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PubMed1999

Timing and cell interactions underlying neural induction in the chick embryo.

Previous studies on neural induction have identified regionally localized inducing activities, signaling molecules, potential competence factors and various other features of this important, early differentiation event. In this paper, we have developed an improved model system for analyzing neural induction and patterning using transverse blastoderm isolates obtained from gastrulating chick embryos. We use this model to establish the timing of neural specification and the spatial distribution of perinodal cells having organizer activity. We show that a tissue that acts either as an organizer or as an inducer of an organizer is spatially co-localized with the prospective neuroectoderm immediately rostral to the primitive streak in the early gastrula. As the primitive streak elongates, this tissue with organizing activity and the prospective neuroectoderm rostral to the streak separate. Furthermore, we show that up to and through the mid-primitive streak stage (i.e., stage 3c/3+), the prospective neuroectoderm cannot self-differentiate (i.e. , express neural markers and acquire neural plate morphology) in isolation from tissue with organizer activity. Signals from the organizer and from other more caudal regions of the primitive streak act on the rostral prospective neuroectoderm and the latter gains potency (i.e., is specified) by the fully elongated primitive streak stage (i.e., stage 3d). Transverse blastoderm isolates containing non-specified, prospective neuroectoderm provide an improved model system for analyzing early signaling events involved in neuraxis initiation and patterning.

Animals↗
PubMed1993

A neural network to analyze fertility data.

OBJECTIVE: To program an artificial intelligence system, a neural network, and use it to predict results of sperm penetration in bovine cervical mucus (Penetrak assay; Serono Laboratories, Norwell, MA) and zona-free hamster egg penetration from the semen analysis. DESIGN: Results of 139 Penetrak assays, 1,416 zona-free hamster egg penetration assays, and the corresponding semen analyses were retrospectively analyzed by an artificial neural network. MAIN OUTCOME MEASURES: Classification errors of the neural network were compared with those of linear and quadratic discriminant function analyses. RESULTS: Data were separated into training and test sets. For the Penetrak result, linear and quadratic discriminant function analysis correctly predicted 58% and 74% of the training set results and only 64.1% and 69.2% of the test data, respectively. The neural network correctly predicted 92% of training set results and 80% of test set results. For the zona-free hamster egg penetration assay outcome, linear and quadratic discriminant function analysis correctly classified 66.3% and 46.0% of the training set and 64.9% and 44.7% of the test set, respectively. The neural network correctly classified 75.7% of the training data and 67.8% of the test data. CONCLUSIONS: Using the semen analysis, the neural network correctly classified 67.8% of zona-free hamster egg penetration assay results and 80% of Penetrak results it had not encountered previously, suggesting that this method of data analysis may be successfully employed to predict fertility potential.

Animals↗
PubMed2007

Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

Female↗
PubMed1998

Microgravity effects on neural retina regeneration in the newt.

Data on forelimb and eye lens regeneration in urodeles under spaceflight conditions (SFC) have been obtained in our previous studies. Today, evidence is available that SFC stimulate regeneration in experimental animals rather than inhibit it. The results of control on-ground experiments with simulated microgravity suggest that the stimulatory effect of SFC is due largely to weightlessness. An original experimental model is proposed, which is convenient for comprehensively analyzing neural regeneration under SFC. The initial results described here concern regeneration of neural retina in Pleurodeles waltl newts exposed to microgravity simulated in radial clinostat. After clinorotation for seven days (until postoperation day 16), a positive effect of altered gravity on structural restoration of detached neural retina was confirmed by a number of criteria. Specifically, an increased number of Mullerian glial cells, an increased relative volume of the plexiform layers, reduced cell death, advanced redifferentiation of retinal pigment epithelium, and extended areas of neural retina reattachment were detected in experimental newts. Moreover, cell proliferation in the inner nuclear layer of neural retina increased as compared with control. Thus, low gravity appears to intensify natural cytological and molecular mechanisms of neural retina regeneration in lower vertebrates.

Animals↗
PubMedDate not supplied

Comparison of diagnostic usefulness of predictive models in preliminary differentiation of adnexal masses.

The purpose of this study was to compare prognostic models evaluating the probability of an ovarian cancer occurrence based on a number of clinical and ultrasonographic data in women with adnexal masses. A total of 686 women with adnexal masses underwent the examinations between 1994 and 2002. The recorded parameters included: age, menopausal status, body mass index, the grayscale and Doppler ultrasonographic examination, and selected markers concentration levels. In order to find the best combination of features, which significantly influences the probability of malignancy, stepwise logistic regression analysis, as well as artificial neural network, was used. The diagnostic efficiency of received models was estimated and compared using receiver-operating characteristics (ROC) curve. The results indicate that 431 and 255 patients had a benign and malignant ovarian tumor, respectively. Application of stepwise logistic regression analysis revealed statistically significant importance of eight features. The sensitivity and specificity for the received model were 65.71% and 77.59%, respectively. Three-layer perceptron network shows 13 features as significant predictors of malignancy. The network gave a sensitivity of 85.7% and specificity of 93.1%. Comparison of area under ROC curve for received models was 0.9679 vs 0.9716. Prognostic values of the analyzed neural model are not optimal but seem to surpass logistic regression model in terms of the predictive possibilities.

Adult↗
PubMed1998

Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuronopathy caused by the expansion of an unstable CAG repeat in the coding region of the androgen receptor (AR) gene. To study AR protein expression in normal and SBMA individuals, we used several antibodies that recognize AR protein, and analyzed neural and nonneural tissues by immunohistochemistry and western blotting. Both the normal and the mutant AR proteins were widely distributed, predominantly, but not exclusively, in the cytoplasm of neurons regardless of the pathological involvement, and predominantly in the nuclei of the nonneural tissues in both normal and SBMA individuals, with different expression levels of AR protein among different tissues. In the motor neurons of SBMA patients, there were AR-immunoreactive ubiquitinated nuclear inclusions that were detected by antibodies that recognize a small portion of the N terminus of the AR protein. Absence of other immunoreactive AR epitopes within the inclusion may be due to altered AR configuration, or masking of AR epitopes by other proteins, or proteolytic cleavage of the AR. Our data show that, in addition to the normal cellular distribution of the AR protein, mutant AR-bearing nuclear inclusions are present in SBMA.

Aged↗
PubMed2002

Dystonia: a disorder of motor programming or motor execution?

For some time, dystonia has been seen as purely a motor disorder. Relatively novel concepts published approximately 10 years ago also presumed that in the development of dystonic dyskinesias, only motor behaviour was abnormal. Neurophysiological observations of various types of dystonic disorders, which were performed using sophisticated electromyography, polymyography, H-reflex examination, long-latency reflex, etc., as well as new insights into the behaviour of dystonia, have urged the inclusion of sensory (particularly somatosensory) mechanisms into the pathophysiological background of dystonia. The major role has been considered to be played by abnormal proprioceptive input by means of the Ia proprioceptive afferents, with the source of this abnormality found in the abnormal processing of muscle spindle afferent information. However, neurophysiological investigations have also provided evidence that the abnormality in the central nervous system is located not only at the spinal and subcortical level, but also at the cortical level; specifically, the cortical excitability and intracortical inhibition have been revealed as abnormal. This evidence was revealed by SEP recordings, paired transcranial magnetic stimulation recordings, and BP and CNV recordings. The current concept of dystonic movement connects the abnormal function of somatosensory pathways and somatosensory analysers with the dystonic performance of motor action, which is based on the abnormality of sensorimotor integration.

Cerebral Cortex↗
PubMed1996

Basic behavior of migratory Schwann cells in peripheral nerve regeneration.

In axonal regeneration after a peripheral nerve injury, Schwann cells migrate from the two nerve ends and at last form a continuous tissue cable across the gap which guides the axons toward the bands of Bungner. However, the behavior of migratory Schwann cells and their possible role are obscure. Using a film model in which the proximal stump of a transected nerve in mice was sandwiched between two thin plastic films, we analyzed neural regeneration in the early phase up to the 6th day after axotomy. Regenerating neurites emerged from the nodes of Ranvier adjacent to the axotomized nerve stump within 3 h after axotomy and extended along the parent nerve onto the film. All of the regenerating neurites on the surface of the film consisted of naked axons for at least 2 days after axotomy. Thereafter, Schwann cells from the proximal nerve migrated along a network of the regenerating axons and then closely attached to the axons, ensheathing them. Some of the Schwann cells advanced ahead of the axonal growth cones and were distributed over regions in which axonal extension was not yet present. As calculated from the time course of regenerating neurites, the velocity of axonal regeneration showed two phases: an initial slow phase (77 mu m/day) up to the 2nd post-operative day followed by a faster phase (283 mu m/day). The first observation of Schwann cells coincided with the onset of the second phase. In addition, the length of regenerating axons on the surface of the film containing many Schwann cells was significantly greater than that on the surface where Schwann cells were not yet present. It meant that migratory Schwann cells stimulated axons to elongate for a longer distance. Furthermore, Schwann cells from a distal stump showed a stronger ability to accelerate the axonal outgrowth than these from a proximal stump.

Animals↗
PubMed2002

An fMRI-constrained MEG source analysis with procedures for dividing and grouping activation.

To analyze neural activity using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), we developed a method for fixing equivalent current dipoles of MEG in activation areas of fMRI. It includes a procedure for dividing large fMRI activation volumes into subvolumes in each of which a dipole is placed and another procedure for grouping neighboring dipoles whose temporal changes are inseparable based on MEG data. To optimize the procedures' parameters, we carried out simulations and found that (1) any single dipole within 10 mm from a true source can explain MEG data with a correlation of 94% on average for the low signal-to-noise ratio of 3 and (2) a neighboring dipole within a few tens of millimeters from the dipole nearest to the true source tends to be highly incorporated in explaining MEG data. We applied the method to data measured in a language experiment and detected 13 significant sources. The results show that the present method is promising for detecting neural activity originating from a number of separate neural sources.

Algorithms↗
PubMedDate not supplied

Long-term changes in the activity of superior colliculus neurons isolated from corticofugal influences.

In acute experiments on nonnarcotized, immobilized cats, spike activity was studied in superior collicular neurons which were isolated from direct, descending cortical influences. Animals were taken for experimentation at various periods (from 3 to 20 months) after the operation which disconnected the cortical connections which projected from one hemisphere. An increase was noted in the regular forms of activity, and there was a decrease in the frequency of group discharges. Evoked activity of the cells was suppressed during the early periods after disconnection of corticocollicular connections. Later (after 9--12 months) its gradual restoration was observed. More than 70% of the neurons again began to respond to adequate stimuli. The sensitivity to moving photic stimuli was restored in only 17% of the neurons studied.

Animals↗
PubMed1981

A rapid procedure for measurement of the free testosterone fraction in human plasma using the centria radioimmunoassay centrifugal analyzer.

Following the incubation of plasma with a tracer amount of tritiated testosterone, the reaction mixture is separated into a sex hormone-binding globulin bound and an unbound fraction of radioligand using DEAE-cellulose columns placed in the incubator-separator module of the Centria radioimmunoassay centrifugal analyzer. Neural Tris-buffer elutes unbound steroid from the matrix, while acidic Tris-buffer can remove the protein-bound fraction in a subsequent step. Complementary and thus qualitatively equal results are obtained when counting either eluate. Comparison of this technique with an ammonium sulfate precipitation method showed high correlation. Free testosterone indices as determined by the Centria modification in a number of prepuberal children, normal men and women, as well as pregnant and hirsute women similar to those previously reported.

Adrenal Hyperplasia, Congenital↗
PubMed2003

Postnatal changes in intrinsic optical responses to peripheral nerve stimulation in the in vivo rat spinal cord.

We previously applied an intrinsic optical imaging technique to the in vivo rat spinal cord, and showed its feasibility for analyzing neural functions. Three- to 7-week-old postnatal and adult (>10-week-old) rats were anesthetized and laminectomy was performed between C5 and Th1 to expose the dorsal surface of the cervical spinal cord. Optical reflectance changes in response to simultaneous stimulation of the median and ulnar nerves were recorded from the spinal cord at a depth corresponding to the dorsal horn (substantia gelatinosa), using a differential video acquisition system. The shape and extent of the area of the evoked optical signals varied during postnatal development. In 3- to 4-week-old rats, the response area was small and ellipsoidal, and constrictions between spinal segments were not clear. As postnatal ages proceeded, the area expanded in a rostrocaudal direction, and the constrictions became clear. In adult rats, the response area exhibited a segmental pattern. At all ages, the optical responses showed trial-to-trial variations. A semiquantitative analysis of the variations in one spinal segment showed that the variations in a mediolateral direction appeared to decrease slightly with development, although statistical differences were insignificant between ages. The dynamical changes in optical response patterns were discussed in relation to postnatal maturation of neural functions in the spinal cord.

Aging↗
PubMed2006

Differential patterns of multisensory interactions in core and belt areas of human auditory cortex.

The auditory cortex is anatomically segregated into a central core and a peripheral belt region, which exhibit differences in preference to bandpassed noise and in temporal patterns of response to acoustic stimuli. While it has been shown that visual stimuli can modify response magnitude in auditory cortex, little is known about differential patterns of multisensory interactions in core and belt. Here, we used functional magnetic resonance imaging and examined the influence of a short visual stimulus presented prior to acoustic stimulation on the spatial pattern of blood oxygen level-dependent signal response in auditory cortex. Consistent with crossmodal inhibition, the light produced a suppression of signal response in a cortical region corresponding to the core. In the surrounding areas corresponding to the belt regions, however, we found an inverse modulation with an increasing signal in centrifugal direction. Our data suggest that crossmodal effects are differentially modulated according to the hierarchical core-belt organization of auditory cortex.

Acoustic Stimulation↗
PubMed1999

Detection of temporal structure depends on spatial structure.

Observers can more easily detect correlated patterns of temporal contrast modulation within hybrid visual images composed of two components when those components are drawn from the same original picture (Blake, R., & Yang, Y. (1997). Proceedings of the National Academy of Science, 94, 7115-7119). To learn whether spatial phase is a mediating variable, we measured thresholds for detection of contrast modulation over time among component gratings while manipulating spatial phase among those components. In Experiment 1, observers more easily detected correlated contrast modulation when two component gratings were aligned in peaks-subtract phase. Experiment 2 showed that this phase-dependent detectability of synchronized contrast modulation is mediated by the phase-dependent, non-linear interaction among spatial frequency channels. The rigorous evaluation of several a priori reasonable hypotheses indicates that the phase-dependent detectability is not based on local spatial features such as local luminance, contrast or luminance gradient. Taken together, our results indicate that the spatial phase relationship and the temporal correlation of contrast modulation of two component gratings are both important for triggering facilitatory interaction between neural analyzers tuned to those gratings.

Contrast Sensitivity↗
PubMed2004

A new model of sensorimotor coupling in the development of speech.

We present a computational model that learns a coupling between motor parameters and their sensory consequences in vocal production during a babbling phase. Based on the coupling, preferred motor parameters and prototypically perceived sounds develop concurrently. Exposure to an ambient language modifies perception to coincide with the sounds from the language. The model develops motor mirror neurons that are active when an external sound is perceived. An extension to visual mirror neurons for oral gestures is suggested.

Artificial Intelligence↗
PubMed2004

The processing of verbs and nouns in neural networks: insights from synthetic brain imaging.

The paper presents a computational model of language in which linguistic abilities evolve in organisms that interact with an environment. Each individual's behavior is controlled by a neural network and we study the consequences in the network's internal functional organization of learning to process different classes of words. Agents are selected for reproduction according to their ability to manipulate objects and to understand nouns (objects' names) and verbs (manipulation tasks). The weights of the agents' neural networks are evolved using a genetic algorithm. Synthetic brain imaging techniques are then used to examine the functional organization of the neural networks. Results show that nouns produce more integrated neural activity in the sensory-processing hidden layer, while verbs produce more integrated synaptic activity in the layer where sensory information is integrated with proprioceptive input. Such findings are qualitatively compared with human brain imaging data that indicate that nouns activate more the posterior areas of the brain related to sensory and associative processing, while verbs activate more the anterior motor areas.

Algorithms↗