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 DETRENDED FLUCTUATION ANALYSIS OF AUTOREGRESSIVE PROCESSES

2007 ◽  
Vol 07 (03) ◽  
pp. L249-L255 ◽  
Author(s):  
VASILE V. MORARIU ◽  
LUIZA BUIMAGA-IARINCA ◽  
CĂLIN VAMOŞ ◽  
ŞTEFAN M. ŞOLTUZ
Keyword(s):  
Long Range ◽  
Detrended Fluctuation Analysis ◽  
Short Range ◽  
Interaction Constant ◽  
Fluctuation Analysis ◽  
Autoregressive Processes ◽  
Long Range Correlations ◽  
Correlation Exponent ◽  
The Relationship ◽  
Detrended Fluctuation

Autoregressive processes (AR) have typical short-range memory. Detrended Fluctuation Analysis (DFA) was basically designed to reveal long-range correlations in non stationary processes. However DFA can also be regarded as a suitable method to investigate both long-range and short-range correlations in non stationary and stationary systems. Applying DFA to AR processes can help understanding the non-uniform correlation structure of such processes. We systematically investigated a first order autoregressive model AR(1) by DFA and established the relationship between the interaction constant of AR(1) and the DFA correlation exponent. The higher the interaction constant the higher is the short-range correlation exponent. They are exponentially related. The investigation was extended to AR(2) processes. The presence of an interaction between distant terms with characteristic time constant in the series, in addition to a near by interaction will increase the correlation exponent and the range of correlation while the effect of a distant negative interaction will significantly decrease the range of interaction, only. This analysis demonstrate the possibility to identify an AR(1) model in an unknown DFA plot or to distinguish between AR(1) and AR(2) models.

The Liberal, The Conservative, and the Pope

Worldview ◽  
1964 ◽  
Vol 7 (11) ◽  
pp. 13-15
Author(s):  
Michael Novak
Keyword(s):  
Civil Rights ◽  
Long Range ◽  
Short Range ◽  
Present Position ◽  
Moral Competence ◽  
Moral Principles ◽  
Political Statement ◽  
Uncertain Future ◽  
The Relationship

Both Catholics and non-Catholics attempt to enlist the Pope as a partisan of one or another political cause: disarmament, socialization, civil rights, aid for underdeveloped nations, the condemnation of a Hitler. The relationship between morality and politics, however, is ambiguous. Good men may well disagree about which long-range or short-range political programs are best calculated to serve man's moral interests. What, then, is the present position of the Catholic—liberal or conservative—when the Pope makes a moral-political statement about the issues of our time?In its general lines, the traditional answer to this question is simple enough. There are three elements to distinguish: (1) moral principles; (2) political programs; (3) concrete decisions. The Pope's moral competence extends most clearly to declarations about principles. In proportion as judgments about historical facts, present trends, and the yet uncertain future are involved in political programs, the Pope's competence becomes increasingly ambiguous; his is increasingly but one of many prophetic voices “crying in the wilderness.”

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.

scholarly journals Individual differences in intrinsic ankle stiffness and their relationship to body sway and ankle torque

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244993
Author(s):  
Tania E. Sakanaka ◽  
Martin Lakie ◽  
Raymond F. Reynolds
Keyword(s):  
Long Range ◽  
Short Range ◽  
Important Determinant ◽  
Quiet Standing ◽  
Body Sway ◽  
Ankle Torque ◽  
Ankle Stiffness ◽  
Stable Conditions ◽  
Two Parameters ◽  
The Relationship

When standing, intrinsic ankle stiffness is smaller when measured using large perturbations, when sway size is large, and when background torque is low. However, there is a large variation in individual intrinsic ankle stiffness. Here we determine if individual variation has consequences for postural control. We examined the relationship between ankle stiffness, ankle torque and body sway across different individuals. Ankle stiffness was estimated in 19 standing participants by measuring torque responses to small, brief perturbations. Perturbation sizes of 0.2 & 0.9 degrees (both lasting 140 ms) measured short- and long-range stiffness respectively, while participants either stood quietly on a fixed platform or were imperceptibly tilted to reduce stability (0.1 Hz sinusoid; 0.2 & 0.4 deg). The spontaneous body sway component (natural random relatively rapid postural adjustments) and background ankle torque were averaged from sections immediately before perturbations. The results show that, first, intrinsic ankle stiffness is positively associated with ankle torque, and that this relationship is stronger for long-range stiffness. Second, intrinsic ankle stiffness is negatively associated with body sway, but, in contrast to the relationship with torque, this relationship is stronger for short-range stiffness. We conclude that high short-range intrinsic ankle stiffness is associated with reduced spontaneous sway, although the causal relationship between these two parameters is unknown. These results suggest that, in normal quiet standing where sway is very small, the most important determinant of intrinsic ankle stiffness may be stillness. In less stable conditions, intrinsic ankle stiffness may be more dependent on ankle torque.

scholarly journals Cardiovascular reactivity and burnout syndrome of medical personnel

2021 ◽  
Vol 284 ◽  
pp. 02019
Author(s):  
Marina Chukhrova ◽  
Sergey Pronin ◽  
Elena Schukina ◽  
Ekaterina Goncharova ◽  
Vera Morozova
Keyword(s):  
Alcohol Consumption ◽  
Cardiovascular System ◽  
Cardiovascular Reactivity ◽  
Medical Personnel ◽  
Burnout Syndrome ◽  
Adaptive Potential ◽  
Negative Effect ◽  
High Level ◽  
The Relationship ◽  
Dose Dependent

Purpose of the study is to analyze the relationship between latent alcohol consumption, burnout syndrome and the cardiovascular system reactivity of nurses. It was shown that the total number of people with burnout syndrome revealed signs of systematic alcohol consumption significantly more often than without signs of EBS (P = 0.001). there were 8% of people in the first group and 23% of people in the second with a high probability of addiction to nicotine and coffee. In a group of people with a high level of alcohol consumption (from 2.6 to 9.9 drinks), a decrease in the adaptive potential of cardiovascular system was revealed in 45% of cases. The dose-dependent effects of alcohol togather with EBS are interrelated with the VLF index. At the same time, pearson’s correlation of the VLF index (neuroendocrine component) with the amount of alcohol consumed was significant rp = 0,291; P = 0,05 (double-sided). The lower activity of alcohol consumption was influenced by the marital status of the surveyed persons, regardless of the service length. It is concluded that alcohol has a negative effect on the cardiovascular system, which leads to a decrease in the professional suitability of medical personnel and a more pronounced burnout syndrome.

Relationship between dose, distance and time in Sonic Hedgehog-mediated regulation of anteroposterior polarity in the chick limb

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4393-4404 ◽  
Author(s):  
Y. Yang ◽  
G. Drossopoulou ◽  
P.T. Chuang ◽  
D. Duprez ◽  
E. Marti ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Long Range ◽  
Sonic Hedgehog ◽  
Mirror Image ◽  
Limb Bud ◽  
Limb Mesenchyme ◽  
Significant Difference ◽  
Zone Of Polarizing Activity ◽  
Anteroposterior Polarity ◽  
Dose Dependent

Anteroposterior polarity in the vertebrate limb is thought to be regulated in response to signals derived from a specialized region of distal posterior mesenchyme, the zone of polarizing activity. Sonic Hedgehog (Shh) is expressed in the zone of polarizing activity and appears to mediate the action of the zone of polarizing activity. Here we have manipulated Shh signal in the limb to assess whether it acts as a long-range signal to directly pattern all the digits. Firstly, we demonstrate that alterations in digit development are dependent upon the dose of Shh applied. DiI-labeling experiments indicate that cells giving rise to the extra digits lie within a 300 microm radius of a Shh bead and that the most posterior digits come from cells that lie very close to the bead. A response to Shh involves a 12–16 hour period in which no irreversible changes in digit pattern occur. Increasing the time of exposure to Shh leads to specification of additional digits, firstly digit 2, then 3, then 4. Cell marking experiments demonstrate that cells giving rise to posterior digits are first specified as anterior digits and later adopt a more posterior character. To monitor the direct range of Shh signalling, we developed sensitive assays for localizing Shh by attaching alkaline phosphatase to Shh and introducing cells expressing these forms into the limb bud. These experiments demonstrate that long-range diffusion across the anteroposterior axis of the limb is possible. However, despite a dramatic difference in their diffusibility in the limb mesenchyme, the two forms of alkaline phosphatase-tagged Shh proteins share similar polarizing activity. Moreover, Shh-N (aminoterminal peptide of Shh)-coated beads and Shh-expressing cells also exhibit similar patterning activity despite a significant difference in the diffusibility of Shh from these two sources. Finally, we demonstrate that when Shh-N is attached to an integral membrane protein, cells transfected with this anchored signal also induce mirror-image pattern duplications in a dose-dependent fashion similar to the zone of polarizing activity itself. These data suggest that it is unlikely that Shh itself signals digit formation at a distance. Beads soaked in Shh-N do not induce Shh in anterior limb mesenchyme ruling out direct propagation of a Shh signal. However, Shh induces dose-dependent expression of Bmp genes in anterior mesenchyme at the start of the promotion phase. Taken together, these results argue that the dose-dependent effects of Shh in the regulation of anteroposterior pattern in the limb may be mediated by some other signal(s). BMPs are plausible candidates.

Some effects of lead at mammalian neuromuscular junction

1984 ◽  
Vol 246 (3) ◽  
pp. C271-C276 ◽  
Author(s):  
J. B. Pickett ◽  
J. C. Bornstein
Keyword(s):  
Transmitter Release ◽  
Present Finding ◽  
Nerve Terminals ◽  
Dependent Manner ◽  
Dose Dependent Fashion ◽  
The Right ◽  
The Relationship ◽  
Dose Dependent ◽  
Microelectrode Techniques ◽  
Burk Plot

The effect of lead on transmitter release was investigated in a rat phrenic nerve-hemidiaphragm preparation using conventional microelectrode techniques. Lead reduced the number of quanta released by a nerve stimulus (m) in a dose-dependent fashion. As extracellular Ca2+ concentration ([Ca2+]o) was varied in the absence of lead, a linear relationship between ln(m) and ln([Ca2+]o) was obtained. Lead shifted the relationship between ln(m) and ln([Ca2+]o) to the right without altering the slope. This suggested lead competed with Ca2+, which was confirmed by using a modified Lineweaver-Burk plot. Lead inhibits Ca2+ entry into frog sympathetic preganglionic nerve terminals, and a similar mechanism may underlie this present finding; such a mechanism, however, could not explain all the observed actions of lead. Lead increased the frequency of spontaneous quantal release in a dose-dependent manner, and 10(-4) M lead doubled the magnitude of facilitation of evoked release seen with five stimuli at 60 Hz. It is suggested that these effects result from inhibition of some, or all, of the nerve terminal's Ca2+ sequestration mechanisms.

scholarly journals Dynamic spatiotemporal patterns of brain connectivity reorganize across development

2020 ◽  
Vol 4 (1) ◽  
pp. 115-133 ◽  
Author(s):  
Jakub Vohryzek ◽  
Alessandra Griffa ◽  
Emeline Mullier ◽  
Cecilia Friedrichs-Maeder ◽  
Corrado Sandini ◽  
...  
Keyword(s):  
White Matter ◽  
Long Range ◽  
Brain Connectivity ◽  
Brain Dynamics ◽  
Functional Changes ◽  
Functional Patterns ◽  
Global Increase ◽  
High Level ◽  
White Matter Connectivity ◽  
The Relationship

Late human development is characterized by the maturation of high-level functional processes, which rely on reshaping of white matter connections, as well as synaptic density. However, the relationship between the whole-brain dynamics and the underlying white matter networks in neurodevelopment is largely unknown. In this study, we focused on how the structural connectome shapes the emerging dynamics of cerebral development between the ages of 6 and 33 years, using functional and diffusion magnetic resonance imaging combined into a spatiotemporal connectivity framework. We defined two new measures of brain dynamics, namely the system diversity and the spatiotemporal diversity, which quantify the level of integration/segregation between functional systems and the level of temporal self-similarity of the functional patterns of brain dynamics, respectively. We observed a global increase in system diversity and a global decrease and local refinement in spatiotemporal diversity values with age. In support of these findings, we further found an increase in the usage of long-range and inter-system white matter connectivity and a decrease in the usage of short-range connectivity with age. These findings suggest that dynamic functional patterns in the brain progressively become more integrative and temporally self-similar with age. These functional changes are supported by a greater involvement of long-range and inter-system axonal pathways.

Plasminogen Interactions with Immobilized Fibrinogen

1989 ◽  
Vol 62 (04) ◽  
pp. 1078-1082 ◽  
Author(s):  
Burt Adelman ◽  
Patricia Ouynn
Keyword(s):  
Immunosorbent Assay ◽  
Aminocaproic Acid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Binding Regions ◽  
Dose Dependent Fashion ◽  
Epsilon Aminocaproic Acid ◽  
Dose Dependent

SummaryThis report describes the binding of plasminogen to fibrinogen adsorbed onto polystyrene wells. Binding was determined by enzyme linked immunosorbent assay. Both glu- and lys-plasminogen bound to immobilized fibrinogen in a dose-dependent fashion. However, more lys- than glu-plasminogen bound when equal concentrations of either were added to immobilized fibrinogen. Plasminogen binding was inhibited by epsilon aminocaproic acid indicating that binding was mediated via lysine-binding regions of plasminogen. Soluble fibrinogen added in excess of immobilized fibrinogen did not compete for plasminogen binding but fibrinogen fragments produced by plasmin digestion of fibrinogen did. Treatment of immobilized fibrinogen with thrombin caused a small but significant (p <0.01) increase in plasminogen binding. These studies demonstrate that immobilized fibrinogen binds both glu- and lys-plasminogen and that binding is mediated via lysine-binding regions. These interactions may facilitate plasminogen binding to fibrinogen adsorbed on to surfaces and to cells such as platelets which bind fibrinogen.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

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