Journal articles on the topic 'Signal activation pattern'
To see the other types of publications on this topic, follow the link: Signal activation pattern.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Signal activation pattern.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Lakatos, Stephen. "Recognition of Complex Auditory-Spatial Patterns." Perception 22, no. 3 (March 1993): 363–74. http://dx.doi.org/10.1068/p220363.
Full textAbstract:
Two experiments were carried out to investigate the perception of complex auditory-spatial patterns. Subjects were asked to identify alphanumeric characters whose patterns could be outlined acoustically through the sequential activation of specific units in a speaker array. Signal bandwidths were varied systematically in both experiments. Signals in experiment 1 had sharp onsets and offsets; envelope shapes in experiment 2 were much more gradual. Subjects showed considerable ability in recognizing alphanumeric patterns traced with signals of varying acoustical composition. Reductions in the steepness of signal attack and decay produced limited declines in pattern recognition ability. Systematic trends in the relation between patterns and the distribution of incorrect responses suggest that subjects performed a pattern-matching task, in which identifications were made on the basis of component features. The unexpected pattern recognition abilities that subjects demonstrated in both experiments suggest that spatial hearing, like vision, has access to mechanisms for amodal spatial representations.
2
Miller, D. T., and R. L. Cagan. "Local induction of patterning and programmed cell death in the developing Drosophila retina." Development 125, no. 12 (June 15, 1998): 2327–35. http://dx.doi.org/10.1242/dev.125.12.2327.
Full textAbstract:
Local cell signaling can pattern the nervous system by directing cell fates, including programmed cell death. In the developing Drosophila retina, programmed cell death is used to remove excess cells between ommatidia. Cell ablation revealed the source and position of signals required for regulating the pattern of programmed cell death among these interommatidial cells. Two types of signals regulate this patterning event. Notch-mediated signals between interommatidial precursors result in removal of unneeded cells. Cone cells and primary pigment cells oppose this signal by supplying a ‘life’-promoting activity; evidence is provided that this signal occurs through localized activation of the EGF Receptor/Ras pathway. Together, these signals refine the highly regular pattern observed in the adult retina.
3
Albarrán-Juárez, Julián, Andras Iring, ShengPeng Wang, Sayali Joseph, Myriam Grimm, Boris Strilic, Nina Wettschureck, Till F. Althoff, and Stefan Offermanns. "Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation." Journal of Experimental Medicine 215, no. 10 (September 7, 2018): 2655–72. http://dx.doi.org/10.1084/jem.20180483.
Full textAbstract:
The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-κB activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y2 receptor, and Gq/G11-mediated signaling. However, only disturbed flow leads to Piezo1- and Gq/G11-mediated integrin activation resulting in focal adhesion kinase-dependent NF-κB activation. Mice with induced endothelium-specific deficiency of Piezo1 or Gαq/Gα11 show reduced integrin activation, inflammatory signaling, and progression of atherosclerosis in atheroprone areas. Our data identify critical steps in endothelial mechanotransduction, which distinguish flow pattern-dependent activation of atheroprotective and atherogenic endothelial signaling and suggest novel therapeutic strategies to treat inflammatory vascular disorders such as atherosclerosis.
4
Hesketh, R., T. A. Moore, S. R. Pennington, G. A. Smith, and J. C. Metcalfe. "Analysis of the primary signals required for activation of the mitogenic pathway in murine thymocytes from protein phosphorylation patterns." Journal of Immunology 145, no. 8 (October 15, 1990): 2571–80. http://dx.doi.org/10.4049/jimmunol.145.8.2571.
Full textAbstract:
Abstract It has been proposed that phorbol esters and the Ca2+ ionophore A23187 are effective comitogens for some species of lymphocytes because together they mimic the normal secondary signals for cell activation by mitogens that cause phosphatidylinositol 4,5-bisphosphate (PtdInsP2) breakdown (e.g., anti-TCR and anti-Thy-1 antibodies and Con A). To test whether activation of protein kinase C and an increase in [Ca2+]i account for the activation of the mitogenic pathway in murine thymocytes by the mitogens that cause PtdInsP2 breakdown, the two-dimensional phosphorylation patterns generated by the three classes of mitogens (protein kinase C activator, Ca2+ ionophore, and activator of PtdInsP2 breakdown) and by activators of cAMP-dependent kinases have been compared. From the phosphorylation patterns, by which each mitogen could be distinguished reproducibly, it was concluded that: 1) The phosphorylation patterns generated by the mitogens that activate PtdInsP2 breakdown are only slightly affected by the removal of extracellular Ca2+ under conditions that abolish the normal rise in [Ca2+]i and do not therefore depend on the activation of Ca2(+)-dependent protein kinases. In contrast, the phosphorylation pattern generated by A23187 is totally dependent on extracellular Ca2+. 2) Neither A23187 nor the mitogens that activate PtdInsP2 breakdown nor activators of cAMP-dependent kinases caused significant activation of protein kinase C assayed by phosphorylation of the diagnostic proteins 80b and 78a. Consistent with this conclusion, only the phorbol esters or oleoyl acyl glycerol caused translocation of protein kinase C activity from the cytosolic to the membrane fraction. 3) Neither A23187 nor the mitogens that cause PtdInsP2 breakdown activated cAMP-dependent kinases. Taken together the data imply that the mitogens that cause PtdInsP2 breakdown must generate an additional, independent primary mitogenic signal. It is suggested that this signal may be the activation of tyrosine kinases (e.g., p56lck) via the TCR and working hypotheses for effective combinations of primary mitogenic signals that will activate DNA synthesis are developed.
5
Lin, Genghong, Feng Jiao, Qiwen Sun, Moxun Tang, Jianshe Yu, and Zhan Zhou. "Linking dynamical complexities from activation signals to transcription responses." Royal Society Open Science 6, no. 3 (March 2019): 190286. http://dx.doi.org/10.1098/rsos.190286.
Full textAbstract:
The transcription of inducible genes involves signalling pathways that induce DNA binding of the downstream transcription factors to form functional promoter states. How the transcription dynamics is linked to the temporal variations of activation signals is far from being fully understood. In this work, we develop a mathematical model with multiple promoter states to address this question. Each promoter state has its own activation and inactivation rates and is selected randomly with a probability that may change in time. Under the activation of constant signals, our analysis shows that if only the activation rates differ among the promoter states, then the mean transcription level m ( t ) displays only a monotone or monophasic growth pattern. In a sharp contrast, if the inactivation rates change with the promoter states, then m ( t ) may display multiphasic growth patterns. Upon the activation of signals that oscillate periodically, m ( t ) also oscillates later, almost periodically at the same frequency, but the magnitude decreases with frequency and is almost completely attenuated at high frequencies. This gives a surprising indication that multiple promoter states could filter out the signal oscillation and the noise in the random promoter state selection, as observed in the transcription of a gene activated by p53 in breast carcinoma cells. Our approach may help develop a theoretical framework to integrate coherently the genetic circuit with the promoter states to elucidate the linkage from the activation signal to the temporal profile of transcription outputs.
6
Kim, Jae Gyu, Sung Joong Lee, and Martin F. Kagnoff. "Nod1 Is an Essential Signal Transducer in Intestinal Epithelial Cells Infected with Bacteria That Avoid Recognition by Toll-Like Receptors." Infection and Immunity 72, no. 3 (March 2004): 1487–95. http://dx.doi.org/10.1128/iai.72.3.1487-1495.2004.
Full textAbstract:
ABSTRACT The transcription factor NF-κB in human intestinal epithelial cells plays a central role in regulating genes that govern the onset of mucosal inflammatory responses following intestinal microbial infection. Nod1 is a cytosolic pattern recognition receptor in mammalian cells that senses components of microbial peptidoglycans and signals the activation of NF-κB. The aim of these studies was to assess the functional importance of Nod1 in activating NF-κB and NF-κB proinflammatory target genes in human intestinal epithelium. Human colon epithelial cells that constitutively express Nod1 were used as a model intestinal epithelium. These cells do not signal through Toll-like receptor 4 (TLR4) or respond to bacterial lipopolysaccharide, but they express functional TLR5 and interleukin 1 (IL-1) receptors that signal the activation of NF-κB in response to bacterial flagellin or IL-1 stimulation. Stable expression of dominant negative (DN) Nod1 in colon epithelial cells prevented IκB kinase and NF-κB activation in response to infection with enteroinvasive Escherichia coli. In contrast, DN Nod1 did not eliminate IL-1 or flagellin-stimulated NF-κB activation. Inhibition of NF-κB was accompanied by inhibition of NF-κB target genes that provide signals for the mucosal influx of neutrophils during intestinal infection. We conclude that signaling through Nod1 is required for activating NF-κB in human intestinal epithelial cells infected with gram-negative enteric bacteria that can bypass TLR activation. Signaling through Nod1 provides the intestinal epithelium with a backup mechanism for rapidly activating innate immunity during infection with a group of highly invasive pathogenic gram-negative bacteria.
7
Xie, Chuyang, Xiguang Gao, Huajun Zhang, and Yingdong Song. "Multiscale acoustic emission of C/SiC mini-composites and damage identification using pattern recognition." Science and Engineering of Composite Materials 27, no. 1 (May 30, 2020): 148–62. http://dx.doi.org/10.1515/secm-2020-0015.
Full textAbstract:
AbstractIn this paper, multiscale acoustic emission (AE) signal analysis was applied to acoustic emission data processing to classify the AE signals produced during the tensile process of C/SiC mini-composites. An established unsupervised clustering algorithm was provided to classify an unknown set of AE data into reasonable classes. In order to correctly match the obtained classes of the AE signals with the damage mode of the sample, three scales of materials were involved. Single fiber tensile test and fiber bundle tensile test were firstly performed to achieve the characteristics of AE signal of fiber fracture. Parameter analysis and waveform analysis were added to extract the different features of each class of signals in the In-situ tensile test of C/SiC mini-composite. The change of strain field on the sample surface analyzed by DIC (Digital Image Correlation) revealed the corresponding relationship between matrix cracking and AE signals. Microscopic examinationwas used to correlate the clusters to the damage mode. By analyzing the evolution process of signal activation for each class against the load, it also provided a reliable basis for the correlation between the obtained classes of the AE signals and the damage mechanism of the material.
8
Haglund, Michael M., Joseph R. Meno, Daryl W. Hochman, Al C. Ngai, and H. Richard Winn. "Correlation of intrinsic optical signal, cerebral blood flow, and evoked potentials during activation of rat somatosensory cortex." Journal of Neurosurgery 109, no. 4 (October 2008): 654–63. http://dx.doi.org/10.3171/jns/2008/109/10/0654.
Full textAbstract:
Object This study was undertaken to test the hypothesis that cerebral blood flow (CBF) and the intrinsic optical signal could be dissociated by altering adenosine receptor activity and to uncover the origin of the optic signal using a cranial window in the anesthetized rat. Methods In anesthetized, ventilated, and temperature-controlled rats with closed cranial windows, the authors evaluated simultaneously the alterations in pial arteriolar diameter, intrinsic optical signals (690 nm), and somatosensory evoked potentials during cortical activation evoked by contralateral sciatic nerve stimulation (SNS). To dissociate the vascular and intrinsic signal, they topically applied the adenosine receptors antagonists theophylline (5 μM), which affects A1 and A2A receptors, and 8-cyclopentyl-1,3-dipropylxanthine (CPX, 1 μM), which blocks the A1 receptor. The former interacts primarily with the vasculature whereas the latter influences the parenchyma exclusively. Results During 20 seconds of contralateral SNS, pial arterioles in the hindlimb somatosensory cortex dilated in a characteristic peak and shoulder pattern. As compared with mock cerebrospinal fluid alone, theophylline significantly (p < 0.05) attenuated SNS-induced vasodilation (mean ± standard deviation 8.1 ± 2.5% vs 21.7 ± 1.9%; 4 rats in each group). In contrast, CPX potentiated vasodilation significantly (p < 0.05) during SNS (54.7 ± 15.8% for the CPX group vs 20.1 ± 1.9% for the controls; 5 rats in each group). The change in optical signal persisted after cessation of SNS in all the animals. Thus, the pattern of change of the optical signal was distinctly different from the pattern of changes in arteriolar diameter (which returned rapidly to baseline). Moreover, the optical signal during SNS was increased by 50% by theophylline and by almost 5-fold by CPX (p < 0.05). The area of change of the intrinsic signal was also increased by the topical application of theophylline and CPX. The somatosensory evoked potential recordings revealed no significant changes after theophylline application, but CPX caused a small diminution of the N1 wave (p < 0.01). Conclusions The noncongruent temporal profiles of the changes in pial arteriolar diameter and optical signal, imaged at 690 nm, indicate that the optical signal at 690 nm is not related to CBF. Alteration of adenosine receptor activity independently changed cortical activity, as measured by the optical signal, and CBF, as determined by pial arteriolar diameter. Manipulation of the adenosine receptor activity during increased cortical activity confirmed the temporal dissociation of optical signal and CBF and provided further evidence for the role of adenosine in regulating CBF.
9
Lima Alberton, Cristine, Stephanie Santana Pinto, Natália Amélia da Silva Azenha, Eduardo Lusa Cadore, Marcus Peikriszwili Tartaruga, Bruno Brasil, and Luiz Fernando Martins Kruel. "Kinesiological Analysis of Stationary Running Performed in Aquatic and Dry Land Environments." Journal of Human Kinetics 49, no. 1 (December 1, 2015): 5–14. http://dx.doi.org/10.1515/hukin-2015-0103.
Full textAbstract:
Abstract The purpose of the present study was to analyze the electromyographic (EMG) signals of the rectus femoris (RF), vastus lateralis (VL), semitendinosus (ST) and short head of the biceps femoris (BF) during the performance of stationary running at different intensities in aquatic and dry land environments. The sample consisted of 12 female volunteers who performed the stationary running exercise in aquatic and dry land environments at a submaximal cadence (80 beats·min-1 controlled by a metronome) and at maximal velocity, with EMG signal measurements from the RF, VL, ST and BF muscles. The results showed a distinct pattern between environments for each muscle examined. For the submaximal cadence of 80 beats·min-1, there was a reduced magnitude of the EMG signal in the aquatic environment, except for the ST muscle, the pattern of which was similar in both environments. In contrast to the submaximal cadence, the pattern of the EMG signal from all of the muscles showed similar magnitudes for both environments and phases of movement at maximal velocity, except for the VL muscle. Therefore, the EMG signals from the RF, VL, ST and BF muscles of women during stationary running had different patterns of activation over the range of motion between aquatic and dry land environments for different intensities. Moreover, the neuromuscular responses of the lower limbs were optimized by an increase in intensity from submaximal cadence to maximal velocity.
10
Berg, Nancy N., Lawrence G. Puente, Wojciech Dawicki, and Hanne L. Ostergaard. "Sustained TCR Signaling Is Required for Mitogen-Activated Protein Kinase Activation and Degranulation by Cytotoxic T Lymphocytes." Journal of Immunology 161, no. 6 (September 15, 1998): 2919–24. http://dx.doi.org/10.4049/jimmunol.161.6.2919.
Full textAbstract:
Abstract Requirements for T cell activation are not fully established. One model is that receptor occupancy and down-regulation are essential for activation, and another, not necessarily mutually exclusive, model is that sustained signals are important. Here we examine the importance of signal duration in T cell activation. First, we demonstrate that immobilized, but not soluble cross-linked, Abs to CD3 stimulate degranulation by CTL. The cross-linked Abs are not deficient in their ability to signal since they stimulate the same tyrosine phosphorylation pattern as immobilized Ab, but it is very transient relative to that stimulated by immobilized Ab. Furthermore, novel decreased migratory forms of Lck occur to a significant extent only after stimulation with immobilized Abs. A dramatic difference in the duration of signals is very evident when mitogen-activated protein kinase (MAPK) activity is examined. Immobilized anti-CD3 stimulates very high levels of MAPK activation that is still detectable 1 h after stimulation. In contrast, cross-linked Ab stimulates only transient and incomplete activation of MAPK. Taken together, these results suggest that TCR engagement and induction of tyrosine phosphorylation alone are not sufficient for T cell activation and that the duration of TCR-stimulated signals is critical to attain a functional response.
11
Pietiäinen, Milla, Marika Gardemeister, Maria Mecklin, Soile Leskelä, Matti Sarvas, and Vesa P. Kontinen. "Cationic antimicrobial peptides elicit a complex stress response in Bacillus subtilis that involves ECF-type sigma factors and two-component signal transduction systems." Microbiology 151, no. 5 (May 1, 2005): 1577–92. http://dx.doi.org/10.1099/mic.0.27761-0.
Full textAbstract:
Stress responses of Bacillus subtilis to membrane-active cationic antimicrobial peptides were studied. Global analysis of gene expression by DNA macroarray showed that peptides at a subinhibitory concentration activated numerous genes. A prominent pattern was the activation of two extracytoplasmic function sigma factor regulons, SigW and SigM. Two natural antimicrobial peptides, LL-37 and PG-1, were weak activators of SigW regulon genes, whereas their synthetic analogue poly-l-lysine was clearly a stronger activator of SigW. It was demonstrated for the first time that LL-37 is a strong and specific activator of the YxdJK two-component systems, one of the three highly homologous two-component systems sensing antimicrobial compounds. YxdJK regulates the expression of the YxdLM ABC transporter. The LiaRS (YvqCE) TCS was also strongly activated by LL-37, but its activation is not LL-37 specific, as was demonstrated by its activation with PG-1 and Triton X-100. Other strongly LL-37-induced genes included yrhH and yhcGHI. Taken together, the responses to cationic antimicrobial peptides revealed highly complex regulatory patterns and induction of several signal transduction pathways. The results suggest significant overlap between different stress regulons and interdependence of signal transduction pathways mediating stress responses.
12
Siefken, Renate, Stefan Klein-Heßling, Edgar Serfling, Roland Kurrle, and Reinhard Schwinzer. "A CD28-Associated Signaling Pathway Leading to Cytokine Gene Transcription and T Cell Proliferation Without TCR Engagement." Journal of Immunology 161, no. 4 (August 15, 1998): 1645–51. http://dx.doi.org/10.4049/jimmunol.161.4.1645.
Full textAbstract:
Abstract Stimulation of resting human T cells with the CD28-specific mAb BW 828 induces proliferation and cytokine synthesis without further requirement for TCR coengagement. This observation prompted us to postulate that signal 2 (costimulatory signal) alone without signal 1 (TCR signal) can activate T cells. To test whether this putative function of CD28 is mediated via a particular signaling pathway, we compared early signaling events initiated in resting T cells by the stimulatory mAb BW 828 with signals triggered by the nonstimulating CD28 mAb 9.3. Stimulation of T cells with BW 828 induced an increase in intracellular Ca2+, but did not lead to detectable activation of the protein kinases p56lck and c-Raf-1. This pathway resulted in the induction of the transcription factors NF-κB, NF-AT, and proteins binding to the CD28 response element of the IL-2 promoter. On the other hand, stimulation of T cells with mAb 9.3 increased the level of intracellular Ca2+ and triggered the activation of p56lck and c-Raf-1, but was unable to induce the binding of transcription factors to the IL-2 promoter. In contrast to the differential signaling of BW 828 and 9.3 in resting T cells, the two mAbs exhibited a similar pattern of early signaling events in activated T cells and Jurkat cells (p56lck activation, association of phosphatidylinositol 3-kinase with CD28), indicating that the signaling capacity of CD28 changes with activation. These data support the view that stimulation through CD28 can induce some effector functions in T cells and suggest that this capacity is associated with a particular pattern of early signaling events.
13
Strother, S. C., K. Rehm, J. R. Anderson, K. A. Schaper, and D. A. Rottenberg. "Localized Signal Effects Cause Differences in Activation-Pattern Reproducibility Across Data Analysis Models." NeuroImage 7, no. 4 (May 1998): S765. http://dx.doi.org/10.1016/s1053-8119(18)31598-2.
Full text
14
Kim, Seong-Cheol, Jee-Sook Hahn, Yoo-Hong Min, Nae-Choon Yoo, Yun-Woong Ko, and Won-Jae Lee. "Constitutive Activation of Extracellular Signal-Regulated Kinase in Human Acute Leukemias: Combined Role of Activation of MEK, Hyperexpression of Extracellular Signal-Regulated Kinase, and Downregulation of a Phosphatase, PAC1." Blood 93, no. 11 (June 1, 1999): 3893–99. http://dx.doi.org/10.1182/blood.v93.11.3893.
Full textAbstract:
Abstract Extracellular signal-regulated kinase (ERK) is an important intermediate in signal transduction pathways that are initiated by many types of cell surface receptors. It is thought to play a pivotal role in integrating and transmitting transmembrane signals required for growth and differentiation. Constitutive activation of ERK in fibroblasts elicits oncogenic transformation, and recently, constitutive activation of ERK has been observed in some human malignancies, including acute leukemia. However, mechanisms underlying constitutive activation of ERK have not been well characterized. In this study, we examined the activation of ERK in 79 human acute leukemia samples and attempted to find factors contributing to constitutive ERK activation. First, we showed that ERK and MEK were constitutively activated in acute leukemias by in vitro kinase assay and immunoblot analysis. However, in only one half of the studied samples, the pattern of ERK activation was similar to that of MEK activation. Next, by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis, we showed hyperexpression of ERK in a majority of acute leukemias. In 17 of 26 cases (65.4%) analyzed by immunoblot, the pattern of ERK expression was similar to that of ERK activation. The fact of constitutive activation of ERK in acute leukemias suggested to us the possibility of an abnormal downregulation mechanism of ERK. Therefore, we examined PAC1, a specific ERK phosphatase predominantly expressed in hematopoietic tissue and known to be upregulated at the transcription level in response to ERK activation. Interestingly, in our study, PAC1 gene expression in acute leukemias showing constitutive ERK activation was significantly lower than that in unstimulated, normal bone marrow (BM) samples showing minimal or no ERK activation (P = .002). Also, a significant correlation was observed between PAC1 downregulation and phosphorylation of ERK in acute leukemias (P= .002). Finally, by further analysis of 26 cases, we showed that a complementary role of MEK activation, ERK hyperexpression, and PAC1 downregulation could contribute to determining the constitutive activation of ERK in acute leukemia. Our results suggest that ERK is constitutively activated in a majority of acute leukemias, and in addition to the activation of MEK, the hyperexpression of ERK and downregulation of PAC1 also contribute to constitutive ERK activation in acute leukemias.
15
Kim, Seong-Cheol, Jee-Sook Hahn, Yoo-Hong Min, Nae-Choon Yoo, Yun-Woong Ko, and Won-Jae Lee. "Constitutive Activation of Extracellular Signal-Regulated Kinase in Human Acute Leukemias: Combined Role of Activation of MEK, Hyperexpression of Extracellular Signal-Regulated Kinase, and Downregulation of a Phosphatase, PAC1." Blood 93, no. 11 (June 1, 1999): 3893–99. http://dx.doi.org/10.1182/blood.v93.11.3893.407k14_3893_3899.
Full textAbstract:
Extracellular signal-regulated kinase (ERK) is an important intermediate in signal transduction pathways that are initiated by many types of cell surface receptors. It is thought to play a pivotal role in integrating and transmitting transmembrane signals required for growth and differentiation. Constitutive activation of ERK in fibroblasts elicits oncogenic transformation, and recently, constitutive activation of ERK has been observed in some human malignancies, including acute leukemia. However, mechanisms underlying constitutive activation of ERK have not been well characterized. In this study, we examined the activation of ERK in 79 human acute leukemia samples and attempted to find factors contributing to constitutive ERK activation. First, we showed that ERK and MEK were constitutively activated in acute leukemias by in vitro kinase assay and immunoblot analysis. However, in only one half of the studied samples, the pattern of ERK activation was similar to that of MEK activation. Next, by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis, we showed hyperexpression of ERK in a majority of acute leukemias. In 17 of 26 cases (65.4%) analyzed by immunoblot, the pattern of ERK expression was similar to that of ERK activation. The fact of constitutive activation of ERK in acute leukemias suggested to us the possibility of an abnormal downregulation mechanism of ERK. Therefore, we examined PAC1, a specific ERK phosphatase predominantly expressed in hematopoietic tissue and known to be upregulated at the transcription level in response to ERK activation. Interestingly, in our study, PAC1 gene expression in acute leukemias showing constitutive ERK activation was significantly lower than that in unstimulated, normal bone marrow (BM) samples showing minimal or no ERK activation (P = .002). Also, a significant correlation was observed between PAC1 downregulation and phosphorylation of ERK in acute leukemias (P= .002). Finally, by further analysis of 26 cases, we showed that a complementary role of MEK activation, ERK hyperexpression, and PAC1 downregulation could contribute to determining the constitutive activation of ERK in acute leukemia. Our results suggest that ERK is constitutively activated in a majority of acute leukemias, and in addition to the activation of MEK, the hyperexpression of ERK and downregulation of PAC1 also contribute to constitutive ERK activation in acute leukemias.
16
Sengupta, Ayan, Stefan Pollmann, and Michael Hanke. "Spatial band-pass filtering aids decoding musical genres from auditory cortex 7T fMRI." F1000Research 7 (February 2, 2018): 142. http://dx.doi.org/10.12688/f1000research.13689.1.
Full textAbstract:
Spatial filtering strategies, combined with multivariate decoding analysis of BOLD images, have been used to investigate the nature of the neural signal underlying the discriminability of brain activity patterns evoked by sensory stimulation -- primarily in the visual cortex. Reported evidence indicates that such signals are spatially broadband in nature, and are not primarily comprised of fine-grained activation patterns. However, it is unclear whether this is a general property of the BOLD signal, or whether it is specific to the details of employed analyses and stimuli. Here we performed an analysis of publicly available, high-resolution 7T fMRI on the response BOLD response to musical genres in primary auditory cortex that matches a previously conducted study on decoding visual orientation from V1. The results show that the pattern of decoding accuracies with respect to different types and levels of spatial filtering is comparable to that obtained from V1, despite considerable differences in the respective cortical circuitry.
17
Sengupta, Ayan, Stefan Pollmann, and Michael Hanke. "Spatial band-pass filtering aids decoding musical genres from auditory cortex 7T fMRI." F1000Research 7 (April 4, 2018): 142. http://dx.doi.org/10.12688/f1000research.13689.2.
Full textAbstract:
Spatial filtering strategies, combined with multivariate decoding analysis of BOLD images, have been used to investigate the nature of the neural signal underlying the discriminability of brain activity patterns evoked by sensory stimulation – primarily in the visual cortex. Previous research indicates that such signals are spatially broadband in nature, and are not primarily comprised of fine-grained activation patterns. However, it is unclear whether this is a general property of the BOLD signal, or whether it is specific to the details of employed analyses and stimuli. Here we applied an analysis strategy from a previous study on decoding visual orientation from V1 to publicly available, high-resolution 7T fMRI on the response BOLD response to musical genres in primary auditory cortex. The results show that the pattern of decoding accuracies with respect to different types and levels of spatial filtering is comparable to that obtained from V1, despite considerable differences in the respective cortical circuitry.
18
Lambert, J. D., and L. M. Nagy. "MAPK signaling by the D quadrant embryonic organizer of the mollusc Ilyanassa obsoleta." Development 128, no. 1 (January 1, 2001): 45–56. http://dx.doi.org/10.1242/dev.128.1.45.
Full textAbstract:
Classical experiments performed on the embryo of the mollusc Ilyanassa obsoleta demonstrate that the 3D macromere acts as an embryonic organizer, by signaling to other cells and inducing them to assume the correct pattern of cell fates. We have discovered that MAP kinase signaling is activated in the cells that require the signal from 3D for normal differentiation. Preventing specification of the D quadrant lineage by removing the polar lobe disrupts the pattern of MAPK activation, as does ablation of the 3D macromere itself. Blocking MAPK activation with the MAP Kinase inhibitor U0126 produces larvae that differentiate the same limited complement of tissues as D quadrant deletions. Our results suggest that the MAP Kinase signaling cascade transduces the inductive signal from 3D and specifies cell fate among the cells that receive the signal.
19
Rodenacker, Karsten, Klaus Hahn, Gerhard Winkler, and Dorothea P. Auer. "SPATIO-TEMPORAL DATA ANALYSIS WITH NON-LINEAR FILTERS: BRAIN MAPPING WITH fMRI DATA." Image Analysis & Stereology 19, no. 3 (May 3, 2011): 189. http://dx.doi.org/10.5566/ias.v19.p189-194.
Full textAbstract:
Spatio-temporal digital data from fMRI (functional Magnetic Resonance Imaging) are used to analyse and to model brain activation. To map brain functions, a well-defined sensory activation is offered to a test person and the hemodynamic response to neuronal activity is studied. This so-called BOLD effect in fMRI is typically small and characterised by a very low signal to noise ratio. Hence the activation is repeated and the three dimensional signal (multi-slice 2D) is gathered during relatively long time ranges (3-5 min). From the noisy and distorted spatio-temporal signal the expected response has to be filtered out. Presented methods of spatio-temporal signal processing base on non-linear concepts of data reconstruction and filters of mathematical morphology (e.g. alternating sequential morphological filters). Filters applied are compared by classifications of activations.
20
Young, Matthew R., Rajalakshmi Nair, Natalie Bucheimer, Preety Tulsian, Nicole Brown, Cristi Chapp, Tin-Chen Hsu, and Nancy H. Colburn. "Transactivation of Fra-1 and Consequent Activation of AP-1 Occur Extracellular Signal-Regulated Kinase Dependently." Molecular and Cellular Biology 22, no. 2 (January 15, 2002): 587–98. http://dx.doi.org/10.1128/mcb.22.2.587-598.2002.
Full textAbstract:
ABSTRACT Mitogen-activated protein (MAP) kinase, extracellular-signal-regulated kinases (ERKs) play an important role in activating AP-1-dependent transcription. Studies using the JB6 mouse epidermal model and a transgenic mouse model have established a requirement for AP-1-dependent transcription in tumor promotion. Tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor induce activator protein 1 (AP-1) activity and neoplastic transformation in JB6 transformation-sensitive (P+) cells, but not in transformation-resistant (P−) variants. The resistance in one of the P− variants can be attributed to the low levels of the MAP kinases, ERKs 1 and 2, and consequent nonresponsiveness to AP-1 activation. The resistant variant is not deficient in c-fos transcription. The purpose of these studies was to define the targets of activated ERK that lead to AP-1 transactivation. The results establish that the transactivation domain of Fra-1 can be activated, that activation of Fra-1 is ERK dependent, and that a putative ERK phosphorylation site must be intact for activation to occur. Fra-1 was activated by TPA in ERK-sufficient P+ cells but not in ERK-deficient P− cells. A similar activation pattern was seen for c-Fos but not for Fra-2. Gel shift analysis identified Fra-1 as distinguishing mitogen-activated (P+) from nonactivated (P−) AP-1 complexes. A second AP-1-nonresponsive P− variant that underexpresses Fra-1 gained AP-1 response upon introduction of a Fra-1 expression construct. These observations suggest that ERK-dependent activation of Fra-1 is required for AP-1 transactivation in JB6 cells.
21
Suñol, Maria, Ignacio Martínez-Zalacaín, Maria Picó-Pérez, Clara López-Solà, Eva Real, Miquel Àngel Fullana, Jesús Pujol, et al. "Differential patterns of brain activation between hoarding disorder and obsessive-compulsive disorder during executive performance." Psychological Medicine 50, no. 4 (March 25, 2019): 666–73. http://dx.doi.org/10.1017/s0033291719000515.
Full textAbstract:
AbstractBackgroundPreliminary evidence suggests that hoarding disorder (HD) and obsessive-compulsive disorder (OCD) may show distinct patterns of brain activation during executive performance, although results have been inconclusive regarding the specific neural correlates of their differential executive dysfunction. In the current study, we aim to evaluate differences in brain activation between patients with HD, OCD and healthy controls (HCs) during response inhibition, response switching and error processing.MethodsWe assessed 17 patients with HD, 18 patients with OCD and 19 HCs. Executive processing was assessed inside a magnetic resonance scanner by means of two variants of a cognitive control protocol (i.e. stop- and switch-signal tasks), which allowed for the assessment of the aforementioned executive domains.ResultsOCD patients performed similar to the HCs, differing only in the number of successful go trials in the switch-signal task. However, they showed an anomalous hyperactivation of the right rostral anterior cingulate cortex during error processing in the switch-signal task. Conversely, HD patients performed worse than OCD and HC participants in both tasks, showing an impulsive-like pattern of response (i.e. shorter reaction time and more commission errors). They also exhibited hyperactivation of the right lateral orbitofrontal cortex during successful response switching and abnormal deactivation of frontal regions during error processing in both tasks.ConclusionsOur results support that patients with HD and OCD present dissimilar cognitive profiles, supported by distinct neural mechanisms. Specifically, while alterations in HD resemble an impulsive pattern of response, patients with OCD present increased error processing during response conflict protocols.
22
Kanasaki, Haruhiko, Gregoy Y. Bedecarrats, Kyung-Yoon Kam, Shuyun Xu, and Ursula B. Kaiser. "Gonadotropin-Releasing Hormone Pulse Frequency-Dependent Activation of Extracellular Signal-Regulated Kinase Pathways in Perifused LβT2 Cells." Endocrinology 146, no. 12 (December 1, 2005): 5503–13. http://dx.doi.org/10.1210/en.2004-1317.
Full textAbstract:
The pattern of GnRH release is associated with differential synthesis and release of LH and FSH. Using a perifusion system, we previously reported that stimulation of the LβT2 cell line with varying GnRH pulse frequencies resulted in differential stimulation of LHβ and FSHβ gene transcription, analogous to previous observations in primary gonadotropes. In the present study, we investigated the patterns of MAPK activation by GnRH and the role of MAPK in mediating the frequency-dependent effects. In static culture, ERK activation in LβT2 cells stimulated with continuous GnRH (10 nm) was maximal by 10 min and persisted for up to 6 h, with a return to basal levels by 20 h. In contrast, stimulation with continuous GnRH (10 nm) in perifused cells resulted in a more sustained activation of ERK. To investigate the effects of GnRH pulse frequency on ERK activation, perifused LβT2 cells were stimulated with pulsatile GnRH at a frequency of one pulse every 30 min or one pulse every 2 h for 20 h (10 nm, 5 min/pulse). After the final GnRH pulse, cells were lysed at frequent intervals and levels of ERK phosphorylation were measured. Under high-frequency conditions, ERK activation was maximal 10 min after the GnRH pulse and returned to baseline levels by 20 min. In contrast, under lower GnRH pulse frequency conditions, ERK activation occurred more rapidly and activation was more sustained, with a slower rate of ERK dephosphorylation. These changes resulted in different levels of nuclear phosphorylated ERK. Blockade of ERK activation abolished GnRH-dependent activation of LHβ and FSHβ transcription at both high and low pulse frequencies. These results demonstrate that in perifused LβT2 cells, distinct patterns of ERK activation/inactivation are regulated by GnRH pulse frequency, and the difference in ERK activation may be important for GnRH pulse frequency-dependent differential stimulation of LHβ and FSHβ gene expression.
23
Wu, Jing, and Emery H. Bresnick. "Glucocorticoid and Growth Factor Synergism Requirement for Notch4 Chromatin Domain Activation." Molecular and Cellular Biology 27, no. 6 (January 12, 2007): 2411–22. http://dx.doi.org/10.1128/mcb.02152-06.
Full textAbstract:
ABSTRACT The Notch signaling pathway modulates cell fate in diverse contexts, including vascular development. Notch4 is selectively expressed in vascular endothelium and regulates vascular remodeling. The signal-dependent transcription factor activator protein 1 (AP-1) activates Notch4 transcription in endothelial cells, but other factors/signals that regulate Notch4 are largely unknown. We demonstrate that, unlike the established transrepression mechanism in which the glucocorticoid receptor (GR) antagonizes AP-1, AP-1 and GR synergistically activated Notch4 transcription in endothelial cells. Fibroblast growth factor 2 (FGF-2) and cortisol induced AP-1 and GR occupancy, respectively, at a Notch4 promoter composite response element consisting of an imperfect half-glucocorticoid response element and an AP-1 motif, which mediated signal-dependent activation. Analysis of Notch4 promoter complex assembly provided evidence that GR and AP-1 independently occupy the composite response element, but AP-1 stabilizes GR occupancy. In multipotent 10T1/2 cells, FGF-2 and cortisol induced a histone modification pattern at the Notch4 locus mimicking that present in endothelial cells and reprogrammed Notch4 from a repressed to an active state. These results establish the molecular basis for a novel AP-1/GR-Notch4 axis in vascular endothelium.
24
Carrasco, Andres, and Stephen G. Lomber. "Neuronal activation times to simple, complex, and natural sounds in cat primary and nonprimary auditory cortex." Journal of Neurophysiology 106, no. 3 (September 2011): 1166–78. http://dx.doi.org/10.1152/jn.00940.2010.
Full textAbstract:
Interactions between living organisms and the environment are commonly regulated by accurate and timely processing of sensory signals. Hence, behavioral response engagement by an organism is typically constrained by the arrival time of sensory information to the brain. While psychophysical response latencies to acoustic information have been investigated, little is known about how variations in neuronal response time relate to sensory signal characteristics. Consequently, the primary objective of the present investigation was to determine the pattern of neuronal activation induced by simple (pure tones), complex (noise bursts and frequency modulated sweeps), and natural (conspecific vocalizations) acoustic signals of different durations in cat auditory cortex. Our analysis revealed three major cortical response characteristics. First, latency measures systematically increase in an antero-dorsal to postero-ventral direction among regions of auditory cortex. Second, complex acoustic stimuli reliably provoke faster neuronal response engagement than simple stimuli. Third, variations in neuronal response time induced by changes in stimulus duration are dependent on acoustic spectral features. Collectively, these results demonstrate that acoustic signals, regardless of complexity, induce a directional pattern of activation in auditory cortex.
25
Wang, Yifei, and Robert J. Binder. "CD91-Dependent Release of IL-1β by GP96 Involves the Activation of the Inflammasome Complex." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 151.23. http://dx.doi.org/10.4049/jimmunol.198.supp.151.23.
Full textAbstract:
Abstract The immunogenic heat shock protein, gp96, binds to CD91 to elite an immune response, characterized by cross-presentation of chaperoned peptides and release of cytokines, including IL-1β. IL-1β is pro-inflammatory cytokine, which is secreted by immune cells upon sensing pathogen associated molecular pattern (PAMP) or damage associated molecular pattern (DAMP). IL-1β is synthesized as a precursor protein, and requires cleavage by Caspase-1 to the matured IL-1β which is released from the cells. Caspase-1 activation requires the inflammasome protein complex. For Inflammasome activation, signal 1 induces pro-inflammatory gene transcription, and signal 2 activates Inflammasome. We have previously shown that gp96 induces NFκB activation and IL-1β secretion via CD91.1 Here we examined the utilization of the inflammasome for IL-1β in this setting. We report that gp96 is able to work as signal 1 to prime production of pro-IL-1β in APCs and in a dose-dependent manner. The kinetics of priming pro-IL-1β differ between gp96 and other PAMPs such as LPS. We will explore the dependence of IL-1β release on the inflammasome.
26
Peng, Yujun, Rowan van Wersch, and Yuelin Zhang. "Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity." Molecular Plant-Microbe Interactions® 31, no. 4 (April 2018): 403–9. http://dx.doi.org/10.1094/mpmi-06-17-0145-cr.
Full textAbstract:
Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane–localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane–localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.
27
Walmsley, M. E., M. J. Guille, D. Bertwistle, J. C. Smith, J. A. Pizzey, and R. K. Patient. "Negative control of Xenopus GATA-2 by activin and noggin with eventual expression in precursors of the ventral blood islands." Development 120, no. 9 (September 1, 1994): 2519–29. http://dx.doi.org/10.1242/dev.120.9.2519.
Full textAbstract:
To increase our understanding of haematopoiesis during early vertebrate development, we have studied the expression pattern of the transcription factor GATA-2 in Xenopus embryos, and asked how this is regulated. We show that the blood island precursors of the ventral mesoderm express GATA-2 RNA at neural tube stages, some 5 hours before globin RNA is detected in their derivatives. Prior to this however, GATA-2 is expressed much more widely within the embryo. Maternal transcripts are uniformly distributed, and zygotic transcription is activated during gastrulation throughout ventral and lateral regions of the embryo, with expression highest in the sensorial ectoderm and only weak in the ventral mesoderm. The domain of GATA-2 expression in neurulae outlines the region of the neural plate and suggests a possible wider role in dorsoventral patterning. To identify the signals involved in regulating this pattern of expression, we performed experiments with embryo explants. GATA-2 is activated autonomously in isolated animal caps and this activation is suppressed by the mesoderm-inducing factor activin, but not by FGF. Thus, the down-regulation of GATA-2 observed in the region of the Spemann organiser may be a response to an activin-like signal emanating from the dorsal-vegetal region or Nieuwkoop centre. GATA-2 activation in animal caps and ventral marginal zones was suppressed by co-culturing with dorsal marginal zones, suggesting that a signal from the Spemann organiser is involved in suppression of GATA-2 in the dorsal region of the embryo. Expression of a candidate for this signal, noggin, had the same effect. Taken together, the observations presented here suggest that GATA-2 activation occurs by default in the absence of signals, that the restriction of its expression within the early embryo is controlled by negative signals emanating from the Nieuwkoop centre and the organiser, and that noggin and activin-like molecules play a role in these signalling pathways.
28
Ivashkiv, L. B., E. M. Schmitt, and A. Castro. "Inhibition of transcription factor Stat1 activity in mononuclear cell cultures and T cells by the cyclic AMP signaling pathway." Journal of Immunology 157, no. 4 (August 15, 1996): 1415–21. http://dx.doi.org/10.4049/jimmunol.157.4.1415.
Full textAbstract:
Abstract Activation of T cells results in a cascade of gene activation and subsequent proliferation and differentiation into effector phenotypes. The regulation of transcription factors belonging to the signal transducer and activator of transcription (STAT) family was analyzed in PHA-activated mononuclear cells and in purified T cells activated by cross-linking cell surface CD3. Cell activation resulted in a delayed induction of STAT DNA-binding activity, which was sustained for several days, was composed predominantly of Stat1 and Stat3, and was blocked by cycloheximide and actinomycin D. Increased Stat1 and Stat3 mRNA and protein levels were detected, respectively 4 and 24 h after activation. Stimulation of the cAMP signal transduction pathway, which skews cytokine production toward a Th2 pattern, resulted in the preferential suppression of Stat1 activity. cAMP inhibited the induction of expression of IL-2 receptor components, but did not inhibit IL-4 receptor alpha-chain and CD69 expression or the induction of activator protein 1 transcription factors. cAMP signaling inhibited Stat1 at several different levels, including suppression of DNA binding and down-regulation of Stat1 protein and mRNA levels. Our results demonstrate the regulation of STAT activity by a signaling pathway that regulates the T cell functional phenotype and is distinct from the cytokine-activated Janus kinase-STAT signaling pathway.
29
DeFilippis, Victor R., David Alvarado, Tina Sali, Stefan Rothenburg, and Klaus Früh. "Human Cytomegalovirus Induces the Interferon Response via the DNA Sensor ZBP1." Journal of Virology 84, no. 1 (October 21, 2009): 585–98. http://dx.doi.org/10.1128/jvi.01748-09.
Full textAbstract:
ABSTRACT Human cytomegalovirus (HCMV) is a member of the betaherpesvirus family that, unlike other herpesviruses, triggers a strong innate immune response in infected cells that includes transcription of the beta interferon gene via activation of interferon regulatory factor 3 (IRF3). IRF3 activation requires signaling from pattern recognition receptors that is initiated by their interaction with specific pathogen-associated molecules. However, while IRF3-activating pathways are increasingly well characterized, the cellular molecules involved in HCMV-mediated IRF3-dependent beta interferon transcription are virtually unknown. We undertook a systematic examination of new and established IRF3-terminal pathway components to identify those that are essential to HCMV-triggered IRF3 activation. We show here that IRF3 activation induced by HCMV infection involves the newly identified protein STING but, in contrast to infections with other herpesviruses, occurs independently of the adaptor molecule IPS-1. We also show that the protein DDX3 contributes to HCMV-triggered expression of beta interferon. Moreover, we identify Z-DNA binding protein 1 (ZBP1) as being essential for IRF3 activation and interferon beta expression triggered by HCMV, as well as being sufficient to enhance HCMV-stimulated beta interferon transcription and secretion. ZBP1 transcription was also found to be induced following exposure to HCMV in a JAK/STAT-dependent manner, thus perhaps also contributing to a positive feedback signal. Finally, we show that constitutive overexpression of ZBP1 inhibits HCMV replication. ZBP1 was recently identified as a cytosolic pattern recognition receptor of double-stranded DNA, and thus, we propose a model for HCMV-mediated IRF3 activation that involves HCMV-associated DNA as the principal innate immune-activating pathogen-associated molecular pattern.
30
Mudter, Jonas, Benno Weigmann, Brigitte Bartsch, Ralf Kiesslich, Dennis Strand, Peter R. Galle, Hans A. Lehr, Jan Schmidt, and Markus F. Neurath. "Activation Pattern of Signal Transducers and Activators of Transcription (STAT) Factors in Inflammatory Bowel Diseases." American Journal of Gastroenterology 100, no. 1 (January 2005): 64–72. http://dx.doi.org/10.1111/j.1572-0241.2005.40615.x.
Full text
31
Rose, D. M., B. W. Winston, E. D. Chan, D. W. Riches, P. Gerwins, G. L. Johnson, and P. M. Henson. "Fc gamma receptor cross-linking activates p42, p38, and JNK/SAPK mitogen-activated protein kinases in murine macrophages: role for p42MAPK in Fc gamma receptor-stimulated TNF-alpha synthesis." Journal of Immunology 158, no. 7 (April 1, 1997): 3433–38. http://dx.doi.org/10.4049/jimmunol.158.7.3433.
Full textAbstract:
Abstract Fc gamma R cross-linking on murine macrophages resulted in the activation of mitogen-activated protein kinase (MAPK) family members p42MAPK, p38, and c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK). The temporal pattern of activation was distinct for each kinase. p42MAPK activation peaked at 5 min after receptor cross-linking, while peak p38 activity occurred 5 to 10 min later. Maximal JNK/SAPK activation occurred 20 min after Fc gamma R cross-linking. The selective MAPK/extracellular signal-regulated kinase-1 (MEK-1) inhibitor PD 098059 inhibited activation of p42MAPK induced by Fc gamma R cross-linking, but not p38 or JNK/SAPK activation. PD 098059 also inhibited the synthesis of TNF-alpha induced by Fc gamma R cross-linking (IC50 approximately 0.1 microM). Together, these results suggest that 1) the activation of MAPKs may play a role in Fc gammaR signal transduction, and 2) the activation of p42MAPK is necessary for Fc gamma R cross-linking-induced TNF-alpha synthesis.
32
Gebert, Carol A., Soo-Hee Park, and David J. Waxman. "Regulation of Signal Transducer and Activator of Transcription (STAT) 5b Activation by the Temporal Pattern of Growth Hormone Stimulation." Molecular Endocrinology 11, no. 4 (April 1, 1997): 400–414. http://dx.doi.org/10.1210/mend.11.4.9904.
Full text
33
Pandey, Sanjay, Saurabh Singh, Vandana Anang, Anant N. Bhatt, K. Natarajan, and Bilikere S. Dwarakanath. "Pattern Recognition Receptors in Cancer Progression and Metastasis." Cancer Growth and Metastasis 8 (January 2015): CGM.S24314. http://dx.doi.org/10.4137/cgm.s24314.
Full textAbstract:
The innate immune system is an integral component of the inflammatory response to pathophysiological stimuli. Toll-like receptors (TLRs) and inflammasomes are the major sensors and pattern recognition receptors (PRRs) of the innate immune system that activate stimulus (signal)-specific proinflammatory responses. Chronic activation of PRRs has been found to be associated with the aggressiveness of various cancers and poor prognosis. Involvement of PRRs was earlier considered to be limited to infection- and injury-driven carcinogenesis, where they are activated by pathogenic ligands. With the recognition of damage-associated molecular patterns (DAMPs) as ligands of PRRs, the role of PRRs in carcinogenesis has also been implicated in other non-pathogen-driven neoplasms. Dying (apoptotic or necrotic) cells shed a plethora of DAMPs causing persistent activation of PRRs, leading to chronic inflammation and carcinogenesis. Such chronic activation of TLRs promotes tumor cell proliferation and enhances tumor cell invasion and metastasis by regulating pro-inflammatory cytokines, metalloproteinases, and integrins. Due to the decisive role of PRRs in carcinogenesis, targeting PRRs appears to be an effective cancer-preventive strategy. This review provides a brief account on the association of PRRs with various cancers and their role in carcinogenesis.
34
Hsieh, P. J., J. T. Colas, and N. Kanwisher. "Spatial pattern of BOLD fMRI activation reveals cross-modal information in auditory cortex." Journal of Neurophysiology 107, no. 12 (June 15, 2012): 3428–32. http://dx.doi.org/10.1152/jn.01094.2010.
Full textAbstract:
Recent findings suggest that neural representations in early auditory cortex reflect not only the physical properties of a stimulus, but also high-level, top-down, and even cross-modal information. However, the nature of cross-modal information in auditory cortex remains poorly understood. Here, we used pattern analyses of fMRI data to ask whether early auditory cortex contains information about the visual environment. Our data show that 1) early auditory cortex contained information about a visual stimulus when there was no bottom-up auditory signal, and that 2) no influence of visual stimulation was observed in auditory cortex when visual stimuli did not provide a context relevant to audition. Our findings attest to the capacity of auditory cortex to reflect high-level, top-down, and cross-modal information and indicate that the spatial patterns of activation in auditory cortex reflect contextual/implied auditory information but not visual information per se.
35
Dhodapkar, Kavita M., Devi Banerjee, John Connolly, Anjli Kukreja, Elyana Matayeva, Maria Concetta Veri, Jeffrey V. Ravetch, Ralph M. Steinman, and Madhav V. Dhodapkar. "Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program." Journal of Experimental Medicine 204, no. 6 (May 14, 2007): 1359–69. http://dx.doi.org/10.1084/jem.20062545.
Full textAbstract:
The ability of dendritic cells (DCs) to activate immunity is linked to their maturation status. In prior studies, we have shown that selective antibody-mediated blockade of inhibitory FcγRIIB receptor on human DCs in the presence of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced immunity to antibody-coated tumor cells. We show that Fcγ receptor (FcγR)–mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene expression pattern, including several inflammation-associated chemokines, as well as type 1 interferon (IFN) response genes, including the activation of signal transducer and activator of transcription 1 (STAT1). FcγR-mediated STAT1 activation is rapid and requires activating FcγRs. However, this IFN response is observed without a detectable increase in the expression of type I IFNs themselves or the need to add exogenous IFNs. Induction of IFN response genes plays an important role in FcγR-mediated effects on DCs, as suppression of STAT1 by RNA interference inhibited FcγR-mediated DC maturation. These data suggest that the balance of activating/inhibitory FcγRs may regulate IFN signaling in myeloid cells. Manipulation of FcγR balance on DCs and monocytes may provide a novel approach to regulating IFN-mediated pathways in autoimmunity and human cancer.
36
Bilder, D., Y. Graba, and M. P. Scott. "Wnt and TGFbeta signals subdivide the AbdA Hox domain during Drosophila mesoderm patterning." Development 125, no. 9 (May 1, 1998): 1781–90. http://dx.doi.org/10.1242/dev.125.9.1781.
Full textAbstract:
Hox genes have large expression domains yet control the formation of fine pattern elements at specific locations. We have examined the mechanism underlying subdivision of the abdominal-A (abdA) Hox domain in the visceral mesoderm. AbdA directs formation of an embryonic midgut constriction at a precise location within the broad and uniform abdA expression domain. The constriction divides the abdA domain of the midgut into two chambers, the anterior one producing the Pointed (Pnt) ETS transcription factors and the posterior one the Odd-paired (Opa) zinc finger protein. Transcription of both pnt and opa is activated by abdA but the adjacent non-overlapping patterns are not due to mutual opa-pnt regulation. Near the anterior limit of the abdA domain, two signals, Dpp (a TGFbeta) and Wg (a Wnt), are produced, in adjacent non-overlapping patterns, under Hox control in mesoderm cells. The two signals are known to regulate local mesodermal cell fates and to signal to the endoderm. We find that, in addition, they precisely subdivide the abdA domain: Wg acts upon anterior abdA domain cells to activate pnt transcription, while Dpp is essential in the same region to prevent abdA from activating opa transcription. pnt activation is required to determine the appropriate numbers of mesodermal cells in the third midgut chamber.
37
Thiel, Gerald, Isabelle Müller, and Oliver G. Rössler. "Signal transduction via TRPM3 channels in pancreatic β-cells." Journal of Molecular Endocrinology 50, no. 3 (March 19, 2013): R75—R83. http://dx.doi.org/10.1530/jme-12-0237.
Full textAbstract:
Transient receptor potential melastatin 3 (TRPM3) channels are non-selective cation channels that are expressed in insulinoma cells and pancreatic β-cells. Stimulation of TRPM3 with the neurosteroid pregnenolone sulfate induces an intracellular signaling cascade, involving a rise in intracellular Ca2+concentration, activation of the protein kinases Raf and ERK, and a change in the gene expression pattern of the cells. In particular, biosynthesis of insulin is altered following activation of TRPM3 by pregnenolone sulfate. Moreover, a direct effect of TRPM3 stimulation on insulin secretion has been reported. The fact that stimulation of TRPM3 induces a signaling cascade that is very similar to the signaling cascade induced by glucose in β-cells suggests that TRPM3 may influence main functions of pancreatic β-cells. The view that TRPM3 represents an ionotropic steroid receptor of pancreatic β-cells linking insulin release with steroid hormone signaling is discussed.
38
Triantafilou, Kathy, Christopher J. K. Ward, Magdalena Czubala, Robert G. Ferris, Emma Koppe, Curt Haffner, Vincent Piguet, et al. "Differential recognition of HIV-stimulated IL-1β and IL-18 secretion through NLR and NAIP signalling in monocyte-derived macrophages." PLOS Pathogens 17, no. 4 (April 16, 2021): e1009417. http://dx.doi.org/10.1371/journal.ppat.1009417.
Full textAbstract:
Macrophages are important drivers of pathogenesis and progression to AIDS in HIV infection. The virus in the later phases of the infection is often predominantly macrophage-tropic and this tropism contributes to a chronic inflammatory and immune activation state that is observed in HIV patients. Pattern recognition receptors of the innate immune system are the key molecules that recognise HIV and mount the inflammatory responses in macrophages. The innate immune response against HIV-1 is potent and elicits caspase-1-dependent pro-inflammatory cytokine production of IL-1β and IL-18. Although, NLRP3 has been reported as an inflammasome sensor dictating this response little is known about the pattern recognition receptors that trigger the “priming” signal for inflammasome activation, the NLRs involved or the HIV components that trigger the response. Using a combination of siRNA knockdowns in monocyte derived macrophages (MDMs) of different TLRs and NLRs as well as chemical inhibition, it was demonstrated that HIV Vpu could trigger inflammasome activation via TLR4/NLRP3 leading to IL-1β/IL-18 secretion. The priming signal is triggered via TLR4, whereas the activation signal is triggered by direct effects on Kv1.3 channels, causing K+ efflux. In contrast, HIV gp41 could trigger IL-18 production via NAIP/NLRC4, independently of priming, as a one-step inflammasome activation. NAIP binds directly to the cytoplasmic tail of HIV envelope protein gp41 and represents the first non-bacterial ligand for the NAIP/NLRC4 inflammasome. These divergent pathways represent novel targets to resolve specific inflammatory pathologies associated with HIV-1 infection in macrophages.
39
Dairaghi, Daniel J., Kenneth S. Soo, Elizabeth R. Oldham, Brett A. Premack, Toshio Kitamura, Kevin B. Bacon, and Thomas J. Schall. "RANTES-Induced T Cell Activation Correlates with CD3 Expression." Journal of Immunology 160, no. 1 (January 1, 1998): 426–33. http://dx.doi.org/10.4049/jimmunol.160.1.426.
Full textAbstract:
Abstract The chemokine RANTES induces a unique biphasic cytoplasmic Ca2+ signal in T cells. The first phase of this signal, similar to that of other chemokines, is G-protein mediated and chemotaxis associated. The second phase of this signal, unique to RANTES and evident at concentrations greater than 100 nM, is tyrosine kinase linked and results in a spectrum of responses similar to those seen with antigenic stimulation of T cells. We show here that certain Jurkat T cells responded to RANTES solely through this latter pathway. A direct correlation between the RANTES-induced second phase response and CD3 expression was demonstrated in these cells. Sorting the Jurkat cells into CD3high and CD3low populations revealed that only the CD3high cells were responsive to RANTES. Furthermore, stimulation of these Jurkat cells with anti-CD3 mAb significantly depresses their subsequent response to RANTES. While a RANTES-specific chemokine receptor is expressed at a low level on these Jurkat cells, the RANTES-induced activation is dependent on the presence of the TCR. Thus, stimulation through TCR may partially account for RANTES’ unique pattern of signaling in T cells.
40
LEDAS, ŽILVINAS, REMIGIJUS ŠIMKUS, and ROMAS BARONAS. "COMPUTATIONAL MODELING OF SELF-ORGANIZATION OF BACTERIAL POPULATION CONSISTING OF SUBPOPULATIONS OF ACTIVE AND PASSIVE CELLS." Journal of Biological Systems 27, no. 03 (September 2019): 365–81. http://dx.doi.org/10.1142/s0218339019500153.
Full textAbstract:
This paper deals with the computational modeling of the bioluminescence pattern formation in suspensions of Escherichia coli bacteria. The aim was to develop a computational model for simulating the bacterial populations consisting of two subpopulations of active and passive cells. A suitable model based on Keller–Segel and Fisher equations was proposed and the spatiotemporal patterns were simulated using the finite difference technique. The influence of cell activation, deactivation, chemotactic sensitivity, growth rate and saturating signal production parameter values on the pattern formation was investigated. The proposed model can be used to effectively simulate quasi-one-dimensional spatiotemporal patterns. We provide a simple qualitative explanation of the experimental results and estimated model parameters. In particular, it is argued that the effective model simulates patterns of evaporation-driven convection in open-to-air suspensions of cells that can be either active or passive.
41
Cintas, Celia, Skyler Speakman, Girmaw Abebe Tadesse, Victor Akinwande, Edward McFowland, and Komminist Weldemariam. "Pattern detection in the activation space for identifying synthesized content." Pattern Recognition Letters 153 (January 2022): 207–13. http://dx.doi.org/10.1016/j.patrec.2021.12.007.
Full text
42
Westgaard, R. H., P. Bonato, and K. A. Holte. "Low-Frequency Oscillations (<0.3 Hz) in the Electromyographic (EMG) Activity of the Human Trapezius Muscle During Sleep." Journal of Neurophysiology 88, no. 3 (September 1, 2002): 1177–84. http://dx.doi.org/10.1152/jn.2002.88.3.1177.
Full textAbstract:
The surface electromyographic (EMG) signal from right and left trapezius muscles and the heart rate were recorded over 24 h in 27 healthy female subjects. The root-mean-square (RMS) value of the surface EMG signals and the heartbeat interval time series were calculated with a time resolution of 0.2 s. The EMG activity during sleep showed long periods with stable mean amplitude, modulated by rhythmic components in the frequency range 0.05–0.2 Hz. The ratio between the amplitude of the oscillatory components and the mean amplitude of the EMG signal was approximately constant over the range within which the phenomenon was observed, corresponding to a peak-to-peak oscillatory amplitude of ∼10% of the mean amplitude. The duration of the periods with stable mean amplitude ranged from a few minutes to ∼1 h, usually interrupted by a sudden change in the activity level or by cessation of the muscle activity. Right and left trapezius muscles presented the same pattern of FM. In supplementary experiments, rhythmic muscle activity pattern was also demonstrated in the upper extremity muscles of deltoid, biceps, and forearm flexor muscles. There was no apparent association between the rhythmic components in the muscle activity pattern and the heart rate variability. To our knowledge, this is the first time that the above-described pattern of EMG activity during sleep is documented. On reanalysis of earlier recorded trapezius motor unit firing pattern in experiments on awake subjects in a situation with mental stress, low-FM of firing with similar frequency content was detected. Possible sources of rhythmic excitation of trapezius motoneurons include slow-wave cortical oscillations represented in descending cortico-spinal pathways, and/or activation by monoaminergic pathways originating in the brain stem reticular formation. The analysis of muscle activity patterns may provide an important new tool to study neural mechanisms in human sleep.
43
Mooney, N. A., C. Grillot-Courvalin, C. Hivroz, L. Y. Ju, and D. Charron. "Early biochemical events after MHC class II-mediated signaling on human B lymphocytes." Journal of Immunology 145, no. 7 (October 1, 1990): 2070–76. http://dx.doi.org/10.4049/jimmunol.145.7.2070.
Full textAbstract:
Abstract These studies examined the role of the MHC class II Ag in signal transduction using human B lymphocytes. Early events in signal transduction were considered including the intracellular calcium [Ca2+)i) flux, the activation of phospholipase C, and induction of protein phosphorylation. The (Ca2+)i was enhanced after incubation of B lymphocytes with several mAb anti-HLA class II and cross-linking with rabbit anti-mouse-F(ab')2. We have also demonstrated an enhancement of the (Ca2+)i in response to a suboptimal concentration of a monoclonal anti-IgM either in the presence of or after preincubation with a mAb anti-HLA class II. The activation of phospholipase C was assessed by measuring the generation of inositol phosphates in permeabilized B lymphocytes. mAb anti-HLA-class II of two different epitopes were used to demonstrate both the (Ca2+)i flux and the generation of inositol phosphates. Two-dimensional gel electrophoresis was used to investigate the phosphorylation pattern of resting B lymphocytes and the changes in the pattern after stimulation with soluble mAb anti-HLA-DR, immobilized mAb anti-HLA-DR, and PMA. In addition to the augmentation of phosphorylation observed with regard to phosphoproteins already present in resting B lymphocytes, new phosphorylations were observed after stimulation by any one of the reagents. Furthermore, stimulation by PMA did not result in an identical pattern to that observed after stimulation by mAb anti-HLA class II. An inhibition of the proliferative response to PMA was demonstrated after prestimulation of cells with immobilized mAb anti-HLA-DR, supporting the notion of a shared pathway of activation. In summary, these data demonstrate signal transduction via MHC class II Ag as assessed by three different measures of early events in human B lymphocyte activation and suggest that a protein kinase C pathway is at least partly involved.
44
Ma’at, Suprapto. "Toll-like Receptor (TLR) dan Imunitas Natura." INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY 15, no. 3 (March 16, 2018): 111. http://dx.doi.org/10.24293/ijcpml.v15i3.978.
Full textAbstract:
In all living species, the first line of defence against microbial aggressions is constituted by innate immunity. Toll-like receptors(TLRs) are a family of pattern recognition receptors that are activated by specific components of microbes and certain host molecules.They constitute the first line of defense against many pathogens and play a crucial role in the function of the innate immune system.Recognition of pathogen-associated molecular pattern (PAMP) by TLR, alone or heterodimerization with other TLR or non-TLR receptors,induces signals responsible for the activation of genes important for an effective host defense, especially proinflammatory cytokines, orinitiates signal transduction pathways, which trigger expression of genes. These gene products control innate immune responses andfurther instruct development of antigen-specific acquired immunity.
45
Greenfeld, Hannah, Jerome Lin, and Mary C. Mullins. "The BMP signaling gradient is interpreted through concentration thresholds in dorsal–ventral axial patterning." PLOS Biology 19, no. 1 (January 22, 2021): e3001059. http://dx.doi.org/10.1371/journal.pbio.3001059.
Full textAbstract:
Bone Morphogenetic Protein (BMP) patterns the dorsal–ventral (DV) embryonic axis in all vertebrates, but it is unknown how cells along the DV axis interpret and translate the gradient of BMP signaling into differential gene activation that will give rise to distinct cell fates. To determine the mechanism of BMP morphogen interpretation in the zebrafish gastrula, we identified 57 genes that are directly activated by BMP signaling. By using Seurat analysis of single-cell RNA sequencing (scRNA-seq) data, we found that these genes are expressed in at least 3 distinct DV domains of the embryo. We distinguished between 3 models of BMP signal interpretation in which cells activate distinct gene expression through interpretation of thresholds of (1) the BMP signaling gradient slope; (2) the BMP signal duration; or (3) the level of BMP signal activation. We tested these 3 models using quantitative measurements of phosphorylated Smad5 (pSmad5) and by examining the spatial relationship between BMP signaling and activation of different target genes at single-cell resolution across the embryo. We found that BMP signaling gradient slope or BMP exposure duration did not account for the differential target gene expression domains. Instead, we show that cells respond to 3 distinct levels of BMP signaling activity to activate and position target gene expression. Together, we demonstrate that distinct pSmad5 threshold levels activate spatially distinct target genes to pattern the DV axis.
46
Kaya, Ali I., Nicole A. Perry, Vsevolod V. Gurevich, and T. M. Iverson. "Phosphorylation barcode-dependent signal bias of the dopamine D1 receptor." Proceedings of the National Academy of Sciences 117, no. 25 (June 5, 2020): 14139–49. http://dx.doi.org/10.1073/pnas.1918736117.
Full textAbstract:
Agonist-activated G protein-coupled receptors (GPCRs) must correctly select from hundreds of potential downstream signaling cascades and effectors. To accomplish this, GPCRs first bind to an intermediary signaling protein, such as G protein or arrestin. These intermediaries initiate signaling cascades that promote the activity of different effectors, including several protein kinases. The relative roles of G proteins versus arrestins in initiating and directing signaling is hotly debated, and it remains unclear how the correct final signaling pathway is chosen given the ready availability of protein partners. Here, we begin to deconvolute the process of signal bias from the dopamine D1 receptor (D1R) by exploring factors that promote the activation of ERK1/2 or Src, the kinases that lead to cell growth and proliferation. We found that ERK1/2 activation involves both arrestin and Gαs, while Src activation depends solely on arrestin. Interestingly, we found that the phosphorylation pattern influences both arrestin and Gαs coupling, suggesting an additional way the cells regulate G protein signaling. The phosphorylation sites in the D1R intracellular loop 3 are particularly important for directing the binding of G protein versus arrestin and for selecting between the activation of ERK1/2 and Src. Collectively, these studies correlate functional outcomes with a physical basis for signaling bias and provide fundamental information on how GPCR signaling is directed.
47
Li, Dan, Hua Li, Shoudan Liang, Jeffrey J. Molldrem, and Qing Ma. "LFA-1 Regulates CD8 + T Cell Activation and Immune Signal Network." Blood 114, no. 22 (November 20, 2009): 1641. http://dx.doi.org/10.1182/blood.v114.22.1641.1641.
Full textAbstract:
Abstract Abstract 1641 Poster Board I-667 LFA-1 regulates T cell activation and signal transduction through the immunological synapse. TCR stimulation rapidly activates LFA-1, which provides unique LFA-1-dependent signals to promote T cell activation. We found LFA-1 directly participates in Erk1/2 signaling upon TCR stimulation in CD8+ T cells. The presence of LFA-1, not ligand binding, is required for the TCR-mediated Erk1/2 signal pathway. LFA-1-KO T cells have defects in sustained Erk1/2 signaling and TCR/CD3 clustering, which subsequently prevents MTOC re-orientation, cell-cycle progression and mitosis. LFA-1 regulates the TCR-mediated Erk1/2 signal pathway in the context of immunological synapse for recruitment and amplification of Erk1/2 signal. In addition, LFA-1 ligation with ICAM-1 generates an additional Erk1/2 signal, which synergizes with the existing TCR-mediated Erk1/2 signal to enhance T cell activation. We demonstrated that the function of LFA-1 is to enhance TCR signaling through the immunological synapse and deliver distinct signal in CD8+ T cell activation. Based on our results, we proposed a model of TCR-mediated and LFA-1-mediated Erk1/2 signal pathways in CD8+ T cell activation. However, the detailed molecular pathways that regulate these processes and global impact on immune functions are poorly defined. With the launching of The Immunological Genome Project, we have generated data with CD8+ T cell expression array to explore and understand the LFA-1 and TCR signaling network. GeneChip hybridization and analysis CD8+ T cells from C57BL/6 mice and LFA-1-KO mice were collected before and after stimulation. Microarray experiments were carried out using the “ Mouse Whole Genome Oligo Microarray Kit” from Agilent. Differentially expressed gene lists between samples were considered significant if their p values were <0.0001 and their fold-change >1.8. The results are summarized below: 1) 641 genes were up-regulated and 174 were down-regulated in unstimulated LFA-1-KO CD8+ T cells comparing to these in unstimulated WT CD8+ T cells; 2)1036 genes were up-regulated and 406 were down-regulated in activated LFA-1-KO CD8+ T cells comparing to these in activated WT CD8+ T cells after 1 hours stimulation with unstimulated CD8+ T cells as control; 3)636 genes were up-regulated and 354 were down-regulated in activated LFA-1-KO CD8+ T cells comparing to these in activated WT CD8+ T cells after 8 hours stimulation with unstimulated CD8+ T cells as control. To estimate which pathways are significantly enriched among the genes that are differentially expressed, we used a database IPA (Ingenuity Pathways Analysis) software. Signaling pathways enriched by the genes differentially expressed in activated LFA-1-KO CD8+ T cells vs WT CD8+ T cells after 8 hours stimulation generated the most highly enriched differentially expressed genes in signaling pathways displayed below: 1) Pattern Recognition Receptors in Recognition of Bacteria and Viruses; 2) Activation of IRF by Cytosolic Pattern Recognition Receptors; 3) Aryl Hydrocarbon Receptor Signaling; 4) IL-10 Signaling; p38 MAPK Signaling; 5) LPS/IL-1 Mediated Inhibition of RXR Function; Cell Cycle: G2/M DNA Damage Checkpoint Regulation; 6) Notch Signaling; Natural Killer Cell Signaling; 7) Cell Cycle: G1/S Checkpoint Regulation and Chemokine Signaling. Furthermore, we examined the biological functions enriched by the genes differentially expressed in activated LFA-1-KO CD8+ T cells vs WT CD8+ T cells. The LFA-1-KO CD8+ T cells vs WT CD8+ T cells after 8 hours stimulation generated the most highly enriched differentially expressed genes in following biological functions: Immunological Disease; Antigen Presentation; Cell-mediated Immune Response; Humoral Immune Response; Inflammatory Response; Cellular Development; Cell-To-Cell Signaling and Interaction; Hematological System Development and Function; Immune Cell Trafficking; Cellular Growth and Proliferation; Inflammatory Disease; Cellular Movement; Hematopoiesis Cell Death; Hematological Disease; Lymphoid Tissue Structure and Development; Infectious Disease; Tissue Development and Cancer. Our results indicate that LFA-1 plays an important role in the immune signal network and has a global impact on immune system. Disclosures No relevant conflicts of interest to declare.
48
Kim, Juhyon, and Hitoshi Kita. "Short-term plasticity shapes activity pattern-dependent striato-pallidal synaptic transmission." Journal of Neurophysiology 109, no. 4 (February 15, 2013): 932–39. http://dx.doi.org/10.1152/jn.00459.2012.
Full textAbstract:
The cortico-striato (Str)-globus pallidus external segment (GPe) projection plays major roles in the control of neuronal activity in the basal ganglia under both normal and pathological conditions. The present study used rat brain-slice preparations to address our hypothesis that the gain of this disynaptic projection is dynamically controlled by activations of short-term plasticity mechanisms of Str-GPe synapses. The Str-GPe projection neurons fire with very different frequency and firing patterns in vivo depending on the condition of the animal. The results show that the Str-GPe synapses have very strong short-term enhancement mechanisms and that repetitive burst activation of the Str-GPe synapses, which mimic oscillatory burst firing of Str neurons, can sustain enhanced states of synaptic transmission for tens of seconds. The results reveal that the short-term enhancement of Str-GPe synapses contributes to the generation of pauses in the firing of GPe neurons and that signal transfer function in the Str-GPe projection is highly dependent on the firing pattern of Str neurons.
49
O’Reilly, Steven. "Pound the alarm: danger signals in rheumatic diseases." Clinical Science 128, no. 5 (November 5, 2014): 297–305. http://dx.doi.org/10.1042/cs20140467.
Full textAbstract:
Damage-associated molecular patterns (DAMPs) are chemically heterogeneous endogenous host molecules rapidly released from damaged or dying cells that incite a sterile inflammatory response mediated via pattern recognition receptors (PRRs). The sources of DAMPs are dead or dying cells or the extracellular matrix and can signal through the PRRs, the Toll-like receptors or cytosolic Nod-like receptors, culminating in nuclear factor κB (NF-κB) activation and pro-inflammatory cytokine secretion. Together, these molecules are involved in sterile inflammation and many are associated with rheumatic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythromatosus, psoriatic arthritis and systemic sclerosis. These diseases are associated with inflammation and many danger signals are found in sites of sterile inflammation and mediate inflammation. The present review examines the role of DAMPs in rheumatic conditions and suggests avenues for their therapeutic modulation.
50
Wu-Hsieh, Betty, Tzu-Hsuan Chang, and Juin-Hua Huang. "Dectin-2 as a Primary Receptor for NLRP3-inflammasome Activation in Dendritic Cell Responses to Histoplasma capsulatum." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 77.23. http://dx.doi.org/10.4049/jimmunol.198.supp.77.23.
Full textAbstract:
Abstract Inflammasome is an intracellular protein complex that serves as cytosolic pattern recognition receptor (PRR) to engage with pathogens and to process cytokines of the interleukin-1 (IL-1) family into bioactive molecules. It has been established that interleukin-1β (IL-1β) is important to host defense against Histoplasma capsulatum infection. However, the detailed mechanism of how H. capsulatum induces inflammasome activation leading to IL-1β production has not been studied. Here, we showed in dendritic cells (DCs) that H. capsulatum triggers caspase-1 activation and IL-1β production through NLRP3 inflammasome. By reciprocal blocking of Dectin-1 or Dectin-2 in receptor-deficient DCs, we discovered that while Dectin-2 operates as a primary receptor, Dectin-1 serves as a secondary one for NLRP3 inflammasome. Both receptors trigger Syk-JNK signal pathway to activate both signal 1 (the transcription of Il1b) and signal 2 (activation of caspase-1). While both K+ efflux and cathepsin B (but not ROS) function as signal 2, viable H. capsulatum triggers profound lysosomal rupture leading to cathepsin B release. Our study demonstrates the role of Dectin-2 and Dectin-1 in host defense against H. capsulatum infection through induction of NLRP3 inflammasome activation and IL-1b production in DCs.