bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of cell cycle by the anaphase spindle midzone
Authors: Murata-Hori Maki , Sluder Greenfield , Wang Yu-li 
Published: January 2005

Abstract1
Background
A number of proteins accumulate in the spindle midzone and midbody of dividing animal cells. Besides proteins essential for cytokinesis, there are also components essential for interphase functions, suggesting that the spindle midzone and/or midbody may play a role in regulating the following cell cycle.

Results
We microsurgically severed NRK epithelial cells during anaphase or telophase, such that the spindle midzone/midbody was associated with only one of the daughter cells. Time-lapse recording of cells severed during early anaphase indicated that the cell with midzone underwent cytokinesis-like cortical contractions and progressed normally through the interphase, whereas the cell without midzone showed no cortical contraction and an arrest or substantial delay in the progression of interphase. Similar microsurgery during telophase showed a normal progression of interphase for both daughter cells with or without the midbody. Microsurgery of anaphase cells treated with cytochalasin D or nocodazole indicated that interphase progression was independent of cortical ingression but dependent on microtubules.

Conclusions
We conclude that the mitotic spindle is involved in not only the separation of chromosomes but also the regulation of cell cycle. The process may involve activation of components in the spindle midzone that are required for the cell cycle, and/or degradation of components that are required for cytokinesis but may interfere with the cell cycle.
The product of the split ends gene is required for the maintenance of positional information during Drosophiladevelopment
Authors: Mace Kimberly , Tugores Antonio 
Published: January 2005

Abstract
Background
The Drosophila split ends (spen) gene encodes a large nuclear protein containing three RNP-type RNA binding motifs, and a conserved transcriptional co-repressor-interacting domain at the C-terminus. Genetic analyses indicate that spen interacts with pathways that regulate the function of Hox proteins, the response to various signaling cascades and cell cycle control. Although spen mutants affect only a small subset of morphological structures in embryos, it has been difficult to find a common theme in spen mutant structural alterations, or in the interactions of spen with known signaling pathways.

Results
By generating clones of spen mutant cells in wing imaginal discs, we show that spen function is required for the correct formation and positioning of veins and mechanosensory bristles both on the anterior wing margin and on the notum, and for the maintenance of planar polarity. Wing vein phenotypic alterations are enhanced by mutations in the crinkled (ck) gene, encoding a non-conventional myosin, and correlate with an abnormal spatial expression of Delta, an early marker of vein formation in third instar wing imaginal discs. Positioning defects were also evident in the organization of the embryonic peripheral nervous system, accompanied by abnormal E-Cadherin expression in the epidermis.

Conclusions
The data presented indicate that the role of spen is necessary to maintain the correct positioning of cells within a pre-specified domain throughout development. Its requirement for epithelial planar polarity, its interaction with ck, and the abnormal E-Cadherin expression associated with spen mutations suggest that spen exerts its function by interacting with basic cellular mechanisms required to maintain multicellular organization in metazoans. This role for spen may explain why mutations in this gene interact with the outcome of multiple signaling pathways.
Structure and evolution of protein interaction networks: a statistical model for link dynamics and gene duplications
Authors: Berg Johannes , Lässig Michael , Wagner Andreas 
Published: January 2005

Abstract
Background
The structure of molecular networks derives from dynamical processes on evolutionary time scales. For protein interaction networks, global statistical features of their structure can now be inferred consistently from several large-throughput datasets. Understanding the underlying evolutionary dynamics is crucial for discerning random parts of the network from biologically important properties shaped by natural selection.

Results
We present a detailed statistical analysis of the protein interactions in Saccharomyces cerevisiae based on several large-throughput datasets. Protein pairs resulting from gene duplications are used as tracers into the evolutionary past of the network. From this analysis, we infer rate estimates for two key evolutionary processes shaping the network: (i) gene duplications and (ii) gain and loss of interactions through mutations in existing proteins, which are referred to as link dynamics. Importantly, the link dynamics is asymmetric, i.e., the evolutionary steps are mutations in just one of the binding parters. The link turnover is shown to be much faster than gene duplications. Both processes are assembled into an empirically grounded, quantitative model for the evolution of protein interaction networks.

Conclusions
According to this model, the link dynamics is the dominant evolutionary force shaping the statistical structure of the network, while the slower gene duplication dynamics mainly affects its size. Specifically, the model predicts (i) a broad distribution of the connectivities (i.e., the number of binding partners of a protein) and (ii) correlations between the connectivities of interacting proteins, a specific consequence of the asymmetry of the link dynamics. Both features have been observed in the protein interaction network of S. cerevisiae.
Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence
Authors: Taudien Stefan , Galgoczy Petra , Huse Klaus , Reichwald Kathrin , Schilhabel Markus , Szafranski Karol , Shimizu Atsushi , Asakawa Shuichi , Frankish Adam , Loncarevic Ivan F , Shimizu Nobuyoshi , Siddiqui Roman , Platzer Matthias 
Published: January 2005

Abstract
Background
Defensins are important components of innate immunity to combat bacterial and viral infections, and can even elicit antitumor responses. Clusters of defensin (DEF) genes are located in a 2 Mb range of the human chromosome 8p23.1. This DEF locus, however, represents one of the regions in the euchromatic part of the final human genome sequence which contains segmental duplications, and recalcitrant gaps indicating high structural dynamics.

Results
We find that inter- and intraindividual genetic variations within this locus prevent a correct automatic assembly of the human reference genome (NCBI Build 34) which currently even contains misassemblies. Manual clone-by-clone alignment and gene annotation as well as repeat and SNP/haplotype analyses result in an alternative alignment significantly improving the DEF locus representation. Our assembly better reflects the experimentally verified variability of DEF gene and DEF cluster copy numbers. It contains an additional DEF cluster which we propose to reside between two already known clusters. Furthermore, manual annotation revealed a novel DEF gene and several pseudogenes expanding the hitherto known DEF repertoire. Analyses of BAC and working draft sequences of the chimpanzee indicates that its DEF region is also complex as in humans and DEF genes and a cluster are multiplied. Comparative analysis of human and chimpanzee DEF genes identified differences affecting the protein structure. Whether this might contribute to differences in disease susceptibility between man and ape remains to be solved. For the determination of individual DEF gene repertoires we provide a molecular approach based on DEF haplotypes.

Conclusions
Complexity and variability seem to be essential genomic features of the human DEF locus at 8p23.1 and provides an ongoing challenge for the best possible representation in the human reference sequence. Dissection of paralogous sequence variations, duplicon SNPs ans multisite variations as well as haplotypes by sequencing based methods is the way for future studies of interindividual DEF locus variability and its disease association.
Prognostic meta-signature of breast cancer developed by two-stage mixture modeling of microarray data
Authors: Shen Ronglai , Ghosh Debashis , Chinnaiyan Arul M 
Published: January 2005

Abstract
Background
An increasing number of studies have profiled tumor specimens using distinct microarray platforms and analysis techniques. With the accumulating amount of microarray data, one of the most intriguing yet challenging tasks is to develop robust statistical models to integrate the findings.

Results
By applying a two-stage Bayesian mixture modeling strategy, we were able to assimilate and analyze four independent microarray studies to derive an inter-study validated "meta-signature" associated with breast cancer prognosis. Combining multiple studies (n = 305 samples) on a common probability scale, we developed a 90-gene meta-signature, which strongly associated with survival in breast cancer patients. Given the set of independent studies using different microarray platforms which included spotted cDNAs, Affymetrix GeneChip, and inkjet oligonucleotides, the individually identified classifiers yielded gene sets predictive of survival in each study cohort. The study-specific gene signatures, however, had minimal overlap with each other, and performed poorly in pairwise cross-validation. The meta-signature, on the other hand, accommodated such heterogeneity and achieved comparable or better prognostic performance when compared with the individual signatures. Further by comparing to a global standardization method, the mixture model based data transformation demonstrated superior properties for data integration and provided solid basis for building classifiers at the second stage. Functional annotation revealed that genes involved in cell cycle and signal transduction activities were over-represented in the meta-signature.

Conclusion
The mixture modeling approach unifies disparate gene expression data on a common probability scale allowing for robust, inter-study validated prognostic signatures to be obtained. With the emerging utility of microarrays for cancer prognosis, it will be important to establish paradigms to meta-analyze disparate gene expression data for prognostic signatures of potential clinical use.
Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes
Authors: Sandelin Albin , Bailey Peter , Bruce Sara , Engström Pär G , Klos Joanna M , Wasserman Wyeth W , Ericson Johan , Lenhard Boris 
Published: January 2005

Abstract
Background
Evolutionarily conserved sequences within or adjoining orthologous genes often serve as critical cis-regulatory regions. Recent studies have identified long, non-coding genomic regions that are perfectly conserved between human and mouse, termed ultra-conserved regions (UCRs). Here, we focus on UCRs that cluster around genes involved in early vertebrate development; genes conserved over 450 million years of vertebrate evolution.

Results
Based on a high resolution detection procedure, our UCR set enables novel insights into vertebrate genome organization and regulation of developmentally important genes. We find that the genomic positions of deeply conserved UCRs are strongly associated with the locations of genes encoding key regulators of development, with particularly strong positional correlation to transcription factor-encoding genes. Of particular importance is the observation that most UCRs are clustered into arrays that span hundreds of kilobases around their presumptive target genes. Such a hallmark signature is present around several uncharacterized human genes predicted to encode developmentally important DNA-binding proteins.

Conclusion
The genomic organization of UCRs, combined with previous findings, suggests that UCRs act as essential long-range modulators of gene expression. The exceptional sequence conservation and clustered structure suggests that UCR-mediated molecular events involve greater complexity than traditional DNA binding by transcription factors. The high-resolution UCR collection presented here provides a wealth of target sequences for future experimental studies to determine the nature of the biochemical mechanisms involved in the preservation of arrays of nearly identical non-coding sequences over the course of vertebrate evolution.
Bioinformatic mapping of AlkB homology domains in viruses
Authors: Bratlie Marit S , Drabløs Finn 
Published: January 2005

Abstract
Background
AlkB-like proteins are members of the 2-oxoglutarate- and Fe(II)-dependent oxygenase superfamily. In Escherichia coli the protein protects RNA and DNA against damage from methylating agents. 1-methyladenine and 3-methylcytosine are repaired by oxidative demethylation and direct reversal of the methylated base back to its unmethylated form. Genes for AlkB homologues are widespread in nature, and Eukaryotes often have several genes coding for AlkB-like proteins. Similar domains have also been observed in certain plant viruses. The function of the viral domain is unknown, but it has been suggested that it may be involved in protecting the virus against the post-transcriptional gene silencing (PTGS) system found in plants. We wanted to do a phylogenomic mapping of viral AlkB-like domains as a basis for analysing functional aspects of these domains, because this could have some relevance for understanding possible alternative roles of AlkB homologues e.g. in Eukaryotes.

Results
Profile-based searches of protein sequence libraries showed that AlkB-like domains are found in at least 22 different single-stranded RNA positive-strand plant viruses, but mainly in a subgroup of the Flexiviridae family. Sequence analysis indicated that the AlkB domains probably are functionally conserved, and that they most likely have been integrated relatively recently into several viral genomes at geographically distinct locations. This pattern seems to be more consistent with increased environmental pressure, e.g. from methylating pesticides, than with interaction with the PTGS system.

Conclusions
The AlkB domain found in viral genomes is most likely a conventional DNA/RNA repair domain that protects the viral RNA genome against methylating compounds from the environment.
A minor alternative transcript of the fumarylacetoacetate hydrolase gene produces a protein despite being likely subjected to nonsense-mediated mRNA decay
Authors: Dreumont Natacha , Maresca Antonella , Boisclair-Lachance Jean-François , Bergeron Anne , Tanguay Robert M 
Published: January 2005

Abstract
Background
Coupling of alternative splicing with nonsense-mediated mRNA decay (NMD) may regulate gene expression. We report here the identification of a nonsense alternative transcript of the fumarylacetoacetate hydrolase (fah) gene, which produces a protein despite the fact that it is subject to NMD.

Results
During the characterization of the effects of the W262X nonsense mutation on FAH mRNA metabolism, two alternative transcripts (del100 and del231) of the fah gene were identified. Del100 lacks exon 8 and as a consequence, the reading frame is shifted and a premature termination codon appears at the 3'end of exon 10. Exons 8 and 9 are skipped in del231, without any disruption of the reading frame. Specific amplification of these transcripts demonstrate that they are produced through minor alternative splicing pathways, and that they are not caused by the W262X mutation per se. As shown with an antiserum raised against the C-terminal part of the putative DEL100 protein, the del100 transcript produces a protein, expressed at different levels in various human tissues. Interestingly, the del100 transcript seems to be subjected to nonsense-mediated mRNA decay, as its level was stabilized following a cycloheximide treatment.

Conclusions
The del100 and del231 transcripts arise due to minor alternative splicing pathways and del100 is likely subjected to nonsense-mediated mRNA decay. However the remaining amount of transcript seems sufficient to produce a protein in different human tissues. This suggests that NMD has a broader role than simply eliminating aberrant transcripts and when coupled to alternative splicing, may act to modulate gene expression, by allowing the production of low amounts of protein.
Context-dependent selection of visuomotor maps
Authors: Salinas Emilio 
Published: January 2005

Abstract
Background
Behavior results from the integration of ongoing sensory signals and contextual information in various forms, such as past experience, expectations, current goals, etc. Thus, the response to a specific stimulus, say the ringing of a doorbell, varies depending on whether you are at home or in someone else's house. What is the neural basis of this flexibility? What mechanism is capable of selecting, in a context-dependent way an adequate response to a given stimulus? One possibility is based on a nonlinear neural representation in which context information regulates the gain of stimulus-evoked responses. Here I explore the properties of this mechanism.

Results
By means of three hypothetical visuomotor tasks, I study a class of neural network models in which any one of several possible stimulus-response maps or rules can be selected according to context. The underlying mechanism based on gain modulation has three key features: (1) modulating the sensory responses is equivalent to switching on or off different subpopulations of neurons, (2) context does not need to be represented continuously, although this is advantageous for generalization, and (3) context-dependent selection is independent of the discriminability of the stimuli. In all cases, the contextual cues can quickly turn on or off a sensory-motor map, effectively changing the functional connectivity between inputs and outputs in the networks.

Conclusions
The modulation of sensory-triggered activity by proprioceptive signals such as eye or head position is regarded as a general mechanism for performing coordinate transformations in vision. The present results generalize this mechanism to situations where the modulatory quantity and the input-output relationships that it selects are arbitrary. The model predicts that sensory responses that are nonlinearly modulated by arbitrary context signals should be found in behavioral situations that involve choosing or switching between multiple sensory-motor maps. Because any relevant circumstancial information can be part of the context, this mechanism may partly explain the complex and rich behavioral repertoire of higher organisms.
Xenon prevents cellular damage in differentiated PC-12 cells exposed to hypoxia
Authors: Petzelt Christian , Blom Per , Schmehl Wolfgang , Müller Jana , Kox Wolfgang J 
Published: January 2005

Abstract
Background
The neuroprotective effect of xenon has been demonstrated for glutamatergic neurons. In the present study it is investigated if dopaminergic neurons, i.e. nerve-growth-factor differentiated PC-12 cells, are protected as well against hypoxia-induced cell damage in the presence of xenon.

Results
Pheochromocytoma cells differentiated by addition of nerve growth factor were placed in a N2-saturated atmosphere, a treatment that induced release of dopamine, reaching a maximum after 30 min. By determining extracellular lactate dehydrogenase concentration as marker for concomitant cellular damage, a substantial increase of enzymatic activity was found for N2-treated cells. Replacement of N2 by xenon in such a hypoxic atmosphere resulted in complete protection against cellular damage and prevention of hypoxia-induced dopamine release. Intracellular buffering of Ca2+ using the Ca-chelator 1, 2-bis(2-Aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl) ester (BAPTA) reduced the neuroprotective effect of xenon indicating the essential participation of intracellular Ca2+-ions in the process of xenon-induced neuroprotection.

Conclusions
The results presented demonstrate the outstanding property of xenon to protect neuron-like cells in a hypoxic situation.
Use of a highly sensitive two-dimensional luminescence imaging system to monitor endogenous bioluminescence in plant leaves
Authors: Flor-Henry Michel , McCabe Tulene C , de Bruxelles Guy L , Roberts Michael R 
Published: January 2005

Abstract
Background
All living organisms emit spontaneous low-level bioluminescence, which can be increased in response to stress. Methods for imaging this ultra-weak luminescence have previously been limited by the sensitivity of the detection systems used.

Results
We developed a novel configuration of a cooled charge-coupled device (CCD) for 2-dimensional imaging of light emission from biological material. In this study, we imaged photon emission from plant leaves. The equipment allowed short integration times for image acquisition, providing high resolution spatial and temporal information on bioluminescence. We were able to carry out time course imaging of both delayed chlorophyll fluorescence from whole leaves, and of low level wound-induced luminescence that we showed to be localised to sites of tissue damage. We found that wound-induced luminescence was chlorophyll-dependent and was enhanced at higher temperatures.

Conclusions
The data gathered on plant bioluminescence illustrate that the equipment described here represents an improvement in 2-dimensional luminescence imaging technology. Using this system, we identify chlorophyll as the origin of wound-induced luminescence from leaves.
Structural equation model testing and the quality of natural killer cell activity measurements
Authors: Hayduk Leslie A , Pazderka-Robinson Hannah , Cummings Greta G , Levers Merry-Jo D , Beres Melanie A 
Published: January 2005

Abstract
Background
Browne et al. [Browne, MacCallum, Kim, Andersen, Glaser: When fit indices and residuals are incompatible. Psychol Methods 2002] employed a structural equation model of measurements of target cell lysing by natural killer cells as an example purportedly demonstrating that small but statistically significant ill model fit can be dismissed as "negligible from a practical point of view".

Methods
Reanalysis of the natural killer cell data reveals that the supposedly negligible ill fit obscured important, systematic, and substantial causal misspecifications.

Results
A clean-fitting structural equation model indicates that measurements employing higher natural-killer-cell to target-cell ratios are more strongly influenced by a progressively intrusive factor, whether or not the natural killer cell activity is activated by recombinant interferon γ (rIFN γ). The progressive influence may reflect independent rate limiting steps in cell recognition and attachment, spatial competition for cell attachment points, or the simultaneous lysings of single target cells by multiple natural killer cells.

Conclusions
If the progressively influential factor is ultimately identified as a mere procedural impediment, the substantive conclusion will be that measurements of natural killer cell activity made at lower effector to target ratios are more valid. Alternatively, if the individual variations in the progressively influential factor are modifiable, this may presage a new therapeutic route to enhancing natural killer cell activity. The methodological conclusion is that, when using structural equation models, researchers should attend to significant model ill fit even if the degree of covariance ill fit is small, because small covariance residuals do not imply that the underlying model misspecifications are correspondingly small or inconsequential.