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At least 613 records · Page 34Linked to original sources
PubMed2003

An in silico exploration of the neutral network in protein sequence space.

Designating amino-acid sequences that fold into a common main-chain structure as "neutral sequences" for the structure, regardless of their function or stability, we investigated the distribution of neutral sequences in protein sequence space. For four distinct target structures (alpha, beta,alpha/beta and alpha+beta types) with the same chain length of 108, we generated the respective neutral sequences by using the inverse folding technique with a knowledge-based potential function. We assumed that neutral sequences for a protein structure have Z scores higher than or equal to fixed thresholds, where thresholds are defined as the Z score for the corresponding native sequence (case 1) or much greater Z score (case 2). An exploring walk simulation suggested that the neutral sequences mapped into the sequence space were connected with each other through straight neutral paths and formed an inherent neutral network over the sequence space. Through another exploring walk simulation, we investigated contiguous regions between or among the neutral networks for the distinct protein structures and obtained the following results. The closest approach distance between the two neutral networks ranged from 5 to 29 on the Hamming distance scale, showing a linear increase against the threshold values. The sequences located at the "interchange" regions between the two neutral networks have intermediate sequence-profile-scores for both corresponding structures. Introducing a "ball" in the sequence space that contains at least one neutral sequence for each of the four structures, we found that the minimal radius of the ball that is centered at an arbitrary position ranged from 35 to 50, while the minimal radius of the ball that is centered at a certain special position ranged from 20 to 30, in the Hamming distance scale. The relatively small Hamming distances (5-30) may support an evolution mechanism by transferring from a network for a structure to another network for a more beneficial structure via the interchange regions.

Amino Acid Sequence↗
PubMed1984

Self-organizing mechanism for the formation of ordered neural mappings.

A model for the formation of ordered neural mappings in general, and of retinotectal connections, in particular is given. The main point came from the theory of "noise induced transitions", i.e. order may be the result of the interplay between deterministic and random interactions. An activity-dependent self-organizing mechanism is presented in terms of modifiable synapses. Simulation experiments were done not only for the normal ontogenetic development but also for the plastic behaviour of the retinotopic connections.

Animals↗
PubMed2006

Definition of homogeneous environmental management units for the Catalan coast.

Geographical areas constitute the basic implementation locus for integrated coastal zone management strategies and activities. Because the definition of territorial planning objectives may be affected by socioeconomic and environmental characteristics, one of the main steps in the process involves dividing the coast into homogeneous environmental management units (HEMUs). This article presents a general and simple method for regionalizing the landside of a coastal zone into HEMUs and illustrates it through application to the Catalan coast. Socioeconomic and natural (biophysical) subsystems were selected as the most appropriate dimensions of the regionalization process. Dimensions were described using 11 spatial themes, which were managed in a geographic information system environment that proved to be an adequate tool for the purpose. A final coastal zone map of four classes of HEMUs connected to local administrative units was obtained, and because it reflects the current natural and socioeconomic dynamics, it can be considered as an initial step in the planning process for the Catalan coast. Although the proposed method was developed based on the characteristics of the Catalan coast, it is general enough to be adapted and applied to most developed or developing coastal areas.

Conservation of Natural Resources↗
PubMed2005

ERK2 is required for FGF1-induced JNK1 phosphorylation in Xenopus oocyte expressing FGF receptor 1.

A possible connection between the ERK2 and JNK1 MAP kinases transduction cascades was investigated in Xenopus oocytes expressing FGFR1 stimulated by FGF1. Injection of various inhibitors for the Shc/Grb2/Ras/Mos/MEK/ERK2 cascade blocked FGF1-induced germinal vesicle breakdown (GVBD), as well as ERK2 and JNK1 phosphorylation. JNK1 was found to be activated downstream of ERK2, since injection of an active ERK2 triggered JNK1 phosphorylation and inhibition of ERK2 either by a MEK inhibitor or the MKP3 phosphatase blocked JNK1 phosphorylation. These results demonstrated that in FGFR1 signalling JNK1 phosphorylation depends on ERK2.

Animals↗
PubMed2006

Ehlers-Danlos syndrome type VIII: periodontitis, easy bruising, marfanoid habitus, and distinctive facies.

An 11-year-old boy had a history of easy bruising and poorly healing wounds since infancy and severe, early-onset periodontitis. He also exhibited mild hypermobility of the small joints of the hands, long limbs with striking arachnodactyly, and a triangular face with delicate features. Analysis of type I and type III collagens revealed no abnormalities. These findings were consistent with a diagnosis of Ehlers-Danlos syndrome type VIII (EDS-VIII), an autosomal dominant connective tissue disorder that was recently mapped to chromosome 12q13. We draw attention to the clinical features that typify EDS-VIII, including extensive pretibial bruising, a marfanoid body habitus, and characteristic facies, as well as childhood onset of progressive periodontal disease.

Age of Onset↗
PubMed2005

Cerebellum and M1 interaction during early learning of timed motor sequences.

We used positron emission tomography (PET) to examine within-day learning of timed motor sequences. The results of this experiment are novel in showing an interaction between cerebellum and primary motor cortex (M1) during learning that appears to be mediated by the dentate nucleus (DN) and in demonstrating that activity in these regions is directly related to performance. Subjects were scanned during learning (LRN) across three blocks of practice and during isochronous (ISO) and perceptual (PER) baseline conditions. CBF was compared across blocks of learning and between the LRN and baseline conditions. Results demonstrated an interaction between the cerebellum and M1 such that earlier, poorer performance was associated with greater activity in the cerebellar hemispheres and later, better performance was associated with greater activity in M1. Inter-regional correlation analyses confirmed that as CBF in the cerebellum decreases, blood flow in M1 increases. Importantly, these analyses also revealed that activity in cerebellar cortex was positively correlated with activity in right DN and that DN activity was negatively correlated with blood flow in M1. Activity in the cerebellar hemispheres early in learning is likely related to error correction mechanisms which optimize movement kinematics resulting in improved performance. Concurrent DN activity may be related to encoding of this information and DN output to M1 may play a role in consolidation processes that lay down motor memories. Increased activity in M1 later in learning may reflect strengthening of synaptic connections associated with changes in motor maps that are characteristic of learning in both animals and humans.

Adult↗
PubMed2005

Neurochemical characterization of hypothalamic neurons involved in attack behavior: glutamatergic dominance and co-expression of thyrotropin-releasing hormone in a subset of glutamatergic neurons.

The electrical stimulation of a specific hypothalamic area rapidly evokes attacks in rats. Noteworthy, attack-related hypothalamic structures were identified in all species studied so far. The area has been extensively mapped in rats, and its anatomical connections have been studied in detail. However, technical difficulties precluded earlier the precise identification of the neural elements mediating the aggressive effects of stimulation. It now appears that a dense and distinct group of glutamatergic cells expressing vesicular glutamate transporter 2 mRNA extends over the entire hypothalamic attack area. Rostral parts overwhelmingly contained glutamatergic neurons. In more caudal parts, glutamatergic and fewer GABAergic neurons were found. The remarkable similarity in the distribution of hypothalamic attack area and glutamatergic cell groups suggests that these cells mediate the aggressive effects of stimulation. Surprisingly, thyrotropin releasing hormone mRNA was co-localized in a subset of glutamatergic neurons. Such neurons were present at all rostro-caudal levels of the hypothalamic attack area, except for that part of the hypothalamic attack area extending into the ventro-lateral part of the ventromedial hypothalamic nucleus. Earlier data on the projections of hypothalamic thyrotropin releasing hormone neurons suggest that this subpopulation plays a specific role in attack behavior. Thus, we identified three neuronal phenotypes in the hypothalamic structure that is involved in the induction of attacks: glutamatergic neurons co-expressing thyrotropin releasing hormone, glutamatergic neurons without thyrotropin releasing hormone, and GABAergic neurons dispersed among the glutamatergic cells. Assessing the specific roles and connections of these neuron subpopulations would contribute to our understanding of the mechanisms underlying attack behavior and aggression.

Aggression↗
PubMed1997

The pathway connecting m2 receptors to the nucleus involves small GTP-binding proteins acting on divergent MAP kinase cascades.

m1 and m2 receptors are traditionally linked to tissue specific functions performed by fully differentiated cells. However, these receptors have been also implicated in growth stimulation. The mechanisms whereby these receptors regulate proliferative signaling pathways are still poorly understood. Furthermore, pharmacological evidence suggest that many growth promoting agents act on Gi coupled receptors, but there is no formal proof that induction of DNA-synthesis results from decreased intracellular levels of cAMP. In our laboratory, we have used the expression of ml and m2 receptors as a model for studying proliferative signaling through G protein-coupled receptors. Currently available evidence suggest that these receptors signal to distinct members of the MAP kinase superfamily, MAP kinase and JNK, through betagamma subunits of heterotrimeric G proteins acting, respectively, on a Ras and Rac1 dependent pathway.

Animals↗
PubMed2002

Learned fear, emotional reactivity and fear of heights: a factor analytic map from a large F(2) intercross of Roman rat strains.

Anxiety-related behaviours were evaluated across various tests in a 800 F(2)-intercross of the Roman high- and low-avoidance inbred rats. These tests either evoke unlearned (open field [OF]; plus-maze [PM]; hole-board [HB]; spontaneous activity [A]; and acoustic startle reflex [ASR]) or learned (classical fear conditioning [CFC]; and shuttlebox avoidance conditioning [SAC]), anxious/fearful responses. Using factor analysis (oblique rotation), we obtained a six-fold solution with 14 variables derived from all tests. These six factors represented SAC, CFC, PM anxiety, PM and OF activity, ASR anxiety, plus a mixed whole of anxious and activity variables (from OF and A), respectively. In searching for a smaller number of meaningful factors, we applied a three-factor solution that coherently corresponded with differentiated facets of fearfulness, rather than with the tests. Results showed that (1) measures of SAC and CFC strongly loaded onto Factor 1, labelled as "Learned Fear"; (2) a blend of almost all variables loaded onto Factor 2, called "Emotional Reactivity"; and (3) open arm behaviour in the PM loaded onto Factor 3, called "Fear of Heights." After discussing limitations of this apparently consistent behavioural map of anxiety, we advance some connections between those factors with quantitative trait loci candidates (genetic markers) as detected in the same sample.

Animals↗
PubMedDate not supplied

Modeling of cyclin-dependent kinase inhibition by 1H-pyrazolo[3,4-d]pyrimidine derivatives using artificial neural network ensembles.

Artificial neural network ensembles were used for modeling the cyclin-dependent kinase inhibition of 1H-pyrazolo[3,4-d]pyrimidine derivatives. The structural characteristics of these inhibitors were encoded in relevant 3D-spatial descriptors extracted by genetic algorithm feature selection. Bayesian-regularized multilayer neural networks, trained by the back-propagation algorithm, were developed using these variables as inputs. The predictive power of the model was tested by leave-one-out cross validation. In addition, for a more rigorous measure of the predictive capacity, multiple validation sets were randomly generated as members of neural network ensembles, which makes doing averaged predictions feasible. In this way, the predictive power was analyzed accounting for the averaged test set R values and test set mean-square errors. Otherwise, Kohonen self-organizing maps were used as an additional tool for the same modeling. The location of the inhibitors in a map facilitates the analysis of the connection between compounds and serves as a useful tool for qualitative predictions.

Algorithms↗
PubMed1992

Stimulus configuration, classical conditioning, and hippocampal function.

Hippocampal participation in classical conditioning is described in terms of a multilayer network that portrays stimulus configuration. The network (a) describes behavior in real time, (b) incorporates a layer of "hidden" units positioned between input and output units, (c) includes inputs that are connected to the output directly as well as indirectly through the hidden-unit layer, and (d) uses a biologically plausible backpropagation procedure to train the hidden-unit layer. Nodes and connections in the neural network are mapped onto regional cerebellar, cortical, and hippocampal circuits, and the effect of lesions of different brain regions is formally studied. Computer simulations of the following classical conditioning paradigms are presented: acquisition of delay and trace conditioning, extinction, acquisition-extinction series of delay conditioning, blocking, over-shadowing, discrimination acquisition, discrimination reversal, feature-positive discrimination, conditioned inhibition, negative patterning, positive patterning, and generalization. The model correctly describes the effect of hippocampal and cortical lesions in many of these paradigms, as well as neural activity in hippocampus and medial septum during classical conditioning. Some of these results might be extended to the description of anterograde amnesia in human patients.

Animals↗
PubMed1996

Piecewise linear models for the quasiperiodic transition to chaos.

We formulate and study analytically and computationally two families of piecewise linear degree one circle maps. These families offer the rare advantage of being non-trivial but essentially solvable models for the phenomenon of mode locking and the quasiperiodic transition to chaos. For instance, for these families, we obtain complete solutions to several questions still largely unanswered for families of smooth circle maps. Our main results describe (1) the sets of maps in these families having some prescribed rotation interval; (2) the boundaries between zero and positive topological entropy and between zero length and non-zero length rotation interval; and (3) the structure and bifurcations of the attractors in one of these families. We discuss the interpretation of these maps as low-order spline approximations to the classic "sine-circle" map and examine more generally the implications of our results for the case of smooth circle maps. We also mention a possible connection to recent experiments on models of a driven Josephson junction. (c) 1996 American Institute of Physics.

Journal Article↗
PubMed1971

Karyological properties of human-mouse somatic hybrids.

Karyological examinations performed 24 hr to 11 days after Sendai virus-induced fusion of mouse cells of the permanent line 3T3 and human diploid cells, suggest that hybrids with extensive loss of human chromosomes derive from fusion involving all the chromosomes of both parental cells. Examination of 39 independent clones isolated from two different crosses between L mouse cells and cells of two permanent human lines, D98/AH2 and VA2, show that the karyotypes of human-mouse hybrids are a function of the interaction between the parental cells: the mouse chromosomal complement may be doubled or not. For the first time, viable hybrids that have retained almost all of the human chromosomes have been isolated.

Animals↗
PubMed2003

A comparison of lactated ringer's solution to hydroxyethyl starch 6% in a model of severe hemorrhagic shock and continuous bleeding in dogs.

UNLABELLED: In this randomized, controlled study in dogs, we examined the short-term effects of blood pressure targeted fluid resuscitation with colloids or crystalloids solutions on systemic oxygen delivery, and lactate blood concentration. Fluid resuscitation using hydroxyethyl starch (HES) 6% to a mean arterial blood pressure (MAP) of 60 mm Hg was compared with lactated Ringer's solution (LR) to a MAP of 60 or 80 mm Hg (LR60 and LR80, respectively). The model was one of withdrawal of blood to a MAP of 40 mm Hg through an arterial catheter that was then connected to a system allowing bleeding to occur throughout the study whenever MAP exceeded 40 mm Hg. Target MAP was maintained for 60 min with a continuous infusion of the designated fluid replacement. All 15 dogs (5 in each group) survived until the last measurement. Blood loss in the LR80 group (2980 +/- 503 mL) (all values mean +/- SD) was larger than in the LR60 and HES60 groups (1800 +/- 389 mL, and 1820 +/- 219 mL, respectively) (P < 0.001). Whereas 840 +/- 219 mL of HES60 was needed to maintain target MAP, 1880 +/- 425 mL of LR was needed in the LR60 group, and 4590 +/- 930 mL in the LR80 group (P < 0.001). Lactate blood concentrations were smaller and delivered O(2) higher in the HES60 group (35 +/- 17 mg/dL and 239 +/- 61 mL/min, respectively) in comparison to the LR60 group (89 +/- 18 mg/dL and 140 +/- 48 mL/min, respectively) and the LR80 group (75 +/- 23 mg/dL and 153 +/- 17 mL/min, respectively) (P = 0.02 and P = 0.026). In conclusion, fluid resuscitation during uncontrolled bleeding, to a target MAP of 60 mm Hg, using HES60 resulted in larger oxygen delivery and smaller systemic lactate A resuscitation to a target MAP of 60 or 80 mm Hg using LR. IMPLICATIONS: Fluid resuscitation to a target mean arterial blood pressure of 60 mm Hg during uncontrolled bleeding resulted in larger oxygen delivery and smaller systemic lactate concentrations when hydroxyethyl starch 6% was used, in comparison to lactated Ringer's solution resuscitation to a target mean arterial blood pressure of 60 or 80 mm Hg.

Animals↗
PubMed2006

Angiosomes of the foot and ankle and clinical implications for limb salvage: reconstruction, incisions, and revascularization.

BACKGROUND: Ian Taylor introduced the angiosome concept, separating the body into distinct three-dimensional blocks of tissue fed by source arteries. Understanding the angiosomes of the foot and ankle and the interaction among their source arteries is clinically useful in surgery of the foot and ankle, especially in the presence of peripheral vascular disease. METHODS: In 50 cadaver dissections of the lower extremity, arteries were injected with methyl methacrylate in different colors and dissected. Preoperatively, each reconstructive patient's vascular anatomy was routinely analyzed using a Doppler instrument and the results were evaluated. RESULTS: There are six angiosomes of the foot and ankle originating from the three main arteries and their branches to the foot and ankle. The three branches of the posterior tibial artery each supply distinct portions of the plantar foot. The two branches of the peroneal artery supply the anterolateral portion of the ankle and rear foot. The anterior tibial artery supplies the anterior ankle, and its continuation, the dorsalis pedis artery, supplies the dorsum of the foot. Blood flow to the foot and ankle is redundant, because the three major arteries feeding the foot have multiple arterial-arterial connections. By selectively performing a Doppler examination of these connections, it is possible to quickly map the existing vascular tree and the direction of flow. CONCLUSIONS: Detailed knowledge of the vascular anatomy of the foot and ankle allows the plastic surgeon to plan vascularly sound reconstructions, the foot and ankle surgeon to design safe exposures of the underlying skeleton, and the vascular surgeon to choose the most effective revascularization for a given wound.

Ankle↗
PubMed2000

Driven, underdamped Frenkel-Kontorova model on a quasiperiodic substrate.

We consider the underdamped dynamics of a chain of atoms subject to a dc driving force and a quasiperiodic substrate potential. The system has three inherent length scales which we take to be mutually incommensurate. We find that when the length scales are related by the spiral mean (a cubic irrational) there exists a value of the interparticle interaction strength above which the static friction is zero. When the length scales are related by the golden mean (a quadratic irrational) the static friction is always nonzero. From considerations based on the connection of this problem to standard map theory, we postulate that zero static friction is generally possible for incommensurate ratios of the length scales involved. However, when the length scales are quadratic irrationals, or have some commensurability with each other, the static friction will be nonzero for all choices of interaction parameters. We also comment on the nature of the depinning mechanisms and the steady states achieved by the moving chain.

Journal Article↗
PubMed2004

Influence of head tissue conductivity in forward and inverse magnetoencephalographic simulations using realistic head models.

The influence of head tissue conductivity on magnetoencephalography (MEG) was investigated by comparing the normal component of the magnetic field calculated at 61 detectors and the localization accuracy of realistic head finite element method (FEM) models using dipolar sources and containing altered scalp, skull, cerebrospinal fluid, gray, and white matter conductivities to the results obtained using a FEM realistic head model with the same dipolar sources but containing published baseline conductivity values. In the models containing altered conductivity values, the tissue conductivity values were varied, one at a time, between 10% and 200% of their baseline values, and then varied simultaneously. Although changes in conductivity values for a single tissue layer often altered the calculated magnetic field and source localization accuracy only slightly, varying multiple conductivity layers simultaneously caused significant discrepancies in calculated results. The conductivity of scalp, and to a lesser extent that of white and gray matter, appears especially influential in determining the magnetic field. Comparing the results obtained from models containing the baseline conductivity values to the results obtained using other published conductivity values suggests that inaccuracies can occur depending upon which tissue conductivity values are employed. We show the importance of accurate head tissue conductivities for MEG source localization in human brain, especially for deep dipole sources or when an accuracy greater than 1.4 cm is needed.

Adult↗