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Control of locomotion in marine mollusk Clione limacina. VIII. Cerebropedal neurons.

1. The pteropod mollusk Clione limacina swims by rhythmical oscillations of two wings, and its spatial orientation during locomotion is determined by tail movements. The majority of neurons responsible for generation of the wing and tail movements are located in the pedal ganglia. On the other hand, the majority of sensory inputs that affect wing and tail movements project to the cerebral ganglia. The goal of the present study was to identify and characterize cerebropedal neurons involved in the control of the swimming central generator or motor neurons of wing and tail muscles. Cerebropedal neurons affecting locomotion-controlling mechanisms are located in the rostromedial (CPA neurons), caudomedial (CPB neurons), and central (CPC neurons) zones of the cerebral ganglia. According to their morphology and effects on pedal mechanisms, 10 groups of the cerebropedal neurons can be distinguished. 2. CPA1 neurons project through the ipsilateral cerebropedal connective to both pedal ganglia. Activation of a CPA1 by current injection resulted in speeding up of the locomotor rhythm and intensification of the firing of the locomotor motor neurons. 3. CPA2 neurons send numerous thin fibers into the ipsi- and contralateral pedal and pleural ganglia through the cerebropedal and cerebropleural connectives. They strongly inhibit the wing muscle motor neurons and, to a lesser extent, slow down the locomotor rhythm. 4. CPB1 neurons project through the contralateral cerebropedal connective to both pedal ganglia. They activate the locomotor generator. 5. CPB2 neurons also project, through the contralateral cerebropedal connective, to both pedal ganglia. They affect wing muscle motor neurons. 6. CPB3 neurons have diverse morphology: they project to the pedal ganglia either through the ipsilateral cerebropedal connective, or through the contralateral one, or through both of them. They affect putative motor neurons of the tail muscles. 7. CPC1, CPC2, and CPC3 neurons project through the ipsilateral cerebropedal connective to both pedal ganglia. They activate the locomotor generator. 8. CPC4 and CPC5 neurons project through the contralateral cerebropedal connective to the contralateral pedal ganglia. They activate the locomotor generator. 9. Serotonergic neurons were mapped in the CNS of Clione by immunohistochemical methods. Location and size of cells in two groups of serotonin-immunoreactive neurons in the cerebral ganglia appeared to be similar to those of CPA1 and CPB1 neurons. This finding suggests a possible mechanism for serotonin's ability to exert a strong excitatory action on the locomotor generator of Clione. 10. The role of different groups of cerebropedal neurons is discussed in relation to different forms of Clione's behavior in which locomotor activity is involved.

Animals↗

Olfactory inputs activate the medial entorhinal cortex via the hippocampus.

The lateral and medial regions of the entorhinal cortex differ substantially in terms of connectivity and pattern of activation. With regard to olfactory input, a detailed and extensive physiological map of the olfactory projection to the entorhinal cortex is missing, even if anatomic studies suggest that the olfactory afferents are confined to the lateral and rostral entorhinal region. We studied the contribution of the medial and lateral entorhinal areas to olfactory processing by analyzing the responses induced by lateral olfactory tract stimulation in different entorhinal subfields of the in vitro isolated guinea pig brain. The pattern of synaptic activation of the medial and lateral entorhinal regions was reconstructed either by performing simultaneous multisite recordings or by applying current source density analysis on field potential laminar profiles obtained with 16-channel silicon probes. Current source density analysis demonstrated the existence of a direct monosynaptic olfactory input into the superficial 300 microm of the most rostral part of the lateral entorhinal cortex exclusively, whereas disynaptic sinks mediated by associative fibers arising from the piriform cortex were observed at 100-350 microm depth in the entire lateral aspect of the cortex. No local field responses were recorded in the medial entorhinal region unless a large population spike was generated in the hippocampus (dentate gyrus and CA1 region) by a stimulus 3-5x the intensity necessary to obtain a maximal monosynaptic response in the piriform cortex. In these conditions, a late sink was recorded at a depth of 600-1000 microm in the medial entorhinal area (layers III-V) 10.6 +/- 0.9 (SD) msec after a population spike was simultaneously recorded in CA1. Diffuse activation of the medial entorhinal region was also obtained by repetitive low-intensity stimulation of the lateral olfactory tract at 2-8 Hz. Higher or lower stimulation frequencies did not induce hippocampal-medial entorhinal cortex activation. These results suggest that the medial and the lateral entorhinal regions have substantially different roles in processing olfactory sensory inputs.

Action Potentials↗

Transformation of computed tomography and magnetic resonance images.

This paper discusses the transformation of computed tomography (CT) and magnetic resonance (MR) images, which maps the stereotactic volumetric cube of one examination to another. There are some mathematical problems connected with the present method. This approach provides a better visual detection and localization of the target point for the neurosurgeon or radiologist.

Humans↗

Impulse propagation in synthetic strands of neonatal cardiac myocytes with genetically reduced levels of connexin43.

Connexin43 (Cx43) is a major determinant of the electrical properties of the myocardium. Closure of gap junctions causes rapid slowing of propagation velocity (theta), but the precise effect of a reduction in Cx43 levels due to genetic manipulation has only partially been clarified. In this study, morphological and electrical properties of synthetic strands of cultured neonatal ventricular myocytes from Cx43+/+ (wild type, WT) and Cx+/- (heterozygote, HZ) mice were compared. Quantitative immunofluorescence analysis of Cx43 demonstrated a 43% reduction of Cx43 expression in the HZ versus WT mice. Cell dimensions, connectivity, and alignment were independent of genotype. Measurement of electrical properties by microelectrodes and optical mapping showed no differences in action potential amplitude or minimum diastolic potential between WT and HZ. However, maximal upstroke velocity of the transmembrane action potential, dV/dtmax, was increased and action potential duration was reduced in HZ versus WT. theta was similar in the two genotypes. Computer simulation of propagation and dV/dtmax showed a relatively small dependence of theta on gap junction coupling, thus explaining the lack of observed differences in theta between WT and HZ. Importantly, the simulations suggested that the difference in dV/dtmax is due to an upregulation of INa in HZ versus WT. Thus, heterozygote-null mutation of Cx43 produces a complex electrical phenotype in synthetic strands that is characterized by both changes in ion channel function and cell-to-cell coupling. The lack of changes in theta in this tissue is explained by the dominating role of myoplasmic resistance and the compensatory increase of dV/dtmax.

Action Potentials↗

[Evaluation of the clinical diagnostic reasoning. Use of dynamic attractors as an alternative].

The purpose of this study was to apply diagnostic clinical reasoning, based upon cognitive teaching, to help the student develop their own mental structure of an ailment or disease. Such a structure is built as mathematical chaotic deterministic type that can be evaluated through identification of dynamic attractors. To achieve our purpose, clinical diagnostic reasoning skills of two groups of students was compared against those of an expert through revision of 17 clinical cases. Such revision, selection of relevant data, allows for construction of conceptual maps in which several dynamic attractors can be identified, based on the largest number of connections that stem from some concepts. In the majority of cases, statistical analysis showed similarity among types of connections established by the expert; several similar dynamic attractors could be identified, leading us to conclude that cognitive-based teaching of diagnostic clinical reasoning is useful in developing this type of skill, and that it can be evaluated through identification of dynamic attractors.

Cross-Sectional Studies↗

[Effect of arousing and somnogenic effects on the hypothalamus on the space-time organization of the internal connections of the somatosensory cortex].

Evoked potentials arising in the somatosensory cortex in response to single local stimulation of a forepaw, were recorded in cats in a state of slow-wave sleep and strained alertness elicited by electric activation of the basal preoptic area and posterior hypothalamus. Structure of connections between cortical points was studied by values of responses' amplitudes by means of correlation and factor analyses. It has been found that the organization of functional connections within the somatosensory cortex is determined by several factors, sensitive to hypothalamic influences. The most specific organization for each state is revealed at the stage of completion of the positive-negative complex of the primary response, which combines with the highest plasticity of connection formation.

Animals↗

[Closing an intra-analyzer temporary connection in visual cortex neuronal element microsystems].

The work was aimed at studying the formation of microsystems of learning neurones in the cortical visual zone of immobilized cats during elaboration of a temporary connection based on a combined stimulation of two its points in acute experiment. 18.6 per cent of the cells developed responses to the stimulus which had been ineffective before conditioning. The most numerous group consisted of units which displayed a complex form of elaborated response. Presumably the untis observed are part of a system of learning neurones controlling the intraanalyser interactions by the mechanism of temporary connection.

Animals↗

[Pallido-thalamic projections of cats].

Projections of the globus pallidus and the entopeduncular nucleus on the thalamic nuclei have been studied in cats by methods of axonal-preterminal degeneration and retrograde cellular degeneration. Together with the known projections of the pallidum on the medial center, ventral anterior and ventral lateral thalamic nuclei, direct projections of the pallidum on the medial dorsal, central lateral and lateral posterior thalamic nuclei have been revealed. In cats not only the entopeduncular nucleus is the source of the fibres projecting on the thalamic nuclei, but also the globus pallidus has direct connections with the thalamic nuclei

Animals↗

[Usefulness of magnetic resonance imaging for managing patients with prosthetic carbon valve in the mitral position].

The safety, findings and clinical usefulness of magnetic resonance (MR) imaging were assessed in patients with a prosthetic carbon valve in the mitral position. In vitro deflection, heating and image distortion due to the magnetic field of a 1.5 tesla MR machine were examined in three carbon valves (CarboMedics, St. Jude Medical and Björk-Shiley valves). In vivo MR imaging of the left ventricular horizontal long-axis, vertical long-axis and short-axis views was performed by electrocardiographically synchronized spin echo and field (gradient) echo techniques in eight patients with prosthetic mitral carbon valves, consisting of six CarboMedics valves, one St. Jude Medical valve and one Björk-Shiley valve. No deflection and significant heating was seen in all three valves in vitro. Although little image distortion was shown in the CarboMedics and St. Jude Medical valves, a small distortion toward the frequency encoded direction was seen in the Björk-Shiley valve but caused no difficulty in assessing the surrounding images. Four of the eight patients had normal sinus rhythm and the other four had atrial fibrillation. The prosthetic valves were depicted as signal voids in the images taken by both spin echo and field echo techniques in vivo. Clear structural information with little image distortion of the adjacent tissues of the prosthetic valves were obtained in all patients, although the image of the Björk-Shiley valve which contained stainless steel in the frame had a slightly stronger distortion than those of the CarboMedics and St. Jude Medical valves which contained titanium. The stainless wire suture material used to close the sternal incision was depicted as a signal void, and the areas of the signal loss were larger in the images taken by the field echo technique than those by the spin echo technique. The images taken by the spin echo technique in patients with atrial fibrillation had reduced quality due to the irregularity of repetition time. Cine MR imaging by the field echo technique showed physiological mitral regurgitant jets as signal loss within the flowing blood, which appeared as high signal intensity, bidirectionally in the bileaflet mechanical valve and unidirectionally in the monoleaflet mechanical valve. An abnormal cavity was seen behind the basal left ventricular myocardium in one patient with a CarboMedics valve. The wall of the abnormal cavity was disrupted abruptly and the rest of the wall consisted of pericardium and adjacent tissue in the image taken by the spin echo technique. The image taken by the field echo technique showed an abnormal jet flow from the basal part of the left ventricular cavity into the abnormal cavity, which was compatible with left ventricular pseudoaneurysm. Two-dimensional echocardiography and Doppler color flow mapping disclosed the abnormal cavity and the abnormal flow inside, but failed to show the connection between the left ventricle and the cavity due to reverberation of the ultrasound signal by the prosthetic valve. These findings suggest that MR imaging is a safe and promising method to assess the complications and valvular function in patients with a prosthetic carbon valve in the mitral position.

Aged↗

[Projections of several intralaminar nuclei of the thalamus to the caudate nucleus in cats].

Direct connections of the central medial, parafascicular and central lateral nuclei of the thalamus with the rostral and caudal parts of the head and the body of the caudate nucleus were studied. The study has revealed that only the central nucleus of the three concerned intralaminar nuclei of the thalamus is projected on the caudate nucleus, head and body. The central medial and parafascicular nucleus of the thalamus does not seem to have direct connections with the caudate nucleus.

Animals↗

Specificity of color connectivity between primate V1 and V2.

To examine the functional interactions between the color and form pathways in the primate visual cortex, we have examined the functional connectivity between pairs of color oriented and nonoriented V1 and V2 neurons in Macaque monkeys. Optical imaging maps for color selectivity, orientation preference, and ocular dominance were used to identify specific functional compartments within V1 and V2 (blobs and thin stripes). These sites then were targeted with multiple electrodes, single neurons isolated, and their receptive fields characterized for orientation selectivity and color selectivity. Functional interactions between pairs of V1 and V2 neurons were inferred by cross-correlation analysis of spike firing. Three types of color interactions were studied: nonoriented V1/nonoriented V2 cell pairs, nonoriented V1/oriented V2 cell pairs, and oriented V1/nonoriented V2 cell pairs. In general, interactions between V1 and V2 neurons are highly dependent on color matching. Different cell pairs exhibited differing dependencies on spatial overlap. Interactions between nonoriented color cells in V1 and V2 are dependent on color matching but not on receptive field overlap, suggesting a role for these interactions in coding of color surfaces. In contrast, interactions between nonoriented V1 and oriented V2 color cells exhibit a strong dependency on receptive field overlap, suggesting a separate pathway for processing of color contour information. Yet another pattern of connectivity was observed between oriented V1 and nonoriented V2 cells; these cells exhibited interactions only when receptive fields were far apart and failed to interact when spatially overlapped. Such interactions may underlie the induction of color and brightness percepts from border contrasts. Our findings thus suggest the presence of separate color pathways between V1 and V2, each with differing patterns of convergence and divergence and distinct roles in color and form vision.

Animals↗

Surgical procedure for the cure of atrioventricular junctional ("AV node") reentrant tachycardia: anatomic and electrophysiologic effects of dissection of the anterior atrionodal connections in a canine model.

OBJECTIVES: This study was undertaken to examine the electrophysiologic and anatomic effects of a surgical procedure that cures the anterior (common) type of atrioventricular (AV) junctional reentrant tachycardia. BACKGROUND: The procedure was designed to interrupt the reentrant circuit at the point of earliest atrial activation during AV junctional reentrant tachycardia, the anterior atrionodal connections. METHODS: Atrioventricular node function and the sequence of electrical excitation of Koch's triangle were examined in 18 dogs. Excitation of Koch's triangle was mapped using a 60-channel mapping system. Surgical dissection was performed in 10 dogs and a sham procedure in 8. After 28 to 35 days, AV node function and the atrial excitation pattern were reassessed. The AV junction was examined using light microscopy. RESULTS: Some degree of AV node damage was visible in all dogs in the dissection group, but it was minor in 40% of cases. The anterior part of the AV node was disconnected from the anterior atrionodal connections in all cases. Anterograde AV node function was mildly impaired. The median AH interval was increased (62 vs. 76 ms [interquartile ranges 48 to 72 and 64 to 104, respectively], p = 0.05), and the AV Wenckebach cycle length was increased (210 vs. 245 ms [interquartile ranges 200 to 230 and 210 to 260, respectively], p = 0.02). The degree of impairment of conduction was directly proportional to the length of dissection (p < 0.05) but not to the degree of damage to the AV node. Ventriculoatrial (VA) conduction was destroyed in 50% of dogs undergoing dissection but in none of those with a sham operation (p < 0.04). The AV node remained responsive to autonomic blocking drugs, and atrial mapping during ventricular pacing revealed that the site of exit from the AV node had been altered. CONCLUSIONS: The atrionodal connections closest to the His bundle are the preferred route of conduction through the AV node during normal AV or VA conduction. Destruction of these connections modifies AV node conduction. The surgical procedure selectively interrupts these connections, and this interruption is likely to be the mechanism of cure.

Animals↗

The gatekeeper residue controls autoactivation of ERK2 via a pathway of intramolecular connectivity.

Studies of protein kinases have identified a "gatekeeper" residue, which confers selectivity for binding nucleotides and small-molecule inhibitors. We report that, in the MAP kinase ERK2, mutations at the gatekeeper residue unexpectedly lead to autoactivation due to enhanced autophosphorylation of regulatory Tyr and Thr sites within the activation lip that control kinase activity. This occurs through an intramolecular mechanism, indicating that the gatekeeper residue indirectly constrains flexibility at the activation lip, precluding access of the phosphoacceptor residues to the catalytic base. Other residues that interact with the gatekeeper site to form a hydrophobic cluster in the N-terminal domain also cause autoactivation when mutated. Hydrogen-exchange studies of a mutant within this cluster reveal perturbations in the conserved DFG motif, predicting a route for side chain connectivity from the hydrophobic cluster to the activation lip. Mutations of residues along this route support this model, explaining how information about the gatekeeper residue identity can be transmitted to the activation lip. Thus, an N-terminal hydrophobic cluster that includes the gatekeeper forms a novel structural unit, which functions to maintain the "off" state of ERK2 before cell signal activation.

Animals↗

Disease map reconstruction.

The analysis of the geographical distribution of disease incidence or prevalence is now of considerable importance for public health workers and epidemiologists alike. Important disease variations often have a spatial expression and so spatial analysis methods are an important additional tool in this connection. In this tutorial I have aimed to highlight the main issues relating to the analysis of disease where the goal is the reduction in noise in a disease map. This area is sometimes simply called disease mapping. A number of modelling approaches to disease mapping are considered and a case study highlighting the methods advocated is also included.

Bayes Theorem↗

Analytical and micropreparative peptide mapping by high performance liquid chromatography/electrospray mass spectrometry of proteins purified by gel electrophoresis.

We report the use of microbore reverse-phase high performance liquid chromatography connected on-line to an electrospray mass spectrometer for the separation/detection of peptides derived by proteolytic digestion of proteins separated by polyacrylamide gel electrophoresis. A small fraction (typically 10% of the total) of the peptides eluting from the column was diverted through a flow-splitting device into the ion source of the mass spectrometer, whereas the majority of the peptide samples was collected for further analyses. We demonstrate the feasibility of obtaining reproducible peptide maps from submicrogram amounts of protein applied to the gel and good correlation of the signal detected by the mass spectrometer with peptide detection by UV absorbance. Furthermore, independently verifiable peptide masses were determined from subpicomole amounts of peptides directed into the mass spectrometer. The method was used to analyze the 265-kDa and the 280-kDa isoforms of the enzyme acetyl-CoA carboxylase isolated from rat liver. The results provide compelling evidence that the two enzyme isoforms are translation products of different genes and suggest that these approaches may be of general utility in the definitive comparison of protein isoforms. We furthermore illustrate that knowledge of peptide masses as determined by this technique provides a major advantage for error-free data interpretation in chemical high-sensitivity peptide sequence analysis.

Acetyl-CoA Carboxylase↗

CTGF expression in mesangial cells: involvement of SMADs, MAP kinase, and PKC.

BACKGROUND: The induction of excess matrix in renal fibrosis seems to be mediated, at least in part, by the transforming growth factor-beta (TGF-beta)-mediated induction of connective tissue growth factor (CTGF) in mesangial cells. METHODS: By examining CTGF protein and mRNA expression and promoter activity in the presence or absence of TGF-beta or inhibitors, the signaling pathways controlling basal and TGF-beta-induced CTGF expression in mesangial cells were investigated. RESULTS: TGF-beta enhances CTGF mRNA and protein expression in mesangial cells. Mutation of a consensus SMAD binding element in the CTGF promoter completely abolished TGF-beta-induced CTGF expression and reduced basal CTGF expression. The previously identified basal control element-1 (BCE-1) site, but not Sp1 contributes to basal CTGF promoter activity. Ras/MEK/ERK, protein kinase C (PKC) and tyrosine kinase activity also contribute to basal and TGF-beta-induced CTGF promoter activity in cultured mesangial cells. CONCLUSIONS: The TGF-beta-induction of CTGF in mesangial cells requires SMADs and PKC/ras/MEK/ERK pathways. SMADs are involved in basal CTGF expression, which presumably reflects the fact that mesangial cells express TGF-beta endogenously. TGF-beta also induces CTGF through ras/MEK/ERK. Inhibiting ras/MEK/ERK seems not to reduce phosphorylation (that is, activation) of SMADs, suggesting that SMADs, although necessary, are insufficient for the TGF-beta-stimulation of the CTGF promoter through ras/MEK/ERK. Thus, maximal TGF-beta induction of CTGF requires synergy between SMAD and ras/MEK/ERK signaling.

Animals↗

Development of an animal genome database and its search system.

An animal genome database has been developed on a Unix workstation and maintained by a relational database management system. This database has focused on the comparative gene mapping between species to assist the mapping of the genes related to phenotypic traits in livestock. The linkage maps, cytogenetic maps, polymerase chain reaction primers of pig, cattle, mouse and human, and their references have been included in the database, and the correspondence among species have been stipulated in the database. In order to search the database effectively, the World Wide Web server (http://ws4.niai.affrc.go.jp/) and the electronic mail server system (e-mail: jgbase-mail@ niai.affrc.go.jp) have been developed on different Unix workstations. These servers are connected to the Internet.

Animals↗

Prediction, assessment and validation of protein interaction maps in bacteria.

High-throughput proteomics technologies, especially the yeast two-hybrid system, produce large volumes of protein-protein interaction data organized in networks. The complete sequencing of many genomes raises questions about the extent to which such networks can be transferred between organisms. We attempted to answer this question using the experimentally derived Helicobacter pylori interaction map and the recently described interacting domain profile pair (IDPP) method to predict a virtual map for Escherichia coli. The extensive literature concerning E.coli was used to assess all predicted interactions and to validate the IDPP method, which clusters protein domains by sequence and connectivity similarities. The IDPP method has a much better heuristic value than methods solely based on protein homology. The IDPP method was further applied to Campylobacter jejuni to generate a virtual interaction map. An in-depth comparison of the chemotaxis pathways predicted in E.coli and C.jejuni led to the proposition of new functional assignments. Finally, the prediction of protein-protein interaction maps across organisms enabled us to validate some of the interactions on the original experimental map.

Bacterial Proteins↗