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PubMed2005

Temporal analysis of the early BMP functions identifies distinct anti-organizer and mesoderm patterning phases.

BMP signaling performs multiple important roles during early embryogenesis. Signaling through the BMP pathway is mediated by different BMP ligands expressed in partially overlapping temporal and spatial patterns. Assignment of different BMP-dependent activities to the individual ligands has relied on the patterns of expression of the various BMP genes. Temporal analysis of BMP signaling prior to and during gastrulation was performed using glucocorticoid-controlled Smad proteins. Overexpression of the BMP-specific Smad1 and Smad5 revealed that suppression of Spemann's organizer formation in Xenopus embryos can only take place by activating the BMP pathway prior to the onset of gastrulation. Blocking BMP signaling with the inhibitory Smad, Smad6, results in dorsalized embryos or secondary axis induction, only when activated up to early gastrula stages. BMP2 efficiently represses organizer-specific transcription from the midblastula transition onwards while BMP4 is unable to prevent the early activation of organizer-specific genes. Manipulation of the BMP pathway during mid/late gastrula affects mesodermal patterning with no external phenotypic effects. These observations suggest that the malformations resulting from inhibition or promotion of organizer formation, ventralized or dorsalized, respectively, are the result of a very early BMP function, through its antagonism of organizer formation. This function is apparently fulfilled by BMP2 and only at its latest phase by BMP4. Subsequently, BMP functions in the patterning of the mesoderm with no apparent phenotypic effects.

Animals↗
PubMed2000

Global patterns in biodiversity.

To a first approximation, the distribution of biodiversity across the Earth can be described in terms of a relatively small number of broad-scale spatial patterns. Although these patterns are increasingly well documented, understanding why they exist constitutes one of the most significant intellectual challenges to ecologists and biogeographers. Theory is, however, developing rapidly, improving in its internal consistency, and more readily subjected to empirical challenge.

Animals↗
PubMed1996

Function of the Eph-related kinase rtk1 in patterning of the zebrafish forebrain.

Early during its development, the vertebrate brain is subdivided into regions that have distinct fates and correlate with the expression domains of regulatory genes, but little is known about the cell-cell interactions that establish this spatial pattern. Candidates for regulating such interactions are the Eph-related receptor tyrosine kinases (RTKs) which have spatially restricted expression in the developing brain. These RTKs may mediate cell-contact-dependent signalling by interacting with membrane-bound ligands, and have been implicated in axon repulsion and the segmental restriction of gene expression in the hindbrain, but nothing is known regarding their function in the rostral neural epithelium. Here we use a dominant-negative approach in the zebrafish embryo to interfere with the function of Rtk1, an Eph-related RTK expressed in the developing diencephalon. We find that expression of a truncated receptor leads to expansion of the eye field into diencephalic territory and loss of diencephalic structures, indicating a role for Rtk1 in patterning the developing forebrain.

Animals↗
PubMed1999

At which steps of spatial working memory processing do striatofrontal circuits intervene in humans?

Striatofrontal circuits have been implicated in spatial working memory in non-human and human primates. To determine at which steps of information processing (stimulus encoding, storage or response programming) they intervene, we compared 32 levodopa-treated patients with idiopathic Parkinson's disease (PD) and 32 matched control subjects in a visuo-spatial pattern span paradigm. Our testing procedure allowed us to evaluate the influence of: (1) the type of encoding (controlled vs free); (2) the nature of interference during a 10 s delay (spatial vs verbal); and (3) response elaboration (reproduction vs error detection). As expected, the performance of control subjects was significantly better in controlled than in free encoding, in verbal than in spatial interference and in detection than in reproduction, clearly demonstrating the sensitivity of the procedure to these factors. Compared to controls, PD patients were impaired in all conditions and the severity of the deficit was significantly correlated with that observed in tests of executive functions. The global pattern of performance, however, was identical to that of controls. These data confirm the involvement of striatofrontal circuits in spatial working memory in humans and suggest that the executive working memory component intervenes at all steps of working memory processing.

Antiparkinson Agents↗
PubMed1990

Developmental expression of regionally specific cell surface antigens in the Xenopus gastrula.

Molecular markers for specific cell lineages would be useful in studies of cellular differentiation. To isolate such markers monoclonal antibodies (MoABs) were raised against plasma membranes isolated from gastrulating Xenopus embryos. Those antibodies that recognized subsets of cells within the embryo were selected by indirect immunofluorescence. The analysis of eight such MoAbs is presented. Western blot analysis showed that all but one MoAb recognized a complex pattern of glycoconjugates associated with glycoproteins. All the antigens recognized by the MoAbs were maternal in origin and displayed similar spatial patterns of pregastrular expression. This pattern of immunoreactivity at the apical surface was inherited passively during cleavage by the resulting superficial blastomeres suggesting that ectodermal specific markers of maternal origin are pre-localized to the cortical ooplasm in mature oocytes. We suggest that these maternal components may be specific glycosyl transferases. Three different patterns of expression were observed during gastrulation as exemplified by MoAbs 1F10C1, 3A4D1, and 6F10B6. MoAb 6F10B6 was specific for both neural and non-neural epithelium. MoAb 3A4D1 was specific for non-neural epidermis. MoAb 1F10C1 appeared to recognize a protein epitope on an extracellular component expressed by the superficial and involuting epithelial cells. The pattern of expression for the 1F10C1 antigen suggests that it may play a role in facilitating the movement of the involuting cells during gastrulation.

Animals↗
PubMed1992

Neural circuit computation: complex patterns in the olfactory bulb.

The olfactory bulb principal neurons show complex responses during olfactory stimulation that are characterized by periods of profound suppression, temporal patterns of activity, and nonmonotonic intensity response functions. The model presented here suggests that these features may arise from changing spatial patterns of activity across the bulbar surface due to restricted (chemotopic) activation in bulbar glomeruli. The model is based on a simplified version of the bulbar neural circuit as it is presently known from anatomical and physiological investigations and provides explanations for several anomalous bulbar response patterns.

Axons↗
PubMed2003

Modeling biological invasions into periodically fragmented environments.

Range expansion of a single species in a regularly striped environment is studied by using an extended Fisher model, in which the rates of diffusion and reproduction periodically fluctuate between favorable and unfavorable habitats. The model is analyzed for two initial conditions: the initial population density is concentrated on a straight line or at the origin. For each case, we derive a mathematical formula which characterizes the spatio-temporal pattern of range expansion. When initial distribution starts from a straight line, it evolves to a traveling periodic wave (TPW), whose frontal speed is analytically determinable. When the range starts from the origin, it tends to expand radially at a constant average speed in each direction (ray speed) keeping its frontal envelope in a similar shape. By examining the relation between the ray speed and the TPW speed, we derive the ray speed in a parametric form, from which the envelope of the expanding range can be predicted. Thus we analyze how the pattern and speed of the range expansion are affected by the pattern and scale of fragmentation, and the qualities of favorable and unfavorable habitats. The major results include: (1). The envelope of the expanding range show a variety of patterns, nearly circular, oval-like, spindle-like, depending on parameter values; (2). All these patterns are elongated in the direction of stripes; (3). When the scale of fragmentation is enlarged without changing the relative spatial pattern, the ray speed in any direction increases, i.e., the rate of range expansion increases.

Algorithms↗
PubMedDate not supplied

Classical polymorphisms in Berbers from Moyen Atlas (Morocco): genetics, geography, and historical evidence in the Mediterranean peoples.

BACKGROUND: Mediterranean population relationships have recently been reviewed through the analysis of classical and DNA markers. The differentiation between Berbers and Arabic-speakers to the south, and the genetic impact of the seven centuries of Muslim domination in the Iberian Peninsula have been among the most interesting questions posed in these studies. AIM: The present study seeks to assess the degree of genetic affinity between the two main population groups of Morocco: Berbers and Arabic-speakers. Data from the Berber study population were also compared with published information on 20 circum-Mediterranean groups. SUBJECTS AND METHODS: A Berber sample of 140 individuals from Moyen Atlas (Morocco) has been characterized using 15 classical markers (ABO, Duffy, MNSs, Rh, ACPl, AKl, ESD, GLOI, 6-PGD, PGMl, GC, HP, PI, PLG and TF). RESULTS: Allele frequencies in the Berbers fit well into the general southern Mediterranean ranges, albeit with some peculiarities, such as the high FY*A, ACPl*C, and PI*S values. The general pattern of relationships among Mediterranean peoples tested by genetic variance analysis was compatible with a north-south geographical differentiation. Spatial auto-correlation analysis in the different geographical regions of the Mediterranean reveals that the highest degree of association between allele frequencies and geographical distances corresponds to the western (41% of significant correlograms) and northern Mediterranean populations (33%). When only southern Mediterranean groups were considered, the degree of geographical structure considerably decreases (11% of significant correlograms). CONCLUSIONS: The different loci studied revealed close similarity between the Berbers and other north African groups, mainly with Moroccan Arabic-speakers, which is in accord with the hypothesis that the current Moroccan population has a strong Berber background. Differences in the spatial pattern of allele frequencies also are compatible with specific population histories in distinct Mediterranean areas, rather than general population movements across the whole region.

Alleles↗
PubMed2006

Spatio-temporal dynamics of alternative male phenotypes in coho salmon populations in response to ocean environment.

1. The coexistence of alternative reproductive phenotypes will probably be shaped by spatial and temporal variability in the environment. However, the effects of such variability on coexistence and the scale at which it operates are seldom understood. 2. To quantify such effects, we examined spatial and temporal dynamics in the abundance and frequency of alternative phenotypes of male coho salmon, Oncorhynchus kisutch Walbaum, which mature as either large fighters (age-3 'hooknoses') or small sneakers (age-2 'jacks'). Using over 20 years of data on coded-wire tagged fish released from nine Oregon hatcheries, we tested for the effects of ocean environment independent of those due to freshwater rearing. 3. Annual fluctuations of the abundance of jack and hooknose males within populations were correlated strongly by brood year (cohort) but not by return year (breeding group). This occurred independently of significant effects of release practice (i.e. the number of fish released, body size at release and date of release), indicating that a synchronized fluctuation in mortality during the first year at sea was the predominant cause. As a result, the annual frequency of the alternative phenotypes at breeding varied considerably within populations. 4. Spatial patterns in the annual fluctuations of the two phenotypes were similar (i.e. synchronous among populations), except that jacks showed local spatial structure (decreased synchrony with distance) not evident among hooknoses. This suggests that oceanic processes affecting the two phenotypes operate at different spatial scales. Despite effects on salmon abundance, the ocean environment had little influence through its effects on salmon growth on the relative frequencies of the alternative phenotypes within and among populations. 5. The results provide insight into the evolutionary dynamics of alternative phenotypes, including an intragenerational time lag that increases annual variability in phenotype frequencies at breeding (return years) and the significance of local freshwater processes, rather than oceanic processes, on phenotype expression. Freshwater processes, such as juvenile growth, timing of migration and breeding competition, operating at evolutionary and intragenerational time-scales, are probably the predominant forces affecting phenotype frequency.

Aging↗
PubMed2002

The central autonomic nervous system: conscious visceral perception and autonomic pattern generation.

The overall organization of the peripheral autonomic nervous system has been known for many decades, but the mechanisms by which it is controlled by the central nervous system are just now coming to light. In particular, two major issues have seen considerable progress in the past decade. First, the pathways that provide visceral sensation to conscious perception at a cortical level have been elucidated in both animals and humans. The nociceptive system runs in parallel to the pathways carrying visceral sensation from the cranial nerves and may be considered in itself a component of visceral sensation. Second, structures in the central nervous system that generate patterns of autonomic response have been identified. These pattern generators are located at multiple levels of the central nervous system, and they can be combined in temporal and spatial patterns to subserve a wide range of behavioral needs.

Animals↗
PubMed1994

Optical mapping of early embryonic expressions of Mg(2+)-/APV-sensitive components of vagal glutaminergic EPSPs in the chick brainstem.

Multiple-site optical recording of transmembrane voltage activity, using a voltage-sensitive dye (NK2761) and a 12 x 12 element photodiode array, was employed to monitor neural responses in the slice preparations that were dissected from 6-9-d-old embryonic brainstems. Transmembrane voltage-related optical responses evoked by a brief square current pulse applied with a microsuction electrode to the vagus nerve were recorded simultaneously from many sites in the preparation. In preparations from 6-d-old embryos, only action potential-related spike-like optical signals were often detected in the normal bathing solution containing 0.5 mM Mg2+. However, in several loci of some preparations, excitatory postsynaptic potential-related slow signals were elicited in a Mg(2+)-free bathing medium, and these elicited slow signals were blocked by DL-2-amino-5-phosphonovaleric acid (2-APV). These results show a possible embryonic expression of NMDA receptor-mediated excitatory postsynaptic potentials. The slow signals were usually detected from tested preparations from 7-9-d-old embryos in normal bathing solution. The later phase of the slow signals was enhanced in a Mg(2+)-free bathing medium, and the enhanced component was also sensitive to 2-APV and insensitive to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). There were regional differences in the degree of the enhancement of the slow signals in the Mg(2+)-free bathing medium, and of the 2-APV-induced reduction of the slow signals. We have constructed early developmental maps of the spatial patterns of the slow signals related to Mg(2+)- and 2-APV-sensitive postsynaptic potentials. These maps reflect the spatial distribution of functional expression of the NMDA receptors during early development of the chick brainstem. The present findings are new data that have not been reported previously, and they have been obtained for the first time using the multiple-site optical recording technique with a voltage-sensitive dye.

2-Amino-5-phosphonovalerate↗
PubMed1995

Differential expression of the fos and jun family members c-fos, fosB, Fra-1, Fra-2, c-jun, junB and junD during human epidermal keratinocyte differentiation.

Activator protein 1 (AP1) family proteins have been implicated in the regulation of genes expressed in the epidermis. However, no comprehensive analysis of the expression patterns of the known AP1 family proteins in the human epidermis or any other terminally differentiating tissue has been performed. In the present study we describe the localization of c-fos, fosB, Fra-1, Fra-2, c-jun, junB and junD in the normal human epidermis. Each is expressed in specific epidermal layers. c-fos is localized in the nuclei of the upper spinous and granular layer cells. FosB is present in the nuclei in all layers. Fra-1 is absent from the basal layer, but is present in all other layers. Fra-2 is detected in all layers, but staining intensity is increased in the upper spinous layer. c-jun staining is limited to the granular layer, while junB and junD are present in all layers. The differentiation-dependent pattern of expression of the AP1 family members suggest an important role for these proteins in specifying the temporal and spatial pattern of gene expression during keratinocyte differentiation.

Animals↗
PubMed1996

Development of astrocytes and their relation to blood vessels in fetal monkey retina.

PURPOSE: To determine the development of astrocytes and their vascular relations in Macaca monkey retina. METHODS: Sections and wholemounts of retinas from fetal day (Fd) 65 to adult animals were analyzed immunohistochemically to detect glial fibrillary acidic protein (GFAP) and vimentin. RESULTS: Astrocytes appeared first near the optic disc, then subsequently further peripherally, but avoided the fovea. In the nerve fiber layer, round and ovoid cells extended processes parallel to ganglion cell axons. In the ganglion cell layer, ovoid and stellate cells exhibited anisotropic processes or a honeycomb network. The inner lamina of astrocytes developed ahead of the outer lamina, and both reached their final positions before birth. Astrocytes lay more peripherally than did developing blood vessels, and the growing edge of nerve fiber layer vessels lay between the two astrocytic layers. Spindle cells, which may be vascular precursor cells, often aligned along linear astrocytic processes. Occasional spindle-shaped cells containing GFAP or vimentin were identified as immature glia. Astrocytes and blood vessels coincided regionally during development, but astrocyte processes were typically not in register with the meshwork of growing blood vessels. Astrocyte-vessel associations increased during fetal life and postnatally. CONCLUSIONS: During development, astrocytes display the same bilaminar pattern and morphologies present in adult retina. Astrocytes and blood vessels exhibit a similar regional distribution, but develop in distinct spatial patterns. Vessel investment by astrocytic processes increases during fetal life but is variable at all ages.

Animals↗
PubMed1971

Pavlovian pattern learning by nonlinear neural networks.

This note describes laws for the anatomy, potentials, spiking rules, and transmitters of some networks of formal neurons that enable them to learn spatial patterns by Pavlovian conditioning. Applications to spacetime pattern learning and operant conditioning are then possible, if the conditioning is viewed as multi-channel Pavlovian conditioning in a highly inhomogeneous anatomy. In suitable anatomies, biases in learning because of axon collaterals with nonuniformly distributed diameters can be corrected if one properly couples the action potential to transmitter potentiation, and chooses signal velocity proportional to axon diameter. These anatomies can contain any number of cells. Anatomies exist in which patterns may be learned without their being practiced overtly, whereas persistent recall of old patterns without the learning of newly imposed patterns is impossible. Physiologically, this constraint has the trivial interpretation that signals from one cell to another first pass through the intervening synaptic knob. Mechanisms that control learning rates at times important to the network (e.g., reward and punishment times) can be discussed. Serial behavior like that described by Lashley is possible: this consists of sequential learning and performance of patterns faster than would be allowed by a motor-feedback control, at velocities influenced by arousal level, with the possibility of abrupt termination of performance if conflicting environmental demands arise. Analogs of pattern completion and mass action exist, as do phase transitions in memory (for some rate parameters and anatomies, memory is rigid, for others, it is plastic). The laws limit the ways in which these networks can be interconnected to yield specific discrimination, learning, memory, and recall capabilities.

Action Potentials↗
PubMed2002

Differing flow patterns between ischemically challenged flap skin and flap skeletal muscle: implications for salvage regimens.

In this study, the authors tested the hypothesis that there is a significant difference in spatial patterns of reflow in skin as opposed to skeletal muscle after an ischemic insult. The authors believe that this pathophysiologic difference between the two flap types has significant implications for flap salvage strategies. Bilateral buttock skin flaps (10 x 18 cm) and latissimus dorsi myocutaneous flaps (10 x 20 cm) were elevated in Landrace pigs (n = 7). Flaps on one side of the animal were randomly assigned to 6 hours of arterial occlusion, with the contralateral side acting as control. At 15 minutes, 1 hour, and 4 hours after reflow, radioactive microspheres (15 microm) were injected into the left ventricle. After 18 hours of reperfusion, skin and muscle viability were estimated by intravenous fluorescein and soaking in nitroblue tetrazolium, respectively. Flow rates in the skin with an ischemia-reperfusion injury were significantly reduced (30 to 53 percent), at all time intervals, compared with controls. The flow rate in the fluorescent skin with ischemia-reperfusion injury of the latissimus dorsi flaps (0.037 ml/min/g at 15 min) was greater than in that of the buttock flaps (0.018 ml/min/g). The muscle flaps with ischemia-reperfusion injury had significantly higher flow rates than control muscle flaps at all time intervals studied (at 1 hour, 0.32 ml/min/g compared with 0.16 ml/min/g, respectively). In flap skeletal muscle, an early hyperemic phase during reperfusion maintains a significant blood flow to all regions, including the area of the flap that is destined for necrosis. In flap skin, however, there is a marked decrease in flow rates. These differences have important implications for the intravascular delivery of therapeutic agents to the damaged portions of the flap. Transdermal drug delivery systems should be explored as an alternative to intravascular regimens for the salvage of flap skin with ischemia-reperfusion injury.

Animals↗
PubMed1998

Lethal P-lacZ insertion lines expressed during pattern respecification in the imaginal discs of Drosophila.

The imaginal discs of Drosophila are a useful experimental system in which we can study the origin and genetic determination of spatial patterns in development. This involves the separation of the disc-cell population into distinct lineage compartments, based on clonally transmitted expression states of a number of known selector genes. However, these commitments can be abrogated and the compartment boundaries redeployed, when repatterning occurs in cultured disc fragments. This has so far only been explained using the idea of positional information. The genetic basis of this property of the imaginal disc system and its relationship to compartments have not been identified. Here we have screened over 470 recessive lethal P-lacZ enhancer-trap insertions from the Berkeley Drosophila Genome Project for expression after cell death, which initiates pattern respecification in the imaginal discs. The positive lines obtained identify essential genes that may be important for pattern formation. Most show patterned imaginal disc expression, and many have maternal or zygotic effects on embryonic development. One is an allele of schnurri, a gene that encodes a component of the decapentaplegic (dpp) signal transduction pathway used for positional signalling in the embryo and in imaginal discs.

Animals↗
PubMed2005

Simulating effects of fire disturbance and climate change on boreal forest productivity and evapotranspiration.

We used a terrestrial ecosystem process model, BIOME-BGC, to investigate historical climate change and fire disturbance effects on regional carbon and water budgets within a 357,500 km(2) portion of the Canadian boreal forest. Historical patterns of increasing atmospheric CO2, climate change, and regional fire activity were used as model drivers to evaluate the relative effects of these impacts to spatial patterns and temporal trends in forest net primary production (NPP) and evapotranspiration (ET). Historical trends of increasing atmospheric CO2 resulted in overall 13% and 5% increases in annual NPP and ET from 1994 to 1996, respectively. NPP was found to be relatively sensitive to changes in air temperature (T(a)), while ET was more sensitive to precipitation (P) change within the ranges of observed climate variability (e.g., +/-2 degrees C for T(a) and +/-20% for P). In addition, the potential effect of climate change related warming on NPP is exacerbated or offset depending on whether these changes are accompanied by respective decreases or increases in precipitation. Historical fire activity generally resulted in reductions of both NPP and ET, which consumed an average of approximately 6% of annual NPP from 1959 to 1996. Areas currently occupied by dry conifer forests were found to be subject to more frequent fire activity, which consumed approximately 8% of annual NPP. The results of this study show that the North American boreal ecosystem is sensitive to historical patterns of increasing atmospheric CO2, climate change and regional fire activity. The relative impacts of these disturbances on NPP and ET interact in complex ways and are spatially variable depending on regional land cover and climate gradients.

Canada↗
PubMed2001

A cellular oscillator model for periodic pattern formation.

In this paper, we present a model for pattern formation in developing organisms that is based on cellular oscillators (CO). An oscillatory process within cells serves as a developmental clock whose period is tightly regulated by cell autonomous or non-autonomous mechanisms. A spatial pattern is generated as a result of an initial temporal ordering of the cell oscillators freezing into spatial order as the clocks slow down and stop at different times or phases in their cycles. We apply a CO model to vertebrate somitogenesis and show that we can reproduce the dynamics of periodic gene expression patterns observed in the pre-somitic mesoderm. We also show how varying somite lengths can be generated with the CO model. We then discuss the model in view of experimental evidence and its relevance to other instances of biological pattern formation, showing its versatility as a pattern generator.

Animals↗