bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variance-modeled posterior inference of microarray data: detecting gene-expression changes in 3T3-L1 adipocytes
Authors: Hsiao A. , Worrall D. S. , Olefsky J. M. , Subramaniam S. 
Published: June 2004

Abstract
Motivation: Microarrays are becoming an increasingly common tool for observing changes in gene expression over a large cross section of the genome. This experimental tool is particularly valuable for understanding the genome-wide changes in gene transcription in response to thiazolidinedione (TZD) treatment. The TZD class of drugs is known to improve insulin-sensitivity in diabetic patients, and is clinically used in treatment regimens. In cells, TZDs bind to and activate the transcriptional activity of peroxisome proliferator-activated receptor gamma (PPAR-γ). Large-scale array analyses will provide some insight into the mechanisms of TZD-mediated insulin sensitization. Unfortunately, a theoretical basis for analyzing array data has not kept pace with the rapid adoption of this tool. The methods that are commonly used, particularly the fold-change approach and the standard t-test, either lack statistical rigor or resort to generalized statistical models that do not accurately estimate variability at low replicate numbers.
Results: We introduce a statistical framework that models the dependence of measurement variance on the level of gene expression in the context of a Bayesian hierarchical model. We compare several methods of parameter estimation and subsequently apply these to determine a set of genes in 3T3-L1 adipocytes that are differentially regulated in response to TZD treatment. When the number of experimental replicates is low (n = 2–3), this approach appears to qualitatively preserve an equivalent degree of specificity, while vastly improving sensitivity over other comparable methods. In addition, the statistical framework developed here can be readily applied to understand the implicit assumptions made in traditional fold-change approaches to array analysis.
Availability: Our statistical approach is implemented as a set of Java-based tools called VAMPIRE, accessible from our website at http://genome.ucsd.edu/VAMPIRE
Evidence that microRNA precursors, unlike other non-coding RNAs, have lower folding free energies than random sequences
Authors: Bonnet Eric , Wuyts Jan , Rouzé Pierre , Van de Peer Yves 
Published: June 2004

Abstract
Motivation: Most non-coding RNAs are characterized by a specific secondary and tertiary structure that determines their function. Here, we investigate the folding energy of the secondary structure of non-coding RNA sequences, such as microRNA precursors, transfer RNAs and ribosomal RNAs in several eukaryotic taxa. Statistical biases are assessed by a randomization test, in which the predicted minimum free energy of folding is compared with values obtained for structures inferred from randomly shuffling the original sequences.
Results: In contrast with transfer RNAs and ribosomal RNAs, the majority of the microRNA sequences clearly exhibit a folding free energy that is considerably lower than that for shuffled sequences, indicating a high tendency in the sequence towards a stable secondary structure. A possible usage of this statistical test in the framework of the detection of genuine miRNA sequences is discussed.
Availability: The dataset, software and additional data files are freely available as supplementary information on our Website.
Supplementary information: http://www.psb.ugent.be/bioinformatics/
A web portal for classification of expression data using maximal margin linear programming
Authors: Antonov Alexey V. , Tetko Igor V. , Prokopenko Volodymyr V. , Kosykh Denis , Mewes Hans W. 
Published: June 2004

Abstract
Summary: The Maximal Margin (MAMA) linear programming classification algorithm has recently been proposed and tested for cancer classification based on expression data. It demonstrated sound performance on publicly available expression datasets. We developed a web interface to allow potential users easy access to the MAMA classification tool. Basic and advanced options provide flexibility in exploitation. The input data format is the same as that used in most publicly available datasets. This makes the web resource particularly convenient for non-expert machine learning users working in the field of expression data analysis.
Availability: The web software developed is available at http://mips.gsf.de/proj/mdcs/. A stand-alone version of the server can be downloaded from this site too.
Phan3D: design of biological phantoms in 3D electron microscopy
Authors: Bilbao-Castro J. R. , Sorzano C. O. S. , García I. , Fernández J. J. 
Published: June 2004

Abstract
Summary: Three-Dimensional Electron Microscopy (3DEM) has turned out to be a major player in structural proteomics. In 3DEM, tens of thousands of EM images from a macromolecule at different views are combined to derive its structure by means of a 3D reconstruction algorithm. However, for an optimal reconstruction, the most suitable algorithm has to be used and its parameters have to be tuned for the macromolecule under study and the experimental conditions found. The use of phantoms is central to objective comparison of reconstruction algorithms and optimization of their parameters. Phan3D is a tool intended to provide a fully visual and interactive environment that facilitates the design of phantoms resembling biological specimens in 3DEM. Phan3D has been developed as an alternative to the tedious, error-prone and old-fashioned phantom design that is based on hand-written text description files.
Availability: Phan3D has been integrated into Xmipp: http://biocomp.cnb.uam.es/Biocomp/public/Software/
The UniMarker (UM) method for synteny mapping of large genomes
Authors: Liao Ben-Yang , Chang Yu-Jung , Ho Jan-Ming , Hwang Ming-Jing 
Published: June 2004

Abstract
Motivation: Synteny mapping, or detecting regions that are orthologous between two genomes, is a key step in studies of comparative genomics. For completely sequenced genomes, this is increasingly accomplished by whole-genome sequence alignment. However, such methods are computationally expensive, especially for large genomes, and require rather complicated post-processing procedures to filter out non-orthologous sequence matches.
Results: We have developed a novel method that does not require sequence alignment for synteny mapping of two large genomes, such as the human and mouse. In this method, the occurrence spectra of genome-wide unique 16mer sequences present in both the human and mouse genome are used to directly detect orthologous genomic segments. Being sequence alignment-free, the method is very fast and able to map the two mammalian genomes in one day of computing time on a single Pentium IV personal computer. The resulting human–mouse synteny map was shown to be in excellent agreement with those produced by the Mouse Genome Sequencing Consortium (MGSC) and by the Ensembl team; furthermore, the syntenic relationship of segments found only by our method was supported by BLASTZ sequence alignment.
Availability: The source code of our method and the resulting human–mouse synteny maps have been placed at http://synteny.ibms.sinica.edu.tw/ for free access.
Supplementary information: Seven supplementary figures can be found at the same website.
Quantitative Leverage Through Qualitative Knowledge: Augmenting the Statistical Analysis of Complex Causes
Authors: Gordon Sanford C. , Smith Alastair 
Published: June 2004

Social scientific theories frequently posit that multiple causal mechanisms may produce the same outcome. Unfortunately, it is not always possible to observe which mechanism was responsible. For example, IMF scholars conjecture that nations enter IMF agreements both out of economic need and for discretionary domestic political reasons. Typically, though, all we observe is the fact of agreement, not its cause. Partial observability probit models (Poirier 1980,Journal of Econometrics12:209–217; Braumoeller 2003,Political Analysis11:209–233) provide one method for the statistical analysis of such phenomena. Unfortunately, they are often plagued by identification and labeling difficulties. Sometimes, however, qualitative studies of particular cases enlighten us about causes when quantitative studies cannot. We propose exploiting this information to lend additional structure to the partial observability approach. Monte Carlo simulation reveals that by anchoring “discernible” causes for a handful of cases about which we possess qualitative information, we obtain greater efficiency. More important, our method proves reliable at recovering unbiased parameter estimates when the partial observability model fails. The paper concludes with an analysis of the determinants of IMF agreements.A member shall be entitled to purchase the currencies of other members from the Fund …[provided] the member represents that it has a need to make the purchase because of its balance of payments or its reserve position or developments in its reserves.—International Monetary Fund Articles of Agreement[IMF] negotiations sometimes enable government leaders to do what they privately wish to do, but are powerless to do domestically.—Robert Putnam (1988, p. 457)
Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease
Authors: Diguet Elsa , Fernagut Pierre‐Olivier , Wei Xing , Du Yansheng , Rouland Richard , Gross Christian , Bezard Erwan , Tison François 
Published: June 2004

AbstractMinocycline has been shown to exert anti‐inflammatory effects underlying its putative neuroprotective properties in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of Parkinson's disease and in the R6/2 mouse model of Huntington's disease (HD). However, contradictory results have recently been reported. We report deleterious effects of minocycline in two phenotypic (toxic) models of Parkinson's disease and HD in monkey and mouse. Of seven MPTP‐intoxicated female cynomolgus monkeys (0.2 mg/kg, i.v. until day 15), three received minocycline (200 mg b.i.d.). While placebo‐MPTP‐treated animals displayed mild parkinsonism at day 15, the minocycline/MPTP‐treated animals tended to be more affected (P = 0.057) and showed a greater loss of putaminal dopaminergic nerve endings (P < 0.0001). In the 3‐nitropropionic acid (3‐NP) mouse model of HD, minocycline (45 mg/kg i.p.) was administered 30 min before each i.p. injection of 3‐NP (b.i.d., cumulated dose, 360 mg/kg in 5 days). Mice receiving minocycline exhibited a worsening of the mean motor score with a slower recovery slope, more impaired general activity and significantly deteriorated performances on the rotarod, pole test and beam‐traversing tasks. The histopathological outcome demonstrated that minocycline‐treated mice presented significantly more severe neuronal cell loss in the dorsal striatum. The effect of minocycline vs. 3‐NP was also investigated on hippocampal and cortical cell cultures. minocycline blocked 3‐NP‐induced neurotoxicity at certain doses (1 mm cortical neurons) but not at higher doses (10 mm). Thus, minocycline may have variable and even deleterious effects in different species and models according to the mode of administration and dose.
Activation of PKC induces rapid morphological plasticity in dendrites of hippocampal neurons via Rac and Rho‐dependent mechanisms
Authors: Pilpel Yair , Segal Menahem 
Published: June 2004

AbstractActivation of protein kinase C (PKC) produced a novel and rapid formation of lamellae over large surfaces of dendrites in cultured hippocampal neurons. This action was dendrite‐specific, involved a postsynaptic locus of activation of PKC and required actin polymerization, but not activation of Erk. Over‐expression of active Rho‐A GTPase converted a mature, highly branched and spiny neuron into a primitive, non‐branching, aspiny neuron. Overexpression of active Rac1 caused massive lamellae formation in the transfected neurons. These morphologically aberrant neurons retained synaptic connectivity with adjacent, normal neurons, as well as the ability to form lamellae in response to PKC. On the other hand, transfection with a dominant negative Rac‐N17 or a toxin C3, Rho‐A‐inactivating plasmid blocked lamellae formation by PKC, but did not prevent PKC‐induced plasticity of synaptic currents. These data indicate that PKC activates two independent molecular pathways, one of which involves Rac1 and Rho‐A, to produce massive actin‐based structural plasticity in dendrites and spines.
Olfactory receptor cells on the cockroach antennae: responses to the direction and rate of change in food odour concentration
Authors: Hinterwirth Armin , Zeiner Reinhard , Tichy Harald 
Published: June 2004

AbstractIn insects, information about food odour is encoded by olfactory receptor cells with characteristic response spectra, located in several types of cuticular sensilla. Within short, hair‐like sensilla on the cockroach's antenna, antagonistic pairs of olfactory receptor cells shape information inflow to the CNS by providing excitatory responses for both increases and decreases in food odour concentration. The segregation of food odour information into parallel ON and OFF responses suggests that temporal concentration changes become enhanced in the sensory output. When food odour concentration changes slowly and continuously up and down with smooth transition from one direction to another, the ON and OFF olfactory cells not only signal a succession of odour concentrations but also the rate with which odour concentration happens to be changing. Access to the values of such cues is of great use to an insect orientating to an odour source. With them they may extract concentration gradients from odour plumes.
Direction tuning of human motion detection determined from a population model
Authors: Maurer J. Peter , Heinrich Thomas S. , Bach Michael 
Published: June 2004

AbstractMass responses that are obtained using electrophysiological or psychophysical techniques are inadequate to characterize motion detectors at the single‐unit level. Therefore, we have modelled a population of motion detectors and fitted their mass response to motion‐onset EEG data. By examining a single unit of the modelled population we could assess the range of directions and the level of adaptation an individual motion detector responded to. Stimuli were patterns of randomly distributed dots. After subjects had adapted to either a non‐moving pattern or to motion in one fixed direction, the pattern moved in one of seven possible test directions. The population model assumed elementary motion detectors with a Gaussian angle‐selectivity profile. The population response was calculated as the sum of all adaptation‐weighted individual responses to the test direction. In all subjects, we observed sizeable effects of adaptation on test directions close to the adapted direction and small amounts of direction‐independent adaptation for all test directions. The model fit explained 75% (Oz) and 94% (lateral derivation) of the total variance and revealed a motion detector bandwidth (full width at half maximum) of 72° (Oz) and 62° (lateral derivation). The maximal adaptation depth was estimated as 72% (Oz) and 66% (lateral derivation). Estimates inferred from the population model representing human motion detectors were found to be close to those obtained by single‐cell data from non‐human primates.
Organization of prefrontal outflow toward frontal motor‐related areas in macaque monkeys
Authors: Takada M. , Nambu A. , Hatanaka N. , Tachibana Y. , Miyachi S. , Taira M. , Inase M. 
Published: June 2004

AbstractLinkage between the prefrontal cortex and the primary motor cortex is mediated by nonprimary motor‐related areas of the frontal lobe. In an attempt to analyse the organization of the prefrontal outflow from area 46 toward the frontal motor‐related areas, we investigated the pattern of projections involving the higher‐order motor‐related areas, such as the presupplementary motor area (pre‐SMA) and the rostral cingulate motor area (CMAr). Tracer injections were made into these motor‐related areas (their forelimb representation) on the medial wall that had been identified electrophysiologically. The following data were obtained from a series of tract‐tracing experiments in Japanese monkeys. (i) Only a few neurons in area 46 were retrogradely labelled from the pre‐SMA and CMAr; (ii) terminal labelling from area 46 occurred sparsely in the pre‐SMA and CMAr; (iii) a dual labelling technique revealed that the sites of overlap of anterograde labelling from area 46 and retrograde labelling from the pre‐SMA and CMAr were evident in the rostral parts of the dorsal and ventral premotor cortices (PMdr and PMvr); (iv) and tracer injections into the PMdr produced neuronal cell labelling in area 46 and terminal labelling in the pre‐SMA and CMAr. The present results indicate that a large portion of the prefrontal signals from area 46 is not directly conveyed to the pre‐SMA and CMAr, but rather indirectly by way of the PMdr and PMvr. This suggests that area 46 exerts its major influence on the cortical motor system via these premotor areas.
Spreading depression enhances the spontaneous epileptiform activity in human neocortical tissues
Authors: Gorji Ali , Speckmann Erwin‐Josef 
Published: June 2004

AbstractSpreading depression (SD) is a well‐known phenomenon in animal models of experimental epilepsy. However, the interaction of SD with epileptiform activity in human neuronal tissues is not clear. The aim of the present study was to investigate the effect of SD on synchronous rhythmic sharp field potentials in human neocortical slices. Spreading depression was elicited in human neocortical slices that exhibited sharp potentials. Extracellular field potentials were recorded from the third and fifth layers. SD significantly enhanced the repetition rate and amplitude of spontaneous rhythmic potentials in all tested slices. The results indicate that SD may facilitate the synchronization of different foci of rhythmic sharp field potentials and increase the excitability in human brain tissue.
Minocycline protects basal forebrain cholinergic neurons from mu p75‐saporin immunotoxic lesioning
Authors: Hunter Christopher L. , Quintero E. Matthew , Gilstrap Lindsay , Bhat Narayan R. , Granholm Ann‐Charlotte 
Published: June 2004

AbstractTwo prominent characteristics of Alzheimer's disease are basal forebrain cholinergic degeneration and neuroinflammation characterized by glial activation and the release of pro‐inflammatory cytokines. Mu p75‐ saporin (SAP) is a novel immunotoxin that mimics the selective loss of basal forebrain cholinergic neurons and induces cognitive impairment in mice. We report that cholinergic cell loss in the medial septal nucleus and ventral diagonal band after i.c.v. injection of mu p75‐SAP is accompanied by simultaneous activation of microglia and astrocytes in the basal forebrain region as well as significant memory loss. Consistent with a role of glial cells in the pathology of Alzheimer's disease, minocycline, a second‐generation tetracycline with known anti‐inflammatory and neuroprotective properties, attenuated mu p75‐SAP‐induced cholinergic cell loss, glial activation and transcription of downstream pro‐inflammatory mediators. In addition to neuroprotection, minocycline treatment mitigated the cognitive impairment that appears to be a functional consequence of mu p75‐SAP lesioning. The current study demonstrates that glial‐related inflammation plays a significant role in the selective neurotoxicity of mu p75‐SAP, and suggests that minocycline may provide a viable therapeutic option for degenerating cholinergic systems.
Spinal NF‐kB activation induces COX‐2 upregulation and contributes to inflammatory pain hypersensitivity
Authors: Lee Kyung‐Min , Kang Bong‐Seok , Lee Hye‐Lim , Son Sun‐Joo , Hwang Sung‐Hun , Kim Dong‐Sun , Park Jae‐Sik , Cho Hee‐Jung 
Published: June 2004

AbstractCyclooxygenase‐2 (COX‐2) is a major contributor to the elevation of spinal prostaglandin E2, which augments the processing of nociceptive stimuli following peripheral inflammation, and dynorphin has been shown to have an important role in acute and chronic pain states. Moreover, the transcription factor, nuclear factor‐kappa B (NF‐kB), regulates the expressions of both COX‐2 and dynorphin. To elucidate the role of spinal NF‐kB in the induction of inflammatory pain hypersensitivity, we examined whether activated NF‐kB affects pain behavior and the expressions of the mRNAs of COX‐2 and prodynorphin following peripheral inflammation. Intrathecal pretreatment with different NF‐kB inhibitors, namely, NF‐kB decoy or pyrrolidine dithiocarbamate, significantly reduced mechanical allodynia and thermal hyperalgesia following unilateral hindpaw inflammation evoked by complete Freund's adjuvant (CFA). These NF‐kB inhibitors also suppressed the activation of spinal NF‐kB and the subsequent remarkable elevation of spinal COX‐2 mRNA, but not that of prodynorphin mRNA. In addition, the activation of spinal NF‐kB following CFA injection was inhibited by intrathecal pretreatments with interleukin‐1β receptor antagonist or caspase‐1 inhibitor. In view of the fact that interleukin‐1 beta (IL‐1β) is the major inducer of spinal COX‐2 upregulation following CFA injection, our results suggest that IL‐1β‐induced spinal COX‐2 upregulation and pain hypersensitivity following peripheral inflammation are mediated through the activation of the NF‐kB‐associated pathways.
Selective antagonism of medial prefrontal cortex D4 receptors decreases fear‐related behaviour in rats
Authors: Shah Akeel A. , Sjovold Travis , Treit Dallas 
Published: June 2004

AbstractIt is well known that the mesolimbocortical dopamine pathway is highly active during periods of stress and fear. However, very little research has directly examined how dopamine receptors in this pathway influence fear‐related behaviour. The present study examined the effects of selective antagonism of D4, D1 and D2 dopamine receptors of the medial prefrontal cortex (MPFC) on rats' fear behaviour in the elevated plus‐maze and the shock‐probe burying tests. The results demonstrated that bilateral intra‐MPFC infusions of the highly selective D4 antagonist, L‐745 870 (0.2, 1 or 10 nmol/0.5 µL), increased the percentage of open‐arm entries and open‐arm time in the elevated plus‐maze test (1 nmol/0.5 µL), and decreased the duration of burying in the shock‐probe test (0.2 or 1 nmol/0.5 µL). Furthermore, none of the doses of the D4 antagonist affected measures of general activity or pain sensitivity. Intra‐MPFC infusions of the D1 antagonist, SCH‐23390 (0.2 or 1 nmol/0.5 µL), or the D2 antagonist, remoxipride (0.2, 1 or 10 nmol/0.5 µL), had no significant behavioural effects in either test. Taken together, these findings suggest that MPFC D4 receptors may play an important role in the mediation of fear‐related behaviour.