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Results for “spatial sequencing”

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At least 757 records · Page 42Linked to original sources

PubMed2000

Diffusion tensor imaging demonstrates deviation of fibres in normal appearing white matter adjacent to a brain tumour.

The objective was to study fibre orientation in the cerebral white matter of a patient with a brain tumour using diffusion tensor imaging (DTI). A patient with a mild left hemiparesis and a tumour in the right frontal lobe and 20 healthy volunteers were scanned with a DTI sequence. The scans were spatially normalised and the fibre orientation in the patient compared with the fibre orientation in normal controls. DTI disclosed a change of the orientation of fibres in the patient compared with normal controls. In the normal appearing white matter adjacent to the tumour fibres deviated from the normal superior inferior orientation in the corona radiata by about 30 degrees. This finding was consistent with a displacement by distant mass effect rather than a destruction of fibres, in agreement with the neurological examination. In conclusion, DTI demonstrated a deviation of fibres in normal appearing white matter adjacent to a tumour. The technique will improve understanding of the effects of structural abnormalities on fibres. This will assist the interpretation of clinical findings and functional imaging studies and guide neurosurgical interventions.

Brain↗

PubMed1990

Variation of contrast between different brain tissues with an MR snapshot technique.

The lack of tissue contrast in gradient-echo sequences with very short repetition times can be overcome by using a single inversion pulse prior to the entire imaging sequence. The contrast can be changed by variation of the time delay between the inversion pulse and the first excitation. This snapshot technique was introduced for very fast acquisition of images, but it also provides images with a strong contrast of gray to white matter and of brain tissue to cerebrospinal fluid. The authors designed a sequence that allows sufficient spatial resolution and good image quality. The measurement time is 1.2 seconds, and the in-plane resolution is 0.8 mm. A large variation in contrast with different inversion times was demonstrated on brain images of volunteers and patients.

Brain↗

PubMed2006

Predicting transcription factor binding sites using local over-representation and comparative genomics.

BACKGROUND: Identifying cis-regulatory elements is crucial to understanding gene expression, which highlights the importance of the computational detection of overrepresented transcription factor binding sites (TFBSs) in coexpressed or coregulated genes. However, this is a challenging problem, especially when considering higher eukaryotic organisms. RESULTS: We have developed a method, named TFM-Explorer, that searches for locally overrepresented TFBSs in a set of coregulated genes, which are modeled by profiles provided by a database of position weight matrices. The novelty of the method is that it takes advantage of spatial conservation in the sequence and supports multiple species. The efficiency of the underlying algorithm and its robustness to noise allow weak regulatory signals to be detected in large heterogeneous data sets. CONCLUSION: TFM-Explorer provides an efficient way to predict TFBS overrepresentation in related sequences. Promising results were obtained in a variety of examples in human, mouse, and rat genomes. The software is publicly available at http://bioinfo.lifl.fr/TFM-Explorer.

Algorithms↗

PubMed2025

Advances in tumor subclone formation and mechanisms of growth and invasion.

Tumor subclones refer to distinct cell populations within the same tumor that possess different genetic characteristics. They play a crucial role in understanding tumor heterogeneity, evolution, and therapeutic resistance. The formation of tumor subclones is driven by several key mechanisms, including the inherent genetic instability of tumor cells, which facilitates the accumulation of novel mutations; selective pressures from the tumor microenvironment and therapeutic interventions, which promote the expansion of certain subclones; and epigenetic modifications, such as DNA methylation and histone modifications, which alter gene expression patterns. Major methodologies for studying tumor subclones include single-cell sequencing, liquid biopsy, and spatial transcriptomics, which provide insights into clonal architecture and dynamic evolution. Beyond their direct involvement in tumor growth and invasion, subclones significantly contribute to tumor heterogeneity, immune evasion, and treatment resistance. Thus, an in-depth investigation of tumor subclones not only aids in guiding personalized precision therapy, overcoming drug resistance, and identifying novel therapeutic targets, but also enhances our ability to predict recurrence and metastasis risks while elucidating the mechanisms underlying tumor heterogeneity. The integration of artificial intelligence, big data analytics, and multi-omics technologies is expected to further advance research in tumor subclones, paving the way for novel strategies in cancer diagnosis and treatment. This review aims to provide a comprehensive overview of tumor subclone formation mechanisms, evolutionary models, analytical methods, and clinical implications, offering insights into precision oncology and future translational research.

Humans↗

PubMed2000

Cerebellar activation during optokinetic stimulation and saccades.

OBJECTIVE: To investigate the activation pattern of cerebellar structures during small-field optokinetic stimulation (OKN) by functional MRI (fMRI) and compare it with that obtained during voluntary saccades and fixation suppression of OKN. METHODS: Functional images were acquired from oblique transverse slices of eight healthy, right-handed volunteers using a radio frequency-spoiled, single-slice, fast low-angle shot (FLASH) pulse sequence with high-spatial resolution. RESULTS: Horizontal OKN and saccades were associated with bilateral activity in the cerebellar hemispheres (superior semilunar lobule, simple lobule, quadrangular lobule, inferior semilunar lobule), the middle cerebellar peduncle, the dentate nucleus, and medially in the culmen and uvula of cerebellar nuclei. The pattern and extent of activation were independent of the stimulus direction for OKN and saccades. During fixation suppression, the extent of activation was significantly diminished (hemispheres) or even absent (uvula, culmen). CONCLUSION: The differential effects of fixation suppression on this complex pattern of cerebellar activation in part allow us to separate visual and attentional from ocular motor processing. Our data agree with behavioral and physiologic animal data about ocular motor processes and motor learning in the vestibulospinal and optokinetic reflex. This suggests that hemispheric cerebellar activity may be mainly associated with changes in attention, whereas vermal activity seems to be associated with ocular motor control, and activity of the dentate nuclei and the cerebellar peduncles seems to be associated with both.

Adult↗

PubMed2004

Function and regulation of FoxF1 during Xenopus gut development.

Development of the visceral mesoderm is a critical process in the organogenesis of the gut. Elucidation of function and regulation of genes involved in the development of visceral mesoderm is therefore essential for an understanding of gut organogenesis. One of the genes specifically expressed in the lateral plate mesoderm, and later in its derivative, the visceral mesoderm, is the Fox gene FoxF1. Its function is critical for Xenopus gut development, and embryos injected with FoxF1 morpholino display abnormal gut development. In the absence of FoxF1 function, the lateral plate mesoderm, and later the visceral mesoderm, does not proliferate and differentiate properly. Region- and stage-specific markers of visceral mesoderm differentiation, such as Xbap and alpha-smooth muscle actin, are not activated. The gut does not elongate and coil. These experiments provide support for the function of FoxF1 in the development of visceral mesoderm and the organogenesis of the gut. At the molecular level, FoxF1 is a downstream target of BMP4 signaling. BMP4 can activate FoxF1 transcription in animal caps and overexpression of FoxF1 can rescue twinning phenotypes, which results from the elimination of BMP4 signaling. The cis-regulatory elements of FoxF1 are located within a 2 kb DNA fragment upstream of the coding region. These sequences can drive correct temporal-spatial expression of a GFP reporter gene in transgenic Xenopus tadpoles. These sequences represent a unique tool, which can be used to specifically alter gene expression in the lateral plate mesoderm.

Animals↗

PubMed1989

Analysis of lens cell fate and eye morphogenesis in transgenic mice ablated for cells of the lens lineage.

Transgenic mice carrying the diphtheria toxin A gene driven by mouse gamma 2-crystallin promoter sequences manifest microphthalmia due to ablation of fiber cells in the ocular lens. Here we map ablation events in the lens by crossing animals hemizygous for the ablation construct with transgenic mice homozygous for the in situ lacZ reporter gene driven by identical gamma 2-crystallin promoter sequences. By comparing the spatial distribution of lacZ-expressing cells and the profile of gamma-crystallin gene expression in the lenses of normal and microphthalmic offspring, the contributions of specific cell types to lens development were examined. The results suggest that phenotypically and developmentally distinct populations of lens fiber cells are able to contribute to the lens nucleus during organogenesis. We also show that dosage of the transgene and its site of integration influence the extent of ablation. In those mice homozygous for the transgene and completely lacking cells of the lens lineage, we show that the sclera, cornea, and ciliary epithelium are reduced in size but, otherwise, reasonably well formed. In contrast, the anterior chamber, iris, and vitreous body are not discernible while the sensory retina is highly convoluted and extensively fills the vitreous chamber.

Animals↗

PubMed1998

Spatial and temporal targeting of gene expression in Drosophila by means of a tetracycline-dependent transactivator system.

In order to evaluate the efficiency of the tetracycline-regulated gene expression system in Drosophila, we have generated transgenic lines expressing a tetracycline-controlled transactivator protein (tTA), with specific expression patterns during embryonic and larval development. These lines were used to direct expression of a tTA-responsive promoter fused to the coding region of either the beta-galactosidase or the homeotic protein Antennapedia (ANTP), under various conditions of tetracycline treatment. We found that expression of beta-galactosidase can be efficiently inhibited in embryos and larvae with tetracycline provided in the food, and that a simple removal of the larvae from tetracycline exposure results in the induction of the enzyme in a time- and concentration-dependent manner. Similar treatments can be used to prevent the lethality associated with the ectopic expression of ANTP in embryos and, subsequently, to control the timing of expression of the homeoprotein ANTP specifically in the antennal imaginal disc. Our results show that the expression of a gene placed under the control of a tetracycline-responsive promoter can be tightly controlled, both spatially by the regulatory sequences driving the expression of tTA and temporally by tetracycline. This provides the basis of a versatile binary system for controlling gene expression in Drosophila, with an additional level of regulation as compared to the general method using the yeast transcription factor GAL4.

Animals↗

PubMed1992

Magnetic resonance imaging of pulsatile cerebrospinal fluid flow by spatial modulation of magnetization.

Various orders of binomial spatial modulation of magnetization sequences up to (1 4 6 4 1) have been tested to find the optimum sequence for clinical application. Stripe width, stripe sharpness and the tolerance of the sequences to radiofrequency non-linearity have been investigated. The (1 3 3 1) sequence was found to be a good compromise between competing design criteria, and its application to viewing pulsatile cerebrospinal fluid motion is described.

Cerebrospinal Fluid↗

PubMed1998

Evocation and characterization of percepts of apparent motion on the face.

The percepts evoked by sequential stimulation of sites in close spatial proximity (< or = 2.5 cm) on the face were studied. Both method-of-limits and magnitude-estimation procedures were used to identify and characterize alterations in the percepts produced by systematic changes in the temporal and spatial parameters of the sequence. Each site was stimulated by a vertically oriented row of miniature vibrating probes. Apparent motion was consistently perceived when the delay between the onsets of sequentially activated rows (interstimulus onset interval, or ISOI) fell within a relatively narrow range of values, the lower limit of which approximated 5 msec. Both the upper limit and the perceived smoothness and continuity of the motion percepts (goodness of motion) increased with the duration for which each row stimulated the skin over the range evaluated, 15-185 msec. For the successive activation of only two rows, goodness of motion was not influenced by changes in their separation from 0.4 to 2.5 cm. The ISOI values at which magnitude estimates of goodness of motion were highest increased with the duration for which each row stimulated the skin. As such, maximum goodness of motion decreased with increases in the apparent velocity of motion. When the number of sequentially activated rows was increased from two to four or more, the quality of the motion percepts improved. For the successive activation of multiple closely spaced rows, values of ISOI at which numerical estimates of goodness of motion were highest approximated integral fractions of the duration for which each row stimulated the skin. In this situation, the probes rose and fell in a regular, step-locked rhythm to simulate an edge-like or rectangular object moving across the skin. The goodness of motion so attained was relatively independent of the apparent velocity of motion.

Adult↗

PubMed2000

In situ diagnosis of human papillomaviruses.

In situ hybridization (ISH) is the demonstration of specific genetic information within a morphologic context. For HPV, colorimetric ISH has the advantage that it can be applied to routine formalin-fixed paraffin embedded tissues. This conserves patient material and permits histologic selection of optimal material for testing. ISH allows for precise spatial localization of viral sequences within tissues. ISH also allows the integration status of HPV to be determined. The major limitations of the method are the potential for error in HPV typing because of probe cross-hybridization and relatively low sensitivity if the method is not fully optimized.

DNA, Viral↗

PubMed2001

Strain-specific effects of amphetamine on prepulse inhibition and patterns of locomotor behavior in mice.

Several reports describe substantive behavioral differences between strains of mice both at baseline and in response to pharmacological manipulations. For example, mouse strain differences have been reported in prepulse inhibition (PPI) and patterns of locomotor activity, two behavioral processes that are altered by dopamine (DA) agonists such as amphetamine. Here, we characterized acoustic and tactile startle reactivity, acoustic PPI, and both the amounts and spatial patterns of locomotor activity in C57BL/6J, 129SvEv (129S6), and 129SvJ (129X1) mice at baseline and in amphetamine dose-response studies. Because hearing loss is common in numerous strains of mice, we also assessed cross-modal PPI using a light prepulse with an airpuff startle stimulus. The results establish that these three inbred strains of mice display both intra- and cross-modal PPI, and that amphetamine decreases PPI and startle reactivity in a dose-, sensory modality-, and strain-specific manner. Furthermore, the amount of locomotor activity and the spatial pattern of motor sequences are altered differentially after treatment with amphetamine in C57BL/6J and 129X1 mice, but not in 129S6 mice. Given that amphetamine releases presynaptic DA, these findings are consistent with the role of DA in the modulation of PPI and motor patterns in mice. These findings highlight the importance of selecting appropriate strains of mice for behavioral, pharmacological, and genetic studies.

Acoustic Stimulation↗

PubMed2000

[Cell activities in primate areas F2 and F4 of the monkey during memorized spatial motor task].

Single-cell activities were recorded in the area F2 of dorsal premotor cortex (PMd) and area F4 of ventral premotor cortex (PMv) while a monkey was performing a memorized spatial motor task of sequence (MSS). For the task of MSS-G, using green light as a cue during the cue period, 78.2% and 41.5% of the task-related neurons exhibited changes in activities in the areas F2 and F4, respectively( (2) 15.2, P<0.005), whereas there were more neurons exhibiting changes in activities in F4 than in F2 during the image and the touch periods. The differences were both statistically significant. Similar results were obtained for the task of MSS-R using red light as a cue. Furthermore, there were more cells responding to the cue signal in F2 than in F4, while the situation was reversed during the image and touch periods. The present findings indicate that neurons in the PMd and PMv examined are differentially involved in the MSS task.

Animals↗

PubMed2002

HLA and sarcoidosis: new pathogenetic insights.

Many theories have been presented to account for the immunological and epidemiological features of sarcoidosis; several lines of study support the prevailing opinion that an environmental agent, possibly microbial in origin, may cause sarcoidosis in a genetically predisposed host. Many polymorphic genes have been suggested to contribute to this genetic susceptibility: genes encoding angiotensin converting enzyme, vitamin D receptor, and interleukin-1, T-cell receptor genes, Gm and Km immunoglobulin genes and, most relevant, HLA genes (classical and non classical). There is also some evidence of an HLA-associated protection against sarcoidosis. The main action of disease-associated HLA molecules is to present specific antigenic peptides in such a way that the recognizing T-lymphocytes initiate an inflammatory response with peculiar pathological consequences. Other, so-called, non-classical HLA genes coding for proteins involved in antigen processing and presentation, namely TAP, LMP and DM, seem to contribute. Particular alleles of the tumor necrosis factor gene cluster (TNFA, LTA, LTB) are known to be associated with peculiar clinical forms of sarcoidosis. For instance, Löfgren's syndrome, which is an acute form of pulmonary sarcoidosis with frequent spontaneous remission, is marked by the TNFA*2, HLA-DR3 haplotype. How many HLA genes are involved is still unknown, but it is now clear that the HLA region is strongly implicated in the development of sarcoidosis. Probably, the future lies in isolating and sequencing the putative peptide bound to susceptible MHC molecules which, activating reactive T-cells, is responsible for disease initiation and/or exacerbation. However, the investigative approach should not be confined only to genomic sequences: the temporal and spatial expression of gene products, the post-transcriptional modification of the protein products will be fundamental in determining the basic functional context of developing sarcoidosis.

Genes, MHC Class I↗

PubMed2002

[Noninvasive vascular diagnosis with magnetic resonance angiography].

Currently contrast medium-enhanced, 3D magnetic resonance angiography enables fast and non-invasive depiction of the arterial vessels in the neck, thorax, abdomen, and limbs, which allows high sensitivity and specificity in the diagnostically evaluation of aneurysms, dissection and arterial stenosis. Intravenous bolus administration of a paramagnetic contrast medium is performed after timing of the bolus arrival time, thus enabling rapid acquisition of 3D datasets with high contrast between vessel lumen and surrounding soft tissue. Thorax and abdomen are examined within one breath-hold, the periphery of the extremities and the supra-aortal vessels can be imagined with longer sequences and even increased spatial resolution. Fast contrast-enhanced 3D magnetic resonance angiography--in combination with flow measurements--carries the potential to replace the additional functional information obtained by conventional digital subtraction angiography.

Angiography, Digital Subtraction↗

PubMed1990

[Spatial association of nucleotide substitutions during the evolution of DNA sequences].

Evolutionary models for estimating the number of nucleotide substitutions between DNA sequences are evaluated with data from histone gene sequences of 7 remote species. It is found that the nucleotide compositions at the third codon position of H2A genes vary greatly among species and are highly correlated with the compositions at the first position of H2A genes, with those at the first and third position of H4 genes and with those in the up- and downstream sequences of H2A genes. This implies the existence of regional constraints over DNA sequences during the evolutionary process, which is different over species. Possible causes for the variations are increment of G + C content in higher eukarotypes, and chromosomal recombination, which brought the histone genes onto different isochores and thus under different selective or mutational pressures. Substitutions at different positions in a codon have been found not to be independent, probably due to multiple substitutions, i.e., single substitution events involving multiple sites. The implication of these results to phylogeny inferring is discussed.

Base Composition↗

PubMed1999

Automated approach for ribosomal intergenic spacer analysis of microbial diversity and its application to freshwater bacterial communities.

An automated method of ribosomal intergenic spacer analysis (ARISA) was developed for the rapid estimation of microbial diversity and community composition in freshwater environments. Following isolation of total community DNA, PCR amplification of the 16S-23S intergenic spacer region in the rRNA operon was performed with a fluorescence-labeled forward primer. ARISA-PCR fragments ranging in size from 400 to 1,200 bp were next discriminated and measured by using an automated electrophoresis system. Database information on the 16S-23S intergenic spacer was also examined, to understand the potential biases in diversity estimates provided by ARISA. In the analysis of three natural freshwater bacterial communities, ARISA was rapid and sensitive and provided highly reproducible community-specific profiles at all levels of replication tested. The ARISA profiles of the freshwater communities were quantitatively compared in terms of both their relative diversity and similarity level. The three communities had distinctly different profiles but were similar in their total number of fragments (range, 34 to 41). In addition, the pattern of major amplification products in representative profiles was not significantly altered when the PCR cycle number was reduced from 30 to 15, but the number of minor products (near the limit of detection) was sensitive to changes in cycling parameters. Overall, the results suggest that ARISA is a rapid and effective community analysis technique that can be used in conjunction with more accurate but labor-intensive methods (e.g., 16S rRNA gene cloning and sequencing) when fine-scale spatial and temporal resolution is needed.

Bacteria↗

PubMed2002

Aromatic side-chain interactions in proteins. II. Near- and far-sequence Phe-X pairs.

We have collected all aromatic pairs (3152) involving an N-phenyl partner in a dataset of 593 proteins of the PDB: 728 of these pairs involve a partner residue less than 6 apart in the sequence. These near-sequence Phe-X pairs correspond to specific conformations that stabilize secondary structures, mainly alpha-helices when the residues are 1, 3, and 4 apart, and beta-strands when they are 2 apart in the sequence. These conformations are not spatially random and have been examined in detail. The remaining phenylalanine pairs (2424) are between partners more than 5 apart in the sequence. Of these far-sequence pairs, 34% of occurrences are in sheets. Next in frequencies are pairs that bridge a beta-strand to a helix (24%), followed by pairs that bridge a beta-strand to a random coiled structure (15%). Helix to helix pairs only constitute 12% of these far-sequence pairs. Analysis of the pairing frequency supports the hypothesis that aromatic interactions are late events of protein folding.

Amino Acids, Aromatic↗