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Target Regions (target + regions)

Distribution by Scientific Domains

Life Sciences	66%
Chemistry	16%

Selected Abstracts

Combining Microarray-based Genomic Selection (MGS) with the Illumina Genome Analyzer Platform to Sequence Diploid Target Regions

ANNALS OF HUMAN GENETICS, Issue 5 2009
David T. Okou
Summary Novel methods of targeted sequencing of unique regions from complex eukaryotic genomes have generated a great deal of excitement, but critical demonstrations of these methods efficacy with respect to diploid genotype calling and experimental variation are lacking. To address this issue, we optimized microarray-based genomic selection (MGS) for use with the Illumina Genome Analyzer (IGA). A set of 202 fragments (304 kb total) contained within a 1.7 Mb genomic region on human chromosome X were MGS/IGA sequenced in ten female HapMap samples generating a total of 2.4 GB of DNA sequence. At a minimum coverage threshold of 5X, 93.9% of all bases and 94.9% of segregating sites were called, while 57.7% of bases (57.4% of segregating sites) were called at a 50X threshold. Data accuracy at known segregating sites was 98.9% at 5X coverage, rising to 99.6% at 50X coverage. Accuracy at homozygous sites was 98.7% at 5X sequence coverage and 99.5% at 50X coverage. Although accuracy at heterozygous sites was modestly lower, it was still over 92% at 5X coverage and increased to nearly 97% at 50X coverage. These data provide the first demonstration that MGS/IGA sequencing can generate the very high quality sequence data necessary for human genetics research. All sequences generated in this study have been deposited in NCBI Short Read Archive (http://www.ncbi.nlm.nih.gov/Traces/sra, Accession # SRA007913). [source]

Sequence-Based Identification of Specific Drug Target Regions in the Thymidylate Synthase Enzyme Family

CHEMMEDCHEM, Issue 3 2008
Stefania Ferrari Dr.
Thymidylate synthases from pathogenic organisms: Sequence analysis and knowledge-based grouping have provided a step forward in the identification of potential drug target regions in thymidylate synthases. This provides a unique approach toward blocking the growth of pathogenic organisms. [source]

Haptic-constraint modeling based on interactive metaballs

COMPUTER ANIMATION AND VIRTUAL WORLDS (PREV: JNL OF VISUALISATION & COMPUTER ANIMATION), Issue 5 2010
Hui Chen
Abstract Adding interactive haptic-constraint sensations is important in interactive computer gaming and 3D shape design. Usually constraints are set on vertices of the object to drive the deformation. How to simulate dynamic force constraints in interactive design is still a challenging task. In this paper, we propose a novel haptic-constraint modeling method based on interactive metaballs, during which the haptic-constraint tools are attracted to the target location and then control the touch-enabled deformation within the constrained areas. The interactive force feedbacks facilitate designers to accurately deform the target regions and fine carve the details as their intention on the objects. Our work studies how to apply touch sensation in such constrained deformations using interactive metaballs, thus users can truly feel and control the soft-touch objects during the deforming interactions. Experimental results show that the dynamic sense of touch during the haptic manipulation is intuitively simulated to users, via the interacting interface we have developed. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Simultaneous detection of genetically modified organisms by multiplex ligation-dependent genome amplification and capillary gel electrophoresis with laser-induced fluorescence

ELECTROPHORESIS, Issue 13 2010
Virginia García-Cañas
Abstract In this work, an innovative method useful to simultaneously analyze multiple genetically modified organisms is described. The developed method consists in the combination of multiplex ligation-dependent genome dependent amplification (MLGA) with CGE and LIF detection using bare-fused silica capillaries. The MLGA process is based on oligonucleotide constructs, formed by a universal sequence (vector) and long specific oligonucleotides (selectors) that facilitate the circularization of specific DNA target regions. Subsequently, the circularized target sequences are simultaneously amplified with the same couple of primers and analyzed by CGE-LIF using a bare-fused silica capillary and a run electrolyte containing 2-hydroxyethyl cellulose acting as both sieving matrix and dynamic capillary coating. CGE-LIF is shown to be very useful and informative for optimizing MLGA parameters such as annealing temperature, number of ligation cycles, and selector probes concentration. We demonstrate the specificity of the method in detecting the presence of transgenic DNA in certified reference and raw commercial samples. The method developed is sensitive and allows the simultaneous detection in a single run of percentages of transgenic maize as low as 1% of GA21, 1% of MON863, and 1% of MON810 in maize samples with signal-to-noise ratios for the corresponding DNA peaks of 15, 12, and 26, respectively. These results demonstrate, to our knowledge for the first time, the great possibilities of MLGA techniques for genetically modified organisms analysis. [source]

Membrane-associated guidance cues direct the innervation of forebrain and midbrain by dorsal raphe-derived serotonergic axons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2005
Audrey Petit
Abstract Unlike many neurons that extend an axon precisely to a single target, individual dorsal raphe 5-HT neurons project to multiple brain regions and their axon terminals often lack classical synaptic specializations. It is not known how 5-HT axon collaterals select between multiple target fields, or even if 5-HT axons require specific guidance cues to innervate their targets. Nor is it known how these axon collaterals are restrained within specific innervation target regions. To investigate this, we challenged explants of dorsal raphe with co-explants, or cell membrane preparations of ventral midbrain, striatum or cerebral cortex. We provide evidence for membrane-associated cues that promote 5-HT axon growth into each of these three target regions. The axon growth-promoting activity was heat-, protease- and phosphatidylinositol-phospholipase-C (PI-PLC)-sensitive. Interestingly, 5-HT axons specifically lost the ability to grow in heterotypic explants, or membrane carpets, following contact with ventral midbrain or striatal, but not cortical, explants or membranes. This inductive activity associated with striatal and ventral midbrain membranes was sensitive to both high salt extraction and PI-PLC treatment. By contrast, the activity that inhibited 5-HT axon growth onto heterotypic membranes was sensitive only to high salt extraction. These results provide evidence that a glycosylphosphatidylinositol (GPI)-linked membrane protein promotes 5-HT axon growth, and that short-range membrane-bound, as well as GPI-linked, molecules contribute to the guidance of 5-HT axon collaterals. These findings suggest that 5-HT axon collaterals acquire a target-induced growth-inhibitory response to alternative targets, increasing their selectivity for the newly innervated field. [source]

Differential effect of oestradiol and astroglia-conditioned media on the growth of hypothalamic neurons from male and female rat brains

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2000
M. J. Cambiasso
Abstract To determine whether soluble products from different CNS regions differ in their ability to support oestrogen-stimulated neurite growth, hypothalamic neurons from sexually segregated embryos were cultured with astroglia-conditioned medium (CM) derived from cortex, striatum and mesencephalon, with or without 17-,-oestradiol 100 n m added to the medium. After 48 h in vitro, neurite outgrowth was quantified by morphometric analysis. Astroglia-CM from mesencephalon (a target for the axons of hypothalamic neurons) induced the greatest axogenic response in males and in this case only a neuritogenic effect could be demonstrated for oestradiol. On the other hand, astroglia-CM from regions that do not receive projections from ventromedial hypothalamus inhibited axon growth. A sexual difference in the response of hypothalamic neurons to astroglia-CM and oestradiol was found; growth of neurons from female foetuses was increased by astroglia-CM from mesencephalon, but no neuritogenic effect could be demonstrated for oestradiol in these cultures. Blot immunobinding demonstrated the presence of receptors for neurotrophic factors in cultures of hypothalamic neurons; Western blot analysis of these cultures demonstrated that oestradiol increased the concentration of trkB and IGF-I R,, whereas trkA was not detected and the concentration of trkC was not modified. These results support the hypothesis that target regions produce some factor(s) that stimulate the growth of axons from projecting neurons and further indicate that in the case of males this effect is modulated by oestradiol, perhaps mediated through the upregulation of trkB and IGF-I receptors. [source]

Specific inhibition of transforming growth factor-,2 expression in human osteoblast cells by antisense phosphorothioate oligonucleotides

FEBS JOURNAL, Issue 8 2001
Zhong-Jian Shen
To elucidate the role of endogenous transforming growth factor (TGF)-,2 on human osteoblast cell, antisense phosphorothioate oligonucleotides (S-ODNs) complementary to regions in mRNA of TGF-,2 were synthesized and examined their effects on TGF-,2 production and cell proliferation in a human osteoblast cell line ROS 17/2. Antisense S-ODNs were designated for three different target regions in the mRNA of TGF-,2. Among several antisense S-ODN analyzed, an oligonucleotide (AS-11) complementary to the translation initiation site of mRNA of TGF-,2 demonstrated a selective and strong inhibitory effect on TGF-,2 production in osteoblast cells. Other antisense S-ODNs which were designated for other regions in mRNA of TGF-,2 and one- or three-base mismatched analogs of AS-11 showed little or much less antisense activities than AS-11. Therefore, the most effective target site in mRNA of TGF-,2 is at the initiation codon region. The antisense effects of AS-11 were observed without reduction of levels of mRNA of TGF-,2. Furthermore, the inhibition of TGF-,2 expression by antisense S-ODN appeared to enhance cell proliferation, demonstrating the growth inhibitory effect of autocrine TGF-,2 in osteoblast cells. [source]

Cortical efferents of the perirhinal, postrhinal, and entorhinal cortices of the rat

HIPPOCAMPUS, Issue 12 2009
Kara L. Agster
Abstract We investigated the cortical efferents of the parahippocampal region by placing injections of the anterograde tracers, Phaseolus vulgaris -leuccoagglutinin, and biotinylated dextran amine, throughout the perirhinal (PER), postrhinal (POR), and entorhinal cortices of the rat brain. The resulting density of labeled fibers was evaluated in 25 subregions of the piriform, frontal, insular, temporal, cingulate, parietal, and occipital areas. The locations of labeled terminal fibers differed substantially depending on whether the location of the injection site was in PER area 35, PER area 36, POR, or the lateral or the medial entorhinal (LEA and MEA). The differences were greater for sensory regions. For example, the POR efferents preferentially target visual and spatial regions, whereas the PER efferents target all sensory modalities. The cortical efferents of each region largely reciprocate the cortical afferents, though the degree of reciprocity varied across originating and target regions. The laminar pattern of terminal fibers was consistent with the notion that the efferents are feedback projections. The density and amount of labeled fibers also differed substantially depending on the regional location of injection sites. PER area 36 and POR give rise to a greater number of heavy projections, followed by PER area 35. LEA also gives rise to widespread cortical efferents, arising mainly from a narrow band of cortex adjacent to the PER. In contrast, the remainder of the LEA and the MEA provides only weak efferents to cortical regions. Prior work has shown that nonspatial and spatial information is transmitted to the hippocampus via the PER-LEA and POR-MEA pathways, respectively. Our findings suggest that the return projections follow the same pathways, though perhaps with less segregration. © 2009 Wiley-Liss, Inc. [source]

Projections of RFamide-related Peptide-3 Neurones in the Ovine Hypothalamus, with Special Reference to Regions Regulating Energy Balance and Reproduction

JOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2009
Y. Qi
RFamide-related peptide-3 (RFRP-3) is a neuropeptide produced in cells of the paraventricular nucleus and dorsomedial nucleus of the ovine hypothalamus. In the present study, we show that these cells project to cells in regions of the hypothalamus involved in energy balance and reproduction. A retrograde tracer (FluoroGold) was injected into either the arcuate nucleus, the lateral hypothalamic area or the ventromedial nucleus. The distribution and number of retrogradely-labelled RFRP-3 neurones was determined. RFRP-3 neurones projected to the lateral hypothalamic area and, to a lesser degree, to the ventromedial nucleus and the arcuate nucleus. Double-label immunohistochemistry was employed to identify cells receiving putative RFRP-3 input to cells in these target regions. RFRP-3 cells were seen to project to neuropeptide Y and pro-opiomelanocortin neurones in the arcuate nucleus, orexin and melanin-concentrating hormone neurones in the lateral hypothalamic area, as well as orexin cells in the dorsomedial nucleus and corticotrophin-releasing hormone and oxytocin cells in the paraventricular nucleus. Neurones expressing gonadotrophin-releasing hormone in the preoptic area were also seen to receive input from RFRP-3 projections. We conclude that RFRP-3 neurones project to hypothalamic regions and cells involved in regulation of energy balance and reproduction in the ovine brain. [source]

Human embryonic stem cell-derived neural precursors develop into neurons and integrate into the host brain

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2006
Daniel J. Guillaume
Abstract Whether and how in-vitro-produced human neural precursors mature and integrate into the brain are crucial to the utility of human embryonic stem (hES) cells in treating neurological disorders. After transplantation into the ventricles of neonatal immune-deficient mice, hES-cell-derived neural precursors stopped expressing the cell division marker Ki67, except in neurogenic areas, and differentiated into neurons and then glia in a temporal course intrinsic to that of human cells regardless of location. The human cells located in the gray matter became neurons in the olfactory bulb and striatum, whereas those in the white matter produced exclusively glia. Importantly, the grafted human cells formed synapses. Thus, the in-vitro-produced human neural precursors follow their intrinsic temporal program to produce neurons and glia and, in response to environmental signals, generate cells appropriate to their target regions and integrate into the brain. © 2006 Wiley-Liss, Inc. [source]

A population genomic approach to map recent positive selection in model species

MOLECULAR ECOLOGY, Issue 16 2008
P. PAVLIDIS
Abstract Based on nearly complete genome sequences from a variety of organisms data on naturally occurring genetic variation on the scale of hundreds of loci to entire genomes have been collected in recent years. In parallel, new statistical tests have been developed to infer evidence of recent positive selection from these data and to localize the target regions of selection in the genome. These methods have now been successfully applied to Drosophila melanogaster, humans, mice and a few plant species. In genomic regions of normal recombination rates, the targets of positive selection have been mapped down to the level of individual genes. [source]

The CitST two-component system regulates the expression of the Mg-citrate transporter in Bacillus subtilis

MOLECULAR MICROBIOLOGY, Issue 4 2000
Hiroki Yamamoto
citS and citT genes encoding a new two-component system were identified in the 71° region between the pel and citM loci on the Bacillus subtilis chromosome. citS- and citT- deficient strains were unable to grow on minimal plates including citrate as a sole carbon source. In addition, a strain deficient in citM, which encodes the secondary transporter of the Mg-citrate complex, exhibited the same phenotype on this medium. Northern blot analysis revealed that citM was polycistronically transcribed with the downstream yflN gene, and that CitS and CitT were necessary for transcription of the citM,yflN operon. Upon addition of 2 mM citrate to DSM, this operon was strongly induced after the middle of the exponential growth phase in the wild type, but not in the citST double null mutant. Moreover, the transcription of this operon was completely repressed in the presence of 1% glucose. We found a sequence exhibiting homology to a catabolite-responsive element (cre) in the citM promoter region. Glucose repression was lost in ccpA and citM,cre mutants. From the result of a citM,promoter deletion experiment, putative CitT target sequences were found to be located around two regions, from ,62 to ,74 and from ,149 to ,189, relative to the citM start point. Furthermore, DNase I footprinting assays revealed that these two CitT target regions extended maximally from ,36 to ,84 and from ,168 to ,194. From these findings, we concluded that the expression of citM is positively regulated by the CitST system and negatively regulated by CcpA. [source]

Cellular configuration of single octopamine neurons in Drosophila

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 12 2010
Sebastian Busch
Abstract Individual median octopamine neurons in the insect central nervous system serve as an excellent model system for comparative neuroanatomy of single identified cells. The median octopamine cluster of the subesophageal ganglion consists of defined sets of paired and unpaired interneurons, which supply the brain and subesophageal ganglion with extensive ramifications. The developmental program underlying the complex cellular network is unknown. Here we map the segmental location and developmental origins of individual octopamine neurons in the Drosophila subesophageal ganglion. We demonstrate that two sets of unpaired median neurons, located in the mandibular and maxillary segments, exhibit the same projection patterns in the brain. Furthermore, we show that the paired and unpaired neurons belong to distinct lineages. Interspecies comparison of median neurons revealed that many individual octopamine neurons in different species project to equivalent target regions. Such identified neurons with similar morphology can derive from distinct lineages in different species (i.e., paired and unpaired neurons). J. Comp. Neurol. 518:2355,2364, 2010. © 2010 Wiley-Liss, Inc. [source]

Neurokinin B-producing projection neurons in the lateral stripe of the striatum and cell clusters of the accumbens nucleus in the rat

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2004
Ligang Zhou
Abstract Neurons producing preprotachykinin B (PPTB), the precursor of neurokinin B, constitute 5% of neurons in the dorsal striatum and project to the substantia innominata (SI) selectively. In the ventral striatum, PPTB-producing neurons are collected mainly in the lateral stripe of the striatum (LSS) and cell clusters of the accumbens nucleus (Acb). In the present study, we first examined the distribution of PPTB-immunoreactive neurons in rat ventral striatum and found that a large part of the PPTB-immunoreactive cell clusters was continuous to the LSS, but a smaller part was not. Thus, we divided the PPTB-immunoreactive cell clusters into the LSS-associated and non-LSS-associated ones. We next investigated the projection targets of the PPTB-producing ventral striatal neurons by combining immunofluorescence labeling and retrograde tracing. After injection of Fluoro-Gold into the basal component of the SI (SIb) and medial part of the interstitial nucleus of posterior limb of the anterior commissure, many PPTB-immunoreactive neurons were retrogradely labeled in the LSS-associated cell clusters and LSS, respectively. When the injection site included the ventral part of the sublenticular component of the SI(SIsl), retrogradely labeled neurons showed PPTB-immunoreactivity frequently in non-LSS-associated cell clusters. Furthermore, these PPTB-immunoreactive projections were confirmed by the double-fluorescence method after anterograde tracer injection into the ventral striatum containing the cell clusters. Since the dorsalmost part of the SIsl is known to receive strong inputs from PPTB-producing dorsal striatal neurons, the present results indicate that PPTB-producing ventral striatal neurons project to basal forebrain target regions in parallel with dorsal striatal neurons without significant convergence. J. Comp. Neurol. 480:143,161, 2004. © 2004 Wiley-Liss, Inc. [source]

NtSET1, a member of a newly identified subgroup of plant SET-domain-containing proteins, is chromatin-associated and its ectopic overexpression inhibits tobacco plant growth

THE PLANT JOURNAL, Issue 4 2001
Wen-Hui Shen
Summary The SET- and chromo-domains are recognized as signature motifs for proteins that contribute to epigenetic control of gene expression through effects on the regional organization of chromatin structure. This paper reports the identification of a novel subgroup of SET-domain-containing proteins in tobacco and Arabidopsis, which show highest homologies with the Drosophila position-effect-variegation repressor protein SU(VAR)3,9 and the yeast centromer silencing protein CLR4. The tobacco SET-domain-containing protein (NtSET1) was fused to the green fluorescence protein (GFP) that serves as a visual marker for localization of the recombinant protein in living cells. Whereas control GFP protein alone was uniformly dispersed within the nucleus and cytoplasm, the NtSET1-GFP fusion protein showed a non-uniform localization to multiple nuclear regions in interphase tobacco TBY2 cells. During mitosis, the NtSET1-GFP associated with condensed chromosomes with a non-random distribution. The NtSET1 thus appears to have distinct target regions in the plant chromatin. Overexpression of the NtSET1-GFP in transgenic tobacco inhibited plant growth, implicating the possible involvement of the NtSET1 in transcriptional repression of growth control genes through the formation of higher-order chromatin domains. [source]

The value of observations.

THE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue 628 2007
II: The value of observations located in singular-vector-based target areas
Abstract Data-assimilation experiments have been run in seven different configurations for two seasons to assess the value of observations taken in target regions identified either using singular vectors (SVs) or randomly, and located over the Pacific or the Atlantic Oceans. The value has been measured by the relative short-range forecast error reduction in downstream areas, specifically a North American region for observations taken in the Pacific Ocean, and a European region for observations taken in the Atlantic Ocean. Overall, results have indicated (1) that observations taken in SV-target areas are on average more valuable than observations taken in randomly selected areas, (2) that it is important that the daily set of singular vectors are used to compute the target areas, and (3) that the value of targeted observations depends on the region, the season and the baseline observing system. If the baseline observing system is data-void over the ocean, then the average value of observations taken in SV-target areas is very high. Considering for example winter 2004, SV-targeted observations over the Pacific (Atlantic) reduce the day-2 forecasts error of 500 hPa geopotential height forecasts in the verification region by 27.5% (19.1%), compared to 15.7% (14.9%) for observations taken in random areas. By contrast, if the baseline observing system is data-rich over the ocean, then the average value of observations taken in SV-target areas is rather small. Considering for example winter 2004, it has been estimated that adding SV-targeted observations over the Pacific (Atlantic) would reduce, on average, the day-2 forecasts error in the verification region by 4.0% (2.0%), compared to 0.5% (1.7%) for observations in random areas. These average results have been confirmed by single-case investigations, and by a careful examination of time series of forecast errors. These results indicate that more accurate assimilation systems that can exploit the potential value of localized observations are needed to increase the average return of investments in targeting field experiments. Copyright © 2007 Royal Meteorological Society [source]