bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bayesian connectivity-based approach to constructing probabilistic gene regulatory networks
Authors: Zhou Xiaobo , Wang Xiaodong , Pal Ranadip , Ivanov Ivan , Bittner Michael , Dougherty Edward R. 
Published: May 2004

Abstract
Motivation: We have hypothesized that the construction of transcriptional regulatory networks using a method that optimizes connectivity would lead to regulation consistent with biological expectations. A key expectation is that the hypothetical networks should produce a few, very strong attractors, highly similar to the original observations, mimicking biological state stability and determinism. Another central expectation is that, since it is expected that the biological control is distributed and mutually reinforcing, interpretation of the observations should lead to a very small number of connection schemes.
Results: We propose a fully Bayesian approach to constructing probabilistic gene regulatory networks (PGRNs) that emphasizes network topology. The method computes the possible parent sets of each gene, the corresponding predictors and the associated probabilities based on a nonlinear perceptron model, using a reversible jump Markov chain Monte Carlo (MCMC) technique, and an MCMC method is employed to search the network configurations to find those with the highest Bayesian scores to construct the PGRN. The Bayesian method has been used to construct a PGRN based on the observed behavior of a set of genes whose expression patterns vary across a set of melanoma samples exhibiting two very different phenotypes with respect to cell motility and invasiveness. Key biological features have been faithfully reflected in the model. Its steady-state distribution contains attractors that are either identical or very similar to the states observed in the data, and many of the attractors are singletons, which mimics the biological propensity to stably occupy a given state. Most interestingly, the connectivity rules for the most optimal generated networks constituting the PGRN are remarkably similar, as would be expected for a network operating on a distributed basis, with strong interactions between the components.
Availability: The appendix is available at http://gspsnap.tamu.edu/gspweb/pgrn/bayes.html username: gspweb password: gsplab.
Supplementary Information: http://gspsnap.tamu.edu/gspweb/pgrn/bayes.html
The Global Error Assessment (GEA) model for the selection of differentially expressed genes in microarray data
Authors: Mansourian Robert , Mutch David M. , Antille Nicolas , Aubert Jerome , Fogel Paul , Le Goff Jean-Marc , Moulin Julie , Petrov Anton , Rytz Andreas , Voegel Johannes J. , Roberts Matthew-Alan 
Published: May 2004

Abstract
Motivation: Microarray technology has become a powerful research tool in many fields of study; however, the cost of microarrays often results in the use of a low number of replicates (k). Under circumstances where k is low, it becomes difficult to perform standard statistical tests to extract the most biologically significant experimental results. Other more advanced statistical tests have been developed; however, their use and interpretation often remain difficult to implement in routine biological research. The present work outlines a method that achieves sufficient statistical power for selecting differentially expressed genes under conditions of low k, while remaining as an intuitive and computationally efficient procedure.
Results: The present study describes a Global Error Assessment (GEA) methodology to select differentially expressed genes in microarray datasets, and was developed using an in vitro experiment that compared control and interferon-γ treated skin cells. In this experiment, up to nine replicates were used to confidently estimate error, thereby enabling methods of different statistical power to be compared. Gene expression results of a similar absolute expression are binned, so as to enable a highly accurate local estimate of the mean squared error within conditions. The model then relates variability of gene expression in each bin to absolute expression levels and uses this in a test derived from the classical ANOVA. The GEA selection method is compared with both the classical and permutational ANOVA tests, and demonstrates an increased stability, robustness and confidence in gene selection. A subset of the selected genes were validated by real-time reverse transcription–polymerase chain reaction (RT–PCR). All these results suggest that GEA methodology is (i) suitable for selection of differentially expressed genes in microarray data, (ii) intuitive and computationally efficient and (iii) especially advantageous under conditions of low k.
Availability: The GEA code for R software is freely available upon request to authors.
Prediction of similarly acting cis-regulatory modules by subsequence profiling and comparative genomics in Drosophila melanogaster and D.pseudoobscura
Authors: Grad Yonatan H. , Roth Frederick P. , Halfon Marc S. , Church George M. 
Published: May 2004

Abstract
Motivation: To date, computational searches for cis-regulatory modules (CRMs) have relied on two methods. The first, phylogenetic footprinting, has been used to find CRMs in non-coding sequence, but does not directly link DNA sequence with spatio-temporal patterns of expression. The second, based on searches for combinations of transcription factor (TF) binding motifs, has been employed in genome-wide discovery of similarly acting enhancers, but requires prior knowledge of the set of TFs acting at the CRM and the TFs' binding motifs.
Results: We propose a method for CRM discovery that combines aspects of both approaches in an effort to overcome their individual limitations. By treating phylogenetically footprinted non-coding regions (PFRs) as proxies for CRMs, we endeavor to find PFRs near co-regulated genes that are comprised of similar short, conserved sequences. Using Markov chains as a convenient formulation to assess similarity, we develop a sampling algorithm to search a large group of PFRs for the most similar subset. When starting with a set of genes involved in Drosophila early blastoderm development and using phylogenetic comparisons of Drosophila melanogaster and D.pseudoobscura genomes, we show here that our algorithm successfully detects known CRMs. Further, we use our similarity metric, based on Markov chain discrimination, in a genome-wide search, and uncover additional known and many candidate early blastoderm CRMs.
Availability: Software is available via http://arep.med.harvard.edu/enhancers
Supplementary information: Can be accessed at http://arep.med.harvard.edu/enhancers
A neural network method for prediction of β-turn types in proteins using evolutionary information
Authors: Kaur Harpreet , Raghava G. P. S. 
Published: May 2004

Abstract
Motivation: The prediction of β-turns is an important element of protein secondary structure prediction. Recently, a highly accurate neural network based method Betatpred2 has been developed for predicting β-turns in proteins using position-specific scoring matrices (PSSM) generated by PSI-BLAST and secondary structure information predicted by PSIPRED. However, the major limitation of Betatpred2 is that it predicts only β-turn and non-β-turn residues and does not provide any information of different β-turn types. Thus, there is a need to predict β-turn types using an approach based on multiple sequence alignment, which will be useful in overall tertiary structure prediction.
Results: In the present work, a method has been developed for the prediction of β-turn types I, II, IV and VIII. For each turn type, two consecutive feed-forward back-propagation networks with a single hidden layer have been used where the first sequence-to-structure network has been trained on single sequences as well as on PSI-BLAST PSSM. The output from the first network along with PSIPRED predicted secondary structure has been used as input for the second-level structure-to-structure network. The networks have been trained and tested on a non-homologous dataset of 426 proteins chains by 7-fold cross-validation. It has been observed that the prediction performance for each turn type is improved significantly by using multiple sequence alignment. The performance has been further improved by using a second level structure-to-structure network and PSIPRED predicted secondary structure information. It has been observed that Type I and II β-turns have better prediction performance than Type IV and VIII β-turns. The final network yields an overall accuracy of 74.5, 93.5, 67.9 and 96.5% with MCC values of 0.29, 0.29, 0.23 and 0.02 for Type I, II, IV and VIII β-turns, respectively, and is better than random prediction.
Availability: A web server for prediction of β-turn types I, II, IV and VIII based on above approach is available at http://www.imtech.res.in/raghava/betaturns/ and http://bioinformatics.uams.edu/mirror/betaturns/ (mirror site).
Ecological anachronisms in the recruitment of temperate light‐demanding tree species in wooded pastures
Authors: BAKKER E. S. , OLFF H. , VANDENBERGHE C. , DE MAEYER K. , SMIT R. , GLEICHMAN J. M. , VERA F. W. M. 
Published: May 2004

Summary

Light‐demanding trees and thorny shrubs in temperate plant communities may reflect adaptations to now‐extinct large grazers, such as aurochs and tarpans, rendering these adaptations ecological anachronisms.
We explored the ecological functions of plant traits of Quercus robur and Prunus spinosa in areas grazed by cattle and horses, the domesticated descendants of aurochs and tarpans. Specifically, we tested the hypothesis that grazing induces a shifting mosaic of grassland, shrub thickets and woodlands through the key process of associational resistance: the protection of palatable young trees by thorny shrubs.
An exclosure experiment with transplanted Q. robur seedlings revealed that Q. robur grew best in grassland exclosures and on the edge of thorny shrub thickets, which may be viewed as an optimal balance between sufficient protection from large herbivores and sufficient light availability.
A cross‐site comparison of four floodplain woodlands in north‐western Europe showed that Q. robur can regenerate in the presence of large herbivores through spatial association with P. spinosa. However, we found that expansion of P. spinosa shrubs and Q. robur coincided with periods of low rabbit abundance and not with livestock density. From this, it appears that the process of associational resistance does not work with rabbits.
Synthesis and applications. With extensive grazing by large (domesticated) grazers in temperate floodplains, a shifting mosaic of grassland, shrubs and trees may develop that has high conservation value. Palatable, light‐demanding Q. robur seedlings can successfully regenerate in spiny P. spinosa shrubs through associational resistance. This process does not offer protection from abundant small herbivores, such as rabbits, that can inhibit the recruitment of shrubs and trees in this mosaic vegetation. In floodplain meadows frequent flooding may be an efficient way to reduce rabbit populations, with dry conditions in summer and wet in winter. When floodplain meadows are combined with adjacent higher grounds, large herbivores can escape the floods through migration.
Modelling integrated weed management of an invasive shrub in tropical Australia
Authors: BUCKLEY YVONNE M. , REES MARK , PAYNTER QUENTIN , LONSDALE MARK 
Published: May 2004

Summary

Where biocontrol programmes for invasive plants are in place, only one‐third are fully successful. Integrated weed management (IWM) emphasizes the use of several complementary control measures.
We used models of increasing complexity to determine which parameters affect site occupancy of an invasive shrub, Mimosa pigra, in tropical Australia. Two introduced biocontrol agents have spatial effects on both plant fecundity and the probability of recolonization after senescence. We incorporated biocontrol effects into IWM models with small‐scale disturbance, such as grazing and pig‐rooting, and large‐scale disturbance, such as mechanical control, herbicide and fire. The models were parameterized from experimental and field data.
The models indicated that reduction in fecundity is not the most important impact of biocontrol; rather it is defoliation at the edges of stands, allowing grasses to out‐compete M. pigra seedlings. We demonstrated that biocontrol alone is only successful at low levels of small‐scale disturbance and seedling survival and, even then, current biocontrol agents would take decades to reduce a stand to < 5% site occupancy.
Our model predicts the most successful IWM strategy to be an application of herbicide in year 1, mechanical control + fire in year 2 and herbicide in year 3, with reduction of small‐scale disturbance where possible. The addition of biocontrol improves the success of this strategy.
Synthesis and applications. Ascertaining how control measures, including biological methods, will influence persistence of an invasive requires models of the target species’ dynamics and its ecosystem. As in previous applications of this model, disturbance is the most important regulator of population size in M. pigra; moderate to high levels of small‐scale disturbance promotes M. pigra occupancy. We have shown that IWM can control M. pigra and that biocontrol is an effective part of this strategy. Reductions in fecundity alone are unlikely to control invasive leguminous shrubs. However, biocontrol agents affect the probability of recolonization after senescence and enhance control. Our recommended 3‐year treatment programme (herbicide : mechanical control + fire : herbicide, with biocontrol) is justifiable in terms of the biology of the system, making it more likely to be acted upon by risk‐averse farmers and land managers.
The effect of patch size and separation on bumblebee foraging in oilseed rape: implications for gene flow
Authors: CRESSWELL JAMES E. , OSBORNE JULIET L. 
Published: May 2004

SummaryTheory predicts that the susceptibility of patches of plants to gene flow mediated by incoming pollinators will depend on the length of pollinator residence (the number of flowers visited during a bout in a patch). We sought to determine whether pollinator residence is sufficiently sensitive to patch size and separation to influence levels of gene flow significantly. We studied oilseed rapeBrassica napusas an exemplar of a conventional animal‐pollinated plant and as a species where there is a risk of genetic escape from genetically modified (GM) varieties.We determined pollinator residence in 36 patches created by mowing an agricultural field of flowering oilseed rape. Each square patch had an edge length of 1, 2, 3, 4, 5 or 10 m. Patches were separated by either 9 m or 18 m from the border of a large unmown area of crop. We used the residence of bumblebees (Bombusspp.) to solve a model of bumblebee‐mediated gene flow.Bumblebee residence increased significantly with patch area, but did not depend on the separation distance of the patch from the large areas of crop. Even in the largest patches, bees visited onlyc. 60 of thec. 1 × 105flowers before leaving.If bumblebees were the sole pollinators, the model predicted that 4–8% of the seed produced by the smaller patches (c. 80–320 plants) had fathers outside the patch, whereas in the larger patches (720–8000 plants) the prediction was 2–4%. Nevertheless, larger patches should produce the greatest number of seeds with extrinsic paternity.Synthesis and applications. Our observations demonstrate that susceptibility to pollinator‐mediated gene flow is liable to decrease systematically as the size of plant patches increases. These findings can inform the management of genetic diversity in and among small or fragmented populations. If the patch size–gene flow relationship that we observed applies to larger scales, the model could estimate gene flow between GM crops and volunteer or feral populations in agricultural landscapes.
Invasive ecotypes tolerate herbivory more effectively than native ecotypes of the Chinese tallow tree Sapium sebiferum
Authors: ROGERS WILLIAM E. , SIEMANN EVAN 
Published: May 2004

Summary

The evolution of increased competitive ability (EICA) hypothesis proposes that exotic plants often become invasive because they have evolved reduced allocation to defence and increased allocation to growth and reproduction in response to low herbivore loads. Previous studies with Chinese tallow tree Sapium sebiferum support EICA predictions of invasive North American ecotypes displaying rapid growth, poorly defended leaves and considerable compensation after defoliation. In contrast, native Asian ecotypes are comparatively slow growing with highly defended leaves and are negatively impacted by mechanical leaf damage. The effects of root damage on the different ecotypes are unknown.
We conducted a full‐factorial pot experiment designed to assess the effects of soil fertility, competition with ryegrass Lolium multiflorum and mechanical root damage on Sapium seedlings derived from seed collections obtained in the ancestral range (native Chinese ecotype) and introduced range (invasive Texas ecotype).
The results, consistent with EICA predictions, revealed that Chinese ecotypes were negatively affected by severing roots, while Texas ecotypes were able to compensate for root damage.
Fertilization increased growth of Chinese ecotypes, but did not reduce the negative effects of root damage enough to allow the seedlings to compensate completely. Competition increased the stem height growth of Chinese ecotypes, but did not affect shoot or root mass. Texas ecotypes were not significantly affected by any experimental treatments.
Synthesis and applications. The results of this study are consistent with previous studies indicating that invasive Sapium has undergone a shift away from possessing costly herbivore defences to producing relatively inexpensive tissues that are capable of rapidly compensating for damage. Evolutionary change is increasingly being recognized as an important factor contributing to the success of exotic plant invaders. Understanding that herbivory tolerance and the compensatory capacity for damage may differ between native and introduced plant ecotypes will be essential for implementing effective control strategies for problematic invasive species.
Role of the Otx1 gene in cell differentiation of mammalian cortex
Authors: Pantò Maria Rosita , Zappalà Agata , Tuorto Francesca , Cicirata Federico 
Published: May 2004

AbstractThis study analyses by immunohistochemical methods the effects of the deletion of the Otx1 gene on 12 areas of the cerebral cortex and on neurons expressing Ca‐binding proteins (CaBP), such as parvalbumin (Pv) and calbindin‐D28K (Cb). We found that the deletion of the Otx1 gene modified differently the various cortical areas. The decrease in cortical thickness ranged from 29.35 to 9.85% and the reduction in cellular population from 35.90 to 3.65% in the different cortical areas. The influence of the Otx1 gene concerns all cortical layers with variable effects on different cortical areas. The cellular population of cerebral cortex considered as a whole was reduced by 20.67%, Pv‐positive (Pv+) cells by 58.01% and Cb‐positive (Cb+) cells by 51.54%. The quantitative distribution of Pv+ and Cb+ cells varied independently in the different cortical areas. Topographic analysis of CaBP cells in Otx1‐null mice (Otx1−/−) showed that Pv+ cells were principally distributed in layers IV and V and Cb+ cells in layers V and VI. Given that in the development of wild‐type mice both cell types first appear in deep layers and later spread to superficial ones, the segregation of CaBP neurons in inner layers of Otx1−/− animals is an index of the immaturity of the cerebral cortex of these animals. This study showed that the Otx1 gene has a more complex role than previously reported, as it is involved in the maturation and differentiation of various cerebral cortices, and, specifically, in the development of CaBP cells.
Functional expression of connexin57 in horizontal cells of the mouse retina
Authors: Hombach Sonja , Janssen‐Bienhold Ulrike , Söhl Goran , Schubert Timm , Büssow Heinrich , Ott Thomas , Weiler Reto , Willecke Klaus 
Published: May 2004

AbstractHorizontal cells are interneurons of the vertebrate retina that exhibit strong electrical and tracer coupling but the identity of the channel‐forming connexins has remained elusive. Here we show that horizontal cells of the mouse retina express connexin57 (Cx57). We have generated Cx57‐deficient mice by replacing the Cx57 coding region with a lacZ reporter gene, expressed under control of the endogenous Cx57 promoter. These mice were fertile and showed no obvious anatomical or behavioural abnormalities. Cx57 mRNA was expressed in the retina of wild‐type littermates but was absent from the retina of Cx57‐deficient mice. Previously reported results that the Cx57 gene was very weakly expressed in several other mouse tissues turned out to be unspecific. Cx57 mRNA is abundantly expressed in the retina and weakly in the thymus of adult mice but absent in all other adult tissues tested, including brain. Furthermore, Cx57 is expressed in embryonic kidney at E16.5 to E18.5 days post‐conception, as indicated by the pattern of lacZ expression. Within the retina, lacZ signals were assigned exclusively to horizontal cells based on co‐localization with cell‐type‐specific marker proteins. Microinjection of Neurobiotin into horizontal cells of isolated retinae revealed less than 1% of tracer coupling in Cx57‐deficient retinae compared with wild‐type controls. Cx57 is the first connexin identified in mammalian horizontal cells and the first connexin whose expression is apparently restricted to only one type of neuron.
Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain
Authors: . Swatton Jane E , Sellers Lynda A. , Faull Richard L.M. , Holland Anthony , Iritani Shuji , Bahn Sabine 
Published: May 2004

IntroductionAbnormal phosphorylation of tau is a feature of Alzheimer's disease (AD), which develops prematurely in Down syndrome (DS) patients. Cognitive impairment is also recognized as a clinical characteristic of schizophrenia, which does not appear to be associated with tau‐aggregate formation. Several kinases can phosphorylate tau in cell‐free assays. Here we show increased activity of mitogen‐activated protein kinases (MAPKs) (including ERK1/2, SAPKs and p38) in post mortem AD and DS brains, which could not be accounted for by expression changes. In contrast, glycogen synthase kinase‐3 activity (GSK‐3αβ) was reduced significantly. Examination of tau in AD and DS using antibodies selective for MAPK phosphorylation sites showed increased immunoreactivity. In addition, phosphorylation of S199, reportedly a selective substrate for cyclin‐dependent kinase‐5 (cdk5) or GSK‐3αβ was only observed in AD samples, which showed a concomitant increase in the expression of p25, the enhancing cofactor for cdk5 activity. However, in schizophrenia brain, MAPK‐phosphorylated tau was unchanged compared to matched controls, despite similar expression levels to those in AD. The activities of the MAPKs and GSK‐3αβ were also unchanged. These data demonstrate that in AD and DS, enhanced MAPK activity, which has an established role in regulating neuronal plasticity and survival, can account for irregular tau phosphorylation, and that the molecular processes involved in these neurodegenerative disorders are distinct from those in schizophrenia. These data also question the significance of GSK‐3αβ, as much previous work carried out in vitro has placed this kinase as a favoured candidate for involvement in the pathological phosphorylation of tau.