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Results for “spatial sequencing”

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At least 235 records · Page 13Linked to original sources

PubMed2001

Limb apraxia: cortical or subcortical.

Ideomotor apraxia is defined as a disturbance in timing, sequencing, and spatial organization of gestural movements. Left hemisphere motor dominance reflected by ideomotor apraxia mainly refers to spatially and temporally complex movements performed outside the natural context. While clinicoanatomical studies have failed to unveil a specific lesion correlating with apraxia, white matter damage-interrupting corticocortical and corticosubcortical connections-seems crucial for the deficit to be persistent and severe. Patients with basal ganglia lesions and disorders, such as Parkinson's disease and progressive supranuclear palsy, may exhibit ideomotor apraxia. The putative roles of the basal ganglia in object-oriented action, and therefore in praxis, would include among others (a) the selection of the kinematic parameters and the direction of arm movements, (b) working as an integral part of brain systems involved in timing and representation of action sequences, (c) encoding behavioral context, and (d) working as a subcortical component of the parietofrontal circuits devoted to sensorimotor transformation (e.g., reaching). Several studies suggest that basal ganglia pathology per se may not cause overt apraxia. However, when it is combined with dysfunction of the cortical components of the neural systems involved in sequencing, sensorimotor transformation, and response selection, different types of ideomotor praxis deficits would become clinically manifested.

Apraxia, Ideomotor↗

PubMed1997

Tactile pattern perception by two fingers: temporal interference and response competition.

The identification of a spatial pattern (target) presented to one fingerpad may be interfered with by the presentation of a second pattern (nontarget) to either the same fingerpad or a second fingerpad. A portion of the interference appears to be due to masking and a portion to response competition. In the present study, vibrotactile spatial patterns were designed to extend over two fingerpads. Target and nontarget patterns were presented to the same two fingerpads with a temporal separation between the two patterns. The function relating target identification to the temporal separation between the target and nontarget was very similar to the functions obtained with one-finger patterns in temporal masking studies. Subsequent measurements showed that a substantial portion of the interference resulted from response competition. Pattern categorization was better when patterns were presented to two fingers on opposite hands than to two fingers on the same hand; however, there was more interference for patterns presented bilaterally than for patterns presented ipsilaterally. The results supported the conclusion that similar processes are involved in the perception of sequences of spatial patterns whether the patterns are presented to one or to two fingers.

Adult↗

PubMed1998

The Marshall R. Urist Young Investigator Award. Gene expression during autograft lumbar spine fusion and the effect of bone morphogenetic protein 2.

A prospective animal study of posterolateral lumbar spine arthrodesis was performed to determine the temporal and spatial pattern of gene expression and to determine the effect of recombinant human bone morphogenetic protein 2 on the gene expression pattern of a healing spine fusion mass. In Group 1, 20 adult New Zealand rabbits underwent L4-L5 posterolateral intertransverse process arthrodesis using autograft alone. Two rabbits were euthanized at each of the following points: 0, 2, and 4 days, and 1, 2, 3, 4, 5, 6, and 10 weeks after surgery. The same surgical technique was used for 16 rabbits in Group II, except that the autograft first was soaked in a solution of recombinant human bone morphogenetic protein 2 before implantation. Ribonucleic acid was extracted from different regions of the fusion mass at each point and analyzed for expression of bone and cartilage related genes using reverse transcription polymerase chain reaction. A reproducible temporal sequence and spatial pattern of gene expression was found in healing spine fusions. In the central portion of the fusion mass a temporal lag in gene expression was observed that parallels the lag in healing within the central zone previously observed in histologic studies. Treatment of bone graft with recombinant human bone morphogenetic protein 2 resulted in an increase in the early expression of bone morphogenetic protein 6 which was associated with expression of higher levels of Type I collagen, osteocalcin, and other bone related genes. These findings suggest that central nonunion may be associated with delayed expression of osteoblast related genes in the central region of the forming fusion mass. The growth factor, recombinant human bone morphogenetic protein 2, increased the level of bone related gene expression throughout the fusion mass, eliminated the delay in healing within the central zone, and may decrease the likelihood of a nonunion.

Animals↗

PubMed2000

A method of measuring three-dimensional scapular attitudes using the optotrak probing system.

OBJECTIVE: To develop a method to obtain accurate three-dimensional scapular attitudes and to assess their concurrent validity and reliability. STUDY DESIGN: In this methodological study, the three-dimensional scapular attitudes were calculated in degrees, using a rotation matrix (cyclic Cardanic sequence), from spatial coordinates obtained with the probing of three non colinear landmarks first on an anatomical model and second on a healthy subject. BACKGROUND: Although abnormal movement of the scapula is related to shoulder impingement syndrome, it is not clearly understood whether or not scapular motion impairment is a predisposing factor. Characterization of three-dimensional scapular attitudes in planes and at joint angles for which sub-acromial impingement is more likely to occur is not known. METHODS: The Optotrak probing system was used. An anatomical model of the scapula was built and allowed us to impose scapular attitudes of known direction and magnitude. A local coordinate reference system was defined with three non colinear anatomical landmarks to assess accuracy and concurrent validity of the probing method with fixed markers. Axial rotation angles were calculated from a rotation matrix using a cyclic Cardanic sequence of rotations. The same three non colinear body landmarks were digitized on one healthy subject and the three dimensional scapular attitudes obtained were compared between sessions in order to assess the reliability. RESULTS AND CONCLUSIONS: The measure of three dimensional scapular attitudes calculated from data using the Optotrak probing system was accurate with means of the differences between imposed and calculated rotation angles ranging from 1.5 degrees to 4.2 degrees. Greatest variations were observed around the third axis of the Cardanic sequence associated with posterior-anterior transverse rotations. The mean difference between the Optotrak probing system method and fixed markers was 1.73 degrees showing a good concurrent validity. Differences between the two methods were generally very low for one and two direction displacements and the largest discrepancies were observed for imposed displacements combining movement about the three axes. The between sessions variation of three dimensional scapular attitudes was less than 10% for most of the arm positions adopted by a healthy subject suggesting a good reliability. The Optotrak probing system used with a standardized protocol lead to accurate, valid and reliable measures of scapular attitudes. RELEVANCE: Although abnormal range of motion of the scapula is often related to shoulder pathologies, reliable outcome measures to quantify three-dimensional scapular motion on subjects are not available. It is important to establish a standardized protocol to characterize three-dimensional scapular motion on subjects using a method for which the accuracy and validity are known. The method used in the present study has provided such a protocol and will now allow to verify to what extent, scapular motion impairment is linked to the development of specific shoulder pathologies.

Biomechanical Phenomena↗

PubMed1998

Immunorecognition, ultrastructure and phosphorylation status of astrocytic gap junctions and connexin43 in rat brain after cerebral focal ischaemia.

Gap junctions between astrocytes support a functional syncytium that is thought to play an important role in neural homeostasis. In order to investigate regulation of this syncytium and of connexin43 (Cx43), a principal astrocytic gap junction protein, we determined the sequelae of gap junction and Cx43 disposition in a rat cerebral focal ischaemia model with various ischaemia/reperfusion times using sequence-specific anti-Cx43 antibodies (designated 13-8300, 18A, 16A and 71-0700) that exhibit differential recognition of Cx43, perhaps reflecting functional aspects of gap junctions. Antibody 13-8300 specifically detects only an unphosphorylated form of Cx43 in both Western blots and tissue sections. In hypothalamus after brief (15 min) ischaemic injury, Cx43 at intact gap junctions undergoes dephosphorylation, accompanied by reduced epitope recognition by antibodies 16A and 71-0700. Tissue examined 24 h after reperfusion showed that these effects were reversible. Astrocytic gap junction internalization occurring 1 h after ischaemia was accompanied by decreased immunodetection with 13-8300. At this time, gap junctions were absent in the ischaemic core, coinciding with a loss of Cx43 recognition with 18A and 13-8300, but elevated labelling of internalized Cx43 with 16A and 71-0700. Unphosphorylated Cx43 persisted at intact gap junctions confined to a thin corridor at the ischaemic penumbra which contained presumptive apoptotic cell profiles. Similar results were obtained in ischaemic striatum and cerebral cortex, though with a delayed time course that depended on the severity of the ischaemic insult. These results demonstrate that astrocytic Cx43 epitope masking, dephosphorylation and cellular redistribution occur after ischaemic brain injury, proceed as a temporally and spatially ordered sequence of events and culminate in differential patterns of Cx43 modification and sequestration at the lesion centre and periphery. These observations suggest an attempt by astrocytes in the vicinity of injury to remodel the junctional syncytium according to altered tissue homeostatic requirements.

Animals↗

PubMed1987

Seven structurally different murine monoclonal galactan-specific antibodies show identity in their galactosyl-binding subsite arrangements.

The constants of association of seven monoclonal antibodies--each capable of binding a tetrasaccharide fragment of a linear beta(1,6)-D-galactopyranan--were measured with a series of galactosyl-ligands some of which carried deoxy-fluoro groups at selected locations. In these oligosaccharide ligands, the galactosyl residues bearing a fluorine-instead of a hydroxyl-group, cannot bind to the highest-binding subsite, which requires hydrogen-bonding. This forces a shift in the saccharide contact-residues, and in this way the relative affinities of the antibody subsites for individual galactosyl residues could be evaluated and compared with those of the four subsites investigated earlier. Correlation of sequence data, spatial structure of J 539 and binding behaviour leads to the exclusion of the third complementarity determining region (CDR) of the H-chain as partaking in the binding, and shows that the galactopyranan antigen probably binds along the lower periphery of the H-L interface of the antibodies, and does so in a groove-type fashion. Each of the seven antibodies has four subsites C, A, B and D in going from the H-to the L-chain, and the relative affinity for "their" galactosyl residue decreases in the order A greater than B greater than C greater than D. The single sugar-binding subsite A accounts for ca 50% of the total binding free energy of the maximally binding tetrasaccharide determinant in all cases.

Amino Acid Sequence↗

PubMed2026

Hypoxia Response Is Associated with Reduced HPV Activity and Tumor Microenvironment Remodeling in Cervical Cancer.

Human papillomavirus (HPV) significantly influences cervical cancer progression and treatment, yet its interactions with the tumor microenvironment remain incompletely understood. We performed single-cell and spatial transcriptomic sequencing on cervical cancer samples to explore these interactions. By aligning sequencing reads to a merged HPV16-human reference genome, we characterized HPV16 heterogeneity and its association with host states at the single-cell and single-gene levels. E5 transcriptional activity was negatively associated with the host interferon response, indicating a role in immune evasion. A hypoxic environment was correlated with the downregulation of E5 activity and elevated MHC-I expression, which may contribute to stronger interactions between hypoxic cancer cells and cytotoxic CD8⁺ T cells. Additionally, HPV16 integration in host cells was associated with increased fatty acid metabolism. These findings suggest that combining anti-angiogenic drugs and fatty acid metabolism inhibitors has the potential to improve cervical cancer treatment.

Cervical cancer↗

PubMed1996

Analysis of functional domain organization in DNA topoisomerase II from humans and Saccharomyces cerevisiae.

The functional domain structure of human DNA topoisomerase IIalpha and Saccharomyces cerevisiae DNA topoisomerase II was studied by investigating the abilities of insertion and deletion mutant enzymes to support mitotic growth and catalyze transitions in DNA topology in vitro. Alignment of the human topoisomerase IIalpha and S. cerevisiae topoisomerase II sequences defined 13 conserved regions separated by less conserved or differently spaced sequences. The spatial tolerance of the spacer regions was addressed by insertion of linkers. The importance of the conserved regions was assessed through deletion of individual domains. We found that the exact spacing between most of the conserved domains is noncritical, as insertions in the spacer regions were tolerated with no influence on complementation ability. All conserved domains, however, are essential for sustained mitotic growth of S. cerevisiae and for enzymatic activity in vitro. A series of topoisomerase II carboxy-terminal truncations were investigated with respect to the ability to support viability, cellular localization, and enzymatic properties. The analysis showed that the divergent carboxy-terminal region of human topoisomerase IIalpha is dispensable for catalytic activity but contains elements that specifically locate the protein to the nucleus.

Amino Acid Sequence↗

PubMed1976

Structural origins of mammalian albumin.

The amino acid sequence and disulfide bridges of bovine serum albumin reveal nine double loops formed by the bridges. The pattern and size of loops and connecting segments between loops indicate that a basic repeating unit (domain) consists of "large double loop-short connecting segment-small double loop-long connecting segment-large double loop-connecting segment between "domains" and repeats exactly three times. Thus, albumin arose by duplication of the primordial single domain gene, followed some time later by a half-gene duplication to give the ancestor of the present triple domain structure. These duplications are estimated to have occurred about 700 million years ago, based on the differences between domain (75 to 82%), the difference between bovine and human albumins (20%),and reported time estimates for globin and immunoglobulin evolution. Still farther back in time, the single domain arose by triplication of a gene of a primordial subdomain of about 77 amino acid residues, consisting of one large double loop with a segment on each end. The structure resulting from this triplication consisted of three large loops and three long connecting segments. Later, a gene deletion for part of a connecting segment and part of the middle large loop occurred to produce the large-small-large loop pattern. A proposed three dimensional structure for the "subdomain" shows spatial and sequence similarity with the G-H helical regions of myoglobin or hemoglobin, suggesting that it arose by duplication and separation of a gene for a C-terminal segment of a primitive globin. The CYS residues were introduced as an adaptive, convergent evolutionary event after separation from globin, but before duplication of the subdomain gene.

Amino Acid Sequence↗

PubMed2002

Evolution of functionally conserved enhancers can be accelerated in large populations: a population-genetic model.

The evolution of cis-regulatory elements (or enhancers) appears to proceed at dramatically different rates in different taxa. Vertebrate enhancers are often very highly conserved in their sequences, and relative positions, across distantly related taxa. In contrast, functionally equivalent enhancers in closely related Drosophila species can differ greatly in their sequences and spatial organization. We present a population-genetic model to explain this difference. The model examines the dynamics of fixation of pairs of individually deleterious, but compensating, mutations. As expected, small populations are predicted to have a high rate of evolution, and the rate decreases with increasing population size. In contrast to previous models, however, this model predicts that the rate of evolution by pairs of compensatory mutations increases dramatically for population sizes above several thousand individuals, to the point of greatly exceeding the neutral rate. Application of this model predicts that species with moderate population sizes will have relatively conserved enhancers, whereas species with larger populations will be expected to evolve their enhancers at much higher rates. We propose that the different degree of conservation seen in vertebrate and Drosophila enhancers may be explained solely by differences in their population sizes and generation times.

Animals↗

PubMedDate not supplied

The effect of vascular curvature on three-dimensional reconstruction of intravascular ultrasound images.

OBJECTIVE: To characterize the effect of vessel curvature on the geometric accuracy of conventional three-dimensional reconstruction (3DR) algorithms for intravascular ultrasound image data. BACKGROUND: A common method of 3DR for intravascular ultrasound image data involves geometric reassembly and volumetric interpolation of a spatially related sequence of tomographic cross sections generated by an ultrasound catheter withdrawn at a constant rate through a vascular segment of interest. The resulting 3DR is displayed as a straight segment, with inherent vascular curvature neglected. Most vascular structures, however, are not straight but curved to some degree. For this reason, vascular curvature may influence the accuracy of computer-generated 3DR. METHODS: We collected image data using three different intravascular ultrasound catheters (2.9 Fr, 4.3 Fr, 8.0 Fr) during a constant-rate pullback of 1 mm/sec through tubing of known diameter with imposed radii of curvature ranging from 2 to 10 cm. Image data were also collected from straight tubing. Image data were digitized at 1.0-mm intervals through a length of 25 mm. Two passes through each radius of curvature were performed with each intravascular ultrasound catheter. 3DR lumen volume for each radius of curvature was compared to that theoretically expected from a straight cylindrical segment. Differences between 3DR lumen volume of theoretical versus curved (actual) tubes were quantified as absolute percentage error and categorized as a function of curvature. Tubing deformation error was quantified by quantitative coronary angiography (QCA). RESULTS: Volumetric errors ranged from 1% to 35%, with an inverse relationship demonstrated between 3DR lumen volume and segmental radius of curvature. Higher curvatures (r < 6.0 cm) induced greater lumen volume error when compared to lower curvatures (r > 6.0 cm). This trend was exhibited for all three catheters and was shown to be independent of tubing deformation artifacts. QCA-determined percentage diameter stenosis indicated no deformation error as a function of curvature. Total volumetric error contributed by tubing deformation was estimated to be 0.05%. CONCLUSIONS: Catheter-dependent geometrical error arises in three-dimensionally reconstructed timed linear pullbacks of intravascular ultrasound images due in part to uniplanar vascular curvature. Three-dimensional reconstruction of timed linear pullbacks is robust for vessels with low radii of curvature; however, careful interpretation of three-dimensional reconstructions from timed linear pullbacks for higher radii of curvature is warranted. These data suggest that methods of spatially correct three-dimensional reconstruction of intravascular ultrasound images should be considered when more pronounced vascular curvature is present.

Algorithms↗

PubMed1999

Humanization of a murine monoclonal antibody by simultaneous optimization of framework and CDR residues.

Optimal protein function often depends on co-operative interactions between amino acid residues distant in the protein primary sequence yet spatially near one another following protein folding. For example, antibody affinity is influenced by interactions of framework residues with complementarity-determining region (CDR) residues. However, despite the abundance of antibody structural information and computational tools the humanization of rodent antibodies for clinical use often results in a significant loss of affinity. To date, antibody engineering efforts have focused either on optimizing CDR residues involved in antigen binding or on optimizing antibody framework residues that serve critical roles in preserving the conformation of CDRs. In the present study a new approach which permits the rapid identification of co-operatively interacting framework and CDR residues was used to simultaneously humanize and optimize a murine antibody directed against CD40. Specifically, a combinatorial library that examined eight potentially important framework positions concomitantly with focused CDR libraries consisting of variants containing random single amino acid mutations in the third CDR of the heavy and light chains was expressed. Multiple anti-CD40 Fab variants containing as few as one murine framework residue and displaying up to approximately 500-fold higher affinity than the initial chimeric Fab were identified. The higher affinity humanized variants demonstrated a co-operative interaction between light chain framework residue Y49 and heavy chain CDR3 residue R/K101 (coupling energy, DeltaGI=0.9 kcal/mol). Screening of combinatorial framework-CDR libraries permits identification of monoclonal antibodies (mAb) with structures optimized for function, including instances in which the antigen induces conformational changes in the mAb. Moreover, the enhanced humanized variants contain fewer murine framework residues and could not be identified by sequential in vitro humanization and affinity muturation strategies. This approach to identifying co-operatively interacting residues is not restricted to antibody-antigen interactions and consequently, may be used broadly to gain insight into protein structure-function relationships, including proteins that serve as catalysts.

Amino Acid Sequence↗

PubMed2000

A weighted least-squares algorithm for estimation and visualization of relative latencies in event-related functional MRI.

The properties of the hemodynamic latencies in functional maps have been relatively unexplored. Accurate methods of estimating hemodynamic latencies are needed to take advantage of this feature of fMRI. A fully automated, weighted least-squares (WLS) method for estimating temporal latencies is reported. Using a weighted linear model, the optimal latency and amplitude of the fMRI response can be determined for those voxels that pass a detection threshold. There is evidence from previous studies that the hemodynamic response may be time-locked to the stimulus within certain limits, less variable earlier in its evolution, and able to resolve information about relative hemodynamic timing. This information can be used to test hypotheses about the sequence and spatial distribution of neural activity. The method can be used to weight the earliest evolution of the hemodynamic response more heavily and decrease bias resulting from the hemodynamic response function. Additionally, the WLS method can control for varying response shapes across the brain and improve latency comparisons between brain regions. The WLS method was developed to study the properties of hemodynamic latencies, which may be increasingly important as event-related fMRI continues to be advanced.

Algorithms↗

PubMed1991

Ultrastructural and morphometric analysis of the separation of two thigh muscles in the chick.

Limb muscles separate from one another in a complex but highly stereotyped sequence and spatial pattern. The process of separation is characterized by the progression of a region of increased extracellular space, the cleavage zone, along the proximodistal axis between the individual muscle anlagen. We analyzed ultrastructurally the muscles and cleavage zone during the separation of two representative muscles, the developing sartorius and iliotibialis in the chick thigh, to establish an accurate baseline for an analysis of the mechanisms of separation. Comparisons of the morphology and distribution of cells before and after separation show no evidence that muscles became separated by the massive influx of an exterior cell population; if populations invade the cleavage zone, they are small. We do find characteristic transitions within the cell population of the cleavage zone in situ that could accomplish cleavage without invoking massive cell movements. These progressive transitions within the cleavage zone include a loss of close cell-cell interactions, an increase in extracellular space, the assumption of a more stellate morphology by mesenchyme cells, and a gradual alteration in the composition of the extracellular matrix from one typical of early muscle to one typical of loose connective tissue. Myotubes do differentiate between the incipient muscles, ruling out the possibility that the location where muscles will separate is defined by sites where myotubes fail to differentiate. Instead, the myotubes in the cleavage zone gradually diminish in number and appear to be specifically recognized and removed from the cleavage zone by phagocytes. We suggest that the transitions within the cleavage zone, including the loss of muscle cells, are a result of the progressive differentiation of loose connective tissue. If so, then the spatial pattern and process of cleavage is a consequence of spatially programmed cell differentiation.

Animals↗

PubMed1996

Observing N-acetyl aspartate via both its N-acetyl and its strongly coupled aspartate groups in in vivo proton magnetic resonance spectroscopy.

The approximately 2.6 ppm aspartate multiplet of N-acetyl aspartate (NAA) is considered a potential source of additional information on N-acetyl aspartate in vivo. Because the aspartate multiplet is the AB part of a strongly coupled ABX system it gives rise, as is shown in the analysis presented, to a significant field-strength dependence in the echo-time-dependent modulations of the response to typical spatial-localization sequences. The echo-time dependence of this response is developed analytically, not only for the STEAM and the PRESS localization sequences, but also for a spin-echo sequence. It is then verified experimentally at 2.35 T. The field-strength dependence of the response is demonstrated by evaluating the changes in the echo-time-dependent responses to each of the three sequences at field strengths of 1.5, 2.35, and 4.0 T. By means of these results, the preferred sequence (PRESS) can be optimized for the NAA aspartate multiplet at each field strength, as is illustrated with the human brain spectra obtained in vivo at 1.5 T. These in vivo spectra compare the optimal, long TE timing (163 ms) with a suboptimal TE (70 ms), for the observation of the approximately 2.6 ppm aspartate resonances of NAA.

Aspartic Acid↗

PubMed1995

A mechanochemical model for adult dermal wound contraction and the permanence of the contracted tissue displacement profile.

The healing of adult mammalian skin wounds involves a complex sequence of spatially and temporally coordinated processes. Wound contraction, by reducing the size of the injury, is an intrinsic component of full-thickness excisional dermal wound healing. The underlying biomechanics of wound contraction, however, are not fully understood, and little is known about the pathogenesis of severe medical conditions known as fibrocontractive diseases. The aim of this work is to investigate a deterministic mathematical model in order to obtain insight into the mechanistic relationships between wound contraction and associated normal and pathological healing processes. The model describes the essential roles of fibroblast and myofibroblast cells, a chemical growth factor and the extracellular matrix which includes type I collagen. The model results are qualitatively consistent with the biology of fibroplasia and wound contraction. It is shown that a contracted state evolves during a (long) transient phase of healing known as "proliferation", while collagen kinetics are fundamental to the considerably longer "remodelling" phase. Some quantitative results, notably on the evolution of wound contraction, compare favourably with experimental data. Application of the model to adult human dermal wound healing in vivo, with a greater understanding of the underlying biological mechanisms involved, may suggest strategies for controlling contraction and fibrocontractive diseases.

Adult↗

PubMed1985

Control of DNA replication and spatial distribution of defined DNA sequences in salivary gland cells of Drosophila melanogaster.

In dividing cells, each sequence replicates exactly once in each S-phase, but in cells with polytene chromosomes, some sequences may replicate more than once or fail to replicate during S-phase. Because of this differential replication, the control of replication in polytene cells must have some unusual features. Dennhöfer (1982a) has recently concluded that the total DNA content of the polytene cells of Drosophila salivary glands exactly doubles in each S-phase. This observation, along with previous studies demonstrating satellite underreplication in salivary gland cells, led us to consider the hypothesis that there is a "doubling of DNA" mechanism for the control of DNA replication in polytene cells. With this mechanism, a doubling of DNA content, rather than the replication of each sequence, would signal the end of a cycle of DNA replication. To test this hypothesis, we have reinvestigated the replication of several sequences (satellite, ribosomal, histone and telomere) in salivary gland cells using quantitative in situ hybridization. We find that underreplication of some sequences does occur. In addition we have repeated Dennhöfer's cytophotometric and labeling studies. In contrast to Dennhöfer, we find that the total DNA contents of nonreplicating nuclei do reflect this partial replication, in accord with Rudkin's (1969) result. We conclude that DNA replication in polytene cells is controlled by modifications of the mechanism operating in dividing cells, where control is sequence autonomous, and not by a "doubling of DNA" mechanism. In situ hybridization to unbroken salivary gland nuclei reveals the distribution of specific sequences. As expected, satellite, histone and 5S sequences are usually in a single cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Dual role of calmodulin in excitable cells.

Consideration of the enzymatic reactions governing calcium channel phosphorylation and dephosphorylation leads one to deduce that there exist separate groups of enzymes, membrane-bound and cytoplasmic that are activated by a common mediator, calmodulin (CaM), whose time-dependent appearance (via diffusion) at both locales is controlled by both intracellular calcium levels and electrostatic interaction with the membrane. In brief, the change in the sign and extent of the electrical charge borne by the modulator in the presence of calcium (Ca) brings about the electrostatic attraction that enables the transport of [Ca-CaM] to the membrane. This translocation of Ca-CaM makes possible a sequential activation of cellular enzymes whose locations differ. The sequence, both spatial and temporal, of the activation of various cellular enzymes by Ca-CaM appears to be a control network shared in common by excitable cells containing a stimulus-response pathway mediated by second messengers.

Adenylyl Cyclases↗