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Results for “spatial sequencing”

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PubMed1990

Molecular action of the l(2)gl tumor suppressor gene of Drosophila melanogaster.

Tumor suppressor genes act as recessive determinants of cancer. These genes contribute to the normal phenotype and are required for regulating cell growth and differentiation during development. Inactivation of tumor suppressor genes leads to an unrestricted pattern of growth in specific cell types. In Drosophila, a series of genes have been identified that cause tissue-specific tumors after mutation. Of these, the lethal(2)giant larvae (l(2)gl) gene is the best studied. Homozygous l(2)gl mutations cause the development of malignant tumors in the brain and the imaginal discs. Genomic DNA from the l(2)gl locus has been cloned, introduced back into the genome of l(2)gl-deficient animals, and shown to reinstate normal development. The nucleotide sequence of the l(2)gl gene has been determined, as well as the sequences of two classes of transcripts. Analysis of the spatial distribution of both l(2)gl transcripts and proteins revealed that during early embryogenesis the l(2)gl gene is uniformly expressed in all cells and tissues. In late embryos, the l(2)gl expression becomes gradually restricted to tissues presenting no morphological or neoplastic alteration in the mutant animals. Further mosaic experiments revealed that l(2)gl gene loss can cause three distinct phenotypes: neoplastic transformation, abnormal differentiation, and normal development. These phenotypes depend upon the extent of gene activity in the stem cells prior to the formation of l(2)gl- clones. These analyses indicate that the critical period for the establishment of tumorigenesis occurs during early embryogenesis at a time when the l(2)gl expression is most intense in all cells.

Animals↗

PubMed2001

Conditional gene knockout using Cre recombinase.

Cre recombinase has become an important instrument for achieving precise genetic manipulation in mice. Many of these desired genetic manipulations rely on Cre's ability to direct spatially and temporally specified excision of a predesignated DNA sequence that has been flanked by directly repeated copies of the loxP recombination site. Success in achieving such conditional mutagenesis in mice depends both on the careful design of conditional alleles and on reliable detection of cre gene expression. These procedures include PCR, immunohistochemistry and the use of a recombination-proficient GFP-tagged Cre protein.

Animals↗

PubMed1975

Susceptibility to interference effects in short-term memory of normal and retarded readers.

The short-term memory for serial order of third and fourth grade normal and retarded readres (Ns = 13) was studied. Six pictures of common objects were spatially presented and subjects were required to reconstruct the sequence. On the first six trials, the same pictures were repeatedly presented in different sequences. On the seventh trial, a new set of stimuli was introduced. Analysis of short-term memory over trials showed that normal and retarded readers were similar on Trial 1 but the performance of retarded readers deteriorated more over trials than the performance of normal readers. Short-term memory of both groups improved on Trial 7. The results indicate a greater susceptibility to interference in the short-term memory of retarded readers.

Child↗

PubMed2005

On the role of verbalization during task set selection: switching or serial order control?

Recent task-switching work in which paper-and-pencil administered single-task lists were compared with task-alternation lists has demonstrated large increases in task-switch costs with concurrent articulatory suppression (AS), implicating a crucial role for verbalization during switching (Baddeley, Chincotta, & Adlam, 2001; Emerson & Miyake, 2003). Experiment 1 replicated this result, using computerized assessment, albeit with much smaller effect sizes than in the original reports. In Experiment 2, AS interference was reduced when a sequential cue (spatial location) that indicated the current position in the sequence of task alternations was given. Finally, in Experiment 3, switch trials and no-switch trials were compared within a block of alternating runs of two tasks. Again, AS interference was obtained mainly when the endogenous sequencing demand was high, and it was comparable for no-switch and switch trials. These results suggest that verbalization may be critical for endogenous maintenance and updating of a sequential plan, rather than exclusively for the actual switching process.

Choice Behavior↗

PubMed2000

Selective attention to the chemosensory modality.

Previous studies have shown that behavioral responses to auditory, visual, and tactile stimuli are modulated by expectancies regarding the likely modality of an upcoming stimulus (see Spence & Driver, 1997). In the present study, we investigated whether people can also selectively attend to the chemosensory modality (involving responses to olfactory, chemical, and painful stimuli). Participants made speeded spatial discrimination responses (left vs. right) to an unpredictable sequence of odor and tactile targets. Odor stimuli were presented to either the left or the right nostril, embedded in a birhinally applied constant airstream. Tactile stimuli were presented to the left or the right hand. On each trial, a symbolic visual cue predicted the likely modality for the upcoming target (the cue was a valid predictor of the target modality on the majority of trials). Response latencies were faster when targets were presented in the expected modality than when they were presented in the unexpected modality, showing for the first time that behavioral responses to chemosensory stimuli can be modulated by selective attention.

Attention↗

PubMedDate not supplied

[Structural aspects of homeodomain interactions with DNA].

This review is devoted to the structural aspects of interaction of homeodomains with DNA. Presented are the list of all homeodomains with known spatial structure and the alignment of their amino acid sequences. The structure of homeodomains and contacts of their amino acid residues with DNA bases and sugar-phosphate backbone are described. The role of water molecules in DNA binding is discussed. Structures of multicomponent protein complexes on DNA including homeodomains are characterized.

Amino Acid Sequence↗

PubMed1992

[Radiological exploration of the shoulder rotator cuff].

Plain X-rays and Lecler's manoeuvre constitute the essential basic assessment in the diagnostic approach to lesions of the rotator cuff. The preoperative assessment of the lesions and the search for associated lesions are based on more or less invasive investigations. For many years, arthrography was the reference examination to establish a precise assessment, but was sometimes insufficient for the diagnosis of small partial non-communicating lesions and certain longstanding massive ruptures. Ultrasonography is an attractive non-invasive technique, but the quality of the results depends on the operator's experience. Although computed tomography and CT arthrography provide a perfect analysis of the anterior aspect of the cuff and evaluate the trophicity of the muscles, they are difficult to interpret, irradiating and sometimes incomplete. MRI, a non-invasive and non-irradiating technique, is the modality of choice due to its excellent contrast resolution and the possibility of multidirectional studies and a spatial resolution which is continually improved by new acquisition sequences and the use of better adapted surface coils.

Arthrography↗

PubMed1991

[Magnetic resonance tomography in the diagnosis of peripheral joints].

Magnetic resonance imaging (MRI) provides an excellent soft tissue contrast with high spatial resolution. Using spin echo and fast gradient echo sequences all relevant joint structures such as the hyaline cartilage, the meniscus, the ligaments, the tendons, the capsulae, and their adjacent muscles and their pathology are visualized. Diagnosis of osteonecrosis, meniscal and cruciate ligament lesions, as well as tumors, represents the major current indication for MRI. Due to its high cost MRI should be employed for the diagnosis of joint disease only to clarify equivocal findings of conventional radiographic, nuclear and tomographic methods. Prior clinical examination and laboratory tests are mandatory. As a component of a stepwise diagnostic approach, MRI often provides reliable differential diagnostic information.

Bone Diseases↗

PubMedDate not supplied

[Vectorcardiographic manifestations of atrial enlargements].

Rational interpretation of changes of the P loop due to atrial enlargements must to rely on the magnitude and spatial orientation of main resultant vectors of the activation sequence of the atria. Under normal conditions, these vectors give rise to a mean vector oriented to the left downward and discretely forward with respect to their point of origin. In the presence of right atrial enlargement, the manifestation of the first vector of atrial depolarization, oriented downward and forward, is increased. This one moves in the same direction as the mean vector of atrial depolarization, originating an elongated P loop of more than 100 mcv in the three planes. Nevertheless, in the horizontal plane, increase of the P loop voltage predominates when hypertrophy exists, while augmentation of its area predominates when dilatation exists. In left atrial enlargement, the manifestation of the second vector of atrial depolarization, oriented to the left and backward, is augmented, and it moves in the same direction as the mean vector of atrial depolarization. For this, the PF loop acquires a characteristic aspect of a boxing glove, an the PH loop becomes diphasic, with its posterior area more or less prominent, or with a typical figure-eight conformation. If a biatrial enlargement is present, the manifestation of both the main resultant vectors of atrial depolarization is accentuated. Therefore the voltage of the diphasic P loop increases. Moreover the Ps loop has a triangular configuration, with its base of 30 msc or more, located below its point of origin. Generally disturbances of interatrial and intraatrial conduction coexist owing to myocardial damage.

Cardiomegaly↗

PubMed1987

Use of interstitial hyperthermia to produce homogeneous heat distribution patterns.

The preliminary experience of the use of a prototype hyperthermia unit (Astro 200) for tumor regression in Howard University Hospital's Department of Radiotherapy is described. The purpose of this study was to produce homogeneous heat distribution patterns within a 5-cm cylinder in the middle of a phantom (ground beef) using radio frequency conducted through electrodes implanted in the medium. Homogeneous heat distribution was achieved by finding the optimal spatial distribution of electrodes within the phantom and by sequencing the radio frequency in the electrodes. Monitored observation revealed a steady state homogeneous temperature of 42.5 °C within a 4-cm diameter. There was a temperature difference of 0.5 °C within 1 cm of the periphery.Heat in the clinical range of 42 to 43 °C has caused tumor regression, and was found to be most effective when combined with another modality of radiation. At Howard University Hospital, hyperthermia is used in conjunction with conventional modalities-surgery, radiotherapy, and chemotherapy-in the treatment of tumors.

Body Temperature↗

PubMedDate not supplied

The principles of NMR imaging and a review of early clinical results.

NMR imaging represents an exciting new development in the field of medicine. In this paper the physical principles of nuclear magnetic resonance imaging are reviewed. In addition the role of the major contrast determinants T1 and T2 relaxation times, proton density and blood flow are discussed. With NMR proton imaging high quality anatomic images may be obtained in the coronal, sagittal or cross axial plane. NMR appears to be a useful modality in the diagnosis of neurologic disease particularly in the posterior fossa or brainstem. Thoracic imaging appears promising due to the high contrast in the mediastinum between structures and mediastinal fat. A wide range of abdominal diseases may also be identified on NMR images. The potential advantages of imaging at higher magnetic field strengths are considered. These include improved spatial resolution and decreased scan times for some pulse sequences.

Abdomen↗

PubMed1983

The emergence of spatial perspective taking: an information-processing alternative to egocentrism.

120 children between ages 4 and 8 were administered a set of 4 visual perspective-taking tasks similar to ones employed in previous investigations. It was hypothesized that children's competence with the tasks would be a function of the number and type of spatial relationships embedded in the stimulus displays. 2 kinds of spatial relationships were described: (1) internal relationships--those between objects within a display; and (2) external relationships--those between the display and a frame of reference. Of the 4 task types, type A tasks necessitated awareness of possible variations in external relations, types B and C tasks required both awareness and computation of changes in those external relationships, and type D tasks required simultaneous coordination of internal and external spatial relationships. It was predicted that the tasks would sequence in terms of difficulty level as A less than B, B = C, and C less than D. Analysis of variance results on the obtained data revealed a good fit with the hypothesized predictions. The findings were discussed in terms of an information-processing analysis of children's performance on perspective-taking tasks.

Child↗

PubMed1981

Psychic structure.

An attempt has been made to define psychic structure in strictly psychological terms. The concept of psychic structure refers to enduring aspects of the personality and to means-end functions that do not have to be created de novo each time one is faced with a similar situation. A psychic structure is a functional organization that generates a range of meaningful contents. Structures are categorical in nature and display relative functional equivalence. The above formulation provides a place for meaning in the theory and distinguishes structured functions from structured contents. The latter are the end product of a behavioural sequence and not centres of action. In this analysis, percepts, thoughts, images, wishes, fantasies, affects and internal objects are contents, not dynamic systems that make things happen. Only people make things happen, employing operational systems as tools of adaptation. Structure formation transform temporal sequences into the units of experience and action. The spatialization of temporal order fosters the treatment of mental processes as if they occupied space in the mind as a place. This error accounts for the ready confounding of structure and content. The present analysis accepts the traditional definition of psychic structure in terms of function and organization, but without recourse to a physicalistic theory of energy and force. The above analysis was applied to a number of special problems in the theory of structure. Consideration was also given to the concept's range of application, systemic relevance and heuristic value.

Humans↗

PubMed1996

[Objective determination of visual acuity. Improvement of an infrared nystagmography method and comparison with pattern visual evoked potentials].

BACKGROUND: The purpose of this study was to optimize a new nystagmographical method of objective assessment of visual acuity and compare it to an electrophysiological method. METHODS: In the nystagmographical method motionless brake marks were superimposed on a moving grating pattern, causing suppression of optokinetic nystagmus (OKN). The smallest brake mark that interrupted the OKN was taken as an objective measure for visual acuity (VA). In the electrophysiological method rapid sequences of high-contrast checkerboard patterns of different spatial frequency were presented in a pattern on-off mode in a foveal field. The VEP response function was extrapolated to 0 microV. The objective values of 94 healthy eyes with artificially reduced vision (VA 0.05-2.0) and 314 eyes with pathological reduction of VA due to different etiologies were compared. RESULTS. The selectivity of the nystagmographical method could be improved. With the exception of strabismic amblyopia, the results were closely correlated with the VA. The least VA could be estimated in steps of 0.06, 0.1, 0.2, 0.5 and 0.8. CONCLUSIONS: The new nystagmographical method yields useful information about the least VA if strabismic amblyopia is excluded.

Adolescent↗

PubMed2006

Multiple testing methods for ChIP-Chip high density oligonucleotide array data.

Cawley et al. (2004) have recently mapped the locations of binding sites for three transcription factors along human chromosomes 21 and 22 using ChIP-Chip experiments. ChIP-Chip experiments are a new approach to the genomewide identification of transcription factor binding sites and consist of chromatin (Ch) immunoprecipitation (IP) of transcription factor-bound genomic DNA followed by high density oligonucleotide hybridization (Chip) of the IP-enriched DNA. We investigate the ChIP-Chip data structure and propose methods for inferring the location of transcription factor binding sites from these data. The proposed methods involve testing for each probe whether it is part of a bound sequence using a scan statistic that takes into account the spatial structure of the data. Different multiple testing procedures are considered for controlling the familywise error rate and false discovery rate. A nested-Bonferroni adjustment, which is more powerful than the traditional Bonferroni adjustment when the test statistics are dependent, is discussed. Simulation studies show that taking into account the spatial structure of the data substantially improves the sensitivity of the multiple testing procedures. Application of the proposed methods to ChIP-Chip data for transcription factor p53 identified many potential target binding regions along human chromosomes 21 and 22. Among these identified regions, 18% fall within a 3 kb vicinity of the 5'UTR of a known gene or CpG island and 31% fall between the codon start site and the codon end site of a known gene but not inside an exon. More than half of these potential target sequences contain the p53 consensus binding site or very close matches to it. Moreover, these target segments include the 13 experimentally verified p53 binding regions of Cawley et al. (2004), as well as 49 additional regions that show higher hybridization signal than these 13 experimentally verified regions.

5' Untranslated Regions↗

PubMed1993

Somatic pairing of centromeres and short arms of chromosome 15 in the hematopoietic and lymphoid system.

Normal human bone marrow and peripheral blood leukocytes as well as malignant cells from a variety of leukemias and lymphomas, demonstrate somatic pairing of centromeres and p arms of chromosome 15 during interphase. This phenomenon, effected by sequences on the p arm and requiring the intranuclear transport of spatial domains for at least one of the homologs, was not seen in amniotic fluid cells, uterine cervical tissue or in tissue fibroblasts. These studies contribute to the recent evidence of somatic pairing of homologous chromosomes in man and provide support for mobile chromosomal domains in interphase. It appears that sequences on the p arm of chromosome 15, possibly the nucleolar organizing genes, are uniquely important in the maturation of benign and malignant cells of hemato-lymphopoietic origin.

Cells, Cultured↗

PubMed2003

Specificity and phenetic relationships of iron- and manganese-containing superoxide dismutases on the basis of structure and sequence comparisons.

The iron- and manganese-containing superoxide dismutases (Fe/Mn-SOD) share the same chemical function and spatial structure but can be distinguished according to their modes of oligomerization and their metal ion specificity. They appear as homodimers or homotetramers and usually require a specific metal for activity. On the basis of 261 aligned SOD sequences and 12 superimposed x-ray structures, two phenetic trees were constructed, one sequence-based and the other structure-based. Their comparison reveals the imperfect correlation of sequence and structural changes; hyperthermophilicity requires the largest sequence alterations, whereas dimer/tetramer and manganese/iron specificities are induced by the most sizable structural differences within the monomers. A systematic investigation of sequence and structure characteristics conserved in all aligned SOD sequences or in subsets sharing common oligomeric and/or metal specificities was performed. Several residues were identified as guaranteeing the common function and dimeric conformation, others as determining the tetramer formation, and yet others as potentially responsible for metal specificity. Some form cation-pi interactions between an aromatic ring and a fully or partially positively charged group, suggesting that these interactions play a significant role in the structure and function of SOD enzymes. Dimer/tetramer- and iron/manganese-specific fingerprints were derived from the set of conserved residues; they can be used to propose selected residue substitutions in view of the experimental validation of our in silico derived hypotheses.

Amino Acid Sequence↗

PubMedDate not supplied

Dissociating verbal and spatial working memory using PET.

Three experiments used position emission tomography (PET) to study the neural basis of human working memory. These studies ask whether different neural circuits underly verbal and spatial memory. In Experiment 1, subjects had to retain for 3 sec. either the names of four letters (verbal memory) or the positions of three dots (spatial memory). The PET results manifested a clear cut double dissociation, as the verbal task activated primarily left-hemisphere regions whereas the spatial task activated only right-hemisphere regions. In Experiment 2, the identical sequence of letters was presented in all conditions, and what varied was whether subjects had to remember the names of the letters (verbal memory) or their positions in the display (spatial memory). In the verbal task, activation was concentrated more in the left than the right hemisphere; in the spatial task, there was substantial activation in both hemispheres, though in key regions, there was more activation in the right than the left hemisphere. Experiment 3 studied only verbal memory, and showed that a continuous memory task activated the same regions as the discrete verbal task used in Experiment 1. Taken together, these results indicate that verbal and spatial working memory are implemented by different neural structures.

Humans↗