WT1 and Sox11 regulate synergistically the promoter of the Wnt4 gene that encodes a critical signal for nephrogenesis

2012 ◽  
Vol 318 (10) ◽  
pp. 1134-1145 ◽  
Author(s):  
Subramanian Murugan ◽  
Jingdong Shan ◽  
Susanne J. Kühl ◽  
Aleksandra Tata ◽  
Ilkka Pietilä ◽  
...  
Keyword(s):  
Critical Signal ◽  
Wnt4 Gene

Effects of Background Event Rate and Critical Signal Amplitude on Vigilance Performance

1974 ◽  
Vol 38 (3_suppl) ◽  
pp. 1175-1181 ◽  
Author(s):  
Kurt R. Metzger ◽  
Joel S. Warm ◽  
Roderick J. Senter
Keyword(s):  
Event Detection ◽  
Detection Probability ◽  
Event Rate ◽  
Signal Amplitude ◽  
Overt Response ◽  
Vigilance Performance ◽  
Background Event ◽  
Critical Signal

Ss monitored a display consisting of the repetitive presentation of pairs of movements of a bar of light. A neutral background event, for which no overt response was required, was a double deflection of 24 mm. The critical signal for detection was a longer deflection in the second movement within an event. Detection probability was greater for incremental excursions of 33% relative to 8.3% of the base movement. This effect was enhanced twofold when the event rate in which the signals were embedded was 21 as compared to 6 events/min. The results are considered in terms of the elicited observing rate hypothesis proposed by Jerison (1970).

scholarly journals Controllable multichannel acousto-optic modulator and frequency synthesizer enabled by nonlinear MEMS resonator

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gayathri Pillai ◽  
Sheng-Shian Li
Keyword(s):  
Signal Processing ◽  
Lead Zirconate Titanate ◽  
Frequency Synthesizer ◽  
Lead Zirconate ◽  
Oxide Semiconductor ◽  
Processing Unit ◽  
Potential Candidate ◽  
Optical Modulators ◽  
Critical Signal ◽  
Processing Technologies

AbstractNonlinear physics-based harmonic generators and modulators are critical signal processing technologies for optical and electrical communication. However, most optical modulators lack multi-channel functionality while frequency synthesizers have deficient control of output tones, and they additionally require vacuum, complicated setup, and high-power configurations. Here, we report a piezoelectrically actuated nonlinear Microelectromechanical System (MEMS) based Single-Input-Multiple-Output multi-domain signal processing unit that can simultaneously generate programmable parallel information channels (> 100) in both frequency and spatial domain. This significant number is achieved through the combined electromechanical and material nonlinearity of the Lead Zirconate Titanate thin film while still operating the device in an ambient environment at Complementary-Metal–Oxide–Semiconductor compatible voltages. By electrically detuning the operation point along the nonlinear regime of the resonator, the number of electrical and light-matter interaction signals generated based on higher-order non-Eigen modes can be controlled meticulously. This tunable multichannel generation enabled microdevice is a potential candidate for a wide variety of applications ranging from Radio Frequency communication to quantum photonics with an attractive MEMS-photonics monolithic integration ability.

scholarly journals Specific Control of Pseudomonas aeruginosa Surface-Associated Behaviors by Two c-di-GMP Diguanylate Cyclases

mBio ◽  
2010 ◽  
Vol 1 (4) ◽  
Author(s):  
Judith H. Merritt ◽  
Dae-Gon Ha ◽  
Kimberly N. Cowles ◽  
Wenyun Lu ◽  
Diana K. Morales ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Extracellular Polysaccharide ◽  
Diguanylate Cyclase ◽  
Flagellar Motility ◽  
Critical Question ◽  
Cyclic Diguanylate ◽  
Critical Signal ◽  
Content Type ◽  
Wide Range

ABSTRACT The signaling nucleotide cyclic diguanylate (c-di-GMP) regulates the transition between motile and sessile growth in a wide range of bacteria. Understanding how microbes control c-di-GMP metabolism to activate specific pathways is complicated by the apparent multifold redundancy of enzymes that synthesize and degrade this dinucleotide, and several models have been proposed to explain how bacteria coordinate the actions of these many enzymes. Here we report the identification of a diguanylate cyclase (DGC), RoeA, of Pseudomonas aeruginosa that promotes the production of extracellular polysaccharide (EPS) and contributes to biofilm formation, that is, the transition from planktonic to surface-dwelling cells. Our studies reveal that RoeA and the previously described DGC SadC make distinct contributions to biofilm formation, controlling polysaccharide production and flagellar motility, respectively. Measurement of total cellular levels of c-di-GMP in ∆roeA and ∆sadC mutants in two different genetic backgrounds revealed no correlation between levels of c-di-GMP and the observed phenotypic output with regard to swarming motility and EPS production. Our data strongly argue against a model wherein changes in total levels of c-di-GMP can account for the specific surface-related phenotypes of P. aeruginosa. IMPORTANCE A critical question in the study of cyclic diguanylate (c-di-GMP) signaling is how the bacterial cell integrates contributions of multiple c-di-GMP-metabolizing enzymes to mediate its cognate functional outputs. One leading model suggests that the effects of c-di-GMP must, in part, be localized subcellularly. The data presented here show that the phenotypes controlled by two different diguanylate cyclase (DGC) enzymes have discrete outputs despite the same total level of c-di-GMP. These data support and extend the model in which localized c-di-GMP signaling likely contributes to coordination of the action of the multiple proteins involved in the synthesis, degradation, and/or binding of this critical signal.

Regulation by thyroid status of c-myc, c-fos and H-ras mRNAs in the rat myocardium

1991 ◽  
Vol 130 (2) ◽  
pp. 239-244 ◽  
Author(s):  
N. K. Green ◽  
M. D. Gammage ◽  
J. A. Franklyn ◽  
M. C. Sheppard
Keyword(s):  
Protein Synthesis ◽  
Thyroid Hormones ◽  
Contractile Protein ◽  
Rat Myocardium ◽  
Direct Effects ◽  
Thyroid Status ◽  
Critical Signal ◽  
Ras Genes ◽  
Intracellular Signals ◽  
Oncogene Products

ABSTRACT Effects of thyroid status on expression of a variety of myocardial genes, such as those encoding contractile proteins, have been reported, as well as interactions between thyroid hormones and developmental and haemodynamic regulation of contractile protein synthesis. In addition, it is clear that developmental and haemodynamic factors regulate expression of specific proto-oncogenes, including c-myc, c-fos and H-ras, in the myocardium but the effect of thyroid status on such proto-oncogene products, which are proposed to play a critical signal-transducing role in the heart, has been previously unexplored. In order to determine whether changes in thyroid status are associated with changes in expression of these putative intracellular signals, we examined the effect of hypothyroidism and tri-iodothyronine (T3) treatment on myocardial levels of c-myc, c-fos and H-ras mRNAs in the rat. The induction of hypothyroidism was associated with a marked increase in myocardial c-myc, c-fos and H-ras mRNAs, changes reversed by 72 h of T3 replacement. Administration of T3 to euthyroid rats had no significant effect on myocardial c-myc or c-fos mRNAs, but inhibition of H-ras mRNA by T3 was evident. These observations demonstrating influences of thyroid status on expression of specific proto-oncogenes suggest that thyroid hormones, as well as exerting direct effects on expression of functionally important myocardial genes, also interact with the cellular transduction pathways mediated by the products of the c-myc, c-fos and H-ras genes. Journal of Endocrinology (1991) 130, 239–244

scholarly journals A Unique GTP-Dependent Sporulation Sensor Histidine Kinase in Bacillus anthracis

2008 ◽  
Vol 191 (3) ◽  
pp. 687-692 ◽  
Author(s):  
Francesca Scaramozzino ◽  
Andrea White ◽  
Marta Perego ◽  
James A. Hoch
Keyword(s):  
Bacillus Anthracis ◽  
Histidine Kinase ◽  
Catalytic Domain ◽  
Coiled Coil ◽  
Reverse Reaction ◽  
Forward Reaction ◽  
Critical Signal ◽  
Sensor Histidine Kinase ◽  
Virulence Plasmids ◽  
Kinase Catalytic Domain

ABSTRACT The Bacillus anthracis BA2291 gene codes for a sensor histidine kinase involved in the induction of sporulation. Genes for orthologs of the sensor domain of the BA2291 kinase exist in virulence plasmids in this organism, and these proteins, when expressed, inhibit sporulation by converting BA2291 to an apparent phosphatase of the sporulation phosphorelay. Evidence suggests that the sensor domains inhibit BA2291 by titrating its activating signal ligand. Studies with purified BA2291 revealed that this kinase is uniquely specific for GTP in the forward reaction and GDP in the reverse reaction. The G1 motif of BA2291 is highly modified from ATP-specific histidine kinases, and modeling this motif in the structure of the kinase catalytic domain suggested how guanine binds to the region. A mutation in the putative coiled-coil linker between the sensor domain and the catalytic domains was found to decrease the rate of the forward autophosphorylation reaction and not affect the reverse reaction from phosphorylated Spo0F. The results suggest that the activating ligand for BA2291 is a critical signal for sporulation and in a limited concentration in the cell. Decreasing the response to it either by slowing the forward reaction through mutation or by titration of the ligand by expressing the plasmid-encoded sensor domains switches BA2291 from an inducer to an inhibitor of the phosphorelay and sporulation.

scholarly journals PET Imaging Radiotracers of Chemokine Receptors

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5174
Author(s):  
Santosh R. Alluri ◽  
Yusuke Higashi ◽  
Kun-Eek Kil
Keyword(s):  
Small Molecules ◽  
Chemokine Receptors ◽  
Brain Disorders ◽  
Infectious Agents ◽  
Cardiovascular Research ◽  
Critical Signal ◽  
Inflammatory Reactions ◽  
Positron Emission

Chemokines and chemokine receptors have been recognized as critical signal components that maintain the physiological functions of various cells, particularly the immune cells. The signals of chemokines/chemokine receptors guide various leukocytes to respond to inflammatory reactions and infectious agents. Many chemokine receptors play supportive roles in the differentiation, proliferation, angiogenesis, and metastasis of diverse tumor cells. In addition, the signaling functions of a few chemokine receptors are associated with cardiac, pulmonary, and brain disorders. Over the years, numerous promising molecules ranging from small molecules to short peptides and antibodies have been developed to study the role of chemokine receptors in healthy states and diseased states. These drug-like candidates are in turn exploited as radiolabeled probes for the imaging of chemokine receptors using noninvasive in vivo imaging, such as positron emission tomography (PET). Recent advances in the development of radiotracers for various chemokine receptors, particularly of CXCR4, CCR2, and CCR5, shed new light on chemokine-related cancer and cardiovascular research and the subsequent drug development. Here, we present the recent progress in PET radiotracer development for imaging of various chemokine receptors.

Central vs. peripheral metabolic control of estrous cycles in Syrian hamsters. I. Lipoprivation

1997 ◽  
Vol 272 (1) ◽  
pp. R400-R405 ◽  
Author(s):  
J. E. Schneider ◽  
A. J. Hall ◽  
G. N. Wade
Keyword(s):  
Fatty Acid ◽  
Metabolic Control ◽  
Metabolic Energy ◽  
Acid Oxidation ◽  
Inhibitory Effects ◽  
Critical Signal ◽  
Estrous Cycles ◽  
Syrian Hamsters ◽  
Sham Surgery ◽  
Circulating Levels

Metabolic energy availability has profound effects on reproduction in a wide variety of species. We have been studying the effects of fasting on estrous cycles in Syrian hamsters as a model system for metabolic control of reproduction. In previous experiments, a 48-h period of fasting inhibited estrous cycles in lean, but not fat, hamsters. In fat hamsters the effects of fasting may have been offset by the presence of high circulating levels of free fatty acids mobilized from lipids in adipose tissue. Consistent with this idea fat hamsters treated with the inhibitor of fatty acid oxidation methyl palmoxirate (MP) showed fasting-induced anestrus. Experiment 1 was designed to examine whether vagally transmitted signals are critical for the inhibitory effects of fasting and MP treatment. Lean or fat hamsters that had received bilateral subdiaphragmatic vagotomy or sham surgery were fasted and treated with MP or vehicle. In vagotomized and sham-operated hamsters, estrous cycles were inhibited in lean fasted hamsters and in fat fasted hamsters treated with MP, but not in fat fasted hamsters treated with vehicle. Thus the results of experiment 1 indicated that vagally transmitted signals about peripheral fatty acid availability are not critical for the effects of these particular metabolic challenges on estrous cycles in Syrian hamsters. In experiment 2, hamsters without food were allowed to ingest pure glucose or fructose solutions or vegetable shortening. One-half of each group was treated with an inhibitor of glucose utilization, 2-deoxy-D-glucose (2-DG), or vehicle. If ingestion of fructose or shortening, but not glucose, had protected hamsters from 2-DG-induced anestrus, this might have indicated that peripheral fuel availability is critical for anestrus. On the contrary, 2-DG treatment induced anestrus regardless of the type of fuel ingested. Neither experiment yielded results that implicated changes in peripheral fuel availability as a critical signal in metabolic control of estrous cycles.

Neuroblastoma

2020 ◽  
pp. 241-252
Author(s):  
Angelika Eggert ◽  
Garrett M. Brodeur ◽  
Gudrun Schleiermacher
Keyword(s):  
Histone Deacetylases ◽  
Solid Tumour ◽  
Malignant Neoplasm ◽  
Clinical Development ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Critical Signal ◽  
Prognostic Utility ◽  
Sympathetic Nervous ◽  
Current Risk

Neuroblastoma, a malignant neoplasm of the sympathetic nervous system, is the most common extracranial solid tumour in childhood. Since its first description in the nineteenth century, its highly heterogeneous clinical presentation has challenged clinicians and fascinated basic researchers. Neuroblastoma serves as a paradigm for the prognostic utility of biological and clinical data and the potential to tailor therapy for patient cohorts at low, intermediate, and high risk for recurrence. This chapter presents an overview of the key genetic, molecular, histological, and clinical features of neuroblastoma, as well as current risk-stratification strategies and therapeutic approaches. It also highlights how our understanding of tumour pathogenesis, coupled with molecular analyses, has illuminated critical signal transduction pathways and key molecules involved in neuroblastoma tumourigenesis, pointing to novel therapeutic targets for clinical development. Future treatment avenues for relapsed neuroblastoma are discussed, including new drugs targeting ALK, MYC/MYCN, histone deacetylases, or MDM2/TP53.

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