bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypothalamic ependymal‐glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing
Authors: García María de los Angeles , Millán Carola , Balmaceda‐Aguilera Carolina , Castro Tamara , Pastor Patricia , Montecinos Hernán , Reinicke Karin , Zúñiga Felipe , Vera Juan Carlos , Oñate Sergio A. , Nualart Francisco 
Published: July 2003

AbstractThe GLUT2 glucose transporter and the K‐ATP‐sensitive potassium channels have been implicated as an integral part of the glucose‐sensing mechanism in the pancreatic islet β cells. The expression of GLUT2 and K‐ATP channels in the hypothalamic region suggest that they are also involved in a sensing mechanism in this area. The hypothalamic glial cells, known as tanycytes α and β, are specialized ependymal cells that bridge the cerebrospinal fluid and the portal blood of the median eminence. We used immunocytochemistry, in situ hybridization and transport analyses to demonstrate the glucose transporters expressed in tanycytes. Confocal microscopy using specific antibodies against GLUT1 and GLUT2 indicated that both transporters are expressed in α and β tanycytes. In addition, primary cultures of mouse hypothalamic tanycytes were found to express both GLUT1 and GLUT2 transporters. Transport studies, including 2‐deoxy‐glucose and fructose uptake in the presence or absence of inhibitors, indicated that these transporters are functional in cultured tanycytes. Finally, our analyses indicated that tanycytes express the K‐ATP channel subunit Kir6.1 in vitro. As the expression of GLUT2 and K‐ATP channel is linked to glucose‐sensing mechanisms in pancreatic β cells, we postulate that tanycytes may be responsible, at least in part, for a mechanism that allows the hypothalamus to detect changes in glucose concentrations.
Epileptiform activity in hippocampal slice cultures exposed chronically to bicuculline: increased gap junctional function and expression
Authors: Samoilova Marina , Li Jianxue , Pelletier Marc R. , Wentlandt Kirsten , Adamchik Yana , Naus Christian C. , Carlen Peter L. 
Published: July 2003

AbstractChronic (18 h) exposure of cultured hippocampal slices to the type‐A GABA receptor blocker, bicuculline methiodide (BMI) 10 μm increased the levels of connexin 43 (Cx43) and connexin 32 (Cx32) mRNAs, but not connexin 26 and connexin 36, as demonstrated by RNase protection assays. The levels of Cx43 and Cx32 proteins in membrane fractions detected by western blotting were also significantly increased. Immunoblotting indicated that BMI also promoted a significant expression of the transcription protein c‐fos. The rate of fluorescence recovery after photobleaching, an index of gap junctional coupling, was also significantly increased, whereas it was blocked by the gap junctional blocker, carbenoxolone (100 μm). Extracellular recordings in CA1 stratum pyramidale, performed in BMI‐free solution, demonstrated that BMI‐exposed cultures possessed synaptic responses characteristic of epileptiform discharges: (i) significantly greater frequency of spontaneous epileptiform discharges, (ii) post‐synaptic potentials with multiple population spikes, and (iii) significantly longer duration of primary afterdischarges. Carbenoxolone (100 μm), but not its inactive analog, oleanolic acid (100 μm), reversibly inhibited spontaneous and evoked epileptiform discharges. The findings of BMI‐induced parallel increases in levels of gap junction expression and function, and the increase in epileptiform discharges, which were sensitive to gap junctional blockers, are consistent with the hypothesis that increased gap junctional communication plays an intrinsic role in the epileptogenic process.
Chronic ethanol consumption enhances internalization of α1 subunit‐containing GABAA receptors in cerebral cortex
Authors: Kumar S. , Kralic J. E. , O'Buckley T. K. , Grobin A. C. , Morrow A. L. 
Published: July 2003

AbstractThe molecular mechanisms that underlie ethanol dependence involve alterations in the functional properties and subunit expression of GABAA receptors. Chronic ethanol exposure decreases GABAA receptor α1 subunits and increases α4 subunit levels in cerebral cortical membranes. This study explored the effect of chronic ethanol exposure on internalization of GABAA/benzodiazepine receptors. Chronic ethanol exposure increased α1 subunit levels by 46 ± 12% and [3H]flunitrazepam binding by 35 ± 9% in the clathrin‐coated vesicle (CCV) fraction. There was a corresponding 34 ± 8% decrease in α1 peptide expression and 37 ± 6% decrease in [3H]flunitrazepam binding in the synaptic fraction. Chronic ethanol consumption also increased the α1 subunit immunoprecipitate in the cytosolic fraction (77 ± 22%), measured by western blot analysis. Moreover, co‐immunoprecipitation of both clathrin and adaptin‐α with α1 subunits was increased in the cytosolic fraction, suggesting that α1 subunit endocytosis is enhanced by chronic ethanol consumption. In contrast, α4 subunit peptide levels were not altered in the CCV fraction despite a 39 ± 13% increase in peptide levels in the synaptic fraction of cortex. Moreover, acute ethanol exposure did not alter α1 subunit peptide expression or [3H]flunitrazepam binding in the synaptic or CCV fractions. These results suggest that chronic ethanol consumption selectively increases internalization of α1 subunit‐containing GABAA receptors in cerebral cortex.
Neuropeptide Y is neuroproliferative for post‐natal hippocampal precursor cells
Authors: Howell Owain W. , Scharfman Helen E. , Herzog Herbert , Sundstrom Lars E. , Beck‐Sickinger Annette , Gray William P. 
Published: July 2003

AbstractNew neurones are produced in the adult hippocampus throughout life and are necessary for certain types of hippocampal learning. Little, however, is known about the control of hippocampal neurogenesis. We used primary hippocampal cultures from early post‐natal rats and neuropeptide Y Y1 receptor knockout mice as well as selective neuropeptide Y receptor antagonists and agonists to demonstrate that neuropeptide Y is proliferative for nestin‐positive, sphere‐forming hippocampal precursor cells and β‐tubulin‐positive neuroblasts and that the neuroproliferative effect of neuropeptide Y is mediated via its Y1 receptor. Immunohistochemistry confirmed Y1 receptor staining on both nestin‐positive cells and β‐tubulin‐positive cells in culture and short pulse 5‐bromo‐2‐deoxyuridine studies demonstrated that neuropeptide Y has a proliferative effect on both cell types. These studies suggest that the proliferation of hippocampal neuroblasts and precursor cells is increased by neuropeptide Y and, therefore, that hippocampal learning and memory may be modulated by neuropeptide Y‐releasing interneurones.
Unification of zero-sum problems, subset sums and covers of ℤ
Authors: Sun Zhi-Wei 
Published: July 2003

In combinatorial number theory, zero-sum problems, subset sums and covers of the integers are three different topics initiated by P. Erdös and investigated by many researchers; they play important roles in both number theory and combinatorics. In this paper we announce some deep connections among these seemingly unrelated fascinating areas, and aim at establishing a unified theory! Our main theorem unifies many results in these three realms and also has applications in many aspects such as finite fields and graph theory. To illustrate this, here we state our extension of the Erdös-Ginzburg-Ziv theorem: If

A
=
{

a

s

(

m
o
d

n

s

)

}

s
=
1

k

A=\{a_{s}(\mathrm {mod}\ n_{s})\}_{s=1}^{k}

covers some integers exactly

2
p
−
1

2p-1

times and others exactly

2
p

2p

times, where

p
p

is a prime, then for any

c

1

,
⋯
,

c

k

∈

Z

/

p

Z

c_{1},\cdots ,c_{k}\in \mathbb {Z}/p\mathbb {Z}

there exists an

I
⊆
{
1
,
⋯
,
k
}

I\subseteq \{1,\cdots ,k\}

such that

∑

s
∈
I

1

/

n

s

=
p

\sum _{s\in I}1/n_{s}=p

and

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s
∈
I

c

s

=
0

\sum _{s\in I}c_{s}=0

.
Bayesian gene/species tree reconciliation
and orthology analysis using MCMC
Authors: Arvestad Lars , Berglund Ann-Charlotte , Lagergren Jens , Sennblad Bengt 
Published: July 2003

Abstract
Motivation: Comparative genomics in general and orthology analysis in particular are becoming increasingly important parts of gene function prediction. Previously, orthology analysis and reconciliation has been performed only with respect to the parsimony model. This discards many plausible solutions and sometimes precludes finding the correct one. In many other areas in bioinformatics probabilistic models have proven to be both more realistic and powerful than parsimony models. For instance, they allow for assessing solution reliability and consideration of alternative solutions in a uniform way. There is also an added benefit in making model assumptions explicit and therefore making model comparisons possible. For orthology analysis, uncertainty has recently been addressed using parsimonious reconciliation combined with bootstrap techniques. However, until now no probabilistic methods have been available.
Results: We introduce a probabilistic gene evolution model based on a birth-death process in which a gene tree evolves ‘inside’ a species tree. Based on this model, we develop a tool with the capacity to perform practical orthology analysis, based on Fitch’s original definition, and more generally for reconciling pairs of gene and species trees. Our gene evolution model is biologically sound (Nei et al., 1997) and intuitively attractive. We develop a Bayesian analysis based on MCMC which facilitates approximation of an a posteriori distribution for reconciliations. That is, we can find the most probable reconciliations and estimate the probability of any reconciliation, given the observed gene tree. This also gives a way to estimate the probability that a pair of genes are orthologs. The main algorithmic contribution presented here consists of an algorithm for computing the likelihood of a given reconciliation. To the best of our knowledge, this is the first successful introduction of this type of probabilistic methods, which flourish in phylogeny analysis, into reconciliation and orthology analysis. The MCMC algorithm has been implemented and, although not yet being in its final form, tests show that it performs very well on synthetic as well as biological data. Using standard correspondences, our results carry over to allele trees as well as biogeography.
Contact: {lottab,jensl}@nada.kth.se, {bengt.sennblad,lars.arvestad}@sbc.su.se
*To whom correspondence should be addressed.
Predicting bacterial transcription units using sequence and expression data
Authors: Bockhorst Joseph , Qiu Yu , Glasner Jeremy , Liu Mingzhu , Blattner Frederick , Craven Mark 
Published: July 2003

Abstract
Motivation: A key aspect of elucidating gene regulation in bacterial genomes is identifying the basic units of transcription. We present a method, based on probabilistic language models, that we apply to predict operons, promoters and terminators in the genome of Escherichia coli K-12. Our approach has two key properties: (i) it provides a coherent set of predictions for related regulatory elements of various types and (ii) it takes advantage of both DNA sequence and gene expression data, including expression measurements from inter-genic probes.
Results: Our experimental results show that we are able to predict operons and localize promoters and terminators with high accuracy. Moreover, our models that use both sequence and expression data are more accurate than those that use only one of these two data sources.
Availability: Our E.coli transcription-unit predictions are available from http://www.biostat.wisc.edu/gene-regulation/
Contact: joebock@biostat.wisc.edu; craven@biostat.wisc.edu
*To whom correspondence should be addressed.
Glocal alignment: finding rearrangements during alignment
Authors: Brudno Michael , Malde Sanket , Poliakov Alexander , Do Chuong B. , Couronne Olivier , Dubchak Inna , Batzoglou Serafim 
Published: July 2003

Abstract
Motivation: To compare entire genomes from different species, biologists increasingly need alignment methods that are efficient enough to handle long sequences, and accurate enough to correctly align the conserved biological features between distant species. The two main classes of pairwise alignments are global alignment, where one string is transformed into the other, and local alignment, where all locations of similarity between the two strings are returned. Global alignments are less prone to demonstrating false homology as each letter of one sequence is constrained to being aligned to only one letter of the other. Local alignments, on the other hand, can cope with rearrangements between non-syntenic, orthologous sequences by identifying similar regions in sequences; this, however, comes at the expense of a higher false positive rate due to the inability of local aligners to take into account overall conservation maps.
Results: In this paper we introduce the notion of glocal alignment, a combination of global and local methods, where one creates a map that transforms one sequence into the other while allowing for rearrangement events. We present Shuffle-LAGAN, a glocal alignment algorithm that is based on the CHAOS local alignment algorithm and the LAGAN global aligner, and is able to align long genomic sequences. To test Shuffle-LAGAN we split the mouse genome into BAC-sized pieces, and aligned these pieces to the human genome. We demonstrate that Shuffle-LAGAN compares favorably in terms of sensitivity and specificity with standard local and global aligners. From the alignments we conclude that about 9% of human/mouse homology may be attributed to small rearrangements, 63% of which are duplications.
Availability: Our systems, supplemental information, and the alignment of the human and mouse genomes using Shuffle-LAGAN are available at http://lagan.stanford.edu/glocal
Contact: serafim@cs.stanford.edu
*To whom correspondence should be addressed.
†These authors contributed equally to the work.
Linking genotype to phenotype: the International Rice Information System (IRIS)
Authors: Bruskiewich Richard M. , Cosico Alexander B. , Eusebio William , Portugal Arllet M. , Ramos Luralyn M. , Reyes Ma. Teresa , Sallan May Ann B. , Ulat Victor Jun M. , Wang Xusheng , McNally Kenneth L. , Sackville Hamilton Ruaraidh , McLaren Christopher Graham 
Published: July 2003

Abstract
The International Rice Information System (IRIS, http://www.iris.irri.org) is the rice implementation of the International Crop Information System (ICIS, http://www.icis.cgiar.org), a database system for the management and integration of global information on genetic resources and germplasm improvement for any crop. Building upon the germplasm genealogy and field data components of ICIS, IRIS is being extended to handle diverse rice genomics data including: genetic mapping, genome annotation, genotype, mutant, transcripteome, proteome and metabolomic data. Users can access information in the database through stand-alone programs and WWW interfaces offering specialist views to researchers with different interests.
Availability: http://bioinformatics.org/project/?group_id=141
Contact: r.bruskiewich@cgiar.org
Keywords: database, crop, rice, germplasm, genotype, phenotype, genomics
*To whom correspondence should be addressed.
Stochastic modeling of RNA pseudoknotted structures: a grammatical
approach
Authors: Cai Liming , Malmberg Russell L. , Wu Yunzhou 
Published: July 2003

Abstract
Motivation: Modeling RNA pseudoknotted structures remains challenging. Methods have previously been developed to model RNA stem-loops successfully using stochastic context-free grammars (SCFG) adapted from computational linguistics; however, the additional complexity of pseudoknots has made modeling them more difficult. Formally a context-sensitive grammar is required, which would impose a large increase in complexity.
Results: We introduce a new grammar modeling approach for RNA pseudoknotted structures based on parallel communicating grammar systems (PCGS). Our new approach can specify pseudoknotted structures, while avoiding context-sensitive rules, using a single CFG synchronized with a number of regular grammars. Technically, the stochastic version of the grammar model can be as simple as an SCFG. As with SCFG, the new approach permits automatic generation of a single-RNA structure prediction algorithm for each specified pseudoknotted structure model. This approach also makes it possible to develop full probabilistic models of pseudoknotted structures to allow the prediction of consensus structures by comparative analysis and structural homology recognition in database searches.
Availability: Prototypes for the automated pseudoknot prediction algorithm are available upon request.
Contact: cai@cs.uga.edu; russell@plantbio.uga.edu
*To whom correspondence should be addressed.
Fast identification and statistical evaluation of
segmental homologies in comparative maps
Authors: Calabrese Peter P. , Chakravarty Sugata , Vision Todd J. 
Published: July 2003

Abstract
Motivation: Chromosomal segments that share common ancestry, either through genomic duplication or species divergence, are said to be segmental homologs of one another. Their identification allows researchers to leverage knowledge of model organisms for use in other systems and is of value for studies of genome evolution. However, identification and statistical evaluation of segmental homologies can be a challenge when the segments are highly diverged.
Results: We describe a flexible dynamic programming algorithm for the identification of segments having multiple homologous features. We model the probability of observing putative segmental homologies by chance and incorporate our findings into the parameterization of the algorithm and the statistical evaluation of its output. Combined, these findings allow segmental homologies to be identified in comparisons within and between genomic maps in a rigorous, rapid, and automated fashion.
Availability: http://www.bio.unc.edu/faculty/vision/lab/
Contact: tjv@bio.unc.edu
Keywords: homology, comparative maps, synteny, genome evolution
*To whom correspondence should be addressed.
PSI: indexing protein structures for fast similarity search
Authors: Camoglu Orhan , Kahveci Tamer , Singh Ambuj K. 
Published: July 2003

Abstract
Motivation: We consider the problem of finding similarities in protein structure databases. Current techniques sequentially compare the given query protein to all of the proteins in the database to find similarities. Therefore, the cost of similarity queries increases linearly as the volume of the protein databases increase. As the sizes of experimentally determined and theoretically estimated protein structure databases grow, there is a need for scalable searching techniques.
Results: Our techniques extract feature vectors on triplets of SSEs (Secondary Structure Elements). Later, these feature vectors are indexed using a multidimensional index structure. For a given query protein, this index structure is used to quickly prune away unpromising proteins in the database. The remaining proteins are then aligned using a popular alignment tool such as VAST. We also develop a novel statistical model to estimate the goodness of a match using the SSEs. Experimental results show that our techniques improve the pruning time of VAST 3 to 3.5 times while maintaining similar sensitivity.
Contact: orhan@cs.ucsb.edu; tamer@cs.ucsb.edu; ambuj@cs.ucsb.edu.
Keywords: Protein structures, feature vectors, indexing
*To whom correspondence should be addressed.
MASS: multiple structural alignment by secondary structures
Authors: Dror O. , Benyamini H. , Nussinov R. , Wolfson H. 
Published: July 2003

Abstract
We present a novel method for multiple alignment of protein structures and detection of structural motifs. To date, only a few methods are available for addressing this task. Most of them are based on a series of pairwise comparisons. In contrast, MASS (Multiple Alignment by Secondary Structures) considers all the given structures at the same time. Exploiting the secondary structure representation aids in filtering out noisy results and in making the method highly efficient and robust. MASS disregards the sequence order of the secondary structure elements. Thus, it can find non-sequential and even non-topological structural motifs. An important novel feature of MASS is subset alignment detection: It does not require that all the input molecules be aligned. Rather, MASS is capable of detecting structural motifs shared only by a subset of the molecules. Given its high efficiency and capability of detecting subset alignments, MASS is suitable for a broad range of challenging applications: It can handle large-scale protein ensembles (on the order of tens) that may be heterogeneous, noisy, topologically unrelated and contain structures of low resolution.
Keywords: Structural Bioinformatics, Subset alignment, Non-sequential alignment, Non-topological motif, Supersecondary structural motif
Availability: MASS program and more information about it are available on http://bioinfo3d.cs.tau.ac.il/MASS
Contact: oranit@post.tau.ac.il
*To whom correspondence should be addressed.
Annotation of bacterial genomes using improved phylogenomic profiles
Authors: Enault F. , Suhre K. , Abergel C. , Poirot O. , Claverie J.-M. 
Published: July 2003

Abstract
Motivation: Phylogenomic profiling is a large-scale comparative genomic method used to infer protein function from evolutionary information first described in a binary form by Pellegrini et al. (1999). Here, we propose improvements of this approach including the use of normalized Blastp bit scores, a normalization of the matrix of profiles to take into account the evolutionary distances between bacteria, the definition of a phylogenomic neighborhood based on continuous pairwise distances between genes and an original annotation procedure including the computation of a p-value for each functional assignment.
Results: The method presented here increases the number of Ecocyc enzymes identified as being evolutionarily related by about 25% with respect to the original binary form (absent/present) method. The fraction of ‘false’ positives is shown to be smaller than 20%. Based on their phylogenomic relationships, genes of unknown function can then be automatically related to annotated genes. Each gene annotation predicted is associated with a p-value, i.e. its probability to be obtained by chance. The validity of this method was extensively tested on a large set of genes of known function using the MultiFun database. We find that 50% of 3122 function attributions that can be made at a p-value level of 10−11 correspond to the actual gene annotation. The method can be readily applied to any newly sequenced microbial genome. In contrast to earlier work on the same topic, our approach avoids the use of arbitrary cut-off values, and provides a reliability estimate of the functional predictions in form of p-values.
Contact: enault@igs.cnrs-mrs.fr
Keywords: phylogenomics, functional prediction, automated annotation, bacteria, evolution.
*To whom correspondence should be addressed.