scholarly journals Alterations to the remote control of Shh gene expression cause congenital abnormalities

2013 ◽  
Vol 368 (1620) ◽  
pp. 20120357 ◽  
Author(s):  
Robert E. Hill ◽  
Laura A. Lettice
Keyword(s):  
Long Range ◽  
Congenital Abnormalities ◽  
Limb Bud ◽  
Temporal Expression ◽  
Developmentally Regulated ◽  
Conserved Sequence ◽  
Regulatory Mutations ◽  
Spatio Temporal ◽  
Relationship Of ◽  
The Relationship

Multi-species conserved non-coding elements occur in the vertebrate genome and are clustered in the vicinity of developmentally regulated genes. Many are known to act as cis -regulators of transcription and may reside at long distances from the genes they regulate. However, the relationship of conserved sequence to encoded regulatory information and indeed, the mechanism by which these contribute to long-range transcriptional regulation is not well understood. The ZRS, a highly conserved cis -regulator, is a paradigm for such long-range gene regulation. The ZRS acts over approximately 1 Mb to control spatio-temporal expression of Shh in the limb bud and mutations within it result in a number of limb abnormalities, including polydactyly, tibial hypoplasia and syndactyly. We describe the activity of this developmental regulator and discuss a number of mechanisms by which regulatory mutations in this enhancer function to cause congenital abnormalities.

LONG-RANGE CORRELATIONS IN THE PHASE-SHIFTS OF NUMERICAL SIMULATIONS OF BIOCHEMICAL OSCILLATIONS AND IN EXPERIMENTAL CARDIAC RHYTHMS

1999 ◽  
Vol 07 (02) ◽  
pp. 113-130 ◽  
Author(s):  
I. M. DE LA FUENTE ◽  
L. MARTINEZ ◽  
J. M. AGUIRREGABIRIA ◽  
J. VEGUILLAS ◽  
M. IRIARTE
Keyword(s):  
Phase Shift ◽  
Periodic Solutions ◽  
Long Range ◽  
Phase Shifts ◽  
Long Range Correlations ◽  
Rescaled Range ◽  
Biochemical Oscillations ◽  
Phase Shift Data ◽  
Relationship Of ◽  
The Relationship

In biochemical dynamical systems during each transition between periodical behaviors, all metabolic intermediaries of the system oscillate with the same frequency but with different phase-shifts. We have studied the behavior of phase-shift records obtained from random transitions between periodic solutions of a biochemical dynamical system. The phase-shift data were analyzed by means of Hurst's rescaled range method (introduced by Mandelbrot and Wallis). The results show the existence of persistent behavior: each value of the phase-shift depends not only on the recent transitions, but also on previous ones. In this paper, the different kind of periodic solutions were determined by different small values of the control parameter. It was assessed the significance of this results through extensive Monte Carlo simulations as well as quantifying the long-range correlations. We have also applied this type of analysis on cardiac rhythms, showing a clear persistent behavior. The relationship of the results with the cellular persistence phenomena conditioned by the past, widely evidenced in experimental observations, is discussed.

scholarly journals Populations of genetic circuits are unable to find the fittest solution in a multilevel genotype–phenotype map

2020 ◽  
Vol 17 (167) ◽  
pp. 20190843 ◽  
Author(s):  
Pablo Catalán ◽  
Susanna Manrubia ◽  
José A. Cuesta
Keyword(s):  
Regulatory Networks ◽  
Expression Patterns ◽  
Genetic Circuits ◽  
Temporal Expression ◽  
Target Pattern ◽  
Temporal Gene Expression ◽  
Genotype Space ◽  
Great Relevance ◽  
Spatio Temporal ◽  
The Relationship

The evolution of gene regulatory networks (GRNs) is of great relevance for both evolutionary and synthetic biology. Understanding the relationship between GRN structure and its function can allow us to understand the selective pressures that have shaped a given circuit. This is especially relevant when considering spatio-temporal expression patterns, where GRN models have been shown to be extremely robust and evolvable. However, previous models that studied GRN evolution did not include the evolution of protein and genetic elements that underlie GRN architecture. Here we use toy LIFE, a multilevel genotype–phenotype map, to show that not all GRNs are equally likely in genotype space and that evolution is biased to find the most common GRNs. toy LIFE rules create Boolean GRNs that, embedded in a one-dimensional tissue, develop a variety of spatio-temporal gene expression patterns. Populations of toy LIFE organisms choose the most common GRN out of a set of equally fit alternatives and, most importantly, fail to find a target pattern when it is very rare in genotype space. Indeed, we show that the probability of finding the fittest phenotype increases dramatically with its abundance in genotype space. This phenotypic bias represents a mechanism that can prevent the fixation in the population of the fittest phenotype, one that is inherent to the structure of genotype space and the genotype–phenotype map.

Probing the Relationship of Long-Range Order in Nanodomain FeCo Alloys with Ternary Additions Using Neutron Diffraction

2009 ◽  
Vol 41 (5) ◽  
pp. 1144-1150 ◽  
Author(s):  
Ralph Gilles ◽  
Michael Hofmann ◽  
Yan Gao ◽  
Frank Johnson ◽  
Luana Iorio ◽  
...  
Keyword(s):  
Neutron Diffraction ◽  
Long Range ◽  
Range Order ◽  
Long Range Order ◽  
Feco Alloys ◽  
Ternary Additions ◽  
Relationship Of ◽  
The Relationship

scholarly journals Top-Down Regulation of Plasticity in the Birdsong System: “Premotor” Activity in the Nucleus HVC Predicts Song Variability Better Than It Predicts Song Features

2008 ◽  
Vol 100 (5) ◽  
pp. 2956-2965 ◽  
Author(s):  
Nancy F. Day ◽  
Amanda K. Kinnischtzke ◽  
Murtaza Adam ◽  
Teresa A. Nick
Keyword(s):  
Brain Activity ◽  
Vocal Learning ◽  
Developmentally Regulated ◽  
Population Activity ◽  
Selective Stabilization ◽  
On Line ◽  
Time Changes ◽  
And Behavior ◽  
Relationship Of ◽  
The Relationship

We studied real-time changes in brain activity during active vocal learning in the zebra finch songbird. The song nucleus HVC is required for the production of learned song. To quantify the relationship of HVC activity and behavior, HVC population activity during repeated vocal sequences (motifs) was recorded and temporally aligned relative to the motif, millisecond by millisecond. Somewhat surprisingly, HVC activity did not reliably predict any vocal feature except amplitude and, to a lesser extent, entropy and pitch goodness (sound periodicity). Variance in “premotor” HVC activity did not reliably predict variance in behavior. In contrast, HVC activity inversely predicted the variance of amplitude, entropy, frequency, pitch, and FM. We reasoned that, if HVC was involved in song learning, the relationship of HVC activity to learned features would be developmentally regulated. To test this hypothesis, we compared the HVC song feature relationships in adults and juveniles in the sensorimotor “babbling” period. We found that the relationship of HVC activity to variance in FM was developmentally regulated, with the greatest difference at an HVC vocalization lag of 50 ms. Collectively, these data show that, millisecond by millisecond, bursts in HVC activity predict song stability on-line during singing, whereas decrements in HVC activity predict plasticity. These relationships between neural activity and plasticity may play a role in vocal learning in songbirds by enabling the selective stabilization of parts of the song that match a learned tutor model.

A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1337-1348 ◽  
Author(s):  
G. Drossopoulou ◽  
K.E. Lewis ◽  
J.J. Sanz-Ezquerro ◽  
N. Nikbakht ◽  
A.P. McMahon ◽  
...  
Keyword(s):  
Long Range ◽  
Short Range ◽  
Limb Bud ◽  
Anteroposterior Patterning ◽  
Dose Dependent Fashion ◽  
Bmp Signalling ◽  
High Level ◽  
The Relationship ◽  
Dose Dependent ◽  
Digit Identity

It has been proposed that digit identity in chick limb bud is specified in a dose-dependent fashion by a long-range morphogen, produced by the polarising region. One candidate is Sonic hedgehog (Shh) protein, but it is not clear whether Shh acts long or short range or via Bmps. Here we dissect the relationship between Shh and Bmp signalling. We show that Shh is necessary not only for initiating bmp2 expression but also for sustaining its expression during the period when additional digits are being specified. We also show that we can reproduce much of the effect of Shh during this period by applying only Bmp2. We further demonstrate that it is Bmps that are responsible for digit specification by transiently adding Noggin or Bmp antibodies to limbs treated with Shh. In such limbs, multiple additional digits still form but they all have the same identity. We also explored time dependency and range of Shh signalling by examining ptc expression. We show that high-level ptc expression is induced rapidly when either Shh beads or polarising regions are grafted to a host limb. Furthermore, we find that high-level ptc expression is first widespread but later more restricted. All these data lead us to propose a new model for digit patterning. We suggest that Shh initially acts long range to prime the region of the limb competent to form digits and thus control digit number. Then later, Shh acts short range to induce expression of Bmps, whose morphogenetic action specifies digit identity.

scholarly journals A Spatio-Temporal Examination of Canada’s Domestic Merger Activity, 1971-1991.

2005 ◽  
Vol 43 (119) ◽  
pp. 239-250 ◽  
Author(s):  
Vincenzo Aliberti ◽  
Milford B. Green
Keyword(s):  
Metropolitan Areas ◽  
Linear Analysis ◽  
Merger Activity ◽  
Spatio Temporal ◽  
Log Linear ◽  
Relationship Of ◽  
The Relationship

This study examines the relationship of Canada's urban centres (Census metropolitan areas), with respect to domestic merger activity for the years 1971, 1976, 1981, 1986 and 1991. Log-linear analysis is employed to provide a descriptive examination of the spatial merger flows for the years in question. It has been determined that from an acquiring and acquired firm perspective, Toronto, Montréal, Calgary and Vancouver, were the cities where the greatest number of merger activity was conducted.

Spatio-Temporal Displacement and Expression of Feeling in Dreams of Emotionally Expressive Persons

1980 ◽  
Vol 51 (2) ◽  
pp. 455-461 ◽  
Author(s):  
Don Kuiken ◽  
Russell Powell
Keyword(s):  
Alternative Hypothesis ◽  
Research Results ◽  
Personal Orientation Inventory ◽  
Spatio Temporal ◽  
Personal Orientation ◽  
Relationship Of ◽  
The Relationship

The present study examined the relationship of expression of feeling during waking to expression of feeling and spatio-temporal displacement in dreams. 41 subjects, each of whom collected either one or two dreams ac home, rated their dreams for expression of feeling, familiarity, and time passed since last experience with selected dream features. They then completed the Personal Orientation Inventory. An independent judge's ratings of expression of feeling in dreams was also obtained. Contrary to expectations, no significant correlations were found between the indices of expression of feeling (Feeling Reactivity, Spontaneity, Aggression) and either the subjects' or the judge's ratings of such expression in dreams. Further, the inventory indices of expression of feeling correlated positively and significantly with spatio-temporal displacement in dreams. These results contradict the theory of Corriere, Hart, Karle, Binder, Gold, and Woldenberg (1977), according to which expression of feeling is inversely related to spario-remporal displacement in dreams. An alternative hypothesis, capable of explaining the present and other research results, implicates expression of feeling in the process of integrating recent events with more remote memories.

Spatio-Temporal Expression and Functional Analysis of miR-206 in Developing Orofacial Tissue

MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 43-60 ◽  
Author(s):  
Partha Mukhopadhyay ◽  
Irina Smolenkova ◽  
Dennis Warner ◽  
Michele M. Pisano ◽  
Robert M. Greene
Keyword(s):  
Temporal Expression ◽  
Cellular Functions ◽  
Developmentally Regulated ◽  
Altered Expression ◽  
Palate Development ◽  
Functional Assays ◽  
Spatiotemporal Expression ◽  
Secondary Palate ◽  
Spatio Temporal ◽  
Functional Analyses

Background:Development of the mammalian palate is dependent on precise, spatiotemporal expression of a panoply of genes. MicroRNAs (miRNAs), the largest family of noncoding RNAs, function as crucial modulators of cell and tissue differentiation, regulating expression of key downstream genes. </P><P> Observations: Our laboratory has previously identified several developmentally regulated miRNAs, including miR-206, during critical stages of palatal morphogenesis. The current study reports spatiotemporal distribution of miR-206 during development of the murine secondary palate (gestational days 12.5-14.5). </P><P> Result and Conclusion: Potential cellular functions and downstream gene targets of miR-206 were investigated using functional assays and expression profiling, respectively. Functional analyses highlighted potential roles of miR-206 in governing TGF&#223;- and Wnt signaling in mesenchymal cells of the developing secondary palate. In addition, altered expression of miR-206 within developing palatal tissue of TGF&#223;3-/- fetuses reinforced the premise that crosstalk between this miRNA and TGF&#223;3 is crucial for secondary palate development.

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