted metastatic risk in SLNB-eligible patients. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells

PubMed Central

Celià-Terrassa, Toni; Meca-Cortés, Óscar; Mateo, Francesca; Martínez de Paz, Alexia; Rubio, Nuria; Arnal-Estapé, Anna; Ell, Brian J.; Bermudo, Raquel; Díaz, Alba; Guerra-Rebollo, Marta; Lozano, Juan José; Estarás, Conchi; Ulloa, Catalina; ρlvarez-Simón, Daniel; Milà, Jordi; Vilella, Ramón; Paciucci, Rosanna; Martínez-Balbás, Marian; García de Herreros, Antonio; Gomis, Roger R.; Kang, Yibin; Blanco, Jerónimo; Fernández, Pedro L.; Thomson, Timothy M.

2012-01-01

Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs. PMID:22505459

Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients

PubMed Central

Loskog, Angelica; Maleka, Aglaia; Mangsbo, Sara; Svensson, Emma; Lundberg, Christina; Nilsson, Anders; Krause, Johan; Agnarsdóttir, Margrét; Sundin, Anders; Ahlström, Håkan; Tötterman, Thomas H; Ullenhag, Gustav

2016-01-01

Background: Current approaches for treating metastatic malignant melanoma (MM) are not effective enough and are associated with serious adverse events. Due to its immunogenicity, melanoma is an attractive target for immunostimulating therapy. In this phase I/IIa study, local AdCD40L immunostimulatory gene therapy was evaluated in patients with MM. Methods: AdCD40L is an adenovirus carrying the gene for CD40 ligand. Patients that failed standard treatments were enrolled. Six patients received four weekly intratumoral AdCD40L injections. Next, nine patients received low-dose cyclophosphamide conditioning before the first and fourth AdCD40L injection. The blood samples were collected at multiple time points for chemistry, haematology and immunology evaluations. Radiology was performed at enrolment and repeated twice after the treatment. Results: AdCD40L was safe with mild transient reactions. No objective responses were recorded by MRI, however, local and distant responses were seen on FDG-PET. The overall survival at 6 months was significantly better when cyclophosphamide was added to AdCD40L. The patients with the best survival developed the highest levels of activated T cells and experienced a pronounced decrease of intratumoral IL8. Conclusions: AdCD40L therapy for MM was well tolerated. Local and distant responses along with better survival in the low-dose cyclophosphamide group are encouraging. PMID:27031851

Clonal evolution and heterogeneity in metastatic head and neck cancer-An analysis of the Austrian Study Group of Medical Tumour Therapy study group.

PubMed

Melchardt, Thomas; Magnes, Teresa; Hufnagl, Clemens; Thorner, Aaron R; Ducar, Matthew; Neureiter, Daniel; Tränkenschuh, Wolfgang; Klieser, Eckhard; Gaggl, Alexander; Rösch, Sebastian; Rasp, Gerd; Hartmann, Tanja N; Pleyer, Lisa; Rinnerthaler, Gabriel; Weiss, Lukas; Greil, Richard; Egle, Alexander

2018-04-01

Tumour heterogeneity and clonal evolution within a cancer patient are deemed responsible for relapse in malignancies and present challenges to the principles of targeted therapy, for which treatment modality is often decided based on the molecular pathology of the primary tumour. Nevertheless, the clonal architecture in distant relapse of head and neck cancer is fairly unknown. For this project, we analysed a cohort of 386 patients within the Austrian Registry of head and neck cancer. We identified 26 patients with material from the primary tumour, the distant metastasis after curative first-line treatment and a germline sample for analysis of clonal evolution. After pathological analyses, these samples were analysed using a targeted massively parallel sequencing (MPS) panel of 257 genes known to be recurrently mutated in head and neck cancer plus a genome-wide SNP-set. Despite histological diagnosis of distant metastasis, no corresponding mutation in the supposed metastases was found in two of 23 (8.6%) evaluable patients suggesting a primary tumour of the lung instead of a distant metastasis of head and neck cancer. We observed a branched pattern of evolution in 31.6% of the analysed patients. This pattern was associated with a shorter time to distant metastasis, compared with a pattern of punctuated evolution. Structural genomic changes over time were also present in 7 of 12 (60%) evaluable patients with metachronous metastases. Targeted MPS demonstrated substantial heterogeneity at the time of diagnosis and a complex pattern of evolution during disease progression in head and neck cancer. Copy number analyses revealed additional changes that were not detected by mutational analyses. Mutational and structural changes contribute to tumour heterogeneity at diagnosis and progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Possible Quantum Absorber Effects in Cortical Synchronization

NASA Astrophysics Data System (ADS)

Kämpf, Uwe

The Wheeler-Feynman transactional "absorber" approach was proposed originally to account for anomalous resonance coupling between spatio-temporally distant measurement partners in entangled quantum states of so-called Einstein-Podolsky-Rosen paradoxes, e.g. of spatio-temporal non-locality, quantum teleportation, etc. Applied to quantum brain dynamics, however, this view provides an anticipative resonance coupling model for aspects of cortical synchronization and recurrent visual action control. It is proposed to consider the registered activation patterns of neuronal loops in so-called synfire chains not as a result of retarded brain communication processes, but rather as surface effects of a system of standing waves generated in the depth of visual processing. According to this view, they arise from a counterbalance between the actual input's delayed bottom-up data streams and top-down recurrent information-processing of advanced anticipative signals in a Wheeler-Feynman-type absorber mode. In the framework of a "time-loop" model, findings about mirror neurons in the brain cortex are suggested to be at least partially associated with temporal rather than spatial mirror functions of visual processing, similar to phase conjugate adaptive resonance-coupling in nonlinear optics.

Predicted sequence of cortical tau and amyloid-β deposition in Alzheimer disease spectrum.

PubMed

Cho, Hanna; Lee, Hye Sun; Choi, Jae Yong; Lee, Jae Hoon; Ryu, Young Hoon; Lee, Myung Sik; Lyoo, Chul Hyoung

2018-04-17

We investigated sequential order between tau and amyloid-β (Aβ) deposition in Alzheimer disease spectrum using a conditional probability method. Two hundred twenty participants underwent 18 F-flortaucipir and 18 F-florbetaben positron emission tomography scans and neuropsychological tests. The presence of tau and Aβ in each region and impairment in each cognitive domain were determined by Z-score cutoffs. By comparing pairs of conditional probabilities, the sequential order of tau and Aβ deposition were determined. Probability for the presence of tau in the entorhinal cortex was higher than that of Aβ in all cortical regions, and in the medial temporal cortices, probability for the presence of tau was higher than that of Aβ. Conversely, in the remaining neocortex above the inferior temporal cortex, probability for the presence of Aβ was always higher than that of tau. Tau pathology in the entorhinal cortex may appear earlier than neocortical Aβ and may spread in the absence of Aβ within the neighboring medial temporal regions. However, Aβ may be required for massive tau deposition in the distant cortical areas. Copyright © 2018 Elsevier Inc. All rights reserved.

High-Speed Incoming Infrared Target Detection by Fusion of Spatial and Temporal Detectors

PubMed Central

Kim, Sungho

2015-01-01

This paper presents a method for detecting high-speed incoming targets by the fusion of spatial and temporal detectors to achieve a high detection rate for an active protection system (APS). The incoming targets have different image velocities according to the target-camera geometry. Therefore, single-target detector-based approaches, such as a 1D temporal filter, 2D spatial filter and 3D matched filter, cannot provide a high detection rate with moderate false alarms. The target speed variation was analyzed according to the incoming angle and target velocity. The speed of the distant target at the firing time is almost stationary and increases slowly. The speed varying targets are detected stably by fusing the spatial and temporal filters. The stationary target detector is activated by an almost zero temporal contrast filter (TCF) and identifies targets using a spatial filter called the modified mean subtraction filter (M-MSF). A small motion (sub-pixel velocity) target detector is activated by a small TCF value and finds targets using the same spatial filter. A large motion (pixel-velocity) target detector works when the TCF value is high. The final target detection is terminated by fusing the three detectors based on the threat priority. The experimental results of the various target sequences show that the proposed fusion-based target detector produces the highest detection rate with an acceptable false alarm rate. PMID:25815448

Operon Formation is Driven by Co-Regulation and Not by Horizontal Gene Transfer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, Morgan N.; Huang, Katherine H.; Arkin, Adam P.

Although operons are often subject to horizontal gene transfer (HGT), non-HGT genes are particularly likely to be in operons. To resolve this apparent discrepancy and to determine whether HGT is involved in operon formation, we examined the evolutionary history of the genes and operons in Escherichia coli K12. We show that genes that have homologs in distantly related bacteria but not in close relatives of E. coli (indicating HGTi) form new operons at about the same rates as native genes. Furthermore, genes in new operons are no more likely than other genes to have phylogenetic trees that are inconsistent withmore » the species tree. In contrast, essential genes and ubiquitous genes without paralogs (genes believed to undergo HGT rarely) often form new operons. We conclude that HGT is not associated with operon formation, but instead promotes the prevalence of pre-existing operons. To explain operon formation, we propose that new operons reduce the amount of regulatory information required to specify optimal expression patterns. Consistent with this hypothesis, operons have greater amounts of conserved regulatory sequences than do individually transcribed genes.« less

Molecular phylogeny and evolution of alcohol dehydrogenase (Adh) genes in legumes

PubMed Central

Fukuda, Tatsuya; Yokoyama, Jun; Nakamura, Toru; Song, In-Ja; Ito, Takuro; Ochiai, Toshinori; Kanno, Akira; Kameya, Toshiaki; Maki, Masayuki

2005-01-01

Background Nuclear genes determine the vast range of phenotypes that are responsible for the adaptive abilities of organisms in nature. Nevertheless, the evolutionary processes that generate the structures and functions of nuclear genes are only now be coming understood. The aim of our study is to isolate the alcohol dehydrogenase (Adh) genes in two distantly related legumes, and use these sequences to examine the molecular evolutionary history of this nuclear gene. Results We isolated the expressed Adh genes from two species of legumes, Sophora flavescens Ait. and Wisteria floribunda DC., by a RT-PCR based approach and found a new Adh locus in addition to homologues of the Adh genes found previously in legumes. To examine the evolution of these genes, we compared the species and gene trees and found gene duplication of the Adh loci in the legumes occurred as an ancient event. Conclusion This is the first report revealing that some legume species have at least two Adh gene loci belonging to separate clades. Phylogenetic analyses suggest that these genes resulted from relatively ancient duplication events. PMID:15836788

Circular DNA Intermediate in the Duplication of Nile Tilapia vasa Genes

PubMed Central

Fujimura, Koji; Conte, Matthew A.; Kocher, Thomas D.

2011-01-01

vasa is a highly conserved RNA helicase involved in animal germ cell development. Among vertebrate species, it is typically present as a single copy per genome. Here we report the isolation and sequencing of BAC clones for Nile tilapia vasa genes. Contrary to a previous report that Nile tilapia have a single copy of the vasa gene, we find evidence for at least three vasa gene loci. The vasa gene locus was duplicated from the original site and integrated into two distant novel sites. For one of these insertions we find evidence that the duplication was mediated by a circular DNA intermediate. This mechanism of gene duplication may explain the origin of isolated gene duplicates during the evolution of fish genomes. These data provide a foundation for studying the role of multiple vasa genes in the development of tilapia gonads, and will contribute to investigations of the molecular mechanisms of sex determination and evolution in cichlid fishes. PMID:22216289

Adaptive Horizontal Gene Transfers between Multiple Cheese-Associated Fungi.

PubMed

Ropars, Jeanne; Rodríguez de la Vega, Ricardo C; López-Villavicencio, Manuela; Gouzy, Jérôme; Sallet, Erika; Dumas, Émilie; Lacoste, Sandrine; Debuchy, Robert; Dupont, Joëlle; Branca, Antoine; Giraud, Tatiana

2015-10-05

Domestication is an excellent model for studies of adaptation because it involves recent and strong selection on a few, identified traits [1-5]. Few studies have focused on the domestication of fungi, with notable exceptions [6-11], despite their importance to bioindustry [12] and to a general understanding of adaptation in eukaryotes [5]. Penicillium fungi are ubiquitous molds among which two distantly related species have been independently selected for cheese making-P. roqueforti for blue cheeses like Roquefort and P. camemberti for soft cheeses like Camembert. The selected traits include morphology, aromatic profile, lipolytic and proteolytic activities, and ability to grow at low temperatures, in a matrix containing bacterial and fungal competitors [13-15]. By comparing the genomes of ten Penicillium species, we show that adaptation to cheese was associated with multiple recent horizontal transfers of large genomic regions carrying crucial metabolic genes. We identified seven horizontally transferred regions (HTRs) spanning more than 10 kb each, flanked by specific transposable elements, and displaying nearly 100% identity between distant Penicillium species. Two HTRs carried genes with functions involved in the utilization of cheese nutrients or competition and were found nearly identical in multiple strains and species of cheese-associated Penicillium fungi, indicating recent selective sweeps; they were experimentally associated with faster growth and greater competitiveness on cheese and contained genes highly expressed in the early stage of cheese maturation. These findings have industrial and food safety implications and improve our understanding of the processes of adaptation to rapid environmental changes. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Adaptive Horizontal Gene Transfers between Multiple Cheese-Associated Fungi

PubMed Central

Ropars, Jeanne; Rodríguez de la Vega, Ricardo C.; López-Villavicencio, Manuela; Gouzy, Jérôme; Sallet, Erika; Dumas, Émilie; Lacoste, Sandrine; Debuchy, Robert; Dupont, Joëlle; Branca, Antoine; Giraud, Tatiana

2015-01-01

Summary Domestication is an excellent model for studies of adaptation because it involves recent and strong selection on a few, identified traits [1–5]. Few studies have focused on the domestication of fungi, with notable exceptions [6–11], despite their importance to bioindustry [12] and to a general understanding of adaptation in eukaryotes [5]. Penicillium fungi are ubiquitous molds among which two distantly related species have been independently selected for cheese making—P. roqueforti for blue cheeses like Roquefort and P. camemberti for soft cheeses like Camembert. The selected traits include morphology, aromatic profile, lipolytic and proteolytic activities, and ability to grow at low temperatures, in a matrix containing bacterial and fungal competitors [13–15]. By comparing the genomes of ten Penicillium species, we show that adaptation to cheese was associated with multiple recent horizontal transfers of large genomic regions carrying crucial metabolic genes. We identified seven horizontally transferred regions (HTRs) spanning more than 10 kb each, flanked by specific transposable elements, and displaying nearly 100% identity between distant Penicillium species. Two HTRs carried genes with functions involved in the utilization of cheese nutrients or competition and were found nearly identical in multiple strains and species of cheese-associated Penicillium fungi, indicating recent selective sweeps; they were experimentally associated with faster growth and greater competitiveness on cheese and contained genes highly expressed in the early stage of cheese maturation. These findings have industrial and food safety implications and improve our understanding of the processes of adaptation to rapid environmental changes. PMID:26412136

Streptococcus pyogenes strains containing emm12 and emm55 possess a novel gene coding for distantly related SIC protein.

PubMed

Hartas, J; Sriprakash, K S

1999-01-01

Streptococcus pyogenes infection and acute glomerulonephritis (AGN), a non-suppurtave disease, are endemic in the Aboriginal people of the Northern Territory (NT) of Australia. Vir typing, a locus-specific polymerase chain reaction (PCR)-based typing method [Gardiner, Hartas, Currie et al PCR Meth Appl 1995 4: 288-93], has revealed high divergence among the NT streptococcal strains. A total of 76 Vir types (VTs) representing about 95% of the NT isolates were screened for sic, a gene for streptococcal inhibitor of complement function, by PCR and hybridization. This revealed that seven VTs are positive for sic, and there are two classes of the gene: those closely related to sic (CRS) originally described by Akesson, Sjoholm & Bjorck [ J. Biol. Chem. 1996 271: 1081-8] and those distantly related to sic (DRS). Among the CRS-positive VTs, VT16, VT78 and VT91 have emm (gene for M protein) encoding type 1 M protein or related specificity, and VT8 and VT101 contain emm57 or related alleles. Chromosomal location of CRS in emm57 is different from that in emm1 or related strains. The DRS-positive VT18 and VT52 contained emm55 and emm12 respectively, which are phylogenetically related. Strains of S. pyogenes types 1, 12, 55 and 57 are known to be associated with AGN. Restricted distribution of CRS and DRS among the M types historically associated with AGN suggests that these sic alleles may have a role in AGN pathogenesis. Copyright 1999 Academic Press.

Molecular analyses of MADS-box genes trace back to Gymnosperms the invention of fleshy fruits.

PubMed

Lovisetto, Alessandro; Guzzo, Flavia; Tadiello, Alice; Toffali, Ketti; Favretto, Alessandro; Casadoro, Giorgio

2012-01-01

Botanical fruits derive from ovaries and their most important function is to favor seed dispersal. Fleshy fruits do so by attracting frugivorous animals that disperse seeds together with their own excrements (endozoochory). Gymnosperms make seeds but have no ovaries to be transformed into fruits. Many species surround their seeds with fleshy structures and use endozoochory to disperse them. Such structures are functionally fruits and can derive from different anatomical parts. Ginkgo biloba and Taxus baccata fruit-like structures differ in their anatomical origin since the outer seed integument becomes fleshy in Ginkgo, whereas in Taxus, the fleshy aril is formed de novo. The ripening characteristics are different, with Ginkgo more rudimentary and Taxus more similar to angiosperm fruits. MADS-box genes are known to be necessary for the formation of flowers and fruits in Angiosperms but also for making both male and female reproductive structures in Gymnosperms. Here, a series of different MADS-box genes have been shown for the first time to be involved also in the formation of gymnosperm fruit-like structures. Apparently, the same gene types have been recruited in phylogenetically distant species to make fleshy structures that also have different anatomical origins. This finding indicates that the main molecular networks operating in the development of fleshy fruits have independently appeared in distantly related Gymnosperm taxa. Hence, the appearance of the seed habit and the accompanying necessity of seed dispersal has led to the invention of the fruit habit that thus seems to have appeared independently of the presence of flowers.

Detection of Evolutionarily Distinct Avian Influenza A Viruses in Antarctica

PubMed Central

Vijaykrishna, Dhanasekaran; Butler, Jeffrey; Baas, Chantal; Maurer-Stroh, Sebastian; Silva-de-la-Fuente, M. Carolina; Medina-Vogel, Gonzalo; Olsen, Bjorn; Kelso, Anne; Barr, Ian G.; González-Acuña, Daniel

2014-01-01

ABSTRACT Distinct lineages of avian influenza viruses (AIVs) are harbored by spatially segregated birds, yet significant surveillance gaps exist around the globe. Virtually nothing is known from the Antarctic. Using virus culture, molecular analysis, full genome sequencing, and serology of samples from Adélie penguins in Antarctica, we confirmed infection by H11N2 subtype AIVs. Their genetic segments were distinct from all known contemporary influenza viruses, including South American AIVs, suggesting spatial separation from other lineages. Only in the matrix and polymerase acidic gene phylogenies did the Antarctic sequences form a sister relationship to South American AIVs, whereas distant phylogenetic relationships were evident in all other gene segments. Interestingly, their neuraminidase genes formed a distant relationship to all avian and human influenza lineages, and the polymerase basic 1 and polymerase acidic formed a sister relationship to the equine H3N8 influenza virus lineage that emerged during 1963 and whose avian origins were previously unknown. We also estimated that each gene segment had diverged for 49 to 80 years from its most closely related sequences, highlighting a significant gap in our AIV knowledge in the region. We also show that the receptor binding properties of the H11N2 viruses are predominantly avian and that they were unable to replicate efficiently in experimentally inoculated ferrets, suggesting their continuous evolution in avian hosts. These findings add substantially to our understanding of both the ecology and the intra- and intercontinental movement of Antarctic AIVs and highlight the potential risk of an incursion of highly pathogenic AIVs into this fragile environment. PMID:24803521

Evolution and diversification of the CYC/TB1 gene family in Asteraceae--a comparative study in Gerbera (Mutisieae) and sunflower (Heliantheae).

PubMed

Tähtiharju, Sari; Rijpkema, Anneke S; Vetterli, Adrien; Albert, Victor A; Teeri, Teemu H; Elomaa, Paula

2012-04-01

Plant-specific TCP domain transcription factors have been shown to regulate morphological novelties during plant evolution, including the complex architecture of the Asteraceae inflorescence that involves different types of flowers. We conducted comparative analysis of the CYCLOIDEA/TEOSINTE BRANCHED1 (CYC/TB1) gene family in Gerbera hybrida (gerbera) and Helianthus annuus (sunflower), two species that represent distant tribes within Asteraceae. Our data confirm that the CYC/TB1 gene family has expanded in Asteraceae, a condition that appears to be connected with the increased developmental complexity and evolutionary success of this large plant family. Phylogenetic analysis of the CYC/TB1 gene family revealed both shared and lineage-specific duplications in gerbera and sunflower, corresponding to the three gene lineages previously identified as specific to core eudicots: CYC1, CYC2, and CYC3. Expression analyses of early stages of flower primordia development indicated that especially within the CYC2 clade, with the greatest number of secondary gene duplications, gene expression patterns are conserved between the species and associated with flower and inflorescence development. All sunflower and gerbera CYC2 clade genes showed differential expression between developing flower types, being upregulated in marginal ray (and trans) flowers. One gene in gerbera (GhCYC3) and two in sunflower (HaCYC2d and HaCYC2c) were indicated to be strong candidates as regulators of ray flower identity, a function that is specific for Asteraceae. Our data further showed that other CYC2 clade genes are likely to have more specialized functions at the level of single flowers, including the late functions in floral reproductive organs that may be more conserved across plant families. The expression patterns of CYC1 and CYC3 clade genes showed more differences between the two species but still pointed to possible conserved functions during vegetative plant development. Pairwise protein-protein interaction assays gave the first molecular evidence that CYC/TB1-like proteins function in complexes. Compared with sunflower, the gerbera proteins showed higher capacity for dimerization, between as well as within CYC clades. Our data from two distant species within the Asteraceae suggest that the expansion and the apparent conservation of especially the CYC2 clade CYC/TB1-like genes are associated with the evolution of the increased complexity of the Asteraceae inflorescence architecture.

Allotetraploid origin and divergence in Eleusine (Chloridoideae, Poaceae): evidence from low-copy nuclear gene phylogenies and a plastid gene chronogram.

PubMed

Liu, Qing; Triplett, Jimmy K; Wen, Jun; Peterson, Paul M

2011-11-01

Eleusine (Poaceae) is a small genus of the subfamily Chloridoideae exhibiting considerable morphological and ecological diversity in East Africa and the Americas. The interspecific phylogenetic relationships of Eleusine are investigated in order to identify its allotetraploid origin, and a chronogram is estimated to infer temporal relationships between palaeoenvironment changes and divergence of Eleusine in East Africa. Two low-copy nuclear (LCN) markers, Pepc4 and EF-1α, were analysed using parsimony, likelihood and Bayesian approaches. A chronogram of Eleusine was inferred from a combined data set of six plastid DNA markers (ndhA intron, ndhF, rps16-trnK, rps16 intron, rps3, and rpl32-trnL) using the Bayesian dating method. The monophyly of Eleusine is strongly supported by sequence data from two LCN markers. In the cpDNA phylogeny, three tetraploid species (E. africana, E. coracana and E. kigeziensis) share a common ancestor with the E. indica-E. tristachya clade, which is considered a source of maternal parents for allotetraploids. Two homoeologous loci are isolated from three tetraploid species in the Pepc4 phylogeny, and the maternal parents receive further support. The A-type EF-1α sequences possess three characters, i.e. a large number of variations of intron 2; clade E-A distantly diverged from clade E-B and other diploid species; and seven deletions in intron 2, implying a possible derivation through a gene duplication event. The crown age of Eleusine and the allotetraploid lineage are 3·89 million years ago (mya) and 1·40 mya, respectively. The molecular data support independent allotetraploid origins for E. kigeziensis and the E. africana-E. coracana clade. Both events may have involved diploids E. indica and E. tristachya as the maternal parents, but the paternal parents remain unidentified. The habitat-specific hypothesis is proposed to explain the divergence of Eleusine and its allotetraploid lineage.

Allotetraploid origin and divergence in Eleusine (Chloridoideae, Poaceae): evidence from low-copy nuclear gene phylogenies and a plastid gene chronogram

PubMed Central

Liu, Qing; Triplett, Jimmy K.; Wen, Jun; Peterson, Paul M.

2011-01-01

Background and Aims Eleusine (Poaceae) is a small genus of the subfamily Chloridoideae exhibiting considerable morphological and ecological diversity in East Africa and the Americas. The interspecific phylogenetic relationships of Eleusine are investigated in order to identify its allotetraploid origin, and a chronogram is estimated to infer temporal relationships between palaeoenvironment changes and divergence of Eleusine in East Africa. Methods Two low-copy nuclear (LCN) markers, Pepc4 and EF-1α, were analysed using parsimony, likelihood and Bayesian approaches. A chronogram of Eleusine was inferred from a combined data set of six plastid DNA markers (ndhA intron, ndhF, rps16-trnK, rps16 intron, rps3, and rpl32-trnL) using the Bayesian dating method. Key Results The monophyly of Eleusine is strongly supported by sequence data from two LCN markers. In the cpDNA phylogeny, three tetraploid species (E. africana, E. coracana and E. kigeziensis) share a common ancestor with the E. indica–E. tristachya clade, which is considered a source of maternal parents for allotetraploids. Two homoeologous loci are isolated from three tetraploid species in the Pepc4 phylogeny, and the maternal parents receive further support. The A-type EF-1α sequences possess three characters, i.e. a large number of variations of intron 2; clade E-A distantly diverged from clade E-B and other diploid species; and seven deletions in intron 2, implying a possible derivation through a gene duplication event. The crown age of Eleusine and the allotetraploid lineage are 3·89 million years ago (mya) and 1·40 mya, respectively. Conclusions The molecular data support independent allotetraploid origins for E. kigeziensis and the E. africana–E. coracana clade. Both events may have involved diploids E. indica and E. tristachya as the maternal parents, but the paternal parents remain unidentified. The habitat-specific hypothesis is proposed to explain the divergence of Eleusine and its allotetraploid lineage. PMID:21880659

The complexity of gene expression dynamics revealed by permutation entropy

PubMed Central

2010-01-01

Background High complexity is considered a hallmark of living systems. Here we investigate the complexity of temporal gene expression patterns using the concept of Permutation Entropy (PE) first introduced in dynamical systems theory. The analysis of gene expression data has so far focused primarily on the identification of differentially expressed genes, or on the elucidation of pathway and regulatory relationships. We aim to study gene expression time series data from the viewpoint of complexity. Results Applying the PE complexity metric to abiotic stress response time series data in Arabidopsis thaliana, genes involved in stress response and signaling were found to be associated with the highest complexity not only under stress, but surprisingly, also under reference, non-stress conditions. Genes with house-keeping functions exhibited lower PE complexity. Compared to reference conditions, the PE of temporal gene expression patterns generally increased upon stress exposure. High-complexity genes were found to have longer upstream intergenic regions and more cis-regulatory motifs in their promoter regions indicative of a more complex regulatory apparatus needed to orchestrate their expression, and to be associated with higher correlation network connectivity degree. Arabidopsis genes also present in other plant species were observed to exhibit decreased PE complexity compared to Arabidopsis specific genes. Conclusions We show that Permutation Entropy is a simple yet robust and powerful approach to identify temporal gene expression profiles of varying complexity that is equally applicable to other types of molecular profile data. PMID:21176199

Structure, Expression, Chromosomal Location and Product of the Gene Encoding Adh2 in Petunia

PubMed Central

Gregerson, R. G.; Cameron, L.; McLean, M.; Dennis, P.; Strommer, J.

1993-01-01

In most higher plants the genes encoding alcohol dehydrogenase comprise a small gene family, usually with two members. The Adh1 gene of Petunia has been cloned and analyzed, but a second identifiable gene was not recovered from any of three genomic libraries. We have therefore employed the polymerase chain reaction to obtain the major portion of a second Adh gene. From sequence, mapping and northern data we conclude this gene encodes ADH2, the major anaerobically inducible Adh gene of Petunia. The availability of both Adh1 and Adh2 from Petunia has permitted us to compare their structures and patterns of expression to those of the well-studied Adh genes of maize, of which one is highly expressed developmentally, while both are induced in response to hypoxia. Despite their evolutionary distance, evidenced by deduced amino acid sequence as well as taxonomic classification, the pairs of genes are regulated in strikingly similar ways in maize and Petunia. Our findings suggest a significant biological basis for the regulatory strategy employed by these distant species for differential expression of multiple Adh genes. PMID:8096485

Long Ago It Was Meant to Be: The Interplay Between Time, Construal, and Fate Beliefs

PubMed Central

Burrus, Jeremy; Roese, Neal J.

2008-01-01

Fate means that an event was meant to be, that is, predetermined by prior unseen forces. Most people believe in fate, which seems at odds with similarly pervasive beliefs that alternative past actions would have brought about different circumstances (i.e., counterfactual beliefs). Two experiments revealed that construal level accounts for the relative plausibility of fate versus counterfactual explanations. Construal was manipulated in Experiment 1, such that goal pursuits framed in abstract (“why?”) as opposed to concrete (“how?”) terms heightened fate but not counterfactual attributions. Extending this finding, Experiment 2 showed that fate judgments were higher for temporally distant than recent past events, an effect mediated by construal perceptions. Neither counterfactual nor luck judgments varied with temporal distance. These findings help to explain how individuals explain complicated yet meaningful life events while extending the reach of Trope and Liberman’s (2003) construal-level theory. PMID:16861309

Spontaneous tempo and rhythmic entrainment in a bonobo (Pan paniscus).

PubMed

Large, Edward W; Gray, Patricia M

2015-11-01

The emergence of speech and music in the human species represent major evolutionary transitions that enabled the use of complex, temporally structured acoustic signals to coordinate social interaction. While the fundamental capacity for temporal coordination with complex acoustic signals has been shown in a few distantly related species, the extent to which nonhuman primates exhibit sensitivity to auditory rhythms remains controversial. In Experiment 1, we assessed spontaneous motor tempo and tempo matching in a bonobo (Pan paniscus), in the context of a social drumming interaction. In Experiment 2, the bonobo spontaneously entrained and synchronized her drum strikes within a range around her spontaneous motor tempo. Our results are consistent with the hypothesis that the evolution of acoustic communication builds upon fundamental neurodynamic mechanisms that can be found in a wide range of species, and are recruited for social interactions. (c) 2015 APA, all rights reserved).

Genome-wide transcriptome study in wheat identified candidate genes related to processing quality, majority of them showing interaction (quality x development) and having temporal and spatial distributions.

PubMed

Singh, Anuradha; Mantri, Shrikant; Sharma, Monica; Chaudhury, Ashok; Tuli, Rakesh; Roy, Joy

2014-01-16

The cultivated bread wheat (Triticum aestivum L.) possesses unique flour quality, which can be processed into many end-use food products such as bread, pasta, chapatti (unleavened flat bread), biscuit, etc. The present wheat varieties require improvement in processing quality to meet the increasing demand of better quality food products. However, processing quality is very complex and controlled by many genes, which have not been completely explored. To identify the candidate genes whose expressions changed due to variation in processing quality and interaction (quality x development), genome-wide transcriptome studies were performed in two sets of diverse Indian wheat varieties differing for chapatti quality. It is also important to understand the temporal and spatial distributions of their expressions for designing tissue and growth specific functional genomics experiments. Gene-specific two-way ANOVA analysis of expression of about 55 K transcripts in two diverse sets of Indian wheat varieties for chapatti quality at three seed developmental stages identified 236 differentially expressed probe sets (10-fold). Out of 236, 110 probe sets were identified for chapatti quality. Many processing quality related key genes such as glutenin and gliadins, puroindolines, grain softness protein, alpha and beta amylases, proteases, were identified, and many other candidate genes related to cellular and molecular functions were also identified. The ANOVA analysis revealed that the expression of 56 of 110 probe sets was involved in interaction (quality x development). Majority of the probe sets showed differential expression at early stage of seed development i.e. temporal expression. Meta-analysis revealed that the majority of the genes expressed in one or a few growth stages indicating spatial distribution of their expressions. The differential expressions of a few candidate genes such as pre-alpha/beta-gliadin and gamma gliadin were validated by RT-PCR. Therefore, this study identified several quality related key genes including many other genes, their interactions (quality x development) and temporal and spatial distributions. The candidate genes identified for processing quality and information on temporal and spatial distributions of their expressions would be useful for designing wheat improvement programs for processing quality either by changing their expression or development of single nucleotide polymorphisms (SNPs) markers.

Genome-wide transcriptome study in wheat identified candidate genes related to processing quality, majority of them showing interaction (quality x development) and having temporal and spatial distributions

PubMed Central

2014-01-01

Background The cultivated bread wheat (Triticum aestivum L.) possesses unique flour quality, which can be processed into many end-use food products such as bread, pasta, chapatti (unleavened flat bread), biscuit, etc. The present wheat varieties require improvement in processing quality to meet the increasing demand of better quality food products. However, processing quality is very complex and controlled by many genes, which have not been completely explored. To identify the candidate genes whose expressions changed due to variation in processing quality and interaction (quality x development), genome-wide transcriptome studies were performed in two sets of diverse Indian wheat varieties differing for chapatti quality. It is also important to understand the temporal and spatial distributions of their expressions for designing tissue and growth specific functional genomics experiments. Results Gene-specific two-way ANOVA analysis of expression of about 55 K transcripts in two diverse sets of Indian wheat varieties for chapatti quality at three seed developmental stages identified 236 differentially expressed probe sets (10-fold). Out of 236, 110 probe sets were identified for chapatti quality. Many processing quality related key genes such as glutenin and gliadins, puroindolines, grain softness protein, alpha and beta amylases, proteases, were identified, and many other candidate genes related to cellular and molecular functions were also identified. The ANOVA analysis revealed that the expression of 56 of 110 probe sets was involved in interaction (quality x development). Majority of the probe sets showed differential expression at early stage of seed development i.e. temporal expression. Meta-analysis revealed that the majority of the genes expressed in one or a few growth stages indicating spatial distribution of their expressions. The differential expressions of a few candidate genes such as pre-alpha/beta-gliadin and gamma gliadin were validated by RT-PCR. Therefore, this study identified several quality related key genes including many other genes, their interactions (quality x development) and temporal and spatial distributions. Conclusions The candidate genes identified for processing quality and information on temporal and spatial distributions of their expressions would be useful for designing wheat improvement programs for processing quality either by changing their expression or development of single nucleotide polymorphisms (SNPs) markers. PMID:24433256

Stress hormones predict hyperbolic time-discount rates six months later in adults.

PubMed

Takahashi, Taiki; Shinada, Mizuho; Inukai, Keigo; Tanida, Shigehito; Takahashi, Chisato; Mifune, Nobuhiro; Takagishi, Haruto; Horita, Yutaka; Hashimoto, Hirofumi; Yokota, Kunihiro; Kameda, Tatsuya; Yamagishi, Toshio

2010-01-01

Stress hormones have been associated with temporal discounting. Although time-discount rate is shown to be stable over a long term, no study to date examines whether individual differences in stress hormones could predict individuals' time-discount rates in the relatively distant future (e.g., six month later), which is of interest in neuroeconomics of stress-addiction association. We assessed 87 participants' salivary stress hormone (cortisol, cortisone, and alpha-amylase) levels and hyperbolic discounting of delayed rewards consisting of three magnitudes, at the time-interval of six months. For salivary steroid assays, we employed a liquid chromatography/ mass spectroscopy (LC/MS) method. The correlations between the stress hormone levels and time-discount rates were examined. We observed that salivary alpha-amylase (sAA) levels were negatively associated with time-discount rates in never-smokers. Notably, salivary levels of stress steroids (i.e., cortisol and cortisone) negatively and positively related to time-discount rates in men and women, respectively, in never-smokers. Ever-smokers' discount rates were not predicted from these stress hormone levels. Individual differences in stress hormone levels predict impulsivity in temporal discounting in the future. There are sex differences in the effect of stress steroids on temporal discounting; while there was no sex defference in the relationship between sAA and temporal discounting.

Amygdala atrophy affects emotion-related activity in face-responsive regions in frontotemporal degeneration.

PubMed

De Winter, François-Laurent; Van den Stock, Jan; de Gelder, Beatrice; Peeters, Ronald; Jastorff, Jan; Sunaert, Stefan; Vanduffel, Wim; Vandenberghe, Rik; Vandenbulcke, Mathieu

2016-09-01

In the healthy brain, modulatory influences from the amygdala commonly explain enhanced activation in face-responsive areas by emotional facial expressions relative to neutral expressions. In the behavioral variant frontotemporal dementia (bvFTD) facial emotion recognition is impaired and has been associated with atrophy of the amygdala. By combining structural and functional MRI in 19 patients with bvFTD and 20 controls we investigated the neural effects of emotion in face-responsive cortex and its relationship with amygdalar gray matter (GM) volume in neurodegeneration. Voxel-based morphometry revealed decreased GM volume in anterior medio-temporal regions including amygdala in patients compared to controls. During fMRI, we presented dynamic facial expressions (fear and chewing) and their spatiotemporally scrambled versions. We found enhanced activation for fearful compared to neutral faces in ventral temporal cortex and superior temporal sulcus in controls, but not in patients. In the bvFTD group left amygdalar GM volume correlated positively with emotion-related activity in left fusiform face area (FFA). This correlation was amygdala-specific and driven by GM in superficial and basolateral (BLA) subnuclei, consistent with reported amygdalar-cortical networks. The data suggests that anterior medio-temporal atrophy in bvFTD affects emotion processing in distant posterior areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dissecting the sea wheatgrass genome to transfer biotic stress resistance and abiotic stress tolerance into wheat

USDA-ARS?s Scientific Manuscript database

Wheat production is facing numerous challenges from biotic and abiotic stresses. Alien gene transfer has been an effective approach for wheat germplasm enhancement. Sea wheatgrass (SWG) (Thinopyrum junceiforme, 2n = 4x = 28, genomes J1J1J2J2) is a distant relative of wheat and a relatively untapped ...

Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer.

PubMed

Neskey, David M; Osman, Abdullah A; Ow, Thomas J; Katsonis, Panagiotis; McDonald, Thomas; Hicks, Stephanie C; Hsu, Teng-Kuei; Pickering, Curtis R; Ward, Alexandra; Patel, Ameeta; Yordy, John S; Skinner, Heath D; Giri, Uma; Sano, Daisuke; Story, Michael D; Beadle, Beth M; El-Naggar, Adel K; Kies, Merrill S; William, William N; Caulin, Carlos; Frederick, Mitchell; Kimmel, Marek; Myers, Jeffrey N; Lichtarge, Olivier

2015-04-01

TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. ©2015 American Association for Cancer Research.

Evolutionary Action score of TP53 (EAp53) identifies high risk mutations associated with decreased survival and increased distant metastases in head and neck cancer

PubMed Central

Neskey, David M.; Osman, Abdullah A.; Ow, Thomas J.; Katsonis, Panagiotis; McDonald, Thomas; Hicks, Stephanie C.; Hsu, Teng-Kuei; Pickering, Curtis R.; Ward, Alexandra; Patel, Ameeta; Yordy, John S.; Skinner, Heath D.; Giri, Uma; Sano, Daisuke; Story, Michael D.; Beadle, Beth M.; El-Naggar, Adel K.; Kies, Merrill S.; William, William N.; Caulin, Carlos; Frederick, Mitchell; Kimmel, Marek; Myers, Jeffrey N.; Lichtarge, Olivier

2015-01-01

TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC) with mutations occurring in over two third of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed Evolutionary Action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations which confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations. PMID:25634208

Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy.

PubMed

Esteva, Francisco J; Sahin, Aysegul A; Cristofanilli, Massimo; Coombes, Kevin; Lee, Sang-Joon; Baker, Joffre; Cronin, Maureen; Walker, Michael; Watson, Drew; Shak, Steven; Hortobagyi, Gabriel N

2005-05-01

To test the ability of a reverse transcriptase-PCR (RT-PCR) assay, based on gene expression profiles, to accurately determine the risk of recurrence in patients with node-negative breast cancer who did not receive systemic therapy using formalin-fixed, paraffin-embedded tissue. A secondary objective was to determine whether the quantitative RT-PCR data correlated with immunohistochemistry assay data regarding estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We obtained archival paraffin-embedded tissue from patients with invasive breast cancer but no axillary lymph node involvement who had received no adjuvant systemic therapy and been followed for at least 5 years. RNA was extracted from three 10-microm-thick sections. The expression of 16 cancer-related genes and 5 reference genes was quantified using RT-PCR. A gene expression algorithm was used to calculate a recurrence score for each patient. We then assessed the ability of the test to accurately predict distant recurrence-free survival in this population. We identified 149 eligible patients. Median age at diagnosis was 59 years; mean tumor diameter was 2 cm; and 69% of tumors were estrogen receptor positive. Median follow-up was 18 years. The 5-year disease-free survival rate for the group was 80%. The 21 gene-based recurrence score was not predictive of distant disease recurrence. However, a high concordance between RT-PCR and immunohistochemical assays for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status was noted. RT-PCR can be done on paraffin-embedded tissue to validate the large numbers of genes associated with breast cancer recurrence. However, further work needs to be done to develop an assay to identify the likelihood of recurrent disease in patients with node-negative breast cancer who do not receive adjuvant tamoxifen or chemotherapy.

Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples

PubMed Central

2011-01-01

Background Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome. Methods We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays. Results Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%. We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the SLC45A3-ELK4 e4-e2 TIC to ERG-negative prostate samples, as confirmed in 20 matched prostate tumor and normal samples and 9 lung cancer cell lines. Conclusions Deep transcriptional sequencing and analysis with targeted and spliced alignment methods can effectively identify TIC events across the genome in individual tissues. Prostate and reference samples exhibit a wide range of TIC events, involving more genes than estimated previously using ESTs. Tissue specificity of TIC events is correlated with expression patterns of the upstream gene. Some TIC events, such as MSMB-NCOA4, may play functional roles in cancer. PMID:21261984

Pyridostigmine for reversal of severe sequelae from botulinum toxin injection.

PubMed

Young, David L; Halstead, Lucinda A

2014-11-01

Botulinum toxin is used to treat a wide range of dystonias in the head and neck. Occasionally, patients receiving laryngeal botulinum toxin experience severe dysphagia, dyspnea, or even distant and autonomic symptoms. Rarely, these patients may require hospitalization with possible intubation and placement of nasogastric tubes. Botulinum antitoxin is not readily available and ineffective once symptoms have progressed, so patients must wait until the toxin wears off over weeks to months. Pyridostigmine prevents the breakdown of acetylcholine at the neuromuscular junction, thus making more neurotransmitter available for the muscles. A retrospective case study of patients receiving botulinum toxin for dystonia in the head and neck from 1998 to 2012 who experienced adverse effects that were successfully treated with pyridostigmine. Twenty cases were selected and reviewed to demonstrate how pyridostigmine was used to modulate severe dysphagia, breathiness, dyspnea, and some distant/autonomic symptoms. Pyridostigmine was well tolerated and resulted in significant symptom improvement. Only one significant adverse effect, bradycardia, occurred in a patient with severe cardiac disease. Given the safety and efficacy of this medication, pyridostigmine should be considered to modulate severe sequelae of botulinum toxin in select patients when conservative management is deemed insufficient. Also, physicians should be aware that patient complaints of symptoms at distant sites and temporally delayed from the injection may be a result of the botulinum toxin and relieved with pyridostigmine. Copyright © 2014 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Morphology and Phylogeny of a New Species of Anaerobic Ciliate, Trimyema finlayi n. sp., with Endosymbiotic Methanogens.

PubMed

Lewis, William H; Sendra, Kacper M; Embley, T Martin; Esteban, Genoveva F

2018-01-01

Many anaerobic ciliated protozoa contain organelles of mitochondrial ancestry called hydrogenosomes. These organelles generate molecular hydrogen that is consumed by methanogenic Archaea, living in endosymbiosis within many of these ciliates. Here we describe a new species of anaerobic ciliate, Trimyema finlayi n. sp., by using silver impregnation and microscopy to conduct a detailed morphometric analysis. Comparisons with previously published morphological data for this species, as well as the closely related species, Trimyema compressum , demonstrated that despite them being similar, both the mean cell size and the mean number of somatic kineties are lower for T. finlayi than for T. compressum , which suggests that they are distinct species. This was also supported by analysis of the 18S rRNA genes from these ciliates, the sequences of which are 97.5% identical (6 substitutions, 1479 compared bases), and in phylogenetic analyses these sequences grouped with other 18S rRNA genes sequenced from previous isolates of the same respective species. Together these data provide strong evidence that T. finlayi is a novel species of Trimyema , within the class Plagiopylea. Various microscopic techniques demonstrated that T. finlayi n. sp. contains polymorphic endosymbiotic methanogens, and analysis of the endosymbionts' 16S rRNA gene showed that they belong to the genus Methanocorpusculum , which was confirmed using fluorescence in situ hybridization with specific probes. Despite the degree of similarity and close relationship between these ciliates, T. compressum contains endosymbiotic methanogens from a different genus, Methanobrevibacter . In phylogenetic analyses of 16S rRNA genes, the Methanocorpusculum endosymbiont of T. finlayi n. sp. grouped with sequences from Methanomicrobia, including the endosymbiont of an earlier isolate of the same species, ' Trimyema sp.,' which was sampled approximately 22 years earlier, at a distant (∼400 km) geographical location. Identification of the same endosymbiont species in the two separate isolates of T. finlayi n. sp. provides evidence for spatial and temporal stability of the Methanocorpusculum-T. finlayi n. sp. endosymbiosis. T. finlayi n. sp. and T. compressum provide an example of two closely related anaerobic ciliates that have endosymbionts from different methanogen genera, suggesting that the endosymbionts have not co-speciated with their hosts.

When do I wear me out? Mental simulation and the diminution of self-control.

PubMed

Macrae, C Neil; Christian, Brittany M; Golubickis, Marius; Karanasiou, Magdalene; Troksiarova, Lenka; McNamara, Diana L; Miles, Lynden K

2014-08-01

Exerting self-control can diminish people's capacity to engage in subsequent acts of behavioral regulation, a phenomenon termed ego depletion. But what of imaginary regulatory experiences-does simulated restraint elicit comparable lapses in self-control? Here we demonstrate such effects under theoretically tractable imagery conditions. Across 3 experiments, temporal, structural, and spatial components of mental simulation were observed to drive the efficacy of imaginary self-control. In Experiment 1, lapses in restraint (i.e., financial impulsivity) were more pronounced when imaginary regulation (i.e., dietary restraint) focused on an event in the near versus distant future. In Experiment 2, comparable effects (i.e., increased stereotyping) emerged when simulated self-control (i.e., emotional suppression) was imagined from a first-person (cf. third-person) visual perspective. In Experiment 3, restraint was diminished (i.e., increased risk taking) when self-regulation (i.e., action control) centered on an event at a near versus distant location. These findings further delineate the conditions under which mental simulation impacts core aspects of social-cognitive functioning. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Two Anatomically and Computationally Distinct Learning Signals Predict Changes to Stimulus-Outcome Associations in Hippocampus.

PubMed

Boorman, Erie D; Rajendran, Vani G; O'Reilly, Jill X; Behrens, Tim E

2016-03-16

Complex cognitive processes require sophisticated local processing but also interactions between distant brain regions. It is therefore critical to be able to study distant interactions between local computations and the neural representations they act on. Here we report two anatomically and computationally distinct learning signals in lateral orbitofrontal cortex (lOFC) and the dopaminergic ventral midbrain (VM) that predict trial-by-trial changes to a basic internal model in hippocampus. To measure local computations during learning and their interaction with neural representations, we coupled computational fMRI with trial-by-trial fMRI suppression. We find that suppression in a medial temporal lobe network changes trial-by-trial in proportion to stimulus-outcome associations. During interleaved choice trials, we identify learning signals that relate to outcome type in lOFC and to reward value in VM. These intervening choice feedback signals predicted the subsequent change to hippocampal suppression, suggesting a convergence of signals that update the flexible representation of stimulus-outcome associations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cancer terminator viruses (CTV): A better solution for viral-based therapy of cancer.

PubMed

Emdad, Luni; Das, Swadesh K; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B

2018-08-01

In principle, viral gene therapy holds significant potential for the therapy of solid cancers. However, this promise has not been fully realized and systemic administration of viruses has not proven as successful as envisioned in the clinical arena. Our research is focused on developing the next generation of efficacious viruses to specifically treat both primary cancers and a major cause of cancer lethality, metastatic tumors (that have spread from a primary site of origin to other areas in the body and are responsible for an estimated 90% of cancer deaths). We have generated a chimeric tropism-modified type 5 and 3 adenovirus that selectively replicates in cancer cells and simultaneously produces a secreted anti-cancer toxic cytokine, melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24), referred to as a Cancer Terminator Virus (CTV) (Ad.5/3-CTV). In preclinical animal models, injection into a primary tumor causes selective cell death and therapeutic activity is also observed in non-injected distant tumors, that is, "bystander anti-tumor activity." To enhance the impact and therapeutic utility of the CTV, we have pioneered an elegant approach in which viruses are encapsulated in microbubbles allowing "stealth delivery" to tumor cells that when treated with focused ultrasound causes viral release killing tumor cells through viral replication, and producing and secreting MDA-7/IL-24, which stimulates the immune system to attack distant cancers, inhibits tumor angiogenesis and directly promotes apoptosis in distant cancer cells. This strategy is called UTMD (ultrasound-targeted microbubble-destruction). This novel CTV and UTMD approach hold significant promise for the effective therapy of primary and disseminated tumors. © 2017 Wiley Periodicals, Inc.

Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20.

PubMed

Mamounas, Eleftherios P; Tang, Gong; Fisher, Bernard; Paik, Soonmyung; Shak, Steven; Costantino, Joseph P; Watson, Drew; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

2010-04-01

The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)-positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20). RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored. In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen-treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment. Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer.

Molecular characterization and expression of microbial inulinase genes.

PubMed

Liu, Guang-Lei; Chi, Zhe; Chi, Zhen-Ming

2013-05-01

Many genes encoding exo- and endo-inulinases from bacteria, yeasts and filamentous fungi have been cloned and characterized. All the inulinases have several conserved motifs, such as WMND(E)PNGL, RDP, EC(V)P, SVEVF, Q and FS(T), which play an important role in inulinase catalysis and substrate binding. However, the exo-inulinases produced by yeasts has no conserved motif SVEVF and the yeasts do not produce any endo-inulinase. Exo- and endo-inulinases found in different microorganisms cluster separately at distant positions from each other. Most of the cloned inulinase genes have been expressed in Yarrowia lipolytica, Saccharomyces cerevisiae, Pichia pastoris, Klyuveromyces lactis and Escherichia coli, respectively. The recombinant inulinases produced and the engineered hosts using the cloned inulinase genes have many potential applications. Expression of most of the inulinase genes is repressed by glucose and fructose and induced by inulin and sucrose. However, the detailed mechanisms of the repression and induction are still unknown.

Predictable transcriptome evolution in the convergent and complex bioluminescent organs of squid

PubMed Central

Pankey, M. Sabrina; Minin, Vladimir N.; Imholte, Greg C.; Suchard, Marc A.; Oakley, Todd H.

2014-01-01

Despite contingency in life’s history, the similarity of evolutionarily convergent traits may represent predictable solutions to common conditions. However, the extent to which overall gene expression levels (transcriptomes) underlying convergent traits are themselves convergent remains largely unexplored. Here, we show strong statistical support for convergent evolutionary origins and massively parallel evolution of the entire transcriptomes in symbiotic bioluminescent organs (bacterial photophores) from two divergent squid species. The gene expression similarities are so strong that regression models of one species’ photophore can predict organ identity of a distantly related photophore from gene expression levels alone. Our results point to widespread parallel changes in gene expression evolution associated with convergent origins of complex organs. Therefore, predictable solutions may drive not only the evolution of novel, complex organs but also the evolution of overall gene expression levels that underlie them. PMID:25336755

Of extracellular matrix, scaffolds, and signaling: Tissuearchitectureregulates development, homeostasis, and cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, Celeste M.; Bissell, Mina J.

2006-03-09

The microenvironment surrounding cells influences gene expression, such that a cell's behavior is largely determined by its interactions with the extracellular matrix, neighboring cells, and soluble cues released locally or by distant tissues. We describe the essential role of context and organ structure in directing mammary gland development and differentiated function, and in determining response to oncogenic insults including mutations. We expand on the concept of 'dynamic reciprocity' to present an integrated view of development, cancer, and aging, and posit that genes are like piano keys: while essential, it is the context that makes the music.

Temporal and tissue-specific regulation of a Brassica napus stearoyl-acyl carrier protein desaturase gene.

PubMed Central

Slocombe, S P; Piffanelli, P; Fairbairn, D; Bowra, S; Hatzopoulos, P; Tsiantis, M; Murphy, D J

1994-01-01

The nucleotide sequence of a Brassica napus stearoyl-acyl carrier protein desaturase gene (Bn10) is presented. This gene is one member of a family of four closely related genes expressed in oilseed rape. The expression of the promoter of this gene in transgenic tobacco was found to be temporally regulated in the developing seed tissues. However, the promoter was also particularly active in other oleogenic tissues such as the tapetum and pollen grains. This raises the interesting question of whether seed-expressed lipid synthesis genes are regulated by separate tissue-specific determinants or by a single factor common to all oleogenic tissues. Parts of the plants undergoing rapid development such as the components of immature flowers and seedlings also exhibited high levels of promoter activity. These tissues are likely to have an elevated requirement for membrane lipid synthesis. Stearoyl-acyl carrier protein desaturase transcript levels have previously been shown to be temporally regulated in the B. napus embryo (S.P. Slocombe, I. Cummins, R.P. Jarvis, D.J. Murphy [1992] Plant Mol Biol 20: 151-155). Evidence is presented demonstrating the induction of desaturase mRNA by abscisic acid in the embryo. PMID:8016261

Heart morphogenesis gene regulatory networks revealed by temporal expression analysis.

PubMed

Hill, Jonathon T; Demarest, Bradley; Gorsi, Bushra; Smith, Megan; Yost, H Joseph

2017-10-01

During embryogenesis the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq timecourse in zebrafish from 30 hpf to 72 hpf and identified 5861 genes with altered expression. We clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis. This approach predicted hundreds of regulatory interactions and found batteries enriched in specific cell and tissue types, indicating that the approach can be used to narrow the search for novel genetic markers and regulatory interactions. Subsequent analyses confirmed the GRN using two mutants, Tbx5 and nkx2-5 , and identified sets of duplicated zebrafish genes that do not show temporal subfunctionalization. This dataset provides an essential resource for future studies on the genetic/epigenetic pathways implicated in congenital heart defects and the mechanisms of cardiac transcriptional regulation. © 2017. Published by The Company of Biologists Ltd.

An Approximation to the Temporal Order in Endogenous Circadian Rhythms of Genes Implicated in Human Adipose Tissue Metabolism

PubMed Central

GARAULET, MARTA; ORDOVÁS, JOSÉ M.; GÓMEZ-ABELLÁN, PURIFICACIÓN; MARTÍNEZ, JOSE A.; MADRID, JUAN A.

2015-01-01

Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT including genes implicated in metabolic processes such as energy intake and expenditure, insulin resistance, adipocyte differentiation, dyslipidemia, and body fat distribution. Visceral and subcutaneous abdominal AT biopsies (n = 6) were obtained from morbid obese women (BMI ≥ 40 kg/m2). To investigate rhythmic expression pattern, AT explants were cultured during 24-h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h using quantitative real-time PCR. Clock genes, glucocorticoid metabolism-related genes, leptin, adiponectin and their receptors were studied. Significant differences were found both in achrophases and relative-amplitude among genes (P <0.05). Amplitude of most genes rhythms was high (>30%). When interpreting the phase map of gene expression in both depots, data indicated that circadian rhythmicity of the genes studied followed a predictable physiological pattern, particularly for subcutaneous AT. Interesting are the relationships between adiponectin, leptin, and glucocorticoid metabolism-related genes circadian profiles. Their metabolic significance is discussed. Visceral AT behaved in a different way than subcutaneous for most of the genes studied. For every gene, protein mRNA levels fluctuated during the day in synchrony with its receptors. We have provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue. PMID:21520059

The Good, The Bad, and The Distant: Soundscape Cues for Larval Fish.

PubMed

Piercy, Julius J B; Smith, David J; Codling, Edward A; Hill, Adam J; Simpson, Stephen D

2016-01-01

Coral reef noise is an important navigation cue for settling reef fish larvae and can thus potentially affect reef population dynamics. Recent evidence has shown that fish are able to discriminate between the soundscapes of different types of habitat (e.g., mangrove and reef). In this study, we investigated whether discernible acoustic differences were present between sites within the same coral reef system. Differences in sound intensity and transient content were found between sites, but site-dependent temporal variation was also present. We discuss the implications of these findings for settling fish larvae.

Diffusion tensor tractography detection of functional pathway for the spread of epileptiform activity between temporal lobe and Rolandic region.

PubMed

Bhardwaj, Ratan D; Mahmoodabadi, Sina Zarei; Otsubo, Hiroshi; Snead, O Carter; Rutka, James T; Widjaja, Elysa

2010-02-01

The aim of the study was to assess the connectivity between magnetoencephalographic (MEG) dipoles in the temporal lobe and Rolandic region in children with temporal lobe epilepsy using diffusion tensor imaging (DTI) tractography. Six pediatric patients with intractable focal epilepsy had MEG performed, which showed MEG dipoles over both temporal and Rolandic regions in a unilateral hemisphere. DTI tractography was performed on each patient. Six control subjects were studied for comparison. Two volumes of interest (VOIs) that encompassed the MEG dipoles were drawn, one placed in temporal lobe and the other in Rolandic region. Similar VOIs were placed in the contralateral side in the patients and on both sides in controls. Fractional anisotropy (FA) and trace of the external capsules were compared between patients and controls. In all patients, a tractography pathway traversing through the external capsule, connecting the temporal and Rolandic MEG dipoles, was visualized. However, on the contralateral hemisphere in each patient, there was no evidence of a similar fiber tract. There was no corresponding tractography pathway identified in either hemisphere within the controls. There were no significant differences in FA and trace between the seizure focus side and contralateral side in the patients. There was no significant difference in FA, but a difference in trace between patients and controls. We have found aberrant tractography pathway traversing through the external capsule, connecting two distant foci of epileptiform activity. Chronic interictal epileptogenic discharge could play a causal role in the de novo organization of these tracts.

Biochemical characterization of an ABC transporter LptBFGC complex required for the outer membrane sorting of lipopolysaccharides.

PubMed

Narita, Shin-ichiro; Tokuda, Hajime

2009-07-07

Seven Lpt proteins (A through G) are thought to be involved in lipopolysaccharide transport from the inner to outer membrane of Escherichia coli. LptB belongs to the ATP-binding cassette transporter superfamily. Although the lptB gene lacks neighboring genes encoding membrane subunits, bioinformatic analyses recently indicated that two distantly located consecutive genes, lptF and lptG, could encode membrane subunits. To examine this possibility, LptB was expressed with LptF and LptG. We report here that both LptF and LptG formed a complex with LptB. Furthermore, an inner membrane protein, LptC, which had been implicated in lipopolysaccharide transport, was also included in this complex.

Evolutionary rewiring of bacterial regulatory networks

PubMed Central

Taylor, Tiffany B.; Mulley, Geraldine; McGuffin, Liam J.; Johnson, Louise J.; Brockhurst, Michael A.; Arseneault, Tanya; Silby, Mark W.; Jackson, Robert W.

2015-01-01

Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks - homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. In our recent study [Taylor, et al. Science (2015), 347(6225)] we find that mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but that such mutations come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs. PMID:28357301

Near-isogenic cotton germplasm lines that differ in fiber-bundle strength have temporal differences in fiber gene expression patterns as revealed by comparative high-throughput profiling.

PubMed

Hinchliffe, Doug J; Meredith, William R; Yeater, Kathleen M; Kim, Hee Jin; Woodward, Andrew W; Chen, Z Jeffrey; Triplett, Barbara A

2010-05-01

Gene expression profiles of developing cotton (Gossypium hirsutum L.) fibers from two near-isogenic lines (NILs) that differ in fiber-bundle strength, short-fiber content, and in fewer than two genetic loci were compared using an oligonucleotide microarray. Fiber gene expression was compared at five time points spanning fiber elongation and secondary cell wall (SCW) biosynthesis. Fiber samples were collected from field plots in a randomized, complete block design, with three spatially distinct biological replications for each NIL at each time point. Microarray hybridizations were performed in a loop experimental design that allowed comparisons of fiber gene expression profiles as a function of time between the two NILs. Overall, developmental expression patterns revealed by the microarray experiment agreed with previously reported cotton fiber gene expression patterns for specific genes. Additionally, genes expressed coordinately with the onset of SCW biosynthesis in cotton fiber correlated with gene expression patterns of other SCW-producing plant tissues. Functional classification and enrichment analysis of differentially expressed genes between the two NILs revealed that genes associated with SCW biosynthesis were significantly up-regulated in fibers of the high-fiber quality line at the transition stage of cotton fiber development. For independent corroboration of the microarray results, 15 genes were selected for quantitative reverse transcription PCR analysis of fiber gene expression. These analyses, conducted over multiple field years, confirmed the temporal difference in fiber gene expression between the two NILs. We hypothesize that the loci conferring temporal differences in fiber gene expression between the NILs are important regulatory sequences that offer the potential for more targeted manipulation of cotton fiber quality.

Clinical significance of nm23 gene expression in gastric cancer.

PubMed

Mönig, Stefan P; Nolden, Brit; Lübke, Thomas; Pohl, Alexandra; Grass, Guido; Schneider, Paul M; Dienes, Hans P; Hölscher, Arnulf H; Baldus, Stephan E

2007-01-01

The expression of the nm23 gene has been associated with the development of metastasis. Numerous studies have shown down-regulation of nm23 expression in metastatic breast and colon cancer. The expression of the putative metastasis-suppressor gene nm23 in gastric carcinoma is controversial. The aim of this study was the analysis of nm23 expression in a large series of gastric cancer patients. In a retrospective immunohistochemical study specimens obtained from 116 gastric cancer patients (mean age 64 years; range: 33-85) who had undergone gastrectomy with extended lymphadenectomy were analyzed. Nm23 expression in the tumor epithelium was studied by immunohistochemistry followed by a semi-quantitative (score 0-3) evaluation. Statistical analysis including Chi-square test, uni- and multivariate survival analyses were performed. The nm23 staining pattern was positive (score 2-3) in 100 (86.2%) specimens and negative (score 0-1) in 16 (13.8%) samples. Lymph node metastasis was found in 65% of the patients. No significant correlations could be determined between nm23 expression and other variables such as gender, age, tumor differentiation, WHO-, Laurén-, Goseki-, or Ming-classification. The intensity of nm23 staining in the tumor cells was not significantly correlated with depth of tumor infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), UICC-stage, or prognosis. Our series did not show a correlation of nm23 expression in terms of lymph node and distant metastasis or prognosis in gastric cancer patients.

Differences in lateral gene transfer in hypersaline versus thermal environments.

PubMed

Rhodes, Matthew E; Spear, John R; Oren, Aharon; House, Christopher H

2011-07-08

The role of lateral gene transfer (LGT) in the evolution of microorganisms is only beginning to be understood. While most LGT events occur between closely related individuals, inter-phylum and inter-domain LGT events are not uncommon. These distant transfer events offer potentially greater fitness advantages and it is for this reason that these "long distance" LGT events may have significantly impacted the evolution of microbes. One mechanism driving distant LGT events is microbial transformation. Theoretically, transformative events can occur between any two species provided that the DNA of one enters the habitat of the other. Two categories of microorganisms that are well-known for LGT are the thermophiles and halophiles. We identified potential inter-class LGT events into both a thermophilic class of Archaea (Thermoprotei) and a halophilic class of Archaea (Halobacteria). We then categorized these LGT genes as originating in thermophiles and halophiles respectively. While more than 68% of transfer events into Thermoprotei taxa originated in other thermophiles, less than 11% of transfer events into Halobacteria taxa originated in other halophiles. Our results suggest that there is a fundamental difference between LGT in thermophiles and halophiles. We theorize that the difference lies in the different natures of the environments. While DNA degrades rapidly in thermal environments due to temperature-driven denaturization, hypersaline environments are adept at preserving DNA. Furthermore, most hypersaline environments, as topographical minima, are natural collectors of cellular debris. Thus halophiles would in theory be exposed to a greater diversity and quantity of extracellular DNA than thermophiles.

Temporal transcriptional logic of dynamic regulatory networks underlying nitrogen signaling and use in plants.

PubMed

Varala, Kranthi; Marshall-Colón, Amy; Cirrone, Jacopo; Brooks, Matthew D; Pasquino, Angelo V; Léran, Sophie; Mittal, Shipra; Rock, Tara M; Edwards, Molly B; Kim, Grace J; Ruffel, Sandrine; McCombie, W Richard; Shasha, Dennis; Coruzzi, Gloria M

2018-06-19

This study exploits time, the relatively unexplored fourth dimension of gene regulatory networks (GRNs), to learn the temporal transcriptional logic underlying dynamic nitrogen (N) signaling in plants. Our "just-in-time" analysis of time-series transcriptome data uncovered a temporal cascade of cis elements underlying dynamic N signaling. To infer transcription factor (TF)-target edges in a GRN, we applied a time-based machine learning method to 2,174 dynamic N-responsive genes. We experimentally determined a network precision cutoff, using TF-regulated genome-wide targets of three TF hubs (CRF4, SNZ, and CDF1), used to "prune" the network to 155 TFs and 608 targets. This network precision was reconfirmed using genome-wide TF-target regulation data for four additional TFs (TGA1, HHO5/6, and PHL1) not used in network pruning. These higher-confidence edges in the GRN were further filtered by independent TF-target binding data, used to calculate a TF "N-specificity" index. This refined GRN identifies the temporal relationship of known/validated regulators of N signaling (NLP7/8, TGA1/4, NAC4, HRS1, and LBD37/38/39) and 146 additional regulators. Six TFs-CRF4, SNZ, CDF1, HHO5/6, and PHL1-validated herein regulate a significant number of genes in the dynamic N response, targeting 54% of N-uptake/assimilation pathway genes. Phenotypically, inducible overexpression of CRF4 in planta regulates genes resulting in altered biomass, root development, and 15 NO 3 - uptake, specifically under low-N conditions. This dynamic N-signaling GRN now provides the temporal "transcriptional logic" for 155 candidate TFs to improve nitrogen use efficiency with potential agricultural applications. Broadly, these time-based approaches can uncover the temporal transcriptional logic for any biological response system in biology, agriculture, or medicine. Copyright © 2018 the Author(s). Published by PNAS.

Novel [NiFe]- and [FeFe]-Hydrogenase Gene Transcripts Indicative of Active Facultative Aerobes and Obligate Anaerobes in Earthworm Gut Contents▿†

PubMed Central

Schmidt, Oliver; Wüst, Pia K.; Hellmuth, Susanne; Borst, Katharina; Horn, Marcus A.; Drake, Harold L.

2011-01-01

The concomitant occurrence of molecular hydrogen (H2) and organic acids along the alimentary canal of the earthworm is indicative of ongoing fermentation during gut passage. Fermentative H2 production is catalyzed by [FeFe]-hydrogenases and group 4 [NiFe]-hydrogenases in obligate anaerobes (e.g., Clostridiales) and facultative aerobes (e.g., Enterobacteriaceae), respectively, functional groups that might respond differently to contrasting redox conditions. Thus, the objectives of this study were to assess the redox potentials of the alimentary canal of Lumbricus terrestris and analyze the hydrogenase transcript diversities of H2 producers in glucose-supplemented gut content microcosms. Although redox potentials in the core of the alimentary canal were variable on an individual worm basis, average redox potentials were similar. The lowest redox potentials occurred in the foregut and midgut regions, averaging 40 and 110 mV, respectively. Correlation plots between hydrogenase amino acid sequences and 16S rRNA gene sequences indicated that closely related hydrogenases belonged to closely related taxa, whereas distantly related hydrogenases did not necessarily belong to distantly related taxa. Of 178 [FeFe]-hydrogenase gene transcripts, 177 clustered in 12 Clostridiales-affiliated operational taxonomic units, the majority of which were indicative of heretofore unknown hydrogenases. Of 86 group 4 [NiFe]-hydrogenase gene transcripts, 79% and 21% were affiliated with organisms in the Enterobacteriaceae and Aeromonadaceae, respectively. The collective results (i) suggest that fermenters must cope with variable and moderately oxidative redox conditions along the alimentary canal, (ii) demonstrate that heretofore undetected hydrogenases are present in the earthworm gut, and (iii) corroborate previous findings implicating Clostridiaceae and Enterobacteriaceae as active fermentative taxa in earthworm gut content. PMID:21784904

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes

PubMed Central

Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak

2017-01-01

Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements. PMID:29232693

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

PubMed

Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak; Levin, Henry L

2017-12-01

Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

Potential Novel Mechanism for Axenfeld-Rieger Syndrome: Deletion of a Distant Region Containing Regulatory Elements of PITX2

PubMed Central

Volkmann, Bethany A.; Zinkevich, Natalya S.; Mustonen, Aki; Schilter, Kala F.; Bosenko, Dmitry V.; Reis, Linda M.; Broeckel, Ulrich; Link, Brian A.

2011-01-01

Purpose. Mutations in PITX2 are associated with Axenfeld-Rieger syndrome (ARS), which involves ocular, dental, and umbilical abnormalities. Identification of cis-regulatory elements of PITX2 is important to better understand the mechanisms of disease. Methods. Conserved noncoding elements surrounding PITX2/pitx2 were identified and examined through transgenic analysis in zebrafish; expression pattern was studied by in situ hybridization. Patient samples were screened for deletion/duplication of the PITX2 upstream region using arrays and probes. Results. Zebrafish pitx2 demonstrates conserved expression during ocular and craniofacial development. Thirteen conserved noncoding sequences positioned within a gene desert as far as 1.1 Mb upstream of the human PITX2 gene were identified; 11 have enhancer activities consistent with pitx2 expression. Ten elements mediated expression in the developing brain, four regions were active during eye formation, and two sequences were associated with craniofacial expression. One region, CE4, located approximately 111 kb upstream of PITX2, directed a complex pattern including expression in the developing eye and craniofacial region, the classic sites affected in ARS. Screening of ARS patients identified an approximately 7600-kb deletion that began 106 to 108 kb upstream of the PITX2 gene, leaving PITX2 intact while removing regulatory elements CE4 to CE13. Conclusions. These data suggest the presence of a complex distant regulatory matrix within the gene desert located upstream of PITX2 with an essential role in its activity and provides a possible mechanism for the previous reports of ARS in patients with balanced translocations involving the 4q25 region upstream of PITX2 and the current patient with an upstream deletion. PMID:20881290

Comparative study of angiostatic and anti-invasive gene expressions as prognostic factors in gastric cancer.

PubMed

Lee, J H; Koh, J T; Shin, B A; Ahn, K Y; Roh, J H; Kim, Y J; Kim, K K

2001-02-01

Genes involving angiogenesis and metastasis play an important role in the progression and infiltration of cancer. We examined the expressions of various angiostatic and potential invasion/metastasis suppressor genes through RT-PCR analyses in 32 gastric cancer specimens with or without distant metastasis. The expressions of the invasion/metastasis suppressor, nm23 and E-cadherin increased much more in the cancer tissue (CT) and metastatic lymph node (MLN) than in the extraneoplastic mucosa (EM) and non-metastatic lymph node (NLN), respectively. The expressions of the angiostatic factor, angiopoietin 2 and thrombospondin 2 increased in the CT and MLN as compared with the EM and NLN, respectively. The newly cloned angiostatic factor, brain-specific angiogenesis inhibitor 1 (BAI1) decreased much more in the CT and MLN than the EM and NLN, respectively. However, BAI1 increased in the CT compared with the EM among the patients with poor prognosis and distant metastasis, such as liver or peritoneum. The expressions of the invasive factor, matrix metalloproteinase-2 and its suppressor, tissue inhibitor metalloproteinase-2 (TIMP-2) increased in the CM as compared with the EM, but the increased expression pattern of these genes in the CT became blunted among the patients with good prognosis. Our results indicate that BAI1 and TIMP-2 expressions in the extraneoplastic mucosa and non-metastatic lymph nodes were not suppressed in the patients with good prognosis, but increased expressions of angiopoietin 2, thrombospondin 2, TIMP-2, nm23 and E-cadherin in the tumor tissue did not lead to a long survival after operation. It is suggested that the extent of BAI1 and TIMP-2 expression in the gastric mucosa may be an important prognostic factor for predicting survival in gastric cancer.

Cost-effectiveness of the 21-gene breast cancer assay in Mexico.

PubMed

Bargalló-Rocha, Juan Enrique; Lara-Medina, Fernando; Pérez-Sánchez, Victor; Vázquez-Romo, Rafael; Villarreal-Garza, Cynthia; Martínez-Said, Hector; Shaw-Dulin, Robin J; Mohar-Betancourt, Alejandro; Hunt, Barnaby; Plun-Favreau, Juliette; Valentine, William J

2015-03-01

The 21-gene breast cancer assay (Oncotype DX(®); Genomic Health, Inc.) is a validated diagnostic test that predicts the likelihood of adjuvant chemotherapy benefit and 10-year risk of distant recurrence in patients with hormone-receptor-positive, human epidermal growth receptor 2-negative, early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Mexico. A Markov model was developed to make long-term projections of distant recurrence, survival, and direct costs in scenarios using conventional diagnostic procedures or the 21-gene assay to inform adjuvant chemotherapy recommendations. Transition probabilities and risk adjustment were taken from published landmark trials. Costs [2011 Mexican Pesos (MXN)] were estimated from an Instituto Mexicano del Seguro Social perspective. Costs and clinical benefits were discounted at 5% annually. Following assay testing, approximately 66% of patients previously receiving chemotherapy were recommended to receive hormone therapy only after consideration of assay results. Furthermore, approximately 10% of those previously allocated hormone therapy alone had their recommendation changed to add chemotherapy. This optimized therapy allocation led to improved mean life expectancy by 0.068 years per patient and increased direct costs by MXN 1707 [2011 United States Dollars (USD) 129] per patient versus usual care. This is equated to an incremental cost-effectiveness ratio (ICER) of MXN 25,244 (USD 1914) per life-year gained. In early-stage breast cancer patients in Mexico, guiding decision making on adjuvant therapy using the 21-gene assay was projected to improve life expectancy in comparison with the current standard of care, with an ICER of MXN 25,244 (USD 1914) per life-year gained, which is within the range generally considered cost-effective.

Phylogenic analysis of the M genes of influenza viruses isolated from free-flying water birds from their Northern Territory to Hokkaido, Japan.

PubMed

Manzoor, Rashid; Sakoda, Yoshihiro; Mweene, Aaron; Tsuda, Yoshimi; Kishida, Noriko; Bai, Gui-Rong; Kameyama, Ken-Ichiro; Isoda, Norikazu; Soda, Kosuke; Naito, Michiko; Kida, Hiroshi

2008-10-01

During 2000-2007, 218 influenza viruses of 28 different combinations of HA (H1-H13) and NA (N1-N9) subtypes were isolated from fecal samples of free-flying water birds at two distant lakes in Hokkaido, Japan. Phylogenic analysis of the matrix (M) genes of 67 strains, selected on the basis of their subtype combinations, revealed that A/duck/Hokkaido/W95/2006 (H10N8) was a reassortant whose M and NA genes [corrected] belonged to North American non-gull-avian and the other six [corrected] genes to Eurasian non-gull-avian lineages. The M genes of other 65 strains belonged to Eurasian non-gull-avian and the one to Eurasian-gull lineages. The M genes of 65 strains were grouped into three different sublineages, indicating that influenza viruses circulating in different populations of free-flying water birds have evolved independently in nature.

Differential gene expression in dentate granule cells in mesial temporal lobe epilepsy with and without hippocampal sclerosis.

PubMed

Griffin, Nicole G; Wang, Yu; Hulette, Christine M; Halvorsen, Matt; Cronin, Kenneth D; Walley, Nicole M; Haglund, Michael M; Radtke, Rodney A; Skene, J H Pate; Sinha, Saurabh R; Heinzen, Erin L

2016-03-01

Hippocampal sclerosis is the most common neuropathologic finding in cases of medically intractable mesial temporal lobe epilepsy. In this study, we analyzed the gene expression profiles of dentate granule cells of patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis to show that next-generation sequencing methods can produce interpretable genomic data from RNA collected from small homogenous cell populations, and to shed light on the transcriptional changes associated with hippocampal sclerosis. RNA was extracted, and complementary DNA (cDNA) was prepared and amplified from dentate granule cells that had been harvested by laser capture microdissection from surgically resected hippocampi from patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis. Sequencing libraries were sequenced, and the resulting sequencing reads were aligned to the reference genome. Differential expression analysis was used to ascertain expression differences between patients with and without hippocampal sclerosis. Greater than 90% of the RNA-Seq reads aligned to the reference. There was high concordance between transcriptional profiles obtained for duplicate samples. Principal component analysis revealed that the presence or absence of hippocampal sclerosis was the main determinant of the variance within the data. Among the genes up-regulated in the hippocampal sclerosis samples, there was significant enrichment for genes involved in oxidative phosphorylation. By analyzing the gene expression profiles of dentate granule cells from surgically resected hippocampal specimens from patients with mesial temporal lobe epilepsy with and without hippocampal sclerosis, we have demonstrated the utility of next-generation sequencing methods for producing biologically relevant results from small populations of homogeneous cells, and have provided insight on the transcriptional changes associated with this pathology. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

PubMed Central

Curtin, James F.; King, Gwendalyn D.; Candolfi, Marianela; Greeno, Remy B.; Kroeger, Kurt M.; Lowenstein, Pedro R.; Castro, Maria G.

2006-01-01

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review. Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as ‘immune privileged’, brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another important aspect of implementing gene therapy in the clinical arena is to be able to image the targeting of the therapeutics to the tumors, treatment effectiveness and progression of disease. We have therefore reviewed the most exciting non-invasive, in vivo imaging techniques which can be used in combination with gene therapy to monitor therapeutic efficacy over time. PMID:16248789

Developmentally distinct MYB genes encode functionally equivalent proteins in Arabidopsis.

PubMed

Lee, M M; Schiefelbein, J

2001-05-01

The duplication and divergence of developmental control genes is thought to have driven morphological diversification during the evolution of multicellular organisms. To examine the molecular basis of this process, we analyzed the functional relationship between two paralogous MYB transcription factor genes, WEREWOLF (WER) and GLABROUS1 (GL1), in Arabidopsis. The WER and GL1 genes specify distinct cell types and exhibit non-overlapping expression patterns during Arabidopsis development. Nevertheless, reciprocal complementation experiments with a series of gene fusions showed that WER and GL1 encode functionally equivalent proteins, and their unique roles in plant development are entirely due to differences in their cis-regulatory sequences. Similar experiments with a distantly related MYB gene (MYB2) showed that its product cannot functionally substitute for WER or GL1. Furthermore, an analysis of the WER and GL1 proteins shows that conserved sequences correspond to specific functional domains. These results provide new insights into the evolution of the MYB gene family in Arabidopsis, and, more generally, they demonstrate that novel developmental gene function may arise solely by the modification of cis-regulatory sequences.

Temporal dynamics of the ABC transporter response to insecticide treatment: insights from the malaria vector Anopheles stephensi

NASA Astrophysics Data System (ADS)

Epis, Sara; Porretta, Daniele; Mastrantonio, Valentina; Urbanelli, Sandra; Sassera, Davide; De Marco, Leone; Mereghetti, Valeria; Montagna, Matteo; Ricci, Irene; Favia, Guido; Bandi, Claudio

2014-12-01

In insects, ABC transporters have been shown to contribute to defence/resistance to insecticides by reducing toxic concentrations in cells/tissues. Despite the extensive studies about this detoxifying mechanism, the temporal patterns of ABC transporter activation have been poorly investigated. Using the malaria vector Anopheles stephensi as a study system, we investigated the expression profile of ABC genes belonging to different subfamilies in permethrin-treated larvae at different time points (30 min to 48 h). Our results showed that the expression of ABCB and ABCG subfamily genes was upregulated at 1 h after treatment, with the highest expression observed at 6 h. Therefore, future investigations on the temporal dynamics of ABC gene expression will allow a better implementation of insecticide treatment regimens, including the use of specific inhibitors of ABC efflux pumps.

THE USE OF GENE ARRAYS TO DETERMINE TEMPORAL GENE INDUCTION IN SHEEPSHEAD MINNOWS EXPOSED TO E2

EPA Science Inventory

Gene arrays provide a means to study differential gene expression in fish exposed to environmental estrogens by providing a "snapshot" of the genes expressed at a given time. Such array data may also uncover previously unknown biochemical pathways affected by estrogenic compounds...

Comparative genomic analysis of bacteriophages specific to the channel catfish pathogen Edwardsiella ictaluri

PubMed Central

2011-01-01

Background The bacterial pathogen Edwardsiella ictaluri is a primary cause of mortality in channel catfish raised commercially in aquaculture farms. Additional treatment and diagnostic regimes are needed for this enteric pathogen, motivating the discovery and characterization of bacteriophages specific to E. ictaluri. Results The genomes of three Edwardsiella ictaluri-specific bacteriophages isolated from geographically distant aquaculture ponds, at different times, were sequenced and analyzed. The genomes for phages eiAU, eiDWF, and eiMSLS are 42.80 kbp, 42.12 kbp, and 42.69 kbp, respectively, and are greater than 95% identical to each other at the nucleotide level. Nucleotide differences were mostly observed in non-coding regions and in structural proteins, with significant variability in the sequences of putative tail fiber proteins. The genome organization of these phages exhibit a pattern shared by other Siphoviridae. Conclusions These E. ictaluri-specific phage genomes reveal considerable conservation of genomic architecture and sequence identity, even with considerable temporal and spatial divergence in their isolation. Their genomic homogeneity is similarly observed among E. ictaluri bacterial isolates. The genomic analysis of these phages supports the conclusion that these are virulent phages, lacking the capacity for lysogeny or expression of virulence genes. This study contributes to our knowledge of phage genomic diversity and facilitates studies on the diagnostic and therapeutic applications of these phages. PMID:21214923

Foreshocks and delayed triggering of the 2016 MW7.1 Te Araroa earthquake and dynamic reinvigoration of its aftershock sequence by the MW7.8 Kaikōura earthquake, New Zealand

NASA Astrophysics Data System (ADS)

Warren-Smith, Emily; Fry, Bill; Kaneko, Yoshihiro; Chamberlain, Calum J.

2018-01-01

We analyze the preparatory period of the September 2016 MW7.1 Te Araroa foreshock-mainshock sequence in the Northern Hikurangi margin, New Zealand, and subsequent reinvigoration of Te Araroa aftershocks driven by a large distant earthquake (the November 2016 MW7.8 Kaikōura earthquake). By adopting a matched-filter detection workflow using 582 well-defined template events, we generate an improved foreshock and aftershock catalog for the Te Araroa sequence (>8,000 earthquakes over 66 d). Templates characteristic of the MW7.1 sequence (including the mainshock template) detect several highly correlating events (ML2.5-3.5) starting 12 min after a MW5.7 foreshock. These pre-cursory events occurred within ∼1 km of the mainshock and migrate bilaterally, suggesting precursory slip was triggered by the foreshock on the MW7.1 fault patch prior to mainshock failure. We extend our matched-filter routine to examine the interactions between high dynamic stresses resulting from passing surface waves of the November 2016 MW7.8 Kaikōura earthquake, and the evolution of the Te Araroa aftershock sequence. We observe a sudden spike in moment release of the aftershock sequence immediately following peak dynamic Coulomb stresses of 50-150 kPa on the MW7.1 fault plane. The triggered increase in moment release culminated in a MW5.1 event, immediately followed by a ∼3 h temporal stress shadow. Our observations document the preparatory period of a major subduction margin earthquake following a significant foreshock, and quantify dynamic reinvigoration of a distant on-going major aftershock sequence amid a period of temporal clustering of seismic activity in New Zealand.

Nonlinear times series analysis of epileptic human electroencephalogram (EEG)

NASA Astrophysics Data System (ADS)

Li, Dingzhou

The problem of seizure anticipation in patients with epilepsy has attracted significant attention in the past few years. In this paper we discuss two approaches, using methods of nonlinear time series analysis applied to scalp electrode recordings, which is able to distinguish between epochs temporally distant from and just prior to, the onset of a seizure in patients with temporal lobe epilepsy. First we describe a method involving a comparison of recordings taken from electrodes adjacent to and remote from the site of the seizure focus. In particular, we define a nonlinear quantity which we call marginal predictability. This quantity is computed using data from remote and from adjacent electrodes. We find that the difference between the marginal predictabilities computed for the remote and adjacent electrodes decreases several tens of minutes prior to seizure onset, compared to its value interictally. We also show that these difl'crcnc es of marginal predictability intervals are independent of the behavior state of the patient. Next we examine the please coherence between different electrodes both in the long-range and the short-range. When time is distant from seizure onsets ("interictally"), epileptic patients have lower long-range phase coherence in the delta (1-4Hz) and beta (18-30Hz) frequency band compared to nonepileptic subjects. When seizures approach (''preictally"), we observe an increase in phase coherence in the beta band. However, interictally there is no difference in short-range phase coherence between this cohort of patients and non-epileptic subjects. Preictally short-range phase coherence also increases in the alpha (10-13Hz) and the beta band. Next we apply the quantity marginal predictability on the phase difference time series. Such marginal predictabilities are lower in the patients than in the non-epileptic subjects. However, when seizure approaches, the former moves asymptotically towards the latter.

Discovery of rare protein-coding genes in model methylotroph Methylobacterium extorquens AM1.

PubMed

Kumar, Dhirendra; Mondal, Anupam Kumar; Yadav, Amit Kumar; Dash, Debasis

2014-12-01

Proteogenomics involves the use of MS to refine annotation of protein-coding genes and discover genes in a genome. We carried out comprehensive proteogenomic analysis of Methylobacterium extorquens AM1 (ME-AM1) from publicly available proteomics data with a motive to improve annotation for methylotrophs; organisms capable of surviving in reduced carbon compounds such as methanol. Besides identifying 2482(50%) proteins, 29 new genes were discovered and 66 annotated gene models were revised in ME-AM1 genome. One such novel gene is identified with 75 peptides, lacks homolog in other methylobacteria but has glycosyl transferase and lipopolysaccharide biosynthesis protein domains, indicating its potential role in outer membrane synthesis. Many novel genes are present only in ME-AM1 among methylobacteria. Distant homologs of these genes in unrelated taxonomic classes and low GC-content of few genes suggest lateral gene transfer as a potential mode of their origin. Annotations of methylotrophy related genes were also improved by the discovery of a short gene in methylotrophy gene island and redefining a gene important for pyrroquinoline quinone synthesis, essential for methylotrophy. The combined use of proteogenomics and rigorous bioinformatics analysis greatly enhanced the annotation of protein-coding genes in model methylotroph ME-AM1 genome. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transcriptome Analysis of Plant Hormone-Related Tomato (Solanum lycopersicum) Genes in a Sunlight-Type Plant Factory.

PubMed

Tanigaki, Yusuke; Higashi, Takanobu; Takayama, Kotaro; Nagano, Atsushi J; Honjo, Mie N; Fukuda, Hirokazu

2015-01-01

In plant factories, measurements of plant conditions are necessary at an early stage of growth to predict harvest times of high value-added crops. Moreover, harvest qualities depend largely on environmental stresses that elicit plant hormone responses. However, the complexities of plant hormone networks have not been characterized under nonstress conditions. In the present study, we determined temporal expression profiles of all genes and then focused on plant hormone pathways using RNA-Seq analyses of gene expression in tomato leaves every 2 h for 48 h. In these experiments, temporally expressed genes were found in the hormone synthesis pathways for salicylic acid, abscisic acid, ethylene, and jasmonic acid. The timing of CAB expression 1 (TOC1) and abscisic acid insensitive 1 (ABA1) and open stomata 1 (OST1) control gating stomata. In this study, compare with tomato and Arabidopsis thaliana, expression patterns of TOC1 have similarity. In contrast, expression patterns of tomato ABI1 and OST1 had expression peak at different time. These findings suggest that the regulation of gating stomata does not depend predominantly on TOC1 and significantly reflects the extracellular environment. The present data provide new insights into relationships between temporally expressed plant hormone-related genes and clock genes under normal sunlight conditions.

Transcriptome Analysis of Plant Hormone-Related Tomato (Solanum lycopersicum) Genes in a Sunlight-Type Plant Factory

PubMed Central

Tanigaki, Yusuke; Higashi, Takanobu; Takayama, Kotaro; Nagano, Atsushi J.; Honjo, Mie N.; Fukuda, Hirokazu

2015-01-01

In plant factories, measurements of plant conditions are necessary at an early stage of growth to predict harvest times of high value-added crops. Moreover, harvest qualities depend largely on environmental stresses that elicit plant hormone responses. However, the complexities of plant hormone networks have not been characterized under nonstress conditions. In the present study, we determined temporal expression profiles of all genes and then focused on plant hormone pathways using RNA-Seq analyses of gene expression in tomato leaves every 2 h for 48 h. In these experiments, temporally expressed genes were found in the hormone synthesis pathways for salicylic acid, abscisic acid, ethylene, and jasmonic acid. The timing of CAB expression 1 (TOC1) and abscisic acid insensitive 1 (ABA1) and open stomata 1 (OST1) control gating stomata. In this study, compare with tomato and Arabidopsis thaliana, expression patterns of TOC1 have similarity. In contrast, expression patterns of tomato ABI1 and OST1 had expression peak at different time. These findings suggest that the regulation of gating stomata does not depend predominantly on TOC1 and significantly reflects the extracellular environment. The present data provide new insights into relationships between temporally expressed plant hormone-related genes and clock genes under normal sunlight conditions. PMID:26624004

Review of the leafhopper genus Penthimia Germar (Hemiptera: Cicadellidae: Deltocephalinae) from the Indian subcontinent with description of seven new species.

PubMed

Shobharani, M; Viraktamath, C A; Webb, M D

2018-01-02

Species of the leafhopper genus Penthimia Germar known from the Indian subcontinent are reviewed based on the examination of type specimens. Seven new species of the genus, Penthimia curvata sp. nov. (Karnataka: Bandipur), P. meghalayensis sp. nov. (Meghalaya: Nangpoh), P. neoattenuata sp. nov. (India: Tamil Nadu), P. ribhoi sp. nov. (India: Meghalaya), P. sahyadrica sp. nov. (Karnataka: Dharmasthala, Agumbe; Kerala: Thekkady), P. spiculata sp. nov. (Karnataka: Nagarahole) and P. tumida sp. nov. (Tamil Nadu: Ootacamund; Kerala: Munnar) are described. The following nomenclatorial changes are proposed: Penthimia alba Zahniser, McKamey Dmitriev, 2012 (replacement name for P. thoracica Distant, 1918, nec Panzer, 1799), syn. nov. of P. quadrinotata Distant, 1918; Neodartus scutellatus Distant, 1908 syn. nov. of Penthimia ereba Distant 1908; P. nilgiriensis Distant, 1918 syn. nov. of P. montana Distant, 1918; P. scutellata (Distant) comb. nov. (from genus Neodartus); a lectotype is designated for P. maculosa Distant, stat. revived, thereby removing its synonymy with P. scapularis Distant. The following other lectotypes are designated: P. attenuata Distant, P. subniger Distant, P. scapularis Distant, P. distanti Baker, P. ereba Distant, N. scutellatus Distant, P. fraterna Distant, P. funebris Distant, P. juno Distant, P. maculosa Distant, P. montana Distant, P. noctua Distant, P. quadrinotata Distant, P. alba Zahniser, McKamey Dmitriev. Examination of types of Penthimia rufopunctata Motschulsky revealed that it belongs to Penthimia and hence it is transferred back to that genus from Neodartus, revised placement. The following species previously included in the genus Penthimia are transferred to the genera Tambila Distant and Vulturnus Kirkaldy: Tambila badia (Distant) comb. nov., T. majuscula (Distant) comb. nov., T. vittatifrons (Distant) comb. nov., T. variabilis (Distant) comb. nov. and Vulturnus flavocapitata (Distant) comb. nov. Three species are treated in a new Penthimia compacta Walker complex, i.e., Penthimia compacta Walker 1851, Penthimia subniger Distant 1908 and Penthimia scapularis Distant 1908. All taxa are described and a key to Penthimiini genera found in the subcontinent and also a key to species of Penthimia are included.

Temporal Gene Expression Kinetics for Human Keratinocytes Exposed to Hyperthermic Stress

PubMed Central

Echchgadda, Ibtissam; Roth, Caleb C.; Cerna, Cesario Z.; Wilmink, Gerald J.

2013-01-01

The gene expression kinetics for human cells exposed to hyperthermic stress are not well characterized. In this study, we identified and characterized the genes that are differentially expressed in human epidermal keratinocyte (HEK) cells exposed to hyperthermic stress. In order to obtain temporal gene expression kinetics, we exposed HEK cells to a heat stress protocol (44 °C for 40 min) and used messenger RNA (mRNA) microarrays at 0 h, 4 h and 24 h post-exposure. Bioinformatics software was employed to characterize the chief biological processes and canonical pathways associated with these heat stress genes. The data shows that the genes encoding for heat shock proteins (HSPs) that function to prevent further protein denaturation and aggregation, such as HSP40, HSP70 and HSP105, exhibit maximal expression immediately after exposure to hyperthermic stress. In contrast, the smaller HSPs, such as HSP10 and HSP27, which function in mitochondrial protein biogenesis and cellular adaptation, exhibit maximal expression during the “recovery phase”, roughly 24 h post-exposure. These data suggest that the temporal expression kinetics for each particular HSP appears to correlate with the cellular function that is required at each time point. In summary, these data provide additional insight regarding the expression kinetics of genes that are triggered in HEK cells exposed to hyperthermic stress. PMID:24709698

Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors

PubMed Central

Cheng, Hui; Ang, Heather Yin-Kuan; A. EL Farran, Chadi; Li, Pin; Fang, Hai Tong; Liu, Tong Ming; Kong, Say Li; Chin, Michael Lingzi; Ling, Wei Yin; Lim, Edwin Kok Hao; Li, Hu; Huber, Tara; Loh, Kyle M.; Loh, Yuin-Han; Lim, Bing

2016-01-01

Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into ‘induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase+ megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo. Molecularly, iHPs transcriptionally resemble native Kit+ hematopoietic progenitors. Mechanistically, reprogramming factor Lmo2 implements a hematopoietic programme in fibroblasts by rapidly binding to and upregulating the Hhex and Gfi1 genes within days. Moreover the reprogramming transcription factors also require extracellular BMP and MEK signalling to cooperatively effectuate reprogramming. Thus, the transcription factors that orchestrate embryonic hematopoiesis can artificially reconstitute this programme in developmentally distant fibroblasts, converting them into engraftable blood progenitors. PMID:27869129

The nucleobase cation symporter 1 of Chlamydomonas reinhardtii and that of the evolutionarily distant Arabidopsis thaliana display parallel function and establish a plant-specific solute transport profile.

PubMed

Schein, Jessica R; Hunt, Kevin A; Minton, Janet A; Schultes, Neil P; Mourad, George S

2013-09-01

The single cell alga Chlamydomonas reinhardtii is capable of importing purines as nitrogen sources. An analysis of the annotated C. reinhardtii genome reveals at least three distinct gene families encoding for known nucleobase transporters. In this study the solute transport and binding properties for the lone C. reinhardtii nucleobase cation symporter 1 (CrNCS1) are determined through heterologous expression in Saccharomyces cerevisiae. CrNCS1 acts as a transporter of adenine, guanine, uracil and allantoin, sharing similar - but not identical - solute recognition specificity with the evolutionary distant NCS1 from Arabidopsis thaliana. The results suggest that the solute specificity for plant NCS1 occurred early in plant evolution and are distinct from solute transport specificities of single cell fungal NCS1 proteins. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The Spatial and Temporal Transcriptomic Landscapes of Ginseng, Panax ginseng C. A. Meyer.

PubMed

Wang, Kangyu; Jiang, Shicui; Sun, Chunyu; Lin, Yanping; Yin, Rui; Wang, Yi; Zhang, Meiping

2015-12-11

Ginseng, including Asian ginseng (Panax ginseng C. A. Meyer) and American ginseng (P. quinquefolius L.), is one of the most important medicinal herbs in Asia and North America, but significantly understudied. This study sequenced and characterized the transcriptomes and expression profiles of genes expressed in 14 tissues and four different aged roots of Asian ginseng. A total of 265.2 million 100-bp clean reads were generated using the high-throughput sequencing platform HiSeq 2000, representing >8.3x of the 3.2-Gb ginseng genome. From the sequences, 248,993 unigenes were assembled for whole plant, 61,912-113,456 unigenes for each tissue and 54,444-65,412 unigenes for different year-old roots. We comprehensively analyzed the unigene sets and gene expression profiles. We found that the number of genes allocated to each functional category is stable across tissues or developmental stages, while the expression profiles of different genes of a gene family or involved in ginsenoside biosynthesis dramatically diversified spatially and temporally. These results provide an overall insight into the spatial and temporal transcriptome dynamics and landscapes of Asian ginseng, and comprehensive resources for advanced research and breeding of ginseng and related species.

Diversity and evolution of the emerging Pandoraviridae family.

PubMed

Legendre, Matthieu; Fabre, Elisabeth; Poirot, Olivier; Jeudy, Sandra; Lartigue, Audrey; Alempic, Jean-Marie; Beucher, Laure; Philippe, Nadège; Bertaux, Lionel; Christo-Foroux, Eugène; Labadie, Karine; Couté, Yohann; Abergel, Chantal; Claverie, Jean-Michel

2018-06-11

With DNA genomes reaching 2.5 Mb packed in particles of bacterium-like shape and dimension, the first two Acanthamoeba-infecting pandoraviruses remained up to now the most complex viruses since their discovery in 2013. Our isolation of three new strains from distant locations and environments is now used to perform the first comparative genomics analysis of the emerging worldwide-distributed Pandoraviridae family. Thorough annotation of the genomes combining transcriptomic, proteomic, and bioinformatic analyses reveals many non-coding transcripts and significantly reduces the former set of predicted protein-coding genes. Here we show that the pandoraviruses exhibit an open pan-genome, the enormous size of which is not adequately explained by gene duplications or horizontal transfers. As most of the strain-specific genes have no extant homolog and exhibit statistical features comparable to intergenic regions, we suggest that de novo gene creation could contribute to the evolution of the giant pandoravirus genomes.

A large deletion in the succinate dehydrogenase B gene (SDHB) in a Japanese patient with abdominal paraganglioma and concomitant metastasis.

PubMed

Kodama, Hitomi; Iihara, Masatoshi; Nissato, Sumiko; Isobe, Kazumasa; Kawakami, Yasushi; Okamoto, Takahiro; Takekoshi, Kazuhiro

2010-01-01

Recently, mutations in nuclear genes encoding two mitochondrial complex II subunit proteins, Succinate dehydrogenase D (SDHD) and SDHB, have been found to be associated with the development of familial pheochromocytomas and paragangliomas (hereditary pheochromocytoma/paraganglioma syndrome: HPPS). Growing evidence suggests that the mutation of SDHB is highly associated with abdominal paraganglioma and the following distant metastasis (malignant paraganglioma). In the present study, we used multiplex ligation dependent probe amplification (MLPA) analysis to identify a large heterozygous SDHB gene deletion encompassing sequences corresponding to the promoter region, in addition to exon 1 and exon 2 malignant paraganglioma patient in whom previously characterized SDHB mutations were undetectable. This is the first Japanese case report of malignant paraganglioma, with a large SDHB deletions. Our present findings strongly support the notion that large deletions in the SDHB gene should be considered in patients lacking characterized SDHB mutations.

The episodic evolution of fibritin: traces of ancient global environmental alterations may remain in the genomes of T4-like phages

PubMed Central

Letarov, A V; Krisch, H M

2013-01-01

The evolutionary adaptation of bacteriophages to their environment is achieved by alterations of their genomes involving a combination of both point mutations and lateral gene transfer. A phylogenetic analysis of a large set of collar fiber protein (fibritin) loci from diverse T4-like phages indicates that nearly all the modular swapping involving the C-terminal domain of this gene occurred in the distant past and has since ceased. In phage T4, this fibritin domain encodes the sequence that mediates both the attachment of the long tail fibers to the virion and also controls, in an environmentally sensitive way, the phage's ability to infect its host bacteria. Subsequent to its distant period of modular exchange, the evolution of fibritin has proceeded primarily by the slow vertical divergence mechanism. We suggest that ancient and sudden changes in the environment forced the T4-like phages to alter fibritin's mode of action or function. The genome's response to such episodes of rapid environmental change could presumably only be achieved quickly enough by employing the modular evolution mechanism. A phylogenetic analysis of the fibritin locus reveals the possible traces of such events within the T4 superfamily's genomes. PMID:24223296

Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

PubMed Central

Matamales, Miriam

2012-01-01

Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance. PMID:24327840

Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

PubMed

Matamales, Miriam

2012-12-19

Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance.

Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

PubMed

Matamales, Miriam

2012-01-01

Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance.

CnidBase: The Cnidarian Evolutionary Genomics Database

PubMed Central

Ryan, Joseph F.; Finnerty, John R.

2003-01-01

CnidBase, the Cnidarian Evolutionary Genomics Database, is a tool for investigating the evolutionary, developmental and ecological factors that affect gene expression and gene function in cnidarians. In turn, CnidBase will help to illuminate the role of specific genes in shaping cnidarian biodiversity in the present day and in the distant past. CnidBase highlights evolutionary changes between species within the phylum Cnidaria and structures genomic and expression data to facilitate comparisons to non-cnidarian metazoans. CnidBase aims to further the progress that has already been made in the realm of cnidarian evolutionary genomics by creating a central community resource which will help drive future research and facilitate more accurate classification and comparison of new experimental data with existing data. CnidBase is available at http://cnidbase.bu.edu/. PMID:12519972

Association mining of mutated cancer genes in different clinical stages across 11 cancer types.

PubMed

Hu, Wangxiong; Li, Xiaofen; Wang, Tingzhang; Zheng, Shu

2016-10-18

Many studies have demonstrated that some genes (e.g. APC, BRAF, KRAS, PTEN, TP53) are frequently mutated in cancer, however, underlying mechanism that contributes to their high mutation frequency remains unclear. Here we used Apriori algorithm to find the frequent mutational gene sets (FMGSs) from 4,904 tumors across 11 cancer types as part of the TCGA Pan-Cancer effort and then mined the hidden association rules (ARs) within these FMGSs. Intriguingly, we found that well-known cancer driver genes such as BRAF, KRAS, PTEN, and TP53 were often co-occurred with other driver genes and FMGSs size peaked at an itemset size of 3~4 genes. Besides, the number and constitution of FMGS and ARs differed greatly among different cancers and stages. In addition, FMGS and ARs were rare in endocrine-related cancers such as breast carcinoma, ovarian cystadenocarcinoma, and thyroid carcinoma, but abundant in cancers contact directly with external environments such as skin melanoma and stomach adenocarcinoma. Furthermore, we observed more rules in stage IV than in other stages, indicating that distant metastasis needed more sophisticated gene regulatory network.

Chromatin landscape and circadian dynamics: Spatial and temporal organization of clock transcription

PubMed Central

Aguilar-Arnal, Lorena; Sassone-Corsi, Paolo

2015-01-01

Circadian rhythms drive the temporal organization of a wide variety of physiological and behavioral functions in ∼24-h cycles. This control is achieved through a complex program of gene expression. In mammals, the molecular clock machinery consists of interconnected transcriptional–translational feedback loops that ultimately ensure the proper oscillation of thousands of genes in a tissue-specific manner. To achieve circadian transcriptional control, chromatin remodelers serve the clock machinery by providing appropriate oscillations to the epigenome. Recent findings have revealed the presence of circadian interactomes, nuclear “hubs” of genome topology where coordinately expressed circadian genes physically interact in a spatial and temporal-specific manner. Thus, a circadian nuclear landscape seems to exist, whose interplay with metabolic pathways and clock regulators translates into specific transcriptional programs. Deciphering the molecular mechanisms that connect the circadian clock machinery with the nuclear landscape will reveal yet unexplored pathways that link cellular metabolism to epigenetic control. PMID:25378702

Orientation-dependent interaction between Drosophila insulators is a property of this class of regulatory elements.

PubMed

Kyrchanova, Olga; Chetverina, Darya; Maksimenko, Oksana; Kullyev, Andrey; Georgiev, Pavel

2008-12-01

Insulators are defined as a class of regulatory elements that delimit independent transcriptional domains within eukaryotic genomes. According to previous data, an interaction (pairing) between some Drosophila insulators can support distant activation of a promoter by an enhancer. Here, we have demonstrated that pairs of well-studied insulators such as scs-scs, scs'-scs', 1A2-1A2 and Wari-Wari support distant activation of the white promoter by the yeast GAL4 activator in an orientation-dependent manner. The same is true for the efficiency of the enhancer that stimulates white expression in the eyes. In all insulator pairs tested, stimulation of the white gene was stronger when insulators were inserted between the eye enhancer or GAL4 and the white promoter in opposite orientations relative to each other. As shown previously, Zw5, Su(Hw) and dCTCF proteins are required for the functioning of different insulators that do not interact with each other. Here, strong functional interactions have been revealed between DNA fragments containing binding sites for either Zw5 or Su(Hw) or dCTCF protein but not between heterologous binding sites [Zw5-Su(Hw), dCTCF-Su(Hw), or dCTCF-Zw5]. These results suggest that insulator proteins can support selective interactions between distant regulatory elements.

Disturbed temporal dynamics of brain synchronization in vision loss.

PubMed

Bola, Michał; Gall, Carolin; Sabel, Bernhard A

2015-06-01

Damage along the visual pathway prevents bottom-up visual input from reaching further processing stages and consequently leads to loss of vision. But perception is not a simple bottom-up process - rather it emerges from activity of widespread cortical networks which coordinate visual processing in space and time. Here we set out to study how vision loss affects activity of brain visual networks and how networks' activity is related to perception. Specifically, we focused on studying temporal patterns of brain activity. To this end, resting-state eyes-closed EEG was recorded from partially blind patients suffering from chronic retina and/or optic-nerve damage (n = 19) and healthy controls (n = 13). Amplitude (power) of oscillatory activity and phase locking value (PLV) were used as measures of local and distant synchronization, respectively. Synchronization time series were created for the low- (7-9 Hz) and high-alpha band (11-13 Hz) and analyzed with three measures of temporal patterns: (i) length of synchronized-/desynchronized-periods, (ii) Higuchi Fractal Dimension (HFD), and (iii) Detrended Fluctuation Analysis (DFA). We revealed that patients exhibit less complex, more random and noise-like temporal dynamics of high-alpha band activity. More random temporal patterns were associated with worse performance in static (r = -.54, p = .017) and kinetic perimetry (r = .47, p = .041). We conclude that disturbed temporal patterns of neural synchronization in vision loss patients indicate disrupted communication within brain visual networks caused by prolonged deafferentation. We propose that because the state of brain networks is essential for normal perception, impaired brain synchronization in patients with vision loss might aggravate the functional consequences of reduced visual input. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spatial and temporal dynamics of the microbial community in the Hanford unconfined aquifer

PubMed Central

Lin, Xueju; McKinley, James; Resch, Charles T; Kaluzny, Rachael; Lauber, Christian L; Fredrickson, James; Knight, Rob; Konopka, Allan

2012-01-01

Pyrosequencing analysis of 16S rRNA genes was used to study temporal dynamics of groundwater bacteria and archaea over 10 months within three well clusters separated by ∼30 m and located 250 m from the Columbia River on the Hanford Site, WA. Each cluster contained three wells screened at different depths ranging from 10 to 17 m that differed in hydraulic conductivities. Representative samples were selected for analyses of prokaryotic 16S and eukaryotic 18S rRNA gene copy numbers. Temporal changes in community composition occurred in all nine wells over the 10-month sampling period. However, there were particularly strong effects near the top of the water table when the seasonal rise in the Columbia River caused river water intrusion at the top of the aquifer. The occurrence and disappearance of some microbial assemblages (such as Actinobacteria ACK-M1) were correlated with river water intrusion. This seasonal impact on microbial community structure was greater in the shallow saturated zone than deeper zone in the aquifer. Spatial and temporal patterns for several 16S rRNA gene operational taxonomic units associated with particular physiological functions (for example, methane oxidizers and metal reducers) suggests dynamic changes in fluxes of electron donors and acceptors over an annual cycle. In addition, temporal dynamics in eukaryotic 18S rRNA gene copies and the dominance of protozoa in 18S clone libraries suggest that bacterial community dynamics could be affected not only by the physical and chemical environment but also by top-down biological control. PMID:22456444

Spatial and temporal dynamics of the microbial community in the Hanford unconfined aquifer.

PubMed

Lin, Xueju; McKinley, James; Resch, Charles T; Kaluzny, Rachael; Lauber, Christian L; Fredrickson, James; Knight, Rob; Konopka, Allan

2012-09-01

Pyrosequencing analysis of 16S rRNA genes was used to study temporal dynamics of groundwater bacteria and archaea over 10 months within three well clusters separated by ~30 m and located 250 m from the Columbia River on the Hanford Site, WA. Each cluster contained three wells screened at different depths ranging from 10 to 17 m that differed in hydraulic conductivities. Representative samples were selected for analyses of prokaryotic 16S and eukaryotic 18S rRNA gene copy numbers. Temporal changes in community composition occurred in all nine wells over the 10-month sampling period. However, there were particularly strong effects near the top of the water table when the seasonal rise in the Columbia River caused river water intrusion at the top of the aquifer. The occurrence and disappearance of some microbial assemblages (such as Actinobacteria ACK-M1) were correlated with river water intrusion. This seasonal impact on microbial community structure was greater in the shallow saturated zone than deeper zone in the aquifer. Spatial and temporal patterns for several 16S rRNA gene operational taxonomic units associated with particular physiological functions (for example, methane oxidizers and metal reducers) suggests dynamic changes in fluxes of electron donors and acceptors over an annual cycle. In addition, temporal dynamics in eukaryotic 18S rRNA gene copies and the dominance of protozoa in 18S clone libraries suggest that bacterial community dynamics could be affected not only by the physical and chemical environment but also by top-down biological control.

Tiger on the prowl: Invasion history and spatio-temporal genetic structure of the Asian tiger mosquito Aedes albopictus (Skuse 1894) in the Indo-Pacific

PubMed Central

Ambrose, Luke; Cooper, Robert D.; Chow, Weng K.; Davis, Joseph B.; Muzari, Mutizwa O.; van den Hurk, Andrew F.; Hall-Mendelin, Sonja; Hasty, Jeomhee M.; Burkot, Thomas R.; Bangs, Michael J.; Reimer, Lisa J.; Butafa, Charles; Lobo, Neil F.; Syafruddin, Din; Maung Maung, Yan Naung; Ahmad, Rohani; Beebe, Nigel W.

2017-01-01

Background Within the last century, increases in human movement and globalization of trade have facilitated the establishment of several highly invasive mosquito species in new geographic locations with concurrent major environmental, economic and health consequences. The Asian tiger mosquito, Aedes albopictus, is an extremely invasive and aggressive daytime-biting mosquito that is a major public health threat throughout its expanding range. Methodology/Principal findings We used 13 nuclear microsatellite loci (on 911 individuals) and mitochondrial COI sequences to gain a better understanding of the historical and contemporary movements of Ae. albopictus in the Indo-Pacific region and to characterize its population structure. Approximate Bayesian computation (ABC) was employed to test competing historical routes of invasion of Ae. albopictus within the Southeast (SE) Asian/Australasian region. Our ABC results show that Ae. albopictus was most likely introduced to New Guinea via mainland Southeast Asia, before colonizing the Solomon Islands via either Papua New Guinea or SE Asia. The analysis also supported that the recent incursion into northern Australia’s Torres Strait Islands was seeded chiefly from Indonesia. For the first time documented in this invasive species, we provide evidence of a recently colonized population (the Torres Strait Islands) that has undergone rapid temporal changes in its genetic makeup, which could be the result of genetic drift or represent a secondary invasion from an unknown source. Conclusions/Significance There appears to be high spatial genetic structure and high gene flow between some geographically distant populations. The species' genetic structure in the region tends to favour a dispersal pattern driven mostly by human movements. Importantly, this study provides a more widespread sampling distribution of the species’ native range, revealing more spatial population structure than previously shown. Additionally, we present the most probable invasion history of this species in the Australasian region using ABC analysis. PMID:28410388

Tiger on the prowl: Invasion history and spatio-temporal genetic structure of the Asian tiger mosquito Aedes albopictus (Skuse 1894) in the Indo-Pacific.

PubMed

Maynard, Andrew J; Ambrose, Luke; Cooper, Robert D; Chow, Weng K; Davis, Joseph B; Muzari, Mutizwa O; van den Hurk, Andrew F; Hall-Mendelin, Sonja; Hasty, Jeomhee M; Burkot, Thomas R; Bangs, Michael J; Reimer, Lisa J; Butafa, Charles; Lobo, Neil F; Syafruddin, Din; Maung Maung, Yan Naung; Ahmad, Rohani; Beebe, Nigel W

2017-04-01

Within the last century, increases in human movement and globalization of trade have facilitated the establishment of several highly invasive mosquito species in new geographic locations with concurrent major environmental, economic and health consequences. The Asian tiger mosquito, Aedes albopictus, is an extremely invasive and aggressive daytime-biting mosquito that is a major public health threat throughout its expanding range. We used 13 nuclear microsatellite loci (on 911 individuals) and mitochondrial COI sequences to gain a better understanding of the historical and contemporary movements of Ae. albopictus in the Indo-Pacific region and to characterize its population structure. Approximate Bayesian computation (ABC) was employed to test competing historical routes of invasion of Ae. albopictus within the Southeast (SE) Asian/Australasian region. Our ABC results show that Ae. albopictus was most likely introduced to New Guinea via mainland Southeast Asia, before colonizing the Solomon Islands via either Papua New Guinea or SE Asia. The analysis also supported that the recent incursion into northern Australia's Torres Strait Islands was seeded chiefly from Indonesia. For the first time documented in this invasive species, we provide evidence of a recently colonized population (the Torres Strait Islands) that has undergone rapid temporal changes in its genetic makeup, which could be the result of genetic drift or represent a secondary invasion from an unknown source. There appears to be high spatial genetic structure and high gene flow between some geographically distant populations. The species' genetic structure in the region tends to favour a dispersal pattern driven mostly by human movements. Importantly, this study provides a more widespread sampling distribution of the species' native range, revealing more spatial population structure than previously shown. Additionally, we present the most probable invasion history of this species in the Australasian region using ABC analysis.

Temporal distance and discrimination: an audit study in academia.

PubMed

Milkman, Katherine L; Akinola, Modupe; Chugh, Dolly

2012-07-01

Through a field experiment set in academia (with a sample of 6,548 professors), we found that decisions about distant-future events were more likely to generate discrimination against women and minorities (relative to Caucasian males) than were decisions about near-future events. In our study, faculty members received e-mails from fictional prospective doctoral students seeking to schedule a meeting either that day or in 1 week; students' names signaled their race (Caucasian, African American, Hispanic, Indian, or Chinese) and gender. When the requests were to meet in 1 week, Caucasian males were granted access to faculty members 26% more often than were women and minorities; also, compared with women and minorities, Caucasian males received more and faster responses. However, these patterns were essentially eliminated when prospective students requested a meeting that same day. Our identification of a temporal discrimination effect is consistent with the predictions of construal-level theory and implies that subtle contextual shifts can alter patterns of race- and gender-based discrimination.

Primary Ewing's Sarcoma of the temporal bone in an infant.

PubMed

Goudarzipour, Kourosh; Shamsian, Shahin; Alavi, Samin; Nourbakhsh, Kazem; Aghakhani, Roxana; Eydian, Zahra; Arzanian, Mohammad Taghi

2015-04-01

Introduction : Ewing's sarcoma is the second most common primary malignant tumor of bone found in children after Osteosarcoma. It accounts for 4-9% of primary malignant bone tumors and it affects bones of the skull or face in only 1-4% of cases. Hence it rarely affects the head and neck. Subject and Method : In this case report, we describe a case of primary Ewing's sarcoma occurring in the temporal bone. The tumor was surgically excised, and the patient underwent chemotherapy for ten months. Results : Neither recurrence nor distant metastasis was noted in these 10 months after surgery but about 18 months after surgery our patient was expired. Conclusion : Although the prognosis of Ewing's sarcoma is generally poor because of early metastasis to the lungs and to other bones, a review of the article suggested that Ewing's sarcoma occurring in the skull can often be successfully managed by intensive therapy with radical excision and chemotherapy. This result was supported by the case reported here.

Tolerance for audiovisual asynchrony is enhanced by the spectrotemporal fidelity of the speaker's mouth movements and speech.

PubMed

Shahin, Antoine J; Shen, Stanley; Kerlin, Jess R

2017-01-01

We examined the relationship between tolerance for audiovisual onset asynchrony (AVOA) and the spectrotemporal fidelity of the spoken words and the speaker's mouth movements. In two experiments that only varied in the temporal order of sensory modality, visual speech leading (exp1) or lagging (exp2) acoustic speech, participants watched intact and blurred videos of a speaker uttering trisyllabic words and nonwords that were noise vocoded with 4-, 8-, 16-, and 32-channels. They judged whether the speaker's mouth movements and the speech sounds were in-sync or out-of-sync . Individuals perceived synchrony (tolerated AVOA) on more trials when the acoustic speech was more speech-like (8 channels and higher vs. 4 channels), and when visual speech was intact than blurred (exp1 only). These findings suggest that enhanced spectrotemporal fidelity of the audiovisual (AV) signal prompts the brain to widen the window of integration promoting the fusion of temporally distant AV percepts.

Investigation of phase synchronization of interictal EEG in right temporal lobe epilepsy

NASA Astrophysics Data System (ADS)

Yu, Haitao; Cai, Lihui; Wu, Xinyu; Song, Zhenxi; Wang, Jiang; Xia, Zijie; Liu, Jing; Cao, Yibin

2018-02-01

Epilepsy is commonly associated with abnormally synchronous activity of neurons located in epileptogenic zones. In this study, we investigated the synchronization characteristic of right temporal lobe epilepsy (RTLE). Multichannel electroencephalography (EEG) data were recorded from the RTLE patients during interictal period and normal controls. Power spectral density was first used to analyze the EEG power for two groups of subjects. It was found that the power of epileptics is increased in the whole brain compared with that of the control. We calculated phase lag index (PLI) to measure the phase synchronization between each pair of EEG signals. A higher degree of synchronization was observed in the epileptics especially between distant channels. In particular, the regional synchronization degree was negatively correlated with power spectral density and the correlation was weaker for epileptics. Moreover, the synchronization degree decayed with the increase of relative distance of channels for both the epilepsy and control, but the dependence was weakened in the former. The obtained results may provide new insights into the generation mechanism of epilepsy.

A dual role for a polyketide synthase in dynemicin enediyne and anthraquinone biosynthesis

NASA Astrophysics Data System (ADS)

Cohen, Douglas R.; Townsend, Craig A.

2018-02-01

Dynemicin A is a member of a subfamily of enediyne antitumour antibiotics characterized by a 10-membered carbocycle fused to an anthraquinone, both of polyketide origin. Sequencing of the dynemicin biosynthetic gene cluster in Micromonospora chersina previously identified an enediyne polyketide synthase (PKS), but no anthraquinone PKS, suggesting gene(s) for biosynthesis of the latter were distant from the core dynemicin cluster. To identify these gene(s), we sequenced and analysed the genome of M. chersina. Sequencing produced a short list of putative PKS candidates, yet CRISPR-Cas9 mutants of each locus retained dynemicin production. Subsequently, deletion of two cytochromes P450 in the dynemicin cluster suggested that the dynemicin enediyne PKS, DynE8, may biosynthesize the anthraquinone. Together with 18O-labelling studies, we now present evidence that DynE8 produces the core scaffolds of both the enediyne and anthraquinone, and provide a working model to account for their formation from the programmed octaketide of the enediyne PKS.

The complete mitochondrial genome sequence of the western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae) contains triplicate putative control regions.

PubMed

Yan, Dankan; Tang, Yunxia; Xue, Xiaofeng; Wang, Minghua; Liu, Fengquan; Fan, Jiaqin

2012-09-10

To investigate the features of the control region (CR) and the gene rearrangement in the mitochondrial (mt) genome of Thysanoptera insects, we sequenced the whole mt genome of the western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae). The mt genome is a circular molecule with 14,889 nucleotides and an A+T content of 76.6%, and it has triplicate putative CRs. We propose that tandem duplication and deletion account for the evolution of the CR and the gene translocations. Intramitochondrial recombination is a plausible model for the gene inversions. We discuss the excessive duplicate CR sequences and the transcription of the rRNA genes, which are distant from one another and from the CR. Finally, we address the significance of the complicated mt genomes in Thysanoptera for the evolution of the CR and the gene arrangement of the mt genome. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development

PubMed Central

Paige, Sharon L.; Thomas, Sean; Stoick-Cooper, Cristi L.; Wang, Hao; Maves, Lisa; Sandstrom, Richard; Pabon, Lil; Reinecke, Hans; Pratt, Gabriel; Keller, Gordon; Moon, Randall T.; Stamatoyannopoulos, John; Murry, Charles E.

2012-01-01

Summary Directed differentiation of human embryonic stem cells (ESCs) into cardiovascular cells provides a model for studying molecular mechanisms of human cardiovascular development. Though it is known that chromatin modification patterns in ESCs differ markedly from those in lineage-committed progenitors and differentiated cells, the temporal dynamics of chromatin alterations during differentiation along a defined lineage have not been studied. We show that differentiation of human ESCs into cardiovascular cells is accompanied by programmed temporal alterations in chromatin structure that distinguish key regulators of cardiovascular development from other genes. We used this temporal chromatin signature to identify regulators of cardiac development, including the homeobox gene MEIS2. We demonstrate using the zebrafish model that MEIS2 is critical for proper heart tube formation and subsequent cardiac looping. Temporal chromatin signatures should be broadly applicable to other models of stem cell differentiation to identify regulators and provide key insights into major developmental decisions. PMID:22981225

Prognostic value of HMGA2, CDK4, and JUN amplification in well-differentiated and dedifferentiated liposarcomas.

PubMed

Saâda-Bouzid, Esma; Burel-Vandenbos, Fanny; Ranchère-Vince, Dominique; Birtwisle-Peyrottes, Isabelle; Chetaille, Bruno; Bouvier, Corinne; Château, Marie-Christine; Peoc'h, Michel; Battistella, Maxime; Bazin, Audrey; Gal, Jocelyn; Michiels, Jean-François; Coindre, Jean-Michel; Pedeutour, Florence; Bianchini, Laurence

2015-11-01

HMGA2, CDK4, and JUN genes have been described as frequently coamplified with MDM2 in atypical lipomatous tumor, well-differentiated liposarcoma, and dedifferentiated liposarcoma. We studied the frequency of amplification of these genes in a series of 48 dedifferentiated liposarcomas and 68 atypical lipomatous tumors/well-differentiated liposarcomas. We correlated their amplification status with clinicopathological features and outcomes. Histologically, both CDK4 (P=0.007) and JUN (P=0.005) amplifications were associated with dedifferentiated liposarcoma, whereas amplification of the proximal parts of HMGA2 (5'-untranslated region (UTR) and exons 1-3) was associated with atypical lipomatous tumor/well-differentiated liposarcoma (P=0.01). CDK4 amplification was associated with axial tumors. Amplification of 5'-UTR and exons 1-3 of HMGA2 was associated with primary status and grade 1. Shorter overall survival was correlated with: age >64 years (P=0.03), chemotherapy used in first intent (P<0.001), no surgery (P=0.003), grade 3 (P<0.001), distant metastasis (P<0.001), node involvement (P=0.006), and CDK4 amplification (P=0.07). In multivariate analysis, distant metastasis (HR=8.8) and grade 3 (HR=18.2) were associated with shorter overall survival. A shorter recurrence-free survival was associated with dedifferentiated liposarcoma (P<0.001), grade 3 (P<0.001), node involvement (P<0.001), distant metastasis (P=0.02), recurrent status (P=0.009), axial location (P=0.001), and with molecular features such as CDK4 (P=0.05) and JUN amplification (P=0.07). Amplification of 5'-UTR and exons 1-3 (P=0.08) and 3'-UTR (P=0.01) of HMGA2 were associated with longer recurrence-free survival. Distant metastasis was associated with shorter recurrence-free survival (HR=5.8) in multivariate analysis. Dedifferentiated liposarcoma type was associated with axial location, grade 3 and recurrent status. In conclusion, we showed that the amplification of HMGA2 was associated with the atypical lipomatous tumor/well-differentiated liposarcoma histological type and a good prognosis, whereas CDK4 and JUN amplifications were associated with dedifferentiated liposarcoma histology and a bad prognosis. In addition, we also provided the first description of the molecular evolution of a well-differentiated liposarcoma into four successive dedifferentiated liposarcoma relapses, which was consistent with our general observations.

HFT events - Shallow moonquakes. [High-Frequency Teleseismic

NASA Technical Reports Server (NTRS)

Nakamura, Y.

1977-01-01

A few large distant seismic events of distinctly high signal frequency, designated HFT (high-frequency teleseismic) events, are observed yearly by the Apollo lunar seismic network. Their sources are located on or near the surface of the moon, leaving a large gap in seismic activity between the zones of HFT sources and deep moonquakes. No strong regularities are found in either their spatial or temporal distributions. Several working hypotheses for the identity of these sources have advanced, but many characteristics of the events seem to favor a hypothesis that they are shallow moonquakes. Simultaneous observations of other lunar phenomena may eventually enable the determination of their true identity.

Patterning in time and space: HoxB cluster gene expression in the developing chick embryo.

PubMed

Gouveia, Analuce; Marcelino, Hugo M; Gonçalves, Lisa; Palmeirim, Isabel; Andrade, Raquel P

2015-01-01

The developing embryo is a paradigmatic model to study molecular mechanisms of time control in Biology. Hox genes are key players in the specification of tissue identity during embryo development and their expression is under strict temporal regulation. However, the molecular mechanisms underlying timely Hox activation in the early embryo remain unknown. This is hindered by the lack of a rigorous temporal framework of sequential Hox expression within a single cluster. Herein, a thorough characterization of HoxB cluster gene expression was performed over time and space in the early chick embryo. Clear temporal collinearity of HoxB cluster gene expression activation was observed. Spatial collinearity of HoxB expression was evidenced in different stages of development and in multiple tissues. Using embryo explant cultures we showed that HoxB2 is cyclically expressed in the rostral presomitic mesoderm with the same periodicity as somite formation, suggesting a link between timely tissue specification and somite formation. We foresee that the molecular framework herein provided will facilitate experimental approaches aimed at identifying the regulatory mechanisms underlying Hox expression in Time and Space.

Patterning in time and space: HoxB cluster gene expression in the developing chick embryo

PubMed Central

Gouveia, Analuce; Marcelino, Hugo M; Gonçalves, Lisa; Palmeirim, Isabel; Andrade, Raquel P

2015-01-01

The developing embryo is a paradigmatic model to study molecular mechanisms of time control in Biology. Hox genes are key players in the specification of tissue identity during embryo development and their expression is under strict temporal regulation. However, the molecular mechanisms underlying timely Hox activation in the early embryo remain unknown. This is hindered by the lack of a rigorous temporal framework of sequential Hox expression within a single cluster. Herein, a thorough characterization of HoxB cluster gene expression was performed over time and space in the early chick embryo. Clear temporal collinearity of HoxB cluster gene expression activation was observed. Spatial collinearity of HoxB expression was evidenced in different stages of development and in multiple tissues. Using embryo explant cultures we showed that HoxB2 is cyclically expressed in the rostral presomitic mesoderm with the same periodicity as somite formation, suggesting a link between timely tissue specification and somite formation. We foresee that the molecular framework herein provided will facilitate experimental approaches aimed at identifying the regulatory mechanisms underlying Hox expression in Time and Space. PMID:25602523

Effects of the distant population density on spatial patterns of demographic dynamics

NASA Astrophysics Data System (ADS)

Tamura, Kohei; Masuda, Naoki

2017-08-01

Spatio-temporal patterns of population changes within and across countries have various implications. Different geographical, demographic and econo-societal factors seem to contribute to migratory decisions made by individual inhabitants. Focusing on internal (i.e. domestic) migration, we ask whether individuals may take into account the information on the population density in distant locations to make migratory decisions. We analyse population census data in Japan recorded with a high spatial resolution (i.e. cells of size 500×500 m) for the entirety of the country, and simulate demographic dynamics induced by the gravity model and its variants. We show that, in the census data, the population growth rate in a cell is positively correlated with the population density in nearby cells up to a distance of 20 km as well as that of the focal cell. The ordinary gravity model does not capture this empirical observation. We then show that the empirical observation is better accounted for by extensions of the gravity model such that individuals are assumed to perceive the attractiveness, approximated by the population density, of the source or destination cell of migration as the spatial average over a circle of radius ≈1 km.

Effects of the distant population density on spatial patterns of demographic dynamics.

PubMed

Tamura, Kohei; Masuda, Naoki

2017-08-01

Spatio-temporal patterns of population changes within and across countries have various implications. Different geographical, demographic and econo-societal factors seem to contribute to migratory decisions made by individual inhabitants. Focusing on internal (i.e. domestic) migration, we ask whether individuals may take into account the information on the population density in distant locations to make migratory decisions. We analyse population census data in Japan recorded with a high spatial resolution (i.e. cells of size 500×500  m ) for the entirety of the country, and simulate demographic dynamics induced by the gravity model and its variants. We show that, in the census data, the population growth rate in a cell is positively correlated with the population density in nearby cells up to a distance of 20 km as well as that of the focal cell. The ordinary gravity model does not capture this empirical observation. We then show that the empirical observation is better accounted for by extensions of the gravity model such that individuals are assumed to perceive the attractiveness, approximated by the population density, of the source or destination cell of migration as the spatial average over a circle of radius ≈1 km.

The Seyfert 2 Galaxy NGC 2110: Hard X-Ray Emission Observed by NuStar and Variability of the Iron K-Alpha Line

NASA Technical Reports Server (NTRS)

Marinucci, A.; Matt, G.; Bianchi, S.; Lu, T. N.; Arevalo, P.; Balokovic, M.; Ballantyne, D.; Bauer, F. E.; Boggs, S. E.; Stern, D.;

Effects of the distant population density on spatial patterns of demographic dynamics

PubMed Central

2017-01-01

Spatio-temporal patterns of population changes within and across countries have various implications. Different geographical, demographic and econo-societal factors seem to contribute to migratory decisions made by individual inhabitants. Focusing on internal (i.e. domestic) migration, we ask whether individuals may take into account the information on the population density in distant locations to make migratory decisions. We analyse population census data in Japan recorded with a high spatial resolution (i.e. cells of size 500×500 m) for the entirety of the country, and simulate demographic dynamics induced by the gravity model and its variants. We show that, in the census data, the population growth rate in a cell is positively correlated with the population density in nearby cells up to a distance of 20 km as well as that of the focal cell. The ordinary gravity model does not capture this empirical observation. We then show that the empirical observation is better accounted for by extensions of the gravity model such that individuals are assumed to perceive the attractiveness, approximated by the population density, of the source or destination cell of migration as the spatial average over a circle of radius ≈1 km. PMID:28878987

The Future is Now: Reducing Psychological Distance to Increase Public Engagement with Climate Change.

PubMed

Jones, Charlotte; Hine, Donald W; Marks, Anthony D G

2017-02-01

Many people perceive climate change as psychologically distant-a set of uncertain events that might occur far in the future, impacting distant places and affecting people dissimilar to themselves. In this study, we employed construal level theory to investigate whether a climate change communication intervention could increase public engagement by reducing the psychological distance of climate change. Australian residents (N = 333) were randomly assigned to one of two treatment conditions: one framed to increase psychological distance to climate change (distal frame), and the other framed to reduce psychological distance (proximal frame). Participants then completed measures of psychological distance of climate change impacts, climate change concern, and intentions to engage in mitigation behavior. Principal components analysis indicated that psychological distance to climate change was best conceptualized as a multidimensional construct consisting of four components: geographic, temporal, social, and uncertainty. Path analysis revealed the effect of the treatment frame on climate change concern and intentions was fully mediated by psychological distance dimensions related to uncertainty and social distance. Our results suggest that climate communications framed to reduce psychological distance represent a promising strategy for increasing public engagement with climate change. © 2016 Society for Risk Analysis.

Time dependent effects of stress prior to encoding on event-related potentials and 24 h delayed retrieval.

PubMed

Quaedflieg, Conny W E M; Schwabe, Lars; Meyer, Thomas; Smeets, Tom

2013-12-01

Stress can exert profound effects on memory encoding. Here, we investigated whether (sub)cortical information processing during encoding and memory retrieval at a 24 h delayed test are affected by the temporal proximity between stress and memory encoding. Sixty-four participants engaged in the Maastricht Acute Stress Test (MAST) or a no-stress control condition either immediately before (i.e., proximate condition) or 30 min before (i.e., distant condition) a picture encoding task. In general, stress decreased the number of freely recalled and recognized pictures and increased the number of false alarms. However, timing of stress exposure did not differentially affect picture recall, recognition or selective attention processes (i.e., LPP). Nevertheless, stress-induced cortisol responses and correctly recognized neutral pictures were positively associated within the proximate stress condition but negatively associated within the distant stress condition. These findings suggest that the time at which a stressor is applied might differentially impact the association between stress-induced cortisol elevations and memory formation and indicate the need for a finer delineation of the time window during which glucocorticoids affect memory formation processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improving Public Engagement With Climate Change: Five "Best Practice" Insights From Psychological Science.

PubMed

van der Linden, Sander; Maibach, Edward; Leiserowitz, Anthony

2015-11-01

Despite being one of the most important societal challenges of the 21st century, public engagement with climate change currently remains low in the United States. Mounting evidence from across the behavioral sciences has found that most people regard climate change as a nonurgent and psychologically distant risk-spatially, temporally, and socially-which has led to deferred public decision making about mitigation and adaptation responses. In this article, we advance five simple but important "best practice" insights from psychological science that can help governments improve public policymaking about climate change. Particularly, instead of a future, distant, global, nonpersonal, and analytical risk that is often framed as an overt loss for society, we argue that policymakers should (a) emphasize climate change as a present, local, and personal risk; (b) facilitate more affective and experiential engagement; (c) leverage relevant social group norms; (d) frame policy solutions in terms of what can be gained from immediate action; and (e) appeal to intrinsically valued long-term environmental goals and outcomes. With practical examples we illustrate how these key psychological principles can be applied to support societal engagement and climate change policymaking. © The Author(s) 2015.

Three-dimensional reconstructions of the bacteriophage CUS-3 virion reveal a conserved coat protein I-domain but a distinct tailspike receptor-binding domain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parent, Kristin N., E-mail: kparent@msu.edu; Tang, Jinghua; Cardone, Giovanni

CUS-3 is a short-tailed, dsDNA bacteriophage that infects serotype K1 Escherichia coli. We report icosahedrally averaged and asymmetric, three-dimensional, cryo-electron microscopic reconstructions of the CUS-3 virion. Its coat protein structure adopts the “HK97-fold” shared by other tailed phages and is quite similar to that in phages P22 and Sf6 despite only weak amino acid sequence similarity. In addition, these coat proteins share a unique extra external domain (“I-domain”), suggesting that the group of P22-like phages has evolved over a very long time period without acquiring a new coat protein gene from another phage group. On the other hand, the morphologymore » of the CUS-3 tailspike differs significantly from that of P22 or Sf6, but is similar to the tailspike of phage K1F, a member of the extremely distantly related T7 group of phages. We conclude that CUS-3 obtained its tailspike gene from a distantly related phage quite recently. - Highlights: • Asymmetric and symmetric three-dimensional reconstructions of phage CUS-3 are presented. • CUS-3 major capsid protein has a conserved I-domain, which is found in all three categories of “P22-like phage”. • CUS-3 has very different tailspike receptor binding domain from those of P22 and Sf6. • The CUS-3 tailspike likely was acquired by horizontal gene transfer.« less

Convergent Differential Regulation of Parvalbumin in the Brains of Vocal Learners

PubMed Central

Hara, Erina; Rivas, Miriam V.; Ward, James M.; Okanoya, Kazuo; Jarvis, Erich D.

2012-01-01

Spoken language and learned song are complex communication behaviors found in only a few species, including humans and three groups of distantly related birds – songbirds, parrots, and hummingbirds. Despite their large phylogenetic distances, these vocal learners show convergent behaviors and associated brain pathways for vocal communication. However, it is not clear whether this behavioral and anatomical convergence is associated with molecular convergence. Here we used oligo microarrays to screen for genes differentially regulated in brain nuclei necessary for producing learned vocalizations relative to adjacent brain areas that control other behaviors in avian vocal learners versus vocal non-learners. A top candidate gene in our screen was a calcium-binding protein, parvalbumin (PV). In situ hybridization verification revealed that PV was expressed significantly higher throughout the song motor pathway, including brainstem vocal motor neurons relative to the surrounding brain regions of all distantly related avian vocal learners. This differential expression was specific to PV and vocal learners, as it was not found in avian vocal non-learners nor for control genes in learners and non-learners. Similar to the vocal learning birds, higher PV up-regulation was found in the brainstem tongue motor neurons used for speech production in humans relative to a non-human primate, macaques. These results suggest repeated convergent evolution of differential PV up-regulation in the brains of vocal learners separated by more than 65–300 million years from a common ancestor and that the specialized behaviors of learned song and speech may require extra calcium buffering and signaling. PMID:22238614

Independent degradation in genes of the plastid ndh gene family in species of the orchid genus Cymbidium (Orchidaceae; Epidendroideae).

PubMed

Kim, Hyoung Tae; Chase, Mark W

2017-01-01

In this paper, we compare ndh genes in the plastid genome of many Cymbidium species and three closely related taxa in Orchidaceae looking for evidence of ndh gene degradation. Among the 11 ndh genes, there were frequently large deletions in directly repeated or AT-rich regions. Variation in these degraded ndh genes occurs between individual plants, apparently at population levels in these Cymbidium species. It is likely that ndh gene transfers from the plastome to mitochondrial genome (chondriome) occurred independently in Orchidaceae and that ndh genes in the chondriome were also relatively recently transferred between distantly related species in Orchidaceae. Four variants of the ycf1-rpl32 region, which normally includes the ndhF genes in the plastome, were identified, and some Cymbidium species contained at least two copies of that region in their organellar genomes. The four ycf1-rpl32 variants seem to have a clear pattern of close relationships. Patterns of ndh degradation between closely related taxa and translocation of ndh genes to the chondriome in Cymbidium suggest that there have been multiple bidirectional intracellular gene transfers between two organellar genomes, which have produced different levels of ndh gene degradation among even closely related species.

In-vivo animation of midazolam-induced electrocorticographic changes in humans.

PubMed

Nishida, Masaaki; Sood, Sandeep; Asano, Eishi

2009-12-15

Previous human studies have demonstrated that midazolam-induced signal changes on scalp EEG recording include widespread augmentation of sigma-oscillations and that the amplitude of such oscillations is correlated to the severity of midazolam-induced amnesia. Still unanswered questions include whether midazolam-induced sigma-augmentation also involves the medial temporal region, which plays a role in memory encoding. Taking advantage of rare and unique opportunities to monitor neuronal activities using intracranial electrocorticography (ECoG) recording, we determined how intravenous administration of midazolam elicited spectral frequency changes in the human cerebral cortex, including the medial temporal region. We studied three children with focal epilepsy who underwent subdural electrode placement and extraoperative ECoG recording for subsequent resection of the seizure focus; an intravenous bolus of midazolam was given to abort an ongoing simple partial seizure or to provide sedation prior to induction of general anesthesia. 'Midazolam-induced ECoG frequency alteration' in sites distant from the seizure focus was sequentially animated on their individual three-dimensional MR images. The common ECoG changes induced by midazolam included gradual augmentation of sigma-oscillations (12-16 Hz) in the widespread non-epileptic regions, including the medial temporal region. The spatial and temporal alteration of ECoG spectral frequency pattern can be appreciated via animation movies. Midazolam-induced sigma-augmentation was observed in the medial temporal region in our relatively small cohort of human subjects. In-vivo animation of ECoG spectral measures provided a unique situation to study the effect of midazolam on neuronal processing in the deep brain regions.

In-vivo animation of midazolam-induced electrocorticographic changes in humans

PubMed Central

Nishida, Masaaki; Sood, Sandeep; Asano, Eishi

2009-01-01

Previous human studies have demonstrated that midazolam-induced signal changes on scalp EEG recording include widespread augmentation of sigma-oscillations and that the amplitude of such oscillations is correlated to the severity of midazolam-induced amnesia. Still unanswered questions include whether midazolam-induced sigma-augmentation also involves the medial temporal region, which plays a role in memory encoding. Taking advantage of rare and unique opportunities to monitor neuronal activities using intracranial electrocorticography (ECoG) recording, we determined how intravenous administration of midazolam induced spectral frequency changes in the human cerebral cortex, including the medial temporal region. We studied three children with focal epilepsy who underwent subdural electrode placement and extraoperative ECoG recording for subsequent resection of the seizure focus; an intravenous bolus of midazolam was given to abort an ongoing simple-partial seizure or to provide sedation prior to induction of general anesthesia. ‘Midazolam-induced ECoG frequency alteration’ in sites distant from the seizure focus was sequentially animated on their individual three-dimensional MR images. The common ECoG changes induced by midazolam included gradual augmentation of sigma-oscillations (12-16 Hz) in the widespread non-epileptic regions, including the medial temporal region. The spatial and temporal alteration of ECoG spectral frequency pattern can be appreciated via animation movies. Midazolam-induced sigma-augmentation was observed in the medial temporal region in our relatively small cohort of human subjects. In-vivo animation of ECoG spectral measures provided a unique situation to study the effect of midazolam on neuronal processing in the deep brain regions. PMID:19733366

Unique Temporal Expression of Triplicated Long-Wavelength Opsins in Developing Butterfly Eyes

PubMed Central

Arikawa, Kentaro; Iwanaga, Tomoyuki; Wakakuwa, Motohiro; Kinoshita, Michiyo

2017-01-01

Following gene duplication events, the expression patterns of the resulting gene copies can often diverge both spatially and temporally. Here we report on gene duplicates that are expressed in distinct but overlapping patterns, and which exhibit temporally divergent expression. Butterflies have sophisticated color vision and spectrally complex eyes, typically with three types of heterogeneous ommatidia. The eyes of the butterfly Papilio xuthus express two green- and one red-absorbing visual pigment, which came about via gene duplication events, in addition to one ultraviolet (UV)- and one blue-absorbing visual pigment. We localized mRNAs encoding opsins of these visual pigments in developing eye disks throughout the pupal stage. The mRNAs of the UV and blue opsin are expressed early in pupal development (pd), specifying the type of the ommatidium in which they appear. Red sensitive photoreceptors first express a green opsin mRNA, which is replaced later by the red opsin mRNA. Broadband photoreceptors (that coexpress the green and red opsins) first express the green opsin mRNA, later change to red opsin mRNA and finally re-express the green opsin mRNA in addition to the red mRNA. Such a unique temporal and spatial expression pattern of opsin mRNAs may reflect the evolution of visual pigments and provide clues toward understanding how the spectrally complex eyes of butterflies evolved. PMID:29238294

Temporal regulation of Stat5 activity in determination of cell differentiation program

PubMed Central

Hoshino, Akemi; Fujii, Hodaka

2007-01-01

Although Stat5 is activated by various cytokines, only ethrytopoietin (Epo) and a small number of cytokines induce Stat5-dependent erythroid differentiation. Here, by using a reporter gene system to monitor transcriptional activity of Stat5, we showed that Epo but not interleukin (IL)-3 supports sustained activation of Stat5, which induces globin gene expression. IL-3 or IL-2 stimulation inhibits Epo-induced globin gene expression. The acidic region of the IL-2 receptor β chain was essential for this inhibition. These results underscore the importance of temporal regulation of Stat activity for regulation of cytokine-specific cell differentiation. PMID:17511959

The Metastasis Suppressor NME1 Regulates Expression of Genes Linked to Metastasis and Patient Outcome in Melanoma and Breast Carcinoma

PubMed Central

MCCORKLE, JOSEPH R.; LEONARD, MARY K.; KRANER, SUSAN D.; BLALOCK, ERIC M.; DEQIN, MA; ZIMMER, STEPHEN G.; KAETZEL, DAVID M.

2015-01-01

NME1 is a well-documented metastasis suppressor gene, with suppressor activity demonstrated across a wide spectrum of human cancers including melanoma and carcinomas of the breast, stomach and thyroid. A primary aim of the current study was to identify profiles of genes whose expression is regulated by NME1 in cell lines of melanoma and thyroid carcinoma origin. Impact of NME1 was determined by forcing its expression transiently in cell lines using a novel Ad5-based adenoviral vector (Ad5-NME1), followed 48 h later by analysis of RNA expression profiles using the U133A microarray chip. Robust NME1 expression was achieved following infection with the Ad5-NME1 adenovirus in the human metastasis-derived cell lines WM1158 (melanoma) and WRO82 (follicular thyroid carcinoma), resulting in wide-ranging effects on gene expression in both settings. A substantial proportion of the NME1-regulated genes identified in the analyses were of clear potential relevance to metastasis, such as matrix metalloproteinase-1 (MMP1), angiopoeitin-2 (ANGPT2), SERPINB9 and colony stimulating factor receptor-2B (CSFR2B). Nine genes were identified (false discovery rate ≥0.1) that were regulated by NME1 in both the WM1158 and WRO82 cell lines, each possessing one of more such metastasis-relevant activities as stress fiber formation and focal adhesion (PPM1E, ZYX, PFN1), chemotaxis (CCR1) epithelial-mesenchymal signaling (WNT1), differentiation and morphogenesis (TBX4, ZFP36L2), and G protein modulation (GPR52 and PFN1). In addition, a number of the NME1-regulated genes were shown to be of prognostic value for distant disease-free survival and overall survival in melanoma and breast cancer. The combined expression of three NME1-regulated genes CSFR2B, MSF4A1 and SERPINB9 provided a strongly synergistic correlation with distant disease-free survival in the basal subtype of breast cancer (p<3.5e−5, hazard ratio=0.33). Our study demonstrates that analysis of NME1-dependent gene expression is a powerful approach for identifying potential modulators of metastatic potential in multiple cancer types, which in turn may represent useful therapeutic targets. The study also highlights NME1-dependent genes as potential prognostic/diagnostic indices, which are profoundly lacking at present in melanoma. PMID:25048347

The metastasis suppressor NME1 regulates expression of genes linked to metastasis and patient outcome in melanoma and breast carcinoma.

PubMed

McCorkle, Joseph R; Leonard, Mary K; Kraner, Susan D; Blalock, Eric M; Ma, Deqin; Zimmer, Stephen G; Kaetzel, David M

2014-01-01

NME1 is a well-documented metastasis suppressor gene, with suppressor activity demonstrated across a wide spectrum of human cancers including melanoma and carcinomas of the breast, stomach and thyroid. A primary aim of the current study was to identify profiles of genes whose expression is regulated by NME1 in cell lines of melanoma and thyroid carcinoma origin. Impact of NME1 was determined by forcing its expression transiently in cell lines using a novel Ad5-based adenoviral vector (Ad5-NME1), followed 48 h later by analysis of RNA expression profiles using the U133A microarray chip. Robust NME1 expression was achieved following infection with the Ad5-NME1 adenovirus in the human metastasis-derived cell lines WM1158 (melanoma) and WRO82 (follicular thyroid carcinoma), resulting in wide-ranging effects on gene expression in both settings. A substantial proportion of the NME1-regulated genes identified in the analyses were of clear potential relevance to metastasis, such as matrix metalloproteinase-1 (MMP1), angiopoietin-2 (ANGPT2), SERPINB9 and colony stimulating factor receptor-2B (CSFR2B). Nine genes were identified (false discovery rate <0.1) that were regulated by NME1 in both the WM1158 and WRO82 cell lines, each possessing one or more such metastasis-relevant activities as stress fiber formation and focal adhesion (PPM1E, ZYX, PFN1), chemotaxis (CCR1) epithelial-mesenchymal signaling (WNT6), differentiation and morphogenesis (TBX4, ZFP36L2), and G protein modulation (GPR52 and PFN1). In addition, a number of the NME1-regulated genes were shown to be of prognostic value for distant disease-free survival and overall survival in melanoma and breast cancer. The combined expression of three NME1-regulated genes CSFR2B, MSF4A1 and SERPINB9 provided a strongly synergistic correlation with distant disease-free survival in the basal subtype of breast cancer (p<3.5e(-5), hazard ratio=0.33). Our study demonstrates that analysis of NME1-dependent gene expression is a powerful approach for identifying potential modulators of metastatic potential in multiple cancer types, which in turn may represent useful therapeutic targets. The study also highlights NME1-dependent genes as potential prognostic/diagnostic indices, which are profoundly lacking at present in melanoma. Copyright© 2014, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Sequential Metabolic Phases as a Means to Optimize Cellular Output in a Constant Environment

PubMed Central

Bockmayr, Alexander; Holzhütter, Hermann-Georg

2015-01-01

Temporal changes of gene expression are a well-known regulatory feature of all cells, which is commonly perceived as a strategy to adapt the proteome to varying external conditions. However, temporal (rhythmic and non-rhythmic) changes of gene expression are also observed under virtually constant external conditions. Here we hypothesize that such changes are a means to render the synthesis of the metabolic output more efficient than under conditions of constant gene activities. In order to substantiate this hypothesis, we used a flux-balance model of the cellular metabolism. The total time span spent on the production of a given set of target metabolites was split into a series of shorter time intervals (metabolic phases) during which only selected groups of metabolic genes are active. The related flux distributions were calculated under the constraint that genes can be either active or inactive whereby the amount of protein related to an active gene is only controlled by the number of active genes: the lower the number of active genes the more protein can be allocated to the enzymes carrying non-zero fluxes. This concept of a predominantly protein-limited efficiency of gene expression clearly differs from other concepts resting on the assumption of an optimal gene regulation capable of allocating to all enzymes and transporters just that fraction of protein necessary to prevent rate limitation. Applying this concept to a simplified metabolic network of the central carbon metabolism with glucose or lactate as alternative substrates, we demonstrate that switching between optimally chosen stationary flux modes comprising different sets of active genes allows producing a demanded amount of target metabolites in a significantly shorter time than by a single optimal flux mode at fixed gene activities. Our model-based findings suggest that temporal expression of metabolic genes can be advantageous even under conditions of constant external substrate supply. PMID:25786979

Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq.

PubMed

Whitmore, S Scott; Wagner, Alex H; DeLuca, Adam P; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Zeng, Shemin; Braun, Terry A; Mullins, Robert F; Scheetz, Todd E

2014-12-01

Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq

PubMed Central

Whitmore, S. Scott; Wagner, Alex H.; DeLuca, Adam P.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Zeng, Shemin; Braun, Terry A.; Mullins, Robert F.; Scheetz, Todd E.

2014-01-01

Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell-types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. PMID:25446321

Suppression subtractive hybridization and comparative expression analysis to identify developmentally regulated genes in filamentous fungi.

PubMed

Gesing, Stefan; Schindler, Daniel; Nowrousian, Minou

2013-09-01

Ascomycetes differentiate four major morphological types of fruiting bodies (apothecia, perithecia, pseudothecia and cleistothecia) that are derived from an ancestral fruiting body. Thus, fruiting body differentiation is most likely controlled by a set of common core genes. One way to identify such genes is to search for genes with evolutionary conserved expression patterns. Using suppression subtractive hybridization (SSH), we selected differentially expressed transcripts in Pyronema confluens (Pezizales) by comparing two cDNA libraries specific for sexual and for vegetative development, respectively. The expression patterns of selected genes from both libraries were verified by quantitative real time PCR. Expression of several corresponding homologous genes was found to be conserved in two members of the Sordariales (Sordaria macrospora and Neurospora crassa), a derived group of ascomycetes that is only distantly related to the Pezizales. Knockout studies with N. crassa orthologues of differentially regulated genes revealed a functional role during fruiting body development for the gene NCU05079, encoding a putative MFS peptide transporter. These data indicate conserved gene expression patterns and a functional role of the corresponding genes during fruiting body development; such genes are candidates of choice for further functional analysis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Histidine-rich stabilized polyplexes for cMet-directed tumor-targeted gene transfer

NASA Astrophysics Data System (ADS)

Kos, Petra; Lächelt, Ulrich; Herrmann, Annika; Mickler, Frauke Martina; Döblinger, Markus; He, Dongsheng; Krhač Levačić, Ana; Morys, Stephan; Bräuchle, Christoph; Wagner, Ernst

2015-03-01

Overexpression of the hepatocyte growth factor receptor/c-Met proto oncogene on the surface of a variety of tumor cells gives an opportunity to specifically target cancerous tissues. Herein, we report the first use of c-Met as receptor for non-viral tumor-targeted gene delivery. Sequence-defined oligomers comprising the c-Met binding peptide ligand cMBP2 for targeting, a monodisperse polyethylene glycol (PEG) for polyplex surface shielding, and various cationic (oligoethanamino) amide cores containing terminal cysteines for redox-sensitive polyplex stabilization, were assembled by solid-phase supported syntheses. The resulting oligomers exhibited a greatly enhanced cellular uptake and gene transfer over non-targeted control sequences, confirming the efficacy and target-specificity of the formed polyplexes. Implementation of endosomal escape-promoting histidines in the cationic core was required for gene expression without additional endosomolytic agent. The histidine-enriched polyplexes demonstrated stability in serum as well as receptor-specific gene transfer in vivo upon intratumoral injection. The co-formulation with an analogous PEG-free cationic oligomer led to a further compaction of pDNA polyplexes with an obvious change of shape as demonstrated by transmission electron microscopy. Such compaction was critically required for efficient intravenous gene delivery which resulted in greatly enhanced, cMBP2 ligand-dependent gene expression in the distant tumor.Overexpression of the hepatocyte growth factor receptor/c-Met proto oncogene on the surface of a variety of tumor cells gives an opportunity to specifically target cancerous tissues. Herein, we report the first use of c-Met as receptor for non-viral tumor-targeted gene delivery. Sequence-defined oligomers comprising the c-Met binding peptide ligand cMBP2 for targeting, a monodisperse polyethylene glycol (PEG) for polyplex surface shielding, and various cationic (oligoethanamino) amide cores containing terminal cysteines for redox-sensitive polyplex stabilization, were assembled by solid-phase supported syntheses. The resulting oligomers exhibited a greatly enhanced cellular uptake and gene transfer over non-targeted control sequences, confirming the efficacy and target-specificity of the formed polyplexes. Implementation of endosomal escape-promoting histidines in the cationic core was required for gene expression without additional endosomolytic agent. The histidine-enriched polyplexes demonstrated stability in serum as well as receptor-specific gene transfer in vivo upon intratumoral injection. The co-formulation with an analogous PEG-free cationic oligomer led to a further compaction of pDNA polyplexes with an obvious change of shape as demonstrated by transmission electron microscopy. Such compaction was critically required for efficient intravenous gene delivery which resulted in greatly enhanced, cMBP2 ligand-dependent gene expression in the distant tumor. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06556e

Inventory and Phylogenetic Analysis of Meiotic Genes in Monogonont Rotifers

PubMed Central

2013-01-01

A long-standing question in evolutionary biology is how sexual reproduction has persisted in eukaryotic lineages. As cyclical parthenogens, monogonont rotifers are a powerful model for examining this question, yet the molecular nature of sexual reproduction in this lineage is currently understudied. To examine genes involved in meiosis, we generated partial genome assemblies for 2 distantly related monogonont species, Brachionus calyciflorus and B. manjavacas. Here we present an inventory of 89 meiotic genes, of which 80 homologs were identified and annotated from these assemblies. Using phylogenetic analysis, we show that several meiotic genes have undergone relatively recent duplication events that appear to be specific to the monogonont lineage. Further, we compare the expression of “meiosis-specific” genes involved in recombination and all annotated copies of the cell cycle regulatory gene CDC20 between obligate parthenogenetic (OP) and cyclical parthenogenetic (CP) strains of B. calyciflorus. We show that “meiosis-specific” genes are expressed in both CP and OP strains, whereas the expression of one of the CDC20 genes is specific to cyclical parthenogenesis. The data presented here provide insights into mechanisms of cyclical parthenogenesis and establish expectations for studies of obligate asexual relatives of monogononts, the bdelloid rotifer lineage. PMID:23487324

Understanding α-globin gene regulation and implications for the treatment of β-thalassemia.

PubMed

Mettananda, Sachith; Gibbons, Richard J; Higgs, Douglas R

2016-03-01

Over the past three decades, a vast amount of new information has been uncovered describing how the globin genes are regulated. This knowledge has provided significant insights into the general understanding of the regulation of human genes. It is now known that molecular defects within and around the α- and β-globin genes, as well as in the distant regulatory elements, can cause thalassemia. Unbalanced production of globin chains owing to defective synthesis of one, and the continued unopposed synthesis of another, is the central causative factor in the cellular pathology and pathophysiology of thalassemia. A large body of clinical, genetic, and experimental evidence suggests that altering globin chain imbalance by reducing the production of α-globin synthesis ameliorates the disease severity in patients with β-thalassemia. With the development of new genetic-based therapeutic tools that have a potential to decrease the expression of a selected gene in a tissue-specific manner, the possibility of decreasing expression of the α-globin gene to improve the clinical severity of β-thalassemia could become a reality. © 2015 New York Academy of Sciences.

Reassortant group A rotavirus from straw-colored fruit bat (Eidolon helvum).

PubMed

Esona, Mathew D; Mijatovic-Rustempasic, Slavica; Conrardy, Christina; Tong, Suxiang; Kuzmin, Ivan V; Agwanda, Bernard; Breiman, Robert F; Banyai, Krisztian; Niezgoda, Michael; Rupprecht, Charles E; Gentsch, Jon R; Bowen, Michael D

2010-12-01

Bats are known reservoirs of viral zoonoses. We report genetic characterization of a bat rotavirus (Bat/KE4852/07) detected in the feces of a straw-colored fruit bat (Eidolon helvum). Six bat rotavirus genes (viral protein [VP] 2, VP6, VP7, nonstructural protein [NSP] 2, NSP3, and NSP5) shared ancestry with other mammalian rotaviruses but were distantly related. The VP4 gene was nearly identical to that of human P[6] rotavirus strains, and the NSP4 gene was closely related to those of previously described mammalian rotaviruses, including human strains. Analysis of partial sequence of the VP1 gene indicated that it was distinct from cognate genes of other rotaviruses. No sequences were obtained for the VP3 and NSP1 genes of the bat rotavirus. This rotavirus was designated G25-P[6]-I15-R8(provisional)-C8-Mx-Ax-N8-T11-E2-H10. Results suggest that several reassortment events have occurred between human, animal, and bat rotaviruses. Several additional rotavirus strains were detected in bats.

Reassortant Group A Rotavirus from Straw-colored Fruit Bat (Eidolon helvum)

PubMed Central

Esona, Mathew D.; Mijatovic-Rustempasic, Slavica; Conrardy, Christina; Tong, Suxiang; Kuzmin, Ivan V.; Agwanda, Bernard; Breiman, Robert F.; Banyai, Krisztian; Niezgoda, Michael; Rupprecht, Charles E.; Gentsch, Jon R.

2010-01-01

Bats are known reservoirs of viral zoonoses. We report genetic characterization of a bat rotavirus (Bat/KE4852/07) detected in the feces of a straw-colored fruit bat (Eidolon helvum). Six bat rotavirus genes (viral protein [VP] 2, VP6, VP7, nonstructural protein [NSP] 2, NSP3, and NSP5) shared ancestry with other mammalian rotaviruses but were distantly related. The VP4 gene was nearly identical to that of human P[6] rotavirus strains, and the NSP4 gene was closely related to those of previously described mammalian rotaviruses, including human strains. Analysis of partial sequence of the VP1 gene indicated that it was distinct from cognate genes of other rotaviruses. No sequences were obtained for the VP3 and NSP1 genes of the bat rotavirus. This rotavirus was designated G25-P[6]-I15-R8(provisional)-C8-Mx-Ax-N8-T11-E2-H10. Results suggest that several reassortment events have occurred between human, animal, and bat rotaviruses. Several additional rotavirus strains were detected in bats. PMID:21122212

Metagenomic Analysis of the Sponge Discodermia Reveals the Production of the Cyanobacterial Natural Product Kasumigamide by 'Entotheonella'.

PubMed

Nakashima, Yu; Egami, Yoko; Kimura, Miki; Wakimoto, Toshiyuki; Abe, Ikuro

2016-01-01

Sponge metagenomes are a useful platform to mine cryptic biosynthetic gene clusters responsible for production of natural products involved in the sponge-microbe association. Since numerous sponge-derived bioactive metabolites are biosynthesized by the symbiotic bacteria, this strategy may concurrently reveal sponge-symbiont produced compounds. Accordingly, a metagenomic analysis of the Japanese marine sponge Discodermia calyx has resulted in the identification of a hybrid type I polyketide synthase-nonribosomal peptide synthetase gene (kas). Bioinformatic analysis of the gene product suggested its involvement in the biosynthesis of kasumigamide, a tetrapeptide originally isolated from freshwater free-living cyanobacterium Microcystis aeruginosa NIES-87. Subsequent investigation of the sponge metabolic profile revealed the presence of kasumigamide in the sponge extract. The kasumigamide producing bacterium was identified as an 'Entotheonella' sp. Moreover, an in silico analysis of kas gene homologs uncovered the presence of kas family genes in two additional bacteria from different phyla. The production of kasumigamide by distantly related multiple bacterial strains implicates horizontal gene transfer and raises the potential for a wider distribution across other bacterial groups.

Association Between the 21-Gene Recurrence Score Assay and Risk of Locoregional Recurrence in Node-Negative, Estrogen Receptor–Positive Breast Cancer: Results From NSABP B-14 and NSABP B-20

PubMed Central

Mamounas, Eleftherios P.; Tang, Gong; Fisher, Bernard; Paik, Soonmyung; Shak, Steven; Costantino, Joseph P.; Watson, Drew; Geyer, Charles E.; Wickerham, D. Lawrence; Wolmark, Norman

2010-01-01

Purpose The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)–positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20). Patients and Methods RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored. Results In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen–treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment. Conclusion Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer. PMID:20065188

Genome-Wide Gene Expression in relation to Age in Large Laboratory Cohorts of Drosophila melanogaster

PubMed Central

Carlson, Kimberly A.; Gardner, Kylee; Pashaj, Anjeza; Carlson, Darby J.; Yu, Fang; Eudy, James D.; Zhang, Chi; Harshman, Lawrence G.

2015-01-01

Aging is a complex process characterized by a steady decline in an organism's ability to perform life-sustaining tasks. In the present study, two cages of approximately 12,000 mated Drosophila melanogaster females were used as a source of RNA from individuals sampled frequently as a function of age. A linear model for microarray data method was used for the microarray analysis to adjust for the box effect; it identified 1,581 candidate aging genes. Cluster analyses using a self-organizing map algorithm on the 1,581 significant genes identified gene expression patterns across different ages. Genes involved in immune system function and regulation, chorion assembly and function, and metabolism were all significantly differentially expressed as a function of age. The temporal pattern of data indicated that gene expression related to aging is affected relatively early in life span. In addition, the temporal variance in gene expression in immune function genes was compared to a random set of genes. There was an increase in the variance of gene expression within each cohort, which was not observed in the set of random genes. This observation is compatible with the hypothesis that D. melanogaster immune function genes lose control of gene expression as flies age. PMID:26090231

Microgeographic and temporal genetic variation in populations of the bluetongue virus vector Culicoides variipennis (Diptera: Ceratopogonidae).

PubMed

Tabachnick, W J

1992-05-01

Seven Colorado populations of the bluetongue virus vector Culicoides varipennis (Coquillett) were analyzed for genetic variation at 19-21 isozyme loci. Permanent populations, which overwinter as larvae, showed little temporal genetic change at 19 loci. PGD and MDH showed seasonal changes in gene frequencies, attributable to selection at two permanent populations. Two temporary populations showed low heterozygosity compared with permanent populations. Independent estimates of gene flow, calculated using FST and the private allele method, were Nm* = 2.15 and 6.95, respectively. Colorado C. variipennis permanent populations showed high levels of gene flow which prevented significant genetic differentiation due to genetic drift. Temporary populations showed significant gene frequency differences from nearby permanent populations due to the "founder effect" associated with chance colonization.

Diurnal oscillation of SBE expression in sorghum endosperm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Chuanxin; Mutisya, J.; Rosenquist, S.

2009-01-15

Spatial and temporal expression patterns of the sorghum SBEI, SBEIIA and SBEIIB genes, encoding, respectively, starch branching enzyme (SBE) I, IIA and IIB, in the developing endosperm of sorghum (Sorghum bicolor) were studied. Full-length genomic and cDNA clones for sorghum was cloned and the SBEIIA cDNA was used together with gene-specific probes for sorghum SBEIIB and SBEI. In contrast to sorghum SBEIIB, which was expressed primarily in endosperm and embryo, SBEIIA was expressed also in vegetative tissues. All three genes shared a similar temporal expression profile during endosperm development, with a maximum activity at 15-24 days after pollination. This ismore » different from barley and maize where SBEI gene activity showed a significantly later onset compared to that of SBEIIA and SBEIIB. Expression of the three SBE genes in the sorghum endosperm exhibited a diurnal rhythm during a 24-h cycle.« less

The human interleukin-1 alpha gene is located on the long arm of chromosome 2 at band q13.

PubMed

Lafage, M; Maroc, N; Dubreuil, P; de Waal Malefijt, R; Pébusque, M J; Carcassonne, Y; Mannoni, P

1989-01-01

Interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) are two biochemically distinct, but distantly related, polypeptidic cytokines that play a key role in inflammation, immunologic reactions, and tissue repair. Recently, it has been shown that IL-1 alpha is identical to hematopoietin 1, which was described as a hematopoietic growth factor acting on early progenitor cells in synergy with other hematopoietic growth factors. In this report we discuss our use of in situ hybridization on human prometaphase cells with a human IL-1 alpha cDNA probe to localize the human IL-1 alpha gene on the proximal part of the long arm of chromosome 2 at band q13, in the same chromosomal region as the IL-1 beta gene.

Sequencing of cDNA Clones from the Genetic Map of Tomato (Lycopersicon esculentum)

PubMed Central

Ganal, Martin W.; Czihal, Rosemarie; Hannappel, Ulrich; Kloos, Dorothee-U.; Polley, Andreas; Ling, Hong-Qing

1998-01-01

The dense RFLP linkage map of tomato (Lycopersicon esculentum) contains >300 anonymous cDNA clones. Of those clones, 272 were partially or completely sequenced. The sequences were compared at the DNA and protein level to known genes in databases. For 57% of the clones, a significant match to previously described genes was found. The information will permit the conversion of those markers to STS markers and allow their use in PCR-based mapping experiments. Furthermore, it will facilitate the comparative mapping of genes across distantly related plant species by direct comparison of DNA sequences and map positions. [cDNA sequence data reported in this paper have been submitted to the EMBL database under accession nos. AA824695–AA825005 and the dbEST_Id database under accession nos. 1546519–1546862.] PMID:9724330

Protocols for Biotechnological Interventions in Improvement of Vanilla (Vanilla planifolia Andrews.).

PubMed

Divakaran, Minoo; Babu, K Nirmal; Peter, K V

2016-01-01

Vanilla (Vanilla planifolia Andrews (syn. V. fragrans Salisb.), a native of Central America, is the primary source of natural vanillin and plays a major role in the global economy. The gene pool of vanilla is threatened by deforestation and overcollection that has resulted in disappearance of natural habitats and wild species. Continuous vegetative propagation and lack of natural seed set and sufficient variations in the gene pool hamper crop improvement programs. In vitro techniques, one of the key tools of plant biotechnology, can be employed for overcoming specific problems, viz. production of disease-free clones, inducing somaclonal variations, developing hybrids, gene pool conservation, incorporating desired traits by distant hybridization, genetic engineering, etc. However, realization of these objectives necessitates standardization of protocols. This chapter describes the various protocols optimized for crop improvement in Vanilla species.

Lung cancer progression and metastasis from the prognostic point of view.

PubMed

Inamura, Kentaro; Ishikawa, Yuichi

2010-08-01

Lung cancer is the leading cause of cancer death in men and women worldwide. Since the occurrence of metastases in distant organs is the major reason for mortality of cancer patients, we need to elucidate the underlying mechanisms. Many studies featuring analysis of gene expression, comparative genomic hybridization and loss of heterozygosity analysis have been performed and generated support for the hypothesis that metastatic potential is acquired early in tumorigenesis. Furthermore, it is now clear that the majority of tumor cells have the potential to metastasize. Although many changes in gene expression profiles have been established retrospectively, translational research is now a high priority to enable clinical application and treatment based on laboratory findings.

Improving draft genome contiguity with reference-derived in silico mate-pair libraries.

PubMed

Grau, José Horacio; Hackl, Thomas; Koepfli, Klaus-Peter; Hofreiter, Michael

2018-05-01

Contiguous genome assemblies are a highly valued biological resource because of the higher number of completely annotated genes and genomic elements that are usable compared to fragmented draft genomes. Nonetheless, contiguity is difficult to obtain if only low coverage data and/or only distantly related reference genome assemblies are available. In order to improve genome contiguity, we have developed Cross-Species Scaffolding-a new pipeline that imports long-range distance information directly into the de novo assembly process by constructing mate-pair libraries in silico. We show how genome assembly metrics and gene prediction dramatically improve with our pipeline by assembling two primate genomes solely based on ∼30x coverage of shotgun sequencing data.

High-throughput analysis of spatio-temporal dynamics in Dictyostelium

PubMed Central

Sawai, Satoshi; Guan, Xiao-Juan; Kuspa, Adam; Cox, Edward C

2007-01-01

We demonstrate a time-lapse video approach that allows rapid examination of the spatio-temporal dynamics of Dictyostelium cell populations. Quantitative information was gathered by sampling life histories of more than 2,000 mutant clones from a large mutagenesis collection. Approximately 4% of the clonal lines showed a mutant phenotype at one stage. Many of these could be ordered by clustering into functional groups. The dataset allows one to search and retrieve movies on a gene-by-gene and phenotype-by-phenotype basis. PMID:17659086

Analysis of Temporal-spatial Co-variation within Gene Expression Microarray Data in an Organogenesis Model

NASA Astrophysics Data System (ADS)

Ehler, Martin; Rajapakse, Vinodh; Zeeberg, Barry; Brooks, Brian; Brown, Jacob; Czaja, Wojciech; Bonner, Robert F.

The gene networks underlying closure of the optic fissure during vertebrate eye development are poorly understood. We used a novel clustering method based on Laplacian Eigenmaps, a nonlinear dimension reduction method, to analyze microarray data from laser capture microdissected (LCM) cells at the site and developmental stages (days 10.5 to 12.5) of optic fissure closure. Our new method provided greater biological specificity than classical clustering algorithms in terms of identifying more biological processes and functions related to eye development as defined by Gene Ontology at lower false discovery rates. This new methodology builds on the advantages of LCM to isolate pure phenotypic populations within complex tissues and allows improved ability to identify critical gene products expressed at lower copy number. The combination of LCM of embryonic organs, gene expression microarrays, and extracting spatial and temporal co-variations appear to be a powerful approach to understanding the gene regulatory networks that specify mammalian organogenesis.

Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls

PubMed Central

Leininger, Elizabeth C.; Kelley, Darcy B.

2013-01-01

Independent or convergent evolution can underlie phenotypic similarity of derived behavioural characters. Determining the underlying neural and neuromuscular mechanisms sheds light on how these characters arose. One example of evolutionarily derived characters is a temporally simple advertisement call of male African clawed frogs (Xenopus) that arose at least twice independently from a more complex ancestral pattern. How did simplification occur in the vocal circuit? To distinguish shared from divergent mechanisms, we examined activity from the calling brain and vocal organ (larynx) in two species that independently evolved simplified calls. We find that each species uses distinct neural and neuromuscular strategies to produce the simplified calls. Isolated  Xenopus borealis brains produce fictive vocal patterns that match temporal patterns of actual male calls; the larynx converts nerve activity faithfully into muscle contractions and single clicks. In contrast, fictive patterns from isolated Xenopus boumbaensis brains are short bursts of nerve activity; the isolated larynx requires stimulus bursts to produce a single click of sound. Thus, unlike X. borealis, the output of the X. boumbaensis hindbrain vocal pattern generator is an ancestral burst-type pattern, transformed by the larynx into single clicks. Temporally simple advertisement calls in genetically distant species of Xenopus have thus arisen independently via reconfigurations of central and peripheral vocal neuroeffectors. PMID:23407829

Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls.

PubMed

Leininger, Elizabeth C; Kelley, Darcy B

2013-04-07

Independent or convergent evolution can underlie phenotypic similarity of derived behavioural characters. Determining the underlying neural and neuromuscular mechanisms sheds light on how these characters arose. One example of evolutionarily derived characters is a temporally simple advertisement call of male African clawed frogs (Xenopus) that arose at least twice independently from a more complex ancestral pattern. How did simplification occur in the vocal circuit? To distinguish shared from divergent mechanisms, we examined activity from the calling brain and vocal organ (larynx) in two species that independently evolved simplified calls. We find that each species uses distinct neural and neuromuscular strategies to produce the simplified calls. Isolated Xenopus borealis brains produce fictive vocal patterns that match temporal patterns of actual male calls; the larynx converts nerve activity faithfully into muscle contractions and single clicks. In contrast, fictive patterns from isolated Xenopus boumbaensis brains are short bursts of nerve activity; the isolated larynx requires stimulus bursts to produce a single click of sound. Thus, unlike X. borealis, the output of the X. boumbaensis hindbrain vocal pattern generator is an ancestral burst-type pattern, transformed by the larynx into single clicks. Temporally simple advertisement calls in genetically distant species of Xenopus have thus arisen independently via reconfigurations of central and peripheral vocal neuroeffectors.

Fundamental statistical relationships between monthly and daily meteorological variables: Temporal downscaling of weather based on a global observational dataset

NASA Astrophysics Data System (ADS)

Sommer, Philipp; Kaplan, Jed

2016-04-01

Accurate modelling of large-scale vegetation dynamics, hydrology, and other environmental processes requires meteorological forcing on daily timescales. While meteorological data with high temporal resolution is becoming increasingly available, simulations for the future or distant past are limited by lack of data and poor performance of climate models, e.g., in simulating daily precipitation. To overcome these limitations, we may temporally downscale monthly summary data to a daily time step using a weather generator. Parameterization of such statistical models has traditionally been based on a limited number of observations. Recent developments in the archiving, distribution, and analysis of "big data" datasets provide new opportunities for the parameterization of a temporal downscaling model that is applicable over a wide range of climates. Here we parameterize a WGEN-type weather generator using more than 50 million individual daily meteorological observations, from over 10'000 stations covering all continents, based on the Global Historical Climatology Network (GHCN) and Synoptic Cloud Reports (EECRA) databases. Using the resulting "universal" parameterization and driven by monthly summaries, we downscale mean temperature (minimum and maximum), cloud cover, and total precipitation, to daily estimates. We apply a hybrid gamma-generalized Pareto distribution to calculate daily precipitation amounts, which overcomes much of the inability of earlier weather generators to simulate high amounts of daily precipitation. Our globally parameterized weather generator has numerous applications, including vegetation and crop modelling for paleoenvironmental studies.

Digital signaling decouples activation probability and population heterogeneity.

PubMed

Kellogg, Ryan A; Tian, Chengzhe; Lipniacki, Tomasz; Quake, Stephen R; Tay, Savaş

2015-10-21

Digital signaling enhances robustness of cellular decisions in noisy environments, but it is unclear how digital systems transmit temporal information about a stimulus. To understand how temporal input information is encoded and decoded by the NF-κB system, we studied transcription factor dynamics and gene regulation under dose- and duration-modulated inflammatory inputs. Mathematical modeling predicted and microfluidic single-cell experiments confirmed that integral of the stimulus (or area, concentration × duration) controls the fraction of cells that activate NF-κB in the population. However, stimulus temporal profile determined NF-κB dynamics, cell-to-cell variability, and gene expression phenotype. A sustained, weak stimulation lead to heterogeneous activation and delayed timing that is transmitted to gene expression. In contrast, a transient, strong stimulus with the same area caused rapid and uniform dynamics. These results show that digital NF-κB signaling enables multidimensional control of cellular phenotype via input profile, allowing parallel and independent control of single-cell activation probability and population heterogeneity.

Gene therapy for prostate cancer: where are we now?

PubMed

Steiner, M S; Gingrich, J R

2000-10-01

The ability to recombine specifically and alter DNA sequences followed by techniques to transfer these sequences or even whole genes into normal and diseased cells has revolutionized medical research and ushered the clinicians of today into the age of gene therapy. We provide urologists a review of relevant background information, outline current treatment strategies and clinical trials, and delineate current challenges facing the field of gene therapy for advanced prostate cancer. We comprehensively reviewed the literature, including PubMed and recent abstract proceedings from national meetings, relevant to gene therapy and advanced prostate cancer. We selected for review literature representative of the principal scientific background for current gene therapy strategies and National Institutes of Health Recombinant DNA Advisory Committee approved clinical trials. Current prostate cancer gene therapy strategies include correcting aberrant gene expression, exploiting programmed cell death pathways, targeting critical cell biological functions, introducing toxic or cell lytic suicide genes, enhancing the immune system antitumor response and combining treatment with conventional cytotoxic chemotherapy or radiation therapy. Many challenges lie ahead for gene therapy, including improving DNA transfer efficiency to cells locally and at distant sites, enhancing levels of gene expression and overcoming immune responses that limit the time that genes are expressed. Nevertheless, despite these current challenges it is almost certain that gene therapy will be part of the urological armamentarium against prostate cancer in this century.

Physiogenomic analysis of localized FMRI brain activity in schizophrenia.

PubMed

Windemuth, Andreas; Calhoun, Vince D; Pearlson, Godfrey D; Kocherla, Mohan; Jagannathan, Kanchana; Ruaño, Gualberto

2008-06-01

The search for genetic factors associated with disease is complicated by the complexity of the biological pathways linking genotype and phenotype. This analytical complexity is particularly concerning in diseases historically lacking reliable diagnostic biological markers, such as schizophrenia and other mental disorders. We investigate the use of functional magnetic resonance imaging (fMRI) as an intermediate phenotype (endophenotype) to identify physiogenomic associations to schizophrenia. We screened 99 subjects, 30 subjects diagnosed with schizophrenia, 13 unaffected relatives of schizophrenia patients, and 56 unrelated controls, for gene polymorphisms associated with fMRI activation patterns at two locations in temporal and frontal lobes previously implied in schizophrenia. A total of 22 single nucleotide polymorphisms (SNPs) in 15 genes from the dopamine and serotonin neurotransmission pathways were genotyped in all subjects. We identified three SNPs in genes that are significantly associated with fMRI activity. SNPs of the dopamine beta-hydroxylase (DBH) gene and of the dopamine receptor D4 (DRD4) were associated with activity in the temporal and frontal lobes, respectively. One SNP of serotonin-3A receptor (HTR3A) was associated with temporal lobe activity. The results of this study support the physiogenomic analysis of neuroimaging data to discover associations between genotype and disease-related phenotypes.

Microvascular Channel Device to Study Aggressiveness in Prostate Cancer Metastasis

DTIC Science & Technology

2014-08-01

contributes to PCa’s distant metastasis, which is mediated via an E- selectin ligand, ESL -1. Consequently, the interaction of E-selectin/ ESL -1 transduces...cancer cell, E-selectin, ESL -1. OVERALL PROJECT SUMMARY A. Major goals of the project: 3 Task 1: Correlation of cancers’ aggressiveness with...Determination of the aggressive/metastatic related gene I. 1. ESL -1 expression is high in rolling cells and tissue When PCa cells come in contact with

A molecular comparison of Alaskan and North East Atlantic Halicondria panicea (Pallas 1766) (Porifera: Demospongiae)

USGS Publications Warehouse

Erpenbeck, Dirk; Knowlton, Anne L.; Talbot, Sandra L.; Highsmith, Ray C.; van Soest, Rob W.M.

2004-01-01

The intraspecific relationships between populations of Alaskan Halichondria cf. panicea are the subjects of ongoing research. In this study we compare CO1 sequences of Alaskan Halichondria cf. panicea with North East Atlantic Halichondria panicea and its sister species Halichondria bowerbanki. Alaskan Halichondria cf. panicea form a well-supported sister group to the European Halichondria panicea/ H. bowerbanki species complex in the resulting gene tree and cluster distantly from their European conspecifics.

From Breast to Bone: Tracking Gene Expression Changes Responsible for Breast Cancer Metastasis in a Humanized Mouse Model with Molecular Imaging

DTIC Science & Technology

2015-11-01

strategies to predict and prevent metastasis. 15. SUBJECT TERMS triple-negative breast cancer, metastasis, p53, BTG2, PDX Models 16. SECURITY CLASSIFICATION...membrane and into the circulation, survival in the circulation, extravasation into distant organs, tumor dormancy, and finally tumor growth in the...sequencing analysis are novel targets for metastasis prevention or are more effective at destroying metastatic cells while minimizing the risk of

The Molecular Basis of the Response to Radiation

DTIC Science & Technology

1999-07-01

S. cerevisiae and S. pombe ). After PCR amplification of human cDNA libraries as described below, PCR products are analyzed on 4% NuSieve agarose...media lacking uracil as well as counterselected against on media containing uracil and 0.1% 5-fluoroorotic acid (5FOA). Induction of the LacZ gene...evolutionarily distant species (S. cerevisiae andS. pombe ) to develop degenerate PCR based primers. For example, a fission yeast homolog of RAD9 named rhp9 was

Genomic Diversity of “Deep Ecotype” Alteromonas macleodii Isolates: Evidence for Pan-Mediterranean Clonal Frames

PubMed Central

López-Pérez, Mario; Gonzaga, Aitor; Rodriguez-Valera, Francisco

2013-01-01

We have compared genomes of Alteromonas macleodii “deep ecotype” isolates from two deep Mediterranean sites and two surface samples from the Aegean and the English Channel. A total of nine different genomes were analyzed. They belong to five clonal frames (CFs) that differ among them by approximately 30,000 single-nucleotide polymorphisms (SNPs) over their core genomes. Two of the CFs contain three strains each with nearly identical genomes (∼100 SNPs over the core genome). One of the CFs had representatives that were isolated from samples taken more than 1,000 km away, 2,500 m deeper, and 5 years apart. These data mark the longest proven persistence of a CF in nature (outside of clinical settings). We have found evidence for frequent recombination events between or within CFs and even with the distantly related A. macleodii surface ecotype. The different CFs had different flexible genomic islands. They can be classified into two groups; one type is additive, that is, containing different numbers of gene cassettes, and is very variable in short time periods (they often varied even within a single CF). The other type was more stable and produced the complete replacement of a genomic fragment by another with different genes. Although this type was more conserved within each CF, we found examples of recombination among distantly related CFs including English Channel and Mediterranean isolates. PMID:23729633

Kiloniella laminariae gen. nov., sp. nov., an alphaproteobacterium from the marine macroalga Laminaria saccharina.

PubMed

Wiese, Jutta; Thiel, Vera; Gärtner, Andrea; Schmaljohann, Rolf; Imhoff, Johannes F

2009-02-01

A novel alphaproteobacterium, strain LD81(T), was isolated from the marine macroalga Laminaria saccharina. The bacterium is mesophilic and shows a typical marine growth response. It is a chemoheterotrophic aerobe with the potential for denitrification. Growth optima are 25 degrees C, pH 5.5 and 3 % NaCl. Strain LD81(T) has a unique phylogenetic position, not fitting any of the known families of the Alphaproteobacteria. The 16S rRNA gene sequence revealed a distant relationship to species of several orders of the Alphaproteobacteria, with less than 90 % sequence similarity. Phylogenetically, strain LD81(T) is related to the type strains of Terasakiella pusilla (88.4 % 16S rRNA gene sequence similarity) and the three Thalassospira species (88.9-89.2 %). It forms a cluster with these bacteria and a novel as-yet undescribed isolate (KOPRI 13522; 96.6 % sequence similarity). Strain LD81(T) has a relatively low DNA G+C content (51.1 mol%) and, due to its distant phylogenetic position from all other alphaproteobacteria, strain LD81(T) (=NCIMB 14374(T) =JCM 14845(T)) is considered as the type strain of a novel species within a new genus, for which the name Kiloniella laminariae gen. nov., sp. nov. is proposed. The genus Kiloniella represents the type of the new family Kiloniellaceae fam. nov. and order Kiloniellales ord. nov.

An analysis of variation in expression of neurofibromatosis (NF) type I (NFI): Evidence for modifying genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Easton, D.F.; Ponder, B.A.J.; Huson, S.M.

Neurofibromatosis (NF) type 1 (NF1) is notable for its variable expression. To determine whether variation in expression has an inherited component, the authors examined 175 individuals in 48 NF families, including six MZ twin pairs. Three quantitative traits were scored - number of cafe-au-lait patches, number of cutaneous neurofibromas, and head circumference; and five binary traits were scored - the presence or absence of plexiform neurofibromas, optic gliomas, scoliosis, epilepsy, and referral for remedial education. For cafe-au-lait patches and neurofibromas, correlation was highest between MZ twins, less high between first-degree relatives, and lower still between more distant relatives. The highmore » correlation between distant relatives suggests that the type of mutation at the NF1 locus itself plays only a minor role. All of the five binary traits, with the exception of plexiformneurofibromas, also showed significant familial clustering. The familial effects for these traits were consistent with polygenic effects, but there were insufficient data to rule out other models, including a significant effect of different NF1 mutations. There was no evidence of any association between the different traits in affected individuals. The authors conclude that the phenotypic expression of NF1 is to a large extent determined by the genotype at other [open quotes]modifying[close quotes] loci and that these modifying genes are trait specific. 22 refs., 8 tabs.« less

Identification of Paramecium bursaria syngens through molecular markers--comparative analysis of three loci in the nuclear and mitochondrial DNA.

PubMed

Greczek-Stachura, Magdalena; Potekhin, Alexey; Przyboś, Ewa; Rautian, Maria; Skoblo, Inna; Tarcz, Sebastian

2012-09-01

This is the first attempt to resolve the phylogenetic relationship between different syngens of Paramecium bursaria and to investigate at a molecular level the intraspecific differentiation of strains originating from very distant geographical locations. Herein we introduce a new collection of five P. bursaria syngens maintained at St Petersburg State University, as the international collection of syngens was lost in the 1960s. To analyze the degree of speciation within Paramecium bursaria, we examined 26 strains belonging to five different syngens from distant and geographically isolated localities using rDNA (ITS1-5.8S-ITS2-5'LSU) fragments, mitochondrial cytochrome c oxidase subunit I (COI), and H4 gene fragments. It was shown that P. bursaria strains of the same syngens cluster together in all three inferred molecular phylogenies. The genetic diversity among the studied P. bursaria strains based on rDNA sequences was rather low. The COI divergence of Paramecium bursaria was also definitely lower than that observed in the Paramecium aurelia complex. The nucleotide sequences of the H4 gene analyzed in the present study indicate the extent of genetic differences between the syngens of Paramecium bursaria. Our study demonstrates the diagnostic value of molecular markers, which are important tools in the identification of Paramecium bursaria syngens. Copyright © 2011 Elsevier GmbH. All rights reserved.

Hypofractionated Radiotherapy Is Superior to Conventional Fractionation in an Orthotopic Model of Anaplastic Thyroid Cancer.

PubMed

Oweida, Ayman; Phan, Andy; Vancourt, Benjamin; Robin, Tyler; Hararah, Mohammad K; Bhatia, Shilpa; Milner, Dallin; Lennon, Shelby; Pike, Laura; Raben, David; Haugen, Bryan; Pozdeyev, Nikita; Schweppe, Rebecca; Karam, Sana D

2018-06-01

Anaplastic thyroid cancer (ATC) is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment, including radiation therapy and chemotherapy, response rates remain <15%, with a median time to progression of less than three months. Recent advances in radiotherapy (RT) delivery and gene-expression profiling may help guide patient selection for personalized therapy. The purpose of this study was to characterize the response to radiation in a panel of ATC cell lines and to test alternative RT fractionation schedules for overcoming radioresistance. The cellular response to radiation was characterized based on clonogenic assays. Radiation response was correlated with microarray gene-expression data. Hypofractionated and conventional RT was tested in an orthotopic ATC tumor model, and tumor growth was assayed locally and distantly with in vivo and ex vivo bioluminescence imaging. A spectrum of radiosensitivities was observed in ATC cell lines. Radioresistant cell lines had higher levels of CXCR4 compared to radiosensitive cell lines. Compared to conventionally fractionated RT, hypofractionated RT resulted in significantly improved tumor growth delay, decreased regional and distant metastases, and improved overall survival. The findings demonstrate the heterogeneity of response to radiation in ATC tumors and the superiority of hypofractionated RT in improving local control, metastatic spread, and survival in preclinical models. These data support the design of clinical trials targeting radioresistant pathways in combination with hypofractionated RT.

Reclassification of Halothiobacillus hydrothermalis and Halothiobacillus halophilus to Guyparkeria gen. nov. in the Thioalkalibacteraceae fam. nov., with emended descriptions of the genus Halothiobacillus and family Halothiobacillaceae.

PubMed

Boden, Rich

2017-10-01

The genus Halothiobacillus contains four species of obligate autotrophs with validly published names, of which Halothiobacillus halophilus and Halothiobacillus hydrothermalis are very distant from the type species - on the basis of the 16S rRNA gene, they have 90.7 % and 90.9 % identity to that of the type species, Halothiobacillus neapolitanus. As these values fall below the Yarza cut-off for the rank of genus, and these two species also show no clear affiliation to the closely related genus Thioalkalibacter, a polyphasic study was undertaken to determine if they represent a separate genus. Unlike Halothiobacillus spp. sensu stricto, H. halophilus and H. hydrothermalis are halophilic (rather than halotolerant) and moderately alkaliphilic (rather than neutrophilic) and additionally do not produce tetrathionate as a detectable intermediate of thiosulfate metabolism, indicating some significant metabolic differences. On the basis of these data and of functional gene examination, it is proposed that they be circumscribed as a new genus Guyparkeria gen.nov, for which the type species is Guyparkeria halophila gen. nov., comb. nov. Additionally, Thioalkalibacter and Guyparkeria gen. nov. fall distant from the Halothiobacillaceae so the Thioalkalibacteraceae fam. nov. is proposed, for which Thioalkalibacter is the type genus. Emended descriptions of Halothiobacillus, Halothiobacillus neapolitanus and the Halothiobacillaceae are provided.

Light Stress-Induced One-Helix Protein of the Chlorophyll a/b-Binding Family Associated with Photosystem I1

PubMed Central

Andersson, Ulrica; Heddad, Mounia; Adamska, Iwona

2003-01-01

The superfamily of light-harvesting chlorophyll a/b-binding (Lhc) proteins in higher plants and green algae is composed of more than 20 different antenna proteins associated either with photosystem I (PSI) or photosystem II (PSII). Several distant relatives of this family with conserved chlorophyll-binding residues and proposed photoprotective functions are induced transiently under various stress conditions. Whereas “classical” Lhc proteins contain three-transmembrane α-helices, their distant relatives span the membrane with between one and four transmembrane segments. Here, we report the identification and isolation of a novel member of the Lhc family from Arabidopsis with one predicted transmembrane α-helix closely related to helix I of Lhc protein from PSI (Lhca4) that we named Ohp2 (for a second one-helix protein of Lhc family described from higher plants). We showed that the Ohp2 gene expression is triggered by light stress and that the Ohp2 transcript and protein accumulated in a light intensity-dependent manner. Other stress conditions did not up-regulate the expression of the Ohp2 gene. Localization studies revealed that Ohp2 is associated with PSI under low- or high-light conditions. Because all stress-induced Lhc relatives reported so far were found in PSII, we propose that the accumulation of Ohp2 might represent a novel photoprotective strategy induced within PSI in response to light stress. PMID:12805611

Distinct Roles of Chromatin Insulator Proteins in Control of the Drosophila Bithorax Complex

PubMed Central

Savitsky, Mikhail; Kim, Maria; Kravchuk, Oksana; Schwartz, Yuri B.

2016-01-01

Chromatin insulators are remarkable regulatory elements that can bring distant genomic sites together and block unscheduled enhancer–promoter communications. Insulators act via associated insulator proteins of two classes: sequence-specific DNA binding factors and “bridging” proteins. The latter are required to mediate interactions between distant insulator elements. Chromatin insulators are critical for correct expression of complex loci; however, their mode of action is poorly understood. Here, we use the Drosophila bithorax complex as a model to investigate the roles of the bridging proteins Cp190 and Mod(mdg4). The bithorax complex consists of three evolutionarily conserved homeotic genes Ubx, abd-A, and Abd-B, which specify anterior–posterior identity of the last thoracic and all abdominal segments of the fly. Looking at effects of CTCF, mod(mdg4), and Cp190 mutations on expression of the bithorax complex genes, we provide the first functional evidence that Mod(mdg4) acts in concert with the DNA binding insulator protein CTCF. We find that Mod(mdg4) and Cp190 are not redundant and may have distinct functional properties. We, for the first time, demonstrate that Cp190 is critical for correct regulation of the bithorax complex and show that Cp190 is required at an exceptionally strong Fub insulator to partition the bithorax complex into two topological domains. PMID:26715665

ULTRAPETALA trxG genes interact with KANADI transcription factor genes to regulate Aradopsis Gynoecium patterning

USDA-ARS?s Scientific Manuscript database

Organ formation relies upon precise patterns of gene expression that are under tight spatial and temporal regulation. Transcription patterns are specified by several cellular processes during development, including chromatin remodeling, but little is known about how chromatin remodeling factors cont...

Transcriptional oscillation of canonical clock genes in mouse peripheral tissues

PubMed Central

Yamamoto, Takuro; Nakahata, Yasukazu; Soma, Haruhiko; Akashi, Makoto; Mamine, Takayoshi; Takumi, Toru

2004-01-01

Background The circadian rhythm of about 24 hours is a fundamental physiological function observed in almost all organisms from prokaryotes to humans. Identification of clock genes has allowed us to study the molecular bases for circadian behaviors and temporal physiological processes such as hormonal secretion, and has prompted the idea that molecular clocks reside not only in a central pacemaker, the suprachiasmatic nuclei (SCN) of hypothalamus in mammals, but also in peripheral tissues, even in immortalized cells. Furthermore, previous molecular dissection revealed that the mechanism of circadian oscillation at a molecular level is based on transcriptional regulation of clock and clock-controlled genes. Results We systematically analyzed the mRNA expression of clock and clock-controlled genes in mouse peripheral tissues. Eight genes (mBmal1, mNpas2, mRev-erbα, mDbp, mRev-erbβ, mPer3, mPer1 and mPer2; given in the temporal order of the rhythm peak) showed robust circadian expressions of mRNAs in all tissues except testis, suggesting that these genes are core molecules of the molecular biological clock. The bioinformatics analysis revealed that these genes have one or a combination of 3 transcriptional elements (RORE, DBPE, and E-box), which are conserved among human, mouse, and rat genome sequences, and indicated that these 3 elements may be responsible for the biological timing of expression of canonical clock genes. Conclusions The observation of oscillatory profiles of canonical clock genes is not only useful for physiological and pathological examination of the circadian clock in various organs but also important for systematic understanding of transcriptional regulation on a genome-wide basis. Our finding of the oscillatory expression of canonical clock genes with a temporal order provides us an interesting hypothesis, that cyclic timing of all clock and clock-controlled genes may be dependent on several transcriptional elements including 3 known elements, E-box, RORE, and DBPE. PMID:15473909

The Genomic Basis of Evolutionary Innovation in Pseudomonas aeruginosa

PubMed Central

Wagner, Andreas; MacLean, R. Craig

2016-01-01

Novel traits play a key role in evolution, but their origins remain poorly understood. Here we address this problem by using experimental evolution to study bacterial innovation in real time. We allowed 380 populations of Pseudomonas aeruginosa to adapt to 95 different carbon sources that challenged bacteria with either evolving novel metabolic traits or optimizing existing traits. Whole genome sequencing of more than 80 clones revealed profound differences in the genetic basis of innovation and optimization. Innovation was associated with the rapid acquisition of mutations in genes involved in transcription and metabolism. Mutations in pre-existing duplicate genes in the P. aeruginosa genome were common during innovation, but not optimization. These duplicate genes may have been acquired by P. aeruginosa due to either spontaneous gene amplification or horizontal gene transfer. High throughput phenotype assays revealed that novelty was associated with increased pleiotropic costs that are likely to constrain innovation. However, mutations in duplicate genes with close homologs in the P. aeruginosa genome were associated with low pleiotropic costs compared to mutations in duplicate genes with distant homologs in the P. aeruginosa genome, suggesting that functional redundancy between duplicates facilitates innovation by buffering pleiotropic costs. PMID:27149698

Upregulation of transcription factor NRF2-mediated oxidative stress response pathway in rat brain under short-term chronic hypobaric hypoxia.

PubMed

Sethy, Niroj Kumar; Singh, Manjulata; Kumar, Rajesh; Ilavazhagan, Govindasamy; Bhargava, Kalpana

2011-03-01

Exposure to high altitude (and thus hypobaric hypoxia) induces electrophysiological, metabolic, and morphological modifications in the brain leading to several neurological clinical syndromes. Despite the known fact that hypoxia episodes in brain are a common factor for many neuropathologies, limited information is available on the underlying cellular and molecular mechanisms. In this study, we investigated the temporal effect of short-term (0-12 h) chronic hypobaric hypoxia on global gene expression of rat brain followed by detailed canonical pathway analysis and regulatory network identification. Our analysis revealed significant alteration of 33, 17, 53, 81, and 296 genes (p < 0.05, <1.5-fold) after 0.5, 1, 3, 6, and 12 h of hypoxia, respectively. Biological processes like regulation, metabolic, and transport pathways are temporally activated along with anti- and proinflammatory signaling networks like PI3K/AKT, NF-κB, ERK/MAPK, IL-6 and IL-8 signaling. Irrespective of exposure durations, nuclear factor (erythroid-derived 2)-like 2 (NRF2)-mediated oxidative stress response pathway and genes were detected at all time points suggesting activation of NRF2-ARE antioxidant defense system. The results were further validated by assessing the expression levels of selected genes in temporal as well as brain regions with quantitative RT-PCR and western blot. In conclusion, our whole brain approach with temporal monitoring of gene expression patterns during hypobaric hypoxia has resulted in (1) deciphering sequence of pathways and signaling networks activated during onset of hypoxia, and (2) elucidation of NRF2-orchestrated antioxidant response as a major intrinsic defense mechanism. The results of this study will aid in better understanding and management of hypoxia-induced brain pathologies.

Evolutionary change in the structure of the regulatory region that drives tissue and temporally regulated expression of alcohol dehydrogenase gene in Drosophila funebris.

PubMed

Amador, A; Papaceit, M; Juan, E

2001-06-01

The Adh locus of Drosophilidae is organized as a single gene transcribed from two spatially and temporally regulated promoters except in species of the repleta group, which have two single promoter genes. Here we show that in Drosophila funebris the Adh gene is transcribed from a single promoter, in both larva and adult, with qualitative and quantitative species specific-differences in tissue distribution. The gene is expressed in larval fat body but in other tissues such as gastric caeca, midgut and Malpighian tubules its expression is reduced compared to most Drosophilidae species, and in adults it is almost limited to the fat body. The comparative analysis of gene expression of two strains, which differ by a duplication, indicates that the cis elements necessary for this pattern of expression in larvae are included in the region of 1.55 kb upstream of the transcription initiation site. This new organization reveals the evolution of a different regulatory strategy to express the Adh gene in the subgenus Drosophila.

Systems biology approach to late-onset Alzheimer's disease genome-wide association study identifies novel candidate genes validated using brain expression data and Caenorhabditis elegans experiments.

PubMed

Mukherjee, Shubhabrata; Russell, Joshua C; Carr, Daniel T; Burgess, Jeremy D; Allen, Mariet; Serie, Daniel J; Boehme, Kevin L; Kauwe, John S K; Naj, Adam C; Fardo, David W; Dickson, Dennis W; Montine, Thomas J; Ertekin-Taner, Nilufer; Kaeberlein, Matt R; Crane, Paul K

2017-10-01

We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci. We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions. We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ toxicity, and NDUFS3, SLC25A11, ATP5H, and APP were differentially expressed in the temporal cortex. Network analyses identified novel LOAD candidate genes. We demonstrated a functional role for four of these in a C. elegans model and found enrichment of differentially expressed genes in the temporal cortex. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Tumour Necrosis Factor-α Gene Polymorphism Is Associated with Metastasis in Patients with Triple Negative Breast Cancer.

PubMed

Li, Hui-Hui; Zhu, Hui; Liu, Li-Sheng; Huang, Yong; Guo, Jun; Li, Jie; Sun, Xin-Ping; Chang, Chun-Xiao; Wang, Zhe-Hai; Zhai, Kan

2015-07-13

Tumour necrosis factor-α (TNF-α) is critical in the regulation of inflammation and tumour progression. TNF-α-308G > A is associated with constitutively elevated TNF-α expression. The purpose of this study was to assess the association between TNF-α-308G > A and breast cancer (BC) risk by subtype and the connection between genotypes and clinical features of BC. A total of 768 patients and 565 controls were enrolled in this study, and genotypes were detected using the TaqMan assay. No effect on susceptibility for any BC subtype was found for the TNF-α-308 polymorphism in our study or in the pooled meta-analysis. This polymorphism was shown to be associated with age at menarche in all BC and in progesterone receptor-negative BC. Interestingly, triple negative breast cancer (TNBC) patients with TNF-α-308A had an increased risk of distant tumour metastasis (OR = 3.80, 95% CI: 1.31-11.02, P = 0.009). Multi-regression analysis showed that TNF-α-308A was also a risk factor for distant tumour metastasis after adjustment for tumour size and lymph node metastasis status (OR = 6.26, 95% CI: 1.88-20.87, P = 0.003). These findings indicate that TNF-α might play a distinct role in the progression of TNBC, especially in distant tumour metastasis of TNBC.

The complete nucleotide sequence of the genome of Barley yellow dwarf virus-RMV reveals it to be a new Polerovirus distantly related to other yellow dwarf viruses

PubMed Central

Krueger, Elizabeth N.; Beckett, Randy J.; Gray, Stewart M.; Miller, W. Allen

2013-01-01

The yellow dwarf viruses (YDVs) of the Luteoviridae family represent the most widespread group of cereal viruses worldwide. They include the Barley yellow dwarf viruses (BYDVs) of genus Luteovirus, the Cereal yellow dwarf viruses (CYDVs) and Wheat yellow dwarf virus (WYDV) of genus Polerovirus. All of these viruses are obligately aphid transmitted and phloem-limited. The first described YDVs (initially all called BYDV) were classified by their most efficient vector. One of these viruses, BYDV-RMV, is transmitted most efficiently by the corn leaf aphid, Rhopalosiphum maidis. Here we report the complete 5612 nucleotide sequence of the genomic RNA of a Montana isolate of BYDV-RMV (isolate RMV MTFE87, Genbank accession no. KC921392). The sequence revealed that BYDV-RMV is a polerovirus, but it is quite distantly related to the CYDVs or WYDV, which are very closely related to each other. Nor is BYDV-RMV closely related to any other particular polerovirus. Depending on the gene that is compared, different poleroviruses (none of them a YDV) share the most sequence similarity to BYDV-RMV. Because of its distant relationship to other YDVs, and because it commonly infects maize via its vector, R. maidis, we propose that BYDV-RMV be renamed Maize yellow dwarf virus-RMV (MYDV-RMV). PMID:23888156

The complete nucleotide sequence of the genome of Barley yellow dwarf virus-RMV reveals it to be a new Polerovirus distantly related to other yellow dwarf viruses.

PubMed

Krueger, Elizabeth N; Beckett, Randy J; Gray, Stewart M; Miller, W Allen

2013-01-01

The yellow dwarf viruses (YDVs) of the Luteoviridae family represent the most widespread group of cereal viruses worldwide. They include the Barley yellow dwarf viruses (BYDVs) of genus Luteovirus, the Cereal yellow dwarf viruses (CYDVs) and Wheat yellow dwarf virus (WYDV) of genus Polerovirus. All of these viruses are obligately aphid transmitted and phloem-limited. The first described YDVs (initially all called BYDV) were classified by their most efficient vector. One of these viruses, BYDV-RMV, is transmitted most efficiently by the corn leaf aphid, Rhopalosiphum maidis. Here we report the complete 5612 nucleotide sequence of the genomic RNA of a Montana isolate of BYDV-RMV (isolate RMV MTFE87, Genbank accession no. KC921392). The sequence revealed that BYDV-RMV is a polerovirus, but it is quite distantly related to the CYDVs or WYDV, which are very closely related to each other. Nor is BYDV-RMV closely related to any other particular polerovirus. Depending on the gene that is compared, different poleroviruses (none of them a YDV) share the most sequence similarity to BYDV-RMV. Because of its distant relationship to other YDVs, and because it commonly infects maize via its vector, R. maidis, we propose that BYDV-RMV be renamed Maize yellow dwarf virus-RMV (MYDV-RMV).

Orientation-dependent interaction between Drosophila insulators is a property of this class of regulatory elements

PubMed Central

Kyrchanova, Olga; Chetverina, Darya; Maksimenko, Oksana; Kullyev, Andrey; Georgiev, Pavel

2008-01-01

Insulators are defined as a class of regulatory elements that delimit independent transcriptional domains within eukaryotic genomes. According to previous data, an interaction (pairing) between some Drosophila insulators can support distant activation of a promoter by an enhancer. Here, we have demonstrated that pairs of well-studied insulators such as scs–scs, scs’–scs’, 1A2–1A2 and Wari–Wari support distant activation of the white promoter by the yeast GAL4 activator in an orientation-dependent manner. The same is true for the efficiency of the enhancer that stimulates white expression in the eyes. In all insulator pairs tested, stimulation of the white gene was stronger when insulators were inserted between the eye enhancer or GAL4 and the white promoter in opposite orientations relative to each other. As shown previously, Zw5, Su(Hw) and dCTCF proteins are required for the functioning of different insulators that do not interact with each other. Here, strong functional interactions have been revealed between DNA fragments containing binding sites for either Zw5 or Su(Hw) or dCTCF protein but not between heterologous binding sites [Zw5–Su(Hw), dCTCF–Su(Hw), or dCTCF–Zw5]. These results suggest that insulator proteins can support selective interactions between distant regulatory elements. PMID:18987002

Temporal course of gene expression during motor memory formation in primary motor cortex of rats.

PubMed

Hertler, B; Buitrago, M M; Luft, A R; Hosp, J A

2016-12-01

Motor learning is associated with plastic reorganization of neural networks in primary motor cortex (M1) that depends on changes in gene expression. Here, we investigate the temporal profile of these changes during motor memory formation in response to a skilled reaching task in rats. mRNA-levels were measured 1h, 7h and 24h after the end of a training session using microarray technique. To assure learning specificity, trained animals were compared to a control group. In response to motor learning, genes are sequentially regulated with high time-point specificity and a shift from initial suppression to later activation. The majority of regulated genes can be linked to learning-related plasticity. In the gene-expression cascade following motor learning, three different steps can be defined: (1) an initial suppression of genes influencing gene transcription. (2) Expression of genes that support translation of mRNA in defined compartments. (3) Expression of genes that immediately mediates plastic changes. Gene expression peaks after 24h - this is a much slower time-course when compared to hippocampus-dependent learning, where peaks of gene-expression can be observed 6-12h after training ended. Copyright © 2016 Elsevier Inc. All rights reserved.

An internal regulatory element controls troponin I gene expression.

PubMed Central

Yutzey, K E; Kline, R L; Konieczny, S F

1989-01-01

During skeletal myogenesis, approximately 20 contractile proteins and related gene products temporally accumulate as the cells fuse to form multinucleated muscle fibers. In most instances, the contractile protein genes are regulated transcriptionally, which suggests that a common molecular mechanism may coordinate the expression of this diverse and evolutionarily unrelated gene set. Recent studies have examined the muscle-specific cis-acting elements associated with numerous contractile protein genes. All of the identified regulatory elements are positioned in the 5'-flanking regions, usually within 1,500 base pairs of the transcription start site. Surprisingly, a DNA consensus sequence that is common to each contractile protein gene has not been identified. In contrast to the results of these earlier studies, we have found that the 5'-flanking region of the quail troponin I (TnI) gene is not sufficient to permit the normal myofiber transcriptional activation of the gene. Instead, the TnI gene utilizes a unique internal regulatory element that is responsible for the correct myofiber-specific expression pattern associated with the TnI gene. This is the first example in which a contractile protein gene has been shown to rely primarily on an internal regulatory element to elicit transcriptional activation during myogenesis. The diversity of regulatory elements associated with the contractile protein genes suggests that the temporal expression of the genes may involve individual cis-trans regulatory components specific for each gene. Images PMID:2725509

Phylogeny and toxicology of Lyngbya wollei (Cyanobacteria, Oscillatoriales) from north-eastern Australia, with a description of Microseira gen. nov.

PubMed

McGregor, Glenn B; Sendall, Barbara C

2015-02-01

Three populations of the freshwater filamentous cyanobacterium Lyngbya wollei (Farlow ex Gomont) Speziale and Dyck have been putatively identified from north-eastern Australia and found to produce the potent cyanotoxin cylindrospermopsin (CYN) and its analog deoxy-cylindrospermopsin (deoxy-CYN). We investigated the phylogeny and toxicology of strains and mats isolated from two of these populations using a combination of molecular and morphological techniques. Morphologically the strains corresponded to the type description, however, the frequency of false-branching was low, and variable over time. Strains and mat samples from both sites were positive for the cyrF and cyrJ genes associated with CYN biosynthesis. Phylogenetic analysis of these genes from Australian L. wollei sequences and comparable cyanobacterial sequences revealed that the genes in L. wollei were more closely related to homologous genes in Oscillatoria sp. PCC 6506 than to homologs in Nostocalean CYN-producers. These data suggest a common evolutionary origin of CYN biosynthesis in L. wollei and Oscillatoria. In both the 16S rRNA and nifH phylogenies, the Australian L. wollei strains formed well-supported clades with United States L. wollei (= Plectonema wollei) strains. Pair-wise sequence similarities within the 16S rRNA clade containing all eleven L. wollei strains were high, ranging from 97% to 100%. This group was distantly related (<92% nucleotide similarity) to other taxa within the group previously considered under the genus Lyngbya sensu lato (C. Agardh ex Gomont). Collectively, these results suggest that this toxigenic group is evolutionarily distinct and sufficiently distant as to be considered a separate genus, which we have described as Microseira gen. nov. and hence transfer to it the type M. wollei comb. nov. © 2014 State of Queensland. Journal of Phycology © 2014 Phycological Society of America.

Structural and transcription analysis of two homologous genes for the P700 chlorophyll a-apoproteins in Chlamydomonas reinhardii: evidence for in vivo trans-splicing

PubMed Central

Kück, Ulrich; Choquet, Yves; Schneider, Michel; Dron, Michel; Bennoun, Pierre

1987-01-01

The two homologous genes for the P700 chlorophyll a-apoproteins (ps1A1 and ps1A2) are encoded by the plastom in the green alga Chlamydomonas reinhardii. The structure and organization of the two genes were determined by comparison with the homologous genes from maize using data from heterologous hybridizations as well as from DNA and RNA sequencing. While the ps1A2 (736 codons) gene shows a continuous gene organization, the ps1A1 (754 codons) gene possesses some unusual features. The discontinuous gene is split into three separate exons which are scattered around the circular chloroplast genome. Exon 1 (86 bp) is separated by ∼50 kb from exon 2 (198 bp), which is located ∼ 90 kb apart from exon 3 (1984 bp). All exons are flanked by intronic sequences of group II. Transcription analysis reveals that the ps1A2 gene hybridizes with a 2.8-kb transcript, while all exon regions of the ps1A1 gene are homologous to a mature mRNA of 2.7 kb. From our data we conclude that the three distantly separated exonic sequences of the ps1A1 gene constitute a functional gene which probably operates by a trans-splicing mechanism. ImagesFig. 3.Fig. 5.Fig. 6. PMID:16453785

Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae) cultivars

PubMed Central

Shahin, Arwa; Smulders, Marinus J. M.; van Tuyl, Jaap M.; Arens, Paul; Bakker, Freek T.

2014-01-01

Next Generation Sequencing (NGS) may enable estimating relationships among genotypes using allelic variation of multiple nuclear genes simultaneously. We explored the potential and caveats of this strategy in four genetically distant Lilium cultivars to estimate their genetic divergence from transcriptome sequences using three approaches: POFAD (Phylogeny of Organisms from Allelic Data, uses allelic information of sequence data), RAxML (Randomized Accelerated Maximum Likelihood, tree building based on concatenated consensus sequences) and Consensus Network (constructing a network summarizing among gene tree conflicts). Twenty six gene contigs were chosen based on the presence of orthologous sequences in all cultivars, seven of which also had an orthologous sequence in Tulipa, used as out-group. The three approaches generated the same topology. Although the resolution offered by these approaches is high, in this case there was no extra benefit in using allelic information. We conclude that these 26 genes can be widely applied to construct a species tree for the genus Lilium. PMID:25368628

Transcriptomic and macroevolutionary evidence for phenotypic uncoupling between frog life history phases

PubMed Central

Wollenberg Valero, Katharina C.; Garcia-Porta, Joan; Rodríguez, Ariel; Arias, Mónica; Shah, Abhijeet; Randrianiaina, Roger Daniel; Brown, Jason L.; Glaw, Frank; Amat, Felix; Künzel, Sven; Metzler, Dirk; Isokpehi, Raphael D.; Vences, Miguel

2017-01-01

Anuran amphibians undergo major morphological transitions during development, but the contribution of their markedly different life-history phases to macroevolution has rarely been analysed. Here we generate testable predictions for coupling versus uncoupling of phenotypic evolution of tadpole and adult life-history phases, and for the underlying expression of genes related to morphological feature formation. We test these predictions by combining evidence from gene expression in two distantly related frogs, Xenopus laevis and Mantidactylus betsileanus, with patterns of morphological evolution in the entire radiation of Madagascan mantellid frogs. Genes linked to morphological structure formation are expressed in a highly phase-specific pattern, suggesting uncoupling of phenotypic evolution across life-history phases. This gene expression pattern agrees with uncoupled rates of trait evolution among life-history phases in the mantellids, which we show to have undergone an adaptive radiation. Our results validate a prevalence of uncoupling in the evolution of tadpole and adult phenotypes of frogs. PMID:28504275

Compact continuous-variable entanglement distillation.

PubMed

Datta, Animesh; Zhang, Lijian; Nunn, Joshua; Langford, Nathan K; Feito, Alvaro; Plenio, Martin B; Walmsley, Ian A

2012-02-10

We introduce a new scheme for continuous-variable entanglement distillation that requires only linear temporal and constant physical or spatial resources. Distillation is the process by which high-quality entanglement may be distributed between distant nodes of a network in the unavoidable presence of decoherence. The known versions of this protocol scale exponentially in space and doubly exponentially in time. Our optimal scheme therefore provides exponential improvements over existing protocols. It uses a fixed-resource module-an entanglement distillery-comprising only four quantum memories of at most 50% storage efficiency and allowing a feasible experimental implementation. Tangible quantum advantages are obtainable by using existing off-resonant Raman quantum memories outside their conventional role of storage.

Neural Cross-Frequency Coupling: Connecting Architectures, Mechanisms, and Functions.

PubMed

Hyafil, Alexandre; Giraud, Anne-Lise; Fontolan, Lorenzo; Gutkin, Boris

2015-11-01

Neural oscillations are ubiquitously observed in the mammalian brain, but it has proven difficult to tie oscillatory patterns to specific cognitive operations. Notably, the coupling between neural oscillations at different timescales has recently received much attention, both from experimentalists and theoreticians. We review the mechanisms underlying various forms of this cross-frequency coupling. We show that different types of neural oscillators and cross-frequency interactions yield distinct signatures in neural dynamics. Finally, we associate these mechanisms with several putative functions of cross-frequency coupling, including neural representations of multiple environmental items, communication over distant areas, internal clocking of neural processes, and modulation of neural processing based on temporal predictions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thrice out of Africa: ancient and recent expansions of the honey bee, Apis mellifera.

PubMed

Whitfield, Charles W; Behura, Susanta K; Berlocher, Stewart H; Clark, Andrew G; Johnston, J Spencer; Sheppard, Walter S; Smith, Deborah R; Suarez, Andrew V; Weaver, Daniel; Tsutsui, Neil D

2006-10-27

We characterized Apis mellifera in both native and introduced ranges using 1136 single-nucleotide polymorphisms genotyped in 341 individuals. Our results indicate that A. mellifera originated in Africa and expanded into Eurasia at least twice, resulting in populations in eastern and western Europe that are geographically close but genetically distant. A third expansion in the New World has involved the near-replacement of previously introduced "European" honey bees by descendants of more recently introduced A. m. scutellata ("African" or "killer" bees). Our analyses of spatial transects and temporal series in the New World revealed differential replacement of alleles derived from eastern versus western Europe, with admixture evident in all individuals.

Spatial correlation of auroral zone geomagnetic variations

NASA Astrophysics Data System (ADS)

Jackel, B. J.; Davalos, A.

2016-12-01

Magnetic field perturbations in the auroral zone are produced by a combination of distant ionospheric and local ground induced currents. Spatial and temporal structure of these currents is scientifically interesting and can also have a significant influence on critical infrastructure.Ground-based magnetometer networks are an essential tool for studying these phenomena, with the existing complement of instruments in Canada providing extended local time coverage. In this study we examine the spatial correlation between magnetic field observations over a range of scale lengths. Principal component and canonical correlation analysis are used to quantify relationships between multiple sites. Results could be used to optimize network configurations, validate computational models, and improve methods for empirical interpolation.

ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of colorectal cancer via the Akt pathway

PubMed Central

Ogawa, Tadashi; Hirohashi, Yoshihiko; Murai, Aiko; Nishidate, Toshihiko; Okita, Kenji; Wang, Liming; Ikehara, Yuzuru; Satoyoshi, Tetsuta; Usui, Akihiro; Kubo, Terufumi; Nakastugawa, Munehide; Kanaseki, Takayuki; Tsukahara, Tomohide; Kutomi, Goro; Furuhata, Tomohisa; Hirata, Koichi; Sato, Noriyuki; Mizuguchi, Toru; Takemasa, Ichiro; Torigoe, Toshihiko

2017-01-01

Colorectal cancer (CRC) is a mortal disease due to treatment resistance, recurrence and distant metastasis. Emerging evidence has revealed that a small sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating cells (CICs) is endowed with high levels of tumor-initiating ability, self-renewal ability and differentiation ability and is responsible for treatment resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is essential to improve current treatments. However, the molecular mechanisms by which CSCs/CICs are maintained are still elusive. In this study, we aimed to determine the molecular mechanisms by which colorectal (CR)-CSCs/CICs in are maintained human primary CRC cells. CR-CSCs/CICs were isolated by sphere-culture and the ALDEFLUOR assay, and transcriptome analysis revealed that the gene ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) was expressed at high levels in CR-CSCs/CICs. Overexpression of ST6GALNAC1 enhanced the expression of sialyl-Tn (STn) antigen, which is carried by the CSC marker CD44, and increased the sphere-forming ability and resistance to a chemotherapeutic reagent. The opposite phenomena were observed by gene knockdown using siRNA. Furthermore, the Akt pathway was activated in ST6GANAC1-overexpressed cells, and activation of the pathway was cancelled by gene knockdown of galectin-3. The results indicate that ST6GALNAC1 has a role in the maintenance of CR-CSCs/CICs by activating the Akt pathway in cooperation with galectin-3 and that ST6GalNAC1 (or STn antigen) might be a reasonable molecule for CSC/CIC-targeting therapy. PMID:29348846

Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution.

PubMed

Hejnol, Andreas; Lowe, Christopher J

2015-12-19

Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of 'evo-devo'. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters-the partitioned brain of arthropods and the ventral centralized nerve cords of annelids-a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited. © 2015 The Authors.

Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution

PubMed Central

Hejnol, Andreas; Lowe, Christopher J.

2015-01-01

Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of ‘evo-devo’. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters—the partitioned brain of arthropods and the ventral centralized nerve cords of annelids—a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited. PMID:26554039

Cytokine-Enhanced Vaccine and Interferon-β plus Suicide Gene Therapy as Surgery Adjuvant Treatments for Spontaneous Canine Melanoma.

PubMed

Finocchiaro, Liliana M E; Fondello, Chiara; Gil-Cardeza, María L; Rossi, Úrsula A; Villaverde, Marcela S; Riveros, María D; Glikin, Gerardo C

2015-06-01

We present here a nonviral immunogene therapy trial for canine malignant melanoma, an aggressive disease displaying significant clinical and histopathological overlapping with human melanoma. As a surgery adjuvant approach, it comprised the co-injection of lipoplexes bearing herpes simplex virus thymidine kinase and canine interferon-β genes at the time of surgery, combined with the periodic administration of a subcutaneous genetic vaccine composed of tumor extracts and lipoplexes carrying the genes of human interleukin-2 and human granulocyte-macrophage colony-stimulating factor. Following complete surgery (CS), the combined treatment (CT) significantly raised the portion of local disease-free canine patients from 11% to 83% and distant metastases-free (M0) from 44% to 89%, as compared with surgery-only-treated controls (ST). Even after partial surgery (PS), CT better controlled the systemic disease (M0: 82%) than ST (M0: 48%). Moreover, compared with ST, CT caused a significant 7-fold (CS) and 4-fold (PS) rise of overall survival, and >17-fold (CS) and >13-fold (PS) rise of metastasis-free survival. The dramatic increase of PS metastasis-free survival (>1321 days) and CS recurrence- and metastasis-free survival (both >2251 days) demonstrated that CT was shifting a rapidly lethal disease into a chronic one. In conclusion, this surgery adjuvant CT was able of significantly delaying or preventing postsurgical recurrence and distant metastasis, increasing disease-free and overall survival, and maintaining the quality of life. The high number of canine patients involved in CT (301) and the extensive follow-up (>6 years) with minimal or absent toxicity warrant the long-term safety and efficacy of this treatment. This successful clinical outcome justifies attempting a similar scheme for human melanoma.

Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up.

PubMed

Finocchiaro, L M E; Glikin, G C

2012-12-01

We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. Toxicity was absent or minimal in all patients (0≤VCOG-CTCAE grade≤1). With respect to surgery-treated controls (ST), the complete surgery (CS) arm of this combined treatment (CT) significantly increased the fraction of local disease-free patients from 13 to 81% and distant metastases free from 32 to 84%. Even though less effective than the CS arm, the partial surgery (PS) arm of this CT was significantly better controlling the disease than only surgery (14% while PS-ST: 0%, P<0.01 and CS-ST: 5%, P<0.05). In addition, CT produced a significant sevenfold (CS) and threefold (PS) increase in overall survival. The CS-CT arm significantly improved both CS-ST metastasis-free- and melanoma overall survival from 99 days (respective ranges: 11-563 and 10-568) to >2848 days (81-2848 and 35-2848). Thus, more of 50% of our CT patients died of melanoma unrelated causes, transforming a lethal disease into a chronic one. Finally, surgery adjuvant CT delayed or prevented post-surgical recurrence and distant metastasis, significantly improved disease-free and overall survival maintaining the quality of life. Long-term safety and efficacy of this treatment are supported by the high number of CT patients (283) and extensive follow-up (>9 years). The successful clinical outcome encourages the further translation of similar approaches to human gene therapy trials.

The 21-gene Recurrence Score® assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial).

PubMed

Penault-Llorca, Frédérique; Filleron, Thomas; Asselain, Bernard; Baehner, Frederick L; Fumoleau, Pierre; Lacroix-Triki, Magali; Anderson, Joseph M; Yoshizawa, Carl; Cherbavaz, Diana B; Shak, Steven; Roca, Lise; Sagan, Christine; Lemonnier, Jérôme; Martin, Anne-Laure; Roché, Henri

2018-05-04

The 21-gene Recurrence Score (RS) result predicts outcome and chemotherapy benefit in node-negative and node-positive (N+), estrogen receptor-positive (ER+) patients treated with endocrine therapy. The purpose of this study was to evaluate the prognostic impact of RS results in N+, hormone receptor-positive (HR+) patients treated with adjuvant chemotherapy (6 cycles of FEC100 vs. 3 cycles of FEC100 followed by 3 cycles of docetaxel 100 mg/m 2 ) plus endocrine therapy (ET) in the PACS-01 trial (J Clin Oncol 2006;24:5664-5671). The current study included 530 HR+/N+ patients from the PACS-01 parent trial for whom specimens were available. The primary objective was to evaluate the relationship between the RS result and distant recurrence (DR). There were 209 (39.4%) patients with low RS (< 18), 159 (30%) with intermediate RS (18-30) and 162 (30.6%) with high RS (≥ 31). The continuous RS result was associated with DR (hazard ratio = 4.14; 95% confidence interval: 2.67-6.43; p <  0.001), adjusting for treatment. In multivariable analysis, the RS result remained a significant predictor of DR (p <  0.001) after adjustment for number of positive nodes, tumor size, tumor grade, Ki-67 (immunohistochemical status), and chemotherapy regimen. There was no statistically significant interaction between RS result and treatment in predicting DR (p = 0.79). After adjustment for clinical covariates, the 21-gene RS result is a significant prognostic factor in N+/HR+ patients receiving adjuvant chemoendocrine therapy. Not applicable.

Predicting Pharmacodynamic Drug-Drug Interactions through Signaling Propagation Interference on Protein-Protein Interaction Networks.

PubMed

Park, Kyunghyun; Kim, Docyong; Ha, Suhyun; Lee, Doheon

2015-01-01

As pharmacodynamic drug-drug interactions (PD DDIs) could lead to severe adverse effects in patients, it is important to identify potential PD DDIs in drug development. The signaling starting from drug targets is propagated through protein-protein interaction (PPI) networks. PD DDIs could occur by close interference on the same targets or within the same pathways as well as distant interference through cross-talking pathways. However, most of the previous approaches have considered only close interference by measuring distances between drug targets or comparing target neighbors. We have applied a random walk with restart algorithm to simulate signaling propagation from drug targets in order to capture the possibility of their distant interference. Cross validation with DrugBank and Kyoto Encyclopedia of Genes and Genomes DRUG shows that the proposed method outperforms the previous methods significantly. We also provide a web service with which PD DDIs for drug pairs can be analyzed at http://biosoft.kaist.ac.kr/targetrw.

Ancient DNA sequence revealed by error-correcting codes.

PubMed

Brandão, Marcelo M; Spoladore, Larissa; Faria, Luzinete C B; Rocha, Andréa S L; Silva-Filho, Marcio C; Palazzo, Reginaldo

2015-07-10

A previously described DNA sequence generator algorithm (DNA-SGA) using error-correcting codes has been employed as a computational tool to address the evolutionary pathway of the genetic code. The code-generated sequence alignment demonstrated that a residue mutation revealed by the code can be found in the same position in sequences of distantly related taxa. Furthermore, the code-generated sequences do not promote amino acid changes in the deviant genomes through codon reassignment. A Bayesian evolutionary analysis of both code-generated and homologous sequences of the Arabidopsis thaliana malate dehydrogenase gene indicates an approximately 1 MYA divergence time from the MDH code-generated sequence node to its paralogous sequences. The DNA-SGA helps to determine the plesiomorphic state of DNA sequences because a single nucleotide alteration often occurs in distantly related taxa and can be found in the alternative codon patterns of noncanonical genetic codes. As a consequence, the algorithm may reveal an earlier stage of the evolution of the standard code.

Ancient DNA sequence revealed by error-correcting codes

PubMed Central

Brandão, Marcelo M.; Spoladore, Larissa; Faria, Luzinete C. B.; Rocha, Andréa S. L.; Silva-Filho, Marcio C.; Palazzo, Reginaldo

2015-01-01

A previously described DNA sequence generator algorithm (DNA-SGA) using error-correcting codes has been employed as a computational tool to address the evolutionary pathway of the genetic code. The code-generated sequence alignment demonstrated that a residue mutation revealed by the code can be found in the same position in sequences of distantly related taxa. Furthermore, the code-generated sequences do not promote amino acid changes in the deviant genomes through codon reassignment. A Bayesian evolutionary analysis of both code-generated and homologous sequences of the Arabidopsis thaliana malate dehydrogenase gene indicates an approximately 1 MYA divergence time from the MDH code-generated sequence node to its paralogous sequences. The DNA-SGA helps to determine the plesiomorphic state of DNA sequences because a single nucleotide alteration often occurs in distantly related taxa and can be found in the alternative codon patterns of noncanonical genetic codes. As a consequence, the algorithm may reveal an earlier stage of the evolution of the standard code. PMID:26159228

Genetic identification of a common collagen disease in Puerto Ricans via identity-by-descent mapping in a health system

PubMed Central

Belbin, Gillian Morven; Odgis, Jacqueline; Sorokin, Elena P; Yee, Muh-Ching; Kohli, Sumita; Glicksberg, Benjamin S; Gignoux, Christopher R; Wojcik, Genevieve L; Van Vleck, Tielman; Jeff, Janina M; Linderman, Michael; Schurmann, Claudia; Ruderfer, Douglas; Cai, Xiaoqiang; Merkelson, Amanda; Justice, Anne E; Young, Kristin L; Graff, Misa; North, Kari E; Peters, Ulrike; James, Regina; Hindorff, Lucia; Kornreich, Ruth; Edelmann, Lisa; Gottesman, Omri; Stahl, Eli EA; Cho, Judy H; Loos, Ruth JF; Bottinger, Erwin P; Nadkarni, Girish N; Abul-Husn, Noura S

2017-01-01

Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with both elevated genetic relatedness and extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease. PMID:28895531

Increased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis.

PubMed

Harms, Kelly L; Chubb, Heather; Zhao, Lili; Fullen, Douglas R; Bichakjian, Christopher K; Johnson, Timothy M; Carskadon, Shannon; Palanisamy, Nallasivam; Harms, Paul W

2017-09-01

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P=.005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Honey Bee Aggression Supports a Link Between Gene Regulation and Behavioral Evolution

USDA-ARS?s Scientific Manuscript database

A prominent theory holds that animal phenotypes arise by evolutionary changes in the regulation of gene expression. Emerging from studies of animal development, evidence for this theory consists largely of differences in temporal or spatial patterns of gene expression that are related to morphologi...

Spatiotemporal proximity effects in visual short-term memory examined by target-nontarget analysis.

PubMed

Sapkota, Raju P; Pardhan, Shahina; van der Linde, Ian

2016-08-01

Visual short-term memory (VSTM) is a limited-capacity system that holds a small number of objects online simultaneously, implying that competition for limited storage resources occurs (Phillips, 1974). How the spatial and temporal proximity of stimuli affects this competition is unclear. In this 2-experiment study, we examined the effect of the spatial and temporal separation of real-world memory targets and erroneously selected nontarget items examined during location-recognition and object-recall tasks. In Experiment 1 (the location-recognition task), our test display comprised either the picture or name of 1 previously examined memory stimulus (rendered above as the stimulus-display area), together with numbered square boxes at each of the memory-stimulus locations used in that trial. Participants were asked to report the number inside the square box corresponding to the location at which the cued object was originally presented. In Experiment 2 (the object-recall task), the test display comprised a single empty square box presented at 1 memory-stimulus location. Participants were asked to report the name of the object presented at that location. In both experiments, nontarget objects that were spatially and temporally proximal to the memory target were confused more often than nontarget objects that were spatially and temporally distant (i.e., a spatiotemporal proximity effect); this effect generalized across memory tasks, and the object feature (picture or name) that cued the test-display memory target. Our findings are discussed in terms of spatial and temporal confusion "fields" in VSTM, wherein objects occupy diffuse loci in a spatiotemporal coordinate system, wherein neighboring locations are more susceptible to confusion. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

An internal regulatory element controls troponin I gene expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yutzey, K.E.; Kline, R.L.; Konieczmy, S.F.

1989-04-01

During skeletal myogenesis, approximately 20 contractile proteins and related gene products temporally accumulate as the cells fuse to form multinucleated muscle fibers. In most instances, the contractile protein genes are regulated transcriptionally, which suggests that a common molecular mechanism may coordinate the expression of this diverse and evolutionarily unrelated gene set. Recent studies have examined the muscle-specific cis-acting elements associated with numerous contractile protein genes. All of the identified regulatory elements are positioned in the 5'-flanking regions, usually within 1,500 base pairs of the transcription start site. Surprisingly, a DNA consensus sequence that is common to each contractile protein genemore » has not been identified. In contrast to the results of these earlier studies, the authors have found that the 5'-flanking region of the quail troponin I (TnI) gene is not sufficient to permit the normal myofiber transcriptional activation of the gene. Instead, the TnI gene utilizes a unique internal regulatory element that is responsible for the correct myofiber-specific expression pattern associated with the TnI gene. This is the first example in which a contractile protein gene has been shown to rely primarily on an internal regulatory element to elicit transcriptional activation during myogenesis. The diversity of regulatory elements associated with the contractile protein genes suggests that the temporal expression of the genes may involve individual cis-trans regulatory components specific for each gene.« less

Combination Gene Therapy for Liver Metastasis of Colon Carcinoma in vivo

NASA Astrophysics Data System (ADS)

Chen, Shu-Hsai; Chen, X. H. Li; Wang, Yibin; Kosai, Ken-Ichiro; Finegold, Milton J.; Rich, Susan S.

1995-03-01

The efficacy of combination therapy with a "suicide gene" and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombinant adenoviral vectors containing various control and therapeutic genes were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals treated with a control vector or a mouse interleukin 2 vector, those treated with a herpes simplex virus thymidine kinase vector, with or without the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with both vectors developed an effective systemic antitumoral immunity against challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the presence of MCA-26 tumor-specific cytolytic CD8^+ T lymphocytes. The results suggest that combination suicide and cytokine gene therapy in vivo can be a powerful approach for treatment of metastatic colon carcinoma in the liver.

Using parentage analysis to examine gene flow and spatial genetic structure.

PubMed

Kane, Nolan C; King, Matthew G

2009-04-01

Numerous approaches have been developed to examine recent and historical gene flow between populations, but few studies have used empirical data sets to compare different approaches. Some methods are expected to perform better under particular scenarios, such as high or low gene flow, but this, too, has rarely been tested. In this issue of Molecular Ecology, Saenz-Agudelo et al. (2009) apply assignment tests and parentage analysis to microsatellite data from five geographically proximal (2-6 km) and one much more distant (1500 km) panda clownfish populations, showing that parentage analysis performed better in situations of high gene flow, while their assignment tests did better with low gene flow. This unusually complete data set is comprised of multiple exhaustively sampled populations, including nearly all adults and large numbers of juveniles, enabling the authors to ask questions that in many systems would be impossible to answer. Their results emphasize the importance of selecting the right analysis to use, based on the underlying model and how well its assumptions are met by the populations to be analysed.

Nonclassical Regulation of Transcription: Interchromosomal Interactions at the Malic enzyme Locus of Drosophila melanogaster

PubMed Central

Lum, Thomas E.; Merritt, Thomas J. S.

2011-01-01

Regulation of transcription can be a complex process in which many cis- and trans-interactions determine the final pattern of expression. Among these interactions are trans-interactions mediated by the pairing of homologous chromosomes. These trans-effects are wide ranging, affecting gene regulation in many species and creating complex possibilities in gene regulation. Here we describe a novel case of trans-interaction between alleles of the Malic enzyme (Men) locus in Drosophila melanogaster that results in allele-specific, non-additive gene expression. Using both empirical biochemical and predictive bioinformatic approaches, we show that the regulatory elements of one allele are capable of interacting in trans with, and modifying the expression of, the second allele. Furthermore, we show that nonlocal factors—different genetic backgrounds—are capable of significant interactions with individual Men alleles, suggesting that these trans-effects can be modified by both locally and distantly acting elements. In sum, these results emphasize the complexity of gene regulation and the need to understand both small- and large-scale interactions as more complete models of the role of trans-interactions in gene regulation are developed. PMID:21900270

Mean field analysis of a spatial stochastic model of a gene regulatory network.

PubMed

Sturrock, M; Murray, P J; Matzavinos, A; Chaplain, M A J

2015-10-01

A gene regulatory network may be defined as a collection of DNA segments which interact with each other indirectly through their RNA and protein products. Such a network is said to contain a negative feedback loop if its products inhibit gene transcription, and a positive feedback loop if a gene product promotes its own production. Negative feedback loops can create oscillations in mRNA and protein levels while positive feedback loops are primarily responsible for signal amplification. It is often the case in real biological systems that both negative and positive feedback loops operate in parameter regimes that result in low copy numbers of gene products. In this paper we investigate the spatio-temporal dynamics of a single feedback loop in a eukaryotic cell. We first develop a simplified spatial stochastic model of a canonical feedback system (either positive or negative). Using a Gillespie's algorithm, we compute sample trajectories and analyse their corresponding statistics. We then derive a system of equations that describe the spatio-temporal evolution of the stochastic means. Subsequently, we examine the spatially homogeneous case and compare the results of numerical simulations with the spatially explicit case. Finally, using a combination of steady-state analysis and data clustering techniques, we explore model behaviour across a subregion of the parameter space that is difficult to access experimentally and compare the parameter landscape of our spatio-temporal and spatially-homogeneous models.

Navigating the complex path between the oxytocin receptor gene (OXTR) and cooperation: an endophenotype approach.

PubMed

Haas, Brian W; Anderson, Ian W; Smith, Jessica M

2013-11-28

Although cooperation represents a core facet of human social behavior there exists considerable variability across people in terms of the tendency to cooperate. One factor that may contribute to individual differences in cooperation is a key gene within the oxytocin (OT) system, the OT reception gene (OXTR). In this article, we aim to bridge the gap between the OXTR gene and cooperation by using an endophenotype approach. We present evidence that the association between the OXTR gene and cooperation may in part be due to how the OXTR gene affects brain systems involved in emotion recognition, empathy/theory of mind, social communication and social reward seeking. There is evidence that the OXTR gene is associated with the functional anatomy of the amygdala, visual cortex (VC), anterior cingulate and superior temporal gyrus (STG). However, it is currently unknown how the OXTR gene may be linked to the functional anatomy of other relevant brain regions that include the fusiform gyrus (FG), superior temporal sulcus (STS), ventromedial prefrontal cortex (VMPFC), temporoparietal junction (TPJ) and nucleus accumbens (NAcc). We conclude by highlighting potential future research directions that may elucidate the path between OXTR and complex behaviors such as cooperation.

Navigating the complex path between the oxytocin receptor gene (OXTR) and cooperation: an endophenotype approach

PubMed Central

Haas, Brian W.; Anderson, Ian W.; Smith, Jessica M.

2013-01-01

Although cooperation represents a core facet of human social behavior there exists considerable variability across people in terms of the tendency to cooperate. One factor that may contribute to individual differences in cooperation is a key gene within the oxytocin (OT) system, the OT reception gene (OXTR). In this article, we aim to bridge the gap between the OXTR gene and cooperation by using an endophenotype approach. We present evidence that the association between the OXTR gene and cooperation may in part be due to how the OXTR gene affects brain systems involved in emotion recognition, empathy/theory of mind, social communication and social reward seeking. There is evidence that the OXTR gene is associated with the functional anatomy of the amygdala, visual cortex (VC), anterior cingulate and superior temporal gyrus (STG). However, it is currently unknown how the OXTR gene may be linked to the functional anatomy of other relevant brain regions that include the fusiform gyrus (FG), superior temporal sulcus (STS), ventromedial prefrontal cortex (VMPFC), temporoparietal junction (TPJ) and nucleus accumbens (NAcc). We conclude by highlighting potential future research directions that may elucidate the path between OXTR and complex behaviors such as cooperation. PMID:24348360

Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

PubMed

Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

2016-01-27

Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation.

Use of linkage disequilibrium approaches to map genes for bipolar disorder in the Costa Rican population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escamilla, M.A.; Reus, V.I.; Smith, L.B.

1996-05-31

Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, should be suitable for LD mapping; this assertion is supported by reconstruction of extended haplotypes shared by distantly related individuals in this population suffering low-frequency hearing loss (LFHL1), which has previously been mapped by linkage analysis. A sampling strategy is described for applying LD methods to map genes for BP, andmore » clinical and demographic characteristics of an initially collected sample are discussed. This sample will provide a complement to a previously collected set of Costa Rican BP families which is under investigation using standard linkage analysis. 42 refs., 4 figs., 2 tabs.« less

Horizontal transfer of short and degraded DNA has evolutionary implications for microbes and eukaryotic sexual reproduction

PubMed Central

Overballe-Petersen, Søren; Willerslev, Eske

2014-01-01

Horizontal gene transfer in the form of long DNA fragments has changed our view of bacterial evolution. Recently, we discovered that such processes may also occur with the massive amounts of short and damaged DNA in the environment, and even with truly ancient DNA. Although it presently remains unclear how often it takes place in nature, horizontal gene transfer of short and damaged DNA opens up the possibility for genetic exchange across distinct species in both time and space. In this essay, we speculate on the potential evolutionary consequences of this phenomenon. We argue that it may challenge basic assumptions in evolutionary theory; that it may have distant origins in life's history; and that horizontal gene transfer should be viewed as an evolutionary strategy not only preceding but causally underpinning the evolution of sexual reproduction. PMID:25143190

Horizontal transfer of short and degraded DNA has evolutionary implications for microbes and eukaryotic sexual reproduction.

PubMed

Overballe-Petersen, Søren; Willerslev, Eske

2014-10-01

Horizontal gene transfer in the form of long DNA fragments has changed our view of bacterial evolution. Recently, we discovered that such processes may also occur with the massive amounts of short and damaged DNA in the environment, and even with truly ancient DNA. Although it presently remains unclear how often it takes place in nature, horizontal gene transfer of short and damaged DNA opens up the possibility for genetic exchange across distinct species in both time and space. In this essay, we speculate on the potential evolutionary consequences of this phenomenon. We argue that it may challenge basic assumptions in evolutionary theory; that it may have distant origins in life's history; and that horizontal gene transfer should be viewed as an evolutionary strategy not only preceding but causally underpinning the evolution of sexual reproduction. © 2014 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Isolation, sequence, and characterization of the Cercospora nicotianae phytoene dehydrogenase gene.

PubMed Central

Ehrenshaft, M; Daub, M E

1994-01-01

We have cloned and sequenced the Cercospora nicotianae gene for the carotenoid biosynthetic enzyme phytoene dehydrogenase. Analysis of the derived amino acid sequence revealed it has greater than 50% identity with its counterpart in Neurospora crassa and approximately 30% identity with prokaryotic phytoene dehydrogenases and is related, but more distantly, to phytoene dehydrogenases from plants and cyanobacteria. Our analysis confirms that phytoene dehydrogenase proteins fall into two groups: those from plants and cyanobacteria and those from eukaryotic and noncyanobacter prokaryotic microbes. Southern analysis indicated that the C. nicotianae phytoene dehydrogenase gene is present in a single copy. Extraction of beta-carotene, the sole carotenoid accumulated by C. nicotianae, showed that both light- and dark-grown cultures synthesize carotenoids, but higher levels accumulate in the light. Northern (RNA) analysis of poly(A)+ RNA, however, showed no differential accumulation of phytoene dehydrogenase mRNA between light- and dark-grown fungal cultures. Images PMID:8085820

Recombination and horizontal transfer of nodulation and ACC deaminase (acdS) genes within Alpha- and Betaproteobacteria nodulating legumes of the Cape Fynbos biome.

PubMed

Lemaire, Benny; Van Cauwenberghe, Jannick; Chimphango, Samson; Stirton, Charles; Honnay, Olivier; Smets, Erik; Muasya, A Muthama

2015-11-01

The goal of this work is to study the evolution and the degree of horizontal gene transfer (HGT) within rhizobial genera of both Alphaproteobacteria (Mesorhizobium, Rhizobium) and Betaproteobacteria (Burkholderia), originating from South African Fynbos legumes. By using a phylogenetic approach and comparing multiple chromosomal and symbiosis genes, we revealed conclusive evidence of high degrees of horizontal transfer of nodulation genes among closely related species of both groups of rhizobia, but also among species with distant genetic backgrounds (Rhizobium and Mesorhizobium), underscoring the importance of lateral transfer of symbiosis traits as an important evolutionary force among rhizobia of the Cape Fynbos biome. The extensive exchange of symbiosis genes in the Fynbos is in contrast with a lack of significant events of HGT among Burkholderia symbionts from the South American Cerrado and Caatinga biome. Furthermore, homologous recombination among selected housekeeping genes had a substantial impact on sequence evolution within Burkholderia and Mesorhizobium. Finally, phylogenetic analyses of the non-symbiosis acdS gene in Mesorhizobium, a gene often located on symbiosis islands, revealed distinct relationships compared to the chromosomal and symbiosis genes, suggesting a different evolutionary history and independent events of gene transfer. The observed events of HGT and incongruence between different genes necessitate caution in interpreting topologies from individual data types. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Steroid hormone induction of temporal gene expression in Drosophila brain neuroblasts generates neuronal and glial diversity.

PubMed

Syed, Mubarak Hussain; Mark, Brandon; Doe, Chris Q

2017-04-10

An important question in neuroscience is how stem cells generate neuronal diversity. During Drosophila embryonic development, neural stem cells (neuroblasts) sequentially express transcription factors that generate neuronal diversity; regulation of the embryonic temporal transcription factor cascade is lineage-intrinsic. In contrast, larval neuroblasts generate longer ~50 division lineages, and currently only one mid-larval molecular transition is known: Chinmo/Imp/Lin-28+ neuroblasts transition to Syncrip+ neuroblasts. Here we show that the hormone ecdysone is required to down-regulate Chinmo/Imp and activate Syncrip, plus two late neuroblast factors, Broad and E93. We show that Seven-up triggers Chinmo/Imp to Syncrip/Broad/E93 transition by inducing expression of the Ecdysone receptor in mid-larval neuroblasts, rendering them competent to respond to the systemic hormone ecdysone. Importantly, late temporal gene expression is essential for proper neuronal and glial cell type specification. This is the first example of hormonal regulation of temporal factor expression in Drosophila embryonic or larval neural progenitors.

Translational Advancement of Somatostatin Gene Delivery for Disease Modification and Cognitive Sparing in Intractable Epilepsy

DTIC Science & Technology

2014-09-01

delivery persistently reduces seizure severity in a rat model of temporal lobe epilepsy ," Session number: 314, Session title: Non-pharmacological...delivery persistently reduces seizure severity in a rat model of temporal lobe epilepsy Location: WCC Hall A-C Presentation time: Monday, Nov 17, 2014...therapeutic potential administered prior to last-resort neurosurgical resections in pharmacoresistant cases of temporal lobe epilepsy . Disclosures: G. Natarajan

nm23-H1 gene driven by hTERT promoter induces inhibition of invasive phenotype and metastasis of lung cancer xenograft in mice.

PubMed

Fan, Yu; Yao, Yibing; Li, Lu; Wu, Zhihao; Xu, Feng; Hou, Mei; Wu, Heng; Shen, Yali; Wan, Haisu; Zhou, Qinghua

2013-02-01

Lung cancer is the leading cause of cancer death in both men and women worldwide. Tumor metastasis is an essential aspect of lung cancer progression and patient death. The nm23-H1 gene has been extensively investigated as a metastasis suppressor gene. Our previous studies have revealed: that a significant relationship exists between the low-level expression nm23-H1 in primary non-small cell lung cancer (NSCLC) with increased metastasis and a poor prognosis; that L9981-nm23-H1 cells (a nm23-H1 transfactant cell) exhibited lower cell proliferation rates, more G0/G1 phase growth, and an increase in apoptosis with a dramatic decrease in the tumor cells' ability to invade than L9981 cells did; and that L9981- nm23-H1 cells also demonstrated a significantly reduced lymph node and distant metastatic capacity in vivo than L9981 cells did in nude mice. In this study, we construct a plasmid containing the nm23-H1 gene, which was driven by the human telomerase reverse transcriptase (hTERT) promoter. We evaluated the anti-invasion and anti-metastatic effects of pGL3-hTP-nm23 on L9981, a human large cell lung cancer cell line with nm23-H1 negative expression, by transwell assay in vitro and bioluminescence in nude mice models. The toxicity of pGL3-hTP-nm23 and its effects on tumor growth were evaluated in nude mice models after gene therapy. The cell cycles, apoptosis, and proliferation of the nm23-H1 transfactant were also detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and flow cytometry (FCM). The results showed that the hTERT-promoter dramatically drives nm23-H1 gene expression, and induces inhibition of cell growth and migration in L9981-luc cells and MRC-5 cells in vitro. nm23-H1 also significantly inhibited the tumorigenesis and distant metastasis of L9981-luc cell in vivo. Moreover, no obvious side effect was detected in normal mouse tissues after intratumoral injection of the vector. The treatment of the nm23-H1 gene driven by hTERT promoter appears to be a promising approach for the gene therapy of nm23-H1 low-expressed tumors. © 2012 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd.

Prdm9 controls activation of mammalian recombination hotspots.

PubMed

Parvanov, Emil D; Petkov, Petko M; Paigen, Kenneth

2010-02-12

Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.

Genetic Determinism of Primary Early-Onset Osteoarthritis.

PubMed

Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

2016-01-01

Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

WP1: transgenic opto-animals

NASA Astrophysics Data System (ADS)

UŻarowska, E.; Czajkowski, Rafał; Konopka, W.

2014-11-01

We aim to create a set of genetic tools where permanent opsin expression (ChR or NpHR) is precisely limited to the population of neurons that express immediate early gene c-fos during a specific temporal window of behavioral training. Since the c-fos gene is only expressed in neurons that form experience-dependent ensemble, this approach will result in specific labeling of a small subset of cells that create memory trace for the learned behavior. To this end we employ two alternative inducible gene expression systems: Tet Expression System and Cre/lox System. In both cases, the temporal window for opsin induction is controlled pharmacologically, by doxycycline or tamoxifen, respectively. Both systems will be used for creating lines of transgenic animals.

Interaction-Free Effects Between Distant Atoms

NASA Astrophysics Data System (ADS)

Aharonov, Yakir; Cohen, Eliahu; Elitzur, Avshalom C.; Smolin, Lee

2018-01-01

A Gedanken experiment is presented where an excited and a ground-state atom are positioned such that, within the former's half-life time, they exchange a photon with 50% probability. A measurement of their energy state will therefore indicate in 50% of the cases that no photon was exchanged. Yet other measurements would reveal that, by the mere possibility of exchange, the two atoms have become entangled. Consequently, the "no exchange" result, apparently precluding entanglement, is non-locally established between the atoms by this very entanglement. This quantum-mechanical version of the ancient Liar Paradox can be realized with already existing transmission schemes, with the addition of Bell's theorem applied to the no-exchange cases. Under appropriate probabilities, the initially-excited atom, still excited, can be entangled with additional atoms time and again, or alternatively, exert multipartite nonlocal correlations in an interaction free manner. When densely repeated several times, this result also gives rise to the Quantum Zeno effect, again exerted between distant atoms without photon exchange. We discuss these experiments as variants of interaction-free-measurement, now generalized for both spatial and temporal uncertainties. We next employ weak measurements for elucidating the paradox. Interpretational issues are discussed in the conclusion, and a resolution is offered within the Two-State Vector Formalism and its new Heisenberg framework.

Interaction-Free Effects Between Distant Atoms

NASA Astrophysics Data System (ADS)

Aharonov, Yakir; Cohen, Eliahu; Elitzur, Avshalom C.; Smolin, Lee

2017-12-01

A Gedanken experiment is presented where an excited and a ground-state atom are positioned such that, within the former's half-life time, they exchange a photon with 50% probability. A measurement of their energy state will therefore indicate in 50% of the cases that no photon was exchanged. Yet other measurements would reveal that, by the mere possibility of exchange, the two atoms have become entangled. Consequently, the "no exchange" result, apparently precluding entanglement, is non-locally established between the atoms by this very entanglement. This quantum-mechanical version of the ancient Liar Paradox can be realized with already existing transmission schemes, with the addition of Bell's theorem applied to the no-exchange cases. Under appropriate probabilities, the initially-excited atom, still excited, can be entangled with additional atoms time and again, or alternatively, exert multipartite nonlocal correlations in an interaction free manner. When densely repeated several times, this result also gives rise to the Quantum Zeno effect, again exerted between distant atoms without photon exchange. We discuss these experiments as variants of interaction-free-measurement, now generalized for both spatial and temporal uncertainties. We next employ weak measurements for elucidating the paradox. Interpretational issues are discussed in the conclusion, and a resolution is offered within the Two-State Vector Formalism and its new Heisenberg framework.

A maize resistance gene functions against bacterial streak disease in rice

PubMed Central

Zhao, Bingyu; Lin, Xinghua; Poland, Jesse; Trick, Harold; Leach, Jan; Hulbert, Scot

2005-01-01

Although cereal crops all belong to the grass family (Poacea), most of their diseases are specific to a particular species. Thus, a given cereal species is typically resistant to diseases of other grasses, and this nonhost resistance is generally stable. To determine the feasibility of transferring nonhost resistance genes (R genes) between distantly related grasses to control specific diseases, we identified a maize R gene that recognizes a rice pathogen, Xanthomonas oryzae pv. oryzicola, which causes bacterial streak disease. Bacterial streak is an important disease of rice in Asia, and no simply inherited sources of resistance have been identified in rice. Although X. o. pv. oryzicola does not cause disease on maize, we identified a maize gene, Rxo1, that conditions a resistance reaction to a diverse collection of pathogen strains. Surprisingly, Rxo1 also controls resistance to the unrelated pathogen Burkholderia andropogonis, which causes bacterial stripe of sorghum and maize. The same gene thus controls resistance reactions to both pathogens and nonpathogens of maize. Rxo1 has a nucleotide-binding site-leucine-rich repeat structure, similar to many previously identified R genes. Most importantly, Rxo1 functions after transfer as a transgene to rice, demonstrating the feasibility of nonhost R gene transfer between cereals and providing a valuable tool for controlling bacterial streak disease. PMID:16230639

A maize resistance gene functions against bacterial streak disease in rice.

PubMed

Zhao, Bingyu; Lin, Xinghua; Poland, Jesse; Trick, Harold; Leach, Jan; Hulbert, Scot

2005-10-25

Although cereal crops all belong to the grass family (Poacea), most of their diseases are specific to a particular species. Thus, a given cereal species is typically resistant to diseases of other grasses, and this nonhost resistance is generally stable. To determine the feasibility of transferring nonhost resistance genes (R genes) between distantly related grasses to control specific diseases, we identified a maize R gene that recognizes a rice pathogen, Xanthomonas oryzae pv. oryzicola, which causes bacterial streak disease. Bacterial streak is an important disease of rice in Asia, and no simply inherited sources of resistance have been identified in rice. Although X. o. pv. oryzicola does not cause disease on maize, we identified a maize gene, Rxo1, that conditions a resistance reaction to a diverse collection of pathogen strains. Surprisingly, Rxo1 also controls resistance to the unrelated pathogen Burkholderia andropogonis, which causes bacterial stripe of sorghum and maize. The same gene thus controls resistance reactions to both pathogens and nonpathogens of maize. Rxo1 has a nucleotide-binding site-leucine-rich repeat structure, similar to many previously identified R genes. Most importantly, Rxo1 functions after transfer as a transgene to rice, demonstrating the feasibility of nonhost R gene transfer between cereals and providing a valuable tool for controlling bacterial streak disease.

Temporal transcriptome changes induced by methyl jasmonate in Salvia sclarea.

PubMed

Hao, Da Cheng; Chen, Shi Lin; Osbourn, Anne; Kontogianni, Vassiliki G; Liu, Li Wei; Jordán, Maria J

2015-03-01

Salvia sclarea is a traditional medicinal and aromatic plant that grows in Europe and produces various economically important compounds, including phenylpropanoid derivatives and terpenoids. Methyl jasmonate (MeJA) is commonly used to elicit plant stress responses. However, how MeJA enhances production of secondary metabolites in S. sclarea is not well understood. We performed a genome-wide analysis of temporal gene expression in S. sclarea leaves and roots. The transcriptome profiles 0, 10 and 26 h after MeJA treatment were analyzed by Illumina RNA-Seq. A total of 16,142 isogenes (average length 866bp; N50 1035bp) were obtained by de novo assembly of 35,757,567 raw sequencing reads. When these sequencing reads were mapped onto the assembled Unigenes, 3236, 2792 and 798 Unigenes were found to be expressed differentially between 0 and 10h, 0 and 26 h, and 10 and 26h, respectively. These included many secondary metabolite biosynthesis, stress and defense-related genes. A qRT-PCR analysis confirmed the expression profiles of selected differentially expressed genes (DEGs) revealed by RNA-Seq data, and also extended our analysis of differential gene expression to 73 h. Our investigations revealed temporal differences in the responses of S. sclarea to MeJA treatment. MeJA treatment induced the expression of a large number of genes involved in phenylpropanoid biosynthesis, especially between 0 and 10h, and 0 and 26 h. Additionally, many genes encoding transcription factors, cytochrome P450s, glycosyltransferases, methyltransferases and transporters were shown to respond to MeJA elicitation. DEGs related to structural molecule activity and cell death showed a significant temporal variation. A chromatographic analysis of metabolites at 26h, 73h and six days after MeJA treatment indicated that these transcriptomic changes precede MeJA-induced changes in secondary metabolite content. This study sheds light on the molecular mechanisms of MeJA elicitation and is helpful in understanding how exogenous MeJA treatment mediates extensive plant transcriptome reprogramming/remodeling. Our results can be utilized to characterize genes related to secondary metabolism and their regulation, and in breeding S. sclarea for desirable chemotypes. Copyright © 2014 Elsevier B.V. All rights reserved.

Compositional trends in aeolian dust along a transect across the southwestern United States

USGS Publications Warehouse

Goldstein, H.L.; Reynolds, R.L.; Reheis, M.C.; Yount, J.C.; Neff, J.C.

2008-01-01

Aeolian dust strongly influences ecology and landscape geochemistry over large areas that span several desert ecosystems of the southwestern United States. This study evaluates spatial and temporal variations and trends of the physical and chemical properties of dust in the southwestern United States by examining dust deposited in natural depressions on high isolated surfaces along a transect from the Mojave Desert to the central Colorado Plateau. Aeolian dust is recognized in these depressions on the basis of textural, chemical, isotopic, and mineralogical characteristics and comparisons of those characteristics to the underlying bedrock units. Spatial and temporal trends suggest that although local dust sources are important to the accumulated material in these depressions, Mojave Desert dust sources may also contribute. Depth trends in the depressions suggest that Mojave sources may have contributed more dust to the Colorado Plateau recently than in the past. These interpretations point to the important roles of far-traveled aeolian dust for landscape geochemistry and imply future changes to soil geochemistry under changing conditions in far-distant dust source areas. Copyright 2008 by the American Geophysical Union.

Structured plasma sheet thinning observed by Galileo and 1984-129

NASA Technical Reports Server (NTRS)

Reeves, G. D.; Belian, R. D.; Fritz, T. A.; Kivelson, M. G.; Mcentire, R. W.; Roelof, E. C.; Wilken, B.; Williams, D. J.

1993-01-01

On December 8, 1990, the Galileo spacecraft used the Earth for a gravity assist on its way to Jupiter. Its trajectory was such that it crossed geosynchronous orbit at approximately local midnight between 1900 and 2000 UT. At the same time, spacecraft 1984-129 was also located at geosynchronous orbit near local midnight. Several flux dropout events were observed when the two spacecraft were in the near-Earth plasma sheet in the same local time sector. Flux dropout events are associated with plasma sheet thinning in the near-profile of the near-Earth plasma sheet while 1984-129 provided an azimuthal profile. With measurements from these two spacecraft we can distinguish between spatial structures and temporal change. Our observations confirm that the geosynchronous flux dropout events are consistent with plasma sheet thinning which changes the spacecraft's magnetic connection from the trapping region to the more distant plasma sheet. However, for this period, thinning occurred on two spatial and temporal scales. The geosynchronous dropouts were highly localized phenomena of 30 min duration superimposed on a more global reconfiguration of the tail lasting approximately 4 hours.

The use of time-series data in the assessment of macrobenthic community change after the cessation of sewage-sludge disposal in Liverpool Bay (UK).

PubMed

Whomersley, P; Schratzberger, M; Huxham, M; Bates, H; Rees, H

2007-01-01

Sewage sludge was disposed of in Liverpool Bay for over 100 years. Annual amounts increased from 0.5 million tonnes per annum in 1900 to approximately 2 million tonnes per annum by 1995. Macrofauna and a suite of environmental variables were collected at a station adjacent to, and a reference station distant from, the disposal site over 13 years, spanning a pre- (1990-1998) and post- (1999-2003) cessation period. Univariate and multivariate analyses of the time-series data showed significant community differences between reference and disposal site stations and multivariate analyses revealed station-specific community development post-disposal. Temporal variability of communities collected at the disposal station post-cessation was higher than during years of disposal, when temporally stable dominance patterns of disturbance-tolerant species had established. Alterations of community structure post-disturbance reflected successional changes possibly driven by facilitation. Subtle faunistic changes at the Liverpool Bay disposal site indicate that the near-field effects of the disposal of sewage sludge were small and therefore could be considered environmentally acceptable.

Transcriptional Coupling of Neighboring Genes and Gene Expression Noise: Evidence that Gene Orientation and Noncoding Transcripts Are Modulators of Noise

PubMed Central

Wang, Guang-Zhong; Lercher, Martin J.; Hurst, Laurence D.

2011-01-01

Abstract How is noise in gene expression modulated? Do mechanisms of noise control impact genome organization? In yeast, the expression of one gene can affect that of a very close neighbor. As the effect is highly regionalized, we hypothesize that genes in different orientations will have differing degrees of coupled expression and, in turn, different noise levels. Divergently organized gene pairs, in particular those with bidirectional promoters, have close promoters, maximizing the likelihood that expression of one gene affects the neighbor. With more distant promoters, the same is less likely to hold for gene pairs in nondivergent orientation. Stochastic models suggest that coupled chromatin dynamics will typically result in low abundance-corrected noise (ACN). Transcription of noncoding RNA (ncRNA) from a bidirectional promoter, we thus hypothesize to be a noise-reduction, expression-priming, mechanism. The hypothesis correctly predicts that protein-coding genes with a bidirectional promoter, including those with a ncRNA partner, have lower ACN than other genes and divergent gene pairs uniquely have correlated ACN. Moreover, as predicted, ACN increases with the distance between promoters. The model also correctly predicts ncRNA transcripts to be often divergently transcribed from genes that a priori would be under selection for low noise (essential genes, protein complex genes) and that the latter genes should commonly reside in divergent orientation. Likewise, that genes with bidirectional promoters are rare subtelomerically, cluster together, and are enriched in essential gene clusters is expected and observed. We conclude that gene orientation and transcription of ncRNAs are candidate modulators of noise. PMID:21402863

Distant drivers or local signals: where do mercury trends in western Arctic belugas originate?

PubMed

Loseto, L L; Stern, G A; Macdonald, R W

2015-03-15

Temporal trends of contaminants are monitored in Arctic higher trophic level species to inform us on the fate, transport and risk of contaminants as well as advise on global emissions. However, monitoring mercury (Hg) trends in species such as belugas challenge us, as their tissue concentrations reflect complex interactions among Hg deposition and methylation, whale physiology, dietary exposure and foraging patterns. The Beaufort Sea beluga population showed significant increases in Hg during the 1990 s; since that time an additional 10 years of data have been collected. During this time of data collection, changes in the Arctic have affected many processes that underlie the Hg cycle. Here, we examine Hg in beluga tissues and investigate factors that could contribute to the observed trends after removing the effect of age and size on Hg concentrations and dietary factors. Finally, we examine available indicators of climate variability (Arctic Oscillation (AO), the Pacific Decadal Oscillation (PDO) and sea-ice minimum (SIM) concentration) to evaluate their potential to explain beluga Hg trends. Results reveal a decline in Hg concentrations from 2002 to 2012 in the liver of older whales and the muscle of large whales. The temporal increases in Hg in the 1990 s followed by recent declines do not follow trends in Hg emission, and are not easily explained by diet markers highlighting the complexity of feeding, food web dynamics and Hg uptake. Among the regional-scale climate variables the PDO exhibited the most significant relationship with beluga Hg at an eight year lag time. This distant signal points us to consider beluga winter feeding areas. Given that changes in climate will impact ecosystems; it is plausible that these climate variables are important in explaining beluga Hg trends. Such relationships require further investigation of the multiple connections between climate variables and beluga Hg. Copyright © 2014 Elsevier B.V. All rights reserved.

Establishment of the Inducible Tet-On System for the Activation of the Silent Trichosetin Gene Cluster in Fusarium fujikuroi

PubMed Central

Janevska, Slavica; Arndt, Birgit; Baumann, Leonie; Apken, Lisa Helene; Mauriz Marques, Lucas Maciel; Humpf, Hans-Ulrich; Tudzynski, Bettina

2017-01-01

The PKS-NRPS-derived tetramic acid equisetin and its N-desmethyl derivative trichosetin exhibit remarkable biological activities against a variety of organisms, including plants and bacteria, e.g., Staphylococcus aureus. The equisetin biosynthetic gene cluster was first described in Fusarium heterosporum, a species distantly related to the notorious rice pathogen Fusarium fujikuroi. Here we present the activation and characterization of a homologous, but silent, gene cluster in F. fujikuroi. Bioinformatic analysis revealed that this cluster does not contain the equisetin N-methyltransferase gene eqxD and consequently, trichosetin was isolated as final product. The adaption of the inducible, tetracycline-dependent Tet-on promoter system from Aspergillus niger achieved a controlled overproduction of this toxic metabolite and a functional characterization of each cluster gene in F. fujikuroi. Overexpression of one of the two cluster-specific transcription factor (TF) genes, TF22, led to an activation of the three biosynthetic cluster genes, including the PKS-NRPS key gene. In contrast, overexpression of TF23, encoding a second Zn(II)2Cys6 TF, did not activate adjacent cluster genes. Instead, TF23 was induced by the final product trichosetin and was required for expression of the transporter-encoding gene MFS-T. TF23 and MFS-T likely act in consort and contribute to detoxification of trichosetin and therefore, self-protection of the producing fungus. PMID:28379186

Establishment of the Inducible Tet-On System for the Activation of the Silent Trichosetin Gene Cluster in Fusarium fujikuroi.

PubMed

Janevska, Slavica; Arndt, Birgit; Baumann, Leonie; Apken, Lisa Helene; Mauriz Marques, Lucas Maciel; Humpf, Hans-Ulrich; Tudzynski, Bettina

2017-04-05

The PKS-NRPS-derived tetramic acid equisetin and its N -desmethyl derivative trichosetin exhibit remarkable biological activities against a variety of organisms, including plants and bacteria, e.g., Staphylococcus aureus . The equisetin biosynthetic gene cluster was first described in Fusarium heterosporum , a species distantly related to the notorious rice pathogen Fusarium fujikuroi . Here we present the activation and characterization of a homologous, but silent, gene cluster in F. fujikuroi . Bioinformatic analysis revealed that this cluster does not contain the equisetin N -methyltransferase gene eqxD and consequently, trichosetin was isolated as final product. The adaption of the inducible, tetracycline-dependent Tet-on promoter system from Aspergillus niger achieved a controlled overproduction of this toxic metabolite and a functional characterization of each cluster gene in F. fujikuroi . Overexpression of one of the two cluster-specific transcription factor (TF) genes, TF22 , led to an activation of the three biosynthetic cluster genes, including the PKS-NRPS key gene. In contrast, overexpression of TF23 , encoding a second Zn(II)₂Cys₆ TF, did not activate adjacent cluster genes. Instead, TF23 was induced by the final product trichosetin and was required for expression of the transporter-encoding gene MFS-T . TF23 and MFS-T likely act in consort and contribute to detoxification of trichosetin and therefore, self-protection of the producing fungus.

YB-1, the E2F Pathway, and Regulation of Tumor Cell Growth

PubMed Central

Samuel, Weini; Cao, Helen; Patel, Rachna; Mehta, Reena; Stern, J. Lewis; Reid, Glen; Woolley, Adele G.; Miller, Lance D.; Black, Michael A; Shelling, Andrew N.; Print, Cristin G.; Braithwaite, Antony W.

2012-01-01

Background Y-box binding factor 1 (YB-1) has been associated with prognosis in many tumor types. Reduced YB-1 expression inhibits tumor cell growth, but the mechanism is unclear. Methods YB-1 mRNA levels were compared with tumor grade and histology using microarray data from 771 breast cancer patients and with disease-free survival and distant metastasis–free survival using data from 375 of those patients who did not receive adjuvant therapy. Microarrays were further searched for genes that had correlated expression with YB-1 mRNA. Small interfering RNA (siRNA) was used to study the effects of reduced YB-1 expression on growth of three tumor cell lines (MCF-7 breast, HCT116 colon, and A549 lung cancer cells), on tumorigenesis by A549 cells in nude mice, and on global transcription in the three cancer cell lines. Reporter gene assays were used to determine whether YB-1 siRNAs affected the expression of E2F1, and chromatin immunoprecipitation was used to determine whether YB-1 bound to various E2F promoters as well as E2F1-regulated promoters. All P values were from two-sided tests. Results YB-1 levels were elevated in more aggressive tumors and were strongly associated with poor disease-free survival and distant metastasis–free survival. YB-1 expression was often associated with the expression of genes with E2F sites in their promoters. Cells expressing YB-1 siRNA grew substantially more slowly than control cells and formed tumors less readily in nude mice. Transcripts that were altered in cancer cell lines with YB-1 siRNA included 32 genes that are components of prognostic gene expression signatures. YB-1 regulated expression of an E2F1 promoter–reporter construct in A549 cells (eg, relative E2F1 promoter activity with control siRNA = 4.04; with YB-1 siRNA = 1.40, difference= −2.64, 95% confidence interval = −3.57 to −1.71, P < .001) and bound to the promoters of several well-defined E2F1 target genes. Conclusion YB-1 expression is associated with the activity of E2F transcription factors and may control tumor cell growth by this mechanism. PMID:22205655

Spatio-temporal filtering techniques for the detection of disaster-related communication.

PubMed

Fitzhugh, Sean M; Ben Gibson, C; Spiro, Emma S; Butts, Carter T

2016-09-01

Individuals predominantly exchange information with one another through informal, interpersonal channels. During disasters and other disrupted settings, information spread through informal channels regularly outpaces official information provided by public officials and the press. Social scientists have long examined this kind of informal communication in the rumoring literature, but studying rumoring in disrupted settings has posed numerous methodological challenges. Measuring features of informal communication-timing, content, location-with any degree of precision has historically been extremely challenging in small studies and infeasible at large scales. We address this challenge by using online, informal communication from a popular microblogging website and for which we have precise spatial and temporal metadata. While the online environment provides a new means for observing rumoring, the abundance of data poses challenges for parsing hazard-related rumoring from countless other topics in numerous streams of communication. Rumoring about disaster events is typically temporally and spatially constrained to places where that event is salient. Accordingly, we use spatio and temporal subsampling to increase the resolution of our detection techniques. By filtering out data from known sources of error (per rumor theories), we greatly enhance the signal of disaster-related rumoring activity. We use these spatio-temporal filtering techniques to detect rumoring during a variety of disaster events, from high-casualty events in major population centers to minimally destructive events in remote areas. We consistently find three phases of response: anticipatory excitation where warnings and alerts are issued ahead of an event, primary excitation in and around the impacted area, and secondary excitation which frequently brings a convergence of attention from distant locales onto locations impacted by the event. Our results demonstrate the promise of spatio-temporal filtering techniques for "tuning" measurement of hazard-related rumoring to enable observation of rumoring at scales that have long been infeasible. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiogenomic Analysis of Localized fMRI Brain Activity in Schizophrenia

PubMed Central

Windemuth, Andreas; Calhoun, Vince D.; Pearlson, Godfrey D.; Kocherla, Mohan; Jagannathan, Kanchana; Ruaño, Gualberto

2009-01-01

The search for genetic factors associated with disease is complicated by the complexity of the biological pathways linking genotype and phenotype. This analytical complexity is particularly concerning in diseases historically lacking reliable diagnostic biological markers, such as schizophrenia and other mental disorders. We investigate the use of functional magnetic resonance imaging (fMRI) as an intermediate phenotype (endophenotype) to identify physiogenomic associations to schizophrenia. We screened 99 subjects, 30 subjects diagnosed with schizophrenia, 13 unaffected relatives of schizophrenia patients, and 56 unrelated controls, for gene polymorphisms associated with fMRI activation patterns at two locations in temporal and frontal lobes previously implied in schizophrenia. A total of 22 single nucleotide polymorphisms (SNPs) in 15 genes from the dopamine and serotonin neurotransmission pathways were genotyped in all subjects. We identified three SNPs in genes that are significantly associated with fMRI activity. SNPs of the dopamine beta-hydroxylase (DBH) gene and of the dopamine receptor D4 (DRD4) were associated with activity in the temporal and frontal lobes, respectively. One SNP of serotonin-3A receptor (HTR3A) was associated with temporal lobe activity. The results of this study support the physiogenomic analysis of neuroimaging data to discover associations between genotype and disease-related phenotypes. PMID:18330705

Identification and temporal expression of putative circadian clock transcripts in the amphipod crustacean Talitrus saltator

PubMed Central

O’Grady, Joseph F.; Hoelters, Laura S.; Swain, Martin T.

2016-01-01

Background Talitrus saltator is an amphipod crustacean that inhabits the supralittoral zone on sandy beaches in the Northeast Atlantic and Mediterranean. T. saltator exhibits endogenous locomotor activity rhythms and time-compensated sun and moon orientation, both of which necessitate at least one chronometric mechanism. Whilst their behaviour is well studied, currently there are no descriptions of the underlying molecular components of a biological clock in this animal, and very few in other crustacean species. Methods We harvested brain tissue from animals expressing robust circadian activity rhythms and used homology cloning and Illumina RNAseq approaches to sequence and identify the core circadian clock and clock-related genes in these samples. We assessed the temporal expression of these genes in time-course samples from rhythmic animals using RNAseq. Results We identified a comprehensive suite of circadian clock gene homologues in T. saltator including the ‘core’ clock genes period (Talper), cryptochrome 2 (Talcry2), timeless (Taltim), clock (Talclk), and bmal1 (Talbmal1). In addition we describe the sequence and putative structures of 23 clock-associated genes including two unusual, extended isoforms of pigment dispersing hormone (Talpdh). We examined time-course RNAseq expression data, derived from tissues harvested from behaviourally rhythmic animals, to reveal rhythmic expression of these genes with approximately circadian period in Talper and Talbmal1. Of the clock-related genes, casein kinase IIβ (TalckIIβ), ebony (Talebony), jetlag (Taljetlag), pigment dispensing hormone (Talpdh), protein phosphatase 1 (Talpp1), shaggy (Talshaggy), sirt1 (Talsirt1), sirt7 (Talsirt7) and supernumerary limbs (Talslimb) show temporal changes in expression. Discussion We report the sequences of principle genes that comprise the circadian clock of T. saltator and highlight the conserved structural and functional domains of their deduced cognate proteins. Our sequencing data contribute to the growing inventory of described comparative clocks. Expression profiling of the identified clock genes illuminates tantalising targets for experimental manipulation to elucidate the molecular and cellular control of clock-driven phenotypes in this crustacean. PMID:27761341

Overdispersion of the Molecular Clock: Temporal Variation of Gene-Specific Substitution Rates in Drosophila

PubMed Central

Hartl, Daniel L.

2008-01-01

Simple models of molecular evolution assume that sequences evolve by a Poisson process in which nucleotide or amino acid substitutions occur as rare independent events. In these models, the expected ratio of the variance to the mean of substitution counts equals 1, and substitution processes with a ratio greater than 1 are called overdispersed. Comparing the genomes of 10 closely related species of Drosophila, we extend earlier evidence for overdispersion in amino acid replacements as well as in four-fold synonymous substitutions. The observed deviation from the Poisson expectation can be described as a linear function of the rate at which substitutions occur on a phylogeny, which implies that deviations from the Poisson expectation arise from gene-specific temporal variation in substitution rates. Amino acid sequences show greater temporal variation in substitution rates than do four-fold synonymous sequences. Our findings provide a general phenomenological framework for understanding overdispersion in the molecular clock. Also, the presence of substantial variation in gene-specific substitution rates has broad implications for work in phylogeny reconstruction and evolutionary rate estimation. PMID:18480070

Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.

PubMed

Vallat, Laurent; Kemper, Corey A; Jung, Nicolas; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Meyer, Nicolas; Pocheville, Arnaud; Fisher, John W; Gribben, John G; Bahram, Seiamak

2013-01-08

Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions--notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.

Time-Resolved Transcriptome Analysis of Bacillus subtilis Responding to Valine, Glutamate, and Glutamine

PubMed Central

Ye, Bang-Ce; Zhang, Yan; Yu, Hui; Yu, Wen-Bang; Liu, Bao-Hong; Yin, Bin-Cheng; Yin, Chun-Yun; Li, Yuan-Yuan; Chu, Ju; Zhang, Si-Liang

2009-01-01

Microorganisms can restructure their transcriptional output to adapt to environmental conditions by sensing endogenous metabolite pools. In this paper, an Agilent customized microarray representing 4,106 genes was used to study temporal transcript profiles of Bacillus subtilis in response to valine, glutamate and glutamine pulses over 24 h. A total of 673, 835, and 1135 amino-acid-regulated genes were identified having significantly changed expression at one or more time points in response to valine, glutamate, and glutamine, respectively, including genes involved in cell wall, cellular import, metabolism of amino-acids and nucleotides, transcriptional regulation, flagellar motility, chemotaxis, phage proteins, sporulation, and many genes of unknown function. Different amino acid treatments were compared in terms of both the global temporal profiles and the 5-minute quick regulations, and between-experiment differential genes were identified. The highlighted genes were analyzed based on diverse sources of gene functions using a variety of computational tools, including T-profiler analysis, and hierarchical clustering. The results revealed the common and distinct modes of action of these three amino acids, and should help to elucidate the specific signaling mechanism of each amino acid as an effector. PMID:19763274

Temporal expression of pecan allergens during nut development

USDA-ARS?s Scientific Manuscript database

Pecan nuts and other tree nuts are among a group of eight foods that most commonly cause food allergy. The growth of pecan nuts is a highly complex process orchestrated by the temporal and spatial expression of specific genes. Three conserved seed-storage proteins from the prolamin and cupin super...

Reconstructing the Evolutionary History of Paralogous APETALA1/FRUITFULL-Like Genes in Grasses (Poaceae)

PubMed Central

Preston, Jill C.; Kellogg, Elizabeth A.

2006-01-01

Gene duplication is an important mechanism for the generation of evolutionary novelty. Paralogous genes that are not silenced may evolve new functions (neofunctionalization) that will alter the developmental outcome of preexisting genetic pathways, partition ancestral functions (subfunctionalization) into divergent developmental modules, or function redundantly. Functional divergence can occur by changes in the spatio-temporal patterns of gene expression and/or by changes in the activities of their protein products. We reconstructed the evolutionary history of two paralogous monocot MADS-box transcription factors, FUL1 and FUL2, and determined the evolution of sequence and gene expression in grass AP1/FUL-like genes. Monocot AP1/FUL-like genes duplicated at the base of Poaceae and codon substitutions occurred under relaxed selection mostly along the branch leading to FUL2. Following the duplication, FUL1 was apparently lost from early diverging taxa, a pattern consistent with major changes in grass floral morphology. Overlapping gene expression patterns in leaves and spikelets indicate that FUL1 and FUL2 probably share some redundant functions, but that FUL2 may have become temporally restricted under partial subfunctionalization to particular stages of floret development. These data have allowed us to reconstruct the history of AP1/FUL-like genes in Poaceae and to hypothesize a role for this gene duplication in the evolution of the grass spikelet. PMID:16816429

The role of semantic self-perceptions in temporal distance perceptions toward autobiographical events: the semantic congruence model.

PubMed

Gebauer, Jochen E; Haddock, Geoffrey; Broemer, Philip; von Hecker, Ulrich

2013-11-01

Why do some autobiographical events feel as if they happened yesterday, whereas others feel like ancient history? Such temporal distance perceptions have surprisingly little to do with actual calendar time distance. Instead, psychologists have found that people typically perceive positive autobiographical events as overly recent, while perceiving negative events as overly distant. The origins of this temporal distance bias have been sought in self-enhancement strivings and mood congruence between autobiographical events and chronic mood. As such, past research exclusively focused on the evaluative features of autobiographical events, while neglecting semantic features. To close this gap, we introduce a semantic congruence model. Capitalizing on the Big Two self-perception dimensions, Study 1 showed that high semantic congruence between recalled autobiographical events and trait self-perceptions render the recalled events subjectively recent. Specifically, interpersonally warm (competent) individuals perceived autobiographical events reflecting warmth (competence) as relatively recent, but warm (competent) individuals did not perceive events reflecting competence (warmth) as relatively recent. Study 2 found that conscious perceptions of congruence mediate these effects. Studies 3 and 4 showed that neither mood congruence nor self-enhancement account for these results. Study 5 extended the results from the Big Two to the Big Five self-perception dimensions, while affirming the independence of the semantic congruence model from evaluative influences. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

PubMed

Martínez-Levy, G A; Rocha, L; Rodríguez-Pineda, F; Alonso-Vanegas, M A; Nani, A; Buentello-García, R M; Briones-Velasco, M; San-Juan, D; Cienfuegos, J; Cruz-Fuentes, C S

2018-05-01

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Evolutionary history of the enolase gene family.

PubMed

Tracy, M R; Hedges, S B

2000-12-23

The enzyme enolase [EC 4.2.1.11] is found in all organisms, with vertebrates exhibiting tissue-specific isozymes encoded by three genes: alpha (alpha), beta (beta), and gamma (gamma) enolase. Limited taxonomic sampling of enolase has obscured the timing of gene duplication events. To help clarify the evolutionary history of the gene family, cDNAs were sequenced from six taxa representing major lineages of vertebrates: Chiloscyllium punctatum (shark), Amia calva (bowfin), Salmo trutta (trout), Latimeria chalumnae (coelacanth), Lepidosiren paradoxa (South American lungfish), and Neoceratodus forsteri (Australian lungfish). Phylogenetic analysis of all enolase and related gene sequences revealed an early gene duplication event prior to the last common ancestor of living organisms. Several distantly related archaebacterial sequences were designated as 'enolase-2', whereas all other enolase sequences were designated 'enolase-1'. Two of the three isozymes of enolase-1, alpha- and beta-enolase, were discovered in actinopterygian, sarcopterygian, and chondrichthian fishes. Phylogenetic analysis of vertebrate enolases revealed that the two gene duplications leading to the three isozymes of enolase-1 occurred subsequent to the divergence of living agnathans, near the Proterozoic/Phanerozoic boundary (approximately 550Mya). Two copies of enolase, designated alpha(1) and alpha(2), were found in the trout and are presumed to be the result of a genome duplication event.

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.

Spatio-temporal control of gene expression and cancer treatment using magnetic resonance imaging-guided focused ultrasound.

PubMed

Moonen, Chrit T W

2007-06-15

Local temperature elevation may be used for tumor ablation, gene expression, drug activation, and gene and/or drug delivery. High-intensity focused ultrasound (HIFU) is the only clinically viable technology that can be used to achieve a local temperature increase deep inside the human body in a noninvasive way. Magnetic resonance imaging (MRI) guidance of the procedure allows in situ target definition and identification of nearby healthy tissue to be spared. In addition, MRI can be used to provide continuous temperature mapping during HIFU for spatial and temporal control of the heating procedure and prediction of the final lesion based on the received thermal dose. The primary purpose of the development of MRI-guided HIFU was to achieve safe noninvasive tissue ablation. The technique has been tested extensively in preclinical studies and is now accepted in the clinic for ablation of uterine fibroids. MRI-guided HIFU for ablation shows conceptual similarities with radiation therapy. However, thermal damage generally shows threshold-like behavior, with necrosis above the critical thermal dose and full recovery below. MRI-guided HIFU is being clinically evaluated in the cancer field. The technology also shows great promise for a variety of advanced therapeutic methods, such as gene therapy. MR-guided HIFU, together with the use of a temperature-sensitive promoter, provides local, physical, and spatio-temporal control of transgene expression. Specially designed contrast agents, together with the combined use of MRI and ultrasound, may be used for local gene and drug delivery.

In silico selection of expression reference genes with demonstrated stability in barley among a diverse set of tissues and cultivars

USDA-ARS?s Scientific Manuscript database

Premise of the study: Reference genes are selected based on the assumption of temporal and spatial expression stability and on their widespread use in model species. They are often used in new target species without validation, presumed as stable. For barley, reference gene validation is lacking, bu...

PlantTribes: a gene and gene family resource for comparative genomics in plants

PubMed Central

Wall, P. Kerr; Leebens-Mack, Jim; Müller, Kai F.; Field, Dawn; Altman, Naomi S.; dePamphilis, Claude W.

2008-01-01

The PlantTribes database (http://fgp.huck.psu.edu/tribe.html) is a plant gene family database based on the inferred proteomes of five sequenced plant species: Arabidopsis thaliana, Carica papaya, Medicago truncatula, Oryza sativa and Populus trichocarpa. We used the graph-based clustering algorithm MCL [Van Dongen (Technical Report INS-R0010 2000) and Enright et al. (Nucleic Acids Res. 2002; 30: 1575–1584)] to classify all of these species’ protein-coding genes into putative gene families, called tribes, using three clustering stringencies (low, medium and high). For all tribes, we have generated protein and DNA alignments and maximum-likelihood phylogenetic trees. A parallel database of microarray experimental results is linked to the genes, which lets researchers identify groups of related genes and their expression patterns. Unified nomenclatures were developed, and tribes can be related to traditional gene families and conserved domain identifiers. SuperTribes, constructed through a second iteration of MCL clustering, connect distant, but potentially related gene clusters. The global classification of nearly 200 000 plant proteins was used as a scaffold for sorting ∼4 million additional cDNA sequences from over 200 plant species. All data and analyses are accessible through a flexible interface allowing users to explore the classification, to place query sequences within the classification, and to download results for further study. PMID:18073194

Biochemical characteristics and gene expression profiles of two paralogous luciferases from the Japanese firefly Pyrocoelia atripennis (Coleoptera, Lampyridae, Lampyrinae): insight into the evolution of firefly luciferase genes.

PubMed

Bessho-Uehara, Manabu; Konishi, Kaori; Oba, Yuichi

2017-08-09

Two paralogous genes of firefly luciferase, Luc1 and Luc2, have been isolated from the species in two subfamilies, Luciolinae and Photurinae, of the family Lampyridae. The gene expression profiles have previously been examined only in the species of Luciolinae. Here we isolated Luc1 and Luc2 genes from the Japanese firefly Pyrocoelia atripennis. This is the first report of the presence of both Luc1 and Luc2 genes in the species of the subfamily Lampyrinae and of the exon-intron structure of Luc2 in the family Lampyridae. The luminescence of both gene products peaked at 547 nm under neutral buffer conditions, and the spectrum of Luc1, but not Luc2, was red-shifted under acidic conditions, as observed for Luc2 in the Luciolinae species. The semi-quantitative reverse transcription-polymerase chain reaction suggested that Luc1 was expressed in lanterns of all the stages except eggs, while Luc2 was expressed in the non-lantern bodies of eggs, prepupae, pupae, and female adults. These expression profiles are consistent with those in the Luciolinae species. Considering the distant phylogenetic relationship between Lampyrinae and Luciolinae in Lampyridae, we propose that fireflies generally possess two different luciferase genes and the biochemical properties and gene expression profiles for each paralog are conserved among lampyrid species.

When outgroups fail; phylogenomics of rooting the emerging pathogen, Coxiella burnetii.

PubMed

Pearson, Talima; Hornstra, Heidie M; Sahl, Jason W; Schaack, Sarah; Schupp, James M; Beckstrom-Sternberg, Stephen M; O'Neill, Matthew W; Priestley, Rachael A; Champion, Mia D; Beckstrom-Sternberg, James S; Kersh, Gilbert J; Samuel, James E; Massung, Robert F; Keim, Paul

2013-09-01

Rooting phylogenies is critical for understanding evolution, yet the importance, intricacies and difficulties of rooting are often overlooked. For rooting, polymorphic characters among the group of interest (ingroup) must be compared to those of a relative (outgroup) that diverged before the last common ancestor (LCA) of the ingroup. Problems arise if an outgroup does not exist, is unknown, or is so distant that few characters are shared, in which case duplicated genes originating before the LCA can be used as proxy outgroups to root diverse phylogenies. Here, we describe a genome-wide expansion of this technique that can be used to solve problems at the other end of the evolutionary scale: where ingroup individuals are all very closely related to each other, but the next closest relative is very distant. We used shared orthologous single nucleotide polymorphisms (SNPs) from 10 whole genome sequences of Coxiella burnetii, the causative agent of Q fever in humans, to create a robust, but unrooted phylogeny. To maximize the number of characters informative about the rooting, we searched entire genomes for polymorphic duplicated regions where orthologs of each paralog could be identified so that the paralogs could be used to root the tree. Recent radiations, such as those of emerging pathogens, often pose rooting challenges due to a lack of ingroup variation and large genomic differences with known outgroups. Using a phylogenomic approach, we created a robust, rooted phylogeny for C. burnetii. [Coxiella burnetii; paralog SNPs; pathogen evolution; phylogeny; recent radiation; root; rooting using duplicated genes.].

Molecular differentiation and phylogenetic relationships of three Angiostrongylus species and Angiostrongylus cantonensis geographical isolates based on a 66-kDa protein gene of A. cantonensis (Nematoda: Angiostrongylidae).

PubMed

Eamsobhana, Praphathip; Lim, Phaik Eem; Zhang, Hongman; Gan, Xiaoxian; Yong, Hoi Sen

2010-12-01

The phylogenetic relationships and molecular differentiation of three species of angiostrongylid nematodes (Angiostrongylus cantonensis, Angiostrongylus costaricensis and Angiostrongylus malaysiensis) were studied using the AC primers for a 66-kDa protein gene of A. cantonensis. The AC primers successfully amplified the genomic DNA of these angiostrongylid nematodes. No amplification was detected for the DNA of Ascaris lumbricoides, Ascaris suum, Anisakis simplex, Gnathostoma spinigerum, Toxocara canis, and Trichinella spiralis. The maximum-parsimony (MP) consensus tree and the maximum-likelihood (ML) tree both showed that the Angiostrongylus taxa could be divided into two major clades - Clade 1 (A. costaricensis) and Clade 2 (A. cantonensis and A. malaysiensis) with a full support bootstrap value. A. costaricensis is the most distant taxon. A. cantonensis is a sister group to A. malaysiensis; these two taxa (species) are clearly separated. There is no clear distinction between the A. cantonensis samples from four different geographical localities (Thailand, China, Japan and Hawaii); only some of the samples are grouped ranging from no support or low support to moderate support of bootstrap values. The published nucleotide sequences of A. cantonensis adult-specific native 66kDa protein mRNA, clone L5-400 from Taiwan (U17585) appear to be very distant from the A. cantonensis samples from Thailand, China, Japan and Hawaii, with the uncorrected p-distance values ranging from 26.87% to 29.92%.

In vivo anti-tumour activity of recombinant MVM parvoviral vectors carrying the human interleukin-2 cDNA.

PubMed

El Bakkouri, Karim; Servais, Charlotte; Clément, Nathalie; Cheong, Siew Chiat; Franssen, Jean-Denis; Velu, Thierry; Brandenburger, Annick

2005-02-01

The natural oncotropism and oncotoxicity of vectors derived from the autonomous parvovirus, minute virus of mice (prototype strain) [MVM(p)], combined with the immunotherapeutic properties of cytokine transgenes, make them interesting candidates for cancer gene therapy. The in vivo anti-tumour activity of a recombinant parvoviral vector, MVM-IL2, was evaluated in a syngeneic mouse melanoma model that is relatively resistant in vitro to the intrinsic cytotoxicity of wild-type MVM(p). In vitro infection of the K1735 melanoma cells prior to their injection resulted in loss of tumorigenicity in 70% of mice (7/10). Tumour-free mice were protected against a challenge with non-infected parental cells. In addition, MVM-IL2-infected tumour cells induced an anti-tumour activity on parental cells injected at a distant location. These non-infected tumour cells were injected either at the same time or 7 days before the injection of MVM-IL2-infected cells. In the latter setting, which mimics a therapeutic model for small tumours, 4/10 mice were still tumour-free after 4 months. Our results show that (i) the MVM-IL2 parvoviral vector efficiently transduces tumour cells; and (ii) the low multiplicity of infection (MOI = 1) used in our experiments was sufficient to elicit an anti-tumour effect on distant cells, which supports further studies on this vector as a new tool for cancer gene therapy. Copyright (c) 2004 John Wiley & Sons, Ltd.

Outbreeding effects in an inbreeding insect, Cimex lectularius.

PubMed

Fountain, Toby; Butlin, Roger K; Reinhardt, Klaus; Otti, Oliver

2015-01-01

In some species, populations with few founding individuals can be resilient to extreme inbreeding. Inbreeding seems to be the norm in the common bed bug, Cimex lectularius, a flightless insect that, nevertheless, can reach large deme sizes and persist successfully. However, bed bugs can also be dispersed passively by humans, exposing inbred populations to gene flow from genetically distant populations. The introduction of genetic variation through this outbreeding could lead to increased fitness (heterosis) or be costly by causing a loss of local adaptation or exposing genetic incompatibility between populations (outbreeding depression). Here, we addressed how inbreeding within demes and outbreeding between distant populations impact fitness over two generations in this re-emerging public health pest. We compared fitness traits of families that were inbred (mimicking reproduction following a founder event) or outbred (mimicking reproduction following a gene flow event). We found that outbreeding led to increased starvation resistance compared to inbred families, but this benefit was lost after two generations of outbreeding. No other fitness benefits of outbreeding were observed in either generation, including no differences in fecundity between the two treatments. Resilience to inbreeding is likely to result from the history of small founder events in the bed bug. Outbreeding benefits may only be detectable under stress and when heterozygosity is maximized without disruption of coadaptation. We discuss the consequences of these results both in terms of inbreeding and outbreeding in populations with genetic and spatial structuring, as well as for the recent resurgence of bed bug populations.

Conserved regulatory elements of the promoter sequence of the gene rpoH of enteric bacteria

PubMed Central

Ramírez-Santos, Jesús; Collado-Vides, Julio; García-Varela, Martin; Gómez-Eichelmann, M. Carmen

2001-01-01

The rpoH regulatory region of different members of the enteric bacteria family was sequenced or downloaded from GenBank and compared. In addition, the transcriptional start sites of rpoH of Yersinia frederiksenii and Proteus mirabilis, two distant members of this family, were determined. Sequences similar to the σ70 promoters P1, P4 and P5, to the σE promoter P3 and to boxes DnaA1, DnaA2, cAMP receptor protein (CRP) boxes CRP1, CRP2 and box CytR present in Escherichia coli K12, were identified in sequences of closely related bacteria such as: E.coli, Shigella flexneri, Salmonella enterica serovar Typhimurium, Citrobacter freundii, Enterobacter cloacae and Klebsiella pneumoniae. In more distant bacteria, Y.frederiksenii and P.mirabilis, the rpoH regulatory region has a distal P1-like σ70 promoter and two proximal promoters: a heat-induced σE-like promoter and a σ70 promoter. Sequences similar to the regulatory boxes were not identified in these bacteria. This study suggests that the general pattern of transcription of the rpoH gene in enteric bacteria includes a distal σ70 promoter, >200 nt upstream of the initiation codon, and two proximal promoters: a heat-induced σE-like promoter and a σ70 promoter. A second proximal σ70 promoter under catabolite-regulation is probably present only in bacteria closely related to E.coli. PMID:11139607

Temporal and spatial transcriptomic and microRNA dynamics of CAM photosynthesis in pineapple.

PubMed

Wai, Ching M; VanBuren, Robert; Zhang, Jisen; Huang, Lixian; Miao, Wenjing; Edger, Patrick P; Yim, Won C; Priest, Henry D; Meyers, Blake C; Mockler, Todd; Smith, J Andrew C; Cushman, John C; Ming, Ray

2017-10-01

The altered carbon assimilation pathway of crassulacean acid metabolism (CAM) photosynthesis results in an up to 80% higher water-use efficiency than C 3 photosynthesis in plants making it a potentially useful pathway for engineering crop plants with improved drought tolerance. Here we surveyed detailed temporal (diel time course) and spatial (across a leaf gradient) gene and microRNA (miRNA) expression patterns in the obligate CAM plant pineapple [Ananas comosus (L.) Merr.]. The high-resolution transcriptome atlas allowed us to distinguish between CAM-related and non-CAM gene copies. A differential gene co-expression network across green and white leaf diel datasets identified genes with circadian oscillation, CAM-related functions, and source-sink relations. Gene co-expression clusters containing CAM pathway genes are enriched with clock-associated cis-elements, suggesting circadian regulation of CAM. About 20% of pineapple microRNAs have diel expression patterns, with several that target key CAM-related genes. Expression and physiology data provide a model for CAM-specific carbohydrate flux and long-distance hexose transport. Together these resources provide a list of candidate genes for targeted engineering of CAM into C 3 photosynthesis crop species. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Transcriptional Modulation of Genes Encoding Structural Characteristics of Differentiating Enterocytes During Development of a Polarized Epithelium In Vitro

PubMed Central

Halbleib, Jennifer M.; Sääf, Annika M.

2007-01-01

Although there is considerable evidence implicating posttranslational mechanisms in the development of epithelial cell polarity, little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized the temporal program of gene expression during cell–cell adhesion–initiated polarization of human Caco-2 cells in tissue culture, which develop structural and functional polarity similar to that of enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts between neighboring cells. Expression of genes involved in cell proliferation was down-regulated concomitant with induction of genes necessary for functional specialization of polarized epithelial cells. Transcriptional up-regulation of these latter genes correlated with formation of important structural and functional features in enterocyte differentiation and establishment of structural and functional cell polarity; components of the apical microvilli were induced as the brush border formed during polarization; as barrier function was established, expression of tight junction transmembrane proteins peaked; transcripts encoding components of the apical, but not the basal-lateral trafficking machinery were increased during polarization. Coordinated expression of genes encoding components of functional cell structures were often observed indicating temporal control of expression and assembly of multiprotein complexes. PMID:17699590

The physics of 2 ≠ 1 + 1

NASA Astrophysics Data System (ADS)

Shih, Yanhua

2007-06-01

One of the most surprising consequences of quantum mechanics is the entanglement of two or more distant particles. In an entangled EPR two-particle system, the value of the momentum (position) for neither single subsystem is determined. However, if one of the subsystems is measured to have a certain momentum (position), the other subsystem is determined to have a unique corresponding value, despite the distance between them. This peculiar behavior of an entangled quantum system has surprisingly been observed experimentally in two-photon temporal and spatial correlation measurements, such as “ghost” interference and “ghost” imaging. This article addresses the fundamental concerns behind these experimental observations and to explore the nonclassical nature of two-photon superposition by emphasizing the physics of 2 ≠ 1 + 1.

Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium.

PubMed

Muranen, Taru A; Blomqvist, Carl; Dörk, Thilo; Jakubowska, Anna; Heikkilä, Päivi; Fagerholm, Rainer; Greco, Dario; Aittomäki, Kristiina; Bojesen, Stig E; Shah, Mitul; Dunning, Alison M; Rhenius, Valerie; Hall, Per; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Chang-Claude, Jenny; Rudolph, Anja; Nordestgaard, Børge G; Couch, Fergus J; Hart, Steven N; Figueroa, Jonine; García-Closas, Montserrat; Fasching, Peter A; Beckmann, Matthias W; Li, Jingmei; Liu, Jianjun; Andrulis, Irene L; Winqvist, Robert; Pylkäs, Katri; Mannermaa, Arto; Kataja, Vesa; Lindblom, Annika; Margolin, Sara; Lubinski, Jan; Dubrowinskaja, Natalia; Bolla, Manjeet K; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Easton, Douglas F; Pharoah, Paul D P; Schmidt, Marjanka K; Nevanlinna, Heli

2016-10-03

P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature. P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly enriched among genes, whose expression differed between p.I157T and non-carrier tumors. Our analyses suggest that there are fundamental differences in breast tumors of CHEK2:p.I157T and c.1100delC carriers. The poor prognosis associated with c.1100delC cannot be generalized to other CHEK2 mutations.

The relationship between quantitative human epidermal growth factor receptor 2 gene expression by the 21-gene reverse transcriptase polymerase chain reaction assay and adjuvant trastuzumab benefit in Alliance N9831.

PubMed

Perez, Edith A; Baehner, Frederick L; Butler, Steven M; Thompson, E Aubrey; Dueck, Amylou C; Jamshidian, Farid; Cherbavaz, Diana; Yoshizawa, Carl; Shak, Steven; Kaufman, Peter A; Davidson, Nancy E; Gralow, Julie; Asmann, Yan W; Ballman, Karla V

2015-10-01

The N9831 trial demonstrated the efficacy of adjuvant trastuzumab for patients with human epidermal growth factor receptor 2 (HER2) locally positive tumors by protein or gene analysis. We used the 21-gene assay to examine the association of quantitative HER2 messenger RNA (mRNA) gene expression and benefit from trastuzumab. N9831 tested the addition of trastuzumab to chemotherapy in stage I-III HER2-positive breast cancer. For two of the arms of the trial, doxorubicin and cyclophosphamide followed by paclitaxel (AC-T) and doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab concurrent chemotherapy-trastuzumab (AC-TH), recurrence score (RS) and HER2 mRNA expression were determined by the 21-gene assay (Oncotype DX®) (negative <10.7, equivocal 10.7 to <11.5, and positive ≥11.5 log2 expression units). Cox regression was used to assess the association of HER2 expression with trastuzumab benefit in preventing distant recurrence. Median follow-up was 7.4 years. Of 1,940 total patients, 901 had consent and sufficient tissue. HER2 by reverse transcriptase polymerase chain reaction (RT-PCR) was negative in 130 (14 %), equivocal in 85 (9 %), and positive in 686 (76 %) patients. Concordance between HER2 assessments was 95 % for RT-PCR versus central immunohistochemistry (IHC) (>10 % positive cells = positive), 91 % for RT-PCR versus central fluorescence in situ hybridization (FISH) (≥2.0 = positive) and 94 % for central IHC versus central FISH. In the primary analysis, the association of HER2 expression by 21-gene assay with trastuzumab benefit was marginally nonsignificant (nonlinear p = 0.057). In hormone receptor-positive patients (local IHC) the association was significant (p = 0.002). The association was nonlinear with the greatest estimated benefit at lower and higher HER2 expression levels. Concordance among HER2 assessments by central IHC, FISH, and RT-PCR were similar and high. Association of HER2 mRNA expression with trastuzumab benefit as measured by time to distant recurrence was nonsignificant. A consistent benefit of trastuzumab irrespective of mHER2 levels was observed in patients with either IHC-positive or FISH-positive tumors. Trend for benefit was observed also for the small groups of patients with negative results by any or all of the central assays. Clinicaltrials.gov NCT00005970 . Registered 5 July 2000.

Mitochondrial markers predict recurrence, metastasis and tamoxifen-resistance in breast cancer patients: Early detection of treatment failure with companion diagnostics.

PubMed

Sotgia, Federica; Fiorillo, Marco; Lisanti, Michael P

2017-09-15

Here, we used a data-mining and informatics approach to discover new biomarkers of resistance to hormonal therapy in breast cancer. More specifically, we investigated whether nuclear-encoded genes associated with mitochondrial biogenesis can be used to predict tumor recurrence, distant metastasis and treatment failure in high-risk breast cancer patients. Overall, this strategy allowed us to directly provide in silico validation of the prognostic value of these mitochondrial components in large and clinically relevant patient populations, with >15 years of follow-up data. For this purpose, we employed a group of 145 ER(+) luminal A breast cancer patients, with lymph-node (LN) metastasis at diagnosis, that were treated with tamoxifen, but not any chemotherapy agents. Using this approach, we identified >60 new individual mitochondrial biomarkers that predicted treatment failure and tumor recurrence, with hazard-ratios (HR) of up to 4.17 ( p =2.2e-07). These include mitochondrial chaperones (HSPD1, HSPA9), membrane proteins (VDAC2, TOMM70A) and anti-oxidants (SOD2), as well as 18 different mitochondrial ribosomal proteins (MRPs) and >20 distinct components of the OXPHOS complexes. In addition, we combined 4 mitochondrial proteins (HSPD1, UQCRB, MRPL15, COX17), to generate a compact mitochondrial gene signature, associated with a HR of 5.34 ( p =1e-09). This signature also successfully predicted distant metastasis and was effective in larger groups of ER(+) ( N =2,447), basal ( N =540) and HER2(+) ( N =193) breast cancers. It was also effective in all breast cancers ( N =3,180), if considered together as a single group. Based on this analysis, we conclude that mitochondrial biogenesis should be considered as a new therapeutic target for overcoming tumor recurrence, distant metastasis and treatment failure in patients with breast cancer. In summary, we identified individual mitochondrial biomarkers and 2 compact mitochondrial gene signatures that can be used to predict tamoxifen-resistance and tumor recurrence, at their initial diagnosis, in patients with advanced breast cancer. In the long-term, these mitochondrial biomarkers could provide a new companion diagnostics platform to help clinicians to accurately predict the response to hormonal therapy in ER(+) breast cancer patients, facilitating more personalized and effective treatment. Similarly, these mitochondrial markers could be used as companion diagnostics, to determine which breast cancer patients would benefit most from clinical treatments with mitochondrially-targeted anti-cancer therapeutics. Finally, we also showed that these mitochondrial markers are superior when directly compared with conventional biomarkers, such as Ki67 and PCNA.

Metagenomic gene annotation by a homology-independent approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Froula, Jeff; Zhang, Tao; Salmeen, Annette

2011-06-02

Fully understanding the genetic potential of a microbial community requires functional annotation of all the genes it encodes. The recently developed deep metagenome sequencing approach has enabled rapid identification of millions of genes from a complex microbial community without cultivation. Current homology-based gene annotation fails to detect distantly-related or structural homologs. Furthermore, homology searches with millions of genes are very computational intensive. To overcome these limitations, we developed rhModeller, a homology-independent software pipeline to efficiently annotate genes from metagenomic sequencing projects. Using cellulases and carbonic anhydrases as two independent test cases, we demonstrated that rhModeller is much faster than HMMERmore » but with comparable accuracy, at 94.5percent and 99.9percent accuracy, respectively. More importantly, rhModeller has the ability to detect novel proteins that do not share significant homology to any known protein families. As {approx}50percent of the 2 million genes derived from the cow rumen metagenome failed to be annotated based on sequence homology, we tested whether rhModeller could be used to annotate these genes. Preliminary results suggest that rhModeller is robust in the presence of missense and frameshift mutations, two common errors in metagenomic genes. Applying the pipeline to the cow rumen genes identified 4,990 novel cellulases candidates and 8,196 novel carbonic anhydrase candidates.In summary, we expect rhModeller to dramatically increase the speed and quality of metagnomic gene annotation.« less

The DAL10 gene from Norway spruce (Picea abies) belongs to a potentially gymnosperm-specific subclass of MADS-box genes and is specifically active in seed cones and pollen cones.

PubMed

Carlsbecker, Annelie; Sundström, Jens; Tandre, Karolina; Englund, Marie; Kvarnheden, Anders; Johanson, Urban; Engström, Peter

2003-01-01

Transcription factors encoded by different members of the MADS-box gene family have evolved central roles in the regulation of reproductive organ development in the flowering plants, the angiosperms. Development of the stamens and carpels, the pollen- and seed-bearing organs, involves the B- and C-organ-identity MADS-box genes. B- and C-type gene orthologs with activities specifically in developing pollen- and seed-bearing organs are also present in the distantly related gymnosperms: the conifers and the gnetophytes. We now report on the characterization of DAL10, a novel MADS-box gene from the conifer Norway spruce, which unlike the B- and C-type conifer genes shows no distinct orthology relationship to any angiosperm gene or clade in phylogenetic analyses. Like the B- and C-type genes, it is active specifically in developing pollen cones and seed cones. In situ RNA localization experiments show DAL10 to be expressed in the cone axis, which carry the microsporophylls of the young pollen cone. In contrast, in the seed cone it is expressed both in the cone axis and in the bracts, which subtend the ovuliferous scales. Expression data and the phenotype of transgenic Arabidopsis plants expressing DAL10 suggest that the gene may act upstream to or in concert with the B- and C-type genes in the establishment of reproductive identity of developing cones.

Correlation between severe infection and breast cancer metastases in the EORTC 10994/BIG 1-00 trial: Investigating innate immunity as a tumour suppressor in breast cancer.

PubMed

Touati, Nathan; Tryfonidis, Konstantinos; Caramia, Franco; Bonnefoi, Hervé; Cameron, David; Slaets, Leen; Parker, Belinda S; Loi, Sherene

2017-02-01

Breast cancer cells which express an innate immune signature regulated by interferon regulatory factor 7 (IRF7) have reduced metastatic potential. Infections can induce interferon signalling and may activate an anti-tumour immune response. We investigated whether 'severe infection' can be a clinical surrogate of this phenomenon and/or the presence of high levels of the IRF7 signature at diagnosis before neo-adjuvant chemotherapy (NACT) is associated with a reduced distant relapse risk, specifically in bones. Clinical data of the European Organisation for Research and Treatment of Cancer 10994/BIG 1-00 phase III trial which randomised 1856 patients treated with NACT between 2001 and 2006, were used. Severe infection was febrile neutropenia or any other grade III-IV infective adverse event during NACT. The IRF7 signature was calculated from gene expression data available for 160 patients on a pre-NACT biopsy. Cox models for distant relapse-free interval (DRFI) investigated the effect of the severe infection and IRF7. Fine and Gray models studied the occurrence of bone metastases as first distant relapse. Median follow-up was 4.8 years. No association between severe infection and DFRI was observed in the entire population (n = 1615 eligible patients) hazard ratio [(HR] = 0.99, 90% CI, confidence interval [CI] = 0.81-1.20). For IRF7 (N = 160), a trend towards an association with DRFI was observed (HR = 0.89 for a 50 unit increase, 90% CI = 0.78-1.02, p = 0.081). Higher levels of the IRF7 signature were significantly associated with a decreased bone metastases risk: (HR = 0.76 for a 50 unit increase, 95% CI, 0.62-0.94, p = 0.012). In this study it was shown that severe infection during NACT was not associated with decreased DRFI while high expression of the IRF7 gene signature was significantly associated with reduced bone relapse. This result may be useful for future adjuvant bisphosphonate/denosumab use. Copyright © 2016 Elsevier Ltd. All rights reserved.

Temporal Changes in Microbial Metagenomic Signatures and Lipid Profiles After Fracturing in the Marcellus Shale

NASA Astrophysics Data System (ADS)

Trexler, R.; Wrighton, K. C.; Pfiffner, S. M.; Wilkins, M.; Daly, R. A.; Mouser, P. J.

2014-12-01

Shale gas formations represent understudied deep biosphere ecosystems with important implications to terrestrial biogeochemical cycles and global energy resources. Recent 16S rRNA gene studies examining temporal microbial community dynamics of returned fluids from hydraulically fractured wells in the Marcellus Shale indicate ecosystem changes from aerobic, low-salt associated microbes in injected fluids to anaerobic, halophilic taxa in produced fluids several months after fracturing. To further characterize changes in the ecology, functional potential and biosignatures of observed taxa, we sequenced genomic DNA from three key time points after fracturing (T7, T82, and T328; Tn, n = days) and analyzed their lipid signatures. The metagenomic profiles verify 16S rRNA gene trends, revealing strain-type changes in dominant Bacteria of Marinobacter, Halomonas, and Halanaerobium and the Archaeal genus Methanolobus through time. Novel species within the γ-Proteobacteria were also observed. Reconstructed genomes show as bioavailable N decreases through time, genes associated with N2 fixing and obtaining N from organic pools (ncd2, nit1, and eutCB) increase in T82 and T328 samples after oxidized nitrogen species (NO3) are depleted. Further, S oxidizing genes were only detected in the T7 sample with incomplete pathways for dissimilatory sulfate reduction (DSR). Later time points showed an increase in abundance of sulfonate importer genes and the anaerobic DSR gene, asrA, suggesting the use of sulfite and sulfonates for S acquisition after sulfate is depleted. Lipid analyses confirmed distinct profiles between T82 and T328 and revealed differences in 16 and 18 C monounsaturated fatty acids, indicative of gram (-) bacteria. The lipid profile from T328 was markedly less diverse than that of T82 and indicated a very limited community, as supported by the 16S rRNA gene and metagenomic data. This research integrates metagenomic data with lipid profiles to characterize temporal changes in biosignatures and the functional potential of N and S metabolic genes of deep shale microbes.

Distant stereoacuity in children with anisometropic amblyopia.

PubMed

Chung, Yeon Woong; Park, Shin Hae; Shin, Sun Young

2017-09-01

To characterize changes in distant stereoacuity using Frisby-Davis Distance test (FD2) and Distant Randot test (DR) during treatment for anisometropic amblyopia, to determine factors that influence posttreatment stereoacuity and to compare the two distant stereotests. Fifty-eight anisometropic amblyopic patients with an interocular difference of ≥1.00 diopter who achieved the visual acuity 20/20 following amblyopia treatment were retrospectively included. Stereoacuity using FD2 and DR for distant and Titmus test for near measurement were assessed and compared at the initial, intermediate, and final visit. Multivariate regression models were used to identify factors associated with initial and final stereoacuity. The two distant stereotests revealed a significant improvement in distant stereoacuity after successful amblyopia treatment. Distant stereoacuity using FD2 showed the greatest improvement during the follow up period. The number of nil scores was higher in DR than FD2 at each period. In multivariate analysis, better final stereoacuity was associated with better initial amblyopic eye acuity in both distant stereotests, but not in the Titmus test. Comparing the two distant stereotests, final stereoacuity using FD2 was associated with initial stereoacuity and was moderately related with the Titmus test at each period, but final stereoacuity using DR was not. Distant stereoacuity measured with both FD2 and DR showed significant improvement when the visual acuity of the amblyopic eye achieved 20/20. Changes in distant stereoacuity by FD2 and DR during the amblyopia treatment were somewhat different.

Genomic Evolution of Breast Cancer Metastasis and Relapse

DOE PAGES

Yates, Lucy R.; Knappskog, Stian; Wedge, David; ...

2017-08-14

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancermore » genes than early drivers. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.« less

Limits to gene flow in a cosmopolitan marine planktonic diatom.

PubMed

Casteleyn, Griet; Leliaert, Frederik; Backeljau, Thierry; Debeer, Ann-Eline; Kotaki, Yuichi; Rhodes, Lesley; Lundholm, Nina; Sabbe, Koen; Vyverman, Wim

2010-07-20

The role of geographic isolation in marine microbial speciation is hotly debated because of the high dispersal potential and large population sizes of planktonic microorganisms and the apparent lack of strong dispersal barriers in the open sea. Here, we show that gene flow between distant populations of the globally distributed, bloom-forming diatom species Pseudo-nitzschia pungens (clade I) is limited and follows a strong isolation by distance pattern. Furthermore, phylogenetic analysis implies that under appropriate geographic and environmental circumstances, like the pronounced climatic changes in the Pleistocene, population structuring may lead to speciation and hence may play an important role in diversification of marine planktonic microorganisms. A better understanding of the factors that control population structuring is thus essential to reveal the role of allopatric speciation in marine microorganisms.

Comparative analysis of bat genomes provides insight into the evolution of flight and immunity.

PubMed

Zhang, Guojie; Cowled, Christopher; Shi, Zhengli; Huang, Zhiyong; Bishop-Lilly, Kimberly A; Fang, Xiaodong; Wynne, James W; Xiong, Zhiqiang; Baker, Michelle L; Zhao, Wei; Tachedjian, Mary; Zhu, Yabing; Zhou, Peng; Jiang, Xuanting; Ng, Justin; Yang, Lan; Wu, Lijun; Xiao, Jin; Feng, Yue; Chen, Yuanxin; Sun, Xiaoqing; Zhang, Yong; Marsh, Glenn A; Crameri, Gary; Broder, Christopher C; Frey, Kenneth G; Wang, Lin-Fa; Wang, Jun

2013-01-25

Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related species, fruit bat Pteropus alecto and insectivorous bat Myotis davidii. We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor κB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.

Genomic Evolution of Breast Cancer Metastasis and Relapse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yates, Lucy R.; Knappskog, Stian; Wedge, David

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancermore » genes than early drivers. Lastly, these include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.« less

Temporal Shift of Circadian-Mediated Gene Expression and Carbon Fixation Contributes to Biomass Heterosis in Maize Hybrids.

PubMed

Ko, Dae Kwan; Rohozinski, Dominica; Song, Qingxin; Taylor, Samuel H; Juenger, Thomas E; Harmon, Frank G; Chen, Z Jeffrey

2016-07-01

Heterosis has been widely used in agriculture, but the molecular mechanism for this remains largely elusive. In Arabidopsis hybrids and allopolyploids, increased photosynthetic and metabolic activities are linked to altered expression of circadian clock regulators, including CIRCADIAN CLOCK ASSOCIATED1 (CCA1). It is unknown whether a similar mechanism mediates heterosis in maize hybrids. Here we report that higher levels of carbon fixation and starch accumulation in the maize hybrids are associated with altered temporal gene expression. Two maize CCA1 homologs, ZmCCA1a and ZmCCA1b, are diurnally up-regulated in the hybrids. Expressing ZmCCA1 complements the cca1 mutant phenotype in Arabidopsis, and overexpressing ZmCCA1b disrupts circadian rhythms and biomass heterosis. Furthermore, overexpressing ZmCCA1b in maize reduced chlorophyll content and plant height. Reduced height stems from reduced node elongation but not total node number in both greenhouse and field conditions. Phenotypes are less severe in the field than in the greenhouse, suggesting that enhanced light and/or metabolic activities in the field can compensate for altered circadian regulation in growth vigor. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis reveals a temporal shift of ZmCCA1-binding targets to the early morning in the hybrids, suggesting that activation of morning-phased genes in the hybrids promotes photosynthesis and growth vigor. This temporal shift of ZmCCA1-binding targets correlated with nonadditive and additive gene expression in early and late stages of seedling development. These results could guide breeding better hybrid crops to meet the growing demand in food and bioenergy.

Global Genetic Response in a Cancer Cell: Self-Organized Coherent Expression Dynamics

PubMed Central

Tsuchiya, Masa; Hashimoto, Midori; Takenaka, Yoshiko; Motoike, Ikuko N.; Yoshikawa, Kenichi

2014-01-01

Understanding the basic mechanism of the spatio-temporal self-control of genome-wide gene expression engaged with the complex epigenetic molecular assembly is one of major challenges in current biological science. In this study, the genome-wide dynamical profile of gene expression was analyzed for MCF-7 breast cancer cells induced by two distinct ErbB receptor ligands: epidermal growth factor (EGF) and heregulin (HRG), which drive cell proliferation and differentiation, respectively. We focused our attention to elucidate how global genetic responses emerge and to decipher what is an underlying principle for dynamic self-control of genome-wide gene expression. The whole mRNA expression was classified into about a hundred groups according to the root mean square fluctuation (rmsf). These expression groups showed characteristic time-dependent correlations, indicating the existence of collective behaviors on the ensemble of genes with respect to mRNA expression and also to temporal changes in expression. All-or-none responses were observed for HRG and EGF (biphasic statistics) at around 10–20 min. The emergence of time-dependent collective behaviors of expression occurred through bifurcation of a coherent expression state (CES). In the ensemble of mRNA expression, the self-organized CESs reveals distinct characteristic expression domains for biphasic statistics, which exhibits notably the presence of criticality in the expression profile as a route for genomic transition. In time-dependent changes in the expression domains, the dynamics of CES reveals that the temporal development of the characteristic domains is characterized as autonomous bistable switch, which exhibits dynamic criticality (the temporal development of criticality) in the genome-wide coherent expression dynamics. It is expected that elucidation of the biophysical origin for such critical behavior sheds light on the underlying mechanism of the control of whole genome. PMID:24831017

Virally mediated gene manipulation in the adult CNS

PubMed Central

Edry, Efrat; Lamprecht, Raphael; Wagner, Shlomo; Rosenblum, Kobi

2011-01-01

Understanding how the CNS functions poses one of the greatest challenges in modern life science and medicine. Studying the brain is especially challenging because of its complexity, the heterogeneity of its cellular composition, and the substantial changes it undergoes throughout its life-span. The complexity of adult brain neural networks results also from the diversity of properties and functions of neuronal cells, governed, inter alia, by temporally and spatially differential expression of proteins in mammalian brain cell populations. Hence, research into the biology of CNS activity and its implications to human and animal behavior must use novel scientific tools. One source of such tools is the field of molecular genetics—recently utilized more and more frequently in neuroscience research. Transgenic approaches in general, and gene targeting in rodents have become fundamental tools for elucidating gene function in the CNS. Although spectacular progress has been achieved over recent decades by using these approaches, it is important to note that they face a number of restrictions. One of the main challenges is presented by the temporal and spatial regulation of introduced genetic manipulations. Viral vectors provide an alternative approach to temporally regulated, localized delivery of genetic modifications into neurons. In this review we describe available technologies for gene transfer into the adult mammalian CNS that use both viral and non-viral tools. We discuss viral vectors frequently used in neuroscience, with emphasis on lentiviral vector (LV) systems. We consider adverse effects of LVs, and the use of LVs for temporally and spatially controllable manipulations. Especially, we highlight the significance of viral vector-mediated genetic manipulations in studying learning and memory processes, and how they may be effectively used to separate out the various phases of learning: acquisition, consolidation, retrieval, and maintenance. PMID:22207836

Remote Optical Switch for Localized and Selective Control of Gene Interference

PubMed Central

Lee, Somin Eunice; Liu, Gang Logan; Kim, Franklin; Lee, Luke P.

2009-01-01

Near infrared-absorbing gold nanoplasmonic particles (GNPs) are used as optical switches of gene interference and are remotely controlled using light. We have tuned optical switches to a wavelength where cellular photodamage is minimized. Optical switches are functionalized with double-stranded oligonucleotides. At desired times and at specific intracellular locations, remote optical excitation is used to liberate gene-interfering oligonucleotides. We demonstrate a novel gene-interfering technique offering spatial and temporal control, which is otherwise impossible using conventional gene-interfering techniques. PMID:19128006

Steroid hormone induction of temporal gene expression in Drosophila brain neuroblasts generates neuronal and glial diversity

PubMed Central

Syed, Mubarak Hussain; Mark, Brandon; Doe, Chris Q

2017-01-01

An important question in neuroscience is how stem cells generate neuronal diversity. During Drosophila embryonic development, neural stem cells (neuroblasts) sequentially express transcription factors that generate neuronal diversity; regulation of the embryonic temporal transcription factor cascade is lineage-intrinsic. In contrast, larval neuroblasts generate longer ~50 division lineages, and currently only one mid-larval molecular transition is known: Chinmo/Imp/Lin-28+ neuroblasts transition to Syncrip+ neuroblasts. Here we show that the hormone ecdysone is required to down-regulate Chinmo/Imp and activate Syncrip, plus two late neuroblast factors, Broad and E93. We show that Seven-up triggers Chinmo/Imp to Syncrip/Broad/E93 transition by inducing expression of the Ecdysone receptor in mid-larval neuroblasts, rendering them competent to respond to the systemic hormone ecdysone. Importantly, late temporal gene expression is essential for proper neuronal and glial cell type specification. This is the first example of hormonal regulation of temporal factor expression in Drosophila embryonic or larval neural progenitors. DOI: http://dx.doi.org/10.7554/eLife.26287.001 PMID:28394252

Comparative genomics reveals convergent evolution between the bamboo-eating giant and red pandas.

PubMed

Hu, Yibo; Wu, Qi; Ma, Shuai; Ma, Tianxiao; Shan, Lei; Wang, Xiao; Nie, Yonggang; Ning, Zemin; Yan, Li; Xiu, Yunfang; Wei, Fuwen

2017-01-31

Phenotypic convergence between distantly related taxa often mirrors adaptation to similar selective pressures and may be driven by genetic convergence. The giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens) belong to different families in the order Carnivora, but both have evolved a specialized bamboo diet and adaptive pseudothumb, representing a classic model of convergent evolution. However, the genetic bases of these morphological and physiological convergences remain unknown. Through de novo sequencing the red panda genome and improving the giant panda genome assembly with added data, we identified genomic signatures of convergent evolution. Limb development genes DYNC2H1 and PCNT have undergone adaptive convergence and may be important candidate genes for pseudothumb development. As evolutionary responses to a bamboo diet, adaptive convergence has occurred in genes involved in the digestion and utilization of bamboo nutrients such as essential amino acids, fatty acids, and vitamins. Similarly, the umami taste receptor gene TAS1R1 has been pseudogenized in both pandas. These findings offer insights into genetic convergence mechanisms underlying phenotypic convergence and adaptation to a specialized bamboo diet.

Comparative genomics reveals convergent evolution between the bamboo-eating giant and red pandas

PubMed Central

Hu, Yibo; Wu, Qi; Ma, Shuai; Ma, Tianxiao; Shan, Lei; Wang, Xiao; Nie, Yonggang; Ning, Zemin; Yan, Li; Xiu, Yunfang; Wei, Fuwen

2017-01-01

Phenotypic convergence between distantly related taxa often mirrors adaptation to similar selective pressures and may be driven by genetic convergence. The giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens) belong to different families in the order Carnivora, but both have evolved a specialized bamboo diet and adaptive pseudothumb, representing a classic model of convergent evolution. However, the genetic bases of these morphological and physiological convergences remain unknown. Through de novo sequencing the red panda genome and improving the giant panda genome assembly with added data, we identified genomic signatures of convergent evolution. Limb development genes DYNC2H1 and PCNT have undergone adaptive convergence and may be important candidate genes for pseudothumb development. As evolutionary responses to a bamboo diet, adaptive convergence has occurred in genes involved in the digestion and utilization of bamboo nutrients such as essential amino acids, fatty acids, and vitamins. Similarly, the umami taste receptor gene TAS1R1 has been pseudogenized in both pandas. These findings offer insights into genetic convergence mechanisms underlying phenotypic convergence and adaptation to a specialized bamboo diet. PMID:28096377

Seasonal variation in denitrification and dissimilatory nitrate reduction to ammonia process rates and corresponding key functional genes along an estuarine nitrate gradient

PubMed Central

Smith, Cindy J.; Dong, Liang F.; Wilson, John; Stott, Andrew; Osborn, A. Mark; Nedwell, David B.

2015-01-01

This research investigated spatial-temporal variation in benthic bacterial community structure, rates of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) processes and abundances of corresponding genes and transcripts at three sites—the estuary-head, mid-estuary and the estuary mouth (EM) along the nitrate gradient of the Colne estuary over an annual cycle. Denitrification rates declined down the estuary, while DNRA rates were higher at the estuary head and middle than the EM. In four out of the six 2-monthly time-points, rates of DNRA were greater than denitrification at each site. Abundance of gene markers for nitrate-reduction (nitrate reductase narG and napA), denitrification (nitrite reductase nirS) and DNRA (DNRA nitrite reductase nrfA) declined along the estuary with significant relationships between denitrification and nirS abundance, and DNRA and nrfA abundance. Spatially, rates of denitrification, DNRA and corresponding functional gene abundances decreased along the estuary. However, temporal correlations between rate processes and functional gene and transcript abundances were not observed. PMID:26082763

Temporal Hierarchy of Gene Expression Mediated by Transcription Factor Binding Affinity and Activation Dynamics

PubMed Central

Gao, Rong

2015-01-01

ABSTRACT Understanding cellular responses to environmental stimuli requires not only the knowledge of specific regulatory components but also the quantitative characterization of the magnitude and timing of regulatory events. The two-component system is one of the major prokaryotic signaling schemes and is the focus of extensive interest in quantitative modeling and investigation of signaling dynamics. Here we report how the binding affinity of the PhoB two-component response regulator (RR) to target promoters impacts the level and timing of expression of PhoB-regulated genes. Information content has often been used to assess the degree of conservation for transcription factor (TF)-binding sites. We show that increasing the information content of PhoB-binding sites in designed phoA promoters increased the binding affinity and that the binding affinity and concentration of phosphorylated PhoB (PhoB~P) together dictate the level and timing of expression of phoA promoter variants. For various PhoB-regulated promoters with distinct promoter architectures, expression levels appear not to be correlated with TF-binding affinities, in contrast to the intuitive and oversimplified assumption that promoters with higher affinity for a TF tend to have higher expression levels. However, the expression timing of the core set of PhoB-regulated genes correlates well with the binding affinity of PhoB~P to individual promoters and the temporal hierarchy of gene expression appears to be related to the function of gene products during the phosphate starvation response. Modulation of the information content and binding affinity of TF-binding sites may be a common strategy for temporal programming of the expression profile of RR-regulated genes. PMID:26015501

Spatial and Temporal Comparison of DNRA Communities in New River Estuary, USA

NASA Astrophysics Data System (ADS)

Song, B.; Lisa, J.; Tobias, C. R.

2016-02-01

Dissimilatory nitrate reduction to ammonium (DNRA) is an important nitrate respiring pathway, competing with denitrification, in various ecosystems. Studies examining the diversity and composition of DNRA communities are limited and their link to DNRA activity is unknown. We conducted a multidisciplinary investigation of sediment communities in the upper reaches of a eutrophic estuary to examine spatial and temporal variation of DNRA community structures and determine their linkage to activities. Sediment samples were collected seasonally from two study sites (AA2 and JAX) in the New River Estuary, North Carolina, USA. 15N-nitrate tracer experiments were conducted to measure potential DNRA rates while abundance of DNRA communities was measured using quantitative PCR of cytochrome C nitrite reductase genes (nrfA). Composition and diversity of DNRA communities were also examined based on next generation sequencing (NGS) of nrfA genes using an Ion Torrent PGM. Bioinformatic analysis was conducted using the FunGene pipeline and Mothur program. Higher DNRA activities were measured at JAX and associated with higher abundance of nrfA genes. Seasonal variation in DNRA rates and nrfA gene abundance was more evident at JAX than AA2. Nitrate concentration and dissolved oxygen in bottom water were significantly and positively correlated with activities and abundance of DNRA communities. The nrfA NGS analysis revealed that spatial variation of DNRA communities was much greater than temporal variation with salinity, dissolved organic carbon, and nitrate as the most important environmental variables affecting these communities. Diversity of DNRA communities was negative correlated with the DNRA rates and nrfA gene abundance, which suggests that dominant members of the DNRA community are responsible for higher rates. Thus, our multidisciplinary study clearly demonstrates the linkage between structure and activities of DNRA communities in the upper reaches of New River Estuary.

Reconstructing Cell Lineages from Single-Cell Gene Expression Data: A Pilot Study

DTIC Science & Technology

2016-08-30

Reconstructing cell lineages from single- cell gene expression data: a pilot study The goal of this pilot study is to develop novel mathematical...methods, by leveraging tools developed in the bifurcation theory, to infer the underlying cell -state dynamics from single- cell gene expression data. Our...proposed method contains two steps. The first step is to reconstruct the temporal order of the cells from gene expression data, whereas the second

PRODIGEN: visualizing the probability landscape of stochastic gene regulatory networks in state and time space.

PubMed

Ma, Chihua; Luciani, Timothy; Terebus, Anna; Liang, Jie; Marai, G Elisabeta

2017-02-15

Visualizing the complex probability landscape of stochastic gene regulatory networks can further biologists' understanding of phenotypic behavior associated with specific genes. We present PRODIGEN (PRObability DIstribution of GEne Networks), a web-based visual analysis tool for the systematic exploration of probability distributions over simulation time and state space in such networks. PRODIGEN was designed in collaboration with bioinformaticians who research stochastic gene networks. The analysis tool combines in a novel way existing, expanded, and new visual encodings to capture the time-varying characteristics of probability distributions: spaghetti plots over one dimensional projection, heatmaps of distributions over 2D projections, enhanced with overlaid time curves to display temporal changes, and novel individual glyphs of state information corresponding to particular peaks. We demonstrate the effectiveness of the tool through two case studies on the computed probabilistic landscape of a gene regulatory network and of a toggle-switch network. Domain expert feedback indicates that our visual approach can help biologists: 1) visualize probabilities of stable states, 2) explore the temporal probability distributions, and 3) discover small peaks in the probability landscape that have potential relation to specific diseases.

Signal transduction in the wound response of tomato plants.

PubMed Central

Bowles, D

1998-01-01

The wound response of tomato plants has been extensively studied, and provides a useful model to understand signal transduction events leading from injury to marker gene expression. The principal markers that have been used in these studies are genes encoding proteinase inhibitor (pin) proteins. Activation of pin genes occurs in the wounded leaf and in distant unwounded leaves of the plant. This paper reviews current understanding of signalling pathways in the wounded leaf, and in the systemically responding unwounded leaves. First, the nature of known elicitors and their potential roles in planta are discussed, in particular, oligogalacturonides, jasmonates and the peptide signal, systemin. Inhibitors of wound-induced proteinase inhibitor (pin) expression are also reviewed, with particular reference to phenolics, sulphydryl reagents and fusicoccin. In each section, results obtained from the bioassay are considered within the wider context of data from mutants and from transgenic plants with altered levels of putative signalling components. Following this introduction, current models for pin gene regulation are described and discussed, together with a summary for the involvement of phosphorylation-dephosphorylation in wound signalling. Finally, a new model for wound-induced pin gene expression is presented, arising from recent data from the author's laboratory. PMID:9800210

Inference of Expanded Lrp-Like Feast/Famine Transcription Factor Targets in a Non-Model Organism Using Protein Structure-Based Prediction

PubMed Central

Ashworth, Justin; Plaisier, Christopher L.; Lo, Fang Yin; Reiss, David J.; Baliga, Nitin S.

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer. PMID:25255272

Inference of expanded Lrp-like feast/famine transcription factor targets in a non-model organism using protein structure-based prediction.

PubMed

Ashworth, Justin; Plaisier, Christopher L; Lo, Fang Yin; Reiss, David J; Baliga, Nitin S

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer.

Plants transformed with a tobacco mosaic virus nonstructural gene sequence are resistant to the virus.

PubMed Central

Golemboski, D B; Lomonossoff, G P; Zaitlin, M

1990-01-01

Nicotiana tabacum cv. Xanthi nn plants were transformed with nucleotides 3472-4916 of tobacco mosaic virus (TMV) strain U1. This sequence contains all but the three 3 terminal nucleotides of the TMV 54-kDa gene, which encodes a putative component of the replicase complex. These plants were resistant to infection when challenged with either TMV U1 virions or TMV U1 RNA at concentrations of up to 500 micrograms/ml or 300 micrograms/ml, respectively, the highest concentrations tested. Resistance was also exhibited when plants were inoculated at 100 micrograms/ml with the closely related TMV mutant YSI/1 but was not shown in plants challenged at the same concentrations with the more distantly related TMV strains U2 or L or cucumber mosaic virus. Although the copy number of the 54-kDa gene sequence varied in individual transformants from 1 to approximately 5, the level of resistance in plants was not dependent on the number of copies of the 54-kDa gene sequence integrated. The transformed plants accumulated a 54-kDa gene sequence-specific RNA transcript of the expected size, but no protein product was detected. Images PMID:2385595

The expression of embryonic primary mesenchyme genes of the sea urchin, Strongylocentrotus purpuratus, in the adult skeletogenic tissues of this and other species of echinoderms.

PubMed

Drager, B J; Harkey, M A; Iwata, M; Whiteley, A H

1989-05-01

Adult tissues of the sea urchin, Strongylocentrotus purpuratus, were analyzed for the products of a set of genes whose expression, in the embryo, is restricted to the skeletogenic primary mesenchyme (PM). Three embryonic PM-specific mRNAs were found to be abundant in adult skeletal tissues (test and lantern), but not in a variety of soft tissues. Homologous mRNAs were also found in skeletal tissues of the congeneric sea urchin, S. droebachiensis, as well as a more distantly related echinoid, Dendraster excentricus, and an asteroid, Evasterias troschellii. The distributions of two of these RNAs were analyzed in regenerating spines of adult S. purpuratus using in situ hybridization. These gene products were localized primarily in the calcoblasts that accumulated at the regeneration site. In nonregenerating spines SpLM 18 RNAs, the most abundant of these gene products, were localized in a small population of noncalcoblast cells scattered through the spine shaft, and were absent from calcoblasts. These observations suggest that a program of gene expression associated with the process of calcification is conserved both developmentally through the period of metamorphosis and evolutionarily among the echinoderms.

Personalized therapeutic strategies for patients with retinitis pigmentosa.

PubMed

Zheng, Andrew; Li, Yao; Tsang, Stephen H

2015-03-01

Retinitis pigmentosa (RP) encompasses many different hereditary retinal degenerations that are caused by a vast array of different gene mutations and have highly variable disease presentations and severities. This heterogeneity poses a significant therapeutic challenge, although an answer may eventually be found through two recent innovations: induced pluripotent stem cells (iPSCs) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome editing. This review discusses the wide-ranging applications of iPSCs and CRISPR-including disease modelling, diagnostics and therapeutics - with an ultimate view towards understanding how these two technologies can come together to address disease heterogeneity and orphan genes in a novel personalized medicine platform. An extensive literature search was conducted in PubMed and Google Scholar, with a particular focus on high-impact research published within the last 1 - 2 years and centered broadly on the subjects of retinal gene therapy, iPSC-derived outer retina cells, stem cell transplantation and CRISPR/Cas gene editing. For the retinal pigment epithelium, autologous transplantation of gene-corrected grafts derived from iPSCs may well be technically feasible in the near future. Photoreceptor transplantation faces more significant unresolved technical challenges but remains an achievable, if more distant, goal given the rapid pace of advancements in the field.

Order Under Uncertainty: Robust Differential Expression Analysis Using Probabilistic Models for Pseudotime Inference

PubMed Central

Campbell, Kieran R.

2016-01-01

Single cell gene expression profiling can be used to quantify transcriptional dynamics in temporal processes, such as cell differentiation, using computational methods to label each cell with a ‘pseudotime’ where true time series experimentation is too difficult to perform. However, owing to the high variability in gene expression between individual cells, there is an inherent uncertainty in the precise temporal ordering of the cells. Pre-existing methods for pseudotime estimation have predominantly given point estimates precluding a rigorous analysis of the implications of uncertainty. We use probabilistic modelling techniques to quantify pseudotime uncertainty and propagate this into downstream differential expression analysis. We demonstrate that reliance on a point estimate of pseudotime can lead to inflated false discovery rates and that probabilistic approaches provide greater robustness and measures of the temporal resolution that can be obtained from pseudotime inference. PMID:27870852

High temporal-resolution view of transcription and chromatin states across distinct metabolic states in budding yeast

PubMed Central

Kuang, Zheng; Cai, Ling; Zhang, Xuekui; Ji, Hongkai; Tu, Benjamin P.; Boeke, Jef D.

2014-01-01

Under continuous, glucose-limited conditions, budding yeast exhibit robust metabolic cycles associated with major oscillations of gene expression. How such fluctuations are linked to changes in chromatin status is not well understood. Here we examine the correlated genome-wide transcription and chromatin states across the yeast metabolic cycle at unprecedented temporal resolution, revealing a “just-in-time supply chain” by which components from specific cellular processes such as ribosome biogenesis become available in a highly coordinated manner. We identify distinct chromatin and splicing patterns associated with different gene categories and determine the relative timing of chromatin modifications to maximal transcription. There is unexpected variation in the chromatin modification and expression relationship, with histone acetylation peaks occurring with varying timing and “sharpness” relative to RNA expression both within and between cycle phases. Chromatin modifier occupancy reveals subtly distinct spatial and temporal patterns compared to the modifications themselves. PMID:25173176

Insights into the degradation capacities of Amycolatopsis tucumanensis DSM 45259 guided by microarray data.

PubMed

Bourguignon, Natalia; Bargiela, Rafael; Rojo, David; Chernikova, Tatyana N; de Rodas, Sara A López; García-Cantalejo, Jesús; Näther, Daniela J; Golyshin, Peter N; Barbas, Coral; Ferrero, Marcela; Ferrer, Manuel

2016-12-01

The analysis of catabolic capacities of microorganisms is currently often achieved by cultivation approaches and by the analysis of genomic or metagenomic datasets. Recently, a microarray system designed from curated key aromatic catabolic gene families and key alkane degradation genes was designed. The collection of genes in the microarray can be exploited to indicate whether a given microbe or microbial community is likely to be functionally connected with certain degradative phenotypes, without previous knowledge of genome data. Herein, this microarray was applied to capture new insights into the catabolic capacities of copper-resistant actinomycete Amycolatopsis tucumanensis DSM 45259. The array data support the presumptive ability of the DSM 45259 strain to utilize single alkanes (n-decane and n-tetradecane) and aromatics such as benzoate, phthalate and phenol as sole carbon sources, which was experimentally validated by cultivation and mass spectrometry. Interestingly, while in strain DSM 45259 alkB gene encoding an alkane hydroxylase is most likely highly similar to that found in other actinomycetes, the genes encoding benzoate 1,2-dioxygenase, phthalate 4,5-dioxygenase and phenol hydroxylase were homologous to proteobacterial genes. This suggests that strain DSM 45259 contains catabolic genes distantly related to those found in other actinomycetes. Together, this study not only provided new insight into the catabolic abilities of strain DSM 45259, but also suggests that this strain contains genes uncommon within actinomycetes.

Genetic Determinants Influencing Human Serum Metabolome among African Americans

PubMed Central

Yu, Bing; Zheng, Yan; Alexander, Danny; Morrison, Alanna C.; Coresh, Josef; Boerwinkle, Eric

2014-01-01

Phenotypes proximal to gene action generally reflect larger genetic effect sizes than those that are distant. The human metabolome, a result of multiple cellular and biological processes, are functional intermediate phenotypes proximal to gene action. Here, we present a genome-wide association study of 308 untargeted metabolite levels among African Americans from the Atherosclerosis Risk in Communities (ARIC) Study. Nineteen significant common variant-metabolite associations were identified, including 13 novel loci (p<1.6×10−10). These loci were associated with 7–50% of the difference in metabolite levels per allele, and the variance explained ranged from 4% to 20%. Fourteen genes were identified within the nineteen loci, and four of them contained non-synonymous substitutions in four enzyme-encoding genes (KLKB1, SIAE, CPS1, and NAT8); the other significant loci consist of eight other enzyme-encoding genes (ACE, GATM, ACY3, ACSM2B, THEM4, ADH4, UGT1A, TREH), a transporter gene (SLC6A13) and a polycystin protein gene (PKD2L1). In addition, four potential disease-associated paths were identified, including two direct longitudinal predictive relationships: NAT8 with N-acetylornithine, N-acetyl-1-methylhistidine and incident chronic kidney disease, and TREH with trehalose and incident diabetes. These results highlight the value of using endophenotypes proximal to gene function to discover new insights into biology and disease pathology. PMID:24625756

Pseudotyped Lentiviral Vectors for Retrograde Gene Delivery into Target Brain Regions

PubMed Central

Kobayashi, Kenta; Inoue, Ken-ichi; Tanabe, Soshi; Kato, Shigeki; Takada, Masahiko; Kobayashi, Kazuto

2017-01-01

Gene transfer through retrograde axonal transport of viral vectors offers a substantial advantage for analyzing roles of specific neuronal pathways or cell types forming complex neural networks. This genetic approach may also be useful in gene therapy trials by enabling delivery of transgenes into a target brain region distant from the injection site of the vectors. Pseudotyping of a lentiviral vector based on human immunodeficiency virus type 1 (HIV-1) with various fusion envelope glycoproteins composed of different combinations of rabies virus glycoprotein (RV-G) and vesicular stomatitis virus glycoprotein (VSV-G) enhances the efficiency of retrograde gene transfer in both rodent and nonhuman primate brains. The most recently developed lentiviral vector is a pseudotype with fusion glycoprotein type E (FuG-E), which demonstrates highly efficient retrograde gene transfer in the brain. The FuG-E–pseudotyped vector permits powerful experimental strategies for more precisely investigating the mechanisms underlying various brain functions. It also contributes to the development of new gene therapy approaches for neurodegenerative disorders, such as Parkinson’s disease, by delivering genes required for survival and protection into specific neuronal populations. In this review article, we report the properties of the FuG-E–pseudotyped vector, and we describe the application of the vector to neural circuit analysis and the potential use of the FuG-E vector in gene therapy for Parkinson’s disease. PMID:28824385

Genetic variability in captive populations of the stingless bee Tetragonisca angustula.

PubMed

Santiago, Leandro R; Francisco, Flávio O; Jaffé, Rodolfo; Arias, Maria C

2016-08-01

Low genetic variability has normally been considered a consequence of animal husbandry and a major contributing factor to declining bee populations. Here, we performed a molecular analysis of captive and wild populations of the stingless bee Tetragonisca angustula, one of the most commonly kept species across South America. Microsatellite analyses showed similar genetic variability between wild and captive populations However, captive populations showed lower mitochondrial genetic variability. Male-mediated gene flow, transport and division of nests are suggested as the most probable explanations for the observed patterns of genetic structure. We conclude that increasing the number of colonies kept through nest divisions does not negatively affect nuclear genetic variability, which seems to be maintained by small-scale male dispersal and human-mediated nest transport. However, the transport of nests from distant localities should be practiced with caution given the high genetic differentiation observed between samples from western and eastern areas. The high genetic structure verified is the result of a long-term evolutionary process, and bees from distant localities may represent unique evolutionary lineages.

Sex differences in cortical thickness and their possible genetic and sex hormonal underpinnings.

PubMed

Savic, I; Arver, S

2014-12-01

Although it has been shown that cortical thickness (Cth) differs between sexes, the underlying mechanisms are unknown. Seeing as XXY males have 1 extra X chromosome, we investigated the possible effects of X- and sex-chromosome dosage on Cth by comparing data from 31 XXY males with 39 XY and 47 XX controls. Plasma testosterone and estrogen were also measured in an effort to differentiate between possible sex-hormone and sex-chromosome gene effects. Cth was calculated with FreeSurfer software. Parietal and occipital Cth was greater in XX females than XY males. In these regions Cth was inversely correlated with z-normalized testosterone. In the motor strip, the cortex was thinner in XY males compared with both XX females and XXY males, indicating the possibility of an X-chromosome gene-dosage effect. XXY males had thinner right superior temporal and left middle temporal cortex, and a thicker right orbitofrontal cortex and lingual cortex than both control groups. Based on these data and previous reports from women with XO monosomy, it is hypothesized that programming of the motor cortex is influenced by processes linked to X-escapee genes, which do not have Y-chromosome homologs, and that programming of the superior temporal cortex is mediated by X-chromosome escapee genes with Y-homologs. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Co-Option and De Novo Gene Evolution Underlie Molluscan Shell Diversity

PubMed Central

Aguilera, Felipe; McDougall, Carmel

2017-01-01

Abstract Molluscs fabricate shells of incredible diversity and complexity by localized secretions from the dorsal epithelium of the mantle. Although distantly related molluscs express remarkably different secreted gene products, it remains unclear if the evolution of shell structure and pattern is underpinned by the differential co-option of conserved genes or the integration of lineage-specific genes into the mantle regulatory program. To address this, we compare the mantle transcriptomes of 11 bivalves and gastropods of varying relatedness. We find that each species, including four Pinctada (pearl oyster) species that diverged within the last 20 Ma, expresses a unique mantle secretome. Lineage- or species-specific genes comprise a large proportion of each species’ mantle secretome. A majority of these secreted proteins have unique domain architectures that include repetitive, low complexity domains (RLCDs), which evolve rapidly, and have a proclivity to expand, contract and rearrange in the genome. There are also a large number of secretome genes expressed in the mantle that arose before the origin of gastropods and bivalves. Each species expresses a unique set of these more ancient genes consistent with their independent co-option into these mantle gene regulatory networks. From this analysis, we infer lineage-specific secretomes underlie shell diversity, and include both rapidly evolving RLCD-containing proteins, and the continual recruitment and loss of both ancient and recently evolved genes into the periphery of the regulatory network controlling gene expression in the mantle epithelium. PMID:28053006

The Methanol Dehydrogenase Gene, mxaF, as a Functional and Phylogenetic Marker for Proteobacterial Methanotrophs in Natural Environments

PubMed Central

Lau, Evan; Fisher, Meredith C.; Steudler, Paul A.; Cavanaugh, Colleen M.

2013-01-01

The mxaF gene, coding for the large (α) subunit of methanol dehydrogenase, is highly conserved among distantly related methylotrophic species in the Alpha-, Beta- and Gammaproteobacteria. It is ubiquitous in methanotrophs, in contrast to other methanotroph-specific genes such as the pmoA and mmoX genes, which are absent in some methanotrophic proteobacterial genera. This study examined the potential for using the mxaF gene as a functional and phylogenetic marker for methanotrophs. mxaF and 16S rRNA gene phylogenies were constructed based on over 100 database sequences of known proteobacterial methanotrophs and other methylotrophs to assess their evolutionary histories. Topology tests revealed that mxaF and 16S rDNA genes of methanotrophs do not show congruent evolutionary histories, with incongruencies in methanotrophic taxa in the Methylococcaceae, Methylocystaceae, and Beijerinckiacea. However, known methanotrophs generally formed coherent clades based on mxaF gene sequences, allowing for phylogenetic discrimination of major taxa. This feature highlights the mxaF gene’s usefulness as a biomarker in studying the molecular diversity of proteobacterial methanotrophs in nature. To verify this, PCR-directed assays targeting this gene were used to detect novel methanotrophs from diverse environments including soil, peatland, hydrothermal vent mussel tissues, and methanotroph isolates. The placement of the majority of environmental mxaF gene sequences in distinct methanotroph-specific clades (Methylocystaceae and Methylococcaceae) detected in this study supports the use of mxaF as a biomarker for methanotrophic proteobacteria. PMID:23451130

Recent Emergence and Spread of an Arctic-Related Phylogenetic Lineage of Rabies Virus in Nepal

PubMed Central

Pant, Ganesh R.; Lavenir, Rachel; Wong, Frank Y. K.; Certoma, Andrea; Larrous, Florence; Bhatta, Dwij R.; Bourhy, Hervé

2013-01-01

Rabies is a zoonotic disease that is endemic in many parts of the developing world, especially in Africa and Asia. However its epidemiology remains largely unappreciated in much of these regions, such as in Nepal, where limited information is available about the spatiotemporal dynamics of the main etiological agent, the rabies virus (RABV). In this study, we describe for the first time the phylogenetic diversity and evolution of RABV circulating in Nepal, as well as their geographical relationships within the broader region. A total of 24 new isolates obtained from Nepal and collected from 2003 to 2011 were full-length sequenced for both the nucleoprotein and the glycoprotein genes, and analysed using neighbour-joining and maximum-likelihood phylogenetic methods with representative viruses from all over the world, including new related RABV strains from neighbouring or more distant countries (Afghanistan, Greenland, Iran, Russia and USA). Despite Nepal's limited land surface and its particular geographical position within the Indian subcontinent, our study revealed the presence of a surprising wide genetic diversity of RABV, with the co-existence of three different phylogenetic groups: an Indian subcontinent clade and two different Arctic-like sub-clades within the Arctic-related clade. This observation suggests at least two independent episodes of rabies introduction from neighbouring countries. In addition, specific phylogenetic and temporal evolution analysis of viruses within the Arctic-related clade has identified a new recently emerged RABV lineage we named as the Arctic-like 3 (AL-3) sub-clade that is already widely spread in Nepal. PMID:24278494

RNA silencing in the life cycle of soybean: multiple restriction systems and spatiotemporal variation associated with plant architecture.

PubMed

Mori, Ayumi; Sato, Hiroshi; Kasai, Megumi; Yamada, Tetsuya; Kanazawa, Akira

2017-06-01

The expression of transgenes introduced into a plant genome is sometimes suppressed by RNA silencing. Although local and systemic spread of RNA silencing have been studied, little is known about the mechanisms underlying spatial and temporal variation in transgene silencing between individual plants or between plants of different generations, which occurs seemingly stochastically. Here, we analyzed the occurrence, spread, and transmission of RNA silencing of the green fluorescent protein (GFP) gene over multiple generations of the progeny of a single soybean transformant. Observation of GFP fluorescence in entire plants of the T 3 -T 5 generations indicated that the initiation and subsequent spread of GFP silencing varied between individuals, although this GFP silencing most frequently began in the primary leaves. In addition, GFP silencing could spread into the outer layer of seed coat tissues but was hardly detectable in the embryos. These results are consistent with the notion that transgene silencing involves its reset during reproductive phase, initiation after germination, and systemic spread in each generation. GFP silencing was absent in the pulvinus, suggesting that its cortical cells inhibit cell-to-cell spread or induction of RNA silencing. The extent of GFP silencing could differ between the stem and a petiole or between petiolules, which have limited vascular bundles connecting them and thus deter long-distant movement of silencing. Taken together, these observations indicate that the initiation and/or spread of RNA silencing depend on specific features of the architecture of the plant in addition to the mechanisms that can be conserved in higher plants.

Phylogenetic relationships among anuran trypanosomes as revealed by riboprinting.

PubMed

Clark, C G; Martin, D S; Diamond, L S

1995-01-01

Twenty trypanosome isolates from Anura (frogs and toads) assigned to several species were characterized by riboprinting-restriction enzyme digestion of polymerase chain reaction amplified small subunit ribosomal RNA genes. Restriction site polymorphisms allowed distinction of all the recognized species and no intraspecific variation in riboprint patterns was detected. Phylogenetic reconstruction using parsimony and distance estimates based on restriction fragment comigration showed Trypanosoma chattoni to be only distantly related to the other species, while T. ranarum and T. fallisi appear to be sister taxa despite showing non-overlapping host specificities.

A meiotic gene regulatory cascade driven by alternative fates for newly synthesized transcripts

PubMed Central

Cremona, Nicole; Potter, Kristine; Wise, Jo Ann

2011-01-01

To determine the relative importance of transcriptional regulation versus RNA processing and turnover during the transition from proliferation to meiotic differentiation in the fission yeast Schizosaccharomyces pombe, we analyzed temporal profiles and effects of RNA surveillance factor mutants on expression of 32 meiotic genes. A comparison of nascent transcription with steady-state RNA accumulation reveals that the vast majority of these genes show a lag between maximal RNA synthesis and peak RNA accumulation. During meiosis, total RNA levels parallel 3′ processing, which occurs in multiple, temporally distinct waves that peak from 3 to 6 h after meiotic induction. Most early genes and one middle gene, mei4, share a regulatory mechanism in which a specialized RNA surveillance factor targets newly synthesized transcripts for destruction. Mei4p, a member of the forkhead transcription factor family, in turn regulates a host of downstream genes. Remarkably, a spike in transcription is observed for less than one-third of the genes surveyed, and even these show evidence of RNA-level regulation. In aggregate, our findings lead us to propose that a regulatory cascade driven by changes in processing and stability of newly synthesized transcripts operates alongside the well-known transcriptional cascade as fission yeast cells enter meiosis. PMID:21148298

Analysis of the GRNs Inference by Using Tsallis Entropy and a Feature Selection Approach

NASA Astrophysics Data System (ADS)

Lopes, Fabrício M.; de Oliveira, Evaldo A.; Cesar, Roberto M.

An important problem in the bioinformatics field is to understand how genes are regulated and interact through gene networks. This knowledge can be helpful for many applications, such as disease treatment design and drugs creation purposes. For this reason, it is very important to uncover the functional relationship among genes and then to construct the gene regulatory network (GRN) from temporal expression data. However, this task usually involves data with a large number of variables and small number of observations. In this way, there is a strong motivation to use pattern recognition and dimensionality reduction approaches. In particular, feature selection is specially important in order to select the most important predictor genes that can explain some phenomena associated with the target genes. This work presents a first study about the sensibility of entropy methods regarding the entropy functional form, applied to the problem of topology recovery of GRNs. The generalized entropy proposed by Tsallis is used to study this sensibility. The inference process is based on a feature selection approach, which is applied to simulated temporal expression data generated by an artificial gene network (AGN) model. The inferred GRNs are validated in terms of global network measures. Some interesting conclusions can be drawn from the experimental results, as reported for the first time in the present paper.

Stress induced gene expression drives transient DNA methylation changes at adjacent repetitive elements.

PubMed

Secco, David; Wang, Chuang; Shou, Huixia; Schultz, Matthew D; Chiarenza, Serge; Nussaume, Laurent; Ecker, Joseph R; Whelan, James; Lister, Ryan

2015-07-21

Cytosine DNA methylation (mC) is a genome modification that can regulate the expression of coding and non-coding genetic elements. However, little is known about the involvement of mC in response to environmental cues. Using whole genome bisulfite sequencing to assess the spatio-temporal dynamics of mC in rice grown under phosphate starvation and recovery conditions, we identified widespread phosphate starvation-induced changes in mC, preferentially localized in transposable elements (TEs) close to highly induced genes. These changes in mC occurred after changes in nearby gene transcription, were mostly DCL3a-independent, and could partially be propagated through mitosis, however no evidence of meiotic transmission was observed. Similar analyses performed in Arabidopsis revealed a very limited effect of phosphate starvation on mC, suggesting a species-specific mechanism. Overall, this suggests that TEs in proximity to environmentally induced genes are silenced via hypermethylation, and establishes the temporal hierarchy of transcriptional and epigenomic changes in response to stress.

A high resolution spatiotemporal atlas of gene expression of the developing mouse brain

PubMed Central

Thompson, Carol L.; Ng, Lydia; Menon, Vilas; Martinez, Salvador; Lee, Chang-Kyu; Glattfelder, Katie; Sunkin, Susan M.; Henry, Alex; Lau, Christopher; Dang, Chinh; Garcia-Lopez, Raquel; Martinez-Ferre, Almudena; Pombero, Ana; Rubenstein, John L.R.; Wakeman, Wayne B.; Hohmann, John; Dee, Nick; Sodt, Andrew J.; Young, Rob; Smith, Kimberly; Nguyen, Thuc-Nghi; Kidney, Jolene; Kuan, Leonard; Jeromin, Andreas; Kaykas, Ajamete; Miller, Jeremy; Page, Damon; Orta, Geri; Bernard, Amy; Riley, Zackery; Smith, Simon; Wohnoutka, Paul; Hawrylycz, Mike; Puelles, Luis; Jones, Allan R.

2015-01-01

SUMMARY To provide a temporal framework for the genoarchitecture of brain development, in situ hybridization data were generated for embryonic and postnatal mouse brain at 7 developmental stages for ~2100 genes, processed with an automated informatics pipeline and manually annotated. This resource comprises 434,946 images, 7 reference atlases, an ontogenetic ontology, and tools to explore co-expression of genes across neurodevelopment. Gene sets coinciding with developmental phenomena were identified. A temporal shift in the principles governing the molecular organization of the brain was detected, with transient neuromeric, plate-based organization of the brain present at E11.5 and E13.5. Finally, these data provided a transcription factor code that discriminates brain structures and identifies the developmental age of a tissue, providing a foundation for eventual genetic manipulation or tracking of specific brain structures over development. The resource is available as the Allen Developing Mouse Brain Atlas (developingmouse.brain-map.org). PMID:24952961

Mono-2-ethylhexyl phthalate disrupts neurulation and modifies the embryonic redox environment and gene expression

PubMed Central

Sant, Karilyn E.; Dolinoy, Dana C.; Jilek, Joseph L.; Sartor, Maureen A.; Harris, Craig

2016-01-01

Mono-2-ethylhexl phthalate (MEHP) is the primary metabolite of di-2-ethylhexyl phthalate (DEHP), a ubiquitous contaminant in plastics. This study sought to determine how structural defects caused by MEHP in mouse whole embryo culture were related to temporal and spatial patterns of redox state and gene expression. MEHP reduced morphology scores along with increased incidence of neural tube defects. Glutathione (GSH) and cysteine (Cys) concentrations fluctuated spatially and temporally in embryo (EMB) and visceral yolk sac (VYS) across the 24h culture. Redox potentials (Eh) for GSSG/GSH were increased by MEHP in EMB (12h) but not in VYS. CySS/CyS Eh in EMB and VYS were significantly increased at 3h and 24h, respectively. Gene expression at 6h showed that MEHP induced selective alterations in EMB and VYS for oxidative phosphorylation and energy metabolism pathways. Overall, MEHP affects neurulation, alters Eh, and spatially alters the expression of metabolic genes in the early organogenesis-stage mouse conceptus. PMID:27167697

Reciprocal Expression of lin-41 and the microRNAs let-7 and mir-125 During Mouse Embryogenesis

PubMed Central

Schulman, Betsy R. Maller; Esquela-Kerscher, Aurora; Slack, Frank J.

2008-01-01

In C. elegans, heterochronic genes control the timing of cell fate determination during development. Two heterochronic genes, let-7 and lin-4, encode microRNAs (miRNAs) that down-regulate a third heterochronic gene lin-41 by binding to complementary sites in its 3’UTR. let-7 and lin-4 are conserved in mammals. Here we report the cloning and sequencing of mammalian lin-41 orthologs. We find that mouse and human lin-41 genes contain predicted conserved complementary sites for let-7 and the lin-4 ortholog, mir-125, in their 3’UTRs. Mouse lin-41 (Mlin-41) is temporally expressed in developing mouse embryos, most dramatically in the limb buds. Mlin-41 is down-regulated during mid-embryogenesis at the time when mouse let-7c and mir-125 RNA levels are up-regulated. Our results suggest that mammalian lin-41 is temporally regulated by miRNAs in order to direct key developmental events such as limb formation. PMID:16247770

Genetics of Temporal Lobe Epilepsy: A Review

PubMed Central

Salzmann, Annick; Malafosse, Alain

2012-01-01

Temporal lobe epilepsy (TLE) is usually regarded as a polygenic and complex disorder. To understand its genetic component, numerous linkage analyses of familial forms and association studies of cases versus controls have been conducted since the middle of the nineties. The present paper lists genetic findings for TLE from the initial segregation analysis to the most recent results published in May 2011. To date, no genes have been clearly related to TLE despite many efforts to do so. However, it is vital to continue replication studies and collaborative attempts to find significant results and thus determine which gene variant combination plays a definitive role in the aetiology of TLE. PMID:22957248

LateBiclustering: Efficient Heuristic Algorithm for Time-Lagged Bicluster Identification.

PubMed

Gonçalves, Joana P; Madeira, Sara C

2014-01-01

Identifying patterns in temporal data is key to uncover meaningful relationships in diverse domains, from stock trading to social interactions. Also of great interest are clinical and biological applications, namely monitoring patient response to treatment or characterizing activity at the molecular level. In biology, researchers seek to gain insight into gene functions and dynamics of biological processes, as well as potential perturbations of these leading to disease, through the study of patterns emerging from gene expression time series. Clustering can group genes exhibiting similar expression profiles, but focuses on global patterns denoting rather broad, unspecific responses. Biclustering reveals local patterns, which more naturally capture the intricate collaboration between biological players, particularly under a temporal setting. Despite the general biclustering formulation being NP-hard, considering specific properties of time series has led to efficient solutions for the discovery of temporally aligned patterns. Notably, the identification of biclusters with time-lagged patterns, suggestive of transcriptional cascades, remains a challenge due to the combinatorial explosion of delayed occurrences. Herein, we propose LateBiclustering, a sensible heuristic algorithm enabling a polynomial rather than exponential time solution for the problem. We show that it identifies meaningful time-lagged biclusters relevant to the response of Saccharomyces cerevisiae to heat stress.

Construction of mutant TKGFP for real-time imaging of temporal dynamics of HIF-1 signal transduction activity mediated by hypoxia and reoxygenation in tumors in living mice.

PubMed

Hsieh, Chia-Hung; Kuo, Jung-Wen; Lee, Yi-Jang; Chang, Chi-Wei; Gelovani, Juri G; Liu, Ren-Shyan

2009-12-01

The herpes simplex virus type 1 thymidine kinase (HSV1-tk)/green fluorescent protein (TKGFP) dual-reporter gene and a multimodality imaging approach play a critical role in monitoring therapeutic gene expression, immune cell trafficking, and protein-protein interactions in translational molecular-genetic imaging. However, the cytotoxicity and low temporal resolution of TKGFP limits its application in studies that require a rapid turnover of the reporter. The purpose of this study was to construct a novel mutant TKGFP fusion reporter gene with low cytotoxicity and high temporal resolution for use in the real-time monitoring of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor 1 (HIF-1) signal transduction activity mediated by hypoxia and reoxygenation in vitro and in vivo. Destabilized TKGFP was produced by inserting the nuclear export signal (NES) sequence at the N terminus and fusing the degradation domain of mouse ornithine decarboxylase (dMODC) at the C terminus. The stability of TKGFP in living NG4TL4 cells was determined by Western blot analysis, HSV1-tk enzyme activity assay, and flow cytometric analysis. The suitability of NESTKGFP:dMODC as a transcription reporter was investigated by linking it to a promoter consisting of 8 copies of hypoxia-responsive elements, whose activities depend on HIF-1. The dynamic transcriptional events mediated by hypoxia and reoxygenation were monitored by NESTKGFP:dMODC or TKGFP and determined by optical imaging and PET. Unlike TKGFP, NESTKGFP:dMODC was unstable in the presence of cycloheximide and showed a short half-life of protein and enzyme activity. Rapid turnover of NESTKGFP:dMODC occurred in a 26S proteasome-dependent manner. Furthermore, NESTKGFP:dMODC showed an upregulated expression and low cytotoxicity in living cells. Studies of hypoxia-responsive TKGFP and NESTKGFP:dMODC expression showed that NESTKGFP:dMODC as a reporter gene had better temporal resolution than did TKGFP for monitoring the dynamic transcriptional events mediated by hypoxia and reoxygenation; the TKGFP expression level was not optimal for the purpose of monitoring. In translational molecular-genetic imaging, NESTKGFP:dMODC as a reporter gene, together with optical imaging and PET, allows the direct monitoring of transcription induction and easy determination of its association with other biochemical changes.

Analysis of temporal gene expression profiles: clustering by simulated annealing and determining the optimal number of clusters.

PubMed

Lukashin, A V; Fuchs, R

2001-05-01

Cluster analysis of genome-wide expression data from DNA microarray hybridization studies has proved to be a useful tool for identifying biologically relevant groupings of genes and samples. In the present paper, we focus on several important issues related to clustering algorithms that have not yet been fully studied. We describe a simple and robust algorithm for the clustering of temporal gene expression profiles that is based on the simulated annealing procedure. In general, this algorithm guarantees to eventually find the globally optimal distribution of genes over clusters. We introduce an iterative scheme that serves to evaluate quantitatively the optimal number of clusters for each specific data set. The scheme is based on standard approaches used in regular statistical tests. The basic idea is to organize the search of the optimal number of clusters simultaneously with the optimization of the distribution of genes over clusters. The efficiency of the proposed algorithm has been evaluated by means of a reverse engineering experiment, that is, a situation in which the correct distribution of genes over clusters is known a priori. The employment of this statistically rigorous test has shown that our algorithm places greater than 90% genes into correct clusters. Finally, the algorithm has been tested on real gene expression data (expression changes during yeast cell cycle) for which the fundamental patterns of gene expression and the assignment of genes to clusters are well understood from numerous previous studies.

Multiway real-time PCR gene expression profiling in yeast Saccharomyces cerevisiae reveals altered transcriptional response of ADH-genes to glucose stimuli.

PubMed

Ståhlberg, Anders; Elbing, Karin; Andrade-Garda, José Manuel; Sjögreen, Björn; Forootan, Amin; Kubista, Mikael

2008-04-16

The large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity for powerful multivariate and multiway studies of biological phenomena. In multiway studies samples are characterized by their expression profiles to monitor changes over time, effect of treatment, drug dosage etc. Here we perform a multiway study of the temporal response of four yeast Saccharomyces cerevisiae strains with different glucose uptake rates upon altered metabolic conditions. We measured the expression of 18 genes as function of time after addition of glucose to four strains of yeast grown in ethanol. The data are analyzed by matrix-augmented PCA, which is a generalization of PCA for 3-way data, and the results are confirmed by hierarchical clustering and clustering by Kohonen self-organizing map. Our approach identifies gene groups that respond similarly to the change of nutrient, and genes that behave differently in mutant strains. Of particular interest is our finding that ADH4 and ADH6 show a behavior typical of glucose-induced genes, while ADH3 and ADH5 are repressed after glucose addition. Multiway real-time PCR gene expression profiling is a powerful technique which can be utilized to characterize functions of new genes by, for example, comparing their temporal response after perturbation in different genetic variants of the studied subject. The technique also identifies genes that show perturbed expression in specific strains.

Multiway real-time PCR gene expression profiling in yeast Saccharomyces cerevisiae reveals altered transcriptional response of ADH-genes to glucose stimuli

PubMed Central

Ståhlberg, Anders; Elbing, Karin; Andrade-Garda, José Manuel; Sjögreen, Björn; Forootan, Amin; Kubista, Mikael

2008-01-01

Background The large sensitivity, high reproducibility and essentially unlimited dynamic range of real-time PCR to measure gene expression in complex samples provides the opportunity for powerful multivariate and multiway studies of biological phenomena. In multiway studies samples are characterized by their expression profiles to monitor changes over time, effect of treatment, drug dosage etc. Here we perform a multiway study of the temporal response of four yeast Saccharomyces cerevisiae strains with different glucose uptake rates upon altered metabolic conditions. Results We measured the expression of 18 genes as function of time after addition of glucose to four strains of yeast grown in ethanol. The data are analyzed by matrix-augmented PCA, which is a generalization of PCA for 3-way data, and the results are confirmed by hierarchical clustering and clustering by Kohonen self-organizing map. Our approach identifies gene groups that respond similarly to the change of nutrient, and genes that behave differently in mutant strains. Of particular interest is our finding that ADH4 and ADH6 show a behavior typical of glucose-induced genes, while ADH3 and ADH5 are repressed after glucose addition. Conclusion Multiway real-time PCR gene expression profiling is a powerful technique which can be utilized to characterize functions of new genes by, for example, comparing their temporal response after perturbation in different genetic variants of the studied subject. The technique also identifies genes that show perturbed expression in specific strains. PMID:18412983

Evolutionary conservation of regulatory elements in vertebrate HOX gene clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santini, Simona; Boore, Jeffrey L.; Meyer, Axel

2003-12-31

Due to their high degree of conservation, comparisons of DNA sequences among evolutionarily distantly-related genomes permit to identify functional regions in noncoding DNA. Hox genes are optimal candidate sequences for comparative genome analyses, because they are extremely conserved in vertebrates and occur in clusters. We aligned (Pipmaker) the nucleotide sequences of HoxA clusters of tilapia, pufferfish, striped bass, zebrafish, horn shark, human and mouse (over 500 million years of evolutionary distance). We identified several highly conserved intergenic sequences, likely to be important in gene regulation. Only a few of these putative regulatory elements have been previously described as being involvedmore » in the regulation of Hox genes, while several others are new elements that might have regulatory functions. The majority of these newly identified putative regulatory elements contain short fragments that are almost completely conserved and are identical to known binding sites for regulatory proteins (Transfac). The conserved intergenic regions located between the most rostrally expressed genes in the developing embryo are longer and better retained through evolution. We document that presumed regulatory sequences are retained differentially in either A or A clusters resulting from a genome duplication in the fish lineage. This observation supports both the hypothesis that the conserved elements are involved in gene regulation and the Duplication-Deletion-Complementation model.« less

Molecular Diversity of Terpene Synthases in the Liverwort Marchantia polymorpha[OPEN

PubMed Central

Zhuang, Xun; Jiang, Zuodong; Jia, Qidong; Babbitt, Patricia C.

2016-01-01

Marchantia polymorpha is a basal terrestrial land plant, which like most liverworts accumulates structurally diverse terpenes believed to serve in deterring disease and herbivory. Previous studies have suggested that the mevalonate and methylerythritol phosphate pathways, present in evolutionarily diverged plants, are also operative in liverworts. However, the genes and enzymes responsible for the chemical diversity of terpenes have yet to be described. In this study, we resorted to a HMMER search tool to identify 17 putative terpene synthase genes from M. polymorpha transcriptomes. Functional characterization identified four diterpene synthase genes phylogenetically related to those found in diverged plants and nine rather unusual monoterpene and sesquiterpene synthase-like genes. The presence of separate monofunctional diterpene synthases for ent-copalyl diphosphate and ent-kaurene biosynthesis is similar to orthologs found in vascular plants, pushing the date of the underlying gene duplication and neofunctionalization of the ancestral diterpene synthase gene family to >400 million years ago. By contrast, the mono- and sesquiterpene synthases represent a distinct class of enzymes, not related to previously described plant terpene synthases and only distantly so to microbial-type terpene synthases. The absence of a Mg2+ binding, aspartate-rich, DDXXD motif places these enzymes in a noncanonical family of terpene synthases. PMID:27650333

Mapping cis-Regulatory Domains in the Human Genome UsingMulti-Species Conservation of Synteny

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahituv, Nadav; Prabhakar, Shyam; Poulin, Francis

2005-06-13

Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A totalmore » of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of chromosomal aberrations leading to position effects (disruption of a genes regulatory environment), observing a clear bias not only for mapping onto CBS but also for longer CBS size. Our results provide a genome wide data set characterizing the regulatory domains of genes and the conserved regulatory elements within them.« less

DAZ Family Proteins, Key Players for Germ Cell Development

PubMed Central

Fu, Xia-Fei; Cheng, Shun-Feng; Wang, Lin-Qing; Yin, Shen; De Felici, Massimo; Shen, Wei

2015-01-01

DAZ family proteins are found almost exclusively in germ cells in distant animal species. Deletion or mutations of their encoding genes usually severely impair either oogenesis or spermatogenesis or both. The family includes Boule (or Boll), Dazl (or Dazla) and DAZ genes. Boule and Dazl are situated on autosomes while DAZ, exclusive of higher primates, is located on the Y chromosome. Deletion of DAZ gene is the most common causes of infertility in humans. These genes, encoding for RNA binding proteins, contain a highly conserved RNA recognition motif and at least one DAZ repeat encoding for a 24 amino acids sequence able to bind other mRNA binding proteins. Basically, Daz family proteins function as adaptors for target mRNA transport and activators of their translation. In some invertebrate species, BOULE protein play a pivotal role in germline specification and a conserved regulatory role in meiosis. Depending on the species, DAZL is expressed in primordial germ cells (PGCs) and/or pre-meiotic and meiotic germ cells of both sexes. Daz is found in fetal gonocytes, spermatogonia and spermatocytes of adult testes. Here we discuss DAZ family genes in a phylogenic perspective, focusing on the common and distinct features of these genes, and their pivotal roles during gametogenesis evolved during evolution. PMID:26327816

Novel mitochondrial gene content and gene arrangement indicate illegitimate inter-mtDNA recombination in the chigger mite, Leptotrombidium pallidum.

PubMed

Shao, Renfu; Mitani, Harumi; Barker, Stephen C; Takahashi, Mamoru; Fukunaga, Masahito

2005-06-01

To better understand the evolution of mitochondrial (mt) genomes in the Acari (mites and ticks), we sequenced the mt genome of the chigger mite, Leptotrombidium pallidum (Arthropoda: Acari: Acariformes). This genome is highly rearranged relative to that of the hypothetical ancestor of the arthropods and the other species of Acari studied. The mt genome of L. pallidum has two genes for large subunit rRNA, a pseudogene for small subunit rRNA, and four nearly identical large noncoding regions. Nineteen of the 22 tRNAs encoded by this genome apparently lack either a T-arm or a D-arm. Further, the mt genome of L. pallidum has two distantly separated sections with identical sequences but opposite orientations of transcription. This arrangement cannot be accounted for by homologous recombination or by previously known mechanisms of mt gene rearrangement. The most plausible explanation for the origin of this arrangement is illegitimate inter-mtDNA recombination, which has not been reported previously in animals. In light of the evidence from previous experiments on recombination in nuclear and mt genomes of animals, we propose a model of illegitimate inter-mtDNA recombination to account for the novel gene content and gene arrangement in the mt genome of L. pallidum.

An Approach for Predicting Essential Genes Using Multiple Homology Mapping and Machine Learning Algorithms.

PubMed

Hua, Hong-Li; Zhang, Fa-Zhan; Labena, Abraham Alemayehu; Dong, Chuan; Jin, Yan-Ting; Guo, Feng-Biao

Investigation of essential genes is significant to comprehend the minimal gene sets of cell and discover potential drug targets. In this study, a novel approach based on multiple homology mapping and machine learning method was introduced to predict essential genes. We focused on 25 bacteria which have characterized essential genes. The predictions yielded the highest area under receiver operating characteristic (ROC) curve (AUC) of 0.9716 through tenfold cross-validation test. Proper features were utilized to construct models to make predictions in distantly related bacteria. The accuracy of predictions was evaluated via the consistency of predictions and known essential genes of target species. The highest AUC of 0.9552 and average AUC of 0.8314 were achieved when making predictions across organisms. An independent dataset from Synechococcus elongatus , which was released recently, was obtained for further assessment of the performance of our model. The AUC score of predictions is 0.7855, which is higher than other methods. This research presents that features obtained by homology mapping uniquely can achieve quite great or even better results than those integrated features. Meanwhile, the work indicates that machine learning-based method can assign more efficient weight coefficients than using empirical formula based on biological knowledge.

Prognostic and functional role of subtype-specific tumor-stroma interaction in breast cancer.

PubMed

Merlino, Giuseppe; Miodini, Patrizia; Callari, Maurizio; D'Aiuto, Francesca; Cappelletti, Vera; Daidone, Maria Grazia

2017-10-01

None of the clinically relevant gene expression signatures available for breast cancer were specifically developed to capture the influence of the microenvironment on tumor cells. Here, we attempted to build subtype-specific signatures derived from an in vitro model reproducing tumor cell modifications after interaction with activated or normal stromal cells. Gene expression signatures derived from HER2+, luminal, and basal breast cancer cell lines (treated by normal fibroblasts or cancer-associated fibroblasts conditioned media) were evaluated in clinical tumors by in silico analysis on published gene expression profiles (GEPs). Patients were classified as microenvironment-positive (μENV+ve), that is, with tumors showing molecular profiles suggesting activation by the stroma, or microenvironment-negative (μENV-ve) based on correlation of their tumors' GEP with the respective subtype-specific signature. Patients with estrogen receptor alpha (ER)+/HER2-/μENV+ve tumors were characterized by 2.5-fold higher risk of developing distant metastases (HR = 2.546; 95% CI: 1.751-3.701, P = 9.84E-07), while μENV status did not affect, or only suggested the risk of distant metastases, in women with HER2+ (HR = 1.541; 95% CI: 0.788-3.012, P = 0.206) or ER-/HER2- tumors (HR = 1.894; 95% CI: 0.938-3.824; P = 0.0747), respectively. In ER+/HER2- tumors, the μENV status remained significantly associated with metastatic progression (HR = 2.098; CI: 1.214-3.624; P = 0.00791) in multivariable analysis including size, age, and Genomic Grade Index. Validity of our in vitro model was also supported by in vitro biological endpoints such as cell growth (MTT assay) and migration/invasion (Transwell assay). In vitro-derived gene signatures tracing the bidirectional interaction with cancer activated fibroblasts are subtype-specific and add independent prognostic information to classical prognostic variables in women with ER+/HER2- tumors. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Reclassification of Theileria annae as Babesia vulpes sp. nov.

PubMed

Baneth, Gad; Florin-Christensen, Monica; Cardoso, Luís; Schnittger, Leonhard

2015-04-08

Theileria annae is a tick-transmitted small piroplasmid that infects dogs and foxes in North America and Europe. Due to disagreement on its placement in the Theileria or Babesia genera, several synonyms have been used for this parasite, including Babesia Spanish dog isolate, Babesia microti-like, Babesia (Theileria) annae, and Babesia cf. microti. Infections by this parasite cause anemia, thrombocytopenia, and azotemia in dogs but are mostly subclinical in red foxes (Vulpes vulpes). Furthermore, high infection rates have been detected among red fox populations in distant regions strongly suggesting that these canines act as the parasite's natural host. This study aims to reassess and harmonize the phylogenetic placement and binomen of T. annae within the order Piroplasmida. Four molecular phylogenetic trees were constructed using a maximum likelihood algorithm based on DNA alignments of: (i) near-complete 18S rRNA gene sequences (n = 76 and n = 93), (ii) near-complete and incomplete 18S rRNA gene sequences (n = 92), and (iii) tubulin-beta gene sequences (n = 32) from B. microti and B. microti-related parasites including those detected in dogs and foxes. All phylogenetic trees demonstrate that T. annae and its synonyms are not Theileria parasites but are most closely related with B. microti. The phylogenetic tree based on the 18S rRNA gene forms two separate branches with high bootstrap value, of which one branch corresponds to Babesia species infecting rodents, humans, and macaques, while the other corresponds to species exclusively infecting carnivores. Within the carnivore group, T. annae and its synonyms from distant regions segregate into a single clade with a highly significant bootstrap value corroborating their separate species identity. Phylogenetic analysis clearly shows that T. annae and its synonyms do not pertain to Theileria and can be clearly defined as a separate species. Based on the facts that T. annae and its synonyms have not been shown to have a leukocyte stage, as expected in Theileria, do not infect humans and rodents as B. microti, and cluster phylogenetically as a separate species, this study proposes to name this parasite Babesia vulpes sp. nov., after its natural host, the red fox V. vulpes.

Development of a multiplex methylation specific PCR suitable for (early) detection of non-small cell lung cancer

PubMed Central

Nawaz, Imran; Qiu, Xiaoming; Wu, Heng; Li, Yang; Fan, Yaguang; Hu, Li-Fu; Zhou, Qinghua; Ernberg, Ingemar

2014-01-01

Lung cancer is a worldwide health problem and a leading cause of cancer-related deaths. Silencing of potential tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event in the initiation and development of cancer. Thus, methylated cancer type-specific TSGs in DNA can serve as useful biomarkers for early cancer detection. We have now developed a “Multiplex Methylation Specific PCR” (MMSP) assay for analysis of the methylation status of multiple potential TSGs by a single PCR reaction. This method will be useful for early diagnosis and treatment outcome studies of non-small cell lung cancer (NSCLC). Genome-wide CpG methylation and expression microarrays were performed on lung cancer tissues and matched distant non-cancerous tissues from three NSCLC patients from China. Thirty-eight potential TSGs were selected and analyzed by methylation PCR on bisulfite treated DNA. On the basis of sensitivity and specificity, six marker genes, HOXA9, TBX5, PITX2, CALCA, RASSF1A, and DLEC1, were selected to establish the MMSP assay. This assay was then used to analyze lung cancer tissues and matched distant non-cancerous tissues from 70 patients with NSCLC, as well as 24 patients with benign pulmonary lesion as controls. The sensitivity of the assay was 99% (69/70). HOXA9 and TBX5 were the 2 most sensitive marker genes: 87% (61/70) and 84% (59/70), respectively. RASSF1A and DLEC1 showed the highest specificity at 99% (69/70). Using the criterion of identifying at least any two methylated marker genes, 61/70 cancer samples were positive, corresponding to a sensitivity of 87% and a specificity of 94%. Early stage I or II NSCLC could even be detected with a 100% specificity and 86% sensitivity. In conclusion, MMSP has the potential to be developed into a population-based screening tool and can be useful for early diagnosis of NSCLC. It might also be suitable for monitoring treatment outcome and recurrence. PMID:24937636

Stage-specific differential gene expression profiling and functional network analysis during morphogenesis of diphyodont dentition in miniature pigs, Sus Scrofa

PubMed Central

2014-01-01

Background Our current knowledge of tooth development derives mainly from studies in mice, which have only one set of non-replaced teeth, compared with the diphyodont dentition in humans. The miniature pig is also diphyodont, making it a valuable alternative model for understanding human tooth development and replacement. However, little is known about gene expression and function during swine odontogenesis. The goal of this study is to undertake the survey of differential gene expression profiling and functional network analysis during morphogenesis of diphyodont dentition in miniature pigs. The identification of genes related to diphyodont development should lead to a better understanding of morphogenetic patterns and the mechanisms of diphyodont replacement in large animal models and humans. Results The temporal gene expression profiles during early diphyodont development in miniature pigs were detected with the Affymetrix Porcine GeneChip. The gene expression data were further evaluated by ANOVA as well as pathway and STC analyses. A total of 2,053 genes were detected with differential expression. Several signal pathways and 151 genes were then identified through the construction of pathway and signal networks. Conclusions The gene expression profiles indicated that spatio-temporal down-regulation patterns of gene expression were predominant; while, both dynamic activation and inhibition of pathways occurred during the morphogenesis of diphyodont dentition. Our study offers a mechanistic framework for understanding dynamic gene regulation of early diphyodont development and provides a molecular basis for studying teeth development, replacement, and regeneration in miniature pigs. PMID:24498892

Analysis of plant hormone profiles in response to moderate dehydration stress.

PubMed

Urano, Kaoru; Maruyama, Kyonoshin; Jikumaru, Yusuke; Kamiya, Yuji; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2017-04-01

Plant responses to dehydration stress are mediated by highly complex molecular systems involving hormone signaling and metabolism, particularly the major stress hormone abscisic acid (ABA) and ABA-dependent gene expression. To understand the roles of plant hormones and their interactions during dehydration, we analyzed the plant hormone profiles with respect to dehydration responses in Arabidopsis thaliana wild-type (WT) plants and ABA biosynthesis mutants (nced3-2). We developed a procedure for moderate dehydration stress, and then investigated temporal changes in the profiles of ABA, jasmonic acid isoleucine (JA-Ile), salicylic acid (SA), cytokinin (trans-zeatin, tZ), auxin (indole-acetic acid, IAA), and gibberellin (GA 4 ), along with temporal changes in the expression of key genes involved in hormone biosynthesis. ABA levels increased in a bi-phasic pattern (at the early and late phases) in response to moderate dehydration stress. JA-Ile levels increased slightly in WT plants and strongly increased in nced3-2 mutant plants at 72 h after the onset of dehydration. The expression profiles of dehydration-inducible genes displayed temporal responses in an ABA-dependent manner. The early phase of ABA accumulation correlated with the expression of touch-inducible genes and was independent of factors involved in the major ABA regulatory pathway, including the ABA-responsive element-binding (AREB/ABF) transcription factor. JA-Ile, SA, and tZ were negatively regulated during the late dehydration response phase. Transcriptome analysis revealed important roles for hormone-related genes in metabolism and signaling during dehydration-induced plant responses. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Turning gene function ON and OFF using sense and antisense photo-morpholinos in zebrafish

PubMed Central

Tallafuss, Alexandra; Gibson, Dan; Morcos, Paul; Li, Yongfu; Seredick, Steve; Eisen, Judith; Washbourne, Philip

2012-01-01

To understand the molecular mechanisms of development it is essential to be able to turn genes on and off at will and in a spatially restricted fashion. Morpholino oligonucleotides (MOs) are very common tools used in several model organisms with which it is possible to block gene expression. Recently developed photo-activated MOs allow control over the onset of MO activity. However, deactivation of photo-cleavable MO activity has remained elusive. Here, we describe photo-cleavable MOs with which it is possible to activate or de-activate MO function by UV exposure in a temporal and spatial manner. We show, using several different genes as examples, that it is possible to turn gene expression on or off both in the entire zebrafish embryo and in single cells. We use these tools to demonstrate the sufficiency of no tail expression as late as tailbud stage to drive medial precursor cells towards the notochord cell fate. As a broader approach for the use of photo-cleavable MOs, we show temporal control over gal4 function, which has many potential applications in multiple transgenic lines. We demonstrate temporal manipulation of Gal4 transgene expression in only primary motoneurons and not secondary motoneurons, heretofore impossible with conventional transgenic approaches. In another example, we follow and analyze neural crest cells that regained sox10 function after deactivation of a photo-cleavable sox10-MO at different time points. Our results suggest that sox10 function might not be critical during neural crest formation. PMID:22492359

3D chromosome rendering from Hi-C data using virtual reality

NASA Astrophysics Data System (ADS)

Zhu, Yixin; Selvaraj, Siddarth; Weber, Philip; Fang, Jennifer; Schulze, Jürgen P.; Ren, Bing

2015-01-01

Most genome browsers display DNA linearly, using single-dimensional depictions that are useful to examine certain epigenetic mechanisms such as DNA methylation. However, these representations are insufficient to visualize intrachromosomal interactions and relationships between distal genome features. Relationships between DNA regions may be difficult to decipher or missed entirely if those regions are distant in one dimension but could be spatially proximal when mapped to three-dimensional space. For example, the visualization of enhancers folding over genes is only fully expressed in three-dimensional space. Thus, to accurately understand DNA behavior during gene expression, a means to model chromosomes is essential. Using coordinates generated from Hi-C interaction frequency data, we have created interactive 3D models of whole chromosome structures and its respective domains. We have also rendered information on genomic features such as genes, CTCF binding sites, and enhancers. The goal of this article is to present the procedure, findings, and conclusions of our models and renderings.

The reverse evolution from multicellularity to unicellularity during carcinogenesis.

PubMed

Chen, Han; Lin, Fangqin; Xing, Ke; He, Xionglei

2015-03-09

Theoretical reasoning suggests that cancer may result from a knockdown of the genetic constraints that evolved for the maintenance of metazoan multicellularity. By characterizing the whole-life history of a xenograft tumour, here we show that metastasis is driven by positive selection for general loss-of-function mutations on multicellularity-related genes. Expression analyses reveal mainly downregulation of multicellularity-related genes and an evolving expression profile towards that of embryonic stem cells, the cell type resembling unicellular life in its capacity of unlimited clonal proliferation. Also, the emergence of metazoan multicellularity ~600 Myr ago is accompanied by an elevated birth rate of cancer genes, and there are more loss-of-function tumour suppressors than activated oncogenes in a typical tumour. These data collectively suggest that cancer represents a loss-of-function-driven reverse evolution back to the unicellular 'ground state'. This cancer evolution model may account for inter-/intratumoural genetic heterogeneity, could explain distant-organ metastases and hold implications for cancer therapy.

Novel Biomarker Candidates for Colorectal Cancer Metastasis: A Meta-analysis of In Vitro Studies

PubMed Central

Long, Nguyen Phuoc; Lee, Wun Jun; Huy, Nguyen Truong; Lee, Seul Ji; Park, Jeong Hill; Kwon, Sung Won

2016-01-01

Colorectal cancer (CRC) is one of the most common and lethal cancers. Although numerous studies have evaluated potential biomarkers for early diagnosis, current biomarkers have failed to reach an acceptable level of accuracy for distant metastasis. In this paper, we performed a gene set meta-analysis of in vitro microarray studies and combined the results from this study with previously published proteomic data to validate and suggest prognostic candidates for CRC metastasis. Two microarray data sets included found 21 significant genes. Of these significant genes, ALDOA, IL8 (CXCL8), and PARP4 had strong potential as prognostic candidates. LAMB2, MCM7, CXCL23A, SERPINA3, ABCA3, ALDH3A2, and POLR2I also have potential. Other candidates were more controversial, possibly because of the biologic heterogeneity of tumor cells, which is a major obstacle to predicting metastasis. In conclusion, we demonstrated a meta-analysis approach and successfully suggested ten biomarker candidates for future investigation. PMID:27688707

Novel Biomarker Candidates for Colorectal Cancer Metastasis: A Meta-analysis of In Vitro Studies.

PubMed

Long, Nguyen Phuoc; Lee, Wun Jun; Huy, Nguyen Truong; Lee, Seul Ji; Park, Jeong Hill; Kwon, Sung Won

2016-01-01

Colorectal cancer (CRC) is one of the most common and lethal cancers. Although numerous studies have evaluated potential biomarkers for early diagnosis, current biomarkers have failed to reach an acceptable level of accuracy for distant metastasis. In this paper, we performed a gene set meta-analysis of in vitro microarray studies and combined the results from this study with previously published proteomic data to validate and suggest prognostic candidates for CRC metastasis. Two microarray data sets included found 21 significant genes. Of these significant genes, ALDOA, IL8 (CXCL8), and PARP4 had strong potential as prognostic candidates. LAMB2, MCM7, CXCL23A, SERPINA3, ABCA3, ALDH3A2, and POLR2I also have potential. Other candidates were more controversial, possibly because of the biologic heterogeneity of tumor cells, which is a major obstacle to predicting metastasis. In conclusion, we demonstrated a meta-analysis approach and successfully suggested ten biomarker candidates for future investigation.

Rodent Zic Genes in Neural Network Wiring.

PubMed

Herrera, Eloísa

2018-01-01

The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

Divergent sorting of a balanced ancestral polymorphism underlies the establishment of gene-flow barriers in Capsella

PubMed Central

Sicard, Adrien; Kappel, Christian; Josephs, Emily B.; Lee, Young Wha; Marona, Cindy; Stinchcombe, John R.; Wright, Stephen I.; Lenhard, Michael

2015-01-01

In the Bateson–Dobzhansky–Muller model of genetic incompatibilities post-zygotic gene-flow barriers arise by fixation of novel alleles at interacting loci in separated populations. Many such incompatibilities are polymorphic in plants, implying an important role for genetic drift or balancing selection in their origin and evolution. Here we show that NPR1 and RPP5 loci cause a genetic incompatibility between the incipient species Capsella grandiflora and C. rubella, and the more distantly related C. rubella and C. orientalis. The incompatible RPP5 allele results from a mutation in C. rubella, while the incompatible NPR1 allele is frequent in the ancestral C. grandiflora. Compatible and incompatible NPR1 haplotypes are maintained by balancing selection in C. grandiflora, and were divergently sorted into the derived C. rubella and C. orientalis. Thus, by maintaining differentiated alleles at high frequencies, balancing selection on ancestral polymorphisms can facilitate establishing gene-flow barriers between derived populations through lineage sorting of the alternative alleles. PMID:26268845

Koi herpesvirus represents a third cyprinid herpesvirus (CyHV-3) in the family Herpesviridae.

PubMed

Waltzek, Thomas B; Kelley, Garry O; Stone, David M; Way, Keith; Hanson, Larry; Fukuda, Hideo; Hirono, Ikuo; Aoki, Takashi; Davison, Andrew J; Hedrick, Ronald P

2005-06-01

The sequences of four complete genes were analysed in order to determine the relatedness of koi herpesvirus (KHV) to three fish viruses in the family Herpesviridae: carp pox herpesvirus (Cyprinid herpesvirus 1, CyHV-1), haematopoietic necrosis herpesvirus of goldfish (Cyprinid herpesvirus 2, CyHV-2) and channel catfish virus (Ictalurid herpesvirus 1, IcHV-1). The genes were predicted to encode a helicase, an intercapsomeric triplex protein, the DNA polymerase and the major capsid protein. The results showed that KHV is related closely to CyHV-1 and CyHV-2, and that the three cyprinid viruses are related, albeit more distantly, to IcHV-1. Twelve KHV isolates from four diverse geographical areas yielded identical sequences for a region of the DNA polymerase gene. These findings, with previously published morphological and biological data, indicate that KHV should join the group of related lower-vertebrate viruses in the family Herpesviridae under the formal designation Cyprinid herpesvirus 3 (CyHV-3).

Breast Cancer Treatment in the Era of Molecular Imaging

PubMed Central

Edelhauser, Gundula; Funovics, Martin

2008-01-01

Summary Molecular imaging employs molecularly targeted probes to visualize and often quantify distinct disease-specific markers and pathways. Modalities like intravital confocal or multiphoton microscopy, near-infrared fluorescence combined with endoscopy, surface reflectance imaging, or fluorescence-mediated tomography, and radionuclide imaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are increasingly used for small animal high-throughput screening, drug development and testing, and monitoring gene therapy experiments. In the clinical treatment of breast cancer, PET and SPECT as well as magnetic resonance-based molecular imaging are already established for the staging of distant disease and intrathoracic nodal status, for patient selection regarding receptor-directed treatments, and to gain early information about treatment efficacy. In the near future, reporter gene imaging during gene therapy and further spatial and qualitative characterization of the disease can become clinically possible with radionuclide and optical methods. Ultimately, it may be expected that every level of breast cancer treatment will be affected by molecular imaging, including screening. PMID:21048912

Amygdala Damage Affects Event-Related Potentials for Fearful Faces at Specific Time Windows

PubMed Central

Rotshtein, Pia; Richardson, Mark P; Winston, Joel S; Kiebel, Stefan J; Vuilleumier, Patrik; Eimer, Martin; Driver, Jon; Dolan, Raymond J

2010-01-01

The amygdala is known to influence processing of threat-related stimuli in distant brain regions, including visual cortex. The time-course of these distant influences is unknown, although this information is important for resolving debates over likely pathways mediating an apparent rapidity in emotional processing. To address this, we recorded event-related potentials (ERPs) to seen fearful face expressions, in preoperative patients with medial temporal lobe epilepsy who had varying degrees of amygdala pathology, plus healthy volunteers. We found that amygdala damage diminished ERPs for fearful versus neutral faces within the P1 time-range, ∼100–150 ms, and for a later component at ∼500–600 ms. Individual severity of amygdala damage determined the magnitude of both these effects, consistent with a causal amygdala role. By contrast, amygdala damage did not affect explicit perception of fearful expressions nor a distinct emotional ERP effect at 150–250 ms. These results demonstrate two distinct time-points at which the amygdala influences fear processing. The data also demonstrate that while not all aspects of expression processing are disrupted by amygdala damage, there is a crucial impact on an early P1 component. These findings are consistent with the existence of multiple processing stages or routes for fearful faces that vary in their dependence on amygdala function. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. PMID:20017134

Dam removal increases American eel abundance in distant headwater streams

USGS Publications Warehouse

Hitt, Nathaniel P.; Eyler, Sheila; Wofford, John E.B.

2012-01-01

American eel Anguilla rostrata abundances have undergone significant declines over the last 50 years, and migration barriers have been recognized as a contributing cause. We evaluated eel abundances in headwater streams of Shenandoah National Park, Virginia, to compare sites before and after the removal of a large downstream dam in 2004 (Embrey Dam, Rappahannock River). Eel abundances in headwater streams increased significantly after the removal of Embrey Dam. Observed eel abundances after dam removal exceeded predictions derived from autoregressive models parameterized with data prior to dam removal. Mann–Kendall analyses also revealed consistent increases in eel abundances from 2004 to 2010 but inconsistent temporal trends before dam removal. Increasing eel numbers could not be attributed to changes in local physical habitat (i.e., mean stream depth or substrate size) or regional population dynamics (i.e., abundances in Maryland streams or Virginia estuaries). Dam removal was associated with decreasing minimum eel lengths in headwater streams, suggesting that the dam previously impeded migration of many small-bodied individuals (<300 mm TL). We hypothesize that restoring connectivity to headwater streams could increase eel population growth rates by increasing female eel numbers and fecundity. This study demonstrated that dams may influence eel abundances in headwater streams up to 150 river kilometers distant, and that dam removal may provide benefits for eel management and conservation at the landscape scale.

131I therapy of thyroid cancer patients.

PubMed

Reiners, C; Farahati, J

1999-12-01

Thyroid cancer is a rare malignancy with wide interethnic and geographic variations. In Germany thyroid carcinoma is the 13th most frequent malignancy (2.7 new cases yearly per 100,000 inhabitants). The overall temporal incidence is increasing slightly in recent years. The most common types of cancer are papillary (60-80%) and follicular cancers (10-20%). The relevant prognostic indicators are tumor stage and distant metastases. The mean survival rates in papillary thyroid cancer usually exceed 90%, whereas in follicular thyroid cancer they amount to approximately 80%. The standard treatment procedure in differentiated papillary and follicular thyroid cancer consists of total thyroidectomy followed by adjuvant ablative therapy with radioiodine. Only in papillary thyroid cancer stage pT1N0M0 lobectomy alone is considered to be appropriate. In patients with locally invasive differentiated thyroid cancers stage pT4 adjuvant percutaneous radiation therapy is a treatment option. Radioiodine therapy has to be performed under the stimulative influence of TSH. Usually TSH suppressive medication with Levothyroxine has to be withdrawn approximately 4 weeks prior to radioiodine therapy. In the future, exogenous stimulation by recombinant TSH may be used instead of thyroid hormone withdrawal. It has been proven by different studies that ablative radioiodine therapy reduces the frequency of recurrences and tumor spread in patients with thyroid cancer significantly. In patients with distant metastases, up to 50% of complete responses may be achieved with radioiodine treatment.

Clinical value of 18 FDG PET/CT in screening for distant metastases in head and neck squamous cell carcinoma.

PubMed

Deurvorst, S E; Hoekstra, O S; Castelijns, J A; Witte, B I; Leemans, C R; de Bree, R

2018-06-01

The detection of distant metastases is of major importance in management of head and neck squamous cell carcinoma patients. All patients underwent 18 FDG PET/CT for the detection of distant metastases. Retrospective single-centre study. Head and neck squamous cell carcinoma patients with high-risk factors for distant metastases. Accuracy of 18 FDG PET/CT for the detection of distant metastases using clinical development of distant metastases and a minimal follow-up of twelve months as reference standard. Comparison of overall survival between patients diagnosed with distant metastases during initial screening and patients diagnosed with distant metastases during follow-up. In 23 (12%) of the 190 patients, 18 FDG PET/CT detected distant metastases at screening. Sensitivity and negative predictive value were 46.2% (95% CI 32.6-59.7) and 82.6% (95% CI 76.8-88.5). No difference in median overall survival from the time of distant metastases detection was found between patients diagnosed with DM during work-up or during follow-up. In head and neck squamous cell carcinoma patients with high-risk factors, 18 FDG PET/CT has a high negative predictive value for the detection of distant metastases and should be used in daily clinical practice, although the sensitivity is limited when long-term follow-up is used as reference standard. © 2018 The Authors. Clinical Otolaryngology Published by John Wiley & Sons Ltd.

Wind Farm Facilities in Germany Kill Noctule Bats from Near and Far

PubMed Central

Lehnert, Linn S.; Kramer-Schadt, Stephanie; Schönborn, Sophia; Lindecke, Oliver; Niermann, Ivo; Voigt, Christian C.

2014-01-01

Over recent years, it became widely accepted that alternative, renewable energy may come at some risk for wildlife, for example, when wind turbines cause large numbers of bat fatalities. To better assess likely populations effects of wind turbine related wildlife fatalities, we studied the geographical origin of the most common bat species found dead below German wind turbines, the noctule bat (Nyctalus noctula). We measured stable isotope ratios of non-exchangeable hydrogen in fur keratin to separate migrants from local individuals, used a linear mixed-effects model to identify temporal, spatial and biological factors explaining the variance in measured stable isotope ratios and determined the geographical breeding provenance of killed migrants using isoscape origin models. We found that 72% of noctule bat casualties (n = 136) were of local origin, while 28% were long-distance migrants. These findings highlight that bat fatalities at German wind turbines may affect both local and distant populations. Our results indicated a sex and age-specific vulnerability of bats towards lethal accidents at turbines, i.e. a relatively high proportion of killed females were recorded among migratory individuals, whereas more juveniles than adults were recorded among killed bats of local origin. Migratory noctule bats were found to originate from distant populations in the Northeastern parts of Europe. The large catchment areas of German wind turbines and high vulnerability of female and juvenile noctule bats call for immediate action to reduce the negative cross-boundary effects of bat fatalities at wind turbines on local and distant populations. Further, our study highlights the importance of implementing effective mitigation measures and developing species and scale-specific conservation approaches on both national and international levels to protect source populations of bats. The efficacy of local compensatory measures appears doubtful, at least for migrant noctule bats, considering the large geographical catchment areas of German wind turbines for this species. PMID:25118805

Wind farm facilities in Germany kill noctule bats from near and far.

PubMed

Lehnert, Linn S; Kramer-Schadt, Stephanie; Schönborn, Sophia; Lindecke, Oliver; Niermann, Ivo; Voigt, Christian C

2014-01-01

Over recent years, it became widely accepted that alternative, renewable energy may come at some risk for wildlife, for example, when wind turbines cause large numbers of bat fatalities. To better assess likely populations effects of wind turbine related wildlife fatalities, we studied the geographical origin of the most common bat species found dead below German wind turbines, the noctule bat (Nyctalus noctula). We measured stable isotope ratios of non-exchangeable hydrogen in fur keratin to separate migrants from local individuals, used a linear mixed-effects model to identify temporal, spatial and biological factors explaining the variance in measured stable isotope ratios and determined the geographical breeding provenance of killed migrants using isoscape origin models. We found that 72% of noctule bat casualties (n = 136) were of local origin, while 28% were long-distance migrants. These findings highlight that bat fatalities at German wind turbines may affect both local and distant populations. Our results indicated a sex and age-specific vulnerability of bats towards lethal accidents at turbines, i.e. a relatively high proportion of killed females were recorded among migratory individuals, whereas more juveniles than adults were recorded among killed bats of local origin. Migratory noctule bats were found to originate from distant populations in the Northeastern parts of Europe. The large catchment areas of German wind turbines and high vulnerability of female and juvenile noctule bats call for immediate action to reduce the negative cross-boundary effects of bat fatalities at wind turbines on local and distant populations. Further, our study highlights the importance of implementing effective mitigation measures and developing species and scale-specific conservation approaches on both national and international levels to protect source populations of bats. The efficacy of local compensatory measures appears doubtful, at least for migrant noctule bats, considering the large geographical catchment areas of German wind turbines for this species.

Sex-biased transcriptome divergence along a latitudinal gradient.

PubMed

Allen, Scott L; Bonduriansky, Russell; Sgro, Carla M; Chenoweth, Stephen F

2017-03-01

Sex-dependent gene expression is likely an important genomic mechanism that allows sex-specific adaptation to environmental changes. Among Drosophila species, sex-biased genes display remarkably consistent evolutionary patterns; male-biased genes evolve faster than unbiased genes in both coding sequence and expression level, suggesting sex differences in selection through time. However, comparatively little is known of the evolutionary process shaping sex-biased expression within species. Latitudinal clines offer an opportunity to examine how changes in key ecological parameters also influence sex-specific selection and the evolution of sex-biased gene expression. We assayed male and female gene expression in Drosophila serrata along a latitudinal gradient in eastern Australia spanning most of its endemic distribution. Analysis of 11 631 genes across eight populations revealed strong sex differences in the frequency, mode and strength of divergence. Divergence was far stronger in males than females and while latitudinal clines were evident in both sexes, male divergence was often population specific, suggesting responses to localized selection pressures that do not covary predictably with latitude. While divergence was enriched for male-biased genes, there was no overrepresentation of X-linked genes in males. By contrast, X-linked divergence was elevated in females, especially for female-biased genes. Many genes that diverged in D. serrata have homologs also showing latitudinal divergence in Drosophila simulans and Drosophila melanogaster on other continents, likely indicating parallel adaptation in these distantly related species. Our results suggest that sex differences in selection play an important role in shaping the evolution of gene expression over macro- and micro-ecological spatial scales. © 2017 John Wiley & Sons Ltd.

Chromosomal Amplification of the blaOXA-58 Carbapenemase Gene in a Proteus mirabilis Clinical Isolate.

PubMed

Girlich, Delphine; Bonnin, Rémy A; Bogaerts, Pierre; De Laveleye, Morgane; Huang, Daniel T; Dortet, Laurent; Glaser, Philippe; Glupczynski, Youri; Naas, Thierry

2017-02-01

Horizontal gene transfer may occur between distantly related bacteria, thus leading to genetic plasticity and in some cases to acquisition of novel resistance traits. Proteus mirabilis is an enterobacterial species responsible for human infections that may express various acquired β-lactam resistance genes, including different classes of carbapenemase genes. Here we report a Proteus mirabilis clinical isolate (strain 1091) displaying resistance to penicillin, including temocillin, together with reduced susceptibility to carbapenems and susceptibility to expanded-spectrum cephalosporins. Using biochemical tests, significant carbapenem hydrolysis was detected in P. mirabilis 1091. Since PCR failed to detect acquired carbapenemase genes commonly found in Enterobacteriaceae, we used a whole-genome sequencing approach that revealed the presence of bla OXA-58 class D carbapenemase gene, so far identified only in Acinetobacter species. This gene was located on a 3.1-kb element coharboring a bla AmpC -like gene. Remarkably, these two genes were bracketed by putative XerC-XerD binding sites and inserted at a XerC-XerD site located between the terminase-like small- and large-subunit genes of a bacteriophage. Increased expression of the two bla genes resulted from a 6-time tandem amplification of the element as revealed by Southern blotting. This is the first isolation of a clinical P. mirabilis strain producing OXA-58, a class D carbapenemase, and the first description of a XerC-XerD-dependent insertion of antibiotic resistance genes within a bacteriophage. This study revealed a new role for the XerC-XerD recombinase in bacteriophage biology. Copyright © 2017 American Society for Microbiology.