PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “spatial sequencing”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources

Defining a novel domain of staphylococcal toxic shock syndrome toxin-1 critical for major histocompatibility complex class II binding, superantigenic activity, and lethality.

Staphylococcal toxic shock syndrome toxin-1 (TSST-1) is implicated in the pathogenesis of superantigen-mediated shock. We previously identified TSST-1 residues G31/S32 to be important for major histocompatibility complex (MHC) class II binding, as well as superantigenic and lethal activities. However, the site-directed TSST-1 mutant toxin, G31R, could still induce mitogenesis and low-level TNF alpha secretion, suggesting that additional MHC class II binding sites other than G31/S32 may exist. In the current study, a TSST-1-neutralizing monoclonal antibody, MAb5, was found to inhibit TSST-1 binding to human peripheral blood mononuclear cells, neutralize TSST-1-induced mitogenesis and cytokine secretion, and protect against TSST-1-induced lethality in vivo. Epitope mapping revealed that MAb5 bound to TSST-1 residues 51-56 (T(51-56); 51YYSPAF56). Peptide T(51-56) was synthesized and found to also inhibit TSST-1 binding to human monocytes as well as TSST-1-induced mitogenesis, cytokine secretion, and lethality in vivo. This T(51-56) epitope, located within the beta 3/beta 4 loop, and the previously identified G31/S32 epitope, within the beta 1/beta 2 loop of TSST-1, are separated within the primary sequence, but spatially juxtaposed to each other. Collectively, these findings suggest that a discontinuous epitope comprising of regions within both the beta 1/beta 2 and beta 3/beta 4 loops, are critical for MHC class II binding, and the consequent superantigenic and lethal activities of TSST-1.

Animals↗

Reconstruction of target speed for the guidance of pursuit eye movements.

We studied how object speed is reconstructed from the responses of motion-selective cells for the generation of a behavior that is tightly linked to the speed of visual motion. In theory, the speed of an object could be estimated either from the speed tuning of the active population of motion-selective cells or from the rate of displacement of activation across the cortical map of visual space. We measured the pursuit eye movements evoked by stimuli containing two conflicting motion components: a local component designed to excite motion-selective cells with a particular speed tuning and a displacement component designed to excite cells with a sequence of spatial receptive fields. Pursuit eye movements were driven primarily by the local-motion component and were affected to only a small degree by the rate of target displacement across visual space. Extracellular single-unit recordings using the same stimuli revealed that the responses of cells in the middle temporal visual area (MT) depended primarily on the local-motion component but were influenced by the displacement component to the same degree as were pursuit eye movements. We conclude that the initiation of pursuit is consistent with a reconstruction of target speed based on the speed tuning of the active population of MT cells.

Acceleration↗

[Dominating motivation in systemic memory mechanisms].

The materials provided in the article support the key role of dominating motivation in the systemic processes of fixation and opening of memory mechanisms. The activating mechanisms of dominating motivations in the systemic architectonics of behavioural acts provide the basis for development of a multicomponent acceptor apparatus of an action outcomes broadly represented in various analysing brain sections. As result of enhancement of action outcomes on acceptors structures, molecular behaviour engrammes form within the functional systems. It is these molecular engrammes that are opened by dominating motivations in the same spatial-temporal sequence in which training takes place, and determine deliberate actions of animals. It was demonstrated that dominating motivation opens genetic information with an approximating-exploratory reaction under strong activation of early genes expression, in particular, of c-fos gene protein. Inherent motivation reactions are not blocked by inhibitors of proteins synthesis, by cycloheximide, in particular. In the process of training animals, i.e., satisfaction of the demands which are the basis of dominating motivations, expression of early genes in reduced, while expression of late genes is initiated. In this case, blockators of protein synthesis begin to produce strong inhibiting impact on behaviour of animals.

Animals↗

[Interactions of chondrocytes and osteoblasts during endochondral bone formation].

During endochondral bone formation, mesenchymal condensations, chondrocyte differentiation and proliferation, termination of proliferation, hypertrophic differentiation, and replacement by bone occur sequentially. This sequence is spatially represented by the structure of the growth plate of the embryo, and reflects the evolution of bone. Endochondral bone formation is mainly regulated by the interactions of chondrocytes and osteoblasts; a variety of signals are implicated in this regulation. The roles of factors regulating chondrocyte proliferation and hypertrophy including the Sox trio, PTH related peptide (PTHrP), Indian hedgehog (Ihh), the runt-related transcription factor (Runx) family, fibroblast growth factor receptor 3 (FGFR3) and bone morphogenetic protein (BMP) and other factors including hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) will be discussed.

Animals↗

[Circahoral rhythms of the skin biopotentials outside of digestion and their relationship to the periodic motility of the gastrointestinal tract].

Circahoral rhythms of the skin surface potentials recorded simultaneously with periodic motor activity of stomach in 4 dogs and 7 healthy subjects revealed the rhythms to be an electrophysiological equivalent of the latter in dogs. A "migration" of the group potentials in a certain spatial-temporal sequence was observed among the leads. It corresponded to the cycles of periodic motor activity of the stomach in dogs. The circahoral rhythms are a major topic for research in humans, too.

Adult↗

Models for positional signalling, the threefold subdivision of segments and the pigmentation pattern of molluscs.

Models of biological pattern formation are discussed. The regulatory features expected from the models are compared to those observed experimentally. It will be shown that: (i) Stable gradients appropriate to supply positional information can be produced by local autocatalysis and long-range inhibition. (ii) Spatially ordered sequences of differentiated cell states can emerge if these cell states mutually activate each other on long range but exclude each other locally. Segmentation results from the repetition of three such cell states, S, A and P (and not of only two, as is usually assumed). With a repetition of three states, each segment has a defined polarity. The confrontation of P cells and S cells lead to the formation of a segment border (...P/SAP/SAP/S...) while the A-P confrontation is a prerequisite for appendage formation. Mutations of Drosophila affecting larval segmentation are discussed in terms of this model. (iii) The two models for the generation of sequences of structures in space (positional information including interpretation versus mutual activation) lead to different predictions with respect to intercalary regeneration. This allows a distinction between the two models on the basis of experiments. (iv) The pigmentation patterns of certain molluscs emerge from a coupled oscillation of cells (that is, a lateral inhibition in time, instead of space). The oblique lines result from a chain of triggering events.

Animals↗

[Participation of the hippocampus in delayed spatial choice and discrimination of time intervals in rhesus macaques].

Participation of the hippocampus in morpho-functional systems of delayed spatial choice and differentiation of trace reflexes to time was shown in 2 macaco rhesus by the method of phase-correlational analysis. Application of 0.05 per cent solution of amysyl into the hippocampus disturbed the behaviour of monkeys, probably, as a result of desintegration of entire morpho-functional system regulating spatial-temporal sequence of nervous processes of delayed behavioural act.

Animals↗

[Genetic control of limb development].

Vertebrate limbs are an amazing example of successful adaptation to various environmental conditions. In higher vertebrates, forelimbs help to fly, swim, walk, dig, grasp or play the Passacaille, yet their basic structure (the sequence and spatial arrangement of bony elements) is always the same. This implies the existence of a unique developmental strategy for building a limb (a limb plan) that imposes early on a basic scheme, on the top of which subsequent species-specific customizations will occur. The description of such a universal limb plan, hence the idea that the genetic and developmental processes that generate this plan are very ancient, has been controversial for about a century. It is worth asking whether recent discoveries of important genes involved in these processes can bring novel arguments to the debate.

Animals↗

[Control of limb morphogenesis by the Hox genes].

Vertebrate limbs are an amazing example of successful adaptation to various environmental conditions. In higher vertebrates, forelimbs help to fly, swim, walk, dig or grasp, yet their basic structure (the sequence and spatial arrangement of bony elements) is always the same. This implies the existence of a unique developmental strategy for building a limb (a limb plan) that imposes early on a basic scheme, on the top of which subsequent species-specific customizations will occur. The description of such a universal limb plan, hence the idea that the genetic and developmental processes that generate this plan are very ancient, has been controversial for about a century. It is worth asking whether recent discoveries of important genes involved in these processes can bring novel arguments to the debate.

Animals↗

Regulation of alternative processing of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2) gene transcripts during muscle differentiation.

The Ca2+ transport ATPases of the sarcoplasmic or endoplasmic reticulum (SERCA) mediate the uptake of Ca2+ into intracellular stores. These Ca2+ pumps are encoded by three different genes. Alternative processing of the SERCA2 messenger generates two different protein isoforms. These two isoforms differ in their C-terminal part and this divergence is responsible for the functional difference between SERCA2a and SERCA2b. The aim of this study was to characterise the cis-active elements and the trans-acting factors required for the generation of the muscle-specific messenger during myogenic differentiation. A competition model between muscle-type splicing and non-muscle polyadenylation was excluded as inactivation of the non-muscle polyadenylation site did not induce muscle-type splicing in non-muscle or in undifferentiated muscle cells. We therefore propose that the expression of the SERCA2a isoform is due to the regulation of the muscle-specific splice process during myogenic differentiation. We characterised the spatial and sequence requirements essential for tissue-specific transcript processing. It was demonstrated that the processing signals in the transcript, i.e. both donor splice sites and the polyadenylation site located in the muscle-specific intron, have to be weak. An exception to this rule is the 3' acceptor splice site that has to be strong in order to get muscle-specific splicing. We also found an inverse relationship between intron length and splice efficiency as shortening the terminal intron resulted in muscle-specific splicing in non-muscle and in undifferentiated muscle cells. Finally, it was demonstrated that sequences around the muscle-specific acceptor region as well as in the muscle-specific exon are required to prevent muscle-specific splicing in undifferentiated muscle cells. Especially a region upstream of the 3' acceptor contains important sequence information required for the inhibition of muscle-specific splicing. It was demonstrated that the trans-acting factors regulating the alternative SERCA2 splicing are muscle specific. First, myogenin, a transcription factor that plays a key role in muscle differentiation, induced muscle-specific SERCA2 splicing in a fibroblast cell line. Second, changes in general splice and polyadenylation efficiency, as observed during B-cell maturation, did not affect SERCA2 splicing. Finally, expression and overexpression studies did not support the hypothesis that changes in the level of the alternative splice factor ASF or other arginine and serine rich proteins are involved in the regulation of muscle-specific splicing. We conclude that muscle-specific SERCA2a expression is a tightly regulated process dependent on the inhibition of the muscle-specific splice process at the 3' end of the primary transcript. During differentiation this inhibition is overcome by the downregulation of an inhibitory factor and/or the expression of a positive trans-acting factor.

Animals↗

A pattern formation mechanism to control spatial organization in the embryo of Drosophila melanogaster.

It is known that cells are already committed to a particular segment at the cellular blastoderm stage during embryogenesis of Drosophila melanogaster. Recently, several segmentation genes have been observed to be expressed in a sequence of banded spatial patterns in the syncytial blastoderm, prior to the formation of the cellular blastoderm. It is demonstrated in this paper that a two component reaction-diffusion (RD) system with net production functions which are antisymmetric with respect to the uniform steady-state values, is capable of producing a sequence of seven spatial patterns in the syncytial blastoderm. The sequence of patterns obtained exhibit a strong preference for banded or striped patterns. The first pattern is a simple anteroposterior gradient while the second is a gradient in the dorsoventral direction. The next five patterns are a sequence of banded patterns which exhibit frequency doubling, i.e. the number of bands in each pattern tend to be double the number in the previous pattern. The predicted pattern sequence is comparable to that observed in the expression of some segmentation genes. It is suggested that a pattern formation mechanism based on such an RD system may exist in the embryo where it produces a sequence of prepatterns to regulate the expression of various segmentation genes leading ultimately to a segmented embryo. There is sufficient spatial information in the sequence of banded prepatterns for the segments to be unique.

Animals↗

Computer-assisted analysis of 4D cardiac MR image sequences after myocardial infarction.

OBJECTIVES: Spatial-temporal MR image sequences of the heart contain information about shape and motion changes and pathological structures after myocardial infarction. In this paper a Heart Analysis Tool (HeAT) for the quantitative analysis of 4D MR image sequences of infarct patients is presented. METHODS: HeAT supports interactive segmentation of anatomical and pathological structures. Registration of Cine- and DE-MR image data is applied to enable their combined evaluation during the analysis process. Partitioning of the myocardium in segments enables the analysis with high local resolution. Corresponding segments are generated and used for inter/intrapatient comparison. Quantitative parameters were extracted and visualized. RESULTS: Parameters like endocard movement in the infarcted area of six infarct patients were computed in HeAT. Parameters in the infarct area show the expected dysfunctional characteristics. Based on theses parameters passive endocardial movement and myocardial areas with decreased contraction could be identified. CONCLUSION: In contrast to other software tools HeAT supports the combination of contour information of Cine-MR and DE-MR, local analysis with high resolution and inter/intra patient comparison. HeAT enables an observer-independent evaluation of the complex cardiac image data. Using HeAT in further studies can increase the understanding of left ventricle (LV) remodeling.

Algorithms↗

Spatially localized generation of nucleotide sequence-specific DNA damage.

Psoralens linked to triplex-forming oligonucleotides (psoTFOs) have been used in conjunction with laser-induced two-photon excitation (TPE) to damage a specific DNA target sequence. To demonstrate that TPE can initiate photochemistry resulting in psoralen-DNA photoadducts, target DNA sequences were incubated with psoTFOs to form triple-helical complexes and then irradiated in liquid solution with pulsed 765-nm laser light, which is half the quantum energy required for conventional one-photon excitation, as used in psoralen + UV A radiation (320-400 nm) therapy. Target DNA acquired strand-specific psoralen monoadducts in a light dose-dependent fashion. To localize DNA damage in a model tissue-like medium, a DNA-psoTFO mixture was prepared in a polyacrylamide gel and then irradiated with a converging laser beam targeting the rear of the gel. The highest number of photoadducts formed at the rear while relatively sparing DNA at the front of the gel, demonstrating spatial localization of sequence-specific DNA damage by TPE. To assess whether TPE treatment could be extended to cells without significant toxicity, cultured monolayers of normal human dermal fibroblasts were incubated with tritium-labeled psoralen without TFO to maximize detectable damage and irradiated by TPE. DNA from irradiated cells treated with psoralen exhibited a 4- to 7-fold increase in tritium activity relative to untreated controls. Functional survival assays indicated that the psoralen-TPE treatment was not toxic to cells. These results demonstrate that DNA damage can be simultaneously manipulated at the nucleotide level and in three dimensions. This approach for targeting photochemical DNA damage may have photochemotherapeutic applications in skin and other optically accessible tissues.

Base Sequence↗

MRI of the pelvis at 3 T: very high spatial resolution with sensitivity encoding and flip-angle sweep technique in clinically acceptable scan time.

OBJECTIVE: The higher signal at 3.0-T allows spatial resolution to be increased without loss in image quality. We evaluated a T2-weighted turbo spin-echo sequence with high spatial resolution (3T-HR) to determine whether this provides clinically useful pelvic MRI. MATERIALS AND METHODS: We designed a sequence with high spatial resolution (3T-HR) (0.45x0.46x4 mm) that was combined with parallel imaging and the variable refocusing angle technique (8.06 min). We examined 23 patients with gynecological disorders using 3T-HR and a standard sequence (3T-SP; 4.03 min; equivalent to 1.5 T). Two radiologists analyzed tissue contrast, signal to noise, detail delineation and artifact level. RESULTS: Tissue contrasts and signal to noise were rated equal. Motion artifacts occurred more often with 3T-SP despite the longer scanning time of 3T-HR. The higher spatial resolution provided additional information in four patients. In two patients small myomas were detected, in one patient a lymph node metastasis was apparent, and in one patient 3T-HR excluded tumor invasion. CONCLUSIONS: High spatial resolution pelvic studies with high image quality can be obtained at 3 T in acceptable scan time. The higher spatial resolution that is feasible at 3 T also provides more clinically relevant information.

Adolescent↗

Perceptual and academic patterns of learning-disabled/gifted students.

This research explored ways gifted children with learning disabilities perceive and recall auditory and visual input and apply this information to reading, mathematics, and spelling. 24 learning-disabled/gifted children and a matched control group of normally achieving gifted students were tested for oral reading, word recognition and analysis, listening comprehension, and spelling. In mathematics, they were tested for numeration, mental and written computation, word problems, and numerical reasoning. To explore perception and memory skills, students were administered formal tests of visual and auditory memory as well as auditory discrimination of sounds. Their responses to reading and to mathematical computations were further considered for evidence of problems in visual discrimination, visual sequencing, and visual spatial areas. Analyses indicated that these learning-disabled/gifted students were significantly weaker than controls in their decoding skills, in spelling, and in most areas of mathematics. They were also significantly weaker in auditory discrimination and memory, and in visual discrimination, sequencing, and spatial abilities. Conclusions are that these underlying perceptual and memory deficits may be related to students' academic problems.

Achievement↗

Hierarchy of regions of amino acid sequence with respect to their role in the protein spatial structure.

The method of the representation of amino acid sequence by graph of the interactions energy between parts of spatial structure has been elaborated. Our method provides the possibility to establish the compatibility between each point of a polypeptide chain and the Van der Waals interactions energy of regions of a native globule adjacent to this amino acid residue. We have undertaken an exhaustive analysis of a set of proteins. Boundaries of domain and module structures have been found. Nonequivalence of different parts of sequences in respect to their contribution to stabilization of the spatial structure of the protein macromolecules has been revealed. On the basis of the number of energetic levels which are necessary to identify all independent parts of the globule, the contribution from each part of the sequence to stabilization of the spatial structure of the globule is defined. Thus, it has been found that the sequence of amino acid residues coincides with the sequence of the numerical values which can be used in turn in formal procedures, such as an alignment, a search of consensus, the recognition of composition peculiarities, etc. An example of the comparison of proteins with various sequence identities is considered to demonstrate the scheme of an alignment procedure.

Amino Acid Sequence↗

Visualization of cranial nerves I-XII: value of 3D CISS and T2-weighted FSE sequences.

The aim of this study was to evaluate the sensitivity of the three-dimensional constructive interference of steady state (3D CISS) sequence (slice thickness 0.7 mm) and that of the T2-weighted fast spin echo (T2-weighted FSE) sequence (slice thickness 3 mm) for the visualization of all cranial nerves in their cisternal course. Twenty healthy volunteers were examined using the T2-weighted FSE and the 3D CISS sequences. Three observers evaluated independently the cranial nerves NI-NXII in their cisternal course. The rates for successful visualization of each nerve for 3D CISS (and for T2-weighted FSE in parentheses) were as follows: NI, NII, NV, NVII, NVIII 40 of 40 (40 of 40), NIII 40 of 40 (18 of 40), NIV 19 of 40 (3 of 40), NVI 39 of 40 (5 of 40), NIX, X, XI 40 of 40 (29 of 40), and NXII 40 of 40 (4 of 40). Most of the cranial nerves can be reliably assessed when using the 3D CISS and the T2-weighted FSE sequences. Increasing the spatial resolution when using the 3D CISS sequence increases the reliability of the identification of the cranial nerves NIII-NXII.

Adult↗

[Functional imaging of the human brain with conventional MRI].

It was shown in 1991 by Belliveau and co-workers that the activation of the human brain can be visualized in a completely noninvasive way by MRI. First publications coming from the US claimed that very high magnetic field strength or echo planar imaging, both available only at a few research sites, would be necessary to do this job. Recently, it was demonstrated that functional imaging of the human brain can be done with high spatial resolution MRI using conventional FLASH-sequences with the commercial widely available 1,5 Tesla systems. First results have been reported for visual as well as primary motor cortex activation in healthy volunteers. The key to a successful application of the conventional technique lies in the design of extremely low bandwidth, long echo-time FLASH-sequences with high spatial resolution.

Adult↗