scholarly journals Rate constants rather than biochemical mechanism determine behaviour of genetic clocks

2008 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Emery Conrad ◽  
Avraham E Mayo ◽  
Alexander J Ninfa ◽  
Daniel B Forger

Many biological systems contain both positive and negative feedbacks. These are often classified as resonators or integrators. Resonators respond preferentially to oscillating signals of a particular frequency. Integrators, on the other hand, accumulate a response to signals. Computational neuroscientists often refer to neurons showing integrator properties as type I neurons and those showing resonator properties as type II neurons. Guantes & Poyatos have shown that type I or type II behaviour can be seen in genetic clocks. They argue that when negative feedback occurs through transcription regulation and post-translationally, genetic clocks act as integrators and resonators, respectively. Here we show that either behaviour can be seen with either design and in a wide range of genetic clocks. This highlights the importance of parameters rather than biochemical mechanism in determining the system behaviour.

2001 ◽  
Vol 38 (02) ◽  
pp. 542-553 ◽  
Author(s):  
Ji Hwan Cha

In this paper two burn-in procedures for a general failure model are considered. There are two types of failure in the general failure model. One is Type I failure (minor failure) which can be removed by a minimal repair or a complete repair and the other is Type II failure (catastrophic failure) which can be removed only by a complete repair. During a burn-in process, with burn-in Procedure I, the failed component is repaired completely regardless of the type of failure, whereas, with burn-in Procedure II, only minimal repair is done for the Type I failure and a complete repair is performed for the Type II failure. In field use, the component is replaced by a new burned-in component at the ‘field use age’ T or at the time of the first Type II failure, whichever occurs first. Under the model, the problems of determining optimal burn-in time and optimal replacement policy are considered. The two burn-in procedures are compared in cases when both the procedures are applicable.


1998 ◽  
Vol 80 (2) ◽  
pp. 914-923 ◽  
Author(s):  
Michinori Kubota ◽  
Ikuo Taniguchi

Kubota, Michinori and Ikuo Taniguchi. Electrophysiological characteristics of classes of neuron in the HVc of the zebra finch. J. Neurophysiol. 80: 914–923, 1998. Whole cell recordings were made from zebra finch HVc neurons in slice preparations. Four distinct classes of neuron were found on the basis of their electrophysiological properties. The morphological characteristics of some of these neurons were also examined by intracellular injection of Lucifer yellow. Type I neurons (21 of 65 cells) had longer time-to-peak of an afterhyperpolarization following an action potential than the other classes. They exhibited both fast and time-dependent inward rectification and an initial high-frequency firing followed by a slower constant firing. Type I neurons had large somata and thick dendrites with many spines. The axons of some of the neurons in this class projected in the direction of area X of the parolfactory lobe. Type II neurons (30 of 65 cells) had a more negative resting membrane potential than the other classes. They exhibited fast inward rectification. Type II neurons could be divided into two subclasses by the absence (IIa; 22 cells) and the presence (IIb; 8 cells) of a low-threshold transient depolarization. Type IIa neurons had relatively small somata and thin, spiny dendrites. The axons of some of the neurons in this class projected in the direction of the robust nucleus of the archistriatum (RA). Type IIb neurons had relatively large somata and thick dendrites with many spines. Type III neurons (6 of 65 cells) had a shorter action-potential duration than the other classes. They exhibited prominent time-dependent inward rectification and a regular tonic firing with little or no accommodation. Type III neurons had beaded, aspiny dendrites. Type IV neurons (8 of 65 cells) had a longer action-potential duration, a much larger input resistance, and longer membrane time constant than the other classes. Type IV neurons had small somata and thin, short, sparsely spiny dendrites. The axons of some of the neurons in this class projected in the direction of the RA. These classes of neuron may play distinct roles in song production and representation in the HVc.


1989 ◽  
Vol 257 (1) ◽  
pp. R87-R95 ◽  
Author(s):  
A. Gnionsahe ◽  
M. Claire ◽  
N. Koechlin ◽  
J. P. Bonvalet ◽  
N. Farman

Distal segment of several amphibians exhibits aldosterone-modulated ion transport properties. On the other hand, A6 cells, derived from Xenopus laevis (XL) kidney, are aldosterone sensitive. We examined the distribution of aldosterone binding sites in isolated tubules of XL compared with rabbit. After incubation with 2 nM [3H]aldosterone, microdissected tubular segments from proximal (PT), distal straight segment (DST), and flask cell collecting (CT) tubules from XL and from rabbit cortical thick ascending limb (CTAL), connecting (CNT), and collecting (CCD) tubules were processed for dry film autoradiography. In XL, specific nuclear labeling of type I (mineralocorticoid) sites was restricted to DST. Labeling of type II (glucocorticoid) sites was present all along the tubule. No specific cytoplasmic labeling was observed, except for type II sites in PT. In the rabbit, aldosterone binds to both type I and type II sites in the three tubular segments studied. In these segments, the binding was about fourfold higher than in DST of XL. These results bring direct evidence in designating the distal tubule of amphibians as a target epithelium for aldosterone. In addition, they suggest that A6 cell line may derive from DST of the Xenopus nephron.


Toxins ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 262 ◽  
Author(s):  
Sabine Brantl ◽  
Peter Müller

Toxin–antitoxin (TA) systems were originally discovered as plasmid maintenance systems in a multitude of free-living bacteria, but were afterwards found to also be widespread in bacterial chromosomes. TA loci comprise two genes, one coding for a stable toxin whose overexpression kills the cell or causes growth stasis, and the other coding for an unstable antitoxin that counteracts toxin action. Of the currently known six types of TA systems, in Bacillus subtilis, so far only type I and type II TA systems were found, all encoded on the chromosome. Here, we review our present knowledge of these systems, the mechanisms of antitoxin and toxin action, and the regulation of their expression, and we discuss their evolution and possible physiological role.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1380 ◽  
Author(s):  
Swayam Prakash Srivastava ◽  
Julie E. Goodwin

The available evidence suggests a complex relationship between diabetes and cancer. Epidemiological data suggest a positive correlation, however, in certain types of cancer, a more complex picture emerges, such as in some site-specific cancers being specific to type I diabetes but not to type II diabetes. Reports share common and differential mechanisms which affect the relationship between diabetes and cancer. We discuss the use of antidiabetic drugs in a wide range of cancer therapy and cancer therapeutics in the development of hyperglycemia, especially antineoplastic drugs which often induce hyperglycemia by targeting insulin/IGF-1 signaling. Similarly, dipeptidyl peptidase 4 (DPP-4), a well-known target in type II diabetes mellitus, has differential effects on cancer types. Past studies suggest a protective role of DPP-4 inhibitors, but recent studies show that DPP-4 inhibition induces cancer metastasis. Moreover, molecular pathological mechanisms of cancer in diabetes are currently largely unclear. The cancer-causing mechanisms in diabetes have been shown to be complex, including excessive ROS-formation, destruction of essential biomolecules, chronic inflammation, and impaired healing phenomena, collectively leading to carcinogenesis in diabetic conditions. Diabetes-associated epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndMT) contribute to cancer-associated fibroblast (CAF) formation in tumors, allowing the epithelium and endothelium to enable tumor cell extravasation. In this review, we discuss the risk of cancer associated with anti-diabetic therapies, including DPP-4 inhibitors and SGLT2 inhibitors, and the role of catechol-o-methyltransferase (COMT), AMPK, and cell-specific glucocorticoid receptors in cancer biology. We explore possible mechanistic links between diabetes and cancer biology and discuss new therapeutic approaches.


1975 ◽  
Vol 53 (1) ◽  
pp. 79-91 ◽  
Author(s):  
Chung-Hsi Huang ◽  
Osvald Knop ◽  
David A. Othen ◽  
Frank W. D. Woodhams ◽  
R. Allan Howie

Cubic M4+P2O7 pyrophosphates of Ti, Zr, Hf, Sn, and Pb have been examined by X-ray powder diffractometry and by infrared, Raman, and Mössbauer 119Sn spectroscopy. The tin compound appeared to be of Chaunac's type I (with P2O7 groups oriented at random) and could be converted to type II (with ordered P2O7 groups) by heating to high temperatures. All the other preparations were of Chaunac's type II. Evidence from lattice parameters and intensity features of the Raman spectra suggests that the cubic MP2O7 pyrophosphates fall in two groups, one containing the compounds of the typical elements (Ge, Sn, Pb) and the other, the compounds of the transition elements. No support has been found for the view that the P—O—P groupings of the pyrophosphate anion in these compounds are linear. The 119Sn chemical shift in SnP2O7 is only slightly less negative than the shift in CuSnF6.4H2O, which makes SnP2O7 one of the most ionic compounds of tetravalent tin known. The observed quadrupole splitting in the Mössbauer spectrum of SnP2O7 arises largely from the contribution of the valence term to the electric field gradient at the Sn atom.


2005 ◽  
Vol 284-286 ◽  
pp. 537-540
Author(s):  
Patricia Valério ◽  
C.C.P. Mendes ◽  
Marivalda Pereira ◽  
Alfredo Goes ◽  
M. Fatima Leite

Osteoblasts constitutively release glutamate and this release appears to be regulated by calcium entry. In this work we investigated if the bioactive glass with 60% of silicon (BG60S) could alter glutamate release by osteoblasts. We demonstrated that osteoblasts incubated with medium containing ionic products from the dissolution of BG60S showed lower release of glutamate when compared to control. Since intracellular calcium (Cai 2+) increase is required for glutamate release we investigated the subcellular distribution of the calcium channel inositol triphosphate receptors (InsP3Rs) in the presence of BG60S compared to control. We found that the type-III InsP3R was not expressed in osteoblast, while the type-II InsP3R was expressed mainly in the cytosol. We also found that the expression of type-II InsP3R decreased in BG60S treated osteoblasts compared to control. On the other hand, we found that the type-I InsP3R was expressed mainly in the nucleus and its expression increased in the presence of the biomaterial.


2005 ◽  
Vol 94 (2) ◽  
pp. 928-933 ◽  
Author(s):  
James B. Fallon ◽  
David L. Morgan

Stochastic resonance describes a phenomenon whereby the addition of “noise” to the input of a nonlinear system can improve sensitivity. “Fully tuneable stochastic resonance” is a particular form of the phenomenon that requires the matching of two time scales: one being that of the subthreshold periodic stimulus of the system and the other being the noise-induced response of the system. First proposed in 1981, stochastic resonance has been reported in a wide range of biological systems; however, conclusive experimental evidence for fully tuneable stochastic resonance in biological systems is limited. Evidence of fully tuneable stochastic resonance in the response of slowly adapting type I mechanoreceptors in the toad is presented. The results are extended to include the first evidence supporting fully tuneable stochastic resonance in psychophysical experiments, namely tactile detection thresholds, indicating that the human CNS is capable of accessing the improved information available via fully tuneable stochastic resonance.


Author(s):  
GWO-LIANG LIAO

This study applies imperfect production processes to obtain in-control state by production correction and reorganization. Production processes are classified into two types of state: one is the type I state (out-of-control state) and the other is the type II state (in-control state). The type I state involves adjustment of the production mechanism. Production correction is either imperfect; worsening a production system, or perfect, returning it to "in-control" conditions. After N type I states, the operating system must be reorganized and returned to the beginning condition. At the beginning of the production of the each renewal cycle, the state of the process is not always to be restored to "in-control". The mean loss cost until "in-control" state, is determined. The existence of a unique and finite optimal N for an imperfect process under certain reasonable conditions is shown. A numerical example is presented.


1996 ◽  
Vol 74 (3) ◽  
pp. 299-314 ◽  
Author(s):  
Steven M. Kolodziejczyk ◽  
Brian K. Hall

The TGF-β superfamily includes a large number of related growth and differentiation factors expressed in virtually all phyla. Superfamily members bind to specific cell surface receptors that activate signal transduction mechanisms to elicit their effects. Candidate receptors fall into two primary groups, termed type I and type II receptors. Both types are serine/threonine kinases. Upon activation by the appropriate ligand, type I and type II receptors physically interact to form hetero-oligomers and subsequently activate intracellular signaling cascades, ultimately regulating gene transcription and expression. In addition, TGF-β binds to a third receptor class, type III, a membrane-anchored proteoglycan lacking the kinase activity typical of signal transducing molecules. Type III receptors appear to regulate ligand availability to type I and type II receptors. Although a number of transduction mechanisms may be available to TGF-β superfamily members, evidence gathered through the use of specific kinase and G-protein inhibitors and through assays measuring activation and levels of signaling intermediates suggests that at least one signaling pathway interacts with Ras and Raf proteins via a G-protein intermediate. Raf begins the cytoplasmic kinase cascade that leads to gene regulation. The myriad responses regulated by TGF-β superfamily members makes the understanding of signal transduction mechanisms utilized by these proteins of great interest to a wide range of biological disciplines.Key words: TGF-β superfamily, serine/threonine kinase receptors, G-proteins, Ras, cytoplasmic kinase cascade.


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