rCBF in radiation necrosis as measured by xenon-enhanced CT

International Nuclear Information System (INIS)

Nakamura, Osamu; Nomura, Kazuhiro; Segawa, Hiromu; Nakagomi, Tadayoshi; Tanaka, Hideki; Yoshimasu, Norio; Takakura, Kintomo.

1986-01-01

We experienced a case of radiation necrosis in which the necrosis occurred two and a half years after radiation therapy against craniopharyngioma. In this case, we evaluated the regional cerebral blood flow (rCBF) by means of the Xe-enhanced CT method and studied the change in rCBF in comparison with the rCBF pattern of brain tumors or cerebral infarctions. In general, rCBF decreased in accordance with the low-density area in a conventional CT scan. The decrease in rCBF was most significant in the white matter, but the rCBF in the thinned cortex was also lowered. On the contrary, that of the basal ganglia was almost completely preserved. The rCBF pattern was different from those of brain tumors or diffuse cerebral infarction caused by the occlusion of the main arteries and was thought to be characteristic of radiation necrosis. Differential diagnosis between radiation necrosis and the recurrence of brain tumor has been thought to be difficult, but with this rCBF analysis the possibility of differential diagnosis between the two lesions was clearly indicated. (author)

Apparent CBF decrease with normal aging due to partial volume effects: MR-based partial volume correction on CBF SPECT.

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Inoue, Kentaro; Ito, Hiroshi; Goto, Ryoi; Nakagawa, Manabu; Kinomura, Shigeo; Sato, Tachio; Sato, Kazunori; Fukuda, Hiroshi

2005-06-01

Several studies using single photon emission tomography (SPECT) have shown changes in cerebral blood flow (CBF) with age, which were associated with partial volume effects by some authors. Some studies have also demonstrated gender-related differences in CBF. The present study aimed to examine age and gender effects on CBF SPECT images obtained using the 99mTc-ethyl cysteinate dimer and a SPECT scanner, before and after partial volume correction (PVC) using magnetic resonance (MR) imaging. Forty-four healthy subjects (29 males and 15 females; age range, 27-64 y; mean age, 50.0 +/- 9.8 y) participated. Each MR image was segmented to yield grey and white matter images and coregistered to a corresponding SPECT image, followed by convolution to approximate the SPECT spatial resolution. PVC-SPECT images were produced using the convoluted grey matter MR (GM-MR) and white matter MR images. The age and gender effects were assessed using SPM99. Decreases with age were detected in the anterolateral prefrontal cortex and in areas along the lateral sulcus and the lateral ventricle, bilaterally, in the GM-MR images and the SPECT images. In the PVC-SPECT images, decreases in CBF in the lateral prefrontal cortex lost their statistical significance. Decreases in CBF with age found along the lateral sulcus and the lateral ventricle, on the other hand, remained statistically significant, but observation of the spatially normalized MR images suggests that these findings are associated with the dilatation of the lateral sulcus and lateral ventricle, which was not completely compensated for by the spatial normalization procedure. Our present study demonstrated that age effects on CBF in healthy subjects could reflect morphological differences with age in grey matter.

Three grape CBF/DREB1 genes respond to low temperature, drought and abscisic acid.

Science.gov (United States)

Xiao, Huogen; Siddiqua, Mahbuba; Braybrook, Siobhan; Nassuth, Annette

2006-07-01

The C-repeat (CRT)-binding factor/dehydration-responsive element (DRE) binding protein 1 (CBF/ DREB1) transcription factors control an important pathway for increased freezing and drought tolerance in plants. Three CBF/DREB1-like genes, CBF 1-3, were isolated from both freezing-tolerant wild grape (Vitis riparia) and freezing-sensitive cultivated grape (Vitis vinifera). The deduced proteins in V. riparia are 63-70% identical to each other and 96-98% identical to the corresponding proteins in V. vinifera. All Vitis CBF proteins are 42-51% identical to AtCBF1 and contain CBF-specific amino acid motifs, supporting their identification as CBF proteins. Grape CBF sequences are unique in that they contain 20-29 additional amino acids and three serine stretches. Agro-infiltration experiments revealed that VrCBF1b localizes to the nucleus. VrCBF1a, VrCBF1b and VvCBF1 activated a green fluorescent protein (GFP) or glucuronidase (GUS) reporter gene behind CRT-containing promoters. Expression of the endogenous CBF genes was low at ambient temperature and enhanced upon low temperature (4 degrees C) treatment, first for CBF1, followed by CBF2, and about 2 d later by CBF3. No obvious significant difference was observed between V. riparia and V. vinifera genes. The expression levels of all three CBF genes were higher in young tissues than in older tissues. CBF1, 2 and 3 transcripts also accumulated in response to drought and exogenous abscisic acid (ABA) treatment, indicating that grape contains unique CBF genes.

The significance of CBF measurements for precise management of carotid stenosis

Energy Technology Data Exchange (ETDEWEB)

Nakagawara, Jyoji; Kamiyama, Kenji; Usui, Reiko; Takeda, Rihei; Nakamura, Hirohiko [Nakamura Memorial Hospital, Sapporo (Japan)

2002-12-01

Severe hemodynamic cerebral ischemia associated with carotid stenosis could be one of the difining characteristics of the high-risk group for carotid endarterectomy (CEA). Measurements of cerebral blood flow (CBF) and vascular reactivity in patients treated with CEA were analyzed to clarify the significance of preoperative evaluation of hemodynamic cerebral ischemia using CBF-SPECT. Both the resting and acetazolamide-activated rCBF, and the severity of the hemodynamic cerebral ischemia (Stage 0-II) were quantified using the {sup 123}I-IMP autoradiography (ARG) method and preoperative cerebral hemodynamics were compared in both symptomatic patients (n=30) and asymptomatic patients (n=24). Postoperative improvement of resting rCBF was estimated in both groups. Stage II ischemia was quantitatively defined as both a resting rCBF of less than 80% of normal mean CBF and a vascular reserve (VR: (acetazolamide-activated rCBF/Resting rCBF-1) x 100%) of less than 10%. In the other 31 patients treated with CEA, postoperative hyperperfusion was investigated using CBF-SPECT within 24 hours after CEA. Preoperatively, Stage II ischemia (hemodynamically compromised state) was observed in 20% of symptomatic patients and 8% of asymptomatic patients. A significant difference in resting rCBF was indicated between symptomatic patients (31.8{+-}6.1 ml/100 g/min) and asymptomatic patients (37.6{+-}6.6 ml/100 g/min)(p<0.002, t-test). Severity of hemodynamic cerebral ischemia was generally moderate in symptomatic patients. Postoperatively, a significant increase of resting CBF was observed in symptomatic patients but not in asymptomatic patients. In the other 31 patients treated by CEA, symptomatic hyperperfusion was observed in 3 of 4 patients with Stage II ischemia and asymptomatic hyperperfusion was indicated in 3 of 4 patients with Stage I ischemia with a VR of less than 10%. Preoperative CBF measurements in patients treated with CEA were significant to define severe hemodynamic

Core binding factor beta (Cbfβ) controls the balance of chondrocyte proliferation and differentiation by upregulating Indian hedgehog (Ihh) expression and inhibiting parathyroid hormone-related protein receptor (PPR) expression in postnatal cartilage and bone formation.

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Tian, Fei; Wu, Mengrui; Deng, Lianfu; Zhu, Guochun; Ma, Junqing; Gao, Bo; Wang, Lin; Li, Yi-Ping; Chen, Wei

2014-07-01

Core binding factor beta (Cbfβ) is essential for embryonic bone morphogenesis. Yet the mechanisms by which Cbfβ regulates chondrocyte proliferation and differentiation as well as postnatal cartilage and bone formation remain unclear. Hence, using paired-related homeobox transcription factor 1-Cre (Prx1-Cre) mice, mesenchymal stem cell-specific Cbfβ-deficient (Cbfβ(f/f) Prx1-Cre) mice were generated to study the role of Cbfβ in postnatal cartilage and bone development. These mutant mice survived to adulthood but exhibited severe sternum and limb malformations. Sternum ossification was largely delayed in the Cbfβ(f/f) Prx1-Cre mice and the xiphoid process was noncalcified and enlarged. In newborn and 7-day-old Cbfβ(f/f) Prx1-Cre mice, the resting zone was dramatically elongated, the proliferation zone and hypertrophic zone of the growth plates were drastically shortened and disorganized, and trabecular bone formation was reduced. Moreover, in 1-month-old Cbfβ(f/f) Prx1-Cre mice, the growth plates were severely deformed and trabecular bone was almost absent. In addition, Cbfβ deficiency impaired intramembranous bone formation both in vivo and in vitro. Interestingly, although the expression of Indian hedgehog (Ihh) was largely reduced, the expression of parathyroid hormone-related protein (PTHrP) receptor (PPR) was dramatically increased in the Cbfβ(f/f) Prx1-Cre growth plate, indicating that that Cbfβ deficiency disrupted the Ihh-PTHrP negative regulatory loop. Chromatin immunoprecipitation (ChIP) analysis and promoter luciferase assay demonstrated that the Runx/Cbfβ complex binds putative Runx-binding sites of the Ihh promoter regions, and also the Runx/Cbfβ complex directly upregulates Ihh expression at the transcriptional level. Consistently, the expressions of Ihh target genes, including CyclinD1, Ptc, and Pthlh, were downregulated in Cbfβ-deficient chondrocytes. Taken together, our study reveals not only that Cbfβ is essential for chondrocyte

Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

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Su Zhen

2011-07-01

Full Text Available Abstract Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants.

Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

Science.gov (United States)

2011-01-01

Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants. PMID:21718548

A comparison of the low temperature transcriptomes and CBF regulons of three plant species that differ in freezing tolerance: Solanum commersonii, Solanum tuberosum, and Arabidopsis thaliana

OpenAIRE

Carvallo, Marcela A.; Pino, María-Teresa; Jeknić, Zoran; Zou, Cheng; Doherty, Colleen J.; Shiu, Shin-Han; Chen, Tony H. H.; Thomashow, Michael F.

2011-01-01

Solanum commersonii and Solanum tuberosum are closely related plant species that differ in their abilities to cold acclimate; whereas S. commersonii increases in freezing tolerance in response to low temperature, S. tuberosum does not. In Arabidopsis thaliana, cold-regulated genes have been shown to contribute to freezing tolerance, including those that comprise the CBF regulon, genes that are controlled by the CBF transcription factors. The low temperature transcriptomes and CBF regulons of ...

rCBF change in the brain of patients with major depressive disorder

International Nuclear Information System (INIS)

Sun Da; Xu Wei; Zhan Hongwei; Liu Hongbiao

2010-01-01

Purpose Major depressive disorder is a frequent emotional mood disorder. To evaluate the changes of brain blood flow in patients with depressive disorder and the correlation between rCBF and clinical feature is very important to diagnosis and treatment of this decease. Methods: Regional cerebral perfusion was investigated using SPECT in 75 patients with depressive disorders. The mean ages of the patients were 41.9 (17-74) Years old. The course of disease was different from several days to over 20 years. Results: 97.3 per cent of patients (73/75) had relative hypoperfusions in some cerebral regions. The patients had a significant decrease of rCBF in the frontal lobesbilaterally, and temporal lobes, basal ganglia, thalamus and parietal lobe. The course of disease and age of the patients had a negative correlation with the changes of rCBF. Conclusion: According to the results of our study, patients with depressive disorders had profound dysfunction of the frontal lobes bilaterally. The temporal cortices and basal ganglia were involved in most patients too. It is coincident with the results of other studies. The function of frontal lobes and temporal lobes is close relation close with affective action, attention, memory, thinking, abstraction, and other brain cognitive function. The clinical symptom of depressive disorder may be relevant with hypoperfusions of frontal lobes and temporal lobes. (authors)

Regional cerebral blood flow (rCBF) in psychiatry: Methodological issues

International Nuclear Information System (INIS)

Prohovnik, I.

1984-01-01

Traditionally, measurements of regional cerebral blood flow (rCBF) have been confined to neurology and nuclear medicine. Only one laboratory had concentrated on using this technique in psychiatric studies. Recently, however, rCBF has been increasingly used in psychiatry, and it seems appropriate at this time to examine the value and limitations of this method. The present article reviews selected methodological issues that may complicate the performance and interpretation of rCBF studies, with the aim of providing some means to evaluate published work and to plan further psychiatric research. In this paper, the term rCBF refers only to the two-dimensional, noninvasive methods that rely on inhalation or intravenous injection of xenon-133. The growing interest of rCBF to psychiatry stems mostly from the fact that this technique can indirectly map cerebral metabolism and, by interface, neural activity or information processing. Regional metabolism and blood flow are closely coupled to the human brain in the absence of gross pathology, and since psychiatric patients rarely present acute neurological abnormalities that might disrupt this coupling, one may infer regional metabolism from flow

An ancient neurotrophin receptor code; a single Runx/Cbfβ complex determines somatosensory neuron fate specification in zebrafish.

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Gau, Philia; Curtright, Andrew; Condon, Logan; Raible, David W; Dhaka, Ajay

2017-07-01

In terrestrial vertebrates such as birds and mammals, neurotrophin receptor expression is considered fundamental for the specification of distinct somatosensory neuron types where TrkA, TrkB and TrkC specify nociceptors, mechanoceptors and proprioceptors/mechanoceptors, respectively. In turn, Runx transcription factors promote neuronal fate specification by regulating neurotrophin receptor and sensory receptor expression where Runx1 mediates TrkA+ nociceptor diversification while Runx3 promotes a TrkC+ proprioceptive/mechanoceptive fate. Here, we report in zebrafish larvae that orthologs of the neurotrophin receptors in contrast to terrestrial vertebrates mark overlapping and distinct subsets of nociceptors suggesting that TrkA, TrkB and TrkC do not intrinsically promote nociceptor, mechanoceptor and proprioceptor/mechanoceptor neuronal fates, respectively. While we find that zebrafish Runx3 regulates nociceptors in contrast to terrestrial vertebrates, it shares a conserved regulatory mechanism found in terrestrial vertebrate proprioceptors/mechanoceptors in which it promotes TrkC expression and suppresses TrkB expression. We find that Cbfβ, which enhances Runx protein stability and affinity for DNA, serves as an obligate cofactor for Runx in neuronal fate determination. High levels of Runx can compensate for the loss of Cbfβ, indicating that in this context Cbfβ serves solely as a signal amplifier of Runx activity. Our data suggests an alteration/expansion of the neurotrophin receptor code of sensory neurons between larval teleost fish and terrestrial vertebrates, while the essential roles of Runx/Cbfβ in sensory neuron cell fate determination while also expanded are conserved.

Low Residual CBF Variability in Alzheimer's Disease after Correction for CO(2) Effect

DEFF Research Database (Denmark)

Rodell, Anders Bertil; Aanerud, Joel; Braendgaard, Hans

2012-01-01

We tested the claim that inter-individual CBF variability in Alzheimer's disease (AD) is substantially reduced after correction for arterial carbon dioxide tension (PaCO(2)). Specifically, we tested whether the variability of CBF in brain of patients with AD differed significantly from brain of age...... for the differences of CO(2) tension, the patients with AD lost the inter-individual CBF variability that continued to characterize the HC subjects. The difference (¿K(1)) between the blood-brain clearances (K(1)) of water (the current measure of CBF) and oxygen (the current measure of oxygen clearance) was reduced......-matched healthy control subjects (HC). To eliminate the CO(2)-induced variability, we developed a novel and generally applicable approach to the correction of CBF for changes of PaCO(2) and applied the method to positron emission tomographic (PET) measures of CBF in AD and HC groups of subjects. After correction...

Recovery from Unrecognized Sleep Loss Accumulated in Daily Life Improved Mood Regulation via Prefrontal Suppression of Amygdala Activity

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Yuki Motomura

2017-06-01

Full Text Available Many modern people suffer from sleep debt that has accumulated in everyday life but is not subjectively noticed [potential sleep debt (PSD]. Our hypothesis for this study was that resolution of PSD through sleep extension optimizes mood regulation by altering the functional connectivity between the amygdala and prefrontal cortex. Fifteen healthy male participants underwent an experiment consisting of a baseline (BL evaluation followed by two successive interventions, namely, a 9-day sleep extension followed by one night of total sleep deprivation (TSD. Tests performed before and after the interventions included a questionnaire on negative mood and neuroimaging with arterial spin labeling MRI for evaluating regional cerebral blood flow (rCBF and functional connectivity. Negative mood and amygdala rCBF were significantly reduced after sleep extension compared with BL. The amygdala had a significant negative functional connectivity with the medial prefrontal cortex (FCamg–MPFC, and this negative connectivity was greater after sleep extension than at BL. After TSD, these indices reverted to the same level as at BL. An additional path analysis with structural equation modeling showed that the FCamg–MPFC significantly explained the amygdala rCBF and that the amygdala rCBF significantly explained the negative mood. These findings suggest that the use of our sleep extension protocol normalized amygdala activity via negative amygdala–MPFC functional connectivity. The resolution of unnoticed PSD may improve mood by enhancing frontal suppression of hyperactivity in the amygdala caused by PSD accumulating in everyday life.

Effect of simulated weightlessness on the expression of Cbfα1 induced by fluid shear stress in MG-63 osteosarcoma cells.

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Yang, Z.; Zhang, S.; Wang, B.; Sun, X. Q.

Objective The role of mechanical load in the functional regulation of osteoblasts becomes an emphasis in osseous biomechanical researches recently This study was aim to explore the effect of flow shear stress on the expression of Cbf alpha 1 in human osteosarcoma cells and to survey its functional alteration in simulated weightlessness Method After cultured for 72 h in two different gravitational environments i e 1G terrestrial gravitational condition and simulated weightlessness condition human osteosarcoma cells MG-63 were treated with 0 5 Pa or 1 5 Pa fluid shear stress FSS in a flow chamber for 15 30 60 min respectively The total RNA in cells was isolated Transcription PCR analysis was made to examine the gene expression of Cbf alpha 1 And the total protein of cells was extracted and the expression of Cbf alpha 1 protein was detected by means of Western Blotting Results MG-63 cultured in 1G condition reacted to FSS treatment with an enhanced expression of Cbf alpha 1 Compared with no FSS control group Cbf alpha 1 mRNA and protein expression increased significantly at 30 and 60 min with the treatment of FSS P 0 01 And there was remarkable difference on the Cbf alpha 1 mRNA and protein expression between the treatments of 0 5 Pa and 1 5 Pa FSS at 30 min or 60 min P 0 01 As to the osteoblasts cultured in simulated weightlessness by using clinostat the expression of Cbf alpha 1 was significantly different between 1G and simulated weightlessness conditions at each test time P 0 05 Compared with no FSS

Tomographic analysis of CBF in cerebral infarction

International Nuclear Information System (INIS)

Segawa, Hiromu; Kimura, Kazumoto; Ueda, Yuichi; Nagai, Masakatsu; Yoshimasu, Norio.

1983-01-01

Cerebral perfusion was examined in various types of occlusive disease by computed tomographic CBF method. The method utilized has several advantages over conventional studies using isotope, providing high resolution images in a direct relation to CT anatomy. Ten representative cases were presented from 25 consective cases of occlusive disease studied by this method. The method included inhalation of 40 to 60% xenon with serial CT scanning for 25 min. K (build-up rate), lambda (partition coefficient) and CBF values were calculated from ΔHU for each pixel and ΔXe in expired air, based on Fick's principle, and displayed on CRT as K-, lambda- and CBF-map separately. CBF for gray matter of normal control was 82 +- 11 ml/100 gm/min and that for white matter was 24 +- 5 ml/100 gm/min. The ischemic threshold for gray matter appeared to be approximately 20 ml/100 gm/min, as blood flow in focus of complete infarction was below this level. Blood flow between 20 - 30 ml/ 100 gm/min caused some change on CT, such as localized atrophy, cortical thinning, loss of distinction between gray and white matter and decreased or increased density, which were considered to be compatible with pathological changes of laminar necrosis or gliosis with neuronal loss. In a case with occlusion of middle cerebral artery with subsequent recanalization, causing hemorrhagic infarct, hyperemia was observed in the infarcted cortex that was enhanced by iodine. Periventricular lucency observed in two cases, where blood flow was decreased below threshold, could be classified as ''watershed infarction'' mainly involving white matter. In moyamoya disease, blood flow in the anterior circulation was decreased near ischemic level, whereas that in basal ganglia and territory of posterior cerebral artery was fairly preserved, which was compatible with general angiographic finding of this disease. (author)

Memory-provoked rCBF-SPECT as a diagnostic tool in Alzheimer's disease?

International Nuclear Information System (INIS)

Sundstroem, Torbjoern; Riklund, Katrine Aa.; Elgh, Eva; Naesman, Birgitta; Larsson, Anne; Nyberg, Lars

2006-01-01

Alzheimer's disease (AD) is a primary degenerative disease that progressively affects all brain functions, with devastating consequences for the patient, the patient's family and society. Rest regional cerebral blood flow (rCBF) could have a strategic role in differentiating between AD patients and normal controls, but its use for this purpose has a low discriminatory capacity. The purpose of this study was to evaluate whether the diagnostic sensitivity of rCBF single-photon emission computed tomography (SPECT) could be increased by using an episodic memory task provocation, i.e. memory-provoked rCBF-SPECT (MP-SPECT). Eighteen persons (73.2±4.8 years) with mild AD and 18 healthy elderly (69.4±3.9 years) were included in the study. The subjects were injected with 99m Tc-hexamethylpropylene amine oxime (HMPAO) during memory provocation with faces and names, followed by an rCBF-SPECT study. The rCBF 99m Tc-HMPAO SPECT images were analysed using statistical parametric mapping (SPM2). Peaks with a false discovery rate corrected value of 0.05 were considered significant. On MP-SPECT, the AD group showed a significant rCBF reduction in the left parietal cortex in comparison with healthy elderly. At rest, no significant group differences were seen. Memory provocation increased the sensitivity of rCBF-SPECT for the detection of AD-related blood flow changes in the brain at the group level. Further studies are needed to evaluate MP-SPECT as a diagnostic tool at the individual level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might be sufficient in the clinical setting. (orig.)

The correlative analysis between CBF measured by SPECT and Chinese reading test in childhood reading disorder

International Nuclear Information System (INIS)

Wu Yonggang; Su Jianzhi; He Jianjun; Yang Zhiwei; Liu Guofeng

2002-01-01

Objective: To investigate changes of cerebral blood flow (CBF) and its association with Chinese reading skill diagnostic test (CRSDT) in childhood reading disorder (RD). Methods: In 25 RD children and 20 age-matched control subjects, the authors quantitatively determined CBF and regional cerebral blood flow (rCBF) with SPECT using the non-blood-withdrew method. The authors studied the correlation between the CBF and the total raw scores by CRSDT. Results: CBF in case group was (38.87 +- 3.77) ml·100 g -1 ·min -1 and was significantly lower than that in control group [43.65 +- 2.64) mL·100 g -1 ·min -1 (P < 0.01)]. These reduction in CBF correlated with the total raw scores by CRSDT. Conclusion: These results suggest the children with reading disorder have CBF reduction and SPECT is useful for evaluation of cerebral functioning in reading disorder children

rCBF measurement by one-point venous sampling with the ARG method

International Nuclear Information System (INIS)

Yoshida, Nobuhiro; Okamoto, Toshiaki; Takahashi, Hidekado; Hattori, Teruo

1997-01-01

We investigated the possibility of using venous blood sampling instead of arterial blood sampling for the current method of ARG (autoradiography) used to determine regional cerebral blood flow (rCBF) on the basis of one session of arterial blood sampling and SPECT. For this purpose, the ratio of the arterial blood radioactivity count to the venous blood radioactivity count, the coefficient of variation, and the correlation and differences between arterial blood-based rCBF and venous blood-based rCBF were analyzed. The coefficient of variation was lowest (4.1%) 20 minutes after injection into the dorsum manus. When the relationship between venous and arterial blood counts was analyzed, arterial blood counts correlated well with venous blood counts collected at the dorsum manus 20 or 30 minutes after intravenous injection and with venous blood counts collected at the wrist 20 minutes after intravenous injection (r=0.97 or higher). The difference from rCBF determined on the basis of arterial blood was smallest (0.7) for rCBF determined on the basis of venous blood collected at the dorsum manus 20 minutes after intravenous injection. (author)

Lambda-guided calculation method (LGC method) for xenon/CT CBF

Energy Technology Data Exchange (ETDEWEB)

Sase, Shigeru [Anzai Medical Co., Ltd., Tokyo (Japan); Honda, Mitsuru; Kushida, Tsuyoshi; Seiki, Yoshikatsu; Machida, Keiichi; Shibata, Iekado [Toho Univ., Tokyo (Japan). School of Medicine

2001-12-01

A quantitative CBF calculation method for xenon/CT was developed by logically estimating time-course change rate (rate constant) of arterial xenon concentration from that of end-tidal xenon concentration. A single factor ({gamma}) was introduced to correlate the end-tidal rate constant (Ke) with the arterial rate constant (Ka) in a simplified equation. This factor ({gamma}) is thought to reflect the diffusing capacity of the lung for xenon. When an appropriate value is given to {gamma}, it is possible to calculate the arterial rate constant (Calculated Ka) from Ke. To determine {gamma} for each xenon/CT CBF examination, a procedure was established which utilizes the characteristics of white matter lambda; lambda refers to xenon brain-blood partition coefficient. Xenon/CT studies were performed on four healthy volunteers. Hemispheric CBF values (47.0{+-}9.0 ml/100 g/min) with use of Calculated Ka were close to the reported normative values. For a 27-year-old healthy man, the rate constant for the common carotid artery was successfully measured and nearly equal to Calculated Ka. The authors conclude the method proposed in this work, lambda-guided calculation method, could make xenon/CT CBF substantially reliable and quantitative by effective use of end-tidal xenon. (author)

Lambda-guided calculation method (LGC method) for xenon/CT CBF

International Nuclear Information System (INIS)

Sase, Shigeru; Honda, Mitsuru; Kushida, Tsuyoshi; Seiki, Yoshikatsu; Machida, Keiichi; Shibata, Iekado

2001-01-01

A quantitative CBF calculation method for xenon/CT was developed by logically estimating time-course change rate (rate constant) of arterial xenon concentration from that of end-tidal xenon concentration. A single factor (γ) was introduced to correlate the end-tidal rate constant (Ke) with the arterial rate constant (Ka) in a simplified equation. This factor (γ) is thought to reflect the diffusing capacity of the lung for xenon. When an appropriate value is given to γ, it is possible to calculate the arterial rate constant (Calculated Ka) from Ke. To determine γ for each xenon/CT CBF examination, a procedure was established which utilizes the characteristics of white matter lambda; lambda refers to xenon brain-blood partition coefficient. Xenon/CT studies were performed on four healthy volunteers. Hemispheric CBF values (47.0±9.0 ml/100 g/min) with use of Calculated Ka were close to the reported normative values. For a 27-year-old healthy man, the rate constant for the common carotid artery was successfully measured and nearly equal to Calculated Ka. The authors conclude the method proposed in this work, lambda-guided calculation method, could make xenon/CT CBF substantially reliable and quantitative by effective use of end-tidal xenon. (author)

Genome-Wide Analysis of the AP2/ERF Family in Eucalyptus grandis: An Intriguing Over-Representation of Stress-Responsive DREB1/CBF Genes

Science.gov (United States)

SanClemente, H.; Mounet, F.; Dunand, C.; Marque, G.; Marque, C.; Teulières, C.

2015-01-01

Background The AP2/ERF family includes a large number of developmentally and physiologically important transcription factors sharing an AP2 DNA-binding domain. Among them DREB1/CBF and DREB2 factors are known as master regulators respectively of cold and heat/osmotic stress responses. Experimental Approaches The manual annotation of AP2/ERF family from Eucalyptus grandis, Malus, Populus and Vitis genomes allowed a complete phylogenetic study for comparing the structure of this family in woody species and the model Arabidopsis thaliana. Expression profiles of the whole groups of EgrDREB1 and EgrDREB2 were investigated through RNAseq database survey and RT-qPCR analyses. Results The structure and the size of the AP2/ERF family show a global conservation for the plant species under comparison. In addition to an expansion of the ERF subfamily, the tree genomes mainly differ with respect to the group representation within the subfamilies. With regard to the E. grandis DREB subfamily, an obvious feature is the presence of 17 DREB1/CBF genes, the maximum reported to date for dicotyledons. In contrast, only six DREB2 have been identified, which is similar to the other plants species under study, except for Malus. All the DREB1/CBF and DREB2 genes from E. grandis are expressed in at least one condition and all are heat-responsive. Regulation by cold and drought depends on the genes but is not specific of one group; DREB1/CBF group is more cold-inducible than DREB2 which is mainly drought responsive. Conclusion These features suggest that the dramatic expansion of the DREB1/CBF group might be related to the adaptation of this evergreen tree to climate changes when it expanded in Australia. PMID:25849589

Genome-wide analysis of the AP2/ERF family in Eucalyptus grandis: an intriguing over-representation of stress-responsive DREB1/CBF genes.

Directory of Open Access Journals (Sweden)

P B Cao

Full Text Available The AP2/ERF family includes a large number of developmentally and physiologically important transcription factors sharing an AP2 DNA-binding domain. Among them DREB1/CBF and DREB2 factors are known as master regulators respectively of cold and heat/osmotic stress responses.The manual annotation of AP2/ERF family from Eucalyptus grandis, Malus, Populus and Vitis genomes allowed a complete phylogenetic study for comparing the structure of this family in woody species and the model Arabidopsis thaliana. Expression profiles of the whole groups of EgrDREB1 and EgrDREB2 were investigated through RNAseq database survey and RT-qPCR analyses.The structure and the size of the AP2/ERF family show a global conservation for the plant species under comparison. In addition to an expansion of the ERF subfamily, the tree genomes mainly differ with respect to the group representation within the subfamilies. With regard to the E. grandis DREB subfamily, an obvious feature is the presence of 17 DREB1/CBF genes, the maximum reported to date for dicotyledons. In contrast, only six DREB2 have been identified, which is similar to the other plants species under study, except for Malus. All the DREB1/CBF and DREB2 genes from E. grandis are expressed in at least one condition and all are heat-responsive. Regulation by cold and drought depends on the genes but is not specific of one group; DREB1/CBF group is more cold-inducible than DREB2 which is mainly drought responsive.These features suggest that the dramatic expansion of the DREB1/CBF group might be related to the adaptation of this evergreen tree to climate changes when it expanded in Australia.

Memory functions and rCBF 99mTc-HMPAO SPET: developing diagnostics in Alzheimer's disease

International Nuclear Information System (INIS)

Elgh, Eva; Naesman, Birgitta; Sundstroem, Torbjoern; Aahlstroem, Katrine Riklund; Nyberg, Lars

2002-01-01

Alzheimer's disease (AD) is a primary degenerative disease of the brain. The prevalence increases with age, with devastating consequences for the individual and society. The aim of this study was to evaluate whether patients with early AD show an altered regional cerebral blood flow (rCBF) compared with control persons. Furthermore, we aimed to investigate the correlation between rCBF in sublobar volumes of the brain and performance on memory tests. Memory tests were chosen to evaluate episodic and semantic memory. Fourteen patients (aged 75.2±8.8 years) with early AD and 15 control persons (aged 71.4±3.2 years) were included. rCBF measurements with single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO) were performed. The rCBF 99m Tc-HMPAO SPET images were spatially transformed to fit a brain atlas and normalised for differences in rCBF (Computerised Brain Atlas software). Cortical and subcortical volumes of interest (VOIs) were analysed and compared. Compared with the controls, AD patients showed a significantly lower rCBF ratio in temporoparietal regions, including the left hippocampus. The diagnostic sensitivity and specificity for AD were high in temporoparietal regions. AD patients had significantly reduced performance on semantic and, in particular, episodic memory tests compared with age-matched normative data, and their performance on several episodic tests correlated with rCBF ratios in parietal and temporal regions, including the left hippocampus. The correlation between rCBF ratio and level of episodic memory performance suggests that abnormalities in rCBF pattern underlie impaired episodic memory functioning in AD. (orig.)

Memory functions and rCBF-99mTc-HMPAO-SPECT: Developing diagnostics in Alzheimer's Disease

International Nuclear Information System (INIS)

Sundstroem, T.; Riklund Ahlstroem, K.; Elgh, E.; Naesman, B.; Nyberg, L.

2002-01-01

Alzheimer's disease (AD) is a primary degenerative disease of the brain. The prevalence increases with age with devastating consequences for the individual and for the society. The aim of this study was to evaluate if patients with early AD show an altered regional cerebral blood flow (rCBF) compared to control persons. The aim was furthermore to investigate the correlation between rCBF in sub-lobar volumes of the brain and performance on memory tests. Memory tests were chosen to evaluate episodic and semantic memory. Fourteen patients (75.2±8.8 yrs) with early AD, and 15 control persons (71.4±3.2 yrs) were included. rCBF measurements with single photon emission computerized tomography (SPECT) using 99m Tc-hexamethyl propylenamine oxime (HMPAO) were performed. The rCBF- 99m Tc-HMPAO-SPECT images were spatially transformed to fit a brain atlas and normalized for differences in rCBF (Computerized Brain Atlas software). Cortical and sub-cortical volumes of interests (VOI) were analyzed and compared. Compared to the controls, AD-patients showed a significantly lower rCBF ratio in temporoparietal regions including left hippocampus. The diagnostic sensitivity and specificity for AD were high in temporoparietal regions. AD-patients had significantly reduced performance on semantic and, in particular, episodic memory tests compared to age matched normative data, and their performance on several episodic tests correlated with rCBF ratios in parietal and temporal regions including left hippocampus. The correlation between rCBF ratio and level of episodic memory performance suggests that abnormalities in rCBF pattern underlie impaired episodic memory functioning in AD

Changes of rCBF on major depressed patients following TMS treatment: and SPM analysis

International Nuclear Information System (INIS)

Zheng, X.M.

2000-01-01

Full text: Changes of regional Cerebral Blood Flow (rCBF) on five drug-resistant depressed patients were examined by Single Photon Emission Computed Tomography (SPECT) with 99 Tc m - Hexamethylpropyleneamine Oxime ( 99 Tc m HMPAO) before and after Transcranial Magnetic Stimulation (TMS). The SPECT images were analysed by Statistical Parametric Mapping (SPM) package. TMS at the left Dorsolateral Prefrontal Cortex (DLPFC) of the depressed patients resulted in an increase of rCBF at a focal region in the vicinity of the stimulation site. No change was observed at any remote region. A 34.8% global CBF reduction for the depressed patients was found in their raw data. SPM analysis of the globally scaled images shows that there are increases of rCBF in the parietal region for the depressed patients. Global CBF scaling might contribute to these increases. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

Priming within and across modalities: exploring the nature of rCBF increases and decreases.

Science.gov (United States)

Badgaiyan, R D; Schacter, D L; Alpert, N M

2001-02-01

Neuroimaging studies suggest that within-modality priming is associated with reduced regional cerebral blood flow (rCBF) in the extrastriate area, whereas cross-modality priming is associated with increased rCBF in prefrontal cortex. To characterize the nature of rCBF changes in within- and cross-modality priming, we conducted two neuroimaging experiments using positron emission tomography (PET). In experiment 1, rCBF changes in within-modality auditory priming on a word stem completion task were observed under same- and different-voice conditions. Both conditions were associated with decreased rCBF in extrastriate cortex. In the different-voice condition there were additional rCBF changes in the middle temporal gyrus and prefrontal cortex. Results suggest that the extrastriate involvement in within-modality priming is sensitive to a change in sensory modality of target stimuli between study and test, but not to a change in the feature of a stimulus within the same modality. In experiment 2, we studied cross-modality priming on a visual stem completion test after encoding under full- and divided-attention conditions. Increased rCBF in the anterior prefrontal cortex was observed in the full- but not in the divided-attention condition. Because explicit retrieval is compromised after encoding under the divided-attention condition, prefrontal involvement in cross-modality priming indicates recruitment of an aspect of explicit retrieval mechanism. The aspect of explicit retrieval that is most likely to be involved in cross-modality priming is the familiarity effect. Copyright 2001 Academic Press.

Exogenous application of molybdenum affects the expression of CBF14 and the development of frost tolerance in wheat.

Science.gov (United States)

Al-Issawi, Mohammed; Rihan, Hail Z; Woldie, Wondwossen Abate; Burchett, Stephen; Fuller, Michael P

2013-02-01

Wheat is able to cold acclimate in response to low temperatures and thereby increase its frost tolerance and the extent of this acclimation is greater in winter genotypes compared to spring genotypes. Such up-regulation of frost tolerance is controlled by Cbf transcription factors. Molybdenum (Mo) application has been shown to enhance frost tolerance of wheat and this study aimed to investigate the effect of Mo on the development of frost tolerance in winter and spring wheat. Results showed that Mo treatment increased the expression of Cbf14 in wheat under non-acclimating condition but did not alter frost tolerance. However, when Mo was applied in conjunction with exposure of plants to low temperature, Mo increased the expression of Cbf14 and enhanced frost tolerance in both spring and winter genotypes but the effect was more pronounced in the winter genotype. It was concluded that the application of Mo could be useful in situations where enhanced frost resistance is required. Further studies are proposed to elucidate the effect of exogenous of applications of Mo on frost resistance in spring and winter wheat at different growth stages. Crown Copyright © 2012. Published by Elsevier Masson SAS. All rights reserved.

Effects of normal aging on regional CBF and CMRO2 in humans

International Nuclear Information System (INIS)

Pantano, P.; Baron, J.C.; Lebrun-Grandie, P.; Duquesnoy, N.; Bousser, M.G.; Comar, D.

1983-07-01

The oxygen-15 continuous inhalation technique and positron emission tomography were used in order to investigate age-related changes of cerebral blood flow (CBF) and oxygen consumption (CMRO 2 ). 27 patients aged 19 to 76 years without evidence of dementia, brain disease or vascular risk factors, were studied. Regional CBF and CMRO 2 were calculated in seven different brain structures. In gray matter CBF and CMRO 2 decreased with aging (respectively 18% and 17%, p 2 was found to be diffuse but to affect principally the frontal and temporo-sylvian cortex. Neuronal loss and/or a diminished metabolic activity of residual neurons are the most likely hypotheses to explain these findings

Sympathetic regulation of cerebral blood flow in humans : a review

NARCIS (Netherlands)

ter Laan, M.; van Dijk, J. M. C.; Elting, J. W. J.; Staal, M. J.; Absalom, A. R.

Cerebral blood flow (CBF) is regulated by vasomotor, chemical, metabolic, and neurogenic mechanisms. Even though the innervation of cerebral arteries is quite extensively described and reviewed in the literature, its role in regulation of CBF in humans remains controversial. We believe that

Cultural differences in hedonic emotion regulation after a negative event.

Science.gov (United States)

Miyamoto, Yuri; Ma, Xiaoming; Petermann, Amelia G

2014-08-01

Beliefs about emotions can influence how people regulate their emotions. The present research examined whether Eastern dialectical beliefs about negative emotions lead to cultural differences in how people regulate their emotions after experiencing a negative event. We hypothesized that, because of dialectical beliefs about negative emotions prevalent in Eastern culture, Easterners are less motivated than Westerners to engage in hedonic emotion regulation-up-regulation of positive emotions and down-regulation of negative emotions. By assessing online reactions to a recent negative event, Study 1 found that European Americans are more motivated to engage in hedonic emotion regulation. Furthermore, consistent with the reported motivation to regulate emotion hedonically, European Americans show a steeper decline in negative emotions 1 day later than do Asians. By examining retrospective memory of reactions to a past negative event, Study 2 further showed that cultural differences in hedonic emotion regulation are mediated by cultural differences in dialectical beliefs about motivational and cognitive utility of negative emotions, but not by personal deservingness or self-efficacy beliefs. These findings demonstrate the role of cultural beliefs in shaping emotion regulation and emotional experiences.

Memory-provoked rCBF-SPECT as a diagnostic tool in Alzheimer's disease?

Energy Technology Data Exchange (ETDEWEB)

Sundstroem, Torbjoern; Riklund, Katrine Aa. [Umeaa University, Umeaa University Hospital, Department of Radiation Sciences, Diagnostic Radiology, Umeaa (Sweden); Elgh, Eva; Naesman, Birgitta [Umeaa University, Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeaa (Sweden); Larsson, Anne [Umeaa University, Department of Radiation Sciences, Radiation Physics, Umeaa (Sweden); Nyberg, Lars [Umeaa University, Department of Psychology, Umeaa (Sweden)

2006-01-01

Alzheimer's disease (AD) is a primary degenerative disease that progressively affects all brain functions, with devastating consequences for the patient, the patient's family and society. Rest regional cerebral blood flow (rCBF) could have a strategic role in differentiating between AD patients and normal controls, but its use for this purpose has a low discriminatory capacity. The purpose of this study was to evaluate whether the diagnostic sensitivity of rCBF single-photon emission computed tomography (SPECT) could be increased by using an episodic memory task provocation, i.e. memory-provoked rCBF-SPECT (MP-SPECT). Eighteen persons (73.2{+-}4.8 years) with mild AD and 18 healthy elderly (69.4{+-}3.9 years) were included in the study. The subjects were injected with{sup 99m}Tc-hexamethylpropylene amine oxime (HMPAO) during memory provocation with faces and names, followed by an rCBF-SPECT study. The rCBF{sup 99m}Tc-HMPAO SPECT images were analysed using statistical parametric mapping (SPM2). Peaks with a false discovery rate corrected value of 0.05 were considered significant. On MP-SPECT, the AD group showed a significant rCBF reduction in the left parietal cortex in comparison with healthy elderly. At rest, no significant group differences were seen. Memory provocation increased the sensitivity of rCBF-SPECT for the detection of AD-related blood flow changes in the brain at the group level. Further studies are needed to evaluate MP-SPECT as a diagnostic tool at the individual level. If a higher sensitivity for AD at the individual level is verified in future studies, a single MP-SPECT study might be sufficient in the clinical setting. (orig.)

Age-related changes in the rCBF in neonates

International Nuclear Information System (INIS)

Song Wenzhong; Chen Changhui; Chen Mingxi; Xie Hongjun; Zhou Aiqun

2001-01-01

Objective: To study the age-related changes of neonatal regional cerebral blood flow (rCBF) [gestation weeks (GW) and days after birth (DAB)]. Methods: Sixteen neonates who had the normal rCBF determined by 99 Tc m -ethylcysteinate dimer (ECD) SPECT imaging and the normal results in the neurological workup after long term clinical follow-up were divided into preterm neonate group (G1: male 3, female 2, GW 34.8 +- 1.2, DAB 7.2 +- 1.3), full-term younger neonate group (G2: male 3, female 2, GW 39.4 +- 1.4, DAB 4.0 +- 1.7) and full-term older neonate (G3: male 5, female 1, GW 40.0 +- 0.8, DAB 14.2 +- 1.9). The radioactivity uptake ratio of different gray matter regions to thalamic region were calculated by ROI. Results: The primary sensomotoric and occipital radioactivity uptake ratio of G1 (0.66 +- 0.08, 0.56 +- 0.10) were significantly lower compared with that of G2 (0.83 +- 0.10, 0.71 +- 0.08, P < 0.05) and G3 (0.94 +- 0.06, 0.79 +- 0.07, P < 0.01). The middle frontal and parietal radioactivity uptake ratio of G1 (0.50 +- 0.07, 0.56 +- 0.10) were significantly lower compared with G3 (0.60 +- 0.05, P < 0.05, 0.69 +- 0.05, P < 0.05). The rCBF of other gray matter regions tended to increase with GW and DAB. The most obvious difference of images between G1 and G2 was at the primary sensomotoric area. Conclusion: These results show that the difference of rCBF between different groups is clearly related to the neonatal age and sequence of neuro-development of the neonates

Reliability and error analysis on xenon/CT CBF

International Nuclear Information System (INIS)

Zhang, Z.

2000-01-01

This article provides a quantitative error analysis of a simulation model of xenon/CT CBF in order to investigate the behavior and effect of different types of errors such as CT noise, motion artifacts, lower percentage of xenon supply, lower tissue enhancements, etc. A mathematical model is built to simulate these errors. By adjusting the initial parameters of the simulation model, we can scale the Gaussian noise, control the percentage of xenon supply, and change the tissue enhancement with different kVp settings. The motion artifact will be treated separately by geometrically shifting the sequential CT images. The input function is chosen from an end-tidal xenon curve of a practical study. Four kinds of cerebral blood flow, 10, 20, 50, and 80 cc/100 g/min, are examined under different error environments and the corresponding CT images are generated following the currently popular timing protocol. The simulated studies will be fed to a regular xenon/CT CBF system for calculation and evaluation. A quantitative comparison is given to reveal the behavior and effect of individual error resources. Mixed error testing is also provided to inspect the combination effect of errors. The experiment shows that CT noise is still a major error resource. The motion artifact affects the CBF results more geometrically than quantitatively. Lower xenon supply has a lesser effect on the results, but will reduce the signal/noise ratio. The lower xenon enhancement will lower the flow values in all areas of brain. (author)

Discrepant 99mTc-ECD images of CBF in patients with subacute cerebral infarction. A comparison of CBF, CMRO2 and 99mTc-HMPAO imaging

International Nuclear Information System (INIS)

Shishido, Fumio; Uemura, Kazuo; Inugami, Atsushi; Ogawa, Toshihide; Fujita, Hideaki; Shimosegawa, Eku; Nagata, Ken.

1995-01-01

Three patients with subacute ischemic cerebral infarction examined by SPECT with 99m Tc-ECD and PET within the same day showed signs of luxury perfusion in the subacute phase, which is between 9 to 20 days after the onset. A 99m Tc-HMPAO SPECT study was also performed within 2 days of the ECD-SPECT study. ECD-SPECT images of three patients displayed a focal decreased uptake in the infarcted lesions, while in infarcted foci, there was almost equivalent or increased CBF compared to normal and unaffected areas, decreased CMRO 2 , and high HMPAO uptake. The ECD-SPECT results were similar to those of CMRO 2 rather than CBF, though the HMPAO-SPECT image was similar to that of CBF. In one patient, HMPAO images revealed hyperfixation of the tracer. In the chronic phase and in the acute phase before 5 days after the onset, there were no discrepancies among the ECD-SPECT, CBF, HMPAO-SPECT, and CMRO 2 images. These observations indicated that 99m Tc-ECD is a good indicator of damaged brain tissues in subacute ischemic infarction. They also suggested that 99m Tc-ECD is a potential agent with which to evaluate cerebral tissue viability in some pathological states of cerebrovascular disease. The characteristics may be suitable for confirming the effects of thrombolytic therapy in acute ischemia, because these conditions often show signs of luxury perfusion when the therapy is successful. (author)

The effect of education on rCBF changes in Alzheimer's disease: a longitudinal SPECT study

International Nuclear Information System (INIS)

Hanyu, Haruo; Sato, Tomohiko; Shimizu, Soichiro; Kanetaka, Hidekazu; Iwamoto, Toshihiko; Koizumi, Kiyoshi

2008-01-01

To determine the relationship of differing levels of education on regional cerebral blood flow (rCBF) in patients with Alzheimer's disease (AD). Fifty-three patients with AD followed-up for an average of 36 months were divided into the high-educated group (HE, ≥12 years of schooling) and low-educated group (LE, 123 I]-iodoamphetamine and the SPECT data were analyzed by 3D-stereotactic surface projections. At initial evaluation, the HE group had greater rCBF deficits in the parietotemporal regions than did the LE group, even though both groups had comparable MMSE and FAST scores. When compared with initial SPECT, follow-up SPECT showed a significant rCBF reduction in widespread regions, including the frontal, parietal, temporal, and limbic lobes of the HE group, while it a significant rCBF reduction in scattered and small regions of the parietotemporal, cingulate, and occipital areas of the LE group, as the HE group had faster cognitive and functional decline than the LE group. The HE group showed lower rCBF at initial SPECT than the LE group, suggesting more advanced AD pathology. As a result, the HE group demonstrated a more extensive and severe reduction of rCBF on follow-up SPECT in association with faster cognitive and functional decline than the LE group. Our SPECT study provides stronger support for the cognitive reserve effects of education in AD. (orig.)

Regional CBF in chronic stable TBI treated with hyperbaric oxygen.

Science.gov (United States)

Barrett, K F; Masel, B; Patterson, J; Scheibel, R S; Corson, K P; Mader, J T

2004-01-01

To investigate whether Hyperbaric Oxygen Therapy (HBO2) could improve neurologic deficits and regional cerebral blood flow (rCBF) in chronic traumatic brain injuries (TBI), the authors employed a nonrandomized control pilot trial. Five subjects, at least three years post head injury, received HBO2. Five head injured controls (HIC) were matched for age, sex, and type of injury. Five healthy subjects served as normal controls. Sixty-eight normal volunteers comprised a reference data bank against which to compare SPECT brain scans. HBO2 subjects received 120 HBO2 in blocks of 80 and 40 treatments with an interval five-month break. Normal controls underwent a single SPECT brain scan, HBO2, and repeat SPECT battery. TBI subjects were evaluated by neurologic, neuropsychometric, exercise testing, and pre and post study MRIs, or CT scans if MRI was contraindicated. Statistical Parametric Mapping was applied to SPECT scans for rCBF analysis. There were no significant objective changes in neurologic, neuropsychometric, exercise testing, MRIs, or rCBF. In this small pilot study, HBO2 did not effect clinical or regional cerebral blood flow improvement in TBI subjects.

Correlative study between a serial changes of rCBF and aphasia in hypertensive intracerebral hemorrhage

International Nuclear Information System (INIS)

Shi Yizhen; He Guangren

1998-01-01

Purpose: To explore the dynamic changes of rCBF of aphasic patients and its correlation with clinical findings. Methods: 32 dominant lateral hypertensive intracerebral hemorrhagic patients underwent the language function evaluation, rCBF tomographic imaging and CT scans. Semiquantitative analysis was used. Results: 1) 19 of 32 cases were aphasia while 13 were not. 2) There was a close correlation between aphasia and the size and location of hematoma. 3) There was only hemonrrhagic foci demonstrated with CT while multiple and extensive cortical hypo-perfused area were found in SPECT, especially in aphasic cases. Frontal and temporal lobes of each aphasia were involved 100%. 4) The rCBF ratio in both Broca's and Wernicke's areas of aphasias were lower than those of non-aphasias (t = 4.31, 5.52, P < 0.001). The degree of rCBF decrement in Wernicke's area varied with different aphasic types, among which the rCBF of sensory aphasia was the lowest (t 2.53, P<0.05). 5) 10 aphasias were followed with SPECT, CT and clinic evaluation 1 week, 1 month and 3 months after hemorrhage respectively. The rCBF ratios in cerebral cortex of 5 recovery cases increased gradually, but not in 5 not recovered cases. Conclusions: SPECT was superior to CT, it can provide useful information for diagnosing and staging aphasias, especially in early stage, and can also assess the prognosis of the disease

A new collimator for measurement of rCBF by means of gamma camera

International Nuclear Information System (INIS)

Zechmann, W.; Oberladstaetter, M.; Raccabona, G.; Vogl, G.; Gerstenbrand, F.

1982-01-01

Atraumatic measurement of rCBF by means of gamma camera and conventional collimators requires high doses of 133 Xenon to obtain high count rates over the cerebral ROI's. The input of time-activity curve of breathing air by means of a probe measurement is not possible on line without difficulties. A new collimator, developed by ours, which is comparable with standard rCBF-Multiprobe systems, which allows high countrates and low dose of 133 Xenon is presented. A special air bypass enables to get the breathing curve with simple ROI technique. The collimator can easily be adapted to the camera by means of an insert adapter ring. With this collimator the rCBF measurement with conventional equipment of a nuclear medicine department is possible. (Author)

Memory functions and rCBF {sup 99m}Tc-HMPAO SPET: developing diagnostics in Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Elgh, Eva; Naesman, Birgitta [Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeaa University, 901 85 Umeaa (Sweden); Sundstroem, Torbjoern; Aahlstroem, Katrine Riklund [Department of Radiation Sciences, Diagnostic Radiology, Umeaa University, Umeaa (Sweden); Nyberg, Lars [Department of Psychology, Umeaa University, Umeaa (Sweden)

2002-09-01

Alzheimer's disease (AD) is a primary degenerative disease of the brain. The prevalence increases with age, with devastating consequences for the individual and society. The aim of this study was to evaluate whether patients with early AD show an altered regional cerebral blood flow (rCBF) compared with control persons. Furthermore, we aimed to investigate the correlation between rCBF in sublobar volumes of the brain and performance on memory tests. Memory tests were chosen to evaluate episodic and semantic memory. Fourteen patients (aged 75.2{+-}8.8 years) with early AD and 15 control persons (aged 71.4{+-}3.2 years) were included. rCBF measurements with single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO) were performed. The rCBF {sup 99m}Tc-HMPAO SPET images were spatially transformed to fit a brain atlas and normalised for differences in rCBF (Computerised Brain Atlas software). Cortical and subcortical volumes of interest (VOIs) were analysed and compared. Compared with the controls, AD patients showed a significantly lower rCBF ratio in temporoparietal regions, including the left hippocampus. The diagnostic sensitivity and specificity for AD were high in temporoparietal regions. AD patients had significantly reduced performance on semantic and, in particular, episodic memory tests compared with age-matched normative data, and their performance on several episodic tests correlated with rCBF ratios in parietal and temporal regions, including the left hippocampus. The correlation between rCBF ratio and level of episodic memory performance suggests that abnormalities in rCBF pattern underlie impaired episodic memory functioning in AD. (orig.)

Cerebral arteriovenous malformations. the relationship between clinical related events and rCBF SPECT imaging

International Nuclear Information System (INIS)

Sun Bo; Shi Xiangen

1996-01-01

To evaluate the relationship between clinical related events and rCBF SPECT imaging in patients with arteriovenous malformations (AVMs), the radioactive counting difference between normal and lesion site was divided by regional pixel considered as ischemic index (II). II was measured in 20 AVM cases and compared with patients' age, sex,neurological history and the size of lesions. The degree of rCBF reduction correlated with clinical neurological manifestation and showed no significant relationship with the age, sex and size of malformed vessels. II in patients with seizures was higher than that in patients with hemorrhage. The rCBF SPECT imaging may be useful for evaluation of the hemodynamics in AVMs

CBF and CMRo2 during craniotomy for small supratentorial cerebral tumours in enflurane anaesthesia. A dose-response study

International Nuclear Information System (INIS)

Madsen, J.B.; Cold, G.E.; Eriksen, H.O.; Eskesen, V.; Blatt-Lyon, B.

1986-01-01

In 14 patients with supratentorial cerebral tumours with midline shift ≤ 10 mm, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRo 2 ) were measured twice on the contralateral side of the craniotomy, using a modification of the Kety and Schmidt method. For induction of anaesthesia, thiopental, fentanyl and pancuronium were used. The anaesthesia was maintained with enflurane 1% in nitrous oxide 67%. Moderate hypocapnia to a level averaging 4.3 kPa was achieved. The patients were divided into two groups. In group 1 (n=7), 1% enflurane was used throughout the anaesthesia, and CBF and CMRo 2 measured about 70 min after induction averaged 30.1 ml 100 g -1 min -1 and 1.98 ml O 2 100 g -1 min -1 , respectively. During the second CBF study 1 h later, CBF and CMRo 2 were unchanged (P>0.05). In group 2 (n=7), the inspiratory enflurane concentration was increased from 1 to 2% after the first CBF measurement. In this group a significant decrease in CMRo 2 was observed, while CBF was unchanged. In six patients EEG was recorded simultaneously with the CBF measurements. In patients subjected to increasing enflurane concentration (Group 2), a suppression in the EEG activity was observed without spike waves. It is concluded that enflurane induces a dose-related decrease in CMRo 2 and suppression in the EEG activity, whereas CBF was unchanged (author)

Noninvasive quantitative assessment of cerebral blood flow (CBF) using Tc-99m ECD SPECT with adjunctive radionuclide angiography in ischemic stroke

International Nuclear Information System (INIS)

Yim, Jun Sung; Choi, Yun Young; Kim, Seung Hyun; Kim, Myung Ho; Cho, Suk Shin

1999-01-01

Quantitative CBF measurements are essential for diagnosing ischemic lesion, evaluating the therapeutic effects and predicting the prognosis of cerebral ischemia. Even though several methods have been introduced, these techniques are too cumbersome and invasive to be applied to routine studies. In this study, a non-invasive simple method for the quantitative angiography. Fifteen normal controls and 27 patients with unilateral carotid ischemic stoke were selected. Brain perfusion index (BPI) of each hemisphere was measured in each subject by acquisition of serial radionuclide angiography after injection of 20mCi of Tc-99m ECD. With Lassen's correction algorithm of curve-linear relationship between the brain activity and blood flow, rCBF on transaxial SPECT slice corresponding with MRI lesion sites (ischemic core, border zone and contralateral mirror locus) were calculated. BPI values for normal controls showed a significant negative correlation with advantage age (r=-0.64, p=0.021) and hemisphric BPI were 11.02±1.6 and 7.8±1.4 for normal controls and patient, respectively. Significant differences were observed between two groups (p=0.0012). rCBF obtained from core zone (12±2.5 ml/100/min), boneder zone (29.2±8.1) and contralateral mirror locus (52.1±15.1) were clearly defined in each subject of patient group. Measurement of BPI and rCBF using Tc-99m ECD SPECT with adjunctive radionuclide angiography could be an useful, simple and non-invasive method in evaluation of the cerebral flood in the ischemic stroke

A study of cerebral hemodynamics in various cerebrovascular disorders by means of rCBF measurement with single photon emission computed tomography

International Nuclear Information System (INIS)

Harano, Hideyuki

1987-01-01

Using single photon emission computed tomography (SPECT) with Xe-133 inhalation method, regional cerebral blood flow (rCBF) was measured for the purpose of analyzing the pathophysiology of various cerebrovascular disorders. Included in this series were 38 normal volunteers (N), 72 patients with ischemic cerebrovascular disease (ICD), 16 with subarachnoid hemorrhage (SAH), 9 with arteriovenous malformation (AVM), 6 with Moyamoya disease (MD), and 4 with hypertensive intracerebral hematoma (HIH). In the N group, rCBF was independent of sex and laterality. Increased rCBF was observed in the frontal region, as compared with other regions. A significantly increased rCBF was observed in the thirties decade of life; the difference in rCBF was, however, not statistically significant above the age of 30 years. In the ICD group, rCBF decreased in association with severer disorder. In cases of severe disorder, a significantly decreased rCBF was observed in the whole area, as compared with the control group. SPECT allowed early detection of decreased rCBF due to vaso-spasm in the SAH group. The groups of AVM, MD, and HIH showed decreased rCBF in the surrounding areas of the lesions. (Namekawa, K.)

Redox Signaling and CBF-Responsive Pathway Are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

Science.gov (United States)

Cheng, Fei; Lu, Junyang; Gao, Min; Shi, Kai; Kong, Qiusheng; Huang, Yuan; Bie, Zhilong

2016-01-01

Salicylic acid (SA) plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus). Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-α-aminooxy-β-phenylpropionic acid (AOPP) increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon. PMID:27777580

Redox Signaling and CBF-Responsive Pathway are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

Directory of Open Access Journals (Sweden)

Fei Cheng

2016-10-01

Full Text Available Salicylic acid (SA plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus. Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-ɑ-aminooxy-β-phenylpropionic acid (AOPP increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon.

Imaging of the appearance time of cerebral blood using [15O]H2O PET for the computation of correct CBF.

Science.gov (United States)

Kudomi, Nobuyuki; Maeda, Yukito; Sasakawa, Yasuhiro; Monden, Toshihide; Yamamoto, Yuka; Kawai, Nobuyuki; Iida, Hidehiro; Nishiyama, Yoshihiro

2013-05-23

Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. Positron emission tomography (PET) with H215O (or C15O2) can quantify CBF and apply kinetic analyses, including autoradiography (ARG) and the basis function methods (BFM). These approaches, however, are sensitive to input function errors such as the appearance time of cerebral blood (ATB), known as the delay time. We estimated brain ATB in an image-based fashion to correct CBF by accounting for differences in computed CBF values using three different analyses: ARG and BFM with and without fixing the partition coefficient. Subject groups included those with no significant disorders, those with elevated cerebral blood volume, and those with reduced CBF. All subjects underwent PET examination, and CBF was estimated using the three analyses. The ATB was then computed from the differences of the obtained CBF values, and ATB-corrected CBF values were computed. ATB was also estimated for regions of interest (ROIs) of multiple cortical regions. The feasibility of the present method was tested in a simulation study. There were no significant differences in the obtained ATB between the image- and ROI-based methods. Significantly later appearance was found in the cerebellum compared to other brain regions for all groups. In cortical regions where CBF was reduced due to occlusive lesions, the ATB was 0.2 ± 1.2 s, which was significantly delayed relative to the contralateral regions. A simulation study showed that the ATB-corrected CBF was less sensitive to errors in input function, and noise on the tissue curve did not enhance the degree of noise on ATB-corrected CBF image. This study demonstrates the potential utility of visualizing the ATB in the brain, enabling the determination of CBF with less sensitivity to error in input function.

dlk acts as a negative regulator of Notch1 activation through interactions with specific EGF-like repeats

International Nuclear Information System (INIS)

Baladron, Victoriano; Ruiz-Hidalgo, Maria Jose; Nueda, Maria Luisa; Diaz-Guerra, Maria Jose M.; Garcia-Ramirez, Jose Javier; Bonvini, Ezio; Gubina, Elena; Laborda, Jorge

2005-01-01

The protein dlk, encoded by the Dlk1 gene, belongs to the Notch epidermal growth factor (EGF)-like family of receptors and ligands, which participate in cell fate decisions during development. The molecular mechanisms by which dlk regulates cell differentiation remain unknown. By using the yeast two-hybrid system, we found that dlk interacts with Notch1 in a specific manner. Moreover, by using luciferase as a reporter gene under the control of a CSL/RBP-Jk/CBF-1-dependent promoter in the dlk-negative, Notch1-positive Balb/c 14 cell line, we found that addition of synthetic dlk EGF-like peptides to the culture medium or forced expression of dlk decreases endogenous Notch activity. Furthermore, the expression of the gene Hes-1, a target for Notch1 activation, diminishes in confluent Balb/c14 cells transfected with an expression construct encoding for the extracellular EGF-like region of dlk. The expression of Dlk1 and Notch1 increases in 3T3-L1 cells maintained in a confluent state for several days, which is associated with a concomitant decrease in Hes-1 expression. On the other hand, the decrease of Dlk1 expression in 3T3-L1 cells by antisense cDNA transfection is associated with an increase in Hes-1 expression. These results suggest that dlk functionally interacts in vivo with Notch1, which may lead to the regulation of differentiation processes modulated by Notch1 activation and signaling, including adipogenesis

Cerebral blood flow (CBF) with 133Xe inhalation method

International Nuclear Information System (INIS)

Kusunoki, Tadaki; Masumura, Michio; Tamaki, Norihiko; Matsumoto, Satoshi; Yamashita, Hideyuki.

1982-01-01

The effects of CO 2 inhalation on the cerebral blood flow (CBF) were examined with 133 Xe inhalation method (Novo Inhalation Cerebrograph) on 9 normal peoples and 20 patients. Nine normal peoples were divided into 3 groups consisting of each 3 peoples, namely young age group, middle age group, and old age group. Each increased CBF (%) by CO 2 inhalation was 40 -- 44 in young age group, 36 -- 37 in middle age group, and 35 -- 36 in old age group in the blood flow of the first compartment (F 1 ), and 27 -- 28 in young age group, 30 -- 31 in middle age group and 23 -- 24 in old age group in the initial slope index (ISI). Each CO 2 reactivity factor (RF) was 5.5 -- 5.8 in young age group, 3.8 -- 4.0 in middle age group and 3.3 in old age group in F 1 , and 3.1 -- 3.2 in young age group, 2.0 -- 3.3 in middle age group, and 1.2 -- 1.3 in old age group in ISI. Twenty patients consisted of 15 patients of occlusive cerebrovascular disease, 2 patients of head injury, 2 patients of normal pressure hydrocephalus and one patient of subarachnoid hemorrhage. RF was abnormally lower than normal value in 5 patients in F 1 , but in 7 in ISI. Clinical benefits of CBF study during CO 2 inhalation with 133 Xe inhalation method were discussed. (author)

CBF and CMRo/sub 2/ during craniotomy for small supratentorial cerebral tumours in enflurane anaesthesia. A dose-response study

Energy Technology Data Exchange (ETDEWEB)

Madsen, J.B.; Cold, G.E.; Eriksen, H.O.; Eskesen, V.; Blatt-Lyon, B.

1986-01-01

In 14 patients with supratentorial cerebral tumors with midline shift less than or equal to 10 mm, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRo/sub 2/) were measured twice on the contralateral side of the craniotomy, using a modification of the Kety and Schmidt method. For induction of anaesthesia, thiopental, fentanyl and pancuronium were used. The anaesthesia was maintained with enflurane 1% in nitrous oxide 67%. Moderate hypocapnia to a level averaging 4.3 kPa was achieved. The patients were divided into two groups. In group 1 (n=7), 1% enflurane was used throughout the anaesthesia, and CBF and CMRo/sub 2/ measured about 70 min after induction averaged 30.1 ml 100 g/sup -1/ min/sub -1/ and 1.98 ml O/sub 2/ 100 g/sup -1/ min/sup -1/, respectively. During the second CBF study 1 h later, CBF and CMRo/sub 2/ were unchanged (P>0.05). In group 2 (n=7), the inspiratory enflurane concentration was increased from 1 to 2% after the first CBF measurement. In this group a significant decrease in CMRo/sub 2/ was observed, while CBF was unchanged. In six patients EEG was recorded simultaneously with the CBF measurements. In patients subjected to increasing enflurane concentration (Group 2), a suppression in the EEG activity was observed without spike waves. It is concluded that enflurane induces a dose-related decrease in CMRo/sub 2/ and suppression in the EEG activity, whereas CBF was unchanged.

Meta-analysis of the effect of overexpression of CBF/DREB family genes on drought stress response

Science.gov (United States)

Transcription factors C-repeat/dehydration-responsive element binding proteins (CBF/DREB) play an important role in plant response to abiotic stresses. Over-expression of various CBF/DREB genes in diverse plants have been reported, but inconsistency of gene donor, recipient genus, parameters used i...

The usefulness of CBF brain SPECT in forensic medicine: the civil law codes cases. A description of four cases

International Nuclear Information System (INIS)

Piskunowicz, M.; Lass, P.; Bandurski, T.; Krzyzanowski, M.

2003-01-01

The aim of this report was to assess the usefulness of cerebral blood flow (CBF) scanning utilising the SPECT technique in forensic medicine cases in the area of civil law cases. CBF SPECT scanning was performed in four patients utilising 99m Tc-ECD and a triple-head gammacamera. In the analysis both the asymmetry index and cerebellar normalisation were applied. Reference values were obtained by studying 30 healthy volunteers. In those cases CBF SPECT scanning played an important role in forensic argument. It influenced the sentence and the amount of financial compensation. CBF SPECT scanning may provide valuable information in forensic medicine argument in civil law cases, but only when taken together with psychometric tests and other neuroimaging methods (CT, MRI). The value of CBF SPECT scanning alone may be limited in judicial proceedings. (author)

A study comparing the use of dynamic CT and Xe-CT CBF for ischemic cerebro-vascular disease

International Nuclear Information System (INIS)

Terada, Tomoaki; Kikuchi, Haruhiko; Kuriyama, Yoshihiro; Nagata, Izumi; Yamagata, Sen; Naruo, Yoshito; Minamikawa, Jun; Kaneko, Takaji; Sakashita, Yoshiharu

1987-01-01

The simultaneous measurement of dynamic computerized tomography scanning (DCT) with an iodine-contrast enhancement material bolus injection and a simultaneous xenon CT-CBF-study was done on 15 patients (8 cases of unilateral internal carotid occlusion; 3, of unilateral middle cerebral arterial occlusion, and 4, without any major cerebral arterial occlusion or significant arterial stenosis) with ischemic cerebro-vascular diseases at the subacute and/or chronic stage. The value of the width and corrected first moment (cMT1) as well as their functional images, as acquired from DCT data, were compared to the 1-CBF value and the 1-CBF map of the xenon CT-CBF-study. A comparison of the functional images of DCT and 1-CBF showed that there was a good correlation between them in the cases without leptomeningeal anastomosis as a collateral circulation. However, a poor correlation between them was found in the cases with leptomeningeal anastomosis as a collateral circulation. The correlation of 1-CBF and 1/width with 1/cMT1 was significant (r = 0.78, p < 0.01) in the former cases, but it was not significant in the latter cases. The results of our data were thought to be due to the difference in the tracer inflow pattern between the cases without leptomeningeal anastomosis and those with it as a collateral circulation. The factor of cerebral blood volume should be considered in a more detailed study, although our cases did not include any patients with acute cerebral infarction or recanalized cases, which are thought to show various changes in the cerebral blood volume. The 1/width and 1/cMT1 values acquired from DCT well reflected the CBF in the cases without leptomeningeal anastomosis as a collateral circulation. (author)

Comparison of rCBF between patients with medial temporal lobe epilepsy and normal controls using H215O PET

International Nuclear Information System (INIS)

Kang, Eun Joo; Lee, Jae Sung; Nam, Hyun Woo; Lee, Sang Kun; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul

2002-01-01

The aim of this study was to identify the brain areas whose regional cerebral blood flow (rCBF) was changed in medial temporal lobe epilepsy (mTLE) using H 2 15 O-PET. 12 patients with mTLE (6 left, 6 right mTLE) and 6 normal controls were scanned during a fixation baseline period and a sensory-motor condition where subjects pressed a button to an upward arrow. A voxel-based analysis using SPM99 software was performed to compare the patient groups with the normal controls for the rCBF during fixation baseline period and for relative changes of rCBF during the sensory-motor task relative to fixation. Duirng the fixation baseline, a significant reduction of rCBF was found posterior insula bilaterally and right frontopolar regions in right mTLE patients compared to the normal controls. In left mTLE patients, the reduction was found in left frontopolar and temporal regions. During the sensory-motor task, rCBF increase over the fixation period, was reduced in left frontal and superior temporal regions in the right mTLE patients whereas in various areas of right hemisphere in left mTLE patients, relative to normal controls. However, the increased rCBF was also found in the left inferior parietal and anterior thalamic/fornix regions in both right and left mTLE patients compared to normal controls. Epilepsy induced changes were found not only in relative increase/ decrease of rCBF during a simple sensory-motor control condition relative to a fixation rest condition but also in the relative rCBF distribution during the rest period

One-year follow-up of neuropsychology, MRI, rCBF and glucose metabolism (rMRGlu) in cerebral microangiopathy

International Nuclear Information System (INIS)

Sabri, O.; Hellwig, D.; Schreckenberger, M.; Kaiser, H.-J.; Wagenknecht, G.; Setani, K.; Reinartz, P.; Zimny, M.; Buell, U.; Schneider, R.; Mull, M.; Ringelstein, E.-B.

2000-01-01

Background: MRI shows lacunar infarctions (LI), deep white matter lesions (DWML) and atrophy in cerebral microangiopathy, which is said to lead to vascular dementia. In a first trial series on 57 patients with confirmed pure cerebral microangiopathy (without concomitant macroangiopathy), neuropsychological impairment and (where present) brain atrophy correlated with decreased rCBF and rMRGlu. LI and DWML did not correlate with either neuropsychological impairment or decreased rCBF/rMRGlu. This study was done one year later to detect changes in any of the study parameters. Methods: 26 patients were re-examined for rCBF, rMRGlu, LI, DWML, atrophy and neuropsychological performance (7 cognitive, 3 mnestic, 4 attentiveness tests). Using a special head holder for exact repositioning, rCBF (SPECT) and rMRGlu (PET) were measured and imaged slice by slice. White matter/cortex were quantified using MRI-defined ROIs. Results: After one year the patients did not show significant decreases in rCBF or rMRGlu either in cortex or in white matter (p>0.05), nor did any patient show LI, DWML or atrophy changes on MRI. There were no significant neuropsychological decreases (p>0.05). (orig.) [de

The study of correlation between neurological function rehabilitation and dynamic change of rCBF in patients with aphasia

International Nuclear Information System (INIS)

Liu Haibo; Song Debiao; Kong Jun; Lv Junfeng; Tian Jing

2004-01-01

Objective: To evaluate the result of SPECT and CT in the patients with acute cerebral infarction and further more, to study the correlation between aphasia and dynamic change of regional cerebral blood flow (rCBF) in patients. Methods: Thirty cases with cerebral infarction of left basal ganglia were divided into two groups according to the presence or absence of aphasia; the vision and semi-ration analysis were used in photograph reading and region of interest (ROI) technology, respectively. Results: 1) Group A: there was a low rCBF in left basal ganglia, the dimension was larger than that in CT. There was also a low rCBF in frontal lobe and temporal lobe. Group B: there was only a low rCBF in left basal ganglia. 2) There were 6 cases with crossed cerebellar diaschisis (CCD) in the patients with aphasia. 3) The comparison about aphasia: the rCBF was higher in language center in the patients with improved language function than that in the patients without language function improvement and the difference between them was significant. Conclusions: The neurological function can be indirectly reflected through the study of the rCBF. At the same time, it may conduce to the locating of the damage in the central nervous system and to the differentiation diagnosis. It may also conduce to the programming of the therapeutic course and prognostication. (authors)

Acute effects of electroconvulsive therapy on regional cerebral blood flow (rCBF) in psychiatric disorders

International Nuclear Information System (INIS)

Prohovnik, I.; Alderson, P.O.; Sackheim, H.A.; Decina, P.; Kahn, D.

1984-01-01

Electroconvulsive therapy (ECT) is frequently used in the treatment of major depression and other psychiatric disorders; its mechanism of action is not established, but previous evidence suggests that it is associated with postictal metabolic suppression. The authors have used measurements of rCBF as an index of cortical metabolic activity to study the acute effects of ECT. Measurements of rCBF were made in 32 cortical regions in 10 patients (pts) following one minute breathing of Xe-133 (5mCi/L); the measurements were performed 30min before and 50min after ECT. Bilateral ECT was administered to six pts (five diagnosed as major depressives and one schizophrenic) and unilateral ECT to four (all diagnosed as unipolar or bipolar affective disorder). The total rCBF material consists of 52 measurements in these pts, made before and after 16 bilateral and 10 unilateral treatments. ECT was found to cause significant reduction of rCBF. Mean hemispheric flows (using the Initial Slope Index to measure grey-matter flow) were reduced by about 5% in both hemispheres following bilateral treatment. Unilateral treatment caused a 9% reduction of flow in the treated hemisphere, but only 2% contralaterally. Regional patterns of flow decreases also differed between the two treatment modes: bilateral frontal reductions were found after bilateral treatment, whereas unilateral ECT caused a widespread flow reduction in the treated hemisphere, and almost no effect contralaterally. These results suggest that rCBF studies are useful for assessing ECT, and indicate that the acute cerebral effects of ECT vary with the mode of treatment

Xenon contrast CT-CBF measurements in patients with pre- and post-correction of platelet hyper-aggregability, and in the white matter lesions

International Nuclear Information System (INIS)

Fujita, Shigekiyo

2004-01-01

About 10 years ago, the author found that, patients with headache, vertigo, dizziness and dementia, had a high prevalence (about 70%) of platelet hyper-aggregability which was especially prevalent (up to 100%) in Binswanger's dementia. Correction of the platelet hyper-aggregability in those patients led to remarkable improvement of symptoms. Based on this effective result with treatment of platelet hyper-aggregability, the author hypothesized that patients may show improvement or recovery of cerebral blood flow from the decreased blood flow by the correction of the platelet hyper-aggregability. The present report consist of two parts: 1) comparison of regional cerebral blood flow (CBF) before and after correction of platelet hyper-aggregability, 2) measurements of CBF in patients with severe white matter lesions, and the CBF within white matter lesions. The results of 1) showed CBF was decreased by about 20 to 30% before treatment and marked increase to normal CBF after correction of platelet hyper-aggregability, particularly in the thalamus and cortex. The increase was statistically significant except in bilateral frontal cortex and bilateral anterior white matter and left posterior white matter. From these results, it is confirmed that platelet hyper-aggregability is associated with decreased CBF, and after correction of platelet hyper-aggregability, CBF increases markedly. The results of 2) showed moderate to severe decreases of blood flow in all areas of the brain, and marked decreases of CBF in white matter lesions, 12.8±2.7 m1/100 g/min on average, which corresponded approximately to 60% of normal white matter CBF. (author)

Clinical application of stable xenon CT-CBF studies without denitrogenation

Energy Technology Data Exchange (ETDEWEB)

Touho, Hajime; Karasawa, Jun; Shishido, Hisashi; Yamada, Keisuke [Osaka Neurological Institute, Toyonaka (Japan)

1990-08-01

Noninvasive and simplified methods for estimating regional cerebral blood flow (CBF) and regional partition coefficient ({lambda}) using the inhalation of stable xenon (Xe{sup s}) and computed tomographic (CT) scanning are described. Thirty percent Xe{sup s} in 70% oxygen was inhaled for 240 seconds and exhaled for 160 seconds during serial CT scanning without denitrogenation in 26 patients with cerebrovascular diseases and four volunteer controls. During the investigation, the end-tidal Xe{sup s} concentration was continuously monitored with a thermoconductivity analyzer to determine the build-up range (A value) and build-up rate constant (K value) of the artery by the curve fitting method. Calculated A and K values were corrected by the following formulae reported previously: for patients aged 0-20 years, A{sub e} = 0.75A{sub a} + 2.15, K{sub e} = 0.67K{sub a} + 0.69; 21-40 years, A{sub e} = 0.56A{sub a} + 3.24, K{sub e} = 0.38K{sub a} + 1.12; 41-60 years, A{sub e} = 0.91A{sub a} + 1.95, K{sub e} = 0.38K{sub a} + 1.32; over 61 years, A{sub e} = 0.52A{sub a} + 3.81, K{sub e} = 0.31K{sub a} + 1.55 (A{sub e} and K{sub e} were calculated with end-tidal Xe{sup s} concentration, A{sub a} and K{sub a} were calculated by direct sampling of arterial blood). A CBF map (f map) and {lambda} map made with corrected A and K values demonstrated reliable distribution. The CBF was high in the gray matter, low in the white matter, and much lower in the infarcted area. {lambda} was high in the white matter, low in the gray matter, and much lower in the infarcted area. Eight patients were examined with and without denitrogenation. Both the f map and {lambda} map with denitrogenation were compatible with those without denitrogenation. Xe{sup s} CT-CBF studies without denitrogenation are useful in clinical neurosurgery and outpatients for estimating regional cerebral circulation. (author).

rCBF activation studies and neuronal circuitry related to vision

NARCIS (Netherlands)

deJong, BM

Three principles of neuronal interaction within cortically distributed networks are discussed PET-rCBF activation methods provide an opportunity to acquire insight in the distribution of functionally related areas of the human brain in vivo. The distinction of visual areas, activated by either

Local CBF, oxygen extraction fraction (OEF) and CMRO/sub 2/: prognostic value in recent supratentorial infarction in humans

Energy Technology Data Exchange (ETDEWEB)

Baron, J C; Rougemont, D; Bousser, M G; Lebrun-Grandie, P; Iba-Zizen, M T; Chiras, J

1983-06-01

Cerebral blood flow (CBF) and oxygen consumption (CMRO/sub 2/) have been measured locally using positron emission tomography (PET) in 25 patients (34 studies) with recent cerebral infarction. The data analysis yielded threshold values for CBF and CMRO/sub 2/ that reliably separated the brain areas spontaneously evolving to necrosis from those maintaining integrity (as determined by C.T. Scanning) but still showing significant changes in CBF and/or CMRO/sub 2/. These results suggest the potential use of PET for estimation of tissue prognosis in recent cerebral infarction.

CBF tomographic measurement with the scintillation camera

International Nuclear Information System (INIS)

Kayayan, R.; Philippon, B.; Pehlivanian, E.

1989-01-01

Single photon emission tomography (SPECT) allows calculation of regional cerebral blood flow (CBF) in multiple cross-sections of the human brain. The methods of Kanno and Lassen is utilized and a study of reproductibility in terms of integration numbers and period of integrations is performed by computer simulation and experimental study with a Gamma-camera. Finally, the possibility of calculating the regional cerabral blood flow with a double headed rotating Gamma-camera by inert gas inhalation, like the Xenon-133 is discussed [fr

Changes of rCBF 99mTc-HMPAO SPECT in a selected disorders

International Nuclear Information System (INIS)

Junik, R.

2003-01-01

With single photon emission computer tomography (SPECT) and HMPAO a noninvasive examination of regional cerebral blood flow can be performed (rCBF). The purpose of the SPECT examinations was to define the location and magnitude of blood flow disorder in selected diseases and the assessment of the results as complementary to morphological tests CT and MRI or functional tests, such as EEG. The examinations were carried out in 455 patients: 91 - patients with depression, 29 - congenital hypothyroidism, 66 - migraine, 34 - epilepsy, 6 - Landau-Kleffner syndrome, 20 - Alzheimer disease, 55 - with suspected Alzheimer disease, 105 - cerebral stroke, and 48 - transient cerebral ischemia. The control group comprised of 26 subjects. The SPECT method was used to perform examinations. The images were evaluated based on semiquantitative method. The asymmetry of activity and activity referred to the referential region were measured using symmetrical ROIs localized in hypoperfusion foci. The differences in perfusion in symmetric locations exceeding 10% were considered abnormal. During the depression stage, in patients with depression, a decrease of rCBF occurred. Regression of depression results in an increase of rCBF almost in the entire cerebrum. In patients with depression, SPECT examination is a useful method to monitor course of a disease and to objectively verify the results of treatment. 2. Disorders of rCBF, a decrease and/or asymmetry, occurred in patients with congenital hypothyroidism, migraine, and epilepsy. 3. There is a relation between patterns of cerebral perfusion in stroke, visible in SPECT image, and an extent and intensity of cerebral ischemia. (author)

One-year follow-up of neuropsychology, MRI, rCBF and glucose metabolism (rMRGlu) in cerebral microangiopathy

Energy Technology Data Exchange (ETDEWEB)

Sabri, O.; Hellwig, D.; Schreckenberger, M.; Kaiser, H.-J.; Wagenknecht, G.; Setani, K.; Reinartz, P.; Zimny, M.; Buell, U. [Department of Nuclear Medicine, Technische Univ. Aachen (Germany); Schneider, R. [Department of Neurology, Technische Univ. Aachen (Germany); Mull, M. [Department of Neuroradiology, Technische Univ. Aachen (Germany); Ringelstein, E.-B. [Department of Neurology, Muenster Univ. (Germany)

2000-07-01

Background: MRI shows lacunar infarctions (LI), deep white matter lesions (DWML) and atrophy in cerebral microangiopathy, which is said to lead to vascular dementia. In a first trial series on 57 patients with confirmed pure cerebral microangiopathy (without concomitant macroangiopathy), neuropsychological impairment and (where present) brain atrophy correlated with decreased rCBF and rMRGlu. LI and DWML did not correlate with either neuropsychological impairment or decreased rCBF/rMRGlu. This study was done one year later to detect changes in any of the study parameters. Methods: 26 patients were re-examined for rCBF, rMRGlu, LI, DWML, atrophy and neuropsychological performance (7 cognitive, 3 mnestic, 4 attentiveness tests). Using a special head holder for exact repositioning, rCBF (SPECT) and rMRGlu (PET) were measured and imaged slice by slice. White matter/cortex were quantified using MRI-defined ROIs. Results: After one year the patients did not show significant decreases in rCBF or rMRGlu either in cortex or in white matter (p>0.05), nor did any patient show LI, DWML or atrophy changes on MRI. There were no significant neuropsychological decreases (p>0.05). (orig.) [German] Ziel: In der MRT zeigen sich bei zerebraler Mikroangiopathie (ZMA) lakunaere Infarkte (LI), Deep White Matter Lesions (DWML) und Atrophie (Atr). Die sogenannte vaskulaere Demenz wurde dabei hauptsaechlich auf die Laesionen der weissen Substanz zurueckgefuehrt. In einer ersten Untersuchungsreihe waren bei 57 Patienten mit gesicherter ZMA nur neuropsychologische Defizite (Nps) und, falls vorhanden, Atr als Grundlage fuer erniedrigte rCBF/rMRGlu-Werte zu eruieren, jedoch nicht LI/DWML. Es sollte geklaert werden, ob sich im Verlauf der Erkrankung nach einem Jahr Veraenderungen dieser Parameter ergeben. Methode: 26 Patienten wurden nach einem Jahr erneut neuropsychologisch untersucht (7 kognitive, 3 mnestrische, 4 Aufmerksamkeitstests). Mittels eines speziellen Kopfhalterungssystems wurden in

The sensitivity of CT and rCBF-studies for the pathology of strokes

International Nuclear Information System (INIS)

Kohlmeyer, K.

1980-01-01

A localized pathology of the cerebral circulation or cerebral metabolism and the morphology of the brain tissue can be visualized by the use of new techniques in radiology and nuclear medicine: measurements of rCBF by radioactive diffusible isotopes, of the densitiy of the brain tissue, by CT, and of the cerebral metabolism regionally by positron-emission tomography. Having studied 475 stroke patients par rCBF measurements and 335 by CT we think it useful to compare the value of these two methods in revealing information on the pathology underlying focal disorders of brain functions due to stroke. (orig./VJ) [de

Cyclosporine A, FK506, and NIM811 ameliorate prolonged CBF reduction and impaired neurovascular coupling after cortical spreading depression

DEFF Research Database (Denmark)

Hansen, Henning Piilgaard; Witgen, Brent Marvin; Rasmussen, Peter

2011-01-01

Cortical spreading depression (CSD) is associated with mitochondrial depolarization, increasing intracellular Ca(2+), and the release of free fatty acids, which favor opening of the mitochondrial permeability transition pore (mPTP) and activation of calcineurin (CaN). Here, we test the hypothesis...... and the specific CaN blocker FK506. Cortical spreading depression was induced in rat frontal cortex. Electrocortical activity was recorded by glass microelectrodes, CBF by laser Doppler flowmetry, and tissue oxygen tension with polarographic microelectrodes. Electrocortical activity, basal CBF, CMRO(2......), and neurovascular and neurometabolic coupling were unaffected by all three drugs under control conditions. NIM811 augmented the rise in CBF observed during CSD. Cyclosporine A and FK506 ameliorated the persistent decrease in CBF after CSD. All three drugs prevented disruption of neurovascular coupling after CSD...

Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute NO-deficiency in rats.

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Béla Horváth

Full Text Available BACKGROUND: Low frequency (4-12 cpm spontaneous fluctuations of the cerebrovascular tone (vasomotion and oscillations of the cerebral blood flow (CBF have been reported in diseases associated with endothelial dysfunction. Since endothelium-derived nitric oxide (NO suppresses constitutively the release and vascular effects of thromboxane A(2 (TXA(2, NO-deficiency is often associated with activation of thromboxane receptors (TP. In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations. METHODOLOGY/PRINCIPAL FINDINGS: Effects of pharmacological modulation of TP-receptor activation and its downstream signaling pathway have been investigated on CBF oscillations (measured by laser-Doppler flowmetry in anesthetized rats and vasomotion (measured by isometric tension recording in isolated rat middle cerebral arteries, MCAs both under physiological conditions and after acute inhibition of NO synthesis. Administration of the TP-receptor agonist U-46619 (1 µg/kg i.v. to control animals failed to induce any changes of the systemic or cerebral circulatory parameters. Inhibition of the NO synthesis by nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.v. resulted in increased mean arterial blood pressure and a decreased CBF accompanied by appearance of CBF-oscillations with a dominant frequency of 148±2 mHz. U-46619 significantly augmented the CBF-oscillations induced by L-NAME while inhibition of endogenous TXA(2 synthesis by ozagrel (10 mg/kg i.v. attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 µM Y-27632. CONCLUSION/SIGNIFICANCE: These results suggest that hypersensitivity of the TP

The temporal deployment of emotion regulation strategies during negative emotional episodes.

Science.gov (United States)

Kalokerinos, Elise K; Résibois, Maxime; Verduyn, Philippe; Kuppens, Peter

2017-04-01

Time is given a central place in theoretical models of emotion regulation (Gross, 1998, 2015), but key questions regarding the role of time remain unanswered. We investigated 2 such unanswered questions. First, we explored when different emotion regulation strategies were used within the course of an emotional episode in daily life. Second, we investigated the association between the temporal deployment of strategies and negative emotional experience. We conducted a daily diary study in which participants (N = 74) drew an intensity profile depicting the temporal unfolding of their negative emotional experience across daily events (N = 480), and mapped their usage of emotion regulation strategies onto this intensity profile. Strategies varied in their temporal deployment, with suppression and rumination occurring more at the beginning of the episode, and reappraisal and distraction occurring more toward the end of the episode. Strategies also varied in their association with negative emotion: rumination was positively associated with negative emotion, and reappraisal and distraction were negatively associated with negative emotion. Finally, both rumination and reappraisal interacted with time to predict negative emotional experience. Rumination was more strongly positively associated with negative emotions at the end of the episode than the beginning, but reappraisal was more strongly negatively associated with negative emotion at the beginning of the episode than the end. These findings highlight the importance of accounting for timing in the study of emotion regulation, as well as the necessity of studying these temporal processes in daily life. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

SPECT image analysis using SPM in patients with parkinson's disease and essential tremor : rCBF correlates of immediate surgical outcome following unilateral thalamo-pallidotomy in PD

International Nuclear Information System (INIS)

Kim, Jong Ho; Kim, Nam Bum; Lee, Uhn

2002-01-01

This study investigated alterations in regional cerebral blood flow (rCBF) in patients with PD and essential tremor (ET) using statistical parametric mapping (SPM) and rCBF correlates of immediate surgical outcome following unilateral thalamo-pallidotomy in patients with PD. Noninvasive rCBF measurements using 99m Tc-ethyl cysteinate dimer (ECD) SPECT were performed on 10 PD (60.5±8.7), 10 ET (55.5±17.7) patients and 10 healthy controls (56.2±12.0). Eight patients with PD following unilateral right thalamo-pallidotomy and five following unilateral left thalamo-pallidotomy underwent pre- and post-operative rCBF SPECT both one week before and after surgery. Acquisition were acquired within 30 min, 360 rotations with 90 projections were collected in a 128 x 128 matrix using a dual head gamma camera (Siemens, Multispect II). Data were analyzed using SPM 99. We found definite bilateral decreased rCBF in perfrontal cortex, bilateral increased rCBF in dentate nucleus of superomedial cerebellum in patients with PD and bilateral increased rCBF in lateral aspect of cerebellum in ET, respectively, compared with healthy controls. In addition, rCBF suspiciousely increased bilaterally in left dorsolateral frontal cortex in ET with equivocal clinical significance. Following 8 right and 5 left unilateral thalamo-pallidotomy in PD patients, immediate postop declines in ipsilateral fronto-temporal and temporal cortical perfusion, respectively, as well as pallidothalamic hypoperfusion were significant. SPM analysis showed that significantly decreased rCBF in bilateral perfrontal cortex and increased rCBF in dentate uncleus of superomedial cerebellum in PD and increased bilateral rCBF in lateral aspect of cerebellum in ET. Unilateral thalamo-pallidotomy in PD patients reduced the immediate post-operative rCBF declines in ipsilateral temporal (frontal) cortex as well as pallidothalamic hypoperfusion which is suggestive of thalamo-cortical diaschisis

Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine

International Nuclear Information System (INIS)

Olesen, J.; Larsen, B.; Lauritzen, M.

1981-01-01

Regional cerebral blood flow (rCBF) was measured in 254 areas of a hemisphere with the xenon 133 intraarterial injection method. Six cases of classic migraine were followed from the normal state into the prodromal phase, and in 3 cases further into the headache phase. One patient with common migraine was similarly followed during his only classic attack. The attacks were initiated by focal hyperemia in 3 patients. During prodromes all patients displayed occipitoparietal rCBF reduction (oligemia), but in only 1 case did the reduction approach critical values. Oligemia gradually spread anteriorly in the course of 15 to 45 minutes. In 4 patients a global oligemia was observed. In 4 patients severe headache was present concomitantly with oligemia and with no sign of hyperemia or nonhomogeneous brain perfusion. The normal rCBF increase during cortical activity (hand movement, speech, and similar activities) was impaired in 6 patients. The results indicate that the vasospastic model of the migraine attack is too simplistic

Three-dimensional stereotactic surface projections of rCBF analysis on the forgetfulness of patients using Mini-Mental State Examination results

International Nuclear Information System (INIS)

Nakatsuka, Hiroki; Matsubara, Ichirou; Ohtani, Haruhiko

2003-01-01

The aim of this single photon emission computed tomography (SPECT) study was to determine the abnormality of the regional cerebral blood flow (rCBF), using a three-dimensional stereotactic surface projection (3D-SSP), in 18 patients referred to the hospital due to forgetfulness. An intergroup comparison, by 3D-SSP analysis, was conducted based on Mini-Mental State Examination (MMSE) results of the total score, time orientation, place orientation, recall, serial sevens and figure copy. In each abnormal group, rCBF was partially decreased in the temporo-parietal cortex, medial temporal structure and posterior cingulate gyrus; these areas with decreased rCBF are similar to the pattern found in Alzheimer's disease. In the abnormal group, at the time of orientation and figure copy, rCBF was decreased in the right parieto-occipital area. (author)

Comparison of rCBF between patients with medial temporal lobe epilepsy and normal controls using H{sub 2}{sup 15}O PET

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Kang, Eun Joo; Lee, Jae Sung; Nam, Hyun Woo; Lee, Sang Kun; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2002-06-01

The aim of this study was to identify the brain areas whose regional cerebral blood flow (rCBF) was changed in medial temporal lobe epilepsy (mTLE) using H{sub 2}{sup 15}O-PET. 12 patients with mTLE (6 left, 6 right mTLE) and 6 normal controls were scanned during a fixation baseline period and a sensory-motor condition where subjects pressed a button to an upward arrow. A voxel-based analysis using SPM99 software was performed to compare the patient groups with the normal controls for the rCBF during fixation baseline period and for relative changes of rCBF during the sensory-motor task relative to fixation. Duirng the fixation baseline, a significant reduction of rCBF was found posterior insula bilaterally and right frontopolar regions in right mTLE patients compared to the normal controls. In left mTLE patients, the reduction was found in left frontopolar and temporal regions. During the sensory-motor task, rCBF increase over the fixation period, was reduced in left frontal and superior temporal regions in the right mTLE patients whereas in various areas of right hemisphere in left mTLE patients, relative to normal controls. However, the increased rCBF was also found in the left inferior parietal and anterior thalamic/fornix regions in both right and left mTLE patients compared to normal controls. Epilepsy induced changes were found not only in relative increase/ decrease of rCBF during a simple sensory-motor control condition relative to a fixation rest condition but also in the relative rCBF distribution during the rest period.

Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation

DEFF Research Database (Denmark)

Kim, S.G.; Rostrup, Egill; Larsson, H.B.

1999-01-01

signal changes were measured simultaneously using the flow-sensitive alternating inversion recovery (FAIR) technique. During hypercapnia established by an end-tidal CO2 increase of 1.46 kPa, CBF in the visual cortex increased by 47.3 +/- 17.3% (mean +/- SD; n = 9), and deltaR2* was -0.478 +/- 0.147 sec......The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging depends on at least partial uncoupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) changes. By measuring CBF and BOLD simultaneously, the relative change in CMRO2 can...

DMPD: Negative regulation of cytoplasmic RNA-mediated antiviral signaling. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18703349 Negative regulation of cytoplasmic RNA-mediated antiviral signaling. Komur...Show Negative regulation of cytoplasmic RNA-mediated antiviral signaling. PubmedID 18703349 Title Negative r...egulation of cytoplasmic RNA-mediated antiviral signaling. Authors Komuro A, Bamm

Combination of dynamic and integral methods for generating reproducible functional CBF images

International Nuclear Information System (INIS)

Lammertsma, A.A.; Cunningham, V.J.; Deiber, M.P.; Heather, J.D.; Bloomfield, P.M.; Nutt, J.; Frackowiak, R.S.; Jones, T.

1990-01-01

A new method to measure regional CBF is presented, applying both dynamic and integral analyses to a dynamic sequence of positron emission tomographic scans collected during and following the administration of H2(15)O (inhalation of C15O2). The dynamic analysis is used to correct continuously monitored arterial whole-blood activity for delay and dispersion relative to tissue scans. An integral analysis including corrections for this delay and dispersion is then used to calculate CBF on a pixel-by-pixel basis. Normal values and reproducibility over a 2-h period are presented, together with the results of validation and simulation studies. The results indicate that the single-tissue compartment model adequately describes the distribution of H2(15)O in the brain, without recourse to postulating a nonexchanging water pool

Altered cerebral blood flow in chronic neck pain patients but not in whiplash patients: a 99mTc-HMPAO rCBF study.

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Sundström, Torbjörn; Guez, Michel; Hildingsson, Christer; Toolanen, Göran; Nyberg, Lars; Riklund, Katrine

2006-08-01

A cross-sectional study to investigate regional cerebral blood flow (rCBF) in patients with chronic whiplash syndrome and chronic neck pain patients without previous history of trauma along with a healthy control group. Chronic neck pain is a common disorder and a history of cervical spine injury including whiplash trauma constitute a risk factor for persistent neck pain. The aetiology of the late whiplash syndrome is unknown with no specific diagnostic criteria based on imaging, physiological, or psychological examination. Earlier studies indicate a parieto-occipital hypoperfusion but it is unclear if the hypoperfusion represents a response to chronic pain. The rCBF was monitored in 45 patients with chronic neck pain: 27 cases with chronic whiplash syndrome and 18 age and gender matched cases with non-traumatic chronic neck pain. The rCBF was estimated with single-photon emission computed tomography (SPECT) using technetium-99m hexamethylpropylene amine oxime (HMPAO). The non-traumatic patients displayed rCBF changes in comparison with the whiplash group and the healthy control group. These changes included rCBF decreases in a right temporal region close to hippocampus, and increased rCBF in left insula. The whiplash group displayed no significant differences in rCBF in comparison with the healthy controls. The present study suggests different pain mechanisms in patients with chronic neck pain of non-traumatic origin compared to those with chronic neck pain due to a whiplash trauma.

What does rCBF-SPECT offer in schizophrenia?

International Nuclear Information System (INIS)

Syed, G.M.S.; Barrett, J.J.; Toone, B.K.

1992-01-01

Schizophrenia is a major psychiatric problem common in the younger population. Structural imaging and findings on autopsy have not yet revealed a specific deficit in these patients. Uncertainty in clinical diagnosis based on a set of signs and symptoms is another drawback in the management of this patient population. Regional cerebral blood flow studies (rCBF) using single photon emission computed tomography (SPECT) offers the opportunity to study the underlying phenomenon and to detect the specific functional deficits in schizophrenia. (Author)

Clinical advances of SPECT rCBF and interventional imaging applied in the diagnosis of dementias

International Nuclear Information System (INIS)

Zhang Kaijun

2002-01-01

Brain perfusion SPECT is a functional and noninvasive neuroimaging technique that allow the investigation of physiological and physiopathologic events in the human brain, including cerebral perfusion and function. Interventional rCBF imaging can also evaluate cerebrovascular reserve. In clinically, rCBF imaging play an important role in the diagnosis and differential diagnosis of dementias, especially vascular and Alzheimer's dementia. If etiology of some types of dementias is determined so that it can be early diagnosed, treated and taken prevention; the partial patients with dementia can get recovery or remission

Negative regulators of brown adipose tissue (BAT)-mediated thermogenesis.

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Sharma, Bal Krishan; Patil, Mallikarjun; Satyanarayana, Ande

2014-12-01

Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. PET-CT scans recently demonstrated the existence of metabolically active BAT in adult humans, which revitalized our interest in BAT. Increasing the amount and/or activity of BAT holds tremendous promise for the treatment of obesity and its associated diseases. PGC1α is the master regulator of UCP1-mediated thermogenesis in BAT. A number of proteins have been identified to influence thermogenesis either positively or negatively through regulating the expression or transcriptional activity of PGC1α. Therefore, BAT activation can be achieved by either inducing the expression of positive regulators of PGC1α or by inhibiting the repressors of the PGC1α/UCP1 pathway. Here, we review the most important negative regulators of PGC1α/UCP1 signaling and their mechanism of action in BAT-mediated thermogenesis. © 2014 Wiley Periodicals, Inc.

The power of extraverts: testing positive and negative mood regulation

Directory of Open Access Journals (Sweden)

Gonzalo Hervas

Full Text Available Extraversion is a personality trait which has been systematically related to positive affect and well-being. One of the mechanisms that may account for these positive outcomes is the ability to regulate the responses to positive, as well as negative, moods. Prior research has found that extraverts' higher positive mood maintenance could explain their higher levels of positive affect. However, research exploring differences between extraverts and introverts in negative mood regulation has yielded mixed results. The aim of the current study was explore the role of different facets of mood regulation displayed by extraverts, ambiverts, and introverts. After been exposed to a sad vs. happy mood induction, participants underwent a mood regulation task. Extraverts and ambiverts exhibited higher positive mood regulation than introverts, but similar mood repair. Thus, this research highlights the importance of positive mood regulation in the psychological functioning of extraverts, and opens new conceptualizations for developing interventions for introverts to improve their positive mood regulation and, hence, overall positive affect and well-being.

Down-regulation of MicroRNAs 222/221 in Acute Myelogenous Leukemia with Deranged Core-Binding Factor Subunits

Directory of Open Access Journals (Sweden)

Matteo Brioschi

2010-11-01

Full Text Available Core-binding factor leukemia (CBFL is a subgroup of acutemyeloid leukemia (AML characterized by genetic mutations involving the subunits of the core-binding factor (CBF. The leukemogenesis model for CBFL posits that one, or more, gene mutations inducing increased cell proliferation and/or inhibition of apoptosis cooperate with CBF mutations for leukemia development. One of the most commonmutations associated with CBF mutations involves the KIT receptor. A high expression of KIT is a hallmark of a high proportion of CBFL. Previous studies indicate that microRNA (MIR 222/221 targets the 3′ untranslated region of the KIT messenger RNA and our observation that AML1 can bind the MIR-222/221 promoter, we hypothesized that MIR-222/221 represents the link between CBF and KIT. Here, we show that MIR-222/221 expression is upregulated after myeloid differentiation of normal bone marrow AC133+ stem progenitor cells. CBFL blasts with either t(8;21 or inv(16 CBF rearrangements with high expression levels of KIT (CD117 display a significantly lower level of MIR-222/221 expression than non-CBFL blasts. Consistently, we found that the t(8;21 AML1-MTG8 fusion protein binds the MIR-222/221 promoter and induces transcriptional repression of a MIR-222/221-LUC reporter. Because of the highly conserved sequence homology, we demonstrated concomitant MIR-222/221 down-regulation and KIT up-regulation in the 32D/WT1 mouse cell model carrying the AML1-MTG16 fusion protein. This study provides the first hint that CBFL-associated fusion proteins may lead to up-regulation of the KIT receptor by down-regulating MIR-222/221, thus explaining the concomitant occurrence of CBF genetic rearrangements and overexpression of wild type or mutant KIT in AML.

Study on localization diagnosis with SPECT rCBF image in childhood epilepsy: in comparison with EEG and MRI findings

International Nuclear Information System (INIS)

Wu Meiqian; Tang Jihong; Wu Jinchang; Shi Yizhen

1999-01-01

Objective: To evaluate the diagnostic value of SPECT rCBF imaging in localization of childhood epileptic foci. Methods: rCBF imaging was performed in 74 epileptic patients not in seizure and 10 epileptic patients right in seizure. EEG was performed in 84, MRI in 67 of the subjects mentioned above. All the results of three modalities were compared with each other. Results: The highest positive rate (82.14%) was found in SPECT rCBF imaging, the positive rate in EEG or MRI was 71.43 or 47.76%. The epileptic foci localized by EEG (60 abnormalities) and by MRI (32 abnormalities) were 70.59% or 58.82% in concordance with those by SPECT, respectively. Conclusions: SPECT rCBF imaging is a sensitive and effective method for epileptic foci localization. It may have some advantages over EEG and MRI in detecting and localizing epileptic foci. However, abnormal SPECT areas may cover some abnormalities which do not belong to epileptic category. A combination of these three methods (SPECT, EEG and MRI) will improve the positive rate and accuracy for localizing

Positron tomography investigation in humans of the local coupling among CBF, oxygen consumption and glucose utilization

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Baron, J C; Rougemont, D; Soussaline, F; Crouzel, C; Bousser, M G; Comar, D

1983-06-01

Positron tomography investigation of the local coupling among cerebral blood flow (CBF), oxygen consumption (CMRO/sub 2/) and glucose utilization (CMRGlc) was performed in 5 controls and 6 ischemic stroke patients, using oxygen 15 inhalation technique immediately followed by I.V. injection of /sup 18/F-Fluoro-Desoxyglucose (/sup 18/FDG). The normal couple among all 3 variables was demonstrated; but on the other hand significant disruption of either or both the CBF-CMRGlc and the CMRO/sub 2/-CMRGlc couples was found in all 6 stroke patients. Comments on these new findings were made.

Usefulness of rCBF analysis in diagnosing Parkinson's disease. Supplemental role with MIBG myocardial scintigraphy

International Nuclear Information System (INIS)

Nagamachi, Shigeki; Wakamatsu, Hideyuki; Kiyohara, Shogo

2008-01-01

123 I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a useful tool for differentiating idiopathic Parkinson's disease (PD) from parkinsonism (PS) caused by other disorders. However, cardiac MIBG uptake is affected by various causes. Alternatively, hypoperfusion in the occipital lobe of PD is reported recently. The objective is to clarify the correlation between regional cerebral blood flow (rCBF) alteration and cardiac MIBG uptake in PD. In addition, we examined whether additional brain perfusion analysis improved the differential diagnostic ability for PD from PS when compared with MIBG scintigraphy alone. Forty-nine patients with PD (27 mild groups: Hoehn and Yahr stages I, II; 22 severe groups: Hoehn and Yahr stages III, IV) and 28 patients with PS participated. We compared absolute rCBF values between PD and PS. In addition, we determined correlation between MIBG parameters and each rCBF value. Finally, we compared the diagnostic ability for the differentiation of PD from PS between two diagnostic criteria, each MIBG index abnormality alone [heart-to-mediastinum ratio, H/M (E) 40%] and each MIBG index abnormality or occipital lobe hypoperfusion ( 123 I-MIBG myocardial imaging can be recommended. (author)

Difficulties in emotion regulation mediate negative and positive affects and craving in alcoholic patients.

Science.gov (United States)

Khosravani, Vahid; Sharifi Bastan, Farangis; Ghorbani, Fatemeh; Kamali, Zoleikha

2017-08-01

The aim of this study was to assess the mediating effects of difficulties in emotion regulation (DER) on the relations of negative and positive affects to craving in alcoholic patients. 205 treatment-seeking alcoholic outpatients were included. DER, positive and negative affects as well as craving were evaluated by the Difficulties in Emotion Regulation Scale (DERS), the Positive/Negative Affect Scales, and the Obsessive Compulsive Drinking Scale (OCDS) respectively. Clinical factors including depression and severity of alcohol dependence were investigated by the Alcohol Use Disorders Identification Test (AUDIT) and the Beck Depression Inventory-II (BDI-II) respectively. Results revealed that both increased negative affect and decreased positive affect indirectly influenced craving through limited access to emotion regulation strategies. It was concluded that limited access to emotion regulation strategies may be important in predicting craving for alcoholics who experience both increased negative affect and decreased positive affect. This suggests that treatment and prevention efforts focused on increasing positive affect, decreasing negative affect and teaching effective regulation strategies may be critical in reducing craving in alcoholic patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hemodynamic evaluation in patients with superficial temporal artery-middle cerebral artery anastomosis; Stable xenon CT-CBF study and acetazolamide

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Touho, Hajime; Karasawa, Jun; Shishido, Hisashi; Morisako, Toshitaka; Yamada, Keisuke; Shibamoto, Keiji [Osaka Neurological Inst., Toyonaka (Japan)

1990-12-01

Sixteen patients with minor completed stroke in the chronic stage underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. The acetazolamide-activated regional cerebral blood flow (rCBF) was measured 20 minutes after the injection using inhalation of stable xenon and computed tomographic scanning (Xe{sup s} CT-CBF study) pre- and postoperatively. Eleven patients (Group 1) showed immediate improvement in neurological state within a few days of the operation, while five (Group 2) showed no improvements. Preoperative rCBF in the ischemic areas without infarction was 30.8+-3.0 ml/100 gm/min in Group 1 and 53.0+-5.2 ml/100 gm/min in Group 2. Preoperative vasodilatory capacity with acetazolamide in Group 1 was 5.7+-8.6 and significantly increased to 19.8+-4.9 after surgery. In Group 2, pre- and postoperative vasodilatory capacity was 12.7+-3.1 and 14.9+-2.9, respectively, and there was no significant change. These results suggested that minor stroke patients with moderate decrease of affected side rCBF (less than 40 ml/100 gm/min) and with hemodynamic impairment may have the surgical indication for STA-MCA anastomosis. (author).

Regional cerebral blood flow (rCBF) measurement using D.S.P.E.C.T. and xenon inhalation: first results in distal encephalic juvenile ischemia

International Nuclear Information System (INIS)

Steinling, M.; Guerouaou, D.; Dubois, P.; Bouchez, P.; Arnott, G.; Vergnes, R.

1984-01-01

Xenon inhalation and D.S.P.E.C.T. were used for rCBF measurement in 16 patients with distal encephalic juvenile ischemia. 8 patients immediately had a second study, 15 minutes after IV injection of 500 mg acetazolamide. Results show that rCBF was abnormal in 13 patients, including some who had only minor clinical symptoms. rCBF measurement complemented neuroradiological data in 12 of 16 cases and proved more informative in 7 cases. Our most striking finding is perhaps that no patient responded normally to acetazolamide injection: three failed to respond and five showed complex (heterogeneous responses). Follow up of these patients will perhaps provide information as to the prognostic value of rCBF and acetazolamide reactivity measurements [fr

Children's Negative Emotionality Combined with Poor Self-Regulation Affects Allostatic Load in Adolescence

Science.gov (United States)

Dich, Nadya; Doan, Stacey; Evans, Gary

2015-01-01

The present study examined the concurrent and prospective, longitudinal effects of childhood negative emotionality and self-regulation on allostatic load (AL), a physiological indicator of chronic stress. We hypothesized that negative emotionality in combination with poor self-regulation would predict elevated AL. Mothers reported on children's…

Dose response from pharmacological interventions for CBF changes in a baboon model using 99Tcm-HMPAO and SPECT

International Nuclear Information System (INIS)

Dormehl, I.C.; Hugo, N.; Oliver, D.W.

1993-01-01

This study assesses the sensitivity of the baboon model under anaesthesia to determine by single photon emission computed tomography (SPECT) and 99 Tc m -hexamethylpropyleneamine oxime (HMPAO) dose responses from drugs (acetazolamide) with known regional cerebral blood flow (rCBF) effects on humans. Three dosages of acetazolamide were chosen: 250, 500 and 750 mg. The effects of these were studied by conventional SPECT 5 min after intravenous (i.v.) administration and compared to previous studies of rCBF with the baboons under anaesthesia only. An additional study concerned the effect of 500 mg acetazolamide at 15 min after administration. Haemodynamic parameters and blood gases were also monitored. No statistically significant regional effects were noted. The largest increase in CBF (39%) was observed from 500 mg acetazolamide after 5 min. This was statistically significantly different from control values only at a 10% level of confidence; then following a 27% increase above control values after 750 mg (5 min). At 15 min 500 mg yielded values lower by 10% than the high dose. No effects were observed from 250 mg acetazolamide; only pO 2 showed changes which largely confirm the CBF findings. The model did not give significant results at a 5% level of confidence but large fluctuations were observed, also in the haemodynamic and blood gas values. At a 10% level a significant dose response was confirmed for acetazolamide. (author)

An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium.

Science.gov (United States)

Droguett, Karla; Rios, Mariana; Carreño, Daniela V; Navarrete, Camilo; Fuentes, Christian; Villalón, Manuel; Barrera, Nelson P

2017-07-15

Extracellular ATP, in association with [Ca 2+ ] i regulation, is required to maintain basal ciliary beat frequency. Increasing extracellular ATP levels increases ciliary beating in airway epithelial cells, maintaining a sustained response by inducing the release of additional ATP. Extracellular ATP levels in the millimolar range, previously associated with pathophysiological conditions of the airway epithelium, produce a transient arrest of ciliary activity. The regulation of ciliary beat frequency is dependent on ATP release by hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of which may even stop ciliary movement. The force exerted by cilia, measured by atomic force microscopy, is reduced following extracellular ATP hydrolysis. This result complements the current understanding of the ciliary beating regulatory mechanism, with special relevance to inflammatory diseases of the airway epithelium that affect mucociliary clearance. Extracellular nucleotides, including ATP, are locally released by the airway epithelium and stimulate ciliary activity in a [Ca 2+ ] i -dependent manner after mechanical stimulation of ciliated cells. However, it is unclear whether the ATP released is involved in regulating basal ciliary activity and mediating changes in ciliary activity in response to chemical stimulation. In the present study, we evaluated ciliary beat frequency (CBF) and ciliary beating forces in primary cultures from mouse tracheal epithelium, using videomicroscopy and atomic force microscopy (AFM), respectively. Extracellular ATP levels and [Ca 2+ ] i were measured by luminometric and fluorimetric assays, respectively. Uptake of ethidium bromide was measured to evaluate hemichannel functionality. We show that hydrolysis of constitutive extracellular ATP levels with apyrase (50 U ml -1 ) reduced basal CBF by 45% and ciliary force by 67%. The apyrase effect on CBF was potentiated by carbenoxolone, a hemichannel inhibitor, and oxidized ATP, an

DMPD: The negative regulation of Toll-like receptor and associated pathways. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17621314 The negative regulation of Toll-like receptor and associated pathways. Lan...) Show The negative regulation of Toll-like receptor and associated pathways. PubmedID 17621314 Title The ne...gative regulation of Toll-like receptor and associated pathways. Authors Lang T,

Preserved benzodiazepine receptors in Alzheimer's disease measured with C-11 flumazenil PET and I-123 iomazenil SPECT in comparison with CBF

International Nuclear Information System (INIS)

Ohyama, Masashi; Kitamura, Shin; Mishina, Masahiro; Katayama, Yasuo; Senda, Michio; Ishiwata, Kiichi; Ishii, Kenji; Toyama, Hinako; Oda, Keiichi

1999-01-01

This study evaluates the regional cerebral blood flow (CBF) with H 2 15 O-PET and the distribution of central benzodiazepine receptor (BZR) with C-11 flumazenil (FMZ) by PET and I-123 iomazenil (IMZ) by SPECT in Alzheimer's disease (AD). In AD, whereas the CBF was diminished in the frontal, temporal, parietal, and occipital cortex, the distribution volume of FMZ and delayed activity of IMZ were relatively preserved in these cortices, suggesting that the BZR reduction, reflecting neuronal loss, is less prominent than the CBF suppression. The mini-mental state examination score (MMS) was weakly correlated with the CBF in the parietal cortex but not with BZR. It is speculated that the neuronal density reflected by BZR is less impaired than the neuronal function assessed with blood flow in the association cortex of AD. High correlation was found between the uptake of FMZ and the delayed activity of IMZ. The delayed image of IMZ-SPECT is clinically useful to evaluate the preservation of neuronal density in the affected temoporoparietal association cortex in AD. (author)

The effect of selective intraarterial infusion of the anticancer agents on cerebral hemodynamics: Concerned with the change of CBF in the non-tumoral tissue. Quantitative evaluation using 123-IMP-SPECT

International Nuclear Information System (INIS)

Hirano, Hiroko; Tomura, Noriaki; Kobayashi, Mitsuru; Ohyama, Yoichi; Watarai, Jiro

1996-01-01

The effect of intraarterial chemotherapy on cerebral blood flow (CBF) of patients with brain tumor was quantitatively studied by means of single photon emission computed tomography (SPECT). The subjects consisted of twenty patients with brain tumor (2 fibrillary astrocytoma grade II, 9 malignant astrocytoma grade III, 7 glioblastoma grade IV, 1 pineoblastoma grade IV and 1 malignant glioma). In twenty patients, twenty-four intraarterial infusions (IAs) were performed. IA chemotherapy was selectively performed through the Tracker-18 catheter, using nimustine (ACNU) in 22 infusions and tumor necrotizing factor-α (TNF) in 2 infusions. CBF was quantitatively measured by Kuhl's method, using N-isopropyl-p= 123 I=-iodoamphetamine (IMP). All patients underwent a baseline SPECT scan 1-10 days prior to IA chemotherapy, and a scan 1-22 days after IA. The change of CBF before and after IA, particularly in the non-tumoral tissue, was highlighted. CBF in the infused region as well as in the non-infused region variously changed after IA. The mean CBF of the whole brain before IA was 47.8±11.9 (mean±SD, n=24) ml/100 ml/min and than after IA was 49.3±12.4. CBF in the infused region changed (-17-+52%) after IA chemotherapy. In 12 patients whose CBF measurement was performed within 5 days after IA, CBF increased in 6 patients compared with that measured before IA. In 3 patients whose CBF measurement was performed more than 10 days after IA, CBF decreased in all of patients. This result suggested that the increase of CBF may possibly be an early change after IA chemotherapy, and that an augmented cellular metabolism and/or acute inflammatory reaction may explain this early change after IA chemotherapy. (author)

Serodiagnosis of sporotrichosis infection in cats by enzyme-linked immunosorbent assay using a specific antigen, SsCBF, and crude exoantigens.

Science.gov (United States)

Fernandes, Geisa Ferreira; Lopes-Bezerra, Leila Maria; Bernardes-Engemann, Andréa Reis; Schubach, Tânia Maria Pacheco; Dias, Maria Adelaide Galvão; Pereira, Sandro Antonio; de Camargo, Zoilo Pires

2011-01-27

The main objective of this study is to standardize an ELISA for the diagnosis of feline sporotrichosis. Sporothrix schenckii is the etiological agent of human and animal sporotrichosis. Cats may act as reservoirs for S. schenckii and can transmit the infection to humans by a bite or scratch. There are few methods for the serological diagnosis of fungal diseases in animals. In this paper, an ELISA test for the diagnosis of cat sporotrichosis is proposed, which detects S. schenckii-specific antibodies in feline sera. Two different kinds of antigens were used: "SsCBF", a specific molecule from S. schenckii that consists of a Con A-binding fraction derived from a peptido-rhamnomannan component of the cell wall, and a S. schenckii crude exoantigen preparation. The ELISA was developed, optimized, and evaluated using sera from 30 cats with proven sporotrichosis (by culture isolation); 22 sera from healthy feral cats from a zoonosis center were used as negative controls. SsCBF showed 90% sensitivity and 96% specificity in ELISA; while crude exoantigens demonstrated 96% sensitivity and 98% specificity. The ELISA assay described here would be a valuable screening tool for the detection of specific S. schenckii antibodies in cats with sporotrichosis. The assay is inexpensive, quick to perform, easy to interpret, and permits the diagnosis of feline sporotrichosis. Copyright © 2010 Elsevier B.V. All rights reserved.

Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators.

Science.gov (United States)

Le Mercier, Isabelle; Lines, J Louise; Noelle, Randolph J

2015-01-01

In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy.

Effect of memantine on CBF and CMRO2 in patients with early Parkinson's disease

DEFF Research Database (Denmark)

Borghammer, P; Vafaee, M; Ostergaard, K

2008-01-01

Objectives –  Parkinson’s disease (PD) may be associated with increased energy metabolism in overactive regions of the basal ganglia. Therefore, we hypothesized that treatment with the N-methyl-d-aspartate receptor (NMDAR) antagonist memantine would decrease regional cerebral blood flow (rCBF) an...... ganglia oxygen consumption, our data suggest that treatment with memantine actively modulates neuronal activity and/or hemodynamic response in basal ganglia of PD patients. This finding may be relevant to the putative neuroprotective properties of NMDAR antagonists.......CBF) and oxygen metabolism in the basal ganglia of patients with early-stage PD. Methods –  Quantitative positron emission tomography (PET) recordings were obtained with [15O]water and [15O]oxygen in 10 patients, scanned first in a baseline condition, and again 6 weeks after treatment with a daily dose of 20 mg...

Resting state rCBF mapping with single-photon emission tomography and positron emission tomography: magnitude and origin of differences

International Nuclear Information System (INIS)

Jonsson, C.; Kimiaei, S.; Larsson, S.A.; Pagani, M.; Ingvar, M.; Thurfjell, L.; Jacobsson, H.

1998-01-01

Single-photon emission tomography (SPET), using technetium-99m hexamethylpropylene amine oxime, and positron emission tomography (PET), using oxygen-15 butanol were compared in six healthy male volunteers with regard to the mapping of resting state regional cerebral blood flow (rCBF). A computerized brain atlas was utilized for 3D regional analyses and comparison of 64 selected and normalized volumes of interest (VOIs). The normalized mean rCBF values in SPET, as compared to PET, were higher in most of the Brodmann areas in the frontal and parietal lobes (4.8% and 8.7% respectively). The average differences were small in the temporal (2.3%) and occipital (1.1%) lobes. PET values were clearly higher in small VOIs like the thalamus (12.3%), hippocampus (12.3%) and basal ganglia (9.9%). A resolution phantom study showed that the in-plane SPET/PET system resolution was 11.0/7.5 mm. In conclusion, SPET and PET data demonstrated a fairly good agreement despite the superior spatial resolution of PET. The differences between SPET and PET rCBF are mainly due to physiological and physical factors, the data processing, normalization and co-registration methods. In order to further improve mapping of rCBF with SPET it is imperative not only to improve the spatial resolution but also to apply accurate correction techniques for scatter, attenuation and non-linear extraction. (orig.)

Cell- and stage-specific chromatin structure across the Complement receptor 2 (CR2/CD21) promoter coincide with CBF1 and C/EBP-beta binding in B cells.

Science.gov (United States)

Cruickshank, Mark N; Fenwick, Emily; Karimi, Mahdad; Abraham, Lawrence J; Ulgiati, Daniela

2009-08-01

Stringent developmental transcription requires multiple transcription factor (TF) binding sites, cell-specific expression of signaling molecules, TFs and co-regulators and appropriate chromatin structure. During B-lymphopoiesis, human Complement receptor 2 (CR2/CD21) is detected on immature and mature B cells but not on B cell precursors and plasma cells. We examined cell- and stage-specific human CR2 gene regulation using cell lines modeling B-lymphopoiesis. Chromatin accessibility assays revealed a region between -409 and -262 with enhanced accessibility in mature B cells and pre-B cells, compared to either non-lymphoid or plasma cell-types, however, accessibility near the transcription start site (TSS) was elevated only in CR2-expressing B cells. A correlation between histone acetylation and CR2 expression was observed, while histone H3K4 dimethylation was enriched near the TSS in both CR2-expressing B cells and non-expressing pre-B cells. Candidate sites within the CR2 promoter were identified which could regulate chromatin, including a matrix attachment region associated with CDP, SATB1/BRIGHT and CEBP-beta sites as well as two CBF1 sites. ChIP assays verified that both CBF1 and C/EBP-beta bind the CR2 promoter in B cells raising the possibility that these factors facilitate or respond to alterations in chromatin structure to control the timing and/or level of CR2 transcription.

Beyond CTLA-4 and PD-1, the generation Z of negative checkpoint regulators.

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Isabelle eLe Mercier

2015-08-01

Full Text Available In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy.

Regulation of positive and negative emotion: Effects of sociocultural context

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Sara A. Snyder

2013-07-01

Full Text Available Previous research has demonstrated that the use of emotion regulation strategies can vary by sociocultural context. In a previous study, we reported changes in the use of two different emotion regulation strategies at an annual alternative cultural event, Burning Man (McRae, Heller, John, & Gross, 2011. In this sociocultural context, as compared to home, participants reported less use of expressive suppression (a strategy generally associated with maladaptive outcomes, and greater use of cognitive reappraisal (a strategy associated with adaptive outcomes. What remained unclear was whether these changes in self-reported emotion regulation strategy use were characterized by changes in the regulation of positive emotion, negative emotion, or both. We addressed this issue in the current study by asking Burning Man participants separate questions about positive and negative emotion. Using multiple datasets, we not only replicated our previous findings, but also found that the decreased use of suppression is primarily driven by reports of decreased suppression of positive emotion at Burning Man. By contrast, the reported increased use of reappraisal is not characterized by differential reappraisal of positive and negative emotion at Burning Man. Moreover, we observed novel individual differences in the magnitude of these effects. The contextual changes in self-reported suppression that we report are strongest for men and younger participants. For those who had previously attended Burning Man, we observed lower levels of self-reported suppression in both sociocultural contexts: Burning Man and home. These findings have implications for understanding the ways in which certain sociocultural contexts may decrease suppression, and possibly minimize its associated maladaptive effects.

Quantification of regional cerebral blood flow (rCBF) measurement with one point sampling by sup 123 I-IMP SPECT

Energy Technology Data Exchange (ETDEWEB)

Munaka, Masahiro [University of Occupational and Enviromental Health, Kitakyushu (Japan); Iida, Hidehiro; Murakami, Matsutaro

1992-02-01

A handy method of quantifying regional cerebral blood flow (rCBF) measurement by {sup 123}I-IMP SPECT was designed. A standard input function was made and the sampling time to calibrate this standard input function by one point sampling was optimized. An average standard input function was obtained from continuous arterial samplings of 12 healthy adults. The best sampling time was the minimum differential value between the integral calculus value of the standard input function calibrated by one point sampling and the input funciton by continuous arterial samplings. This time was 8 minutes after an intravenous injection of {sup 123}I-IMP and an error was estimated to be {+-}4.1%. The rCBF values by this method were evaluated by comparing them with the rCBF values of the input function with continuous arterial samplings in 2 healthy adults and a patient with cerebral infarction. A significant correlation (r=0.764, p<0.001) was obtained between both. (author).

N-wasp is essential for the negative regulation of B cell receptor signaling.

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Chaohong Liu

2013-11-01

Full Text Available Negative regulation of receptor signaling is essential for controlling cell activation and differentiation. In B-lymphocytes, the down-regulation of B-cell antigen receptor (BCR signaling is critical for suppressing the activation of self-reactive B cells; however, the mechanism underlying the negative regulation of signaling remains elusive. Using genetically manipulated mouse models and total internal reflection fluorescence microscopy, we demonstrate that neuronal Wiskott-Aldrich syndrome protein (N-WASP, which is coexpressed with WASP in all immune cells, is a critical negative regulator of B-cell signaling. B-cell-specific N-WASP gene deletion causes enhanced and prolonged BCR signaling and elevated levels of autoantibodies in the mouse serum. The increased signaling in N-WASP knockout B cells is concurrent with increased accumulation of F-actin at the B-cell surface, enhanced B-cell spreading on the antigen-presenting membrane, delayed B-cell contraction, inhibition in the merger of signaling active BCR microclusters into signaling inactive central clusters, and a blockage of BCR internalization. Upon BCR activation, WASP is activated first, followed by N-WASP in mouse and human primary B cells. The activation of N-WASP is suppressed by Bruton's tyrosine kinase-induced WASP activation, and is restored by the activation of SH2 domain-containing inositol 5-phosphatase that inhibits WASP activation. Our results reveal a new mechanism for the negative regulation of BCR signaling and broadly suggest an actin-mediated mechanism for signaling down-regulation.

Melatonin-induced CBF/DREB1s are essential for diurnal change of disease resistance and CCA1 expression in Arabidopsis.

Science.gov (United States)

Shi, Haitao; Wei, Yunxie; He, Chaozu

2016-03-01

Melatonin (N-acetyl-5-methoxytryptamine) is an important regulator of circadian rhythms and immunity in animals. However, the diurnal changes of endogenous melatonin and melatonin-mediated diurnal change of downstream responses remain unclear in Arabidopsis. Using the publicly available microarray data, we found that the transcript levels of two melatonin synthesis genes (serotonin N-acetyltransferase (SNAT) and caffeate O-methyltransferase (COMT)) and endogenous melatonin level were regulated by diurnal cycles, with different magnitudes of change. Moreover, the transcripts of C-repeat-binding factors (CBFs)/Drought response element Binding 1 factors (DREB1s) were co-regulated by exogenous melatonin and diurnal changes, indicating the possible correlation among clock, endogenous melatonin level and AtCBFs expressions. Interestingly, diurnal change of plant immunity against Pst DC3000 and CIRCADIANCLOCK ASSOCIATED 1 (CCA1) expression were largely lost in AtCBFs knockdown line-amiR-1. Taken together, this study identifies the molecular pathway underlying the diurnal changes of immunity in Arabidopsis. Notably, the diurnal changes of endogenous melatonin may regulate corresponding changes of AtCBF/DREB1s expression and their underlying diurnal cycle of plant immunity and AtCCA1. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

dRYBP contributes to the negative regulation of the Drosophila Imd pathway.

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Ricardo Aparicio

Full Text Available The Drosophila humoral innate immune response fights infection by producing antimicrobial peptides (AMPs through the microbe-specific activation of the Toll or the Imd signaling pathway. Upon systemic infection, the production of AMPs is both positively and negatively regulated to reach a balanced immune response required for survival. Here, we report the function of the dRYBP (drosophila Ring and YY1 Binding Protein protein, which contains a ubiquitin-binding domain, in the Imd pathway. We have found that dRYBP contributes to the negative regulation of AMP production: upon systemic infection with Gram-negative bacteria, Diptericin expression is up-regulated in the absence of dRYBP and down-regulated in the presence of high levels of dRYBP. Epistatic analyses using gain and loss of function alleles of imd, Relish, or skpA and dRYBP suggest that dRYBP functions upstream or together with SKPA, a member of the SCF-E3-ubiquitin ligase complex, to repress the Imd signaling cascade. We propose that the role of dRYBP in the regulation of the Imd signaling pathway is to function as a ubiquitin adaptor protein together with SKPA to promote SCF-dependent proteasomal degradation of Relish. Beyond the identification of dRYBP as a novel component of Imd pathway regulation, our results also suggest that the evolutionarily conserved RYBP protein may be involved in the human innate immune response.

Resting state rCBF mapping with single-photon emission tomography and positron emission tomography: magnitude and origin of differences

Energy Technology Data Exchange (ETDEWEB)

Jonsson, C.; Kimiaei, S.; Larsson, S.A. [Section of Nuclear Medicine, Department of Hospital Physics, Karolinska Hospital and Department of Medical Radiation Physics, Stockholm University, Stockholm (Sweden); Pagani, M. [Institute of Experimental Medicine, CNR, Rome (Italy); Ingvar, M. [Section of Cognitive Neurophysiology, Karolinska Hospital, Stockholm (Sweden); Thurfjell, L. [Center of Image Analysis, Uppsala University, Uppsala (Sweden); Jacobsson, H. [Department of Diagnostic Radiology, Karolinska Hospital, Stockholm (Sweden)

1998-02-01

Single-photon emission tomography (SPET), using technetium-99m hexamethylpropylene amine oxime, and positron emission tomography (PET), using oxygen-15 butanol were compared in six healthy male volunteers with regard to the mapping of resting state regional cerebral blood flow (rCBF). A computerized brain atlas was utilized for 3D regional analyses and comparison of 64 selected and normalized volumes of interest (VOIs). The normalized mean rCBF values in SPET, as compared to PET, were higher in most of the Brodmann areas in the frontal and parietal lobes (4.8% and 8.7% respectively). The average differences were small in the temporal (2.3%) and occipital (1.1%) lobes. PET values were clearly higher in small VOIs like the thalamus (12.3%), hippocampus (12.3%) and basal ganglia (9.9%). A resolution phantom study showed that the in-plane SPET/PET system resolution was 11.0/7.5 mm. In conclusion, SPET and PET data demonstrated a fairly good agreement despite the superior spatial resolution of PET. The differences between SPET and PET rCBF are mainly due to physiological and physical factors, the data processing, normalization and co-registration methods. In order to further improve mapping of rCBF with SPET it is imperative not only to improve the spatial resolution but also to apply accurate correction techniques for scatter, attenuation and non-linear extraction. (orig.) With 6 figs., 3 tabs., 23 refs.

Quantitative kinetic analysis of PET amyloid imaging agents [11C]BF227 and [18F]FACT in human brain

International Nuclear Information System (INIS)

Shidahara, Miho; Watabe, Hiroshi; Tashiro, Manabu; Okamura, Nobuyuki; Furumoto, Shozo; Watanuki, Shoichi; Furukawa, Katsutoshi; Arakawa, Yuma; Funaki, Yoshihito; Iwata, Ren; Gonda, Kohsuke; Kudo, Yukitsuka; Arai, Hiroyuki; Ishiwata, Kiichi; Yanai, Kazuhiko

2015-01-01

Introduction: The purpose of this study was to compare two amyloid imaging agents, [ 11 C]BF227 and [ 18 F]FACT (derivative from [ 11 C]BF227) through quantitative pharmacokinetics analysis in human brain. Methods: Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer’s disease (AD) patients with [ 11 C]BF227 and 10 HC subjects and 10 probable AD patients with [ 18 F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients. Results: For [ 11 C]BF227, there were no significant difference of V T (2TCM, 1TCM) and SUV in all regions (Student t-test; p < 0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p < 0.05) between the HC and AD groups. For [ 18 F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p < 0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different. Conclusion: This study revealed that although the PET amyloid imaging agents [ 11 C]BF227 and [ 18 F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the

RAGE, receptor of advanced glycation endoproducts, negatively regulates chondrocytes differentiation.

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Tatsuya Kosaka

Full Text Available RAGE, receptor for advanced glycation endoproducts (AGE, has been characterized as an activator of osteoclastgenesis. However, whether RAGE directly regulates chondrocyte proliferation and differentiation is unclear. Here, we show that RAGE has an inhibitory role in chondrocyte differentiation. RAGE expression was observed in chondrocytes from the prehypertrophic to hypertrophic regions. In cultured cells, overexpression of RAGE or dominant-negative-RAGE (DN-RAGE demonstrated that RAGE inhibited cartilaginous matrix production, while DN-RAGE promoted production. Additionally, RAGE regulated Ihh and Col10a1 negatively but upregulated PTHrP receptor. Ihh promoter analysis and real-time PCR analysis suggested that downregulation of Cdxs was the key for RAGE-induced inhibition of chondrocyte differentiation. Overexpression of the NF-κB inhibitor I-κB-SR inhibited RAGE-induced NF-κB activation, but did not influence inhibition of cartilaginous matrix production by RAGE. The inhibitory action of RAGE was restored by the Rho family GTPases inhibitor Toxin B. Furthermore, inhibitory action on Ihh, Col10a1 and Cdxs was reproduced by constitutively active forms, L63RhoA, L61Rac, and L61Cdc42, but not by I-κB-SR. Cdx1 induced Ihh and Col10a1 expressions and directly interacted with Ihh promoter. Retinoic acid (RA partially rescued the inhibitory action of RAGE. These data combined suggests that RAGE negatively regulates chondrocyte differentiation at the prehypertrophic stage by modulating NF-κB-independent and Rho family GTPases-dependent mechanisms.

Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making

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Anne M. Farrell

2018-02-01

Full Text Available Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI study, we evaluated how fixed wage (FW incentives and performance-based (PB financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.

Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making.

Science.gov (United States)

Farrell, Anne M; Goh, Joshua O S; White, Brian J

2018-01-01

Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.

Metacognitive emotion regulation: children's awareness that changing thoughts and goals can alleviate negative emotions.

Science.gov (United States)

Davis, Elizabeth L; Levine, Linda J; Lench, Heather C; Quas, Jodi A

2010-08-01

Metacognitive emotion regulation strategies involve deliberately changing thoughts or goals to alleviate negative emotions. Adults commonly engage in this type of emotion regulation, but little is known about the developmental roots of this ability. Two studies were designed to assess whether 5- and 6-year-old children can generate such strategies and, if so, the types of metacognitive strategies they use. In Study 1, children described how story protagonists could alleviate negative emotions. In Study 2, children recalled times that they personally had felt sad, angry, and scared and described how they had regulated their emotions. In contrast to research suggesting that young children cannot use metacognitive regulation strategies, the majority of children in both studies described such strategies. Children were surprisingly sophisticated in their suggestions for how to cope with negative emotions and tailored their regulatory responses to specific emotional situations. Copyright 2010 APA

Negative regulation of quorum-sensing systems in Pseudomonas aeruginosa by ATP-dependent Lon protease.

Science.gov (United States)

Takaya, Akiko; Tabuchi, Fumiaki; Tsuchiya, Hiroko; Isogai, Emiko; Yamamoto, Tomoko

2008-06-01

Lon protease, a member of the ATP-dependent protease family, regulates numerous cellular systems by degrading specific substrates. Here, we demonstrate that Lon is involved in the regulation of quorum-sensing (QS) signaling systems in Pseudomonas aeruginosa, an opportunistic human pathogen. The organism has two acyl-homoserine lactone (HSL)-mediated QS systems, LasR/LasI and RhlR/RhlI. Many reports have demonstrated that these two systems are regulated and interconnected by global regulators. We found that lon-disrupted cells overproduce pyocyanin, the biosynthesis of which depends on the RhlR/RhlI system, and show increased levels of a transcriptional regulator, RhlR. The QS systems are organized hierarchically: the RhlR/RhlI system is subordinate to LasR/LasI. To elucidate the mechanism by which Lon negatively regulates RhlR/RhlI, we examined the effect of lon disruption on the LasR/LasI system. We found that Lon represses the expression of LasR/LasI by degrading LasI, an HSL synthase, leading to negative regulation of the RhlR/RhlI system. RhlR/RhlI was also shown to be regulated by Lon independently of LasR/LasI via regulation of RhlI, an HSL synthase. In view of these findings, it is suggested that Lon protease is a powerful negative regulator of both HSL-mediated QS systems in P. aeruginosa.

Processing and regulation of negative emotions in anorexia nervosa: An fMRI study

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Maria Seidel

Full Text Available Theoretical models and recent advances in the treatment of anorexia nervosa (AN have increasingly focused on the role of alterations in the processing and regulation of emotions. To date, however, our understanding of these changes is still limited and reports of emotional dysregulation in AN have been based largely on self-report data, and there is a relative lack of objective experimental evidence or neurobiological data.The current functional magnetic resonance imaging (fMRI study investigated the hemodynamic correlates of passive viewing and voluntary downregulation of negative emotions by means of the reappraisal strategy detachment in AN patients. Detachment is regarded as adaptive regulation strategy associated with a reduction in emotion-related amygdala activity and increased recruitment of prefrontal brain regions associated with cognitive control processes. Emotion regulation efficacy was assessed via behavioral arousal ratings and fMRI activation elicited by an established experimental paradigm including negative images. Participants were instructed to either simply view emotional pictures or detach themselves from feelings triggered by the stimuli.The sample consisted of 36 predominantly adolescent female AN patients and a pairwise age-matched healthy control group. Behavioral and neuroimaging data analyses indicated a reduction of arousal and amygdala activity during the regulation condition for both patients and controls. However, compared with controls, individuals with AN showed increased activation in the amygdala as well as in the right dorsolateral prefrontal cortex (dlPFC during the passive viewing of aversive compared with neutral pictures.These results extend previous findings indicative of altered processing of salient emotional stimuli in AN, but do not point to a general deficit in the voluntary regulation of negative emotions. Increased dlPFC activation in AN during passive viewing of negative stimuli is in line with

Negative regulation of neuronal cell differentiation by INHAT subunit SET/TAF-Iβ.

Science.gov (United States)

Kim, Dong-Wook; Kim, Kee-Beom; Kim, Ji-Young; Lee, Kyu-Sun; Seo, Sang-Beom

2010-09-24

Epigenetic modification plays an important role in transcriptional regulation. As a subunit of the INHAT (inhibitor of histone acetyltransferases) complex, SET/TAF-Iβ evidences transcriptional repression activity. In this study, we demonstrate that SET/TAF-Iβ is abundantly expressed in neuronal tissues of Drosophila embryos. It is expressed at high levels prior to and in early stages of neuronal development, and gradually reduced as differentiation proceeds. SET/TAF-Iβ binds to the promoters of a subset of neuronal development markers and negatively regulates the transcription of these genes. The results of this study show that the knockdown of SET/TAF-Iβ by si-RNA induces neuronal cell differentiation, thus implicating SET/TAF-Iβ as a negative regulator of neuronal development. Copyright © 2010 Elsevier Inc. All rights reserved.

Parental reactions to children's negative emotions: relationships with emotion regulation in children with an anxiety disorder.

Science.gov (United States)

Hurrell, Katherine E; Hudson, Jennifer L; Schniering, Carolyn A

2015-01-01

Research has demonstrated that parental reactions to children's emotions play a significant role in the development of children's emotion regulation (ER) and adjustment. This study compared parent reactions to children's negative emotions between families of anxious and non-anxious children (aged 7-12) and examined associations between parent reactions and children's ER. Results indicated that children diagnosed with an anxiety disorder had significantly greater difficulty regulating a range of negative emotions and were regarded as more emotionally negative and labile by their parents. Results also suggested that mothers of anxious children espoused less supportive parental emotional styles when responding to their children's negative emotions. Supportive and non-supportive parenting reactions to children's negative emotions related to children's emotion regulation skills, with father's non-supportive parenting showing a unique relationship to children's negativity/lability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Local application of 133Xenon for measurement of regional cerebral blood flow (rCBF) during halothane, enflurane, and isoflurane anesthesia in humans

International Nuclear Information System (INIS)

Eintrei, C.; Leszniewski, W.; Carlsson, C.

1985-01-01

It is well known that halothane causes an increase in cerebral blood flow (CBF). In this study the effects of halothane, enflurane, and isoflurane on regional cerebral blood flow (rCBF) in humans were determined in the presence of 70% N 2 O at a combined MAC concentration of 1.5. CBF was determined in 24 patients from the washout of locally applied 133 Xenon with the use of an external scintillation. All 24 patients (control n = 6, halothane n = 6, enflurane n = 6, and isoflurane n = 6) were undergoing neurosurgical procedures. All patients were anesthetized with thiopental, fentanyl, droperidol, and 70% N 2 O in oxygen and paralyzed with pancuronium. The measurements were performed after the dura had been opened and before definitive surgery. The first measurement was done in the absence of any volatile agent, and the wash-out curve was registered for 6 min. The second measurement was done after one of the volatile agents had been added for at least 20 min and had reached a concentration of 0.58% for halothane, 1.14% for enflurane, or 1.0% for isoflurane in the expiratory gases in order to obtain about 1.5 MAC with each volatile anesthetic. The anesthetic concentrations were measured with the Engstroem multigas analyzer EMMA. The physiologic variables changed very little throughout the period of observation. Body temperature, heart rate, blood pressure, PaCO 2 , and PaO 2 were stable. Ephedrine was used to maintain a stable arterial pressure. At approximately 1.5 MAC, halothane (plus N 2 O) increased rCBF to nearly three times (166%) the control value, while enflurane induced only a slight increase (35%) in rCBF

CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast.

Science.gov (United States)

Převorovský, Martin; Oravcová, Martina; Zach, Róbert; Jordáková, Anna; Bähler, Jürg; Půta, František; Folk, Petr

2016-11-16

For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former 2 implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals.

Effects of exogenous salicylic acid on physiological traits and CBF gene expression in peach floral organs under freezing stress

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Zhang Binbin

2017-01-01

Full Text Available To elucidate the effects of exogenous salicylic acid (SA treatment on the cold resistance of peach flower, the floral organs of two peach cultivars were treated with 20 mg/L SA and stored at 0°C for observation and sample collection. Water application was the control. After a treatment period, the anther relative water content of the control and SA-treated flowers decreased. The extent of the reduction was greater in the control, suggesting that the SA treatment significantly helped to maintain the anther water content of peach. Analysis of the stigma relative electric conductivity revealed that the SA treatment prevented membrane injury during the low temperature treatment. Additionally, we measured CBF gene expression at low temperature in the petal, stigma and ovary. The expression was markedly upregulated in the cold-treated floral organs. CBF gene expression after SA treatment was higher than in the control when cold conditions continued. These results suggest that the effects of SA on ameliorating the freezing injury to peach floral organs and on enhancing cold tolerance may be associated with the induction of CBF gene.

Comparison of D2 receptor binding (123I-IBZM) and rCBF (99mTc-HMPAO) in extrapyramidal disorders

International Nuclear Information System (INIS)

Saur, H.B.; Bartenstein, P.; Schober, O.; Oberwittler, C.; Lerch, H.; Masur, H.

1994-01-01

The aim of this SPECT study was to determine whether there is a correlation between rCBF ( 99m Tc-HMPAO) and D2 receptor binding ( 123 I-IBZM) in disorders of the extrapyramidal system and in which situation the 99 MTc-HMPAO scan could predict the outcome of the 123 I-IBZM study. 13 patients with Parkinson's syndrome and 13 patients with hyperkinetic extrapyramidal disorders were studied. In all patients the two SPECT studies were performed within 2-7 days. ROIs were placed over the basal ganglia (BG), the frontal cortex (FC) and the cerebellum (CE). The ratios BG/FC and BG/CE were calculated. In both groups the scatter was lower when the frontal cortex was used as reference region. Among the patients with hyperkinetic extrapyramidal hyperkinetic extrapyramidal disorders the two patients with Huntington's chorea had lower rCBF and D2 receptor binding compared to other hyperkinetic extrapyramidal disorders. There was no correlation between D2 receptor binding and rCBF in the basal ganglia. The 99 MTc-HMPAO studies did not provide clinically useful information, except in Huntington's chorea. (orig.) [de

Facial expression primes and implicit regulation of negative emotion.

Science.gov (United States)

Yoon, HeungSik; Kim, Shin Ah; Kim, Sang Hee

2015-06-17

An individual's responses to emotional information are influenced not only by the emotional quality of the information, but also by the context in which the information is presented. We hypothesized that facial expressions of happiness and anger would serve as primes to modulate subjective and neural responses to subsequently presented negative information. To test this hypothesis, we conducted a functional MRI study in which the brains of healthy adults were scanned while they performed an emotion-rating task. During the task, participants viewed a series of negative and neutral photos, one at a time; each photo was presented after a picture showing a face expressing a happy, angry, or neutral emotion. Brain imaging results showed that compared with neutral primes, happy facial primes increased activation during negative emotion in the dorsal anterior cingulated cortex and the right ventrolateral prefrontal cortex, which are typically implicated in conflict detection and implicit emotion control, respectively. Conversely, relative to neutral primes, angry primes activated the right middle temporal gyrus and the left supramarginal gyrus during the experience of negative emotion. Activity in the amygdala in response to negative emotion was marginally reduced after exposure to happy primes compared with angry primes. Relative to neutral primes, angry facial primes increased the subjectively experienced intensity of negative emotion. The current study results suggest that prior exposure to facial expressions of emotions modulates the subsequent experience of negative emotion by implicitly activating the emotion-regulation system.

A technique for a rapid imaging of regional CBF and partition coefficient using dynamic SPECT and N-isopropyl-p-[123I]iodoamphetamine (123I-IMP)

International Nuclear Information System (INIS)

Itoh, Hiroshi; Iida, Hidehiro; Murakami, Matsutaro

1993-01-01

IMP (iodoamphetamine) is a flow tracer due to a large first pass extraction fraction and high affinity in the brain, but significant clearance from the brain causes change of distribution when the beginning time of scan is delayed. The purpose of the present study was to develop a new method to rapidly calculate a quantitative cerebral blood flow (CBF) image by taking clearance effects into account. A dynamic SPECT scan was performed on 5 subjects (4 patients with cerebral infarction and one normal volunteer) following slow intravenous infusion of 123 I-IMP. The arterial input function was obtained by frequent blood sampling and by measuring an octanol extraction ratio for each sample. Firstly, non-linear least square fitting (NLS) was performed to investigate the tracer kinetics of 123 I-IMP. The 3 compartment model analysis yielded negligibly small k 3 (retaining rate constant) (0.0056±0.0128 (ml/ml/min)), and consistent k 1 (transport rate constant) with those determined by 2 compartment model (2CM) analysis (r=0.96, p 1 was consistent with CBF measured by 15 O water PET technique. These observations suggested the validity of using 2CM for describing the IMP tracer kinetics. Secondly, a weighted integration (WI) technique has been implemented to calculate rapidly images of CBF and partition coefficient (V d ). The WI technique yielded values of CBF (k 1 ) and V d (k 1 /k 2 ). They were confirmed to be consistent with those determined by NLS technique (CBF; r=0.99, p d ; r=0.99, p 1 agreed well with PET CBF (r=0.91, p d in infarcted patients. This supports an importance for calculating V d image. V d image will provide additional clinical information because 123 I-IMP binding mechanism may be related to cell viability. (author)

Attachment's Links With Adolescents' Social Emotions: The Roles of Negative Emotionality and Emotion Regulation.

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Murphy, Tia Panfile; Laible, Deborah J; Augustine, Mairin; Robeson, Lindsay

2015-01-01

Recent research has attempted to explain the mechanisms through which parental attachment affects social and emotional outcomes (e.g., Burnette, Taylor, Worthington, & Forsyth, 2007 ; Panfile & Laible, 2012 ). The authors' goal was to examine negative emotionality and emotion regulation as mediators of the associations that attachment has with empathy, forgiveness, guilt, and jealousy. One hundred forty-eight adolescents reported their parental attachment security, general levels of negative emotionality and abilities to regulate emotional responses, and tendencies to feel empathy, forgiveness, guilt, and jealousy. Results revealed that attachment security was associated with higher levels of empathy, forgiveness, and guilt, but lower levels of jealousy. In addition, emotion regulation mediated the links attachment shared with both empathy and guilt, such that higher levels of attachment security were linked with greater levels of emotion regulation, which led to greater levels of empathy and guilt. Alternatively, negative emotionality mediated the links attachment shared with both forgiveness and jealousy, such that higher levels of attachment security were associated with lower levels of negative emotionality, which in turn was linked to lower levels of forgiveness and higher levels of jealousy. This study provides a general picture of how attachment security may play a role in shaping an individual's levels of social emotions.

Negative regulation of EGFR/MAPK pathway by Pumilio in Drosophila melanogaster.

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Sung Yun Kim

Full Text Available In Drosophila melanogaster, specification of wing vein cells and sensory organ precursor (SOP cells, which later give rise to a bristle, requires EGFR signaling. Here, we show that Pumilio (Pum, an RNA-binding translational repressor, negatively regulates EGFR signaling in wing vein and bristle development. We observed that loss of Pum function yielded extra wing veins and additional bristles. Conversely, overexpression of Pum eliminated wing veins and bristles. Heterozygotes for Pum produced no phenotype on their own, but greatly enhanced phenotypes caused by the enhancement of EGFR signaling. Conversely, over-expression of Pum suppressed the effects of ectopic EGFR signaling. Components of the EGFR signaling pathway are encoded by mRNAs that have Nanos Response Element (NRE-like sequences in their 3'UTRs; NREs are known to bind Pum to confer regulation in other mRNAs. We show that these NRE-like sequences bind Pum and confer repression on a luciferase reporter in heterologous cells. Taken together, our evidence suggests that Pum functions as a negative regulator of EGFR signaling by directly targeting components of the pathway in Drosophila.

Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine

DEFF Research Database (Denmark)

Olesen, J; Larsen, B; Lauritzen, M

1981-01-01

anteriorly in the course of 15 to 45 minutes. In 4 patients a global oligemia was observed. In 4 patients severe headache was present concomitantly with oligemia and with no sign of hyperemia or nonhomogeneous brain perfusion. The normal rCBF increase during cortical activity (hand movement, speech...

Brain regions involved in voluntary movements as revealed by radioisotopic mapping of CBF or CMR-glucose changes

DEFF Research Database (Denmark)

Lassen, N A; Ingvar, D H

1990-01-01

Mapping of cortical and subcortical grey matter active during voluntary movements by means of measurements of local increases of CBF or CMR-Glucose is reviewed. Most of the studies concern observations in man during hand movements using the intracarotid Xenon-133 injection technique, an approach...... that only allows to image the cortex of the hemisphere on one side (the injected side) of the brain. The results show that simple static or repetitive movements mainly activate the contralateral primary hand area (MI and SI); complex preprogrammed or spontaneous purposeful movements the supplementary motor...... area SMA on both sides increase in CBF/CMR-glucose and even internally ("mentally") going through the trained movements, causes such changes; complex purposeful movements also activate the premotor cortex, a response that is bilateral with greatest response contralaterally. Studies in patients...

A Lexical Framework for Semantic Annotation of Positive and Negative Regulation Relations in Biomedical Pathways

DEFF Research Database (Denmark)

Zambach, Sine; Lassen, Tine

presented here, we analyze 6 frequently used verbs denoting the regulation relations regulates, positively regulates and negatively regulates through corpus analysis, and propose a formal representation of the acquired knowledge as domain speci¯c semantic frames. The acquired knowledge patterns can thus...

Automatic control of negative emotions: evidence that structured practice increases the efficiency of emotion regulation.

Science.gov (United States)

Christou-Champi, Spyros; Farrow, Tom F D; Webb, Thomas L

2015-01-01

Emotion regulation (ER) is vital to everyday functioning. However, the effortful nature of many forms of ER may lead to regulation being inefficient and potentially ineffective. The present research examined whether structured practice could increase the efficiency of ER. During three training sessions, comprising a total of 150 training trials, participants were presented with negatively valenced images and asked either to "attend" (control condition) or "reappraise" (ER condition). A further group of participants did not participate in training but only completed follow-up measures. Practice increased the efficiency of ER as indexed by decreased time required to regulate emotions and increased heart rate variability (HRV). Furthermore, participants in the ER condition spontaneously regulated their negative emotions two weeks later and reported being more habitual in their use of ER. These findings indicate that structured practice can facilitate the automatic control of negative emotions and that these effects persist beyond training.

Separation of input function for rapid measurement of quantitative CMRO2 and CBF in a single PET scan with a dual tracer administration method

International Nuclear Information System (INIS)

Kudomi, Nobuyuki; Watabe, Hiroshi; Hayashi, Takuya; Iida, Hidehiro

2007-01-01

Cerebral metabolic rate of oxygen (CMRO 2 ), oxygen extraction fraction (OEF) and cerebral blood flow (CBF) images can be quantified using positron emission tomography (PET) by administrating 15 O-labelled water (H 15 2 O) and oxygen ( 15 O 2 ). Conventionally, those images are measured with separate scans for three tracers C 15 O for CBV, H 15 2 O for CBF and 15 O 2 for CMRO 2 , and there are additional waiting times between the scans in order to minimize the influence of the radioactivity from the previous tracers, which results in a relatively long study period. We have proposed a dual tracer autoradiographic (DARG) approach (Kudomi et al 2005), which enabled us to measure CBF, OEF and CMRO 2 rapidly by sequentially administrating H 15 2 O and 15 O 2 within a short time. Because quantitative CBF and CMRO 2 values are sensitive to arterial input function, it is necessary to obtain accurate input function and a drawback of this approach is to require separation of the measured arterial blood time-activity curve (TAC) into pure water and oxygen input functions under the existence of residual radioactivity from the first injected tracer. For this separation, frequent manual sampling was required. The present paper describes two calculation methods: namely a linear and a model-based method, to separate the measured arterial TAC into its water and oxygen components. In order to validate these methods, we first generated a blood TAC for the DARG approach by combining the water and oxygen input functions obtained in a series of PET studies on normal human subjects. The combined data were then separated into water and oxygen components by the present methods. CBF and CMRO 2 were calculated using those separated input functions and tissue TAC. The quantitative accuracy in the CBF and CMRO 2 values by the DARG approach did not exceed the acceptable range, i.e., errors in those values were within 5%, when the area under the curve in the input function of the second tracer

Interictal SPECT of rCBF is of clinical utility in the preoperative evaluation of patients with partial epilepsy

DEFF Research Database (Denmark)

Andersen, A R; Hansen, B A; Høgenhaven, H

1996-01-01

Fifty-eight patients with drug-resistant partial epilepsy were studied preoperatively by interictal rCBF measurements using 99mTc-HMPAO and a dedicated brain SPECT camera (Tomomatic 64). Follow-up of seizure outcome, using the "Engel score", was at least 3 years. The data were analyzed in a blinded...... set-up, first visually and subsequently quantitatively by an automatic regional analysis. By visual analysis 95% of the patients were considered abnormal in one part of the brain, of whom 27% were abnormal on CT, 45% on MRI and 98% on scalp EEG. Using a quantitative regional analysis subdividing each...... patients ictal SPECT of rCBF was additionally performed. In 2 cases it added further information to the patient evaluation....

Interictal SPECT of rCBF is of clinical utility in the preoperative evaluation of patients with partial epilepsy

DEFF Research Database (Denmark)

Andersen, A.R.; Hansen, B.A.; Hogenhaven, H

1996-01-01

Fifty-eight patients with drug-resistant partial epilepsy were studied preoperatively by interictal rCBF measurements using 99mTc-HMPAO and a dedicated brain SPECT camera (Tomomatic 64). Follow-up of seizure outcome, using the 'Engel score', was at least 3 years. The data were analyzed in a blinded...... set-up, first visually and subsequently quantitatively by an automatic regional analysis. By visual analysis 95% of the patients were considered abnormal in one part of the brain, of whom 27% were abnormal on CT, 45% on MRI and 98% on scalp EEG. Using a quantitative regional analysis subdividing each...... patients ictal SPECT of rCBF was additionally performed. In 2 cases it added further information to the patient evaluation...

Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

Directory of Open Access Journals (Sweden)

Jenkins Dafyd J

2008-01-01

Full Text Available Abstract Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusion Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic

Amelioration of rCBF and PbtO2 following TBI at high altitude by hyperbaric oxygen pre-conditioning.

Science.gov (United States)

Hu, Shengli; Li, Fei; Luo, Haishui; Xia, Yongzhi; Zhang, Jiuquan; Hu, Rong; Cui, Gaoyu; Meng, Hui; Feng, Hua

2010-03-01

Hypobaric hypoxia at high altitude can lead to brain damage and pre-conditioning with hyperbaric oxygen (HBO) can reduce ischemic/hypoxic brain injury. This study investigates the effects of high altitude on traumatic brain injury (TBI) and examines the neuroprotection provided by HBO preconditioning against TBI. Rats were randomly divided into four groups: HBO pre-conditioning group (HBOP, n=10), high altitude group (HA, n=10), plain control group (PC, n=10) and plain sham operation group (sham, n=10). All groups were subjected to head trauma by weight drop device except for the sham group. Rats from each group were examined for neurological function, regional cerebral blood flow (rCBF) and brain tissue oxygen pressure (PbtO(2)) and were killed for analysis by transmission electron microscope. The score of neurological deficits in the HA group was highest, followed by the HBOP group and the PC group, respectively. Both rCBF and PbtO(2) were the lowest in the HA group. Brain morphology and structure seen via the transmission electron microscope was diminished in the HA group, while fewer pathological injuries occurred in the HBOP and PC groups. High altitude aggravates TBI significantly and HBO pre-conditioning can attenuate TBI in rats at high altitude by improvement of rCBF and PbtO(2). Pre-treatment with HBO might be beneficial for people traveling to high altitude locations.

Improvement in regional CBF by L-serine contributes to its neuroprotective effect in rats after focal cerebral ischemia.

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Tao-Jie Ren

Full Text Available To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF. Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1 reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2 improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3 increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca(2+-activated K(+ channels on the cerebral blood vessel endothelium.

Transcription Factor Foxo1 Is a Negative Regulator of NK Cell Maturation and Function

Science.gov (United States)

Deng, Youcai; Kerdiles, Yann; Chu, Jianhong; Yuan, Shunzong; Wang, Youwei; Chen, Xilin; Mao, Hsiaoyin; Zhang, Lingling; Zhang, Jianying; Hughes, Tiffany; Deng, Yafei; Zhang, Qi; Wang, Fangjie; Zou, Xianghong; Liu, Chang-Gong; Freud, Aharon G.; Li, Xiaohui; Caligiuri, Michael A; Vivier, Eric; Yu, Jianhua

2015-01-01

SUMMARY Little is known about the role of negative regulators in controlling natural killer (NK) cell development and effector functions. Foxo1 is a multifunctional transcription factor of the forkhead family. Using a mouse model of conditional deletion in NK cells, we found that Foxo1 negatively controlled NK cell differentiation and function. Immature NK cells expressed abundant Foxo1 and little Tbx21 relative to mature NK cells, but these two transcription factors reversed their expression as NK cells proceeded through development. Foxo1 promoted NK cell homing to lymph nodes through upregulating CD62L expression, and impaired late-stage maturation and effector functions by repressing Tbx21 expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in heterozygous Tbx21+/− mice. Collectively, our data reveal a regulatory pathway by which the negative regulator Foxo1 and the positive regulator Tbx21 play opposing roles in controlling NK cell development and effector functions. PMID:25769609

Mothers' responses to children's negative emotions and child emotion regulation: the moderating role of vagal suppression.

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Perry, Nicole B; Calkins, Susan D; Nelson, Jackie A; Leerkes, Esther M; Marcovitch, Stuart

2012-07-01

The current study examined the moderating effect of children's cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and nonsupportive responses) and children's emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children's negative emotions and children's regulatory behaviors. Observed distraction, an adaptive self-regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children's vagal suppression moderated the association between mothers' nonsupportive emotion socialization and children's emotion regulation behaviors such that nonsupportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children's emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against nonsupportive emotion socialization. Copyright © 2011 Wiley Periodicals, Inc.

Instrumental motives in negative emotion regulation in daily life: Frequency, consistency, and predictors.

Science.gov (United States)

Kalokerinos, Elise K; Tamir, Maya; Kuppens, Peter

2017-06-01

People regulate their emotions not only for hedonic reasons but also for instrumental reasons, to attain the potential benefits of emotions beyond pleasure and pain. However, such instrumental motives have rarely been examined outside the laboratory as they naturally unfold in daily life. To assess whether and how instrumental motives operate outside the laboratory, it is necessary to examine them in response to real and personally relevant stimuli in ecologically valid contexts. In this research, we assessed the frequency, consistency, and predictors of instrumental motives in negative emotion regulation in daily life. Participants (N = 114) recalled the most negative event of their day each evening for 7 days and reported their instrumental motives and negative emotion goals in that event. Participants endorsed performance motives in approximately 1 in 3 events and social, eudaimonic, and epistemic motives in approximately 1 in 10 events. Instrumental motives had substantially higher within- than between-person variance, indicating that they were context-dependent. Indeed, although we found few associations between instrumental motives and personality traits, relationships between instrumental motives and contextual variables were more extensive. Performance, social, and epistemic motives were each predicted by a unique pattern of contextual appraisals. Our data demonstrate that instrumental motives play a role in daily negative emotion regulation as people encounter situations that pose unique regulatory demands. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Statistical parametric mapping in the detection of rCBF changes in mild Alzheimer's disease

International Nuclear Information System (INIS)

Rowe, C.; Barnden, L.; Boundy, K.; McKinnon, J.; Liptak, M.

1998-01-01

Full text: Reduction in temporoparietal regional cerebral blood flow (rCBF) is proportional to the degree of cognitive deficit in patients with Alzheimer's Disease (AD). The characteristic pattern is readily apparent in advanced disease but is often subtle in early stage AD, reducing the clinical value of SPECT in the management of this condition. We have previously reported that Statistical Parametric Mapping (SPM95) revealed significant temporoparietal hypoperfusion when 10 patients with mild AD (classified by the Clinical Dementia Rating Scale) were compared to 10 age matched normals. We have now begun to evaluate the sensitivity and specificity of SPM95 in individuals with mild AD by comparison to our bank of 39 normals (30 female, 9 male, age range 26 to 74, mean age 52). Preliminary results reveal low sensitivity (<40%) when the standard reference region for normalization (i.e. global brain counts) is used. Better results are expected from normalizing to the cerebellum or basal ganglia and this is under investigation. An objective method to improve the accuracy of rCBF imaging for the diagnosis of early AD would be very useful in clinical practice. This study will demonstrate whether SPM can fulfill this role

Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction

Science.gov (United States)

DelloStritto, Daniel J.; Connell, Patrick J.; Dick, Gregory M.; Fancher, Ibra S.; Klarich, Brittany; Fahmy, Joseph N.; Kang, Patrick T.; Chen, Yeong-Renn; Damron, Derek S.; Thodeti, Charles K.

2016-01-01

We demonstrated previously that TRPV1-dependent coupling of coronary blood flow (CBF) to metabolism is disrupted in diabetes. A critical amount of H2O2 contributes to CBF regulation; however, excessive H2O2 impairs responses. We sought to determine the extent to which differential regulation of TRPV1 by H2O2 modulates CBF and vascular reactivity in diabetes. We used contrast echocardiography to study TRPV1 knockout (V1KO), db/db diabetic, and wild type C57BKS/J (WT) mice. H2O2 dose-dependently increased CBF in WT mice, a response blocked by the TRPV1 antagonist SB366791. H2O2-induced vasodilation was significantly inhibited in db/db and V1KO mice. H2O2 caused robust SB366791-sensitive dilation in WT coronary microvessels; however, this response was attenuated in vessels from db/db and V1KO mice, suggesting H2O2-induced vasodilation occurs, in part, via TRPV1. Acute H2O2 exposure potentiated capsaicin-induced CBF responses and capsaicin-mediated vasodilation in WT mice, whereas prolonged luminal H2O2 exposure blunted capsaicin-induced vasodilation. Electrophysiology studies re-confirms acute H2O2 exposure activated TRPV1 in HEK293A and bovine aortic endothelial cells while establishing that H2O2 potentiate capsaicin-activated TRPV1 currents, whereas prolonged H2O2 exposure attenuated TRPV1 currents. Verification of H2O2-mediated activation of intrinsic TRPV1 specific currents were found in isolated mouse coronary endothelial cells from WT mice and decreased in endothelial cells from V1KO mice. These data suggest prolonged H2O2 exposure impairs TRPV1-dependent coronary vascular signaling. This may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes. PMID:26907473

A comprehensive protein-protein interactome for yeast PAS kinase 1 reveals direct inhibition of respiration through the phosphorylation of Cbf1.

Science.gov (United States)

DeMille, Desiree; Bikman, Benjamin T; Mathis, Andrew D; Prince, John T; Mackay, Jordan T; Sowa, Steven W; Hall, Tacie D; Grose, Julianne H

2014-07-15

Per-Arnt-Sim (PAS) kinase is a sensory protein kinase required for glucose homeostasis in yeast, mice, and humans, yet little is known about the molecular mechanisms of its function. Using both yeast two-hybrid and copurification approaches, we identified the protein-protein interactome for yeast PAS kinase 1 (Psk1), revealing 93 novel putative protein binding partners. Several of the Psk1 binding partners expand the role of PAS kinase in glucose homeostasis, including new pathways involved in mitochondrial metabolism. In addition, the interactome suggests novel roles for PAS kinase in cell growth (gene/protein expression, replication/cell division, and protein modification and degradation), vacuole function, and stress tolerance. In vitro kinase studies using a subset of 25 of these binding partners identified Mot3, Zds1, Utr1, and Cbf1 as substrates. Further evidence is provided for the in vivo phosphorylation of Cbf1 at T211/T212 and for the subsequent inhibition of respiration. This respiratory role of PAS kinase is consistent with the reported hypermetabolism of PAS kinase-deficient mice, identifying a possible molecular mechanism and solidifying the evolutionary importance of PAS kinase in the regulation of glucose homeostasis. © 2014 DeMille et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

When less is more: Effects of the availability of strategic options on regulating negative emotions.

Science.gov (United States)

Bigman, Yochanan E; Sheppes, Gal; Tamir, Maya

2017-09-01

Research in several domains suggests that having strategic options is not always beneficial. In this paper, we tested whether having strategic options (vs. not) is helpful or harmful for regulating negative emotions. In 5 studies (N = 151) participants were presented with 1 or more strategic options prior to watching aversive images and using the selected strategic option. Across studies, we found that people reported less intense negative emotions when the strategy they used to regulate their emotions was presented as a single option, rather than as 1 of several options. This was regardless of whether people could choose between the options (Studies 3-5) or not (Studies 1, 2, and 4), and specific to negative (but not neutral) images (Study 5). A sixth study addressed an explanation based on demand characteristics, showing that participants expected to feel more positive when having more than 1 option. The findings indicate that having strategic options for regulating negative emotions can sometimes be costly. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Mutation analysis of the negative regulator cyclin G2 in gastric cancer

African Journals Online (AJOL)

Jane

2011-10-24

Oct 24, 2011 ... Key words: Cyclin G2, gastric cancer, negative regulator, mutation screen. INTRODUCTION ... cerebellum, thymus, spleen, prostate, kidney and the immune ..... and B cell antigen receptor-mediated cell cycle arrest. J. Biol.

Modeling the role of negative cooperativity in metabolic regulation and homeostasis.

Directory of Open Access Journals (Sweden)

Eliot C Bush

Full Text Available A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous.

A Comparison of Autonomous Regulation and Negative Self-Evaluative Emotions as Predictors of Smoking Behavior Change among College Students

Science.gov (United States)

Lee, Hyoung S.; Catley, Delwyn; Harris, Kari Jo

2011-01-01

This study compared autonomous self-regulation and negative self-evaluative emotions as predictors of smoking behavior change in college student smokers (N=303) in a smoking cessation intervention study. Although the two constructs were moderately correlated, latent growth curve modeling revealed that only autonomous regulation, but not negative self-evaluative emotions, was negatively related to the number of days smoked. Results suggest that the two variables tap different aspects of motivation to change smoking behaviors, and that autonomous regulation predicts smoking behavior change better than negative self-evaluative emotions. PMID:21911436

A comparison of autonomous regulation and negative self-evaluative emotions as predictors of smoking behavior change among college students.

Science.gov (United States)

Lee, Hyoung S; Catley, Delwyn; Harris, Kari Jo

2012-05-01

This study compared autonomous self-regulation and negative self-evaluative emotions as predictors of smoking behavior change in college student smokers (N = 303) in a smoking cessation intervention study. Although the two constructs were moderately correlated, latent growth curve modeling revealed that only autonomous regulation, but not negative self-evaluative emotions, was negatively related to the number of days smoked. Results suggest that the two variables tap different aspects of motivation to change smoking behaviors, and that autonomous regulation predicts smoking behavior change better than negative self-evaluative emotions.

Expression of Androgen Receptor Is Negatively Regulated By p53

Directory of Open Access Journals (Sweden)

Fatouma Alimirah

2007-12-01

Full Text Available Increased expression of androgen receptor (AR in prostate cancer (PC is associated with transition to androgen independence. Because the progression of PC to advanced stages is often associated with the loss of p53 function, we tested whether the p53 could regulate the expression of AR gene. Here we report that p53 negatively regulates the expression of AR in prostate epithelial cells (PrECs. We found that in LNCaP human prostate cancer cells that express the wild-type p53 and AR and in human normal PrECs, the activation of p53 by genotoxic stress or by inhibition of p53 nuclear export downregulated the expression of AR. Furthermore, forced expression of p53 in LNCaP cells decreased the expression of AR. Conversely, knockdown of p53 expression in LNCaP cells increased the AR expression. Consistent with the negative regulation of AR expression by p53, the p53-null HCT116 cells expressed higher levels of AR compared with the isogenic HCT116 cells that express the wildtype p53. Moreover, we noted that in etoposide treated LNCaP cells p53 bound to the promoter region of the AR gene, which contains a potential p53 DNA-binding consensus sequence, in chromatin immunoprecipitation assays. Together, our observations provide support for the idea that the loss of p53 function in prostate cancer cells contributes to increased expression of AR.

Maternal depression and anxiety, social synchrony, and infant regulation of negative and positive emotions.

Science.gov (United States)

Granat, Adi; Gadassi, Reuma; Gilboa-Schechtman, Eva; Feldman, Ruth

2017-02-01

Maternal postpartum depression (PPD) exerts long-term negative effects on infants; yet the mechanisms by which PPD disrupts emotional development are not fully clear. Utilizing an extreme-case design, 971 women reported symptoms of depression and anxiety following childbirth and 215 high and low on depressive symptomatology reported again at 6 months. Of these, mothers diagnosed with major depressive disorder (n = 22), anxiety disorders (n = 19), and controls (n = 59) were visited at 9 months. Mother-infant interaction was microcoded for maternal and infant's social behavior and synchrony. Infant negative and positive emotional expression and self-regulation were tested in 4 emotion-eliciting paradigms: anger with mother, anger with stranger, joy with mother, and joy with stranger. Infants of depressed mothers displayed less social gaze and more gaze aversion. Gaze and touch synchrony were lowest for depressed mothers, highest for anxious mothers, and midlevel among controls. Infants of control and anxious mothers expressed less negative affect with mother compared with stranger; however, maternal presence failed to buffer negative affect in the depressed group. Maternal depression chronicity predicted increased self-regulatory behavior during joy episodes, and touch synchrony moderated the effects of PPD on infant self-regulation. Findings describe subtle microlevel processes by which maternal depression across the postpartum year disrupts the development of infant emotion regulation and suggest that diminished social synchrony, low differentiation of attachment and nonattachment contexts, and increased self-regulation during positive moments may chart pathways for the cross-generational transfer of emotional maladjustment from depressed mothers to their infants. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Overexpression of a wheat (Triticum aestivum L.) bZIP transcription factor gene, TabZIP6, decreased the freezing tolerance of transgenic Arabidopsis seedlings by down-regulating the expression of CBFs.

Science.gov (United States)

Cai, Wangting; Yang, Yaling; Wang, Weiwei; Guo, Guangyan; Liu, Wei; Bi, Caili

2018-03-01

The basic leucine zipper (bZIP) proteins play important roles against abiotic stress in plants, including cold stress. However, most bZIPs involved in plant freezing tolerance are positive regulators. Only a few bZIPs function negatively in cold stress response. In this study, TabZIP6, a Group C bZIP transcription factor gene from common wheat (Triticum aestivum L.), was cloned and characterized. The transcript of TabZIP6 was strongly induced by cold treatment (4 °C). TabZIP6 is a nuclear-localized protein with transcriptional activation activity. Arabidopsis plants overexpressing TabZIP6 showed decreased tolerance to freezing stress. Microarray as well as quantitative real-time PCR (qRT-PCR) analysis showed that CBFs and some key COR genes, including COR47 and COR15B, were down-regulated by cold treatment in TabZIP6-overexpressing Arabidopsis lines. TabZIP6 was capable of binding to the G-box motif and the CBF1 and CBF3 promoters in yeast cells. A yeast two-hybrid assay revealed that TabZIP6, as well as the other two Group S bZIP proteins involved in cold stress tolerance in wheat, Wlip19 and TaOBF1, can form homodimers by themselves and heterodimers with each other. These results suggest that TabZIP6 may function negatively in the cold stress response by binding to the promoters of CBFs, and thereby decreasing the expression of downstream COR genes in TabZIP6-overexpressing Arabidopsis seedlings. Copyright © 2018. Published by Elsevier Masson SAS.

The carboxy-terminal domain of Dictyostelium C-module-binding factor is an independent gene regulatory entity.

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Jörg Lucas

Full Text Available The C-module-binding factor (CbfA is a multidomain protein that belongs to the family of jumonji-type (JmjC transcription regulators. In the social amoeba Dictyostelium discoideum, CbfA regulates gene expression during the unicellular growth phase and multicellular development. CbfA and a related D. discoideum CbfA-like protein, CbfB, share a paralogous domain arrangement that includes the JmjC domain, presumably a chromatin-remodeling activity, and two zinc finger-like (ZF motifs. On the other hand, the CbfA and CbfB proteins have completely different carboxy-terminal domains, suggesting that the plasticity of such domains may have contributed to the adaptation of the CbfA-like transcription factors to the rapid genome evolution in the dictyostelid clade. To support this hypothesis we performed DNA microarray and real-time RT-PCR measurements and found that CbfA regulates at least 160 genes during the vegetative growth of D. discoideum cells. Functional annotation of these genes revealed that CbfA predominantly controls the expression of gene products involved in housekeeping functions, such as carbohydrate, purine nucleoside/nucleotide, and amino acid metabolism. The CbfA protein displays two different mechanisms of gene regulation. The expression of one set of CbfA-dependent genes requires at least the JmjC/ZF domain of the CbfA protein and thus may depend on chromatin modulation. Regulation of the larger group of genes, however, does not depend on the entire CbfA protein and requires only the carboxy-terminal domain of CbfA (CbfA-CTD. An AT-hook motif located in CbfA-CTD, which is known to mediate DNA binding to A+T-rich sequences in vitro, contributed to CbfA-CTD-dependent gene regulatory functions in vivo.

Wheat CBL-interacting protein kinase 25 negatively regulates salt tolerance in transgenic wheat

OpenAIRE

Jin, Xia; Sun, Tao; Wang, Xiatian; Su, Peipei; Ma, Jingfei; He, Guangyuan; Yang, Guangxiao

2016-01-01

CBL-interacting protein kinases are involved in plant responses to abiotic stresses, including salt stress. However, the negative regulating mechanism of this gene family in response to salinity is less reported. In this study, we evaluated the role of TaCIPK25 in regulating salt response in wheat. Under conditions of high salinity, TaCIPK25 expression was markedly down-regulated in roots. Overexpression of TaCIPK25 resulted in hypersensitivity to Na+ and superfluous accumulation of Na+ in tr...

Age Differences in the Influence of Induced Negative Emotion on Decision-Making: The Role of Emotion Regulation.

Science.gov (United States)

You, Xuqun; Ju, Chengting; Wang, Mo; Zhang, Baoshan; Liu, Pei

2017-11-19

In this study, we hypothesized that there is an age difference in the influence of negative emotion on decision-making and that this age difference is related to emotion regulation strategies. We carried out two studies. In the first, the older and younger adults completed the ultimatum game (UG) while in either an induced negative emotional or a neutral context. In the second, both the older and younger adults completed the UG while in an induced negative emotion while using either emotion reappraisal or expressive suppression to regulate their emotions during the task. The first study showed that, unlike younger adults, the older adults made similar choices in the neutral and negative induction groups. In addition, the older adults predominantly used a reappraisal strategy in both the negative and neutral emotional states, whereas the younger adults predominantly used a suppression strategy in the negative emotional state. In the second study, after the emotion regulation strategies were experimentally manipulated so that both age groups used the same strategy, we found no age difference in decision-making. Our findings indicated that the influence of negative emotion on decision-making differs between older and younger adults and that this age difference was associated with their different emotion regulation processes. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A nonparametric mean-variance smoothing method to assess Arabidopsis cold stress transcriptional regulator CBF2 overexpression microarray data.

Science.gov (United States)

Hu, Pingsha; Maiti, Tapabrata

2011-01-01

Microarray is a powerful tool for genome-wide gene expression analysis. In microarray expression data, often mean and variance have certain relationships. We present a non-parametric mean-variance smoothing method (NPMVS) to analyze differentially expressed genes. In this method, a nonlinear smoothing curve is fitted to estimate the relationship between mean and variance. Inference is then made upon shrinkage estimation of posterior means assuming variances are known. Different methods have been applied to simulated datasets, in which a variety of mean and variance relationships were imposed. The simulation study showed that NPMVS outperformed the other two popular shrinkage estimation methods in some mean-variance relationships; and NPMVS was competitive with the two methods in other relationships. A real biological dataset, in which a cold stress transcription factor gene, CBF2, was overexpressed, has also been analyzed with the three methods. Gene ontology and cis-element analysis showed that NPMVS identified more cold and stress responsive genes than the other two methods did. The good performance of NPMVS is mainly due to its shrinkage estimation for both means and variances. In addition, NPMVS exploits a non-parametric regression between mean and variance, instead of assuming a specific parametric relationship between mean and variance. The source code written in R is available from the authors on request.

Flg22-Triggered Immunity Negatively Regulates Key BR Biosynthetic Genes.

Science.gov (United States)

Jiménez-Góngora, Tamara; Kim, Seong-Ki; Lozano-Durán, Rosa; Zipfel, Cyril

2015-01-01

In plants, activation of growth and activation of immunity are opposing processes that define a trade-off. In the past few years, the growth-promoting hormones brassinosteroids (BR) have emerged as negative regulators of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), promoting growth at the expense of defense. The crosstalk between BR and PTI signaling was described as negative and unidirectional, since activation of PTI does not affect several analyzed steps in the BR signaling pathway. In this work, we describe that activation of PTI by the bacterial PAMP flg22 results in the reduced expression of BR biosynthetic genes. This effect does not require BR perception or signaling, and occurs within 15 min of flg22 treatment. Since the described PTI-induced repression of gene expression may result in a reduction in BR biosynthesis, the crosstalk between PTI and BR could actually be negative and bidirectional, a possibility that should be taken into account when considering the interaction between these two pathways.

BRAFV600E negatively regulates the AKT pathway in melanoma cell lines.

Science.gov (United States)

Chen, Brenden; Tardell, Christine; Higgins, Brian; Packman, Kathryn; Boylan, John F; Niu, Huifeng

2012-01-01

Cross-feedback activation of MAPK and AKT pathways is implicated as a resistance mechanism for cancer therapeutic agents targeting either RAF/MEK or PI3K/AKT/mTOR. It is thus important to have a better understanding of the molecular resistance mechanisms to improve patient survival benefit from these agents. Here we show that BRAFV600E is a negative regulator of the AKT pathway. Expression of BRAFV600E in NIH3T3 cells significantly suppresses MEK inhibitor (RG7167) or mTORC1 inhibitor (rapamycin) induced AKT phosphorylation (pAKT) and downstream signal activation. Treatment-induced pAKT elevation is found in BRAF wild type melanoma cells but not in a subset of melanoma cell lines harboring BRAFV600E. Knock-down of BRAFV600E in these melanoma cells elevates basal pAKT and downstream signals, whereas knock-down of CRAF, MEK1/2 or ERK1/2 or treatment with a BRAF inhibitor have no impact on pAKT. Mechanistically, we show that BRAFV600E interacts with rictor complex (mTORC2) and regulates pAKT through mTORC2. BRAFV600E is identified in mTORC2 after immunoprecipitation of rictor. Knock-down of rictor abrogates BRAFV600E depletion induced pAKT. Knock-down of BRAFV600E enhances cellular enzyme activity of mTORC2. Aberrant activation of AKT pathway by PTEN loss appears to override the negative impact of BRAFV600E on pAKT. Taken together, our findings suggest that in a subset of BRAFV600E melanoma cells, BRAFV600E negatively regulates AKT pathway in a rictor-dependent, MEK/ERK and BRAF kinase-independent manner. Our study reveals a novel molecular mechanism underlying the regulation of feedback loops between the MAPK and AKT pathways.

BRAFV600E negatively regulates the AKT pathway in melanoma cell lines.

Directory of Open Access Journals (Sweden)

Brenden Chen

Full Text Available Cross-feedback activation of MAPK and AKT pathways is implicated as a resistance mechanism for cancer therapeutic agents targeting either RAF/MEK or PI3K/AKT/mTOR. It is thus important to have a better understanding of the molecular resistance mechanisms to improve patient survival benefit from these agents. Here we show that BRAFV600E is a negative regulator of the AKT pathway. Expression of BRAFV600E in NIH3T3 cells significantly suppresses MEK inhibitor (RG7167 or mTORC1 inhibitor (rapamycin induced AKT phosphorylation (pAKT and downstream signal activation. Treatment-induced pAKT elevation is found in BRAF wild type melanoma cells but not in a subset of melanoma cell lines harboring BRAFV600E. Knock-down of BRAFV600E in these melanoma cells elevates basal pAKT and downstream signals, whereas knock-down of CRAF, MEK1/2 or ERK1/2 or treatment with a BRAF inhibitor have no impact on pAKT. Mechanistically, we show that BRAFV600E interacts with rictor complex (mTORC2 and regulates pAKT through mTORC2. BRAFV600E is identified in mTORC2 after immunoprecipitation of rictor. Knock-down of rictor abrogates BRAFV600E depletion induced pAKT. Knock-down of BRAFV600E enhances cellular enzyme activity of mTORC2. Aberrant activation of AKT pathway by PTEN loss appears to override the negative impact of BRAFV600E on pAKT. Taken together, our findings suggest that in a subset of BRAFV600E melanoma cells, BRAFV600E negatively regulates AKT pathway in a rictor-dependent, MEK/ERK and BRAF kinase-independent manner. Our study reveals a novel molecular mechanism underlying the regulation of feedback loops between the MAPK and AKT pathways.

Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

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Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo, E-mail: pompeo.volpe@unipd.it

2013-07-15

Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.

Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

International Nuclear Information System (INIS)

Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo

2013-01-01

Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α 1 -adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy

CBL-interacting protein kinase 6 negatively regulates immune response to Pseudomonas syringae in Arabidopsis.

Science.gov (United States)

Sardar, Atish; Nandi, Ashis Kumar; Chattopadhyay, Debasis

2017-06-15

Cytosolic calcium ion (Ca2+) is an essential mediator of the plant innate immune response. Here, we report that a calcium-regulated protein kinase Calcineurin B-like protein (CBL)-interacting protein kinase 6 (CIPK6) functions as a negative regulator of immunity against the bacterial pathogen Pseudomonas syringae in Arabidopsis thaliana. Arabidopsis lines with compromised expression of CIPK6 exhibited enhanced disease resistance to the bacterial pathogen and to P. syringae harboring certain but not all avirulent effectors, while restoration of CIPK6 expression resulted in abolition of resistance. Plants overexpressing CIPK6 were more susceptible to P. syringae. Enhanced resistance in the absence of CIPK6 was accompanied by increased accumulation of salicylic acid and elevated expression of defense marker genes. Salicylic acid accumulation was essential for improved immunity in the absence of CIPK6. CIPK6 negatively regulated the oxidative burst associated with perception of pathogen-associated microbial patterns (PAMPs) and bacterial effectors. Accelerated and enhanced activation of the mitogen-activated protein kinase cascade in response to bacterial and fungal elicitors was observed in the absence of CIPK6. The results of this study suggested that CIPK6 negatively regulates effector-triggered and PAMP-triggered immunity in Arabidopsis. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Potential language and attentional networks revealed through factor analysis of rCBF data measured with SPECT

DEFF Research Database (Denmark)

McLaughlin, T; Steinberg, B; Christensen, B

1992-01-01

's area (left hemisphere), when subjects listened to narrative speech, compared to white noise (baseline). No significant rCBF differences were detected with this test during dichotic stimulation vs. white noise. A more sophisticated statistical method (factor analysis) disclosed patterns of functionally...... brain networks involved in (I) auditory/linguistic, (II) attentional, and (III) visual imaging activity....

PhERF6, interacting with EOBI, negatively regulates fragrance biosynthesis in petunia flowers.

Science.gov (United States)

Liu, Fei; Xiao, Zhina; Yang, Li; Chen, Qian; Shao, Lu; Liu, Juanxu; Yu, Yixun

2017-09-01

In petunia, the production of volatile benzenoids/phenylpropanoids determines floral aroma, highly regulated by development, rhythm and ethylene. Previous studies identified several R2R3-type MYB trans-factors as positive regulators of scent biosynthesis in petunia flowers. Ethylene response factors (ERFs) have been shown to take part in the signal transduction of hormones, and regulation of metabolism and development processes in various plant species. Using virus-induced gene silencing technology, a negative regulator of volatile benzenoid biosynthesis, PhERF6, was identified by a screen for regulators of the expression of genes related to scent production. PhERF6 expression was temporally and spatially connected with scent production and was upregulated by exogenous ethylene. Up-/downregulation of the mRNA level of PhERF6 affected the expression of ODO1 and several floral scent-related genes. PhERF6 silencing led to a significant increase in the concentrations of volatiles emitted by flowers. Yeast two-hybrid, bimolecular fluorescence complementation and co-immunoprecipitation assays indicated that PhERF6 interacted with the N-terminus of EOBI, which includes two DNA binding domains. Our results show that PhERF6 negatively regulates volatile production in petunia flowers by competing for the binding of the c-myb domains of the EOBI protein with the promoters of genes related to floral scent. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

A New Framework for the Assessment of Cerebral Hemodynamics Regulation in Neonates Using NIRS

NARCIS (Netherlands)

Caicedo, Alexander; Alderliesten, Thomas; Naulaers, Gunnar; Lemmers, Petra; van Bel, Frank; Van Huffel, Sabine

2016-01-01

We present a new framework for the assessment of cerebral hemodynamics regulation (CHR) in neonates using near-infrared spectroscopy (NIRS). In premature infants, NIRS measurements have been used as surrogate variables for cerebral blood flow (CBF) in the assessment of cerebral autoregulation (CA).

[Regulation of Positive and Negative Emotions as Mediator between Maternal Emotion Socialization and Child Problem Behavior].

Science.gov (United States)

Fäsche, Anika; Gunzenhauser, Catherine; Friedlmeier, Wolfgang; von Suchodoletz, Antje

2015-01-01

The present study investigated five to six year old children's ability to regulate negative and positive emotions in relation to psychosocial problem behavior (N=53). It was explored, whether mothers' supportive and nonsupportive strategies of emotion socialization influence children's problem behavior by shaping their emotion regulation ability. Mothers reported on children's emotion regulation and internalizing and externalizing problem behavior via questionnaire, and were interviewed about their preferences for socialization strategies in response to children's expression of negative affect. Results showed that children with more adaptive expression of adequate positive emotions had less internalizing behavior problems. When children showed more control of inadequate negative emotions, children were less internalizing as well as externalizing in their behavior. Furthermore, results indicated indirect relations of mothers' socialization strategies with children's problem behavior. Control of inadequate negative emotions mediated the link between non-supportive strategies on externalizing problem behavior. Results suggest that emotion regulatory processes should be part of interventions to reduce the development of problematic behavior in young children. Parents should be trained in dealing with children's emotions in a constructive way.

The effect of arousal on regulation of negative emotions using cognitive reappraisal: An ERP study.

Science.gov (United States)

Langeslag, Sandra J E; Surti, Kruti

2017-08-01

Because the effectiveness of the emotion regulation strategy cognitive reappraisal may vary with emotion intensity, we investigated how stimulus arousal affects reappraisal success. Participants up- and down-regulated emotional responses using cognitive reappraisal to low and high arousing unpleasant pictures while the electroencephalogram (EEG) was recorded. Up-regulation resulted in more negative self-reported valence, while down-regulation resulted in less negative self-reported valence regardless of stimulus arousal, suggesting that subjective reappraisal success does not vary with emotional intensity. Participants felt that down-regulation of emotional responses to low arousing unpleasant pictures was easiest, which is in line with previous findings that participants showed a greater preference for reappraisal in low than high arousing situations. The late positive potential (LPP) amplitude was enhanced by down-regulation of high arousing unpleasant pictures. Even though this effect was unexpected and is opposite to the typical effect of down-regulation on the LPP, it is in line with several previous studies. Potential explanations for LPP regulation effects in the unexpected direction, such as strategy selection and task design, are evaluated. Suggestions and recommendations for future research are discussed, including using trial-by-trial manipulation of regulation instructions and studying the effect of stimulus arousal on up- and down-regulation of positive emotions. Copyright © 2017 Elsevier B.V. All rights reserved.

Emotion regulation strategies mediate the associations of positive and negative affect to upper extremity physical function.

Science.gov (United States)

Talaei-Khoei, Mojtaba; Nemati-Rezvani, Hora; Fischerauer, Stefan F; Ring, David; Chen, Neal; Vranceanu, Ana-Maria

2017-05-01

The Gross process model of emotion regulation holds that emotion-eliciting situations (e.g. musculoskeletal illness) can be strategically regulated to determine the final emotional and behavioral response. Also, there is some evidence that innate emotional traits may predispose an individual to a particular regulating coping style. We enrolled 107 patients with upper extremity musculoskeletal illness in this cross-sectional study. They completed self-report measures of positive and negative affect, emotion regulation strategies (cognitive reappraisal and expressive suppression), upper extremity physical function, pain intensity, and demographics. We used Preacher and Hayes' bootstrapping approach to process analysis to infer the direct effect of positive and negative affect on physical function as well as their indirect effects through activation of emotion regulation strategies. Negative affect was associated with decreased physical function. The association was partly mediated by expressive suppression (b (SE)=-.10 (.05), 95% BCa CI [-.21, -.02]). Positive affect was associated with increased physical function. Cognitive reappraisal partially mediated this association (b (SE)=.11 (.05), 95% BCa CI [.03, .24]). After controlling for pain intensity, the ratio of the mediated effect to total effect grew even larger in controlled model comparing to uncontrolled model (33% vs. 26% for expressive suppression and 32% vs. 30% for cognitive reappraisal). The relationships between affect, emotion regulation strategies and physical function appear to be more dependent on the emotional response to an orthopedic condition rather than the intensity of the nociceptive stimulation of the pain. Findings support integration of emotion regulation training in skill-based psychotherapy in this population to mitigate the effect of negative affect and enhance the influence of positive affect on physical function. Copyright © 2017 Elsevier Inc. All rights reserved.

Imaging of dopamine transporters with 99Tcm-TRODAT-1, rCBF and MRI in animal model of parkinson disease

International Nuclear Information System (INIS)

Deng Haoyu; Wang Wei; Li Xinhui; Yu Xiaoping

2001-01-01

Objective: To study the relationship between radioactivity distribution and changes of regional cerebral blood flow (rCBF) and tissue structure in the striatum of Parkinson disease (PD) model monkeys with 99 Tc m - TRODAT-1 and to estimate the value of imaging with 99 Tc m -TRODAT-1 in early diagnosis of PD. Methods: 99 Tc m -TRODAT-1 and rCBF imaging were performed on five monkeys before and after being made into a single side PD model. Two of the 5 PD model monkeys also received MRI. Results: In 99 Tc m -TRODAT-1 imaging the radioactivity ratio of striatum to cerebellum (S/C) in the normal monkeys was 1.48 at 180 min after injection of the imaging agent, the ratio of radioactivity in PD model monkeys in their destroyed striatum to that in cerebellum and in normal side striatum were 0.96 and 1.43, respectively. There was no difference in rCBF perfusion between normal and destroyed striatum of the PD model monkeys and between striatum tissue in two hemispheres of the normal monkeys either. The destruction of the tissue structure was not detected in PD model monkeys with MRI. Conclusions: 90 Tc m -TRODAT-1 can specifically bind dopamine transporters (DAT), sensitively display DAT uptake decrease ahead of the structural damage and cerebral blood flow perfusion decrease in PD model monkeys. It could become a useful imaging modality for the early diagnosis of PD

TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

International Nuclear Information System (INIS)

Shibata, Mio; Sato, Tomonobu; Nukiwa, Ryota; Ariga, Tadashi; Hatakeyama, Shigetsugu

2012-01-01

Highlights: ► NF-κB plays an important role in cell survival and carcinogenesis. ► TRIM45 negatively regulates TNFα-induced NF-κB-mediated transcription. ► TRIM45 overexpression suppresses cell growth. ► TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth. -- Abstract: The NF-κB signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-κB is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-κB signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin–proteasome system. It has been reported that overexpression of TRIM45, one of the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNFα-induced NF-κB-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-κB signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth.

Trait Affect, Emotion Regulation, and the Generation of Negative and Positive Interpersonal Events.

Science.gov (United States)

Hamilton, Jessica L; Burke, Taylor A; Stange, Jonathan P; Kleiman, Evan M; Rubenstein, Liza M; Scopelliti, Kate A; Abramson, Lyn Y; Alloy, Lauren B

2017-07-01

Positive and negative trait affect and emotion regulatory strategies have received considerable attention in the literature as predictors of psychopathology. However, it remains unclear whether individuals' trait affect is associated with responses to state positive affect (positive rumination and dampening) or negative affect (ruminative brooding), or whether these affective experiences contribute to negative or positive interpersonal event generation. Among 304 late adolescents, path analyses indicated that individuals with higher trait negative affect utilized dampening and brooding rumination responses, whereas those with higher trait positive affect engaged in rumination on positive affect. Further, there were indirect relationships between trait negative affect and fewer positive and negative interpersonal events via dampening, and between trait positive affect and greater positive and negative interpersonal events via positive rumination. These findings suggest that individuals' trait negative and positive affect may be associated with increased utilization of emotion regulation strategies for managing these affects, which may contribute to the occurrence of positive and negative events in interpersonal relationships. Copyright © 2017. Published by Elsevier Ltd.

High mobility group protein DSP1 negatively regulates HSP70 transcription in Crassostrea hongkongensis

Energy Technology Data Exchange (ETDEWEB)

Miao, Zongyu; Xu, Delin; Cui, Miao; Zhang, Qizhong, E-mail: zhangqzdr@126.com

2016-06-10

HSP70 acts mostly as a molecular chaperone and plays important roles in facilitating the folding of nascent peptides as well as the refolding or degradation of the denatured proteins. Under stressed conditions, the expression level of HSP70 is upregulated significantly and rapidly, as is known to be achieved by various regulatory factors controlling the transcriptional level. In this study, a high mobility group protein DSP1 was identified by DNA-affinity purification from the nuclear extracts of Crassostrea hongkongensis using the ChHSP70 promoter as a bait. The specific interaction between the prokaryotically expressed ChDSP1 and the FITC-labeled ChHSP70 promoter was confirmed by EMSA analysis. ChDSP1 was shown to negatively regulate ChHSP70 promoter expression by Luciferase Reporter Assay in the heterologous HEK293T cells. Both ChHSP70 and ChDSP1 transcriptions were induced by either thermal or CdCl{sub 2} stress, while the accumulated expression peaks of ChDSP1 were always slightly delayed when compared with that of ChHSP70. This indicates that ChDSP1 is involved, very likely to exert its suppressive role, in the recovery of the ChHSP70 expression from the induced level to its original state. This study is the first to report negative regulator of HSP70 gene transcription, and provides novel insights into the mechanisms controlling heat shock protein expression. -- Highlights: •HMG protein ChDSP1 shows affinity to ChHSP70 promoter in Crassostrea hongkongensis. •ChDSP1 negatively regulates ChHSP70 transcription. •ChHSP70 and ChDSP1 transcriptions were coordinately induced by thermal/Cd stress. •ChDSP1 may contribute to the recovery of the induced ChHSP70 to its original state. •This is the first report regarding negative regulator of HSP70 transcription.

Negative regulation of MAP kinase signaling in Drosophila by Ptp61F/PTP1B.

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Tchankouo-Nguetcheu, Stéphane; Udinotti, Mario; Durand, Marjorie; Meng, Tzu-Ching; Taouis, Mohammed; Rabinow, Leonard

2014-10-01

PTP1B is an important negative regulator of insulin and other signaling pathways in mammals. However, the role of PTP1B in the regulation of RAS-MAPK signaling remains open to deliberation, due to conflicting evidence from different experimental systems. The Drosophila orthologue of mammalian PTP1B, PTP61F, has until recently remained largely uncharacterized. To establish the potential role of PTP61F in the regulation of signaling pathways in Drosophila and particularly to help resolve its fundamental function in RAS-MAPK signaling, we generated a new allele of Ptp61F as well as employed both RNA interference and overexpression alleles. Our results validate recent data showing that the activity of insulin and Abl kinase signaling is increased in Ptp61F mutants and RNA interference lines. Importantly, we establish negative regulation of the RAS/MAPK pathway by Ptp61F activity in whole animals. Of particular interest, our results document the modulation of hyperactive MAP kinase activity by Ptp61F alleles, showing that the phosphatase intervenes to directly or indirectly regulate MAP kinase itself.

The Role of Depression and Negative Affect Regulation Expectancies in Tobacco Smoking among College Students

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Schleicher, Holly E.; Harris, Kari Jo; Catley, Delwyn; Nazir, Niaman

2009-01-01

Objective: Expectancies about nicotine's ability to alleviate negative mood states may play a role in the relationship between smoking and depression. The authors examined the role of negative affect regulation expectancies as a potential mediator of depression (history of depression and depressive symptoms) and smoking among college students.…

When death is not a problem: Regulating implicit negative affect under mortality salience.

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Lüdecke, Christina; Baumann, Nicola

2015-12-01

Terror management theory assumes that death arouses existential anxiety in humans which is suppressed in focal attention. Whereas most studies provide indirect evidence for negative affect under mortality salience by showing cultural worldview defenses and self-esteem strivings, there is only little direct evidence for implicit negative affect under mortality salience. In the present study, we assume that this implicit affective reaction towards death depends on people's ability to self-regulate negative affect as assessed by the personality dimension of action versus state orientation. Consistent with our expectations, action-oriented participants judged artificial words to express less negative affect under mortality salience compared to control conditions whereas state-oriented participants showed the reversed pattern. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Quorum sensing negatively regulates chitinase in Vibrio harveyi.

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Defoirdt, Tom; Darshanee Ruwandeepika, H A; Karunasagar, Indrani; Boon, Nico; Bossier, Peter

2010-02-01

Quorum sensing, bacterial cell-to-cell communication, regulates the virulence of Vibrio harveyi towards different hosts. Chitinase can be considered as a virulence factor because it helps pathogenic bacteria to attach to the host and to penetrate its tissues (e.g. in case of shrimp). Here, we show that quorum sensing negatively regulates chitinase in V. harveyi. Chitinolytic activity towards natural chitin from crab shells, the synthetic chitin derivative chitin azure, and fluorogenic chitin oligomers was significantly higher in a mutant in which the quorum-sensing system is completely inactivated when compared with a mutant in which the system is maximally active. Furthermore, the addition of signal molecule containing cell-free culture fluids decreased chitinase activity in a Harveyi Autoinducer 1 and Autoinducer 2-deficient double mutant. Finally, chitinase A mRNA levels were fivefold lower in the mutant in which the quorum-sensing system is maximally active when compared with the mutant in which the system is completely inactivated. [Correction added on 25 September 2009, after first online publication: the preceding sentence was corrected from 'Finally, chitinase A mRNA levels were fivefold lower in the mutant in which the quorum-sensing system is completely inactivated when compared with the mutant in which the system is maximally active.'] We argue that this regulation might help the vibrios to switch between host-associated and free-living life styles. © 2009 Society for Applied Microbiology and Blackwell Publishing Ltd.

Mothering, fathering, and the regulation of negative and positive emotions in high-functioning preschoolers with autism spectrum disorder.

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Hirschler-Guttenberg, Yael; Golan, Ofer; Ostfeld-Etzion, Sharon; Feldman, Ruth

2015-05-01

Children with autism spectrum disorder (ASD) exhibit difficulties in regulating emotions and authors have called to study the specific processes underpinning emotion regulation (ER) in ASD. Yet, little observational research examined the strategies preschoolers with ASD use to regulate negative and positive emotions in the presence of their mothers and fathers. Forty preschoolers with ASD and 40 matched typically developing children and their mothers and fathers participated. Families were visited twice for identical battery of paradigms with mother or father. Parent-child interactions were coded for parent and child behaviors and children engaged in ER paradigms eliciting negative (fear) and positive (joy) emotions with each parent. ER paradigms were microcoded for negative and positive emotionality, ER strategies, and parent regulation facilitation. During free play, mothers' and fathers' sensitivity and warm discipline were comparable across groups; however, children with ASD displayed lower positive engagement and higher withdrawal. During ER paradigms, children with ASD expressed less positive emotionality overall and more negative emotionality during fear with father. Children with ASD used more simple self-regulatory strategies, particularly during fear, but expressed comparable levels of assistance seeking behavior toward mother and father in negative and positive contexts. Parents of children with ASD used less complex regulation facilitation strategies, including cognitive reappraisal and emotional reframing, and employed simple tactics, such as physical comforting to manage fear and social gaze to maintain joy. Findings describe general and parent- and emotion-specific processes of child ER and parent regulation facilitation in preschoolers with ASD. Results underscore the ability of such children to seek parental assistance during moments of high arousal and the parents' sensitive adaptation to their children's needs. Reduced positive emotionality

Impaired down-regulation of negative emotion in self-referent social situations in bipolar disorder

DEFF Research Database (Denmark)

Kjærstad, Hanne L; Vinberg, Maj; Goldin, Philippe R

2016-01-01

naturally or dampen their emotional response to positive and negative social scenarios and associated self-beliefs. They were also given an established experimental task for comparison, involving reappraisal of negative affective picture stimuli, as well as a questionnaire of habitual ER strategies. BD...... patients showed reduced ability to down-regulate emotional responses in negative, but not positive, social scenarios relative to healthy controls and UD patients. In contrast, there were no between-group differences in the established ER task or in self-reported habitual reappraisal strategies. Findings...

Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

International Nuclear Information System (INIS)

Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In; Choi, Myung-Soo; Inn, Kyung-Soo

2013-01-01

Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways

Reduced CBF recovery detected by longitudinal 3D-SSP SPECT analyses predicts outcome of postoperative patients after subarachnoid haemorrhage.

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Mutoh, Tatsushi; Totsune, Tomoko; Takenaka, Shunsuke; Tatewaki, Yasuko; Nakagawa, Manabu; Suarez, Jose I; Taki, Yasuyuki; Ishikawa, Tatsuya

2018-02-01

The aim of this study was to evaluate the impact of cerebral blood flow (CBF) recovery obtained from brain single-photon emission computed tomography (SPECT) images on postoperative outcome after aneurysmal subarachnoid haemorrhage (SAH). Twenty-nine patients who had undergone surgical clipping for ruptured anterior communicating artery aneurysms were analyzed prospectively. Routine measurements of CBF were performed using technetium-99 m hexamethyl propyleneamine oxine SPECT on days 4 and 14 after SAH. Regional voxel data analyzed by three dimensional stereotactic surface projection (3D-SSP) were compared between patients and age-matched normal database (NDB). In 3D-SSP analysis of all patients, cortical hypoperfusion around the surgical site in bilateral frontal lobes was evident on day 4 (P SSP SPECT image analyses can be a potential predictor of poor prognosis in postoperative patients after SAH. © 2017 John Wiley & Sons Australia, Ltd.

How is emotional awareness related to emotion regulation strategies and self-reported negative affect in the general population?

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Subic-Wrana, Claudia; Beutel, Manfred E; Brähler, Elmar; Stöbel-Richter, Yve; Knebel, Achim; Lane, Richard D; Wiltink, Jörg

2014-01-01

The Levels of Emotional Awareness Scale (LEAS) as a performance task discriminates between implicit or subconscious and explicit or conscious levels of emotional awareness. An impaired awareness of one's feeling states may influence emotion regulation strategies and self-reports of negative emotions. To determine this influence, we applied the LEAS and self-report measures for emotion regulation strategies and negative affect in a representative sample of the German general population. A short version of the LEAS, the Hospital Anxiety and Depression Scale (HADS) and the Emotion Regulation Questionnaire (ERQ), assessing reappraisal and suppression as emotion regulation strategies, were presented to N = 2524 participants of a representative German community study. The questionnaire data were analyzed with regard to the level of emotional awareness. LEAS scores were independent from depression, but related to self-reported anxiety. Although of small or medium effect size, different correlational patters between emotion regulation strategies and negative affectivity were related to implict and explict levels of emotional awareness. In participants with implicit emotional awareness, suppression was related to higher anxiety and depression, whereas in participants with explicit emotional awareness, in addition to a positive relationship of suppression and depression, we found a negative relationship of reappraisal to depression. These findings were independent of age. In women high use of suppression and little use of reappraisal were more strongly related to negative affect than in men. Our first findings suggest that conscious awareness of emotions may be a precondition for the use of reappraisal as an adaptive emotion regulation strategy. They encourage further research in the relation between subconsious and conscious emotional awareness and the prefarance of adaptive or maladaptive emotion regulation strategies The correlational trends found in a representative

Impact of physical maltreatment on the regulation of negative affect and aggression.

Science.gov (United States)

Shackman, Jessica E; Pollak, Seth D

2014-11-01

Physically maltreated children are at risk for developing externalizing behavioral problems characterized by reactive aggression. The current experiment tested the relationships between individual differences in a neural index of social information processing, histories of child maltreatment, child negative affect, and aggressive behavior. Fifty boys (17 maltreated) performed an emotion recognition task while the P3b component of the event-related potential was recorded to index attention allocation to angry faces. Children then participated in a peer-directed aggression task. Negative affect was measured by recording facial electromyography, and aggression was indexed by the feedback that children provided to a putative peer. Physically maltreated children exhibited greater negative affect and more aggressive behavior, compared to nonmaltreated children, and this relationship was mediated by children's allocation of attention to angry faces. These data suggest that physical maltreatment leads to inappropriate regulation of both negative affect and aggression, which likely place maltreated children at increased risk for the development and maintenance of externalizing behavior disorders.

Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer.

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Wang, Xiao-Feng; Zhang, Xiao-Wei; Hua, Rui-Xi; Du, Yi-Qun; Huang, Ming-Zhu; Liu, Yong; Cheng, Yu Fang; Guo, Wei-Jian

2016-09-27

Mel-18, a polycomb group protein, has been reported to act as a tumor suppressor and be down-regulated in several human cancers including gastric cancer. It was also found that Mel-18 negatively regulates self-renewal of hematopoietic stem cells and breast cancer stem cells (CSCs). This study aimed to clarify its role in gastric CSCs and explore the mechanisms. We found that low-expression of Mel-18 was correlated with poor prognosis and negatively correlated with overexpression of stem cell markers Oct4, Sox2, and Gli1 in 101 gastric cancer tissues. Mel-18 was down-regulated in cultured spheroid cells, which possess CSCs, and overexpression of Mel-18 inhibits cells sphere-forming ability and tumor growth in vivo. Besides, Mel-18 was lower-expressed in ovary metastatic lesions compared with that in primary lesions of gastric cancer, and Mel-18 overexpression inhibited the migration ability of gastric cancer cells. Interestingly, overexpression of Mel-18 resulted in down-regulation of miR-21 in gastric cancer cells and the expression of Mel-18 was negatively correlated with the expression of miR-21 in gastric cancer tissues. Furthermore, miR-21 overexpression partially restored sphere-forming ability, migration potential and chemo-resistance in Mel-18 overexpressing gastric cancer cells. These results suggests Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer cells.

Improved wound management by regulated negative pressure-assisted wound therapy and regulated, oxygen- enriched negative pressure-assisted wound therapy through basic science research and clinical assessment

Directory of Open Access Journals (Sweden)

Moris Topaz

2012-01-01

Full Text Available Regulated negative pressure-assisted wound therapy (RNPT should be regarded as a state-of-the-art technology in wound treatment and the most important physical, nonpharmaceutical, platform technology developed and applied for wound healing in the last two decades. RNPT systems maintain the treated wound′s environment as a semi-closed, semi-isolated system applying external physical stimulations to the wound, leading to biological and biochemical effects, with the potential to substantially influence wound-host interactions, and when properly applied may enhance wound healing. RNPT is a simple, safe, and affordable tool that can be utilized in a wide range of acute and chronic conditions, with reduced need for complicated surgical procedures, and antibiotic treatment. This technology has been shown to be effective and safe, saving limbs and lives on a global scale. Regulated, oxygen-enriched negative pressure-assisted wound therapy (RO-NPT is an innovative technology, whereby supplemental oxygen is concurrently administered with RNPT for their synergistic effect on treatment and prophylaxis of anaerobic wound infection and promotion of wound healing. Understanding the basic science, modes of operation and the associated risks of these technologies through their fundamental clinical mechanisms is the main objective of this review.

Chondroitin sulfate addition to CD44H negatively regulates hyaluronan binding

International Nuclear Information System (INIS)

Ruffell, Brian; Johnson, Pauline

2005-01-01

CD44 is a widely expressed cell adhesion molecule that binds hyaluronan, an extracellular matrix glycosaminoglycan, in a tightly regulated manner. This regulated interaction has been implicated in inflammation and tumor metastasis. CD44 exists in the standard form, CD44H, or as higher molecular mass isoforms due to alternative splicing. Here, we identify serine 180 in human CD44H as the site of chondroitin sulfate addition and show that lack of chondroitin sulfate addition at this site enhances hyaluronan binding by CD44. A CD44H-immunoglobulin fusion protein expressed in HEK293 cells, and CD44H expressed in murine L fibroblast cells were modified by chondroitin sulfate, as determined by reduced sulfate incorporation after chondroitinase ABC treatment. Mutation of serine 180 or glycine 181 in CD44H reduced chondroitin sulfate addition and increased hyaluronan binding, indicating that serine 180 is the site for chondroitin sulfate addition in CD44H and that this negatively regulates hyaluronan binding

Self-regulation as a mediator between sibling relationship quality and early adolescents' positive and negative outcomes.

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Padilla-Walker, Laura M; Harper, James M; Jensen, Alexander C

2010-08-01

The current study examined the role of adolescents' self-regulation as a mediator between sibling relationship quality and adolescent outcomes, after controlling for the quality of the parent-child relationship. Participants were 395 families (282 two parent; 113 single parent) with an adolescent child (M age of child at Time 1 = 11.15, SD = .96, 49% female) who took part in [project name masked for blind review] at both Time 1 and Time 2. Path analysis via structural equation modeling suggested that sibling affection was longitudinally and positively related to self-regulation and prosocial behaviors, and negatively related to externalizing behaviors; while sibling hostility was positively, and having a sister was negatively related to internalizing behaviors (in general, paths were stronger for adolescents from two- vs. single-parent families). There was also evidence that adolescents' self-regulation partially mediated the relation between sibling affection and positive and negative adolescent outcomes. The discussion focuses on the importance of continued research examining the mechanisms through which the sibling relationship influences development during adolescence.

Accounting for the role of hematocrit in between-subject variations of MRI-derived baseline cerebral hemodynamic parameters and functional BOLD responses.

Science.gov (United States)

Xu, Feng; Li, Wenbo; Liu, Peiying; Hua, Jun; Strouse, John J; Pekar, James J; Lu, Hanzhang; van Zijl, Peter C M; Qin, Qin

2018-01-01

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T 1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO 2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO 2 to maintain constant CMRO 2 . Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%-22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

DMPD: When signaling pathways collide: positive and negative regulation of toll-likereceptor signal transduction. [Dynamic Macrophage Pathway CSML Database

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Full Text Available 18631453 When signaling pathways collide: positive and negative regulation of toll-...uction. PubmedID 18631453 Title When signaling pathways collide: positive and neg...l) Show When signaling pathways collide: positive and negative regulation of toll-likereceptor signal transd...likereceptor signal transduction. O'Neill LA. Immunity. 2008 Jul 18;29(1):12-20. (.png) (.svg) (.html) (.csm

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway.

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Liu, Yunxia; Dong, Weibing; Shao, Jing; Wang, Yibin; Zhou, Meiyi; Sun, Haipeng

2017-01-01

Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation.

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway

Directory of Open Access Journals (Sweden)

Yunxia Liu

2017-10-01

Full Text Available Recent studies have linked branched-chain amino acid (BCAA with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15 is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation.

Negative regulation of Toll-like receptor signaling plays an essential role in homeostasis of the intestine.

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Biswas, Amlan; Wilmanski, Jeanette; Forsman, Huamei; Hrncir, Tomas; Hao, Liming; Tlaskalova-Hogenova, Helena; Kobayashi, Koichi S

2011-01-01

A healthy intestinal tract is characterized by controlled homeostasis due to the balanced interaction between commensal bacteria and the host mucosal immune system. Human and animal model studies have supported the hypothesis that breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel diseases. However, it is not well understood how intestinal microflora stimulate the intestinal mucosal immune system and how such activation is regulated. Using a spontaneous, commensal bacteria-dependent colitis model in IL-10-deficient mice, we investigated the role of TLR and their negative regulation in intestinal homeostasis. In addition to IL-10(-/-) MyD88(-/-) mice, IL-10(-/-) TLR4(-/-) mice exhibited reduced colitis compared to IL-10(-/-) mice, indicating that TLR4 signaling plays an important role in inducing colitis. Interestingly, the expression of IRAK-M, a negative regulator of TLR signaling, is dependent on intestinal commensal flora, as IRAK-M expression was reduced in mice re-derived into a germ-free environment, and introduction of commensal bacteria into germ-free mice induced IRAK-M expression. IL-10(-/-) IRAK-M(-/-) mice exhibited exacerbated colitis with increased inflammatory cytokine gene expression. Therefore, this study indicates that intestinal microflora stimulate the colitogenic immune system through TLR and negative regulation of TLR signaling is essential in maintaining intestinal homeostasis. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evidence for the negative impact of reward on self-regulated learning.

Science.gov (United States)

Wehe, Hillary S; Rhodes, Matthew G; Seger, Carol A

2015-01-01

The undermining effect refers to the detrimental impact rewards can have on intrinsic motivation to engage in a behaviour. The current study tested the hypothesis that participants' self-regulated learning behaviours are susceptible to the undermining effect. Participants were assigned to learn a set of Swahili-English word pairs. Half of the participants were offered a reward for performance, and half were not offered a reward. After the initial study phase, participants were permitted to continue studying the words during a free period. The results were consistent with an undermining effect: Participants who were not offered a reward spent more time studying the words during the free period. The results suggest that rewards may negatively impact self-regulated learning behaviours and provide support for the encouragement of intrinsic motivation.

HDAC3 Is a Critical Negative Regulator of Long-Term Memory Formation

Science.gov (United States)

McQuown, Susan C.; Barrett, Ruth M.; Matheos, Dina P.; Post, Rebecca J.; Rogge, George A.; Alenghat, Theresa; Mullican, Shannon E.; Jones, Steven; Rusche, James R.; Lazar, Mitchell A.; Wood, Marcelo A.

2011-01-01

Gene expression is dynamically regulated by chromatin modifications on histone tails, such as acetylation. In general, histone acetylation promotes transcription, whereas histone deacetylation negatively regulates transcription. The interplay between histone acetyl-transerases and histone deacetylases (HDACs) is pivotal for the regulation of gene expression required for long-term memory processes. Currently, very little is known about the role of individual HDACs in learning and memory. We examined the role of HDAC3 in long-term memory using a combined genetic and pharmacologic approach. We used HDAC3–FLOX genetically modified mice in combination with adeno-associated virus-expressing Cre recombinase to generate focal homozygous deletions of Hdac3 in area CA1 of the dorsal hippocampus. To complement this approach, we also used a selective inhibitor of HDAC3, RGFP136 [N-(6-(2-amino-4-fluorophenylamino)-6-oxohexyl)-4-methylbenzamide]. Immunohistochemistry showed that focal deletion or intrahippocampal delivery of RGFP136 resulted in increased histone acetylation. Both the focal deletion of HDAC3 as well as HDAC3 inhibition via RGFP136 significantly enhanced long-term memory in a persistent manner. Next we examined expression of genes implicated in long-term memory from dorsal hippocampal punches using quantitative reverse transcription-PCR. Expression of nuclear receptor subfamily 4 group A, member 2 (Nr4a2) and c-fos was significantly increased in the hippocampus of HDAC3–FLOX mice compared with wild-type controls. Memory enhancements observed in HDAC3–FLOX mice were abolished by intrahippocampal delivery of Nr4a2 small interfering RNA, suggesting a mechanism by which HDAC3 negatively regulates memory formation. Together, these findings demonstrate a critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation. PMID:21228185

Delayed reflow of an ischemic infarct after spontaneous thrombolysis studied by CBF tomography using SPECT and Tc-99m HMPAO

DEFF Research Database (Denmark)

Companioni, J M; Lassen, N A; Tfelt-Hansen, P

1991-01-01

A patient with a large ischemic infarct in the left middle cerebral artery territory was studied six times in the acute/subacute phase by cerebral blood flow (CBF) tomography using Tc-99m-HMPAO. The SPECT instrument used was a brain dedicated highly sensitive four-camera system (TOMOMATIC 232...

Compromised Cerebral Blood Flow(CBF) in Congestive Heart Failure (CHB): non-invasive quantification with {sup 99m}Tc-ECD radionuclide angiography

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Seung; Kim, Jae Joong; Lim, Ki Chun; Lee, Hee Kyung; Moon, Dae Hyuk [Ulsan University College of Medicine, Seoul (Korea, Republic of)

2002-07-01

Recent reports revealed that cerebral metabolism in CHF was abnormally deranged and proposed as a potential marker of disease severity. Since deranged cerebral metabolism in CHF may result from compromised cerebral perfusion, quantification of CHF may be useful for accurate risk stratification of CHF. Therefore, we investigated whether CHF in patients with CHF is compromised and correlated with clinical parameters. Fifteen patients (M/F:11/5, 45{+-}9yr) with CHF (LVEF<40%) and 7 healthy controls (M/F:5/2, 41{+-}8yr) were prospectively studied. All patients underwent radionuclide angiography including cerebral hemispheres and aortic arch using {sup 99m}Tc-ECD. Global CBF was measured non-invasively by the application of Patlak graphical plot analysis. All patients were also evaluated using a standardized protocol that included echocardiography and clinical evaluation. Global CBF (40.3{+-}5.2 ml/min/100g) of the patients with CHF were significantly lower than those (49.7{+-}2.4 ml/min/100g) of controls (p<0.01). Global CBF were correlated with NYHA functional class (r=-0.617, p=0.43), but not correlated with other clinical parameters such as age (r=-0.463, p=0.082), duration (r=0.237, p>0.1), systolic BP (r=-0.063, p>0.5), LVEF (r=-0.13, p>0.1), LV dimension(r=0.139, p>0.5), and PV pressure gradients (r=0.072, p>0.5). Cerebral perfusion of the patients with CHF was compromised and not correlated with cardiopulmonary hemodynamic parameters.

Cerebral Blood Flow and Amyloid-β Interact to Affect Memory Performance in Cognitively Normal Older Adults

Directory of Open Access Journals (Sweden)

Katherine J. Bangen

2017-06-01

Full Text Available Cerebral blood flow (CBF alterations and amyloid-β (Aβ accumulation have been independently linked to cognitive deficits in older adults at risk for dementia. Less is known about how CBF and Aβ may interact to affect cognition in cognitively normal older adults. Therefore, we examined potential statistical interactions between CBF and Aβ status in regions typically affected in Alzheimer’s disease (AD within a sample of older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI study. Sixty-two cognitively normal participants (mean age = 72 years underwent neuroimaging and memory testing. Arterial spin labeling magnetic resonance imaging was used to quantify CBF and florbetapir PET amyloid imaging was used to measure Aβ deposition. Aβ status (i.e., positivity versus negativity was determined based on established cutoffs (Landau et al., 2013. The Rey Auditory Verbal Learning Test was used to assess memory. Linear regression models adjusted for age, education, and sex, demonstrated significant interactions between CBF and Aβ status on memory performance. Among Aβ positive older adults, there were significant negative associations between higher CBF in hippocampus, posterior cingulate, and precuneus and poorer memory performance. In contrast, among Aβ negative older adults, there were no significant associations between CBF and cognition. Our findings extend previous CBF studies of dementia risk by reporting interactions between Aβ status and CBF on memory performance in a sample of well-characterized, cognitively normal older adults. Results suggest that differential CBF-cognition associations can be identified in healthy, asymptomatic Aβ positive older adults relative to Aβ negative individuals. Associations between higherCBF and poorer memory among Aβ positive older adults may reflect a cellular and/or vascular compensatory response to pathologic processes whereby higher CBF is needed to maintain normal memory

Mindfulness in schizophrenia: Associations with self-reported motivation, emotion regulation, dysfunctional attitudes, and negative symptoms.

Science.gov (United States)

Tabak, Naomi T; Horan, William P; Green, Michael F

2015-10-01

Mindfulness-based interventions are gaining empirical support as alternative or adjunctive treatments for a variety of mental health conditions, including anxiety, depression, and substance use disorders. Emerging evidence now suggests that mindfulness-based treatments may also improve clinical features of schizophrenia, including negative symptoms. However, no research has examined the construct of mindfulness and its correlates in schizophrenia. In this study, we examined self-reported mindfulness in patients (n=35) and controls (n=25) using the Five-Facet Mindfulness Questionnaire. We examined correlations among mindfulness, negative symptoms, and psychological constructs associated with negative symptoms and adaptive functioning, including motivation, emotion regulation, and dysfunctional attitudes. As hypothesized, patients endorsed lower levels of mindfulness than controls. In patients, mindfulness was unrelated to negative symptoms, but it was associated with more adaptive emotion regulation (greater reappraisal) and beliefs (lower dysfunctional attitudes). Some facets of mindfulness were also associated with self-reported motivation (behavioral activation and inhibition). These patterns of correlations were similar in patients and controls. Findings from this initial study suggest that schizophrenia patients may benefit from mindfulness-based interventions because they (a) have lower self-reported mindfulness than controls and (b) demonstrate strong relationships between mindfulness and psychological constructs related to adaptive functioning. Copyright © 2015 Elsevier B.V. All rights reserved.

In vivo detection of prion amyloid plaques using [11C]BF-227 PET

International Nuclear Information System (INIS)

Okamura, Nobuyuki; Yanai, Kazuhiko; Shiga, Yusei; Itoyama, Yasuhito; Furumoto, Shozo; Tashiro, Manabu; Tsuboi, Yoshio; Furukawa, Katsutoshi; Arai, Hiroyuki; Iwata, Ren; Kudo, Yukitsuka; Doh-ura, Katsumi

2010-01-01

In vivo detection of pathological prion protein (PrP) in the brain is potentially useful for the diagnosis of transmissible spongiform encephalopathies (TSEs). However, there are no non-invasive ante-mortem means for detection of pathological PrP deposition in the brain. The purpose of this study is to evaluate the amyloid imaging tracer BF-227 with positron emission tomography (PET) for the non-invasive detection of PrP amyloid in the brain. The binding ability of BF-227 to PrP amyloid was investigated using autoradiography and fluorescence microscopy. Five patients with TSEs, including three patients with Gerstmann-Straeussler-Scheinker disease (GSS) and two patients with sporadic Creutzfeldt-Jakob disease (CJD), underwent [ 11 C]BF-227 PET scans. Results were compared with data from 10 normal controls and 17 patients with Alzheimer's disease (AD). The regional to pons standardized uptake value ratio was calculated as an index of BF-227 retention. Binding of BF-227 to PrP plaques was confirmed using brain samples from autopsy-confirmed GSS cases. In clinical PET study, significantly higher retention of BF-227 was detected in the cerebellum, thalamus and lateral temporal cortex of GSS patients compared to that in the corresponding tissues of normal controls. GSS patients also showed higher retention of BF-227 in the cerebellum, thalamus and medial temporal cortex compared to AD patients. In contrast, the two CJD patients showed no obvious retention of BF-227 in the brain. Although [ 11 C]BF-227 is a non-specific imaging marker of cerebral amyloidosis, it is useful for in vivo detection of PrP plaques in the human brain in GSS, based on the regional distribution of the tracer. PET amyloid imaging might provide a means for both early diagnosis and non-invasive disease monitoring of certain forms of TSEs. (orig.)

Interictal rCBF SPECT, MRI and Surgical Outcome of Intractable Temporal Lobe Epilepsy

International Nuclear Information System (INIS)

Zeon, Seok Kil; Joo, Yang Goo; Lee, Sang Doe; Son, Eun Ik; Lee, Young Hwan

1994-01-01

Interictal single photon emission computed tomography of regional cerebral blood flow (rCBF SPECT) in 18 intractable temporal lobe epilepsy patients (8 male and 10 female patients: average 23.5 years old) were compared with 2.0 T magnetic resonance imaging (MRI). And surgical outcome was analysed with the findings, symptom duration and lateralization of temporal lobe. Preoperatively rCRF SPECT was done in all 18 patients with intravenous injection of 740 MRq 99 m T c-HMPAO. MRI was also done preoperatively in 13 patients. Surgical outcome was classified by Engel's outcome classification (four part classification recommended at the first Palm Desert conference). rCRF SPECT detected correctly lateralising abnormality of temporal lobe hypoperfusion in 13/ 18 (72.2%), contralateral temporal lobe hypoperfusion in 2/18 (11.1%) and showed no definite abnormality in 3/18 (16.7%). The positive predictive value of unilateral temporal lobe hypoperfusion was 87%. MRI detected correct localising abnormality in 8/13 (61.5%), such as hippocampal atrophy (7/13), asymmetric temporal horn (6/13), anterior temporal lobe atrophy (1/13), increased signal intensity from hippocampus (1/13) and calcific density (1/13), and no abnormal finding was noted in 5/13 (38.5%), There was no false positive findings and the positive predictive value of MRI was 100%, Only 2 cases showed same lateralization findings in rCBF SPECT and MRI. There was no significant correlation between symptom duration and no abnormal findings on SPECT or MRI. Surgical outcome showed class I in 15/18 (83.3%), and class II in 2/18 (11.1%). One case of no abnormal finding in both SPECT and MRI showed class III surgical outcome. No class IV surgical out.come was noted. Surgical outcome, lateralization of epileptic focus in temporal lobe and abnormal findings in rCBR SPECT or MRI were not significantly correlated.

Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation.

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Kelly E Roney

Full Text Available Plexins are cell surface receptors widely studied in the nervous system, where they mediate migration and morphogenesis though the Rho family of small GTPases. More recently, plexins have been implicated in immune processes including cell-cell interaction, immune activation, migration, and cytokine production. Plexin-B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. The function of Plexin-B2 in the immune system is unknown. This report shows that Plexin-B2 is highly expressed on cells of the innate immune system in the mouse, including macrophages, conventional dendritic cells, and plasmacytoid dendritic cells. However, Plexin-B2 does not appear to regulate the production of proinflammatory cytokines, phagocytosis of a variety of targets, or directional migration towards chemoattractants or extracellular matrix in mouse macrophages. Instead, Plxnb2(-/- macrophages have greater cellular motility than wild type in the unstimulated state that is accompanied by more active, GTP-bound Rac and Cdc42. Additionally, Plxnb2(-/- macrophages demonstrate faster in vitro wound closure activity. Studies have shown that a closely related family member, Plexin-B1, binds to active Rac and sequesters it from downstream signaling. The interaction of Plexin-B2 with Rac has only been previously confirmed in yeast and bacterial overexpression assays. The data presented here show that Plexin-B2 functions in mouse macrophages as a negative regulator of the GTPases Rac and Cdc42 and as a negative regulator of basal cell motility and wound healing.

Regional cerebral blood flow (rCBF) measurement by 133Xe inhalation (Inhamatic 33rCBF measuring instrument)

International Nuclear Information System (INIS)

Kuroda, Kiyoshi; Onodera, Hideki; Endo, Hideo.

1982-01-01

The rCBF and its patterns obtained by 133 Xe inhalation on 20 healthy subjects were studied. In a group of subjects aged 25 years or less, the fast flow (F1) representing the mean cerebral blood flow (MCBF) was 97.1 +- 15.7 m1/100 g/min (abbreviated as m1) in the left hemisphere and 96.6 +- 16.8 m1 in the right; and the initial slope index (ISI), 65.8 +- 10.4 m1 for the left and 65.1 +- 10.7 m1 for the right. In a group of subjects aged 25 or more, F1 was 83.5 +- 10.1 m1 for the left and 84.8 +- 9.6 m1 for the right; and ISI, 55.7 +- 6.9 m1 for the left and 55.8 +- 6.7 m1 for the right. In both groups, F1 showed a hyperfrontal pattern in which F1 was higher than MCBF in the frontal region by about 10%, and ISI showed high values primarily in the sylvian fissure. With respect to the variation of F1 values from the 1st to 2nd measurements, MCBF was 7.6 +- 5.1% in the left hemisphere and 9.0 +- 4.7% in the right; and ISI, 14.6 +- 5.1% in the left and 14.4 +- 10.6% in the right. Thus, F1 values showed higher reproducibility. Depending on the difference in start fit time (SFT), both F1 and ISI values showed great changes, particularly so when SFT was close to the peak of the head curve. (Chiba, N.)

Cerebrovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage

DEFF Research Database (Denmark)

Ansar, Saema; Vikman, Petter; Nielsen, Marianne

2007-01-01

with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 microl blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular studies...

Sustained Expression of Negative Regulators of Myelination Protects Schwann Cells from Dysmyelination in a Charcot-Marie-Tooth 1B Mouse Model.

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Florio, Francesca; Ferri, Cinzia; Scapin, Cristina; Feltri, M Laura; Wrabetz, Lawrence; D'Antonio, Maurizio

2018-05-02

Schwann cell differentiation and myelination in the PNS are the result of fine-tuning of positive and negative transcriptional regulators. As myelination starts, negative regulators are downregulated, whereas positive ones are upregulated. Fully differentiated Schwann cells maintain an extraordinary plasticity and can transdifferentiate into "repair" Schwann cells after nerve injury. Reactivation of negative regulators of myelination is essential to generate repair Schwann cells. Negative regulators have also been implicated in demyelinating neuropathies, although their role in disease remains elusive. Here, we used a mouse model of Charcot-Marie-Tooth neuropathy type 1B (CMT1B), the P0S63del mouse characterized by ER stress and the activation of the unfolded protein response, to show that adult Schwann cells are in a partial differentiation state because they overexpress transcription factors that are normally expressed only before myelination. We provide evidence that two of these factors, Sox2 and Id2, act as negative regulators of myelination in vivo However, their sustained expression in neuropathy is protective because ablation of Sox2 or/and Id2 from S63del mice of both sexes results in worsening of the dysmyelinating phenotype. This is accompanied by increased levels of mutant P0 expression and exacerbation of ER stress, suggesting that limited differentiation may represent a novel adaptive mechanism through which Schwann cells counter the toxic effect of a mutant terminal differentiation protein. SIGNIFICANCE STATEMENT In many neuropathies, Schwann cells express high levels of early differentiation genes, but the significance of these altered expression remained unclear. Because many of these factors may act as negative regulators of myelination, it was suggested that their misexpression could contribute to dysmyelination. Here, we show that the transcription factors Sox2 and Id2 act as negative regulators of myelination in vivo , but that their sustained

Arabidopsis phosphoinositide-specific phospholipase C 4 negatively regulates seedling salt tolerance.

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Xia, Keke; Wang, Bo; Zhang, Jiewei; Li, Yuan; Yang, Hailian; Ren, Dongtao

2017-08-01

Previous physiological and pharmacological studies have suggested that the activity of phosphoinositide-specific phospholipase C (PI-PLC) plays an important role in regulating plant salt stress responses by altering the intracellular Ca 2+ concentration. However, the individual members of plant PLCs involved in this process need to be identified. Here, the function of AtPLC4 in the salt stress response of Arabidopsis seedlings was analysed. plc4 mutant seedlings showed hyposensitivity to salt stress compared with Col-0 wild-type seedlings, and the salt hyposensitive phenotype could be complemented by the expression of native promoter-controlled AtPLC4. Transgenic seedlings with AtPLC4 overexpression (AtPLC4 OE) exhibited a salt-hypersensitive phenotype, while transgenic seedlings with its inactive mutant expression (AtPLC4m OE) did not exhibit this phenotype. Using aequorin as a Ca 2+ indicator in plc4 mutant and AtPLC4 OE seedlings, AtPLC4 was shown to positively regulate the salt-induced Ca 2+ increase. The salt-hypersensitive phenotype of AtPLC4 OE seedlings was partially rescued by EGTA. An analysis of salt-responsive genes revealed that the transcription of RD29B, MYB15 and ZAT10 was inversely regulated in plc4 mutant and AtPLC4 OE seedlings. Our findings suggest that AtPLC4 negatively regulates the salt tolerance of Arabidopsis seedlings, and Ca 2+ may be involved in regulating this process. © 2017 John Wiley & Sons Ltd.

A Loss-of-Function Screen for Phosphatases that Regulate Neurite Outgrowth Identifies PTPN12 as a Negative Regulator of TrkB Tyrosine Phosphorylation

DEFF Research Database (Denmark)

Ambjørn, Malene; Dubreuil, Véronique; Miozzo, Federico

2013-01-01

Alterations in function of the neurotrophin BDNF are associated with neurodegeneration, cognitive decline, and psychiatric disorders. BDNF promotes axonal outgrowth and branching, regulates dendritic tree morphology and is important for axonal regeneration after injury, responses that largely....... This approach identified phosphatases from diverse families, which either positively or negatively modulate BDNF-TrkB-mediated neurite outgrowth, and most of which have little or no previously established function related to NT signaling. "Classical" protein tyrosine phosphatases (PTPs) accounted for 13......% of the candidate regulatory phosphatases. The top classical PTP identified as a negative regulator of BDNF-TrkB-mediated neurite outgrowth was PTPN12 (also called PTP-PEST). Validation and follow-up studies showed that endogenous PTPN12 antagonizes tyrosine phosphorylation of TrkB itself, and the downstream...

Overexpression of a repressor MdMYB15L negatively regulates anthocyanin and cold tolerance in red-fleshed callus.

Science.gov (United States)

Xu, Haifeng; Yang, Guanxian; Zhang, Jing; Wang, Yicheng; Zhang, Tianliang; Wang, Nan; Jiang, Shenghui; Zhang, Zongying; Chen, Xuesen

2018-04-14

The cold-induced metabolic pathway and anthocyanin biosynthesis play important roles in plant growth. In this study, we identified a bHLH binding motif in the MdMYB15L protein using protein sequence analyses. Yeast two-hybrid and pull-down assays showed that MdMYB15L could interact with MdbHLH33. Overexpressing MdMYB15L in red-fleshed callus inhibited the expression of MdCBF2 and resulted in reduced cold tolerance but did not affect anthocyanin levels. Chip-PCR and EMSA analysis showed that MdMYB15L could bind the type II cis-acting element found in the MdCBF2 promoter. Overexpressing MdMYB15L in red-fleshed callus overexpressing MdbHLH33 also reduced cold tolerance and reduced MdbHLH33-induced anthocyanin biosynthesis. Knocking out the bHLH binding sequence of MdMYB15L (LBSMdMYB15L) prevented LBSMdMYB15L from interacting with MdbHLH33. Overexpressing LBSMdMYB15L in red-fleshed callus overexpressing MdbHLH33 also reduced cold tolerance and reduced MdbHLH33-induced anthocyanin biosynthesis. Together, these results suggested that an apple repressor MdMYB15L might play a key role in the cold signaling and anthocyanin metabolic pathways. Copyright © 2018 Elsevier Inc. All rights reserved.

Cyclooxygenases 1 and 2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic intermittent hypoxia: implications for sleep apnea.

Science.gov (United States)

Beaudin, Andrew E; Pun, Matiram; Yang, Christina; Nicholl, David D M; Steinback, Craig D; Slater, Donna M; Wynne-Edwards, Katherine E; Hanly, Patrick J; Ahmed, Sofia B; Poulin, Marc J

2014-05-09

Obstructive sleep apnea (OSA) is associated with increased risk of cardiovascular and cerebrovascular disease resulting from intermittent hypoxia (IH)-induced inflammation. Cyclooxygenase (COX)-formed prostanoids mediate the inflammatory response, and regulate blood pressure and cerebral blood flow (CBF), but their role in blood pressure and CBF responses to IH is unknown. Therefore, this study's objective was to determine the role of prostanoids in cardiovascular and cerebrovascular responses to IH. Twelve healthy, male participants underwent three, 6-hour IH exposures. For 4 days before each IH exposure, participants ingested a placebo, indomethacin (nonselective COX inhibitor), or Celebrex(®) (selective COX-2 inhibitor) in a double-blind, randomized, crossover study design. Pre- and post-IH blood pressure, CBF, and urinary prostanoids were assessed. Additionally, blood pressure and urinary prostanoids were assessed in newly diagnosed, untreated OSA patients (n=33). Nonselective COX inhibition increased pre-IH blood pressure (P ≤ 0.04) and decreased pre-IH CBF (P=0.04) while neither physiological variable was affected by COX-2 inhibition (P ≥ 0.90). Post-IH, MAP was elevated (P ≤ 0.05) and CBF was unchanged with placebo and nonselective COX inhibition. Selective COX-2 inhibition abrogated the IH-induced MAP increase (P=0.19), but resulted in lower post-IH CBF (P=0.01). Prostanoids were unaffected by IH, except prostaglandin E2 was elevated with the placebo (P=0.02). Finally, OSA patients had elevated blood pressure (P ≤ 0.4) and COX-1 formed thromboxane A2 concentrations (P=0.02). COX-2 and COX-1 have divergent roles in modulating vascular responses to acute and chronic IH. Moreover, COX-1 inhibition may mitigate cardiovascular and cerebrovascular morbidity in OSA. www.clinicaltrials.gov. Unique identifier: NCT01280006.

A Longitudinal Study of Emotion Regulation, Emotion Lability-Negativity, and Internalizing Symptomatology in Maltreated and Nonmaltreated Children

Science.gov (United States)

Kim-Spoon, Jungmeen; Cicchetti, Dante; Rogosch, Fred A.

2013-01-01

The longitudinal contributions of emotion regulation and emotion lability-negativity to internalizing symptomatology were examined in a low-income sample (171 maltreated and 151 nonmaltreated children, from age 7 to 10 years). Latent difference score models indicated that for both maltreated and nonmaltreated children, emotion regulation was a…

Orphan Nuclear Receptor ERRα Controls Macrophage Metabolic Signaling and A20 Expression to Negatively Regulate TLR-Induced Inflammation.

Science.gov (United States)

Yuk, Jae-Min; Kim, Tae Sung; Kim, Soo Yeon; Lee, Hye-Mi; Han, Jeongsu; Dufour, Catherine Rosa; Kim, Jin Kyung; Jin, Hyo Sun; Yang, Chul-Su; Park, Ki-Sun; Lee, Chul-Ho; Kim, Jin-Man; Kweon, Gi Ryang; Choi, Hueng-Sik; Vanacker, Jean-Marc; Moore, David D; Giguère, Vincent; Jo, Eun-Kyeong

2015-07-21

The orphan nuclear receptor estrogen-related receptor α (ERRα; NR3B1) is a key metabolic regulator, but its function in regulating inflammation remains largely unknown. Here, we demonstrate that ERRα negatively regulates Toll-like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and fine-tuning of metabolic reprogramming in macrophages. ERRα-deficient (Esrra(-/-)) mice showed increased susceptibility to endotoxin-induced septic shock, leading to more severe pro-inflammatory responses than control mice. ERRα regulated macrophage inflammatory responses by directly binding the promoter region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition, Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial respiratory function and biogenesis. Further, ERRα was required for the regulation of NF-κB signaling by controlling p65 acetylation via maintenance of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously unappreciated role for ERRα as a negative regulator of TLR-induced inflammatory responses through inducing Tnfaip3 transcription and controlling the metabolic reprogramming. Copyright © 2015 Elsevier Inc. All rights reserved.

Statistical parametric mapping analysis of the relationship between regional cerebral blood flow and symptom clusters of the depressive mood in patients with pre-dialytic chronic kidney disease

International Nuclear Information System (INIS)

Kim, Seong-Jang; Song, Sang Heon; Kim, Ji Hoon; Kwak, Ihm Soo

2008-01-01

The aim of this study is to investigate the relationship between regional cerebral blood flow (rCBF) and symptom clusters of depressive mood in pre-dialytic chronic kidney disease (CKD). Twenty-seven patients with stage 4-5 CKD were subjected to statistical parametric mapping analysis of brain single-photon emission computed tomography. Correlation analyses between separate symptom clusters of depressive mood and rCBF were done. The first factor (depressive mood) was negatively correlated with rCBF in the right insula, posterior cingulate gyrus, and left superior temporal gyrus, and positively correlated with rCBF in the left fusiform gyrus. The second factor (insomnia) was negatively correlated with rCBF in the right middle frontal gyrus, bilateral cingulate gyri, right insula, right putamen, and right inferior parietal lobule, and positively correlated with rCBF in left fusiform gyrus and bilateral cerebellar tonsils. The third factor (anxiety and psychomotor aspects) was negatively correlated with rCBF in the left inferior frontal gyms, right superior frontal gyms, right middle temporal gyrus, right superior temporal gyrus, and left superior frontal gyrus, and positively correlated with rCBF in the right ligual gyrus and right parahippocampal gyrus. In this study, the separate symptom clusters were correlated with specific rCBF patterns similar to those in major depressive disorder patients without CKD. However, some areas with discordant rCBF patterns were also noted when compared with major depressive disorder patients. Further larger scale investigations are needed. (author)

Maternal Self-Regulation, Relationship Adjustment, and Home Chaos: Contributions to Infant Negative Emotionality

Science.gov (United States)

Bridgett, David J.; Burt, Nicole M.; Laake, Lauren M.; Oddi, Kate B.

2013-01-01

There has been increasing interest in the direct and indirect effects of parental self-regulation on children’s outcomes. In the present investigation, the effects of maternal self-regulation, home chaos, and inter-parental relationship adjustment on broad and specific indicators of infant negative emotionality (NE) were examined. A sample of maternal caregivers and their 4-month-old infants (N = 85) from a rural community participated. Results demonstrated that better maternal self-regulation was associated with lower infant NE broadly, as well as with lower infant sadness and distress to limitations/frustration and better falling reactivity (i.e. emotion regulation), specifically. Maternal self-regulation also predicted less chaotic home environments and better maternal inter-parental relationship adjustment. Findings also supported the indirect effects of maternal self-regulation on broad and specific indicators of infant NE through home chaos and maternal relationship adjustment. Some differential effects were also identified. Elevated home chaos appeared to specifically affect infant frustration/distress to limitations whereas maternal relationship adjustment affected broad infant NE, as well as several specific indicators of infant NE: frustration/distress to limitations, sadness, and falling reactivity. In conjunction with other recent investigations that have reported the effects of maternal self-regulation on parenting, the findings in the present investigation suggest that parental self-regulation may influence children’s outcomes through several proximal environmental pathways. PMID:23748168

Cerebrovascular regulation in men and women: stimulus-specific role of cyclooxygenase.

Science.gov (United States)

Peltonen, Garrett L; Harrell, John W; Rousseau, Cameron L; Ernst, Brady S; Marino, Mariah L; Crain, Meghan K; Schrage, William G

2015-07-01

Greater cerebral artery vasodilation mediated by cyclooxygenase (COX) in female animals is unexplored in humans. We hypothesized that young, healthy women would exhibit greater basal cerebral blood flow (CBF) and greater vasodilation during hypoxia or hypercapnia compared to men, mediated by a larger contribution of COX. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 42 adults (24 women, 18 men; 24 ± 1 years) during two visits, in a double-blind, placebo-controlled design (COX inhibition, 100 mg oral indomethacin, Indo). Women were studied early in the follicular phase of the menstrual cycle (days 1-5). Two levels of isocapnic hypoxia (SPO2 = 90% and 80%) were induced for 5-min each. Separately, hypercapnia was induced by increasing end-tidal carbon dioxide (PETCO 2) 10 mmHg above baseline. A positive change in MCAv (ΔMCAv) reflected vasodilation. Basal MCAv was greater in women compared to men (P women exhibit greater basal CBF than men, but similar vasodilatory responses to hypoxia and hypercapnia. Moreover, COX is not obligatory for hypoxic vasodilation, but plays a vital and similar role in the regulation of basal CBF (~30%) and hypercapnic response (~55%) between sexes. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

miR-367 promotes proliferation and invasion of hepatocellular carcinoma cells by negatively regulating PTEN

Energy Technology Data Exchange (ETDEWEB)

Meng, Xiangrui, E-mail: mengxiangruibb2008@163.com [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Fan, Qingxia [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

2016-01-29

MicroRNAs play important roles in the carcinogenesis of many types of cancers by inhibiting gene expression at posttranscriptional level. However, the roles of microRNAs in hepatocellular carcinoma, are still unclear. Here, we identified that miR-367 promotes hepatocellular carcinoma (HCC) cell proliferation by negatively regulates its target gene PTEN. The expression of miR-367 and PTEN are significantly inverse correlated in 35 HCC patients. In HCC cell line, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-367, while miR-367 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-367 mimics significantly promoted the migration and invasion of HCC cells, whereas miR-367 inhibitors significantly reduced cell migration and invasion. Luciferase assays confirmed that miR-367 directly bound to the 3'untranslated region of PTEN, and western blotting showed that miR-367 suppressed the expression of PTEN at the protein levels. This study indicated that miR-367 negatively regulates PTEN and promotes proliferation and invasion of HCC cells. Thus, miR-367 may represent a potential therapeutic target for HCC intervention. - Highlights: • miR-367 mimics promote the proliferation and invasion of HCC cells. • miR-367 inhibitors inhibit the proliferation and invasion of HCC cells. • miR-367 targets 3′UTR of PTEN in HCC cells. • miR-367 negatively regulates PTEN in HCC cells.

Vitamin a is a negative regulator of osteoblast mineralization.

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Thomas Lind

Full Text Available An excessive intake of vitamin A has been associated with an increased risk of fractures in humans. In animals, a high vitamin A intake leads to a reduction of long bone diameter and spontaneous fractures. Studies in rodents indicate that the bone thinning is due to increased periosteal bone resorption and reduced radial growth. Whether the latter is a consequence of direct effects on bone or indirect effects on appetite and general growth is unknown. In this study we therefore used pair-feeding and dynamic histomorphometry to investigate the direct effect of a high intake of vitamin A on bone formation in rats. Although there were no differences in body weight or femur length compared to controls, there was an approximately halved bone formation and mineral apposition rate at the femur diaphysis of rats fed vitamin A. To try to clarify the mechanism(s behind this reduction, we treated primary human osteoblasts and a murine preosteoblastic cell line (MC3T3-E1 with the active metabolite of vitamin A; retinoic acid (RA, a retinoic acid receptor (RAR antagonist (AGN194310, and a Cyp26 inhibitor (R115866 which blocks endogenous RA catabolism. We found that RA, via RARs, suppressed in vitro mineralization. This was independent of a negative effect on osteoblast proliferation. Alkaline phosphatase and bone gamma carboxyglutamate protein (Bglap, Osteocalcin were drastically reduced in RA treated cells and RA also reduced the protein levels of Runx2 and Osterix, key transcription factors for progression to a mature osteoblast. Normal osteoblast differentiation involved up regulation of Cyp26b1, the major enzyme responsible for RA degradation, suggesting that a drop in RA signaling is required for osteogenesis analogous to what has been found for chondrogenesis. In addition, RA decreased Phex, an osteoblast/osteocyte protein necessary for mineralization. Taken together, our data indicate that vitamin A is a negative regulator of osteoblast mineralization.

ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

LENUS (Irish Health Repository)

Liu, Jinghua

2010-05-15

Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll\\/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.

The early diagnostic value of oral acetazolamide load combined with SPECT rCBF imaging in patients with transient ischemia attack in brain

International Nuclear Information System (INIS)

Liu Xintong; Zheng Zhiping; Qiao Suixian; Tang Anwu

2001-01-01

Objective: In order to assess the diagnostic value of acetazolamide (ACZ) combined with rCBF-SPECT imaging in patients with transient ischemia attack (TIA). Methods: SPECT imaging was performed before and after oral ACZ with visual and semiquantitative analysis of the images. Blood gas analysis was done before and after ACZ administration either. Results: After ACZ loading, in normal group, 99 Tc m -ECD was distributed symmetrically on correspondent parts of the brain and rCBF was generally increased. The blood pH was decreased and blood PCO 2 was increased, respectively in TIA group, the positive rate of hypoperfusion foci on SPECT images were increased from 5/6 to 6/6 in symptomatic patients and from 60% to 92% in asymptomatic patients. The total positive rate was 93%. Conclusion: Oral ACZ before SPECT imaging is a simple, reliable way for early diagnosis in patients with TIA

HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans.

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Won Hee Jung

2010-11-01

Full Text Available The fungal pathogen Cryptococcus neoformans is a major cause of illness in immunocompromised individuals such as AIDS patients. The ability of the fungus to acquire nutrients during proliferation in host tissue and the ability to elaborate a polysaccharide capsule are critical determinants of disease outcome. We previously showed that the GATA factor, Cir1, is a major regulator both of the iron uptake functions needed for growth in host tissue and the key virulence factors such as capsule, melanin and growth at 37°C. We are interested in further defining the mechanisms of iron acquisition from inorganic and host-derived iron sources with the goal of understanding the nutritional adaptation of C. neoformans to the host environment. In this study, we investigated the roles of the HAP3 and HAPX genes in iron utilization and virulence. As in other fungi, the C. neoformans Hap proteins negatively influence the expression of genes encoding respiratory and TCA cycle functions under low-iron conditions. However, we also found that HapX plays both positive and negative roles in the regulation of gene expression, including a positive regulatory role in siderophore transporter expression. In addition, HapX also positively regulated the expression of the CIR1 transcript. This situation is in contrast to the negative regulation by HapX of genes encoding GATA iron regulatory factors in Aspergillus nidulans and Schizosaccharomyces pombe. Although both hapX and hap3 mutants were defective in heme utilization in culture, only HapX made a contribution to virulence, and loss of HapX in a strain lacking the high-affinity iron uptake system did not cause further attenuation of disease. Therefore, HapX appears to have a minimal role during infection of mammalian hosts and instead may be an important regulator of environmental iron uptake functions. Overall, these results indicated that C. neoformans employs multiple strategies for iron acquisition during infection.

Support vector machine-based classification of neuroimages in Alzheimer’s disease: direct comparison of FDG-PET, rCBF-SPECT and MRI data acquired from the same individuals

Directory of Open Access Journals (Sweden)

Luiz K. Ferreira

2017-10-01

Full Text Available Objective: To conduct the first support vector machine (SVM-based study comparing the diagnostic accuracy of T1-weighted magnetic resonance imaging (T1-MRI, F-fluorodeoxyglucose-positron emission tomography (FDG-PET and regional cerebral blood flow single-photon emission computed tomography (rCBF-SPECT in Alzheimer’s disease (AD. Method: Brain T1-MRI, FDG-PET and rCBF-SPECT scans were acquired from a sample of mild AD patients (n=20 and healthy elderly controls (n=18. SVM-based diagnostic accuracy indices were calculated using whole-brain information and leave-one-out cross-validation. Results: The accuracy obtained using PET and SPECT data were similar. PET accuracy was 68∼71% and area under curve (AUC 0.77∼0.81; SPECT accuracy was 68∼74% and AUC 0.75∼0.79, and both had better performance than analysis with T1-MRI data (accuracy of 58%, AUC 0.67. The addition of PET or SPECT to MRI produced higher accuracy indices (68∼74%; AUC: 0.74∼0.82 than T1-MRI alone, but these were not clearly superior to the isolated neurofunctional modalities. Conclusion: In line with previous evidence, FDG-PET and rCBF-SPECT more accurately identified patients with AD than T1-MRI, and the addition of either PET or SPECT to T1-MRI data yielded increased accuracy. The comparable SPECT and PET performances, directly demonstrated for the first time in the present study, support the view that rCBF-SPECT still has a role to play in AD diagnosis.

Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.

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Yan, Meiping; Zhang, Xinhua; Chen, Ao; Gu, Wei; Liu, Jie; Ren, Xiaojiao; Zhang, Jianping; Wu, Xiaoxiong; Place, Aaron T; Minshall, Richard D; Liu, Guoquan

2017-11-01

Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2-containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1-SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1-VE-cadherin association and promoted VE-cadherin-actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2- via association with ICAM-1-mediates ICAM-1-induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.-Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction. © FASEB.

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway

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Yunxia Liu; Weibing Dong; Jing Shao; Yibin Wang; Meiyi Zhou; Haipeng Sun

2017-01-01

Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively cont...

NKG2H-Expressing T Cells Negatively Regulate Immune Responses

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Daniela Dukovska

2018-03-01

Full Text Available The biology and function of NKG2H receptor, unlike the better characterized members of the NKG2 family NKG2A, NKG2C, and NKG2D, remains largely unclear. Here, we show that NKG2H is able to associate with the signaling adapter molecules DAP12 and DAP10 suggesting that this receptor can signal for cell activation. Using a recently described NKG2H-specific monoclonal antibody (mAb, we have characterized the expression and function of lymphocytes that express this receptor. NKG2H is expressed at the cell surface of a small percentage of peripheral blood mononuclear cell (PBMC and is found more frequently on T cells, rather than NK cells. Moreover, although NKG2H is likely to trigger activation, co-cross-linking of this receptor with an NKG2H-specific mAb led to decreased T cell activation and proliferation in polyclonal PBMC cultures stimulated by anti-CD3 mAbs. This negative regulatory activity was seen only after cross-linking with NKG2H, but not NKG2A- or NKG2C-specific monoclonal antibodies. The mechanism underlying this negative effect is as yet unclear, but did not depend on the release of soluble factors or recognition of MHC class I molecules. These observations raise the intriguing possibility that NKG2H may be a novel marker for T cells able to negatively regulate T cell responses.

Expectancies for Social Support and Negative Mood Regulation Mediate the Relationship between Childhood Maltreatment and Self-Injury

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Fiona Tresno

2016-07-01

Full Text Available Nonsuicidal self-injury (NSSI is common among young people. A majority of individuals who injure themselves do so to alleviate negative affect, as most self-injurers report difficulties with mood regulation. Trauma in childhood is an important risk factor that may cause individuals to develop poor interpersonal relations and impaired emotion-regulation, leading to the use of non-adaptive coping strategies such as NSSI. This study examined factors contributing to self-injury, focusing on the link from childhood maltreatment, through mood regulation expectancies and expectancies for social support (father, mother, and friends, to self-injury. Understanding how these variables relate to NSSI is crucial for early identification of individuals at risk of NSSI. Participants were 377 Japanese university students. Lifetime prevalence of self-injury was 20% among the sample. Results showed childhood maltreatment is a strong predictor that increases the risk for NSSI. However, expectancies for social support and mood regulation seem to be potential protective factors. Mood regulation expectancies mediate the relationship between childhood maltreatment and self-injury. In addition, expectancies for social support were indirectly linked with NSSI through negative mood regulation expectancies. It appears that perceived support from father and friends increases one's confidence in regulating difficult emotions, which in turn reduces risk for NSSI. Results suggest that strong expectancies for social support, especially from friends, increase one's confidence in regulating emotion, which contributes as a protective factor against self-injury.

Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression

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Makino, Yuichi; Cao, Renhai; Svensson, Kristian; Bertilsson, Göran; Asman, Mikael; Tanaka, Hirotoshi; Cao, Yihai; Berkenstam, Anders; Poellinger, Lorenz

2001-11-01

Alteration of gene expression is a crucial component of adaptive responses to hypoxia. These responses are mediated by hypoxia-inducible transcription factors (HIFs). Here we describe an inhibitory PAS (Per/Arnt/Sim) domain protein, IPAS, which is a basic helix-loop-helix (bHLH)/PAS protein structurally related to HIFs. IPAS contains no endogenous transactivation function but demonstrates dominant negative regulation of HIF-mediated control of gene expression. Ectopic expression of IPAS in hepatoma cells selectively impairs induction of genes involved in adaptation to a hypoxic environment, notably the vascular endothelial growth factor (VEGF) gene, and results in retarded tumour growth and tumour vascular density in vivo. In mice, IPAS was predominantly expressed in Purkinje cells of the cerebellum and in corneal epithelium of the eye. Expression of IPAS in the cornea correlates with low levels of expression of the VEGF gene under hypoxic conditions. Application of an IPAS antisense oligonucleotide to the mouse cornea induced angiogenesis under normal oxygen conditions, and demonstrated hypoxia-dependent induction of VEGF gene expression in hypoxic corneal cells. These results indicate a previously unknown mechanism for negative regulation of angiogenesis and maintenance of an avascular phenotype.

Nfatc2 and Tob1 have non-overlapping function in T cell negative regulation and tumorigenesis.

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Sarah L May

Full Text Available Nfatc2 and Tob1 are intrinsic negative regulators of T cell activation. Nfatc2-deficient and Tob1-deficient T cells show reduced thresholds of activation; however, whether these factors have independent or overlapping roles in negative regulation of T cell responses has not been previously examined. Here, we show that Nfatc2 knockout (KO but not Tob1 KO mice have age-associated accumulation of persistently activated T cells in vivo and expansion of the CD44+ memory cell compartment and age-associated lymphocytic infiltrates in visceral organs, without significant changes in numbers of CD4+CD25+Foxp3+ regulatory T cells (Treg. In vitro, CD4+CD25- "conventional" T cells (Tconvs from both KO strains showed greater proliferation than wild type (WT Tconvs. However, while Tregs from Nfatc2 KO mice retained normal suppressive function, Tregs from Tob1 KOs had enhanced suppressive activity. Nfatc2 KO Tconvs expanded somewhat more rapidly than WT Tconvs under conditions of homeostatic proliferation, but their accelerated growth capacity was negated, at least acutely, in a lymphoreplete environment. Finally, Nfatc2 KO mice developed a previously uncharacterized increase in B-cell malignancies, which was not accelerated by the absence of Tob1. The data thus support the prevailing hypothesis that Nfatc2 and Tob1 are non-redundant regulators of lymphocyte homeostasis.

Integrating and differentiating aspects of self-regulation: effortful control, executive functioning, and links to negative affectivity.

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Bridgett, David J; Oddi, Kate B; Laake, Lauren M; Murdock, Kyle W; Bachmann, Melissa N

2013-02-01

Subdisciplines within psychology frequently examine self-regulation from different frameworks despite conceptually similar definitions of constructs. In the current study, similarities and differences between effortful control, based on the psychobiological model of temperament (Rothbart, Derryberry, & Posner, 1994), and executive functioning are examined and empirically tested in three studies (n = 509). Structural equation modeling indicated that effortful control and executive functioning are strongly associated and overlapping constructs (Study 1). Additionally, results indicated that effortful control is related to the executive function of updating/monitoring information in working memory, but not inhibition (Studies 2 and 3). Study 3 also demonstrates that better updating/monitoring information in working memory and better effortful control were uniquely linked to lower dispositional negative affect, whereas the executive function of low/poor inhibition was uniquely associated with an increased tendency to express negative affect. Furthermore, dispositional negative affect mediated the links between effortful control and, separately, the executive function of updating/monitoring information in working memory and the tendency to express negative affect. The theoretical implications of these findings are discussed, and a potential framework for guiding future work directed at integrating and differentiating aspects of self-regulation is suggested. PsycINFO Database Record (c) 2013 APA, all rights reserved.

A large family of antivirulence regulators modulates the effects of transcriptional activators in Gram-negative pathogenic bacteria.

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Araceli E Santiago

2014-05-01

Full Text Available We have reported that transcription of a hypothetical small open reading frame (orf60 in enteroaggregative E. coli (EAEC strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44-100% similarity to at least fifty previously undescribed small (<10 kDa hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators for this family.

Brassinosteroid-Induced Transcriptional Repression and Dephosphorylation-Dependent Protein Degradation Negatively Regulate BIN2-Interacting AIF2 (a BR Signaling-Negative Regulator) bHLH Transcription Factor.

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Kim, Yoon; Song, Ji-Hye; Park, Seon-U; Jeong, You-Seung; Kim, Soo-Hwan

2017-02-01

Brassinosteroids (BRs) are plant polyhydroxy-steroids that play important roles in plant growth and development via extensive signal integration through direct interactions between regulatory components of different signaling pathways. Recent studies have shown that diverse helix-loop-helix/basic helix-loop-helix (HLH/bHLH) family proteins are actively involved in control of BR signaling pathways and interact with other signaling pathways. In this study, we show that ATBS1-INTERACTING FACTOR 2 (AIF2), a nuclear-localized atypical bHLH transcription factor, specifically interacts with BRASSINOSTEROID-INSENSITIVE 2 (BIN2) among other BR signaling molecules. Overexpression of AIF2 down-regulated transcript expression of growth-promoting genes, thus resulting in retardation of growth. AIF2 renders plants hyposensitive to BR-induced root growth inhibition, but shows little effects on BR-promoted hypocotyl elongation. Notably, AIF2 was dephosphorylated by BR, and the dephosphorylated AIF2 was subject to proteasome-mediated degradation. AIF2 degradation was greatly induced by BR and ABA, but relatively slightly by other hormones such as auxin, gibberellin, cytokinin and ethylene. Moreover, AIF2 transcription was significantly suppressed by a BRI1/BZR1-mediated BR signaling pathway through a direct binding of BRASSINAZOLE RESISTANT 1 (BZR1) to the BR response element (BRRE) region of the AIF2 promoter. In conclusion, our study suggests that BIN2-driven AIF2 phosphorylation could augment the BIN2/AIF2-mediated negative circuit of BR signaling pathways, and the BR-induced transcriptional repression and protein degradation negatively regulate AIF2 transcription factor, reinforcing the BZR1/BES1-mediated positive BR signaling pathway. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Role of NeuroD1 on the negative regulation of Pomc expression by glucocorticoid.

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Rehana Parvin

Full Text Available The mechanism of the negative regulation of proopiomelanocortin gene (Pomc by glucocorticoids (Gcs is still unclear in many points. Here, we demonstrated the involvement of neurogenic differentiation factor 1 (NeuroD1 in the Gc-mediated negative regulation of Pomc. Murine pituitary adrenocorticotropic hormone (ACTH producing corticotroph tumor-derived AtT20 cells were treated with dexamethasone (DEX (1-100 nM and cultured for 24 hrs. Thereafter, Pomc mRNA expression was studied by quantitative real-time PCR and rat Pomc promoter (-703/+58 activity was examined by luciferase assay. Both Pomc mRNA expression and Pomc promoter activity were inhibited by DEX in a dose-dependent manner. Deletion and point mutant analyses of Pomc promoter suggested that the DEX-mediated transcriptional repression was mediated via E-box that exists at -376/-371 in the promoter. Since NeuroD1 is known to bind to and activate E-box of the Pomc promoter, we next examined the effect of DEX on NeuroD1 expression. Interestingly, DEX dose-dependently inhibited NeuroD1 mRNA expression, mouse NeuroD1 promoter (-2.2-kb activity, and NeuroD1 protein expression in AtT20 cells. In addition, we confirmed the inhibitory effect of DEX on the interaction of NeuroD1 and E-box on Pomc promoter by chromatin immunoprecipitation (ChIP assay. Finally, overexpression of mouse NeuroD1 could rescue the DEX-mediated inhibition of Pomc mRNA expression and Pomc promoter activity. Taken together, it is suggested that the suppression of NeuroD1 expression and the inhibition of NeuroD1/E-box interaction may play an important role in the Gc-mediated negative regulation of Pomc.

Chondroitin-4-sulfation negatively regulates axonal guidance and growth

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Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas E.; Unsworth, Edward; Goldsmith, Paul; Yu, Zu-Xi; Tan, Fei; Santiago, Lizzie; Mills, Edward M.; Wang, Yu; Symes, Aviva J.; Geller, Herbert M.

2008-01-01

Summary Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition, and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate (CS) mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated CS GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings provide the evidence showing that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function. PMID:18768934

In vivo detection of prion amyloid plaques using [{sup 11}C]BF-227 PET

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Okamura, Nobuyuki; Yanai, Kazuhiko [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Shiga, Yusei; Itoyama, Yasuhito [Tohoku University School of Medicine, Department of Neurology, Sendai (Japan); Furumoto, Shozo [Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Tashiro, Manabu [Tohoku University, Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Sendai (Japan); Tsuboi, Yoshio [Fukuoka University School of Medicine, Department of Neurology, Fukuoka (Japan); Furukawa, Katsutoshi; Arai, Hiroyuki [Institute of Development, Aging, and Cancer, Tohoku University, Department of Geriatrics and Gerontology, Division of Brain Sciences, Sendai (Japan); Iwata, Ren [Tohoku University, Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Innovation of New Biomedical Engineering Center, Sendai (Japan); Doh-ura, Katsumi [Tohoku University School of Medicine, Department of Prion Research, 2-1 Seiryo-machi, Aoba-ku, Sendai (Japan)

2010-05-15

In vivo detection of pathological prion protein (PrP) in the brain is potentially useful for the diagnosis of transmissible spongiform encephalopathies (TSEs). However, there are no non-invasive ante-mortem means for detection of pathological PrP deposition in the brain. The purpose of this study is to evaluate the amyloid imaging tracer BF-227 with positron emission tomography (PET) for the non-invasive detection of PrP amyloid in the brain. The binding ability of BF-227 to PrP amyloid was investigated using autoradiography and fluorescence microscopy. Five patients with TSEs, including three patients with Gerstmann-Straeussler-Scheinker disease (GSS) and two patients with sporadic Creutzfeldt-Jakob disease (CJD), underwent [{sup 11}C]BF-227 PET scans. Results were compared with data from 10 normal controls and 17 patients with Alzheimer's disease (AD). The regional to pons standardized uptake value ratio was calculated as an index of BF-227 retention. Binding of BF-227 to PrP plaques was confirmed using brain samples from autopsy-confirmed GSS cases. In clinical PET study, significantly higher retention of BF-227 was detected in the cerebellum, thalamus and lateral temporal cortex of GSS patients compared to that in the corresponding tissues of normal controls. GSS patients also showed higher retention of BF-227 in the cerebellum, thalamus and medial temporal cortex compared to AD patients. In contrast, the two CJD patients showed no obvious retention of BF-227 in the brain. Although [{sup 11}C]BF-227 is a non-specific imaging marker of cerebral amyloidosis, it is useful for in vivo detection of PrP plaques in the human brain in GSS, based on the regional distribution of the tracer. PET amyloid imaging might provide a means for both early diagnosis and non-invasive disease monitoring of certain forms of TSEs. (orig.)

Zebrafish foxo3b negatively regulates canonical Wnt signaling to affect early embryogenesis.

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Xun-wei Xie

Full Text Available FOXO genes are involved in many aspects of development and vascular homeostasis by regulating cell apoptosis, proliferation, and the control of oxidative stress. In addition, FOXO genes have been showed to inhibit Wnt/β-catenin signaling by competing with T cell factor to bind to β-catenin. However, how important of this inhibition in vivo, particularly in embryogenesis is still unknown. To demonstrate the roles of FOXO genes in embryogenesis will help us to further understand their relevant physiological functions. Zebrafish foxo3b gene, an orthologue of mammalian FOXO3, was expressed maternally and distributed ubiquitously during early embryogenesis and later restricted to brain. After morpholino-mediated knockdown of foxo3b, the zebrafish embryos exhibited defects in axis and neuroectoderm formation, suggesting its critical role in early embryogenesis. The embryo-developmental marker gene staining at different stages, phenotype analysis and rescue assays revealed that foxo3b acted its role through negatively regulating both maternal and zygotic Wnt/β-catenin signaling. Moreover, we found that foxo3b could interact with zebrafish β-catenin1 and β-catenin2 to suppress their transactivation in vitro and in vivo, further confirming its role relevant to the inhibition of Wnt/β-catenin signaling. Taken together, we revealed that foxo3b played a very important role in embryogenesis and negatively regulated maternal and zygotic Wnt/β-catenin signaling by directly interacting with both β-catenin1 and β-catenin2. Our studies provide an in vivo model for illustrating function of FOXO transcription factors in embryogenesis.

Peroxiredoxin II is an antioxidant enzyme that negatively regulates collagen-stimulated platelet function.

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Jang, Ji Yong; Wang, Su Bin; Min, Ji Hyun; Chae, Yun Hee; Baek, Jin Young; Yu, Dae-Yeul; Chang, Tong-Shin

2015-05-01

Collagen-induced platelet signaling is mediated by binding to the primary receptor glycoprotein VI (GPVI). Reactive oxygen species produced in response to collagen have been found to be responsible for the propagation of GPVI signaling pathways in platelets. Therefore, it has been suggested that antioxidant enzymes could down-regulate GPVI-stimulated platelet activation. Although the antioxidant enzyme peroxiredoxin II (PrxII) has emerged as having a role in negatively regulating signaling through various receptors by eliminating H2O2 generated upon receptor stimulation, the function of PrxII in collagen-stimulated platelets is not known. We tested the hypothesis that PrxII negatively regulates collagen-stimulated platelet activation. We analyzed PrxII-deficient murine platelets. PrxII deficiency enhanced GPVI-mediated platelet activation through the defective elimination of H2O2 and the impaired protection of SH2 domain-containing tyrosine phosphatase 2 (SHP-2) against oxidative inactivation, which resulted in increased tyrosine phosphorylation of key components for the GPVI signaling cascade, including Syk, Btk, and phospholipase Cγ2. Interestingly, PrxII-mediated antioxidative protection of SHP-2 appeared to occur in the lipid rafts. PrxII-deficient platelets exhibited increased adhesion and aggregation upon collagen stimulation. Furthermore, in vivo experiments demonstrated that PrxII deficiency facilitated platelet-dependent thrombus formation in injured carotid arteries. This study reveals that PrxII functions as a protective antioxidant enzyme against collagen-stimulated platelet activation and platelet-dependent thrombosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition

DEFF Research Database (Denmark)

Schäfer, Katharina; Blankenburg, Felix; Kupers, Ron

2012-01-01

that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI. The negative BOLD signal in ipsilateral SI......) at the ipsilateral finger during concomitant stimulation of the contralateral median nerve increased significantly, suggesting augmented functional inhibition. Since the CPT in the ipsilateral hallux did not significantly change in response to median nerve stimulation, it is more likely that the CPT......-increase for the finger is due to functional inhibition (Kastrup et al., 2008) than to changes in selective attention. In conclusion, our data provide evidence that stimulus-induced reductions in relative rCBF may underlie the negative BOLD signal, which in turn may reflect increments in functional inhibition....

WRKY54 and WRKY70 co-operate as negative regulators of leaf senescence in Arabidopsis thaliana

OpenAIRE

Besseau, Sébastien; Li, Jing; Palva, E. Tapio

2012-01-01

The plant-specific WRKY transcription factor (TF) family with 74 members in Arabidopsis thaliana appears to be involved in the regulation of various physiological processes including plant defence and senescence. WRKY53 and WRKY70 were previously implicated as positive and negative regulators of senescence, respectively. Here the putative function of other WRKY group III proteins in Arabidopsis leaf senescence has been explored and the results suggest the involvement of two additional WRKY TF...

The negative cell cycle regulator, Tob (transducer of ErbB-2), is involved in motor skill learning

International Nuclear Information System (INIS)

Wang Xinming; Gao Xiang; Zhang Xuehan; Tu Yanyang; Jin Meilei; Zhao Guoping; Yu Lei; Jing Naihe; Li Baoming

2006-01-01

Tob (transducer of ErbB-2) is a negative cell cycle regulator with anti-proliferative activity in peripheral tissues. Our previous study identified Tob as a protein involved in hippocampus-dependent memory consolidation (M.L. Jin, X.M. Wang, Y.Y. Tu, X.H. Zhang, X. Gao, N. Guo, Z.Q. Xie, G.P. Zhao, N.H. Jing, B.M. Li, Y.Yu, The negative cell cycle regulator, Tob (Transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory, Neuroscience 131 (2005) 647-659). Here, we provide evidence that Tob in the central nervous system is engaged in acquisition of motor skill. Tob has a relatively high expression in the cerebellum. Tob expression is up-regulated in the cerebellum after rats receive training on a rotarod-running task. Rats infused with Tob antisense oligonucleotides into the 4th ventricle exhibit a severe deficit in running on a rotating rod or walking across a horizontally elevated beam

SACE_3986, a TetR family transcriptional regulator, negatively controls erythromycin biosynthesis in Saccharopolyspora erythraea.

Science.gov (United States)

Wu, Panpan; Pan, Hui; Zhang, Congming; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhou, Ying; Ye, Bang-ce; Weaver, David T; Zhang, Lixin; Zhang, Buchang

2014-07-01

Erythromycin, a medically important antibiotic, is produced by Saccharopolyspora erythraea. Unusually, the erythromycin biosynthetic gene cluster lacks a regulatory gene, and the regulation of its biosynthesis remains largely unknown. In this study, through gene deletion, complementation and overexpression experiments, we identified a novel TetR family transcriptional regulator SACE_3986 negatively regulating erythromycin biosynthesis in S. erythraea A226. When SACE_3986 was further inactivated in an industrial strain WB, erythromycin A yield of the mutant was increased by 54.2 % in average compared with that of its parent strain, displaying the universality of SACE_3986 as a repressor for erythromycin production in S. erythraea. qRT-PCR analysis indicated that SACE_3986 repressed the transcription of its adjacent gene SACE_3985 (which encodes a short-chain dehydrogenase/reductase), erythromycin biosynthetic gene eryAI and the resistance gene ermE. As determined by EMSA analysis, purified SACE_3986 protein specifically bound to the intergenic region between SACE_3985 and SACE_3986, whereas it did not bind to the promoter regions of eryAI and ermE. Furthermore, overexpression of SACE_3985 in A226 led to enhanced erythromycin A yield by at least 32.6 %. These findings indicate that SACE_3986 is a negative regulator of erythromycin biosynthesis, and the adjacent gene SACE_3985 is one of its target genes. The present study provides a basis to increase erythromycin production by engineering of SACE_3986 and SACE_3985 in S. erythraea.

SALT-RESPONSIVE ERF1 is a negative regulator of grain filling and gibberellin-mediated seedling establishment in rice.

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Schmidt, Romy; Schippers, Jos H M; Mieulet, Delphine; Watanabe, Mutsumi; Hoefgen, Rainer; Guiderdoni, Emmanuel; Mueller-Roeber, Bernd

2014-02-01

Grain quality is an important agricultural trait that is mainly determined by grain size and composition. Here, we characterize the role of the rice transcription factor (TF) SALT-RESPONSIVE ERF1 (SERF1) during grain development. Through genome-wide expression profiling and chromatin immunoprecipitation, we found that SERF1 directly regulates RICE PROLAMIN-BOX BINDING FACTOR (RPBF), a TF that functions as a positive regulator of grain filling. Loss of SERF1 enhances RPBF expression resulting in larger grains with increased starch content, while SERF1 overexpression represses RPBF resulting in smaller grains. Consistently, during grain filling, starch biosynthesis genes such as GRANULE-BOUND STARCH SYNTHASEI (GBSSI), STARCH SYNTHASEI (SSI), SSIIIa, and ADP-GLUCOSE PYROPHOSPHORYLASE LARGE SUBUNIT2 (AGPL2) are up-regulated in SERF1 knockout grains. Moreover, SERF1 is a direct upstream regulator of GBSSI. In addition, SERF1 negatively regulates germination by controlling RPBF expression, which mediates the gibberellic acid (GA)-induced expression of RICE AMYLASE1A (RAmy1A). Loss of SERF1 results in more rapid seedling establishment, while SERF1 overexpression has the opposite effect. Our study reveals that SERF1 represents a negative regulator of grain filling and seedling establishment by timing the expression of RPBF.

MicroRNA, miR-374b, directly targets Myf6 and negatively regulates C2C12 myoblasts differentiation

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Ma, Zhiyuan; Sun, Xiaorui; Xu, Dequan; Xiong, Yuanzhu; Zuo, Bo, E-mail: zuobo@mail.hzau.edu.cn

2015-11-27

Myogenesis is a complex process including myoblast proliferation, differentiation and myotube formation and is controlled by myogenic regulatory factors (MRFs), MyoD, MyoG, Myf5 and Myf6 (also known as MRF4). MicroRNA is a kind of ∼22 nt-long non-coding small RNAs, and act as key transcriptional or post-transcriptional regulators of gene expression. Identification of miRNAs involved in the regulation of muscle genes could improve our understanding of myogenesis process. In this study, we investigated the regulation of Myf6 gene by miRNAs. We showed that miR-374b specifically bound to the 3'untranslated region (UTR) of Myf6 and down-regulated the expression of Myf6 gene at both mRNA and protein level. Furthermore, miR-374b is ubiquitously expressed in the tissues of adult C57BL6 mouse, and the mRNA abundance increases first and then decreases during C2C12 myoblasts differentiation. Over-expression of miR-374b impaired C2C12 cell differentiation, while inhibiting miR-374b expression by 2′-O-methyl antisense oligonucleotides promoted C2C12 cell differentiation. Taken together, our findings identified miR-374b directly targets Myf6 and negatively regulates myogenesis. - Highlights: • MiR-374b directly targets 3′UTR of Myf6. • MiR-374b negatively regulates Myf6 in C2C12 cells. • MiR-374b abundance significiently changes during C2C12 cells differentiation. • MiR-374b negatively regulates C2C12 cells differentiation.

EGR-1 and DUSP-1 are important negative regulators of pro-allergic responses in airway epithelium

NARCIS (Netherlands)

Golebski, Korneliusz; van Egmond, Danielle; de Groot, Esther J.; Roschmann, Kristina I. L.; Fokkens, Wytske J.; van Drunen, Cornelis M.

2015-01-01

Background: Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state. Objective: To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could

Regional cerebral blood flow (rCBF) in schizophrenia during verbal memory activation: a 99mTc-HMPAO single photon emission tomography (SPET) study.

Science.gov (United States)

Busatto, G F; Costa, D C; Ell, P J; Pilowsky, L S; David, A S; Kerwin, R W

1994-05-01

Regional cerebral blood flow (rCBF) was investigated in a group of medicated DSM-III-R schizophrenic patients and age, sex and handedness matched normal volunteers using a split-dose 99mTc-HMPAO Single Photon Emission Tomography (SPET) protocol. Measures were taken during the performance of a verbal memory task aimed at activating the left medial temporal lobe, a region repeatedly suggested to be structurally abnormal in schizophrenia. In normal subjects, the performance of the task was associated with significant rCBF increases in the left medial temporal, left inferior frontal and anterior cingulate cortices, and right cerebellum. Despite their significantly poorer performance on the memory task, the degree of medial temporal activation measured in the schizophrenic patients was not significantly different from that found in the control group. This finding suggests that memory deficits in schizophrenia do not necessarily imply failure to activate the left medial temporal lobe as assessed by 99mTc-HMPAO SPET.

Correlation of experimental rCBF determinations in goats with flow measurements from a Doppler-modified carotid artery shunt

International Nuclear Information System (INIS)

Loftus, C.M.; Silvidi, J.A.; Becker, J.A.; Miller, B.V.; Bernstein, D.D.

1989-01-01

A carotid artery shunt system has been developed that continuously monitors blood flow rates by embedding a Doppler crystal in the shunt wall. The crystal ranges through a liquid lens that enables it to be placed without violation of the shunt lumen. Because the crystal is at a fixed angle (45 degrees) to the axis of blood flow and the diameter of the lumen remains constant, a linear relationship exists between flow rates and the Doppler velocity signal. This shunt system was previously tested in vitro using a pulsatile pump and was found to be accurate to within 4.7% of the actual flow rate. In the present study, animal (goat) experiments were performed consisting of simultaneous carotid shunt flow and bilateral rCBF measurements by the radiolabeled microsphere technique to determine in vivo the accuracy of this Doppler modified shunt and to ascertain the ability of shunt flow to increase in the face of acute contralateral carotid occlusion. Data from five animals show that in vivo shunt flow can be recorded to within 13% of control rCBF and that shunt flow increases nearly 50% under conditions of distal demand (contralateral carotid occlusion). This device may prove useful in laboratory studies of carotid shunt dynamics and in clinical practice to quickly detect correctable shunt flow abnormalities

An intravenous isotope method for measuring regional cerebral blood flow (rCBF) and volume (rCBV)

International Nuclear Information System (INIS)

Kuikka, J.; Ahonen, A.; Koivula, A.; Kallanranta, T.; Laitinen, J.

1977-01-01

The regional cerebal blood flow (rCBF), initial slope index (ISI), transfer time (t - sub(h)) and volume (rCBV) were measured simultaneously in 43 hospital patients using a 133 Xe intravenous injection method and quantitative dynamic 99 Tcsup(m) brain scintigraphy. The measurements were made with a gamma camera and the data processing interfaced with a small digital computer. The mean values and standard deviations were obtained from 50 control hemispheres standardized to the age of 40 years. Good agreement was found between the blood flow values determined from the intra-arterial and intravenous injection techniques. (author)

BRAFV600E Negatively Regulates the AKT Pathway in Melanoma Cell Lines

OpenAIRE

Chen, Brenden; Tardell, Christine; Higgins, Brian; Packman, Kathryn; Boylan, John F.; Niu, Huifeng

2012-01-01

Cross-feedback activation of MAPK and AKT pathways is implicated as a resistance mechanism for cancer therapeutic agents targeting either RAF/MEK or PI3K/AKT/mTOR. It is thus important to have a better understanding of the molecular resistance mechanisms to improve patient survival benefit from these agents. Here we show that BRAFV600E is a negative regulator of the AKT pathway. Expression of BRAFV600E in NIH3T3 cells significantly suppresses MEK inhibitor (RG7167) or mTORC1 inhibitor (rapamy...

CIR, a corepressor of CBF1, binds to PAP-1 and effects alternative splicing

International Nuclear Information System (INIS)

Maita, Hiroshi; Kitaura, Hirotake; Ariga, Hiroyoshi; Iguchi-Ariga, Sanae M.M.

2005-01-01

We have reported that PAP-1, a product of a causative gene for autosomal retinitis pigmentosa, plays a role in splicing. In this study, CIR, a protein originally identified as a CBF1-interacting protein and reported to act as a transcriptional corepressor, was identified as a PAP-1 binding protein and its function as a splicing factor was investigated. In addition to a basic lysine and acidic serine-rich (BA) domain and a zinc knuckle-like motif, CIR has an arginine/serine dipeptide repeat (RS) domain in its C terminal region. The RS domain has been reported to be present in the superfamily of SR proteins, which are involved in splicing reactions. We generated CIR mutants with deletions of each BA and RS domain and studied their subcellular localizations and interactions with PAP-1 and other SR proteins, including SC35, SF2/ASF, and U2AF 35 . CIR was found to interact with U2AF 35 through the BA domain, with SC35 and SF2/ASF through the RS domain, and with PAP-1 outside the BA domain in vivo and in vitro. CIR was found to be colocalized with SC35 and PAP-1 in nuclear speckles. Then the effect of CIR on splicing was investigated using the E1a minigene as a reporter in HeLa cells. Ectopic expression of CIR with the E1a minigene changed the ratio of spliced isoforms of E1a that were produced by alternative selection of 5'-splice sites. These results indicate that CIR is a member of the family of SR-related proteins and that CIR plays a role in splicing regulation

RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

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Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

2011-01-05

The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

Fat mass and obesity associated gene (FTO expression is regulated negatively by the transcription factor Foxa2.

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Jianjin Guo

Full Text Available Fat mass and obesity associated gene (FTO is the first gene associated with body mass index (BMI and risk for diabetes. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. To investigate the transcriptional regulation of FTO expression, we created 5'-deletion constructs of the FTO promoter to determine which transcription factors are most relevant to FTO expression. The presence of an activation region at -201/+34 was confirmed by luciferase activity analysis. A potential Foxa2 (called HNF-3β binding site and an upstream stimulatory factor (USF-binding site was identified in the -100 bp fragment upstream of the transcription start site (TSS. Furthermore, using mutagenesis, we identified the Foxa2 binding sequence (-26/-14 as a negative regulatory element to the activity of the human FTO promoter. The USF binding site did not affect the FTO promoter activity. Chromatin immunoprecipitation (ChIP assays were performed to confirm Foxa2 binding to the FTO promoter. Overexpression of Foxa2 in HEK 293 cells significantly down-regulated FTO promoter activity and expression. Conversely, knockdown of Foxa2 by siRNA significantly up-regulated FTO expression. These findings suggest that Foxa2 negatively regulates the basal transcription and expression of the human FTO gene.

Effect of Negative Pressure on Proliferation, Virulence Factor Secretion, Biofilm Formation, and Virulence-Regulated Gene Expression of Pseudomonas aeruginosa In Vitro

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Guo-Qi Wang

2016-01-01

Full Text Available Objective. To investigate the effect of negative pressure conditions induced by NPWT on P. aeruginosa. Methods. P. aeruginosa was cultured in a Luria–Bertani medium at negative pressure of −125 mmHg for 24 h in the experimental group and at atmospheric pressure in the control group. The diameters of the colonies of P. aeruginosa were measured after 24 h. ELISA kit, orcinol method, and elastin-Congo red assay were used to quantify the virulence factors. Biofilm formation was observed by staining with Alexa Fluor® 647 conjugate of concanavalin A (Con A. Virulence-regulated genes were determined by quantitative RT-PCR. Results. As compared with the control group, growth of P. aeruginosa was inhibited by negative pressure. The colony size under negative pressure was significantly smaller in the experimental group than that in the controls (p<0.01. Besides, reductions in the total amount of virulence factors were observed in the negative pressure group, including exotoxin A, rhamnolipid, and elastase. RT-PCR results revealed a significant inhibition in the expression level of virulence-regulated genes. Conclusion. Negative pressure could significantly inhibit the growth of P. aeruginosa. It led to a decrease in the virulence factor secretion, biofilm formation, and a reduction in the expression level of virulence-regulated genes.

delta-EF1 is a negative regulator of Ihh in the developing growth plate.

Science.gov (United States)

Bellon, Ellen; Luyten, Frank P; Tylzanowski, Przemko

2009-11-30

Indian hedgehog (Ihh) regulates proliferation and differentiation of chondrocytes in the growth plate. Although the biology of Ihh is currently well documented, its transcriptional regulation is poorly understood. delta-EF1 is a two-handed zinc finger/homeodomain transcriptional repressor. Targeted inactivation of mouse delta-EF1 leads to skeletal abnormalities including disorganized growth plates, shortening of long bones, and joint fusions, which are reminiscent of defects associated with deregulation of Ihh signaling. Here, we show that the absence of delta-EF1 results in delayed hypertrophic differentiation of chondrocytes and increased cell proliferation in the growth plate. Further, we demonstrate that delta-EF1 binds to the putative regulatory elements in intron 1 of Ihh in vitro and in vivo, resulting in down-regulation of Ihh expression. Finally, we show that delta-EF1 haploinsufficiency leads to a postnatal increase in trabecular bone mass associated with enhanced Ihh expression. In summary, we have identified delta-EF1 as an in vivo negative regulator of Ihh expression in the growth plate.

PKC{eta} is a negative regulator of AKT inhibiting the IGF-I induced proliferation

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Shahaf, Galit; Rotem-Dai, Noa; Koifman, Gabriela; Raveh-Amit, Hadas; Frost, Sigal A.; Livneh, Etta, E-mail: etta@bgu.ac.il

2012-04-15

The PI3K-AKT pathway is frequently activated in human cancers, including breast cancer, and its activation appears to be critical for tumor maintenance. Some malignant cells are dependent on activated AKT for their survival; tumors exhibiting elevated AKT activity show sensitivity to its inhibition, providing an Achilles heel for their treatment. Here we show that the PKC{eta} isoform is a negative regulator of the AKT signaling pathway. The IGF-I induced phosphorylation on Ser473 of AKT was inhibited by the PKC{eta}-induced expression in MCF-7 breast adenocarcinoma cancer cells. This was further confirmed in shRNA PKC{eta}-knocked-down MCF-7 cells, demonstrating elevated phosphorylation on AKT Ser473. While PKC{eta} exhibited negative regulation on AKT phosphorylation it did not alter the IGF-I induced ERK phosphorylation. However, it enhanced ERK phosphorylation when stimulated by PDGF. Moreover, its effects on IGF-I/AKT and PDGF/ERK pathways were in correlation with cell proliferation. We further show that both PKC{eta} and IGF-I confer protection against UV-induced apoptosis and cell death having additive effects. Although the protective effect of IGF-I involved activation of AKT, it was not affected by PKC{eta} expression, suggesting that PKC{eta} acts through a different route to increase cell survival. Hence, our studies show that PKC{eta} provides negative control on AKT pathway leading to reduced cell proliferation, and further suggest that its presence/absence in breast cancer cells will affect cell death, which could be of therapeutic value.

Critical role of types 2 and 3 deiodinases in the negative regulation of gene expression by T₃in the mouse cerebral cortex.

Science.gov (United States)

Hernandez, Arturo; Morte, Beatriz; Belinchón, Mónica M; Ceballos, Ainhoa; Bernal, Juan

2012-06-01

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T(3) to nuclear receptors. Brain T(3) concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T(4) and T(3). We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T(3) led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T(3) treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T(3) action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T(3) concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

MYB52 Negatively Regulates Pectin Demethylesterification in Seed Coat Mucilage.

Science.gov (United States)

Shi, Dachuan; Ren, Angyan; Tang, Xianfeng; Qi, Guang; Xu, Zongchang; Chai, Guohua; Hu, Ruibo; Zhou, Gongke; Kong, Yingzhen

2018-04-01

Pectin, which is a major component of the plant primary cell walls, is synthesized and methyl-esterified in the Golgi apparatus and then demethylesterified by pectin methylesterases (PMEs) located in the cell wall. The degree of methylesterification affects the functional properties of pectin, and thereby influences plant growth, development and defense. However, little is known about the mechanisms that regulate pectin demethylesterification. Here, we show that in Arabidopsis ( Arabidopsis thaliana ) seed coat mucilage, the absence of the MYB52 transcription factor is correlated with an increase in PME activity and a decrease in the degree of pectin methylesterification. Decreased methylesterification in the myb52 mutant is also correlated with an increase in the calcium content of the seed mucilage. Chromatin immunoprecipitation analysis and molecular genetic studies suggest that MYB52 transcriptionally activates PECTIN METHYLESTERASE INHIBITOR6 ( PMEI6 ), PMEI14 , and SUBTILISIN-LIKE SER PROTEASE1.7 ( SBT1.7 ) by binding to their promoters. PMEI6 and SBT1.7 have previously been shown to be involved in seed coat mucilage demethylesterification. Our characterization of two PMEI14 mutants suggests that PMEI14 has a role in seed coat mucilage demethylesterification, although its activity may be confined to the seed coat in contrast to PMEI6, which functions in the whole seed. Our demonstration that MYB52 negatively regulates pectin demethylesterification in seed coat mucilage, and the identification of components of the molecular network involved, provides new insight into the regulatory mechanism controlling pectin demethylesterification and increases our understanding of the transcriptional regulation network involved in seed coat mucilage formation. © 2018 American Society of Plant Biologists. All Rights Reserved.

Cassava C-repeat binding factor 1 gene responds to low temperature and enhances cold tolerance when overexpressed in Arabidopsis and cassava.

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An, Dong; Ma, Qiuxiang; Wang, Hongxia; Yang, Jun; Zhou, Wenzhi; Zhang, Peng

2017-05-01

Cassava MeCBF1 is a typical CBF transcription factor mediating cold responses but its low expression in apical buds along with a retarded response cause inefficient upregulation of downstream cold-related genes, rendering cassava chilling-sensitive. Low temperature is a major abiotic stress factor affecting survival, productivity and geographic distribution of important crops worldwide. The C-repeat/dehydration-responsive element binding transcription factors (CBF/DREB) are important regulators of abiotic stress response in plants. In this study, MeCBF1, a CBF-like gene, was identified in the tropical root crop cassava (Manihot esculenta Crantz). The MeCBF1 encodes a protein that shares strong homology with DREB1As/CBFs from Arabidopsis as well as other species. The MeCBF1 was localized to the nucleus and is mainly expressed in stem and mature leaves, but not in apical buds or stem cambium. MeCBF1 expression was not only highly responsive to cold, but also significantly induced by salt, PEG and ABA treatment. Several stress-associated cis-elements were found in its promoter region, e.g., ABRE-related, MYC recognition sites, and MYB responsive element. Compared with AtCBF1, the MeCBF1 expression induced by cold in cassava was retarded and upregulated only after 4 h, which was also confirmed by its promoter activity. Overexpression of MeCBF1 in transgenic Arabidopsis and cassava plants conferred enhanced crytolerance. The CBF regulon was smaller and not entirely co-regulated with MeCBF1 expression in overexpressed cassava. The retarded MeCBF1 expression in response to cold and attenuated CBF-regulon might lead cassava to chilling sensitivity.

Neuropsychological functions and rCBF SPECT in Parkinson's disease patients considered candidates for deep brain stimulation

International Nuclear Information System (INIS)

Paschali, Anna; Lakiotis, Velissarios; Vassilakos, Paulos; Messinis, Lambros; Lyros, Epameinondas; Papathanasopoulos, Panagiotis; Constantoyannis, Costas; Kefalopoulou, Zinovia

2009-01-01

In the present study, we examined relationships between neuropsychological functions and brain single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) observed at presurgical evaluation for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD) patients. Twenty advanced non-demented PD patients, candidates for DBS surgery, underwent perfusion brain SPECT study and neuropsychological assessment prior to surgery (range: 30-50 days). Patients were further assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H and Y) scale. During all assessments patients were ''on'' standard medication. NeuroGam software, which permits voxel by voxel analysis, was used to compare the brain perfusion of PD patients with a normal database adjusted for sex and age. Neuropsychological scores were compared to age, education and sex-adjusted normative databases. Our results indicated that the distribution of rCBF showed significant differences when compared to an age- and sex-adjusted normative database. We found impaired blood flow in 17 (85%) of our patients in the left prefrontal lobe, in 14 (70%) in the right prefrontal lobe and in 11 (55%) in the left frontal and right parietal lobes. Neuropsychological testing revealed that 18 (90%) of our patients had significant impairments in measures of executive functions (set-shifting) and 15 (75%) in response inhibition. Furthermore, we found significant correlations between measures of visual attention, executive functions and the right frontal lobe region. The presence of widespread blood flow reduction was observed mainly in the frontal lobes of dementia-free patients with advanced PD. Furthermore, performance on specific cognitive measures was highly related to perfusion brain SPECT findings. (orig.)

Mechanisms of JAK/STAT pathway negative regulation by the short coreceptor Eye Transformer/Latran.

Science.gov (United States)

Fisher, Katherine H; Stec, Wojciech; Brown, Stephen; Zeidler, Martin P

2016-02-01

Transmembrane receptors interact with extracellular ligands to transduce intracellular signaling cascades, modulate target gene expression, and regulate processes such as proliferation, apoptosis, differentiation, and homeostasis. As a consequence, aberrant signaling events often underlie human disease. Whereas the vertebrate JAK/STAT signaling cascade is transduced via multiple receptor combinations, the Drosophila pathway has only one full-length signaling receptor, Domeless (Dome), and a single negatively acting receptor, Eye Transformer/Latran (Et/Lat). Here we investigate the molecular mechanisms underlying Et/Lat activity. We demonstrate that Et/Lat negatively regulates the JAK/STAT pathway activity and can bind to Dome, thus reducing Dome:Dome homodimerization by creating signaling-incompetent Dome:Et/Lat heterodimers. Surprisingly, we find that Et/Lat is able to bind to both JAK and STAT92E but, despite the presence of putative cytokine-binding motifs, does not detectably interact with pathway ligands. We find that Et/Lat is trafficked through the endocytic machinery for lysosomal degradation but at a much slower rate than Dome, a difference that may enhance its ability to sequester Dome into signaling-incompetent complexes. Our data offer new insights into the molecular mechanism and regulation of Et/Lat in Drosophila that may inform our understanding of how short receptors function in other organisms. © 2016 Fisher et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during flow-dependent vascular remodeling.

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Jun Yu

Full Text Available Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (-/- is associated with activation of the platelet derived growth factor (PDGF signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (-/- mice. Moreover, nitric oxide (NO negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence.

Procyanidin dimer B2-mediated IRAK-M induction negatively regulates TLR4 signaling in macrophages

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Sung, Nak-Yun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Yang, Mi-So [Department of Microbiology, Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Song, Du-Sub [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); School of life sciences and Biotechnology, Korea University 5-ka, Anam-Dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of); Kim, Jae-Kyung; Park, Jong-Heum; Song, Beom-Seok; Park, Sang-Hyun; Lee, Ju-Woon [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Park, Hyun-Jin [School of life sciences and Biotechnology, Korea University 5-ka, Anam-Dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of); Kim, Jae-Hun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Baek, E-mail: ebbyun80@kaeri.re.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Hong, E-mail: ehbyun80@kongju.ac.k [Department of Food Science and Technology, Kongju National University, Yesan 340-800 (Korea, Republic of)

2013-08-16

Highlights: •Pro B2 elevated the expression of IRAK-M, a negative regulator of TLR signaling. •LPS-induced expression of cell surface molecules was inhibited by Pro B2. •LPS-induced production of pro-inflammatory cytokines was inhibited by Pro B2. •Pro B2 inhibited LPS-induced activation of MAPKs and NF-κB through IRAK-M. •Pro B2 inactivated naïve T cells by inhibiting LPS-induced cytokines via IRAK-M. -- Abstract: Polyphenolic compounds have been found to possess a wide range of physiological activities that may contribute to their beneficial effects against inflammation-related diseases; however, the molecular mechanisms underlying this anti-inflammatory activity are not completely characterized, and many features remain to be elucidated. In this study, we investigated the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by procyanidin dimer B2 (Pro B2) in macrophages. Pro B2 markedly elevated the expression of the interleukin (IL)-1 receptor-associated kinase (IRAK)-M protein, a negative regulator of TLR signaling. Lipopolysaccharide (LPS)-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1β, IL-6, and IL-12p70) were inhibited by Pro B2, and this action was prevented by IRAK-M silencing. In addition, Pro B2-treated macrophages inhibited LPS-induced activation of mitogen-activated protein kinases such as extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase and the translocation of nuclear factor κB and p65 through IRAK-M. We also found that Pro B2-treated macrophages inactivated naïve T cells by inhibiting LPS-induced interferon-γ and IL-2 secretion through IRAK-M. These novel findings provide new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and the immune-pharmacological role of Pro B2 in the immune response against the development

Thyroid hormone negatively regulates CDX2 and SOAT2 mRNA expression via induction of miRNA-181d in hepatic cells

Energy Technology Data Exchange (ETDEWEB)

Yap, Chui Sun; Sinha, Rohit Anthony [Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, 8, College Road, Singapore 169857 (Singapore); Ota, Sho; Katsuki, Masahito [Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan); Yen, Paul Michael, E-mail: paul.yen@duke-nus.edu.sg [Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, 8, College Road, Singapore 169857 (Singapore)

2013-11-01

Highlights: •Thyroid hormone induces miR-181d expression in human hepatic cells and mouse livers. •Thyroid hormone downregulates CDX2 and SOAT2 (or ACAT2) via miR-181d. •miR-181d reduces cholesterol output from human hepatic cells. -- Abstract: Thyroid hormones (THs) regulate transcription of many metabolic genes in the liver through its nuclear receptors (TRs). Although the molecular mechanisms for positive regulation of hepatic genes by TH are well understood, much less is known about TH-mediated negative regulation. Recently, several nuclear hormone receptors were shown to downregulate gene expression via miRNAs. To further examine the potential role of miRNAs in TH-mediated negative regulation, we used a miRNA microarray to identify miRNAs that were directly regulated by TH in a human hepatic cell line. In our screen, we discovered that miRNA-181d is a novel hepatic miRNA that was regulated by TH in hepatic cell culture and in vivo. Furthermore, we identified and characterized two novel TH-regulated target genes that were downstream of miR-181d signaling: caudal type homeobox 2 (CDX2) and sterol O-acyltransferase 2 (SOAT2 or ACAT2). CDX2, a known positive regulator of hepatocyte differentiation, was regulated by miR-181d and directly activated SOAT2 gene expression. Since SOAT2 is an enzyme that generates cholesteryl esters that are packaged into lipoproteins, our results suggest miR-181d plays a significant role in the negative regulation of key metabolic genes by TH in the liver.

All-trans retinoic acid negatively regulates cytotoxic activities of nature killer cell line 92

International Nuclear Information System (INIS)

Li Ang; He Meilan; Wang Hui; Qiao Bin; Chen Ping; Gu Hua; Zhang Mengjie; He Shengxiang

2007-01-01

NK cells are key components of innate immune systems and their activities are regulated by cytokines and hormones. All-trans retinoic acid (ATRA), as a metabolite of vitamin A and an immunomodulatory hormone, plays an important role in regulating immune responses. In the present study, we investigated the effect of ATRA on human NK cell line NK92. We found that ATRA dose-dependently suppressed cytotoxic activities of NK92 cells without affecting their proliferation. To explore the mechanisms underlying the ATRA influence on NK92 cells, we examined the production of cytokines (TNF-α, IFN-γ), gene expression of cytotoxic-associated molecules (perforin, granzyme B, nature killer receptors (NCRs), and NKG2D), and the activation of NF-κB pathways related with immune response. Our results demonstrated that ATRA suppressed NF-κB activity and prevented IκBα degradation in a dose-dependent way, inhibited IFN-γ production and gene expression of granzyme B and NKp46. Our findings suggest that ATRA is a negative regulator of NK92 cell activation and may act as a potential regulator of anti-inflammatory functions in vivo

Early-Occurring Maternal Depression and Maternal Negativity in Predicting Young Children's Emotion Regulation and Socioemotional Difficulties

Science.gov (United States)

Maughan, Angeline; Cicchetti, Dante; Toth, Sheree L.; Rogosch, Fred A.

2007-01-01

This longitudinal investigation examined the effects of maternal depression and concomitant negative parenting behaviors on children's emotion regulation patterns and socioemotional functioning. One hundred fifty-one mothers and their children were assessed when children were approximately 1 1/2-, 3-, 4-, and 5-years of age. Ninety-three of the…

Local cerebral blood flow (1CBF) and oxygen consumption (1CMRO2) in evolving irreversible ischemic infarction: a study with positron tomography and oxygen-15

International Nuclear Information System (INIS)

Baron, J.C.; Rougemont, D.; Lebrun-Grandie, P.; Comar, D.; Bousser, M.G.; Bories, J.; Castaigne, P.; Cabanis, E.

1982-09-01

In 25 patients suffering from cerebral ischemia set up in the area of the internal carotid artery the local cerebral blood flow (lCBF) and local cerebral oxygen consumption (lCMRO 2 ) were measured by the method of continuous inhalation of oxygen 15-labelled gas combined with positron emission tomography. These two local parameters and their ratio, the local oxygen extraction rate (lO 2 E), were studied inside the brain region tending spontaneously towards ischemic necrosis, a zone defined by means of repeated tomodensitometric examinations. The essential facts observed are the variability of the lCBF and the lO 2 E values, from extremely low to extremely high, whereas the collapse of the lCMRO 2 is constant. Consequently this last parameter alone would be a good prognostic index, an lCMRO 2 decrease to a level below about 70% of the controlateral value indicating that the necrosis is spontaneously irreparable. These results are discussed in the light of published data

Purification and Crystallization of Murine Myostatin: A Negative Regulator of Muscle Mass

Science.gov (United States)

Hong, Young S.; Adamek, Daniel; Bridge, Kristi; Malone, Christine C.; Young, Ronald B.; Miller, Teresa; Karr, Laurel

2004-01-01

Myostatin (MSTN) has been crystallized and its preliminary X-ray diffraction data were collected. MSTN is a negative regulator of muscle growt/differentiation and suppressor of fat accumulation. It is a member of TGF-b family of proteins. Like other members of this family, the regulation of MSTN is critically tied to its process of maturation. This process involves the formation of a homodimer followed by two proteolytic steps. The first proteolytic cleavage produces a species where the n-terminal portion of the dimer is covalently separated from, but remains non-covalently bound to, the c-terminal, functional, portion of the protein. The protein is activated upon removal of the n-terminal "pro-segment" by a second n-terminal proteolytic cut by BMP-1 in vivo, or by acid treatment in vitro. Understanding the structural nature and physical interactions involved in these regulatory processes is the objective of our studies. Murine MSTN was purified from culture media of genetically engineered Chinese Hamster Ovary cells by multicolumn purification process and crystallized using the vapor diffusion method.

Perfectionism and negative/positive affect associations: the role of cognitive emotion regulation and perceived distress/coping.

Science.gov (United States)

Castro, Juliana; Soares, Maria João; Pereira, Ana T; Macedo, António

2017-01-01

To explore 1) if perfectionism, perceived distress/coping, and cognitive emotion regulation (CER) are associated with and predictive of negative/positive affect (NA/PA); and 2) if CER and perceived distress/coping are associated with perfectionism and if they mediate the perfectionism-NA/PA associations. There is a distinction between maladaptive and adaptive perfectionism in its association with NA/PA. CER and perceived distress/coping may mediate the maladaptive/adaptive perfectionism and NA/PA associations. 344 students (68.4% girls) completed the Hewitt & Flett and the Frost Multidimensional Perfectionism Scales, the Composite Multidimensional Perfectionism Scale, the Profile of Mood States, the Perceived Stress Scale, and the Cognitive Emotion Regulation Questionnaire. NA predictors were maladaptive/adaptive perfectionism, maladaptive CER and perceived distress (positively), positive reappraisal and planning, and perceived coping (negatively). PA predictors were maladaptive/adaptive perfectionism and perceived distress (negatively), positive reappraisal and planning, positive refocusing and perceived coping (positively). The association between maladaptive perfectionism and NA was mediated by maladaptive CER/low adaptive CER, perceived distress/low coping. Maladaptive perfectionism and low PA association was mediated by perceived distress. High PA was determined by low maladaptive perfectionism and this association was mediated by adaptive REC and coping. Adaptive perfectionism and NA association was mediated by maladaptive CER and perceived distress. CER and perceived distress/coping are associated and mediate the perfectionism-NA/PA associations.

Reciprocal regulation of annexin A2 and EGFR with Her-2 in Her-2 negative and herceptin-resistant breast cancer.

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Praveenkumar K Shetty

Full Text Available Alternative survival pathways are commonly seen to be upregulated upon inhibition of receptor tyrosine kinases (RTK, including Her-2. It is established that treatment with Herceptin leads to selective overexpression and activation of epidermal growth factor receptor (EGFR and Src which further contributes to oncogenesis in Herceptin resistant and triple negative breast cancer (TNBC patients. Here, we show a co-regulated upregulation in the expression of Annexin A2 (AnxA2, a known substrate of Src and one of the regulators of EGFR receptor endocytosis, in Herceptin resistant and Her-2 negative breast cancer. Immunohistochemical expression analysis revealed a reciprocal regulation between Her-2 and AnxA2 in breast cancer clinical samples as well as in cell lines as confirmed by protein and RNA analysis. The siRNA and Herceptin mediated downregulation/inhibition of Her-2 in Her-2 amplified cells induced AnxA2 expression and membrane translocation. In this study we report a possible involvement of AnxA2 in maintaining constitutively activated EGFR downstream signaling intermediates and hence in cell proliferation, migration and viability. This effect was consistent in Herceptin resistant JIMT-1 cells as well as in Her-2 negative breast cancer. The siRNA mediated AnxA2 downregulation leads to increased apoptosis, decreased cell viability and migration. Our studies further indicate the role of AnxA2 in EGFR-Src membrane bound signaling complex and ligand induced activation of downstream signaling pathways. Targeting this AnxA2 dependent positive regulation of EGFR signaling cascade may be of therapeutic value in Her-2 negative breast cancer.

Different Fear-Regulation Behaviors in Toddlerhood: Relations to Preceding Infant Negative Emotionality, Maternal Depression, and Sensitivity

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Gloggler, Bettina; Pauli-Pott, Ursula

2008-01-01

In the study presented, the development of different fear regulation behaviors and their associations with preceding maternal sensitivity and depression is addressed. A sample of 64 mother-child pairs was examined at the children's ages of 4, 12, and 30 months. Four-month negative reactivity and 12- and 30- month behavioral inhibition and fear…

Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y

International Nuclear Information System (INIS)

Jaeaeskelaeinen, T.; Huhtakangas, J.; Maeenpaeae, P.H.

2005-01-01

The negative regulation of the human parathyroid hormone (PTH) gene by biologically active vitamin D 3 (1,25-dihydroxyvitamin D 3 ; 1,25(OH) 2 D 3 ) was studied in rat pituitary GH4C1 cells, which express factors needed for the negative regulation. We report here that NF-Y binds to sequences downstream of the site previously reported to bind the vitamin D receptor (VDR). Additional binding sites for NF-Y reside in the near vicinity and were shown to be important for full activity of the PTH gene promoter. VDR and NF-Y were shown to exhibit mutually exclusive binding to the VDRE region. According to our results, sequestration of binding partners for NF-Y by VDR also affects transcription through a NF-Y consensus binding element in GH4C1 but not in ROS17/2.8 cells. These results indicate that 1,25(OH) 2 D 3 may affect transcription of the human PTH gene both by competitive binding of VDR and NF-Y, and by modulating transcriptional activity of NF-Y

Dynamic susceptibility contrast (DSC) perfusion MRI in differential diagnosis between radionecrosis and neoangiogenesis in cerebral metastases using rCBV, rCBF and K2.

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Muto, Mario; Frauenfelder, Giulia; Senese, Rossana; Zeccolini, Fabio; Schena, Emiliano; Giurazza, Francesco; Jäger, Hans Rolf

2018-07-01

Distinction between treatment-related changes and tumour recurrence in patients who have received radiation treatment for brain metastases can be difficult on conventional MRI. In this study, we investigated the ability of dynamic susceptibility contrast (DSC) perfusion in differentiating necrotic changes from pathological angiogenesis and compared measurements of relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and K2, using a dedicated software. Twenty-nine patients with secondary brain tumors were included in this retrospective study and underwent DSC perfusion MRI with a 3-month follow-up imaging after chemo- or radiation-therapy. Region-of-interests were drawn around the contrast enhancing lesions and measurements of rCBV, rCBF and K2 were performed in all patients. Based on subsequent histological examination or clinico-radiological follow-up, the cohort was divided in two groups: recurrent disease and stable disease. Differences between the two groups were analyzed using the Student's t test. Sensitivity, specificity and diagnostic accuracy of rCBV measurements were analyzed considering three different cut-off values. Between patients with and without disease, only rCBV and rCBF values were significant (p < 0.05). The only cut-off value giving the best diagnostic accuracy of 100% was rCBV = 2.1 (sensitivity = 100%; specificity = 100%). Patients with tumor recurrence showed a higher mean value of rCBV (mean = 4.28, standard deviation = 2.09) than patients with necrotic-related changes (mean = 0.77, standard deviation = 0.44). DSC-MRI appears a clinically useful method to differentiate between tumor recurrence, tumor necrosis and pseudoprogression in patients treated for cerebral metastases. Relative CBV using a cut-off value of 2.1 proved to be the most accurate and reliable parameter.

Small kinetochore associated protein (SKAP promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19.

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Shan Lu

Full Text Available Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19. We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19.

Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts.

LENUS (Irish Health Repository)

Burke, J P

2012-02-01

BACKGROUND: Fibroblasts isolated from strictures in Crohn\\'s disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. RESULTS: Crohn\\'s stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF. CONCLUSION: Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells.

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Fonseca, Sonya G; Ishigaki, Shinsuke; Oslowski, Christine M; Lu, Simin; Lipson, Kathryn L; Ghosh, Rajarshi; Hayashi, Emiko; Ishihara, Hisamitsu; Oka, Yoshitomo; Permutt, M Alan; Urano, Fumihiko

2010-03-01

Wolfram syndrome is an autosomal-recessive disorder characterized by insulin-dependent diabetes mellitus, caused by nonautoimmune loss of beta cells, and neurological dysfunctions. We have previously shown that mutations in the Wolfram syndrome 1 (WFS1) gene cause Wolfram syndrome and that WFS1 has a protective function against ER stress. However, it remained to be determined how WFS1 mitigates ER stress. Here we have shown in rodent and human cell lines that WFS1 negatively regulates a key transcription factor involved in ER stress signaling, activating transcription factor 6alpha (ATF6alpha), through the ubiquitin-proteasome pathway. WFS1 suppressed expression of ATF6alpha target genes and repressed ATF6alpha-mediated activation of the ER stress response element (ERSE) promoter. Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading to suppression of ER stress signaling. Consistent with these data, beta cells from WFS1-deficient mice and lymphocytes from patients with Wolfram syndrome exhibited dysregulated ER stress signaling through upregulation of ATF6alpha and downregulation of HRD1. These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes.

proBDNF Negatively Regulates Neuronal Remodeling, Synaptic Transmission, and Synaptic Plasticity in Hippocampus

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Jianmin Yang

2014-05-01

Full Text Available Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP via TrkB activation. BDNF is initially translated as proBDNF, which binds p75NTR. In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75NTR. Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF.

SarA is a negative regulator of Staphylococcus epidermidis biofilm formation

DEFF Research Database (Denmark)

Martin, Christer; Heinze, C.; Busch, M.

2012-01-01

Biofilm formation is essential for Staphylococcus epidermidis pathogenicity in implant-associated infections. Nonetheless, large proportions of invasive S. epidermidis isolates fail to show accumulative biofilm growth in vitro. We here tested the hypothesis that this apparent paradox is related...... virulence. Genetic analysis revealed that inactivation of sarA induced biofilm formation via over-expression of the giant 1 MDa extracellular matrix binding protein (Embp), serving as an intercellular adhesin. In addition to Embp, increased extracellular DNA (eDNA) release significantly contributed...... to biofilm formation in mutant 1585ΔsarA. Increased eDNA amounts indirectly resulted from up-regulation of metalloprotease SepA, leading to boosted processing of major autolysin AtlE, in turn inducing augmented autolysis and release of chromosomal DNA. Hence, this study identifies sarA as a negative...

The maize WRKY transcription factor ZmWRKY17 negatively regulates salt stress tolerance in transgenic Arabidopsis plants.

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Cai, Ronghao; Dai, Wei; Zhang, Congsheng; Wang, Yan; Wu, Min; Zhao, Yang; Ma, Qing; Xiang, Yan; Cheng, Beijiu

2017-12-01

We cloned and characterized the ZmWRKY17 gene from maize. Overexpression of ZmWRKY17 in Arabidopsis led to increased sensitivity to salt stress and decreased ABA sensitivity through regulating the expression of some ABA- and stress-responsive genes. The WRKY transcription factors have been reported to function as positive or negative regulators in many different biological processes including plant development, defense regulation and stress response. This study isolated a maize WRKY gene, ZmWRKY17, and characterized its role in tolerance to salt stress by generating transgenic Arabidopsis plants. Expression of the ZmWRKY17 was up-regulated by drought, salt and abscisic acid (ABA) treatments. ZmWRKY17 was localized in the nucleus with no transcriptional activation in yeast. Yeast one-hybrid assay showed that ZmWRKY17 can specifically bind to W-box, and it can activate W-box-dependent transcription in planta. Heterologous overexpression of ZmWRKY17 in Arabidopsis remarkably reduced plant tolerance to salt stress, as determined through physiological analyses of the cotyledons greening rate, root growth, relative electrical leakage and malondialdehyde content. Additionally, ZmWRKY17 transgenic plants showed decreased sensitivity to ABA during seed germination and early seedling growth. Transgenic plants accumulated higher content of ABA than wild-type (WT) plants under NaCl condition. Transcriptome and quantitative real-time PCR analyses revealed that some stress-related genes in transgenic seedlings showed lower expression level than that in the WT when treated with NaCl. Taken together, these results suggest that ZmWRKY17 may act as a negative regulator involved in the salt stress responses through ABA signalling.

Models of Aire-dependent gene regulation for thymic negative selection

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Dina eDanso-Abeam

2011-05-01

Full Text Available Mutations in the Autoimmune Regulator (AIRE gene lead to Autoimmune Polyendocrinopathy Syndrome type 1 (APS1, characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, with AIRE driving the expression of tissue restricted antigens (TRAs in the epithelial cells of the thymic medulla. This TRA expression results in effective negative selection of TRA-reactive thymocytes, preventing autoimmune disease. At the molecular level, the mechanism by which AIRE initiates TRA expression in the thymic medulla remains unclear. Multiple different models for the molecular mechanism have been proposed, ranging from classical transcriptional activity, to random induction of gene expression, to epigenetic tag recognition effect, to altered cell biology. In this review, we evaluate each of these models and discuss their relative strengths and weaknesses.

The trans-kingdom identification of negative regulators of pathogen hypervirulence.

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Brown, Neil A; Urban, Martin; Hammond-Kosack, Kim E

2016-01-01

Modern society and global ecosystems are increasingly under threat from pathogens, which cause a plethora of human, animal, invertebrate and plant diseases. Of increasing concern is the trans-kingdom tendency for increased pathogen virulence that is beginning to emerge in natural, clinical and agricultural settings. The study of pathogenicity has revealed multiple examples of convergently evolved virulence mechanisms. Originally described as rare, but increasingly common, are interactions where a single gene deletion in a pathogenic species causes hypervirulence. This review utilised the pathogen-host interaction database (www.PHI-base.org) to identify 112 hypervirulent mutations from 37 pathogen species, and subsequently interrogates the trans-kingdom, conserved, molecular, biochemical and cellular themes that cause hypervirulence. This study investigates 22 animal and 15 plant pathogens including 17 bacterial and 17 fungal species. Finally, the evolutionary significance and trans-kingdom requirement for negative regulators of hypervirulence and the implication of pathogen hypervirulence and emerging infectious diseases on society are discussed. © FEMS 2015.

Lack of Csk-mediated negative regulation in a unicellular SRC kinase.

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Schultheiss, Kira P; Suga, Hiroshi; Ruiz-Trillo, Iñaki; Miller, W Todd

2012-10-16

Phosphotyrosine-based signaling plays a vital role in cellular communication in multicellular organisms. Unexpectedly, unicellular choanoflagellates (the closest phylogenetic group to metazoans) possess numbers of tyrosine kinases that are comparable to those in complex metazoans. Here, we have characterized tyrosine kinases from the filasterean Capsaspora owczarzaki, a unicellular protist representing the sister group to choanoflagellates and metazoans. Two Src-like tyrosine kinases have been identified in C. owczarzaki (CoSrc1 and CoSrc2), both of which have the arrangement of SH3, SH2, and catalytic domains seen in mammalian Src kinases. In Capsaspora cells, CoSrc1 and CoSrc2 localize to punctate structures in filopodia that may represent primordial focal adhesions. We have cloned, expressed, and purified both enzymes. CoSrc1 and CoSrc2 are active tyrosine kinases. Mammalian Src kinases are normally regulated in a reciprocal fashion by autophosphorylation in the activation loop (which increases activity) and by Csk-mediated phosphorylation of the C-terminal tail (which inhibits activity). Similar to mammalian Src kinases, the enzymatic activities of CoSrc1 and CoSrc2 are increased by autophosphorylation in the activation loop. We have identified a Csk-like kinase (CoCsk) in the genome of C. owczarzaki. We cloned, expressed, and purified CoCsk and found that it has no measurable tyrosine kinase activity. Furthermore, CoCsk does not phosphorylate or regulate CoSrc1 or CoSrc2 in cells or in vitro, and CoSrc1 and CoSrc2 are active in Capsaspora cell lysates. Thus, the function of Csk as a negative regulator of Src family kinases appears to have arisen with the emergence of metazoans.

Plasma Membrane CRPK1-Mediated Phosphorylation of 14-3-3 Proteins Induces Their Nuclear Import to Fine-Tune CBF Signaling during Cold Response.

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Liu, Ziyan; Jia, Yuxin; Ding, Yanglin; Shi, Yiting; Li, Zhen; Guo, Yan; Gong, Zhizhong; Yang, Shuhua

2017-04-06

In plant cells, changes in fluidity of the plasma membrane may serve as the primary sensor of cold stress; however, the precise mechanism and how the cell transduces and fine-tunes cold signals remain elusive. Here we show that the cold-activated plasma membrane protein cold-responsive protein kinase 1 (CRPK1) phosphorylates 14-3-3 proteins. The phosphorylated 14-3-3 proteins shuttle from the cytosol to the nucleus, where they interact with and destabilize the key cold-responsive C-repeat-binding factor (CBF) proteins. Consistent with this, the crpk1 and 14-3-3κλ mutants show enhanced freezing tolerance, and transgenic plants overexpressing 14-3-3λ show reduced freezing tolerance. Further study shows that CRPK1 is essential for the nuclear translocation of 14-3-3 proteins and for 14-3-3 function in freezing tolerance. Thus, our study reveals that the CRPK1-14-3-3 module transduces the cold signal from the plasma membrane to the nucleus to modulate CBF stability, which ensures a faithfully adjusted response to cold stress of plants. Copyright © 2017 Elsevier Inc. All rights reserved.

Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

International Nuclear Information System (INIS)

Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha; Jeong, Jae Hoon; Pak, Youngmi Kim

2014-01-01

Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations

Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders

OpenAIRE

Gery, Sigal; Gueller, Saskia; Chumakova, Katya; Kawamata, Norihiko; Liu, Liqin; Koeffler, H. Phillip

2007-01-01

Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk i...

Emotion Risk-Factor in Patients with Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study).

Science.gov (United States)

Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghei, Abbas

2015-05-17

Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) Was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases.

Emotion Risk-Factor in Patients With Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study)

Science.gov (United States)

Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghaei, Abbas

2016-01-01

Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases. PMID:26234976

Relationship between SPECT regional cerebral blood flow imaging and cognitive function in school-age children with epilepsy

International Nuclear Information System (INIS)

Liu Jiangyan; Chen Xuehong; Wang Zhengjiang; Hu Jingui; Feng Jianzhong; Li Yimin; Lu Xiujuan

2006-01-01

Objective: To explore the feature of SPECT regional cerebral blood flow(rCBF) imaging, the cognitive functions and the relationship between them in school-age children with primary epilepsy. Methods: 99 Tc m -ethylene cysteinate dimer (ECD) brain imaging was performed on 32 school-age children with primary generalized tonic and (or) clonic seizures(GTCS). Cognitive functions were also evaluated in all patients and normal children. Relationship between cognitive function and rCBF was compared. Results: (1) Thirty of 32 (93.8%) patients were abnormal on SPECT imaging. Fifty areas of 29 cases showed decreased rCBF, the percentage of decreased rCBF was (21.07 ± 7.09)%; 2 areas of 1 case showed increased rCBF, the percentage of increased rCBF was (32.22 ± 4.31)%. 92.3% of the epileptic foci were located in frontal, temporal, parietal and occipital cortexes. (2) Verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ) and full-scale intelligence quotient (FIQ) of children with epilepsy were significantly lower than those of the controls, and there were some cognitive skewnesses in children with epilepsy (VIQ >PIQ). (3)There was negative correlation between the number of foci and VIQ, PIQ, FIQ, the correlation coefficients were -0.543 (P=0.002), -0.469 (P=0.009), -0.578 (P=0.001); there was negative correlation between the extent of foci and VIQ, PIQ, FIQ, the correlation coefficients were -0.560 (P=0.003), -0.142 (P=0.016), -0.582 (P=0.001); there was no significant correlation between all the IQ of cognitive test and the percentage of changed rCBF. Conclusions: SPECT rCBF imaging may be useful for the localization of epileptic focus. Some of school-age children with epilepsy have impairment of the cognitive function, its magnitude is negative correlated with the number and extent of epileptic foci. (authors)

Regulation of cerebrospinal fluid production by caffeine consumption

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Yoon Sik

2009-09-01

Full Text Available Abstract Background Caffeine is the most commonly consumed psycho-stimulant in the world. The effects of caffeine on the body have been extensively studied; however, its effect on the structure of the brain has not been investigated to date. Results In the present study we found that the long-term consumption of caffeine can induce ventriculomegaly; this was observed in 40% of the study rats. In the caffeine-treated rats with ventriculomegaly, there was increased production of CSF, associated with the increased expression of Na+, K+-ATPase and increased cerebral blood flow (CBF. In contrast to the chronic effects, acute treatment with caffeine decreased the production of CSF, suggesting 'effect inversion' associated with caffeine, which was mediated by increased expression of the A1 adenosine receptor, in the choroid plexus of rats chronically treated with caffeine. The involvement of the A1 adenosine receptor in the effect inversion of caffeine was further supported by the induction of ventriculomegaly and Na+, K+-ATPase, in A1 agonist-treated rats. Conclusion The results of this study show that long-term consumption of caffeine can induce ventriculomegaly, which is mediated in part by increased production of CSF. Moreover, we also showed that adenosine receptor signaling can regulate the production of CSF by controlling the expression of Na+, K+-ATPase and CBF.

Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control.

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Amélie Avet-Rochex

2014-09-01

Full Text Available Neuronal differentiation is exquisitely controlled both spatially and temporally during nervous system development. Defects in the spatiotemporal control of neurogenesis cause incorrect formation of neural networks and lead to neurological disorders such as epilepsy and autism. The mTOR kinase integrates signals from mitogens, nutrients and energy levels to regulate growth, autophagy and metabolism. We previously identified the insulin receptor (InR/mTOR pathway as a critical regulator of the timing of neuronal differentiation in the Drosophila melanogaster eye. Subsequently, this pathway has been shown to play a conserved role in regulating neurogenesis in vertebrates. However, the factors that mediate the neurogenic role of this pathway are completely unknown. To identify downstream effectors of the InR/mTOR pathway we screened transcriptional targets of mTOR for neuronal differentiation phenotypes in photoreceptor neurons. We identified the conserved gene unkempt (unk, which encodes a zinc finger/RING domain containing protein, as a negative regulator of the timing of photoreceptor differentiation. Loss of unk phenocopies InR/mTOR pathway activation and unk acts downstream of this pathway to regulate neurogenesis. In contrast to InR/mTOR signalling, unk does not regulate growth. unk therefore uncouples the role of the InR/mTOR pathway in neurogenesis from its role in growth control. We also identified the gene headcase (hdc as a second downstream regulator of the InR/mTOR pathway controlling the timing of neurogenesis. Unk forms a complex with Hdc, and Hdc expression is regulated by unk and InR/mTOR signalling. Co-overexpression of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified. Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem

CBF before and after extracranial-intracranial bypass surgery in patients with ischemic cerebrovascular disease studied with 133Xe-inhalation tomography

DEFF Research Database (Denmark)

Vorstrup, S; Lassen, N A; Henriksen, L

1985-01-01

Cerebral blood flow (CBF) was studied by 133Xenon inhalation tomography in 22 patients with symptoms of ischemic cerebrovascular disease before and after establishment of an extracranial-intracranial bypass shunt. Selection of patients for shunting was based on angiographically demonstrated...... arterial occlusions and on the finding of focal low flow areas corresponding to the clinical symptoms, that consisted mainly of minor stroke with good remission and with or without subsequent TIAs. It was required that the area of low flow should clearly exceed the CT lesion present in practically all...

Abscisic acid negatively regulates post-penetration resistance of Arabidopsis to the biotrophic powdery mildew fungus.

Science.gov (United States)

Xiao, Xiang; Cheng, Xi; Yin, Kangquan; Li, Huali; Qiu, Jin-Long

2017-08-01

Pytohormone abscisic acid (ABA) plays important roles in defense responses. Nonetheless, how ABA regulates plant resistance to biotrophic fungi remains largely unknown. Arabidopsis ABA-deficient mutants, aba2-1 and aba3-1, displayed enhanced resistance to the biotrophic powdery mildew fungus Golovinomyces cichoracearum. Moreover, exogenously administered ABA increased the susceptibility of Arabidopsis to G. cichoracearum. Arabidopsis ABA perception components mutants, abi1-1 and abi2-1, also displayed similar phenotypes to ABA-deficient mutants in resistance to G. cichoracearum. However, the resistance to G. cichoracearum is not changed in downstream ABA signaling transduction mutants, abi3-1, abi4-1, and abi5-1. Microscopic examination revealed that hyphal growth and conidiophore production of G. cichoracearum were compromised in the ABA deficient mutants, even though pre-penetration and penetration growth of the fungus were not affected. In addition, salicylic acid (SA) and MPK3 are found to be involved in ABA-regulated resistance to G. cichoracearum. Our work demonstrates that ABA negatively regulates post-penetration resistance of Arabidopsis to powdery mildew fungus G. cichoracearum, probably through antagonizing the function of SA.

Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

KAUST Repository

Frei dit Frey, Nicolas; Garcia, Ana; Bigeard, Jean; Zaag, Rim; Bueso, Eduardo; Garmier, Marie; Pateyron, Sté phanie; de Tauzia-Moreau, Marie-Ludivine; Brunaud, Vé ronique; Balzergue, Sandrine; Colcombet, Jean; Aubourg, Sé bastien; Martin-Magniette, Marie-Laure; Hirt, Heribert

2014-01-01

-induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76

TRAF family member-associated NF-κB activator (TANK) induced by RANKL negatively regulates osteoclasts survival and function.

Science.gov (United States)

Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

2012-01-01

Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and confirmed by western blot and quantitative RT-PCR. Bone marrow macrophages (BMMs) transduced with lentivirus carrying tank-shRNA were induced to form osteoclast in the presence of RANKL and M-CSF. Tank expression was downregulated by 90% by Tank-shRNA, which is confirmed by western blot. Compared with wild-type (WT) cells, osteoclastogenesis of Tank-silenced BMMs was increased, according to tartrate-resistant acid phosphatase (TRAP) stain on day 5 and day 7. Number of bone resorption pits by Tank-silenced osteoclasts was increased by 176% compared with WT cells, as shown by wheat germ agglutinin (WGA) stain and scanning electronic microscope (SEM) analysis. Survival rate of Tank-silenced mature osteoclast is also increased. However, acid production of Tank-knockdown cells was not changed compared with control cells. IκBα phosphorylation is increased in tank-silenced cells, indicating that TANK may negatively regulate NF-κB activity in osteoclast. In conclusion, Tank, whose expression is increased during osteoclastogenesis, inhibits osteoclast formation, activity and survival, by regulating NF-κB activity and c-FLIP expression. Tank enrolls itself in a negative feedback loop in bone resorption. These results may provide means for therapeutic intervention in diseases of excessive bone resorption.

Elongated Hypocotyl 5-Homolog (HYH Negatively Regulates Expression of the Ambient Temperature-Responsive MicroRNA Gene MIR169

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Phanu T. Serivichyaswat

2017-12-01

Full Text Available Arabidopsis microRNA169 (miR169 is an ambient temperature-responsive microRNA that plays an important role in stress responses and the floral transition. However, the transcription factors that regulate the expression of MIR169 have remained unknown. In this study, we show that Elongated Hypocotyl 5-Homolog (HYH directly binds to the promoter of MIR169a and negatively regulates its expression. Absolute quantification identified MIR169a as the major locus producing miR169. GUS reporter assays revealed that the deletion of a 498-bp fragment (–1,505 to –1,007, relative to the major transcriptional start site of MIR169a abolished its ambient temperature-responsive expression. DNA-affinity chromatography followed by liquid chromatography-mass spectrometry analysis identified transcription factor HYH as a trans-acting factor that binds to the 498-bp promoter fragment of pri-miR169a. Electrophoretic mobility shift assays and chromatin immunoprecipitation–quantitative PCR demonstrated that the HYH.2 protein, a predominant isoform of HYH, directly associated with a G-box-like motif in the 498-bp fragment of pri-miR169a. Higher enrichment of HYH.2 protein on the promoter region of MIR169a was seen at 23°C, consistent with the presence of more HYH.2 protein in the cell at the temperature. Transcript levels of pri-miR169a increased in hyh mutants and decreased in transgenic plants overexpressing HYH. Consistent with the negative regulation of MIR169a by HYH, the diurnal levels of HYH mRNA and pri-miR169a showed opposite patterns. Taken together, our results suggest that HYH is a transcription factor that binds to a G-box-like motif in the MIR169a promoter and negatively regulates ambient temperature-responsive expression of MIR169a at higher temperatures in Arabidopsis.

Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis

OpenAIRE

Kai Shu; Ying Qi; Feng Chen; Yongjie Meng; Xiaofeng Luo; Haiwei Shuai; Wenguan Zhou; Jun Ding; Junbo Du; Jiang Liu; Feng Yang; Qiang Wang; Weiguo Liu; Taiwen Yong; Xiaochun Wang

2017-01-01

Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA) while positively mediating abscisic acid (ABA) biogenesis, which leads to a decrease i...

Defective interleukin-4/Stat6 activity correlates with increased constitutive expression of negative regulators SOCS-3, SOCS-7, and CISH in colon cancer cells.

Science.gov (United States)

Liu, Xiao Hong; Xu, Shuang Bing; Yuan, Jia; Li, Ben Hui; Zhang, Yan; Yuan, Qin; Li, Pin Dong; Li, Feng; Zhang, Wen Jie

2009-12-01

Interleukin-4 (IL-4)-induced Stat6 activities (phenotypes) vary among human cancer cells, of which the HT-29 cell line carries an active Stat6(high) phenotype, while Caco-2 carries a defective Stat6(null) phenotype, respectively. Cancer cells with Stat6(high) show resistance to apoptosis and exaggerated metastasis, suggesting the clinical significance of Stat6 phenotypes. We previously showed that Stat6(high) HT-29 cells exhibited low constitutive expression of Stat6-negative regulators SOCS-1 and SHP-1 because of gene hypermethylation. This study further examined the constitutive expression of other closely related SOCS family numbers including SOCS-3, SOCS-5, SOCS-7, and CISH using RT-PCR. Similar to SOCS-1 and SHP-1, Stat6(high) HT-29 cells expressed low constitutive mRNA of SOCS-3, SOCS-7, and CISH than Stat6(null) Caco-2 cells. Interestingly, DNA demethylation using 5-aza-2'-deoxycytidine in HT-29 cells up-regulated mRNA expression of the above genes, indicating a hypermethylation status, which was confirmed by methylation-specific sequencing in selected SOCS-3 gene. Furthermore, defective Stat6(null) Caco-2 exhibited impaired phosphorylation of Stat6 after IL-4 stimulation by flow cytometry, in keeping with the notion of an over-performed negative regulation. The findings that IL-4/Stat6 phenotypes show differential expression of multiple negative regulators suggest a model that a collective force of powerful negative regulators, directly and indirectly, acts on Stat6 activation, which may result in differential Stat6 phenotypes.

Altered cerebral blood flow in chronic neck pain patients but not in whiplash patients: a 99mTc-HMPAO rCBF study

OpenAIRE

Sundström, Torbjörn; Guez, Michel; Hildingsson, Christer; Toolanen, Göran; Nyberg, Lars; Riklund, Katrine

2006-01-01

A cross-sectional study to investigate regional cerebral blood flow (rCBF) in patients with chronic whiplash syndrome and chronic neck pain patients without previous history of trauma along with a healthy control group. Chronic neck pain is a common disorder and a history of cervical spine injury including whiplash trauma constitute a risk factor for persistent neck pain. The aetiology of the late whiplash syndrome is unknown with no specific diagnostic criteria based on imaging, physiologica...

miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang; Xue, Jun; Shao, Xue-jun, E-mail: xuejunshao@hotmail.com

2015-04-03

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.

Crosstalk of PmCBFs and PmDAMs Based on the Changes of Phytohormones under Seasonal Cold Stress in the Stem of Prunus mume

Directory of Open Access Journals (Sweden)

Kai Zhao

2018-01-01

Full Text Available Plants facing the seasonal variations always need a growth restraining mechanism when temperatures turn down. C-repeat binding factor (CBF genes work essentially in the cold perception. Despite lots of researches on CBFs, the multiple crosstalk is still interesting on their interaction with hormones and dormancy-associated MADS (DAM genes in the growth and dormancy control. Therefore, this study highlights roles of PmCBFs in cold-induced dormancy from different orgens. And a sense-response relationship between PmCBFs and PmDAMs is exhibited in this process, jointly regulated by six PmCBFs and PmDAM4–6. Meantime, GA3 and ABA showed negative and positive correlation with PmCBFs expression levels, respectively. We also find a high correlation between IAA and PmDAM1–3. Finally, we display the interaction mode of PmCBFs and PmDAMs, especially PmCBF1-PmDAM1. These results can disclose another view of molecular mechanism in plant growth between cold-response pathway and dormancy regulation together with genes and hormones.

Changes in regional cerebral blood flow in the right cortex homologous to left language areas are directly affected by left hemispheric damage in aphasic stroke patients: evaluation by Tc-ECD SPECT and novel analytic software.

Science.gov (United States)

Uruma, G; Kakuda, W; Abo, M

2010-03-01

The objective of this study was to clarify the influence of regional cerebral blood flow (rCBF) changes in language-relevant areas of the dominant hemisphere on rCBF in each region in the non-dominant hemisphere in post-stroke aphasic patients. The study subjects were 27 aphasic patients who suffered their first symptomatic stroke in the left hemisphere. In each subject, we measured rCBF by means of 99mTc-ethylcysteinate dimmer single photon emission computed tomography (SPECT). The SPECT images were analyzed by the statistical imaging analysis programs easy Z-score Imaging System (eZIS) and voxel-based stereotactic extraction estimation (vbSEE). Segmented into Brodmann Area (BA) levels, Regions of Interest (ROIs) were set in language-relevant areas bilaterally, and changes in the relative rCBF as average negative and positive Z-values were computed fully automatically. To assess the relationship between rCBF changes of each ROIs in the left and right hemispheres, the Spearman ranked correlation analysis and stepwise multiple regression analysis were applied. Globally, a negative and asymmetric influence of rCBF changes in the language-relevant areas of the dominant hemisphere on the right hemisphere was found. The rCBF decrease in left BA22 significantly influenced the rCBF increase in right BA39, BA40, BA44 and BA45. The results suggested that the chronic increase in rCBF in the right language-relevant areas is due at least in part to reduction in the trancallosal inhibitory activity of the language-dominant left hemisphere caused by the stroke lesion itself and that these relationships are not always symmetric.

Neuropsychological functions and rCBF SPECT in Parkinson's disease patients considered candidates for deep brain stimulation

Energy Technology Data Exchange (ETDEWEB)

Paschali, Anna; Lakiotis, Velissarios; Vassilakos, Paulos [University of Patras Medical School, Department of Nuclear Medicine, Patras (Greece); Messinis, Lambros; Lyros, Epameinondas; Papathanasopoulos, Panagiotis [University of Patras Medical School, Department of Neurology, Neuropsychology Section, Patras (Greece); Constantoyannis, Costas; Kefalopoulou, Zinovia [University of Patras Medical School, Department of Neurosurgery, Patras (Greece)

2009-11-15

In the present study, we examined relationships between neuropsychological functions and brain single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) observed at presurgical evaluation for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD) patients. Twenty advanced non-demented PD patients, candidates for DBS surgery, underwent perfusion brain SPECT study and neuropsychological assessment prior to surgery (range: 30-50 days). Patients were further assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H and Y) scale. During all assessments patients were ''on'' standard medication. NeuroGam software, which permits voxel by voxel analysis, was used to compare the brain perfusion of PD patients with a normal database adjusted for sex and age. Neuropsychological scores were compared to age, education and sex-adjusted normative databases. Our results indicated that the distribution of rCBF showed significant differences when compared to an age- and sex-adjusted normative database. We found impaired blood flow in 17 (85%) of our patients in the left prefrontal lobe, in 14 (70%) in the right prefrontal lobe and in 11 (55%) in the left frontal and right parietal lobes. Neuropsychological testing revealed that 18 (90%) of our patients had significant impairments in measures of executive functions (set-shifting) and 15 (75%) in response inhibition. Furthermore, we found significant correlations between measures of visual attention, executive functions and the right frontal lobe region. The presence of widespread blood flow reduction was observed mainly in the frontal lobes of dementia-free patients with advanced PD. Furthermore, performance on specific cognitive measures was highly related to perfusion brain SPECT findings. (orig.)

Orphan nuclear receptor Nur77 is a novel negative regulator of endothelin-1 expression in vascular endothelial cells.

Science.gov (United States)

Qin, Qing; Chen, Ming; Yi, Bing; You, Xiaohua; Yang, Ping; Sun, Jianxin

2014-12-01

Endothelin-1 (ET-1) produced by vascular endothelial cells plays essential roles in the regulation of vascular tone and development of cardiovascular diseases. The objective of this study is to identify novel regulators implicated in the regulation of ET-1 expression in vascular endothelial cells (ECs). By using quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), we show that either ectopic expression of orphan nuclear receptor Nur77 or pharmacological activation of Nur77 by 6-mercaptopurine (6-MP) substantially inhibits ET-1 expression in human umbilical vein endothelial cells (HUVECs), under both basal and thrombin-stimulated conditions. Furthermore, thrombin-stimulated ET expression is significantly augmented in both Nur77 knockdown ECs and aort from Nur77 knockout mice, suggesting that Nur77 is a negative regulator of ET-1 expression. Inhibition of ET-1 expression by Nur77 occurs at gene transcriptional levels, since Nur77 potently inhibits ET-1 promoter activity, without affecting ET-1 mRNA stability. As shown in electrophoretic mobility shift assay (EMSA), Nur77 overexpression markedly inhibits both basal and thrombin-stimulated transcriptional activity of AP-1. Mechanistically, we demonstrate that Nur77 specially interacts with c-Jun and inhibits AP-1 dependent c-Jun promoter activity, which leads to a decreased expression of c-Jun, a critical component involved in both AP-1 transcriptional activity and ET-1 expression in ECs. These findings demonstrate that Nur77 is a novel negative regulator of ET-1 expression in vascular ECs through an inhibitory interaction with the c-Jun/AP-1 pathway. Activation of Nur77 may represent a useful therapeutic strategy for preventing certain cardiovascular diseases, such as atherosclerosis and pulmonary artery hypertension. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional analysis of Arabidopsis immune-related MAPKs uncovers a role for MPK3 as negative regulator of inducible defences

KAUST Repository

Frei dit Frey, Nicolas

2014-06-30

Background Mitogen-activated protein kinases (MAPKs) are key regulators of immune responses in animals and plants. In Arabidopsis, perception of microbe-associated molecular patterns (MAMPs) activates the MAPKs MPK3, MPK4 and MPK6. Increasing information depicts the molecular events activated by MAMPs in plants, but the specific and cooperative contributions of the MAPKs in these signalling events are largely unclear. Results In this work, we analyse the behaviour of MPK3, MPK4 and MPK6 mutants in early and late immune responses triggered by the MAMP flg22 from bacterial flagellin. A genome-wide transcriptome analysis reveals that 36% of the flg22-upregulated genes and 68% of the flg22-downregulated genes are affected in at least one MAPK mutant. So far MPK4 was considered as a negative regulator of immunity, whereas MPK3 and MPK6 were believed to play partially redundant positive functions in defence. Our work reveals that MPK4 is required for the regulation of approximately 50% of flg22-induced genes and we identify a negative role for MPK3 in regulating defence gene expression, flg22-induced salicylic acid accumulation and disease resistance to Pseudomonas syringae. Among the MAPK-dependent genes, 27% of flg22-upregulated genes and 76% of flg22-downregulated genes require two or three MAPKs for their regulation. The flg22-induced MAPK activities are differentially regulated in MPK3 and MPK6 mutants, both in amplitude and duration, revealing a highly interdependent network. Conclusions These data reveal a new set of distinct functions for MPK3, MPK4 and MPK6 and indicate that the plant immune signalling network is choreographed through the interplay of these three interwoven MAPK pathways.

Response and binding elements for ligand-dependent positive transcription factors integrate positive and negative regulation of gene expression

International Nuclear Information System (INIS)

Rosenfeld, M.G.; Glass, C.K.; Adler, S.; Crenshaw, E.B. III; He, X.; Lira, S.A.; Elsholtz, H.P.; Mangalam, H.J.; Holloway, J.M.; Nelson, C.; Albert, V.R.; Ingraham, H.A.

1988-01-01

Accurate, regulated initiation of mRNA transcription by RNA polymerase II is dependent on the actions of a variety of positive and negative trans-acting factors that bind cis-acting promoter and enhancer elements. These transcription factors may exert their actions in a tissue-specific manner or function under control of plasma membrane or intracellular ligand-dependent receptors. A major goal in the authors' laboratory has been to identify the molecular mechanisms responsible for the serial activation of hormone-encoding genes in the pituitary during development and the positive and negative regulation of their transcription. The anterior pituitary gland contains phenotypically distinct cell types, each of which expresses unique trophic hormones: adrenocorticotropic hormone, thyroid-stimulating hormone, prolactin, growth hormone, and follicle-stimulating hormone/luteinizing hormone. The structurally related prolactin and growth hormone genes are expressed in lactotrophs and somatotrophs, respectively, with their expression virtually limited to the pituitary gland. The reported transient coexpression of these two structurally related neuroendocrine genes raises the possibility that the prolactin and growth hormone genes are developmentally controlled by a common factor(s)

The Relations Between Maternal Prenatal Anxiety or Stress and Child's Early Negative Reactivity or Self-Regulation: A Systematic Review.

Science.gov (United States)

Korja, Riikka; Nolvi, Saara; Grant, Kerry Ann; McMahon, Cathy

2017-12-01

In the present review, we examine the association between maternal prenatal stress or anxiety and children's early negative reactivity or self-regulation. The review includes 32 studies that focus on pregnancy-related anxiety, state or trait anxiety, perceived stress, and stressful life events in relation to child's crying, temperament, or behavior during the first 2 years of life. We searched four electronic databases and 32 studies were selected based on the inclusion criteria. Twenty-three studies found an association between maternal prenatal anxiety or stress and a child's negative reactivity or self-regulation, and typically the effect sizes varied from low to moderate. The association was found regardless of the form of prenatal stress or anxiety and the trimester in which the prenatal stress or anxiety was measured. In conclusion, several forms of prenatal anxiety and stress may increase the risk of emotional and self-regulatory difficulties during the first 2 years of life.

Regulation of cerebral blood flow in patients with autonomic dysfunction and severe postural hypotension

DEFF Research Database (Denmark)

Hesse, Birger; Mehlsen, Jesper; Boesen, Finn

2002-01-01

Whether cerebral blood flow (CBF) autoregulation is maintained in autonomic dysfunction has been debated for a long time, and the rather sparse data available are equivocal. The relationship between CBF and mean arterial blood pressure (MABP) was therefore tested in eight patients with symptoms...

Quantitative statistical analysis of cis-regulatory sequences in ABA/VP1- and CBF/DREB1-regulated genes of Arabidopsis.

Science.gov (United States)

Suzuki, Masaharu; Ketterling, Matthew G; McCarty, Donald R

2005-09-01

We have developed a simple quantitative computational approach for objective analysis of cis-regulatory sequences in promoters of coregulated genes. The program, designated MotifFinder, identifies oligo sequences that are overrepresented in promoters of coregulated genes. We used this approach to analyze promoter sequences of Viviparous1 (VP1)/abscisic acid (ABA)-regulated genes and cold-regulated genes, respectively, of Arabidopsis (Arabidopsis thaliana). We detected significantly enriched sequences in up-regulated genes but not in down-regulated genes. This result suggests that gene activation but not repression is mediated by specific and common sequence elements in promoters. The enriched motifs include several known cis-regulatory sequences as well as previously unidentified motifs. With respect to known cis-elements, we dissected the flanking nucleotides of the core sequences of Sph element, ABA response elements (ABREs), and the C repeat/dehydration-responsive element. This analysis identified the motif variants that may correlate with qualitative and quantitative differences in gene expression. While both VP1 and cold responses are mediated in part by ABA signaling via ABREs, these responses correlate with unique ABRE variants distinguished by nucleotides flanking the ACGT core. ABRE and Sph motifs are tightly associated uniquely in the coregulated set of genes showing a strict dependence on VP1 and ABA signaling. Finally, analysis of distribution of the enriched sequences revealed a striking concentration of enriched motifs in a proximal 200-base region of VP1/ABA and cold-regulated promoters. Overall, each class of coregulated genes possesses a discrete set of the enriched motifs with unique distributions in their promoters that may account for the specificity of gene regulation.

Asymmetry of cerebral blood flow in patients with senile dementia of Alzheimer type by SPECT using I-123 IMP

Energy Technology Data Exchange (ETDEWEB)

Arai, Hisayuki; Hanyu, Haruo; Kobayashi, Yasutaka; Hatano, Nobuyoshi; Katsunuma, Hideyo; Suzuki, Takanari; Amino, Saburo [Tokyo Medical Coll. (Japan)

1990-12-01

Regional cerebral blood flow (rCBF) was determined by single photon emission CT (SPECT) with N-isopropyl-p-({sup 123}I)iodoamphetamine in 22 patients with clinically diagnosed senile dementia of Alzheimer type (SDAT) and in 18 age matched controls. We calculated asymmetry indices (AIs) of rCBF for matched right-left regions of interest. rCBF of parietal lobe in SDAT patients was significantly most laterally asymmetrycal, but the least in occipital lobe. Lateral asymmetry of rCBF in SDAT patients correlated with asymmetry of language and visuospatial functions; decreased rCBF in the left parietal lobe was associated with language dysfunction, and that in the right parietal lobe, with viduospatial dysfunction. Furthermore cerebellar AIs correlated negatively with those of the cerebral hemisphere and lower frontal region in SDAT patients. The results demonstrate that rCBF measurement by {sup 123}I-IMP SPECT is useful to detect lateral asymmetry in reduction of rCBF in SDAT. (author).

Asymmetry of cerebral blood flow in patients with senile dementia of Alzheimer type by SPECT using I-123 IMP

International Nuclear Information System (INIS)

Arai, Hisayuki; Hanyu, Haruo; Kobayashi, Yasutaka; Hatano, Nobuyoshi; Katsunuma, Hideyo; Suzuki, Takanari; Amino, Saburo

1990-01-01

Regional cerebral blood flow (rCBF) was determined by single photon emission CT (SPECT) with N-isopropyl-p-[ 123 I]iodoamphetamine in 22 patients with clinically diagnosed senile dementia of Alzheimer type (SDAT) and in 18 age matched controls. We calculated asymmetry indices (AIs) of rCBF for matched right-left regions of interest. rCBF of parietal lobe in SDAT patients was significantly most laterally asymmetrycal, but the least in occipital lobe. Lateral asymmetry of rCBF in SDAT patients correlated with asymmetry of language and visuospatial functions; decreased rCBF in the left parietal lobe was associated with language dysfunction, and that in the right parietal lobe, with viduospatial dysfunction. Furthermore cerebellar AIs correlated negatively with those of the cerebral hemisphere and lower frontal region in SDAT patients. The results demonstrate that rCBF measurement by 123 I-IMP SPECT is useful to detect lateral asymmetry in reduction of rCBF in SDAT. (author)

The Putative PAX8/PPARγ Fusion Oncoprotein Exhibits Partial Tumor Suppressor Activity through Up-Regulation of Micro-RNA-122 and Dominant-Negative PPARγ Activity.

Science.gov (United States)

Reddi, Honey V; Madde, Pranathi; Milosevic, Dragana; Hackbarth, Jennifer S; Algeciras-Schimnich, Alicia; McIver, Bryan; Grebe, Stefan K G; Eberhardt, Norman L

2011-01-01

In vitro studies have demonstrated that the PAX8/PPARγ fusion protein (PPFP), which occurs frequently in follicular thyroid carcinomas (FTC), exhibits oncogenic activity. However, paradoxically, a meta-analysis of extant tumor outcome studies indicates that 68% of FTC-expressing PPFP are minimally invasive compared to only 32% of those lacking PPFP (χ(2) = 6.86, P = 0.008), suggesting that PPFP favorably impacts FTC outcomes. In studies designed to distinguish benign thyroid neoplasms from thyroid carcinomas, the previously identified tumor suppressor miR-122, a major liver micro-RNA (miR) that is decreased in hepatocellular carcinoma, was increased 8.9-fold (P negative PPARγ mutant in WRO cells was less effective than PPFP at inhibiting xenograft tumor progression (1.8-fold [P negative PPARγ activity. Up-regulation of miR-122 negatively regulates ADAM-17, a known downstream target, in thyroid cells, suggesting an antiangiogenic mechanism in thyroid carcinoma. This latter inference is directly supported by reduced CD-31 expression in WRO xenografts expressing PPFP, miR-122, and DN-PPARγ. We conclude that, in addition to its apparent oncogenic potential in vitro, PPFP exhibits paradoxical tumor suppressor activity in vivo, mediated by multiple mechanisms including up-regulation of miR-122 and dominant-negative inhibition of PPARγ activity.

Ethylene response factor AtERF72 negatively regulates Arabidopsis thaliana response to iron deficiency.

Science.gov (United States)

Liu, Wei; Li, Qiwei; Wang, Yi; Wu, Ting; Yang, Yafei; Zhang, Xinzhong; Han, Zhenhai; Xu, Xuefeng

2017-09-23

Ethylene regulates the plant's response to stress caused by iron (Fe) deficiency. However, specific roles of ERF proteins in response to Fe deficiency remain poorly understood. Here, we investigated the role of ERF72 in response to iron deficiency in Arabidopsis thaliana. In this study, the levels of the ethylene response factor AtERF72 increased in leaves and roots induced under the iron deficient conditions. erf72 mutant plants showed increased growth compared to wild type (WT) when grown in iron deficient medium for 5 d. erf72 mutants had increased root H + velocity and the ferric reductase activity, and increase in the expression of the iron deficiency response genes iron-regulated transporter 1 (IRT1) and H + -ATPase (HA2) levels in iron deficient conditions. Compared to WT plants, erf72 mutants retained healthy chloroplast structure with significantly higher Fe and Mg content, and decreased chlorophyll degradation gene pheophorbide a oxygenase (PAO) and chlorophyllase (CLH1) expression when grown in iron deficient media. Yeast one-hybrid analysis showed that ERF72 could directly bind to the promoter regions of iron deficiency responses genes IRT1, HA2 and CLH1. Based on our results, we suggest that ethylene released from plants under iron deficiency stress can activate the expression of ERF72, which responds to iron deficiency in the negative regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of recirculation and regional counting rate on reliability of noninvasive bicompartmental CBF measurements

International Nuclear Information System (INIS)

Herholz, K.

1985-01-01

Based on data from routine intravenous Xe133-rCBF studies in 50 patients, using Obrist's algorithm the effect of counting rate statistics and amount of recirculating activity on reproducibility of results was investigated at five simulated counting rate levels. Dependence of the standard deviation of compartmental and noncompartmental flow parameters on recirculation and counting rate was determined by multiple linear regression analysis. Those regression equations permit determination of the optimum accuracy that may be expected from individual flow measurements. Mainly due to a delay of the start-of-fit time an exponential increase in standard deviation of flow measurements was observed as recirculation increased. At constant start-of-fit, however, a linear increase in standard deviation of compartmental flow parameters only was found, while noncompartmental results remained constant. Therefore, and in regard to other studies of potential sources of error, an upper limit of 2.5 min for the start-of-fit time and usage of noncompartmental flow parameters for measurements affected by high recirculation are suggested

Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO/sub 2/

Energy Technology Data Exchange (ETDEWEB)

Murkin, J.M.; Farrar, J.K.; Tweed, W.A.; McKenzie, F.N.; Guiraudon, G.

1987-09-01

Measurement of /sup 133/Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO/sub 2/ at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO/sub 2/ of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.

Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO2

International Nuclear Information System (INIS)

Murkin, J.M.; Farrar, J.K.; Tweed, W.A.; McKenzie, F.N.; Guiraudon, G.

1987-01-01

Measurement of 133 Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO 2 at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO 2 of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption

Osteocalcin as a negative regulator of serum leptin concentration in humans: insight from triathlon competitions.

Science.gov (United States)

Guadalupe-Grau, Amelia; Ara, Ignacio; Dorado, Cecilia; Vicente-Rodríguez, German; Perez-Gomez, Jorge; Cabrero, Javier Chavarren; Serrano-Sanchez, José A; Santana, Alfredo; Calbet, Jose A L

2010-10-01

Osteocalcin is a hormone produced by osteoblasts which acts as a negative regulator of fat mass, protecting against diet induced obesity and insulin resistance in rodents. To determine if an acute increase in osteocalcin concentration is associated with opposed changes in circulating leptin levels and insulin resistance we studied 15 middle and long distance male triathletes, (age 32.1 ± 6.9 years), before and 48 h after an Olympic (OT) or an Ironman (IT) triathlon competition. Muscle power, anaerobic capacity, body composition (dual-energy X-ray absorptiometry), and serum concentrations of testosterone, dihydrotestosterone, osteocalcin, leptin, glucose, insulin and insulin resistance (HOMA) were determined pre- and post-race. Pre- and 48 h post-race total and regional lean body mass was not altered, but fat mass was similarly increased (~250 g) 48 h after the competitions. This elicited an increase in plasma leptin of 33% after the IT while it remained unchanged after the OT, likely due to a 25% increase in plasma osteocalcin which occurred only after the OT (all p < 0.05). Post-race HOMA remained unchanged in OT and IT. Performance was normalized 48 h after the competitions, with the exception of a slightly lower jumping capacity after the IT. Serum testosterone concentration tended to decrease by 10% after the IT whilst dihydrotestosterone was reduced by 24% after the IT. In conclusion, an acute increase in serum osteocalcin concentration blunts the expected increase of serum leptin concentration that should occur with fat mass gain. This study provides evidence for osteocalcin as a negative regulator of serum leptin in humans.

PTP1B is a negative regulator of interleukin 4–induced STAT6 signaling

Science.gov (United States)

Lu, Xiaoqing; Malumbres, Raquel; Shields, Benjamin; Jiang, Xiaoyu; Sarosiek, Kristopher A.; Natkunam, Yasodha

2008-01-01

Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed enzyme shown to negatively regulate multiple tyrosine phosphorylation-dependent signaling pathways. PTP1B can modulate cytokine signaling pathways by dephosphorylating JAK2, TYK2, and STAT5a/b. Herein, we report that phosphorylated STAT6 may serve as a cytoplasmic substrate for PTP1B. Overexpression of PTP1B led to STAT6 dephosphorylation and the suppression of STAT6 transcriptional activity, whereas PTP1B knockdown or deficiency augmented IL-4–induced STAT6 signaling. Pretreatment of these cells with the PTK inhibitor staurosporine led to sustained STAT6 phosphorylation consistent with STAT6 serving as a direct substrate of PTP1B. Furthermore, PTP1B-D181A “substrate-trapping” mutants formed stable complexes with phosphorylated STAT6 in a cellular context and endogenous PTP1B and STAT6 interacted in an interleukin 4 (IL-4)–inducible manner. We delineate a new negative regulatory loop of IL-4–JAK-STAT6 signaling. We demonstrate that IL-4 induces PTP1B mRNA expression in a phosphatidylinositol 3-kinase–dependent manner and enhances PTP1B protein stability to suppress IL-4–induced STAT6 signaling. Finally, we show that PTP1B expression may be preferentially elevated in activated B cell–like diffuse large B-cell lymphomas. These observations identify a novel regulatory loop for the regulation of IL-4–induced STAT6 signaling that may have important implications in both neoplastic and inflammatory processes. PMID:18716132

Cerebral blood flow response to functional activation

DEFF Research Database (Denmark)

Paulson, Olaf B; Hasselbalch, Steen G; Rostrup, Egill

2010-01-01

Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only inc...... the cerebral tissue's increased demand for glucose supply during neural activation with recent evidence supporting a key function for astrocytes in rCBF regulation....

Research on the relationship between SPECT and cognitional potential of patients with cerebral infarction

International Nuclear Information System (INIS)

Zhao Heqing; Bao Shiyao; He Guangren

1995-01-01

The relationships among the regional cerebral blood flow (rCBF), the diaschisis and the change of cognitional potential in cerebral infarction are discussed. In 46 patients the ratio of rCBF was obtained by brain blood perfusion SPECT imaging. The cognitional potential was produced by evoking P300 wave with auditory Oddball model. The rCBF in infarct and its surrounding area decreased. The ratio of rCBF was less than 0.9. The detection of cognitional potential showed that the latency of P300 was delayed or negative. There was a significant correlation between the change of rCBF and the latency of P300 (r s = 0.876, P<0.001). The hypoperfusion of cerebral blood flow and diaschisis resulted in the cognitive impairment. There was a positive correlation between the cognitive impairment and the site and magnitude of decreased rCBF

Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line

International Nuclear Information System (INIS)

Xue, Jiangnan; Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili

2011-01-01

Research highlights: → LAIR-1 is expressed on human megakaryocytes from an early stage. → Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. → LAIR-1 negatively regulates the differentiation of primary megakaryocytic progenitors. -- Abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34 + CD41a + and CD41a + CD42b + cells. LAIR-1 is also detectable in a fraction of human cord blood CD34 + cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34 + cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

An evaluation of the regional cerebral blood flow (rCBF) measurement by xenon-enhanced dynamic CT with helical scanning technique and the functional imaging by multiplanar reconstruction (MPR). Fundamental study and clinical application

International Nuclear Information System (INIS)

Watanabe, Kenichi

1997-01-01

We evaluated the quantitative rCBF by xenon-enhanced dynamic CT with helical scanning technique on all brain regions, and also examined clinical usefulness of coronal and sagittal section images which are similar to SPECT images obtained by the functional multiplanar reconstitution (MPR) imaging of many successive flow maps. We used 14 clinical cases. The conventional xenon-enhanced CT was simple and ideal method to measure rCBF, however, it had disadvantages; it gives a few laminagraphical images or only the axial directional images, compared to SPECT or PET. There is a risk to overlook lesions out of the image or not to obtain the whole images of the lesion. Although the helical scanning technique has a methodological characteristics to use adjacent data for the image reconstitution, it is by no means inferior to the conventional method in the contrast resolution or the image resolution when the co-helical function and an appropriate reconstituted function were used. It has an advantage to scan all brain regions by only one cycle of scanning. Furthermore on making good use of the property that the helical scanning technique can give the successive data, we can observe rCBF by coronal and sagittal images when many flow maps were made up by reconstituted images of the narrow steps. This shows the clinical usefulness of this technique. One of the future problem to be solved is to decrease the exposure dose. (K.H.)

Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

Science.gov (United States)

Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

2009-01-01

Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive Chlamydia trachomatis Biovars

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Michael John Patton

2018-01-01

Full Text Available Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease. C. trachomatis isolates are classified into 2 biovars—lymphogranuloma venereum (LGV and trachoma—which are distinguished biologically by their natural host cell infection tropism. LGV biovars infect macrophages and are invasive, whereas trachoma biovars infect oculo-urogenital epithelial cells and are noninvasive. The C. trachomatis plasmid is an important virulence factor in the pathogenesis of these infections. Central to its pathogenic role is the transcriptional regulatory function of the plasmid protein Pgp4, which regulates the expression of plasmid and chromosomal virulence genes. As many gene regulatory functions are post-transcriptional, we employed a comparative proteomic study of cells infected with plasmid-cured C. trachomatis serovars A and D (trachoma biovar, a L2 serovar (LGV biovar, and the L2 serovar transformed with a plasmid containing a nonsense mutation in pgp4 to more completely elucidate the effects of the plasmid on chlamydial infection biology. Our results show that the Pgp4-dependent elevations in the levels of Pgp3 and a conserved core set of chromosomally encoded proteins are remarkably similar for serovars within both C. trachomatis biovars. Conversely, we found a plasmid-dependent, Pgp4-independent, negative regulation in the expression of the chlamydial protease-like activity factor (CPAF for the L2 serovar but not the A and D serovars. The molecular mechanism of plasmid-dependent negative regulation of CPAF expression in the LGV serovar is not understood but is likely important to understanding its macrophage infection tropism and invasive infection nature.

Mycobacterium tuberculosis maltosyltransferase GlgE, a genetically validated antituberculosis target, is negatively regulated by Ser/Thr phosphorylation.

Science.gov (United States)

Leiba, Jade; Syson, Karl; Baronian, Grégory; Zanella-Cléon, Isabelle; Kalscheuer, Rainer; Kremer, Laurent; Bornemann, Stephen; Molle, Virginie

2013-06-07

GlgE is a maltosyltransferase involved in the biosynthesis of α-glucans that has been genetically validated as a potential therapeutic target against Mycobacterium tuberculosis. Despite also making α-glucan, the GlgC/GlgA glycogen pathway is distinct and allosterically regulated. We have used a combination of genetics and biochemistry to establish how the GlgE pathway is regulated. M. tuberculosis GlgE was phosphorylated specifically by the Ser/Thr protein kinase PknB in vitro on one serine and six threonine residues. Furthermore, GlgE was phosphorylated in vivo when expressed in Mycobacterium bovis bacillus Calmette-Guérin (BCG) but not when all seven phosphorylation sites were replaced by Ala residues. The GlgE orthologues from Mycobacterium smegmatis and Streptomyces coelicolor were phosphorylated by the corresponding PknB orthologues in vitro, implying that the phosphorylation of GlgE is widespread among actinomycetes. PknB-dependent phosphorylation of GlgE led to a 2 orders of magnitude reduction in catalytic efficiency in vitro. The activities of phosphoablative and phosphomimetic GlgE derivatives, where each phosphorylation site was substituted with either Ala or Asp residues, respectively, correlated with negative phosphoregulation. Complementation studies of a M. smegmatis glgE mutant strain with these GlgE derivatives, together with both classical and chemical forward genetics, were consistent with flux through the GlgE pathway being correlated with GlgE activity. We conclude that the GlgE pathway appears to be negatively regulated in actinomycetes through the phosphorylation of GlgE by PknB, a mechanism distinct from that known in the classical glycogen pathway. Thus, these findings open new opportunities to target the GlgE pathway therapeutically.

Brain-Derived Neurotrophic Factor Val66Met Polymorphism Affects the Relationship Between an Anxiety-Related Personality Trait and Resting Regional Cerebral Blood Flow.

Science.gov (United States)

Wei, Shau-Ming; Eisenberg, Daniel P; Nabel, Katherine G; Kohn, Philip D; Kippenhan, J Shane; Dickinson, Dwight; Kolachana, Bhaskar; Berman, Karen F

2017-03-01

Brain-derived neurotrophic factor (BDNF) is an important modulator of constitutive stress responses mediated by limbic frontotemporal circuits, and its gene contains a functional polymorphism (Val66Met) that may influence trait stress sensitivity. Reports of an association of this polymorphism with anxiety-related personality traits have been controversial and without clear neurophysiological support. We, therefore, determined the relationship between resting regional cerebral blood flow (rCBF) and a well-validated measure of anxiety-related personality, the TPQ Harm Avoidance (HA) scale, as a function of BDNF Val66Met genotype. Sixty-four healthy participants of European ancestry underwent resting H215O positron emission tomography scans. For each genotype group separately, we first determined the relationship between participants' HA scores and their resting rCBF values in each voxel across the entire brain, and then directly compared these HA-rCBF relationships between Val66Met genotype groups. HA-rCBF relationships differed between Val homozygotes and Met carriers in several regions relevant to stress regulation: subgenual cingulate, orbital frontal cortex, and the hippocampal/parahippocampal region. In each of these areas, the relationship was positive in Val homozygotes and negative in Met carriers. These data demonstrate a coupling between trait anxiety and basal resting blood flow in frontolimbic neurocircuitry that may be determined in part by genetically mediated BDNF signaling. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A G-protein β subunit, AGB1, negatively regulates the ABA response and drought tolerance by down-regulating AtMPK6-related pathway in Arabidopsis.

Directory of Open Access Journals (Sweden)

Dong-bei Xu

Full Text Available Heterotrimeric G-proteins are versatile regulators involved in diverse cellular processes in eukaryotes. In plants, the function of G-proteins is primarily associated with ABA signaling. However, the downstream effectors and the molecular mechanisms in the ABA pathway remain largely unknown. In this study, an AGB1 mutant (agb1-2 was found to show enhanced drought tolerance, indicating that AGB1 might negatively regulate drought tolerance in Arabidopsis. Data showed that AGB1 interacted with protein kinase AtMPK6 that was previously shown to phosphorylate AtVIP1, a transcription factor responding to ABA signaling. Our study found that transcript levels of three ABA responsive genes, AtMPK6, AtVIP1 and AtMYB44 (downstream gene of AtVIP1, were significantly up-regulated in agb1-2 lines after ABA or drought treatments. Other ABA-responsive and drought-inducible genes, such as RD29A (downstream gene of AtMYB44, were also up-regulated in agb1-2 lines. Furthermore, overexpression of AtVIP1 resulted in hypersensitivity to ABA at seed germination and seedling stages, and significantly enhanced drought tolerance in transgenic plants. These results suggest that AGB1 was involved in the ABA signaling pathway and drought tolerance in Arabidopsis through down-regulating the AtMPK6, AtVIP1 and AtMYB44 cascade.

Monitoring variables affecting positron emission tomography measurements of cerebral blood flow in anaesthetized pigs

DEFF Research Database (Denmark)

Alstrup, Aage Kristian Olsen; Zois, Nora Elisabeth; Simonsen, Mette

Background: Positron emission tomography (PET) imaging of anaesthetised pig brains is a useful tool in neuroscience. Stable cerebral blood flow (CBF) is essential for PET, since variations can affect the kinetics of several radiotracers. However, the impact of physiological factors regulating CBF...

Electrical modulation of the sympathetic nervous system in order to augment cerebral blood flow : a protocol for an experimental study

NARCIS (Netherlands)

Ter Laan, Mark; van Dijk, J. Marc C.; Staal, Michiel J.; Elting, Jan-Willem J.

2011-01-01

Introduction: Cerebral blood flow (CBF) is regulated by several mechanisms. Neurogenic control has been a matter of debate, even though several publications reported the effects of changes in sympathetic tone on CBF. Transcutaneous electrical nerve stimulation and spinal-cord stimulation have been

CPC, a single-repeat R3 MYB, is a negative regulator of anthocyanin biosynthesis in Arabidopsis.

Science.gov (United States)

Zhu, Hui-Fen; Fitzsimmons, Karen; Khandelwal, Abha; Kranz, Robert G

2009-07-01

Single-repeat R3 MYB transcription factors like CPC (CAPRICE) are known to play roles in developmental processes such as root hair differentiation and trichome initiation. However, none of the six Arabidopsis single-repeat R3 MYB members has been reported to regulate flavonoid biosynthesis. We show here that CPC is a negative regulator of anthocyanin biosynthesis. In the process of using CPC to test GAL4-dependent driver lines, we observed a repression of anthocyanin synthesis upon GAL4-mediated CPC overexpression. We demonstrated that this is not due to an increase in nutrient uptake because of more root hairs. Rather, CPC expression level tightly controls anthocyanin accumulation. Microarray analysis on the whole genome showed that, of 37 000 features tested, 85 genes are repressed greater than three-fold by CPC overexpression. Of these 85, seven are late anthocyanin biosynthesis genes. Also, anthocyanin synthesis genes were shown to be down-regulated in 35S::CPC overexpression plants. Transient expression results suggest that CPC competes with the R2R3-MYB transcription factor PAP1/2, which is an activator of anthocyanin biosynthesis genes. This report adds anthocyanin biosynthesis to the set of programs that are under CPC control, indicating that this regulator is not only for developmental programs (e.g. root hairs, trichomes), but can influence anthocyanin pigment synthesis.

amiA is a negative regulator of acetamidase expression in Mycobacterium smegmatis

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Turner Jane

2001-08-01

Full Text Available Abstract Background The acetamidase of Mycobacterium smegmatis is a highly inducible enzyme. Expression of this enzyme is increased 100-fold when the substrate acetamide is present. The acetamidase gene is found immediately downstream of three open reading frames. Two of these are proposed to be involved in regulation. Results We constructed a deletion mutant in one of the upstream ORFs (amiA. This mutant (Mad1 showed a constitutively high level of acetamidase expression. We identified four promoters in the upstream region using a β-galactosidase reporter gene. One of these (P2 was inducible in the wild-type, but was constitutively active in Mad1. Conclusions These results demonstrate that amiA encodes a negative regulatory protein which interacts with P2. Since amiA has homology to DNA-binding proteins, it is likely that it exerts the regulatory effect by binding to the promoter to prevent transcription.

Sequence and function of LuxO, a negative regulator of luminescence in Vibrio harveyi.

Science.gov (United States)

Bassler, B L; Wright, M; Silverman, M R

1994-05-01

Density-dependent expression of luminescence in Vibrio harveyi is regulated by the concentration of extracellular signal molecules (autoinducers) in the culture medium. A recombinant clone that restored function to one class of spontaneous dim mutants was found to encode a function required for the density-dependent response. Transposon Tn5 insertions in the recombinant clone were isolated, and the mutations were transferred to the genome of V. harveyi for examination of mutant phenotypes. Expression of luminescence in V. harveyi strains with transposon insertions in one locus, luxO, was independent of the density of the culture and was similar in intensity to the maximal level observed in wild-type bacteria. Sequence analysis of luxO revealed one open reading frame that encoded a protein, LuxO, similar in amino acid sequence to the response regulator domain of the family of two-component, signal transduction proteins. The constitutive phenotype of LuxO- mutants indicates that LuxO acts negatively to control expression of luminescence, and relief of repression by LuxO in the wild type could result from interactions with other components in the Lux signalling system.

miR-375-3p negatively regulates osteogenesis by targeting and decreasing the expression levels of LRP5 and β-catenin.

Directory of Open Access Journals (Sweden)

Tianhao Sun

Full Text Available Wnt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition, the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis. Secondly, miR-375-3p targeted low-density lipoprotein receptor-related protein 5 (LRP5, a co-receptor of the Wnt signaling pathways, and β-catenin as determined by luciferase activity assay, and it decreased the expression levels of LRP5 and β-catenin. Thirdly, the decline of protein levels of β-catenin was determined by immunocytochemistry and immunofluorescence. Finally, silence of LRP5 in osteoblast precursor cells resulted in diminished cell viability and cell proliferation as detected by WST-1-based colorimetric assay. Additionally, all the parameters including the relative bone volume from μCT measurement suggested that LRP5 knockout in mice resulted in a looser and worse-connected trabeculae. The mRNA levels of important negative modulators relating to osteogenesis increased after the functions of LRP5 were blocked in mice. Last but not least, the expression levels of LRP5 increased during the osteogenesis of MC3T3-E1, while the levels of β-catenin decreased in bone tissues from osteoporotic patients with vertebral compression fractures. In conclusion, we revealed miR-375-3p negatively regulated osteogenesis by targeting LRP5 and β-catenin. In addition, loss of functions of LRP5 damaged bone formation in vivo. Clinically, miR-375-3p and its targets might be used as diagnostic biomarkers for osteoporosis and might be also as novel therapeutic agents in osteoporosis

Regional cerebral blood flow during the auditory oddball task measured by positron emission tomography

International Nuclear Information System (INIS)

Mochida, Masahiko

1997-01-01

Regional cerebral blood flow (rCBF) was measured by employing PET in nine healthy right-handed male subjects, while they simultaneously performed the auditory oddball task using tone bursts. Results showed that the rCBF value was highest in the transverse gyrus of Heschl in both right and left hemispheres. When comparing the rCBF values between right and left hemispheres, four areas had higher rCBF values in the left hemisphere and eight areas had higher rCBF values in the right hemisphere. Of these, the anterior and posterior parts of the superior temporal gyrus, especially, showed significant differences. The hemispheric differences in the rCBF values of the auditory areas can be attributed to the performance of the oddball task which requires higher processing of non verbal auditory input. The P300 amplitude which reflects the amount of the allocated information processing resources correlated positively with rCBF in the following areas: left piriform cortex, the transverse gyrus of Heschl in both left and right hemispheres. Mean-while, P300 amplitude correlated negatively with rCBF in the nucleus accumbens septi in both right and left hemispheres. The N100 amplitude evoked by frequent stimulus did not correlate with rCBF in almost all ROIs. (K.H.)

Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Science.gov (United States)

Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

2018-03-15

Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

TRAF Family Member-Associated NF-κB Activator (TANK) Induced by RANKL Negatively Regulates Osteoclasts Survival and Function

OpenAIRE

Mengrui Wu, Yiping Wang, Lianfu Deng, Wei Chen, Yi-Ping Li

2012-01-01

Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation...

TRAF Family Member-Associated NF-κB Activator (TANK) Induced by RANKL Negatively Regulates Osteoclasts Survival and Function

OpenAIRE

Wu, Mengrui; Wang, Yiping; Deng, Lianfu; Chen, Wei; Li, Yi-Ping

2012-01-01

Osteoclasts are the principle bone-resorbing cells. Precise control of balanced osteoclast activity is indispensable for bone homeostasis. Osteoclast activation mediated by RANK-TRAF6 axis has been clearly identified. However, a negative regulation-machinery in osteoclast remains unclear. TRAF family member-associated NF-κB activator (TANK) is induced by about 10 folds during osteoclastogenesis, according to a genome-wide analysis of gene expression before and after osteoclast maturation, and...

Perfusion deficits and functional connectivity alterations in patients with post-traumatic stress disorder

Science.gov (United States)

Liu, Yang; Li, Baojuan; Zhang, Xi; Zhang, Linchuan; Li, Liang; Lu, Hongbing

2016-03-01

To explore the alteration in cerebral blood flow (CBF) and functional connectivity between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, survived from the same coal mine flood disaster. In this study, a processing pipeline using arterial spin labeling (ASL) sequence was proposed. Considering low spatial resolution of ASL sequence, a linear regression method was firstly used to correct the partial volume (PV) effect for better CBF estimation. Then the alterations of CBF between two groups were analyzed using both uncorrected and PV-corrected CBF maps. Based on altered CBF regions detected from the CBF analysis as seed regions, the functional connectivity abnormities in PTSD patients was investigated. The CBF analysis using PV-corrected maps indicates CBF deficits in the bilateral frontal lobe, right superior frontal gyrus and right corpus callosum of PTSD patients, while only right corpus callosum was identified in uncorrected CBF analysis. Furthermore, the regional CBF of the right superior frontal gyrus exhibits significantly negative correlation with the symptom severity in PTSD patients. The resting-state functional connectivity indicates increased connectivity between left frontal lobe and right parietal lobe. These results indicate that PV-corrected CBF exhibits more subtle perfusion changes and may benefit further perfusion and connectivity analysis. The symptom-specific perfusion deficits and aberrant connectivity in above memory-related regions may be putative biomarkers for recent onset PTSD induced by a single prolonged trauma exposure and help predict the severity of PTSD.

The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus.

Science.gov (United States)

Danger, Jessica L; Makthal, Nishanth; Kumaraswami, Muthiah; Sumby, Paul

2015-12-01

The group A Streptococcus (GAS; Streptococcus pyogenes) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to the prtF1 and prtF2 mRNAs within their 5' untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and the prtF1 and prtF2 mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection. More than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

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Yang, Bin [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Li, Wei [Department of Gerontology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qichang [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Qin, Tao [Department of Hepatobiliary Pancreatic Surgery, People' s Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou 450003 (China); Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Liu, Sanguang, E-mail: sanguang1998@sina.com [Department of Hepatobiliary Surgery, The Second Hospital, Hebei Medical University, Shijiazhuang 050000 (China); Song, Zifang, E-mail: zsong@hust.edu.cn [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China)

2015-07-17

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

International Nuclear Information System (INIS)

Yang, Bin; Li, Wei; Zheng, Qichang; Qin, Tao; Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen; Liu, Sanguang; Song, Zifang

2015-01-01

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation

Evidence for the negative regulation of phytase gene expression in Streptomyces lividans and Streptomyces coelicolor.

Science.gov (United States)

Boukhris, Ines; Dulermo, Thierry; Chouayekh, Hichem; Virolle, Marie-Joëlle

2016-01-01

Sco7697, a gene encoding a phytase, enzyme able to degrade phytate (myo-inositol 1,2,3,4,5,6-hexakis phosphate), the most abundant phosphorus storing compound in plants is present in the genome of S. coelicolor, a soil born bacteria with a saprophytic lifestyle. The expression of this gene was previously shown to be induced in conditions of Pi limitation by the response regulator PhoP binding to an operator sequence, the PHO box, located upstream of the -35 promoter sequence. A close examination of the promoter region of sco7697 revealed the presence of another putative operator site, a Direct Repeat (DR), located downstream of the -10 promoter sequence. In order to determine whether this DR played a role in regulation of sco7697 expression, different variants of the phytase gene promoter region were transcriptionally fused to the ß-glucuronidase reporter gene (GUS). As expected, deletion of the PHO box led to abolition of sco7697 induction in conditions of Pi limitation. Interestingly, alteration of the DR correlated with a dramatic increase of GUS expression but only when PhoP was present. These results demonstrated that this DR is the site of strong negative regulation by an unknown repressor. The latter would impede the necessary activation of phytase expression by PhoP. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Somatotype and body composition of referees and assistant referees from the CBF

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Cassiano Ricardo Rech

2008-04-01

Full Text Available The aim of this study was to determine and compare the somatotype and body composition of principal soccer referees and assistant soccer referees from the state of Paraná in Brazil, all working for the Brazilian Soccer Confederation – (CBF Confederaçao Brasileira de Futebol. Twenty-five referees participated in this study: 12 principal referees (PR and 13 assistant referees (AR, all male. The variables body mass, height, skinfolds, body girth and bone diameters were collected with the aim of estimating the referees’ body composition and determining their somatotypes. Data are presented in the form of descriptive statistics. Comparisons between the PR and AR groups were made using Student’s t test for independent samples. The PR referees had a mean age of 38.5 + 5.1 years of age, body mass of 80.9 + 7.61 Kg, mean height of 179 + 3.3 cm and an average percentage of fat of 20.81 + 3.29%. The AR group were significantly younger on average (37.3 + 3.1 years old, p Resumo O objetivo do presente estudo foi determinar e comparar o somatotipo e a composição corporal de árbitros e árbitros assistentes de futebol do Estado do Paraná, Brasil, que atuam junto à Confederação Brasileira de Futebol (CBF. Participaram do estudo 25 árbitros, sendo 12 árbitros principais (AP e 13 árbitros assistentes (AA ambos do sexo masculino. As variáveis de massa corporal, estatura, espessura de dobras cutâneas, perímetros corporais e diâmetros ósseos foram coletados com a finalidade de estimar a composição corporal e determinar o somatotipo dos árbitros. Os dados são apresentados mediante estatística descritiva, a comparação entre os grupos de AP e AA foi realizada por meio do teste “t” de student para amostras independentes. Os AP apresentaram uma idade média de 38,5±5,1 anos, massa corporal de 80,9±7,61 kg, estatura 179±3,3 cm e um percentual de gordura médio de 20,81±3,29 %. O grupo de AA apresentou uma idade média menor (37,3±3

Molecular cloning and characterization of a novel freezing-inducible DREB1/CBF transcription factor gene in boreal plant Iceland poppy (Papaver nudicaule

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Zhuo Huang

Full Text Available Abstract DREB1 of the AP2/ERF superfamily plays a key role in the regulation of plant response to low temperatures. In this study, a novel DREB1/CBF transcription factor, PnDREB1, was isolated from Iceland poppy (Papaver nudicaule, a plant adaptive to low temperature environments. It is homologous to the known DREB1s of Arabidopsis and other plant species. It also shares similar 3D structure, and conserved and functionally important motifs with DREB1s of Arabidopsis. The phylogenetic analysis indicated that the AP2 domain of PnDREB1 is similar to those of Glycine max, Medicago truncatula, and M. sativa. PnDREB1 is constitutively expressed in diverse tissues and is increased in roots. qPCR analyses indicated that PnDREB1 is significantly induced by freezing treatment as well as by abscissic acid. The expression levels induced by freezing treatment were higher in the variety with higher degree of freezing tolerance. These results suggested that PnDREB1 is a novel and functional DREB1 transcription factor involved in freezing response and possibly in other abiotic stresses. Furthermore, the freezing-induction could be suppressed by exogenous gibberellins acid, indicating that PnDREB1 might play some role in the GA signaling transduction pathway. This study provides a basis for better understanding the roles of DREB1 in adaption of Iceland poppy to low temperatures.

Perfusion deficits detected by arterial spin-labeling in patients with TIA with negative diffusion and vascular imaging.

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Qiao, X J; Salamon, N; Wang, D J J; He, R; Linetsky, M; Ellingson, B M; Pope, W B

2013-01-01

A substantial portion of clinically diagnosed TIA cases is imaging-negative. The purpose of the current study is to determine if arterial spin-labeling is helpful in detecting perfusion abnormalities in patients presenting clinically with TIA. Pseudocontinuous arterial spin-labeling with 3D background-suppressed gradient and spin-echo was acquired on 49 patients suspected of TIA within 24 hours of symptom onset. All patients were free of stroke history and had no lesion-specific findings on general MR, DWI, and MRA sequences. The calculated arterial spin-labeling CBF maps were scored from 1-3 on the basis of presence and severity of perfusion disturbance by 3 independent observers blinded to patient history. An age-matched cohort of 36 patients diagnosed with no cerebrovascular events was evaluated as a control. Interobserver agreement was assessed by use of the Kendall concordance test. Scoring of perfusion abnormalities on arterial spin-labeling scans of the TIA cohort was highly concordant among the 3 observers (W = 0.812). The sensitivity and specificity of arterial spin-labeling in the diagnosis of perfusion abnormalities in TIA was 55.8% and 90.7%, respectively. In 93.3% (70/75) of the arterial spin-labeling CBF map readings with positive scores (≥2), the brain regions where perfusion abnormalities were identified by 3 observers matched with the neurologic deficits at TIA onset. In this preliminary study, arterial spin-labeling showed promise in the detection of perfusion abnormalities that correlated with clinically diagnosed TIA in patients with otherwise normal neuroimaging results.

Cutaneous and subcutaneous blood flow measurements in psoriasis

International Nuclear Information System (INIS)

Klemp, P.

1987-01-01

The experiments - published in 7 papers in The Journal of Investigative Dermatology 1983-86 - have demonstrated: 1. The accuracy of the local 133 Xe washout method is about 15% for estimation of the cutaneous blood flow (CBF), and about 10% for subcutaneous blood flow measurements (SBF). In measurements of absolute CBF values a graphic curve resolution of the washout curve should alwaus be performed. Otherwise the CBF might be considerably underestimated. 2. CdTe(Cl) mini-detectors can be attached directly to the skin, and might yield measurements of both CBF and SBF that can substitute for those made with conventional detectors. 3. The laser Doppler measurements could not be correlated to quantitative measurements of the CBF. 4. The tissue-to-blood partition coefficient for 133 Xe of lesional psoriatic skin (LS) is increased. 5. In untreated, LS of patients with active psoriasis the CBF is about a factor of 10 times higher than the CBF of normal individuals. In non-lesional skin (NLS) of patients with active psoriasis the CBF is about a factor of 2 higher than the CBF of normal individuals. However, the CBF did not differ in NLS of patients with minimal skin manifestations. The high CBF decreases gradualy during antipsoriatic treatment. 6. A paradoxical autoregulation of the CBF was observed in LS. 7. The high CBF is not due to a maximally dilated vascular bed. 8. The SBF in LS areas was a factor of higher than the SBF in normal individuals. 9. A normal, local regulation of the SBF was found. (author)

Negative regulation of parathyroid hormone-related protein expression by steroid hormones

International Nuclear Information System (INIS)

Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

2011-01-01

Highlights: → Steroid hormones repress expression of PTHrP in the cell lines where the corresponding nuclear receptors are expressed. → Nuclear receptors are required for suppression of PTHrP expression by steroid hormones, except for androgen receptor. → Androgen-induced suppression of PTHrP expression appears to be mediated by estrogen receptor. -- Abstract: Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

Stable xenon CT CBF measurements in prevalent cerebrovascular disorders (stroke)

International Nuclear Information System (INIS)

Meyer, J.S.; Okayasu, H.; Tachibana, H.; Okabe, T.

1984-01-01

Local cerebral blood flow (LCBF) and local tissue: blood partition coefficient (L lambda) values were measured for small volumes of gray or white matter by CT CBF. Single compartment analysis was used but fitted to infinity in normal volunteers aged between 20 to 100 years (N . 20). Hemispheric LCBF and L lambda values were compared to those of 61 age matched patients with transient ischemic attacks (TIAs, N . 10), reversible ischemic neurologic deficits (RINDS, N . 10), acute and chronic cerebral infarctions associated with emboli from atherosclerotic plaques or complete occlusion of internal carotid or middle cerebral arteries (n . 9) or of cardiac origin (N . 3), cerebral hemorrhage (N . 1), multi-infarct dementia (MID) (N . 11) and arteriovenous malformations (AVM) (N . 17). In normal aging, L lambda s were normal, but LCBF showed diffuse age-related declines. Symptomatic cerebrovascular disease was characterized by accentuation of age-related LCBF declines. TIAs with unilateral ICA occlusion showed bilateral reductions of LCBF more evident in ischemic hemispheres. TIAs due to fibrino-platelet emboli from ulcerated, non-occlusive ICA plaques were characterized by transient unilateral, localized LCBF reductions. All TIAs showed normal L lambda values. RINDS showed both LCBF and L lambda reductions. Larger embolic infarctions of ICA origin, whether acute or chronic, showed zones of zero flow with surrounding reductions of LCBF and L lambda values. Recent cerebral embolism of cardiac origin likewise exhibited zones of zero flow surrounded by reduced LCBF and L lambda values; but in chronic stages LCBF and L lambda values adjacent to zero flow zones were normal. MID was characterized by patchy reductions of LCBF and L lambda values throughout both hemispheres. Brain tissues surrounding AVM showed normal L lambda values but LCBF values were reduced due to steal

Post-translational regulation enables robust p53 regulation.

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Shin, Yong-Jun; Chen, Kai-Yuan; Sayed, Ali H; Hencey, Brandon; Shen, Xiling

2013-08-30

The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance towards fluctuations and disturbances. Interestingly, the p53 level is controlled by post-translational regulation rather than transcriptional regulation in this feedback mechanism. We analyzed the dynamics of this feedback to understand whether post-translational regulation provides any advantages over transcriptional regulation in regard to disturbance rejection. When a disturbance happens, even though negative feedback reduces the steady-state error, it can cause a system to become less stable and transiently overshoots, which may erroneously trigger downstream reactions. Therefore, the system needs to balance the trade-off between steady-state and transient errors. Feedback control and adaptive estimation theories revealed that post-translational regulation achieves a better trade-off than transcriptional regulation, contributing to a more steady level of p53 under the influence of noise and disturbances. Furthermore, post-translational regulation enables cells to respond more promptly to stress conditions with consistent amplitude. However, for better disturbance rejection, the p53- Mdm2 negative feedback has to pay a price of higher stochastic noise. Our analyses suggest that the p53-Mdm2 feedback favors regulatory mechanisms that provide the optimal trade-offs for dynamic control.

Ubiquitin carboxyl terminal hydrolase L1 negatively regulates TNFα-mediated vascular smooth muscle cell proliferation via suppressing ERK activation

International Nuclear Information System (INIS)

Ichikawa, Tomonaga; Li, Jinqing; Dong, Xiaoyu; Potts, Jay D.; Tang, Dong-Qi; Li, Dong-Sheng; Cui, Taixing

2010-01-01

Deubiquitinating enzymes (DUBs) appear to be critical regulators of a multitude of processes such as proliferation, apoptosis, differentiation, and inflammation. We have recently demonstrated that a DUB of ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) inhibits vascular lesion formation via suppressing inflammatory responses in vasculature. However, the precise underlying mechanism remains to be defined. Herein, we report that a posttranscriptional up-regulation of UCH-L1 provides a negative feedback to tumor necrosis factor alpha (TNFα)-mediated activation of extracellular signal-regulated kinases (ERK) and proliferation in vascular smooth muscle cells (VSMCs). In rat adult VSMCs, adenoviral over-expression of UCH-L1 inhibited TNFα-induced activation of ERK and DNA synthesis. In contrast, over-expression of UCH-L1 did not affect platelet derived growth factor (PDGF)-induced VSMC proliferation and activation of growth stimulating cascades including ERK. TNFα hardly altered UCH-L1 mRNA expression and stability; however, up-regulated UCH-L1 protein expression via increasing UCH-L1 translation. These results uncover a novel mechanism by which UCH-L1 suppresses vascular inflammation.

Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

Science.gov (United States)

Davey, Jonathan R.; Watt, Kevin I.; Parker, Benjamin L.; Chaudhuri, Rima; Ryall, James G.; Cunningham, Louise; Qian, Hongwei; Sartorelli, Vittorio; Chamberlain, Jeffrey; James, David E.

2016-01-01

The transforming growth factor-β (TGF-β) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-β network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-β network–responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles. PMID:27182554

TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.

Science.gov (United States)

McNab, Finlay W; Ewbank, John; Rajsbaum, Ricardo; Stavropoulos, Evangelos; Martirosyan, Anna; Redford, Paul S; Wu, Xuemei; Graham, Christine M; Saraiva, Margarida; Tsichlis, Philip; Chaussabel, Damien; Ley, Steven C; O'Garra, Anne

2013-08-15

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of mortality and morbidity worldwide, causing ≈ 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL-12, IL-1, and TNF-α, as well as IFN-γ and CD4(+) Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I IFN have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL-10 is known to inhibit the immune response to M. tuberculosis in murine models through the negative regulation of key proinflammatory cytokines and the subsequent Th1 response. We show in this study, using a combination of transcriptomic analysis, genetics, and pharmacological inhibitors, that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I IFN production. The TPL-2-ERK1/2 signaling pathway regulated production by macrophages of several cytokines important in the immune response to M. tuberculosis as well as regulating induction of a large number of additional genes, many in a type I IFN-dependent manner. In the absence of TPL-2 in vivo, excess type I IFN promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I IFN may promote susceptibility to this important disease.

The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling

DEFF Research Database (Denmark)

Ungureanu, Daniela; Wu, Jinhua; Pekkala, Tuija

2011-01-01

Human JAK2 tyrosine kinase mediates signaling through numerous cytokine receptors. The JAK2 JH2 domain functions as a negative regulator and is presumed to be a catalytically inactive pseudokinase, but the mechanism(s) for its inhibition of JAK2 remains unknown. Mutations in JH2 lead to increased...... JAK2 activity, contributing to myeloproliferative neoplasms (MPNs). Here we show that JH2 is a dual-specificity protein kinase that phosphorylates two negative regulatory sites in JAK2: Ser523 and Tyr570. Inactivation of JH2 catalytic activity increased JAK2 basal activity and downstream signaling....... Notably, different MPN mutations abrogated JH2 activity in cells, and in MPN (V617F) patient cells phosphorylation of Tyr570 was reduced, suggesting that loss of JH2 activity contributes to the pathogenesis of MPNs. These results identify the catalytic activity of JH2 as a previously unrecognized...

Correlation between quantitative EEG and cerebral blood flow and oxygen metabolism in patients with dementia of Alzheimer type

International Nuclear Information System (INIS)

Kudoh, Masako; Takahashi, Satoshi; Yonezawa, Hisashi

1997-01-01

Quantitative scalp EEG and cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) measured by the steady-state 15 O technique and positron emission tomography were studied in 19 patients with mild to moderate dementia of Alzheimer type (DAT) and age-matched controls (EEG=19, PET=6). Scalp electrodes were placed according to the international 10-20 method except for Cz, T3, and T4. To evaluate the relative changes in power for each frequency band between the two groups, the percentage power fraction (percentage power for each frequency band at a site compared to the total power at that site; %delta for 2.0-3.8 Hz, %theta for 4.0-7.8 Hz, %alpha for 8.0-12.8 Hz, %beta for 13.0-25.4 Hz) was calculated. Compared with controls, DAT patients showed a significant decrease in %alpha, while significant increases in %theta at all electrodes, and significant increases in %delta at the temporal, parietal and occipital electrodes were observed. The patient group displayed a significant decrease in rCBF and rCMRO 2 in the parietal, temporal and frontal cortices, but the reduction in rCMRO 2 was less remarkable than that of rCBF. %Theta at P3, O1 and O2 showed a significant negative correlation with rCBF, and %theta at P3, O1showed a significant negative correlation with rCMRO 2 . %Delta at P3, P4 and T5 was significantly negatively correlated with rCBF in the corresponding regions, and %alpha at almost all the electrodes (except O1, F3, P3) was significantly positively correlated with rCBF in the corresponding regions. %Delta and %alpha did not show any significant correlation with rCMRO 2 . (author)

Monitoring variables affecting positron emission tomography measurements of cerebral blood flow in anaesthetized pigs

DEFF Research Database (Denmark)

Alstrup, Aage Kristian Olsen; Zois, Nora Elisabeth; Simonsen, Mette

2018-01-01

Background Positron emission tomography (PET) imaging of anaesthetized pig brains is a useful tool in neuroscience. Stable cerebral blood flow (CBF) is essential for PET, since variations can affect the distribution of several radiotracers. However, the effect of physiological factors regulating...... and the monitoring parameters. Results No significant statistical correlations were found between CBF and the nine monitoring variables. However, we found that arterial carbon dioxide tension (PaCO2) and body temperature were important predictors of CBF that should be observed and kept constant. In addition, we...... found that long-duration anaesthesia was significantly correlated with high heart rate, low arterial oxygen tension, and high body temperature, but not with CBF. Conclusions The findings indicate that PaCO2 and body temperature are crucial for maintaining stable levels of CBF and thus optimizing PET...

Expression of alkyl hydroperoxide reductase is regulated negatively by OxyR1 and positively by RpoE2 sigma factor in Azospirillum brasilense Sp7.

Science.gov (United States)

Singh, Sudhir; Dwivedi, Susheel Kumar; Singh, Vijay Shankar; Tripathi, Anil Kumar

2016-10-01

OxyR proteins are LysR-type transcriptional regulators, which play an important role in responding to oxidative stress in bacteria. Azospirillum brasilense Sp7 harbours two copies of OxyR. The inactivation of the oxyR1, the gene organized divergently to ahpC in A. brasilense Sp7, led to an increased tolerance to alkyl hydroperoxides, which was corroborated by an increase in alkyl hydroperoxide reductase (AhpC) activity, enhanced expression of ahpC :lacZ fusion and increased synthesis of AhpC protein in the oxyR1::km mutant. The upstream region of ahpC promoter harboured a putative OxyR binding site, T-N11-A. Mutation of T, A or both in the T-N11-Amotif caused derepression of ahpC in A. brasilense suggesting that T-N11-A might be the binding site for a negative regulator. Retardation of the electrophoretic mobility of the T-N11-A motif harbouring oxyR1-ahpC intergenic DNA by recombinant OxyR1, under reducing as well as oxidizing conditions, indicated that OxyR1 acts as a negative regulator of ahpC in A. brasilense. Sequence of the promoter of ahpC, predicted on the basis of transcriptional start site, and an enhanced expression of ahpC:lacZ fusion in chrR2::km mutant background suggested that ahpC promoter was RpoE2 dependent. Thus, this study shows that in A. brasilense Sp7, ahpC expression is regulated negatively by OxyR1 but is regulated positively by RpoE2, an oxidative-stress-responsive sigma factor. It also shows that OxyR1 regulates the expression RpoE1, which is known to play an important role during photooxidative stress in A. brasilense.

miR-146a negatively regulates the induction of proinflammatory cytokines in response to Japanese encephalitis virus infection in microglial cells.

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Deng, Minnan; Du, Ganqin; Zhao, Jiegang; Du, Xiaowei

2017-06-01

Increasing evidence confirms the involvement of virus infection and miRNA, such as miR-146a, in neuroinflammation-associated epilepsy. In the present study, we investigated the upregulation of miR-146a with RT-qPCR and in situ hybridization methods in a mice infection model of Japanese encephalitis virus (JEV) and in vitro. Subsequently we investigated the involvement of miR-146a in modulating JEV-induced neuroinflammation. It was demonstrated that JEV infection promoted miR-146a production in BALB/c mice brain and in cultured mouse microglial C8-B4 cells, along with pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, IFN-β and IFN-α. We also found that miR-146a exerted negative regulatory effects upon IL-1β, IL-6, TNF-α, IFN-β and IFN-α in C8-B4 cells. Accordingly, miR-146a downregulation with a miR-146a inhibitor promoted the upregulation of IL-1β, IL-6, TNF-α, IFN-β and IFN-α, whereas miR-146a upregulation with miR-146a mimics reduced the upregulation of these cytokines. Moreover, miR-146a exerted no regulation upon JEV growth in C8-B4 cells. In conclusion, JEV infection upregulated miR-146a and pro-inflammatory cytokine production, in mice brain and in cultured C8-B4 cells. Furthermore, miR-146a negatively regulated the production of JEV-induced pro-inflammatory cytokines, in virus growth independent fashion, identifying miR-146a as a negative feedback regulator in JEV-induced neuroinflammation, and possibly in epilepsy.

Time-dependent correlation of cerebral blood flow with oxygen metabolism in activated human visual cortex as measured by fMRI.

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Lin, Ai-Ling; Fox, Peter T; Yang, Yihong; Lu, Hanzhang; Tan, Li-Hai; Gao, Jia-Hong

2009-01-01

The aim of this study was to investigate the relationship between relative cerebral blood flow (delta CBF) and relative cerebral metabolic rate of oxygen (delta CMRO(2)) during continuous visual stimulation (21 min at 8 Hz) with fMRI biophysical models by simultaneously measuring of BOLD, CBF and CBV fMRI signals. The delta CMRO(2) was determined by both a newly calibrated single-compartment model (SCM) and a multi-compartment model (MCM) and was in agreement between these two models (P>0.5). The duration-varying delta CBF and delta CMRO(2) showed a negative correlation with time (r=-0.97, PSCM, an incorrect and even an opposite appearance of the flow-metabolism relationship during prolonged visual stimulation (positively linear coupling) can result. The time-dependent negative correlation between flow and metabolism demonstrated in this fMRI study is consistent with a previous PET observation and further supports the view that the increase in CBF is driven by factors other than oxygen demand and the energy demands will eventually require increased aerobic metabolism as stimulation continues.

Utility of cerebral circulation evaluation in acute traumatic brain injuries

International Nuclear Information System (INIS)

Honda, Mitsuru; Sakata, Yoshihito; Haga, Daisuke; Nomoto, Jun; Noguchi, Yoshitaka; Seiki, Yoshikatsu; Machida, Keiichi; Sase, Shigeru

2007-01-01

Severe traumatic brain injury (TBI) is well-known to cause dynamic changes in cerebral blood flow (CBF). Specifically, TBI has been reported to cause decreases in cerebral blood flow (CBF). In this study, we measured CBF, mean transit time (MTT) and cerebral blood volume (CBV) after TBI. Our purpose was investigate the possibility of assessing TBI outcome and severity with these physiological parameters, and the clinical utility of cerebral circulation evaluation for brain-oriented intensive care. In 37 patients with TBI, xenon-enhanced CT (Xe-CT) and perfusion CT were performed on days 1-3 post-event (phase II). We measured CBF using Xe-CT and MTT by Perfusion CT and calculated CBV using an AZ-7000W98 computer system. Relative intra cranicol pressure (ICP) and CBF showed significant negative correlations. Relative ICP and MTT showed significant positive correlations. Outcomes, correlated with valuse of CBF and MIT. Significant differences in CBF and MTT were found between favorable outcome group (good recovery (GR) and moderate disability (MD)) and poor outcome group (severe disability (SD), vegetative state (VS), and dead (D)). We could estimate the outcome of patients after TBI by analyzing values of CBF and MTT with a probability of 74%. We evaluated cerebral circulation status in patients with TBI by CBF and MTT. These tests can help to optimize management and improve outcome in patients with severe TBI. (author)

Negative regulation of NOD1 mediated angiogenesis by PPARγ-regulated miR-125a

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Kang, Hyesoo; Park, Youngsook; Lee, Aram; Seo, Hyemin; Kim, Min Jung; Choi, Jihea; Jo, Ha-neul; Jeong, Ha-neul; Cho, Jin Gu; Chang, Woochul; Lee, Myeong-Sok; Jeon, Raok; Kim, Jongmin

2017-01-01

Infection with pathogens activates the endothelial cell and its sustained activation may result in impaired endothelial function. Endothelial dysfunction contributes to the pathologic angiogenesis that is characteristic of infection-induced inflammatory pathway activation. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor which recognizes bacterial molecules and stimulates an immune reaction in various cells; however, the underlying molecular mechanisms in the regulation of inflammation-triggered angiogenesis are not fully understood. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated miR-125a serves as an important regulator of NOD1 agonist-mediated angiogenesis in endothelial cells by directly targeting NOD1. Treatment of human umbilical vein endothelial cells with natural PPARγ ligand, 15-Deoxy-Delta12,14-prostaglandin J2, led to inhibition of NOD1 expression; contrarily, protein levels of NOD1 were significantly increased by PPARγ knockdown. We report that PPARγ regulation of NOD1 expression is a novel microRNA-mediated regulation in endothelial cells. MiR-125a expression was markedly decreased in human umbilical vein endothelial cells subjected to PPARγ knockdown while 15-Deoxy-Delta12,14-prostaglandin J2 treatment increased the level of miR-125a. In addition, NOD1 is closely regulated by miR-125a, which directly targets the 3′ untranslated region of NOD1. Moreover, both overexpression of miR-125a and PPARγ activation led to inhibition of NOD1 agonist-induced tube formation in endothelial cells. Finally, NOD1 agonist increased the formation of cranial and subintestinal vessel plexus in zebrafish, and this effect was abrogated by concurrent PPARγ activation. Overall, these findings identify a PPARγ-miR-125a-NOD1 signaling axis in endothelial cells that is critical in the regulation of inflammation-mediated angiogenesis. - Highlights: • Expression of NOD1 is regulated by

A limitation of the split-dose method for evaluating rCBF changes using 99mTc-ECD and SPECT

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Odano, Ikuo; Takahashi, Makoto; Noguchi, Eikichi; Ohtaki, Hiro; Shibaki, Mitsurou; Kasahara, Tosifumi; Hatano, Masayoshi; Ohkubo, Masaki.

1997-01-01

The purpose of the study is to validate the split-dose method corrected with dose ratio of 99m Tc-ECD for brain perfusion scan. A dose of 600 MBq of 99m Tc-ECD was divided into two with various dose ratios from 1 : 1 to 1 : 4, and injected to eleven patients with various cerebral diseases. A lesser dose of 99m Tc-ECD was injected under a control state for the first SPECT scan, and 15 min SPECT scan was performed 10 min after injection with a triple-head high resolution gamma camera. After the scan, the other dose of 99m Tc-ECD was injected under the same control state and the second SPECT scan was performed as same as above. A ratio of the activity of the first scan to the net activity of the second scan corrected by dose ratio, defined as K, was measured in brain regions of each subject. Expected value of K was 1, but the value was distributed with large variations in each subject. The mean % error of the K value was 10.4±4.9%. Hence it is considered that activity changes by more than 20% from the control values should be required to detect a significant rCBF change in an activation SPECT study. Then, we proposed a new method in which the activity of both two SPECT scans was normalized by cerebellar or occipital activity and compared. The ratio obtained by the proposed method came closer to 1 with less variations and with less mean % error in comparison with those of K value obtained by the dose-correction method. Although the proposed method has a limitation in the use of an activation study loaded with Diamox, it may be useful to evaluate an alteration of rCBF in the study such as postural testing or finger-moving test. (author)

Central Role of Core Binding Factor β2 in Mucosa-Associated Lymphoid Tissue Organogenesis in Mouse.

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Nagatake, Takahiro; Fukuyama, Satoshi; Sato, Shintaro; Okura, Hideaki; Tachibana, Masashi; Taniuchi, Ichiro; Ito, Kosei; Shimojou, Michiko; Matsumoto, Naomi; Suzuki, Hidehiko; Kunisawa, Jun; Kiyono, Hiroshi

2015-01-01

Mucosa-associated lymphoid tissue (MALT) is a group of secondary and organized lymphoid tissue that develops at different mucosal surfaces. Peyer's patches (PPs), nasopharynx-associated lymphoid tissue (NALT), and tear duct-associated lymphoid tissue (TALT) are representative MALT in the small intestine, nasal cavity, and lacrimal sac, respectively. A recent study has shown that transcriptional regulators of core binding factor (Cbf) β2 and promotor-1-transcribed Runt-related transcription factor 1 (P1-Runx1) are required for the differentiation of CD3-CD4+CD45+ lymphoid tissue inducer (LTi) cells, which initiate and trigger the developmental program of PPs, but the involvement of this pathway in NALT and TALT development remains to be elucidated. Here we report that Cbfβ2 plays an essential role in NALT and TALT development by regulating LTi cell trafficking to the NALT and TALT anlagens. Cbfβ2 was expressed in LTi cells in all three types of MALT examined. Indeed, similar to the previous finding for PPs, we found that Cbfβ2-/- mice lacked NALT and TALT lymphoid structures. However, in contrast to PPs, NALT and TALT developed normally in the absence of P1-Runx1 or other Runx family members such as Runx2 and Runx3. LTi cells for NALT and TALT differentiated normally but did not accumulate in the respective lymphoid tissue anlagens in Cbfβ2-/- mice. These findings demonstrate that Cbfβ2 is a central regulator of the MALT developmental program, but the dependency of Runx proteins on the lymphoid tissue development would differ among PPs, NALT, and TALT.

Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects

International Nuclear Information System (INIS)

Fox, P.T.; Raichle, M.E.

1986-01-01

Coupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) was studied using multiple sequential administrations of 15 O-labeled radiotracers and positron emission tomography. In the resting state an excellent correlation between CBF and CMRO 2 was found when paired measurements of CBF and CMRO 2 from multiple (30-48) brain regions were tested in each of 33 normal subjects. Regional uncoupling of CBF and CMRO 2 was found, however, during neuronal activation induced by somatosensory stimulation. Stimulus-induced focal augmentation of cerebral blood flow (29% mean) far exceeded the concomitant local increase in tissue metabolic rate (mean, 5%), when resting-state and stimulated-state measurements were obtained in each of 9 subjects. Stimulus duration had no significant effect on response magnitude or on the degree of CBF-CMRO 2 uncoupling observed. Dynamic, physiological regulation of CBF by a mechanism (neuronal or biochemical) dependent on neuronal firing per se, but independent of the cerebral metabolic rate of oxygen, is hypothesized

Src-family kinases negatively regulate NFAT signaling in resting human T cells.

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Alan Baer

Full Text Available T cell signaling is required for activation of both natural and therapeutic T cells including chimeric antigen receptor (CAR T cells. Identification of novel factors and pathways regulating T cell signaling may aid in development of effective T cell therapies. In resting human T cells, the majority of Src-family of tyrosine kinases (SFKs are inactive due to phosphorylation of a conserved carboxy-terminal tyrosine residue. Recently, a pool of enzymatically active SFKs has been identified in resting T cells; however, the significance of these is incompletely understood. Here, we characterized the role of active SFKs in resting human T cells. Pharmacologic inhibition of active SFKs enhanced distal TCR signaling as measured by IL-2 release and CD25 surface expression following TCR-independent activation. Mechanistically, inhibition of the active pool of SFKs induced nuclear translocation of NFAT1, and enhanced NFAT1-dependent signaling in resting T cells. The negative regulation of NFAT1 signaling was in part mediated by the Src-kinase Lck as human T cells lacking Lck had increased levels of nuclear NFAT1 and demonstrated enhanced NFAT1-dependent gene expression. Inhibition of active SFKs in resting primary human T cells also increased nuclear NFAT1 and enhanced NFAT1-dependent signaling. Finally, the calcineurin inhibitor FK506 and Cyclosporin A reversed the effect of SFKs inhibition on NFAT1. Together, these data identified a novel role of SFKs in preventing aberrant NFAT1 activation in resting T cells, and suggest that maintaining this pool of active SFKs in therapeutic T cells may increase the efficacy of T cell therapies.

An unusual spliced variant of DELLA protein, a negative regulator of gibberellin signaling, in lettuce.

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Sawada, Yoshiaki; Umetsu, Asami; Komatsu, Yuki; Kitamura, Jun; Suzuki, Hiroyuki; Asami, Tadao; Fukuda, Machiko; Honda, Ichiro; Mitsuhashi, Wataru; Nakajima, Masatoshi; Toyomasu, Tomonobu

2012-01-01

DELLA proteins are negative regulators of the signaling of gibberellin (GA), a phytohormone regulating plant growth. DELLA degradation is triggered by its interaction with GID1, a soluble GA receptor, in the presence of bioactive GA. We isolated cDNA from a spliced variant of LsDELLA1 mRNA in lettuce, and named it LsDELLA1sv. It was deduced that LsDELLA1sv encodes truncated LsDELLA1, which has DELLA and VHYNP motifs at the N terminus but lacks part of the C-terminal GRAS domain. The recombinant LsDELLA1sv protein interacted with both Arabidopsis GID1 and lettuce GID1s in the presence of GA. A yeast two-hybrid assay suggested that LsDELLA1sv interacted with LsDELLA1. The ratio of LsDELLA1sv to LsDELLA1 transcripts was higher in flower samples at the late reproductive stage and seed samples (dry seeds and imbibed seeds) than in the other organ samples examined. This study suggests that LsDELLA1sv is a possible modulator of GA signaling in lettuce.

Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders.

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Gery, Sigal; Gueller, Saskia; Chumakova, Katya; Kawamata, Norihiko; Liu, Liqin; Koeffler, H Phillip

2007-11-01

Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk in UT7-MPLW515L cells enhances proliferation. Lnk blocks the activation of Jak2, Stat3, Erk, and Akt in these cells. Furthermore, MPLW515L-expressing cells are more susceptible to Lnk inhibitory functions than their MPL wild-type (MPLWT)-expressing counterparts. Lnk associates with activated MPLWT and MPLW515L and colocalizes with the receptors at the plasma membrane. The SH2 domain of Lnk is essential for its binding and for its down-regulation of MPLWT and MPLW515L. Lnk itself is tyrosine-phosphorylated following thrombopoietin stimulation. Further elucidating the cellular pathways that attenuate MPLW515L will provide insight into the pathogenesis of MPD and could help develop specific therapeutic approaches.

Metabolism of choline in brain of the aged CBF-1 mouse

International Nuclear Information System (INIS)

Saito, M.; Kindel, G.; Karczmar, A.G.; Rosenberg, A.

1986-01-01

In order to quantify the changes that occur in the cholinergic central nervous system with aging, we have compared acetylcholine (Ach) formation in brain cortex slice preparations from 2-year-old aged CBF-1 mouse brains and compared the findings with those in 2-4-month-old young adult mouse brain slices. Incorporation of exogenous radioactively labelled choline (31 nM [ 3 H] choline) into acetyl choline in incubated brain slices was linear with time for 90 min. Percentage of total choline label distributed into Ach remained constant from 5 min after starting the incubation to 90 min. In contrast, distribution of label into intracellular free choline (Ch) and phosphorylcholine (Pch) changed continuously over this period suggesting that the Ch pool for Ach synthesis in brain cortex is different from that for Pch synthesis. Incorporation of radioactivity into Ach was not influenced by administration of 10 microM eserine, showing that the increment of radioactivity in Ach reflects rate of Ach formation, independently from degradation by acetylcholine esterases. Under our experimental conditions, slices from cortices of aged 24-month-old mouse brain showed a significantly greater (27%) incorporation of radioactivity into intracellular Ach than those from young, 2-4-month-old, brain cortices. Inhibitors of Ach release, 1 mM ATP or GABA, had no effect. Since concentration of radioactive precursor in the incubation medium was very low (31 nM), the Ch pool for Ach synthesis in slices was labelled without measurably changing the size of the endogenous pool. These data suggest a compensatory acceleration of Ach synthesis or else a smaller precursor pool specific for Ach synthesis into which labelled Ch migrated in aged brain

Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis.

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Shu, Kai; Qi, Ying; Chen, Feng; Meng, Yongjie; Luo, Xiaofeng; Shuai, Haiwei; Zhou, Wenguan; Ding, Jun; Du, Junbo; Liu, Jiang; Yang, Feng; Wang, Qiang; Liu, Weiguo; Yong, Taiwen; Wang, Xiaochun; Feng, Yuqi; Yang, Wenyu

2017-01-01

Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA) while positively mediating abscisic acid (ABA) biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN), an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde) level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA 1 , GA 3 , and GA 4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA 1 /ABA, GA 3 /ABA, and GA 4 /ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis

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Kai Shu

2017-08-01

Full Text Available Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA while positively mediating abscisic acid (ABA biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN, an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA1, GA3, and GA4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA1/ABA, GA3/ABA, and GA4/ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

The role of emotion regulation in situational empathy-related responding and prosocial behaviour in the presence of negative affect.

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Hein, Sascha; Röder, Mandy; Fingerle, Michael

2016-12-15

Empathy and prosocial behaviour are crucial factors for children's positive social adjustment. Contemporary models of empathy highlight the capacity to regulate vicariously experienced emotions as a precursor to empathy-related responses (e.g., prosocial behaviour). The goal of this study was to examine the role of emotion regulation (ER) in situational empathy-related responding and prosocial behaviour. A sample of 157 children (76 boys and 81 girls; M age = 9.94 years) participated in a two-tiered interview procedure that utilised vignettes to assess empathy and prosocial behaviour. Between both phases of the interview, a negative affect was induced to investigate the influence of ER on the change between the two phases. Results from a latent change model showed that ER strategies positively predicted change scores, that is, children with higher abilities to regulate emotions showed a higher increase in empathy and prosocial behaviour. Implications for the promotion of social-emotional learning in school are discussed. © 2016 International Union of Psychological Science.

Reduction of cerebral blood flow in subclinical hepatic encephalopathy and its correlation with plasma-free tryptophan

International Nuclear Information System (INIS)

Rodriguez, G.; Testa, R.; Celle, G.; Gris, A.; Marenco, S.; Nobili, F.; Novellone, G.; Rosadini, G.

1987-01-01

Cerebral blood flow (CBF), measured by the noninvasive xenon-133 inhalation method, EEG, and plasma levels of ammonia (NH 3 ) and free tryptophan were determined in 18 hospitalized cirrhotic patients affected with subclinical hepatic encephalopathy, as diagnosed by the Kurtz test. CBF results were significantly lower (p less than 0.001) in the patients' group as compared with a sex- and age-matched normal control population, although seven patients had values in the normal range. NH 3 was increased only in six, while free tryptophan was increased in all but two patients. A significant negative correlation (p = 0.02) between CBF and free tryptophan was found, even though it appears to be difficult to interpret. We suggest that CBF impairment in some cirrhotic patients with subclinical hepatic encephalopathy may be related to the systemic metabolic derangement caused by the liver disease; free tryptophan could have some implication in producing CBF reduction

A negative regulation loop of long noncoding RNA HOTAIR and p53 in non-small-cell lung cancer

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Zhai N

2016-09-01

Full Text Available Nailiang Zhai,1 Yongfu Xia,1 Rui Yin,2 Jinping Liu,3 Fuquan Gao1 1Department of Respiratory Medicine, Affiliated Hospital of Binzhou Medical University, 2Department of Respiratory Medicine, People’s Hospital of Binzhou City, 3Department of Pharmacology, Binzhou Medical University, Binzhou, Shandong, People’s Republic of China Abstract: Non-small-cell lung cancer (NSCLC is one of the leading causes of cancer-related death worldwide, and the 5-year survival rate is still low despite advances in diagnosis and therapeutics. A long noncoding RNA (lncRNA HOX antisense intergenic RNA (HOTAIR has been revealed to play important roles in NSCLC carcinogenesis but the detailed mechanisms are still unclear. In the current study, we aimed to investigate the regulation between the lncRNA HOTAIR and p53 in the NSCLC patient samples and cell lines. Our results showed that HOTAIR expression was significantly higher in the cancer tissues than that in the adjacent normal tissue, and was negatively correlated with p53 functionality rather than expression. When p53 was overexpressed in A549 cells, the lncRNA HOTAIR expression was downregulated, and the cell proliferation rate and cell invasion capacity decreased as a consequence. We identified two binding sites of p53 on the promoter region of HOTAIR, where the p53 protein would bind to and suppress the HOTAIR mRNA transcription. Inversely, overexpression of lncRNA HOTAIR inhibited the expression of p53 in A549 cells. Mechanistic studies revealed that HOTAIR modified the promoter of p53 and enhanced histone H3 lysine 27 trimethylation (H3K27me3. These studies identified a specific negative regulation loop of lncRNA HOTAIR and p53 in NSCLC cells, which revealed a new understanding of tumorigenesis in p53 dysfunction NSCLC cells. Keywords: NSCLC, LncRNA HOTAIR, p53, negative loop

Cerebral Blood Flow during Rest Associates with General Intelligence and Creativity

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Takeuchi, Hikaru; Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Nagase, Tomomi; Nouchi, Rui; Kawashima, Ryuta

2011-01-01

Recently, much scientific attention has been focused on resting brain activity and its investigation through such methods as the analysis of functional connectivity during rest (the temporal correlation of brain activities in different regions). However, investigation of the magnitude of brain activity during rest has focused on the relative decrease of brain activity during a task, rather than on the absolute resting brain activity. It is thus necessary to investigate the association between cognitive factors and measures of absolute resting brain activity, such as cerebral blood flow (CBF), during rest (rest-CBF). In this study, we examined this association using multiple regression analyses. Rest-CBF was the dependent variable and the independent variables included two essential components of cognitive functions, psychometric general intelligence and creativity. CBF was measured using arterial spin labeling and there were three analyses for rest-CBF; namely mean gray matter rest-CBF, mean white matter rest-CBF, and regional rest-CBF. The results showed that mean gray and white matter rest-CBF were significantly and positively correlated with individual psychometric intelligence. Furthermore, mean white matter rest-CBF was significantly and positively correlated with creativity. After correcting the effect of mean gray matter rest-CBF the significant and positive correlation between regional rest-CBF in the perisylvian anatomical cluster that includes the left superior temporal gyrus and insula and individual psychometric intelligence was found. Also, regional rest-CBF in the precuneus was significantly and negatively correlated with individual creativity. Significance of these results of regional rest-CBF did not change when the effect of regional gray matter density was corrected. The findings showed mean and regional rest-CBF in healthy young subjects to be correlated with cognitive functions. The findings also suggest that, even in young cognitively intact

A Novel TetR Family Transcriptional Regulator, CalR3, Negatively Controls Calcimycin Biosynthesis in Streptomyces chartreusis NRRL 3882

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Lixia Gou

2017-11-01

Full Text Available Calcimycin is a unique ionophoric antibiotic that is widely used in biochemical and pharmaceutical applications, but the genetic basis underlying the regulatory mechanisms of calcimycin biosynthesis are unclear. Here, we identified the calR3 gene, which encodes a novel TetR family transcriptional regulator and exerts a negative effect on calcimycin biosynthesis. Disruption of calR3 in Streptomyces chartreusis NRRL 3882 led to significantly increased calcimycin and its intermediate cezomycin. Gene expression analysis showed that the transcription of calR3 and its adjacent calT gene were dramatically enhanced (30- and 171-fold, respectively in GLX26 (ΔcalR3 mutants compared with the wild-type strains. Two CalR3-binding sites within the bidirectional calR3-calT promoter region were identified using a DNase I footprinting assay, indicating that CalR3 directly repressed the transcription of its own gene and the calT gene. In vitro electrophoretic mobility shift assays suggested that both calcimycin and cezomycin can act as CalR3 ligands to induce CalR3 to dissociate from its binding sites. These findings indicate negative feedback for the regulation of CalR3 in calcimycin biosynthesis and suggest that calcimycin production can be improved by manipulating its biosynthetic machinery.

Enhanced Mucosal Defense and Reduced Tumor Burden in Mice with the Compromised Negative Regulator IRAK-M

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Daniel E. Rothschild

2017-02-01

Full Text Available Aberrant inflammation is a hallmark of inflammatory bowel disease (IBD and colorectal cancer. IRAK-M is a critical negative regulator of TLR signaling and overzealous inflammation. Here we utilize data from human studies and Irak-m−/− mice to elucidate the role of IRAK-M in the modulation of gastrointestinal immune system homeostasis. In human patients, IRAK-M expression is up-regulated during IBD and colorectal cancer. Further functional studies in mice revealed that Irak-m−/− animals are protected against colitis and colitis associated tumorigenesis. Mechanistically, our data revealed that the gastrointestinal immune system of Irak-m−/− mice is highly efficient at eliminating microbial translocation following epithelial barrier damage. This attenuation of pathogenesis is associated with expanded areas of gastrointestinal associated lymphoid tissue (GALT, increased neutrophil migration, and enhanced T-cell recruitment. Further evaluation of Irak-m−/− mice revealed a splice variant that robustly activates NF-κB signaling. Together, these data identify IRAK-M as a potential target for future therapeutic intervention.

SIRT6 Acts as a Negative Regulator in Dengue Virus-Induced Inflammatory Response by Targeting the DNA Binding Domain of NF-κB p65

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Pengcheng Li

2018-04-01

Full Text Available Dengue virus (DENV is a mosquito-borne single-stranded RNA virus causing human disease with variable severity. The production of massive inflammatory cytokines in dengue patients has been associated with dengue disease severity. However, the regulation of these inflammatory responses remains unclear. In this study, we report that SIRT6 is a negative regulator of innate immune responses during DENV infection. Silencing of Sirt6 enhances DENV-induced proinflammatory cytokine and chemokine production. Overexpression of SIRT6 inhibits RIG-I-like receptor (RLR and Toll-like receptor 3 (TLR3 mediated NF-κB activation. The sirtuin core domain of SIRT6 is required for the inhibition of NF-κB p65 function. SIRT6 interacts with the DNA binding domain of p65 and competes with p65 to occupy the Il6 promoter during DENV infection. Collectively, our study demonstrates that SIRT6 negatively regulates DENV-induced inflammatory response via RLR and TLR3 signaling pathways.

Impaired down-regulation of negative emotion in self-referent social situations in bipolar disorder: A pilot study of a novel experimental paradigm.

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Kjærstad, Hanne L; Vinberg, Maj; Goldin, Philippe R; Køster, Nicolai; Støttrup, Mette Marie D; Knorr, Ulla; Kessing, Lars V; Miskowiak, Kamilla W

2016-04-30

Emotion dysregulation is a core feature of bipolar disorder (BD) that persists into periods of remission. Neuroimaging studies show aberrant neural responses during emotion regulation (ER) in patients with BD relative to healthy controls, but behavioural evidence for ER deficits is sparse and conflicting. This study aimed to explore ER in BD using a novel, personally relevant experimental paradigm. Twenty patients with BD and 20 patients with unipolar disorder (UD), in full or partial remission, and 20 healthy controls were given a novel computerised test. Participants were instructed to react naturally or dampen their emotional response to positive and negative social scenarios and associated self-beliefs. They were also given an established experimental task for comparison, involving reappraisal of negative affective picture stimuli, as well as a questionnaire of habitual ER strategies. BD patients showed reduced ability to down-regulate emotional responses in negative, but not positive, social scenarios relative to healthy controls and UD patients. In contrast, there were no between-group differences in the established ER task or in self-reported habitual reappraisal strategies. Findings highlight the novel social scenario paradigm as a sensitive test for detection of ER difficulties in BD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gibberellin Application at Pre-Bloom in Grapevines Down-Regulates the Expressions of VvIAA9 and VvARF7, Negative Regulators of Fruit Set Initiation, during Parthenocarpic Fruit Development

Science.gov (United States)

Jung, Chan Jin; Hur, Youn Young; Yu, Hee-Ju; Noh, Jung-Ho; Park, Kyo-Sun; Lee, Hee Jae

2014-01-01

Fruit set is initiated only after fertilization and is tightly regulated primarily by gibberellins (GAs) and auxins. The application of either of these hormones induces parthenocarpy, fruit set without fertilization, but the molecular mechanism underlying this induction is poorly understood. In the present study, we have shown that the parthenocarpic fruits induced by GA application at pre-bloom result from the interaction of GA with auxin signaling. The transcriptional levels of the putative negative regulators of fruit set initiation, including Vitis auxin/indole-3-acetic acid transcription factor 9 (VvIAA9), Vitis auxin response factor 7 (VvARF7), and VvARF8 were monitored during inflorescence development in seeded diploid ‘Tamnara’ grapevines with or without GA application. Without GA application, VvIAA9, VvARF7, and VvARF8 were expressed at a relatively high level before full bloom, but decreased thereafter following pollination. After GA application at 14 days before full bloom (DBF); however, the expression levels of VvIAA9 and VvARF7 declined at 5 DBF prior to pollination. The effects of GA application on auxin levels or auxin signaling were also analyzed by monitoring the expression patterns of auxin biosynthesis genes and auxin-responsive genes with or without GA application. Transcription levels of the auxin biosynthesis genes Vitis anthranilate synthase β subunit (VvASB1-like), Vitis YUCCA2 (VvYUC2), and VvYUC6 were not significantly changed by GA application. However, the expressions of Vitis Gretchen Hagen3.2 (VvGH3.2) and VvGH3.3, auxin-responsive genes, were up-regulated from 2 DBF to full bloom with GA application. Furthermore, the Vitis GA signaling gene, VvDELLA was up-regulated by GA application during 12 DBF to 7 DBF, prior to down-regulation of VvIAA9 and VvARF7. These results suggest that VvIAA9 and VvARF7 are negative regulators of fruit set initiation in grapevines, and GA signaling is integrated with auxin signaling via VvDELLA during

An Arabidopsis SUMO E3 Ligase, SIZ1, Negatively Regulates Photomorphogenesis by Promoting COP1 Activity

KAUST Repository

Lin, Xiao-Li; Niu, De; Hu, Zi-Liang; Kim, Dae Heon; Jin, Yin Hua; Cai, Bin; Liu, Peng; Miura, Kenji; Yun, Dae-Jin; Kim, Woe-Yeon; Lin, Rongcheng; Jin, Jing Bo

2016-01-01

COP1 (CONSTITUTIVE PHOTOMORPHOGENIC 1), a ubiquitin E3 ligase, is a central negative regulator of photomorphogenesis. However, how COP1 activity is regulated by post-translational modifications remains largely unknown. Here we show that SUMO (small ubiquitin-like modifier) modification enhances COP1 activity. Loss-of-function siz1 mutant seedlings exhibit a weak constitutive photomorphogenic phenotype. SIZ1 physically interacts with COP1 and mediates the sumoylation of COP1. A K193R substitution in COP1 blocks its SUMO modification and reduces COP1 activity in vitro and in planta. Consistently, COP1 activity is reduced in siz1 and the level of HY5, a COP1 target protein, is increased in siz1. Sumoylated COP1 may exhibits higher transubiquitination activity than does non-sumoylated COP1, but SIZ1-mediated SUMO modification does not affect COP1 dimerization, COP1-HY5 interaction, and nuclear accumulation of COP1. Interestingly, prolonged light exposure reduces the sumoylation level of COP1, and COP1 mediates the ubiquitination and degradation of SIZ1. These regulatory mechanisms may maintain the homeostasis of COP1 activity, ensuing proper photomorphogenic development in changing light environment. Our genetic and biochemical studies identify a function for SIZ1 in photomorphogenesis and reveal a novel SUMO-regulated ubiquitin ligase, COP1, in plants.

An Arabidopsis SUMO E3 Ligase, SIZ1, Negatively Regulates Photomorphogenesis by Promoting COP1 Activity

KAUST Repository

Lin, Xiao-Li

2016-04-29

COP1 (CONSTITUTIVE PHOTOMORPHOGENIC 1), a ubiquitin E3 ligase, is a central negative regulator of photomorphogenesis. However, how COP1 activity is regulated by post-translational modifications remains largely unknown. Here we show that SUMO (small ubiquitin-like modifier) modification enhances COP1 activity. Loss-of-function siz1 mutant seedlings exhibit a weak constitutive photomorphogenic phenotype. SIZ1 physically interacts with COP1 and mediates the sumoylation of COP1. A K193R substitution in COP1 blocks its SUMO modification and reduces COP1 activity in vitro and in planta. Consistently, COP1 activity is reduced in siz1 and the level of HY5, a COP1 target protein, is increased in siz1. Sumoylated COP1 may exhibits higher transubiquitination activity than does non-sumoylated COP1, but SIZ1-mediated SUMO modification does not affect COP1 dimerization, COP1-HY5 interaction, and nuclear accumulation of COP1. Interestingly, prolonged light exposure reduces the sumoylation level of COP1, and COP1 mediates the ubiquitination and degradation of SIZ1. These regulatory mechanisms may maintain the homeostasis of COP1 activity, ensuing proper photomorphogenic development in changing light environment. Our genetic and biochemical studies identify a function for SIZ1 in photomorphogenesis and reveal a novel SUMO-regulated ubiquitin ligase, COP1, in plants.

Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes.

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Li, Xian; Lee, Youn Ju; Jin, Fansi; Park, Young Na; Deng, Yifeng; Kang, Youra; Yang, Ju Hye; Chang, Jae-Hoon; Kim, Dong-Young; Kim, Jung-Ae; Chang, Young-Chae; Ko, Hyun-Jeong; Kim, Cheorl-Ho; Murakami, Makoto; Chang, Hyeun Wook

2017-07-25

Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo. Sirt1 inhibition of FcεRI signaling also involved an alternative component, PTP1B, which attenuated the inhibitory AMPK pathway and conversely enhanced the stimulatory Syk pathway, uncovering a novel role of this phosphatase. Moreover, a Sirt1 activator resveratrol stimulated the inhibitory AMPK axis, with reciprocal suppression of the stimulatory PTP1B/Syk axis, thus potently inhibiting anaphylaxis. Overall, our results provide a molecular explanation for the beneficial role of Sirt1 in allergy and underscore a potential application of Sirt1 activators as a new class of anti-allergic agents.

SNT-2 interacts with ERK2 and negatively regulates ERK2 signaling in response to EGF stimulation

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Huang Lin; Gotoh, Noriko; Zhang Shengliang; Shibuya, Masabumi; Yamamoto, Tadashi; Tsuchida, Nobuo

2004-01-01

The control of cellular responses with fibroblast growth factors and neurotrophins is mediated through membrane-linked docking proteins, SNT (suc1-binding neurotrophic target)-1/FRS2α and SNT-2/FRS2β. ERK1/2 are members of the mitogen-activated protein kinase family that regulate diverse cellular activities in response to various stimuli. Here, we demonstrate that SNT-2 does not become tyrosine phosphorylated significantly in response to EGF but forms a complex with ERK2 via the region of 186-252 amino acid residues, and the complex formation is enhanced upon EGF stimulation. SNT-2 downregulates ERK2 phosphorylation, suppresses and delays ERK2 nuclear accumulation which occurs following EGF stimulation. In contrast, the mutant SNT-2 which carries deletion of 186-252 amino acids and lacks ERK2 binding does not have these effects. These observations suggest that SNT-2 negatively regulates ERK2 signaling activated via EGF stimulation through direct binding to ERK2

Tomato NAC transcription factor SlSRN1 positively regulates defense response against biotic stress but negatively regulates abiotic stress response.

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Bo Liu

Full Text Available Biotic and abiotic stresses are major unfavorable factors that affect crop productivity worldwide. NAC proteins comprise a large family of transcription factors that play important roles in plant growth and development as well as in responses to biotic and abiotic stresses. In a virus-induced gene silencing-based screening to identify genes that are involved in defense response against Botrytis cinerea, we identified a tomato NAC gene SlSRN1 (Solanum lycopersicum Stress-related NAC1. SlSRN1 is a plasma membrane-localized protein with transactivation activity in yeast. Expression of SlSRN1 was significantly induced by infection with B. cinerea or Pseudomonas syringae pv. tomato (Pst DC3000, leading to 6-8 folds higher than that in the mock-inoculated plants. Expression of SlSRN1 was also induced by salicylic acid, jasmonic acid and 1-amino cyclopropane-1-carboxylic acid and by drought stress. Silencing of SlSRN1 resulted in increased severity of diseases caused by B. cinerea and Pst DC3000. However, silencing of SlSRN1 resulted in increased tolerance against oxidative and drought stresses. Furthermore, silencing of SlSRN1 accelerated accumulation of reactive oxygen species but attenuated expression of defense genes after infection by B. cinerea. Our results demonstrate that SlSRN1 is a positive regulator of defense response against B. cinerea and Pst DC3000 but is a negative regulator for oxidative and drought stress response in tomato.

Neurovascular-neuroenergetic coupling axis in the brain: master regulation by nitric oxide and consequences in aging and neurodegeneration.

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Lourenço, Cátia F; Ledo, Ana; Barbosa, Rui M; Laranjinha, João

2017-07-01

The strict energetic demands of the brain require that nutrient supply and usage be fine-tuned in accordance with the specific temporal and spatial patterns of ever-changing levels of neuronal activity. This is achieved by adjusting local cerebral blood flow (CBF) as a function of activity level - neurovascular coupling - and by changing how energy substrates are metabolized and shuttled amongst astrocytes and neurons - neuroenergetic coupling. Both activity-dependent increase of CBF and O 2 and glucose utilization by active neural cells are inextricably linked, establishing a functional metabolic axis in the brain, the neurovascular-neuroenergetic coupling axis. This axis incorporates and links previously independent processes that need to be coordinated in the normal brain. We here review evidence supporting the role of neuronal-derived nitric oxide ( • NO) as the master regulator of this axis. Nitric oxide is produced in tight association with glutamatergic activation and, diffusing several cell diameters, may interact with different molecular targets within each cell type. Hemeproteins such as soluble guanylate cyclase, cytochrome c oxidase and hemoglobin, with which • NO reacts at relatively fast rates, are but a few of the key in determinants of the regulatory role of • NO in the neurovascular-neuroenergetic coupling axis. Accordingly, critical literature supporting this concept is discussed. Moreover, in view of the controversy regarding the regulation of catabolism of different neural cells, we further discuss key aspects of the pathways through which • NO specifically up-regulates glycolysis in astrocytes, supporting lactate shuttling to neurons for oxidative breakdown. From a biomedical viewpoint, derailment of neurovascular-neuroenergetic axis is precociously linked to aberrant brain aging, cognitive impairment and neurodegeneration. Thus, we summarize current knowledge of how both neurovascular and neuroenergetic coupling are compromised in

Suppressor of Overexpression of CO 1 Negatively Regulates Dark-Induced Leaf Degreening and Senescence by Directly Repressing Pheophytinase and Other Senescence-Associated Genes in Arabidopsis.

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Chen, Junyi; Zhu, Xiaoyu; Ren, Jun; Qiu, Kai; Li, Zhongpeng; Xie, Zuokun; Gao, Jiong; Zhou, Xin; Kuai, Benke

2017-03-01

Although the biochemical pathway of chlorophyll (Chl) degradation has been largely elucidated, how Chl is rapidly yet coordinately degraded during leaf senescence remains elusive. Pheophytinase (PPH) is the enzyme for catalyzing the removal of the phytol group from pheophytin a , and PPH expression is significantly induced during leaf senescence. To elucidate the transcriptional regulation of PPH , we used a yeast ( Saccharomyces cerevisiae ) one-hybrid system to screen for its trans-regulators. SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1), a key flowering pathway integrator, was initially identified as one of the putative trans-regulators of PPH After dark treatment, leaves of an SOC1 knockdown mutant ( soc1-6 ) showed an accelerated yellowing phenotype, whereas those of SOC1 -overexpressing lines exhibited a partial stay-green phenotype. SOC1 and PPH expression showed a negative correlation during leaf senescence. Substantially, SOC1 protein could bind specifically to the CArG box of the PPH promoter in vitro and in vivo, and overexpression of SOC1 significantly inhibited the transcriptional activity of the PPH promoter in Arabidopsis ( Arabidopsis thaliana ) protoplasts. Importantly, soc1-6 pph-1 (a PPH knockout mutant) double mutant displayed a stay-green phenotype similar to that of pph-1 during dark treatment. These results demonstrated that SOC1 inhibits Chl degradation via negatively regulating PPH expression. In addition, measurement of the Chl content and the maximum photochemical efficiency of photosystem II of soc1-6 and SOC1-OE leaves after dark treatment suggested that SOC1 also negatively regulates the general senescence process. Seven SENESCENCE-ASSOCIATED GENES ( SAGs ) were thereafter identified as its potential target genes, and NONYELLOWING1 and SAG113 were experimentally confirmed. Together, we reveal that SOC1 represses dark-induced leaf Chl degradation and senescence in general in Arabidopsis. © 2017 American Society of Plant Biologists. All

The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.

Science.gov (United States)

Zhang, Yiguo; Qiu, Lu; Li, Shaojun; Xiang, Yuancai; Chen, Jiayu; Ren, Yonggang

2014-01-01

The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.

A negative regulator encoded by a rice WRKY gene represses both abscisic acid and gibberellins signaling in aleurone cells.

Science.gov (United States)

Zhang, Zhong-Lin; Shin, Margaret; Zou, Xiaolu; Huang, Jianzhi; Ho, Tun-hua David; Shen, Qingxi J

2009-05-01

Abscisic acid (ABA) and gibberellins (GAs) control several developmental processes including seed maturation, dormancy, and germination. The antagonism of these two hormones is well-documented. However, recent data from transcription profiling studies indicate that they can function as agonists in regulating the expression of many genes although the underlying mechanism is unclear. Here we report a rice WRKY gene, OsWRKY24, which encodes a protein that functions as a negative regulator of both GA and ABA signaling. Overexpression of OsWRKY24 via particle bombardment-mediated transient expression in aleurone cells represses the expression of two reporter constructs: the beta-glucuronidase gene driven by the GA-inducible Amy32b alpha-amylase promoter (Amy32b-GUS) and the ABA-inducible HVA22 promoter (HVA22-GUS). OsWRKY24 is unlikely a general repressor because it has little effect on the expression of the luciferase reporter gene driven by a constitutive ubiquitin promoter (UBI-Luciferase). As to the GA signaling, OsWRKY24 differs from OsWRKY51 and -71, two negative regulators specifically function in the GA signaling pathway, in several ways. First, OsWRKY24 contains two WRKY domains while OsWRKY51 and -71 have only one; both WRKY domains are essential for the full repressing activity of OsWRKY24. Second, binding of OsWRKY24 to the Amy32b promoter appears to involve sequences in addition to the TGAC cores of the W-boxes. Third, unlike OsWRKY71, OsWRKY24 is stable upon GA treatment. Together, these data demonstrate that OsWRKY24 is a novel type of transcriptional repressor that inhibits both GA and ABA signaling.

Regional cerebral blood flow in schizophrenia

International Nuclear Information System (INIS)

Kanoh, Masayuki

1989-01-01

Regional cerebral blood flow (rCBF) was measured at rest using the 133 Xe inhalation technique in 40 DSM-III-diagnosed schizophrenics (22 males, 18 females: mean age 35.0 years, range 20-49 years) and 31 age-and sex-matched normal controls (16 males, 15 females: mean age 34.3 years, range 21-49 years). The absolute value (AV) and the percent value (PV) of the rCBF in schizophrenics were compared with those in controls. Correlations between rCBF and the Brief Psychiatric Rating Scale (BPRS) scores or the performance of Wisconsin Card Sorting Test (WCST) were examined in schizophrenics. Schizophrenics showed significantly lower AVs in all brain regions examined and a significantly lower PV in the left superior frontal region than controls. The hyperfrontal rCBF distribution which was found in both hemispheres in controls, was absent in the left hemisphere in schizophrenics. In schizophrenics, superior frontal blood flows were significantly negatively correlated with the negative symptom scores of the BPRS but not with the total scores and the positive symptom scores of the BPRS. In schizophrenics, inferior frontal blood flows were significantly correlated with the number of sorting categories achieved. These results indicate that rCBF in schizophrenia is reduced in the whole brain and especially in the left superior frontal region. These findings suggest a frontal lobe dysfunction in schizophrenia. (author)

First Episode Schizophrenia Regional Cerebral Blood Flow Assessment after Atypical Antipsychotics

International Nuclear Information System (INIS)

Rimbu, A.; Mititelu, R.; Marinescu, G.; Ghita, S.; Mazilu, C.; Codorean, I.; Gheorghe, M.

2006-01-01

Full text: Aim: Since regional cerebral blood flow (rCBF) findings in schizophrenic patients are inconsistent, the aim of our study was to evaluate and compare rCBF in the first episode of schizophrenia, before and after atypical antipsychotic treatment. Method: 21 patients who met criteria for schizophrenia were assessed PANSS score and tomographic brain perfusion (SPECT). The treatment was administered for 10-12 weeks and the dose was 4.8mg/day Risperidone, 11.6mg/day Olanzepine, 440mg/day Quetiapine. After finishing treatment all patients underwent a control SPECT study. Results: PANSS scores revealed two groups: group A-14 patients with predominant positive symptoms; 9 received Olanzapine and 5 Quetiapine. In group B -7 patients with predominant negative symptoms received Risperidone. Positive symptoms were associated with hypoperfusion in posterior parietal regions and superior temporal gyrus, bilaterally; for negative symptoms we found hypoperfusion in prefrontal cortex, predominantly in left side and a hyper perfusion in left basal ganglia. All patients that received atypical antipsychotic drugs had clinical improvement and decreases in PANSS scores; the control SPECT analysis revealed the same cortical changes as first studies in 15 patients and an increase of the rCBF in frontal lobes for 4 patients. 14 patients we noticed an increased rCBF at subcortical level, especially in left caudate nuclei. Conclusions: We found nonspecific features of rCBF in patients with first episode of schizophrenia, suggesting a perfusion dynamic balance rather than a fixed model. Those aspects are much more related to clinical symptoms, than to the therapeutical response. The rCBF changes in subcortical level after treatment (64.4% increase of rCBF; 35.6% not modified), can have a good prognostic value for therapeutic response. (author)

A limitation of the split-dose method for evaluating rCBF changes using {sup 99m}Tc-ECD and SPECT

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Odano, Ikuo; Takahashi, Makoto; Noguchi, Eikichi; Ohtaki, Hiro; Shibaki, Mitsurou; Kasahara, Tosifumi; Hatano, Masayoshi [Niigata Univ. (Japan). School of Medicine; Ohkubo, Masaki

1997-05-01

The purpose of the study is to validate the split-dose method corrected with dose ratio of {sup 99m}Tc-ECD for brain perfusion scan. A dose of 600 MBq of {sup 99m}Tc-ECD was divided into two with various dose ratios from 1 : 1 to 1 : 4, and injected to eleven patients with various cerebral diseases. A lesser dose of {sup 99m}Tc-ECD was injected under a control state for the first SPECT scan, and 15 min SPECT scan was performed 10 min after injection with a triple-head high resolution gamma camera. After the scan, the other dose of {sup 99m}Tc-ECD was injected under the same control state and the second SPECT scan was performed as same as above. A ratio of the activity of the first scan to the net activity of the second scan corrected by dose ratio, defined as K, was measured in brain regions of each subject. Expected value of K was 1, but the value was distributed with large variations in each subject. The mean % error of the K value was 10.4{+-}4.9%. Hence it is considered that activity changes by more than 20% from the control values should be required to detect a significant rCBF change in an activation SPECT study. Then, we proposed a new method in which the activity of both two SPECT scans was normalized by cerebellar or occipital activity and compared. The ratio obtained by the proposed method came closer to 1 with less variations and with less mean % error in comparison with those of K value obtained by the dose-correction method. Although the proposed method has a limitation in the use of an activation study loaded with Diamox, it may be useful to evaluate an alteration of rCBF in the study such as postural testing or finger-moving test. (author)

Phytochrome-interacting factors PIF4 and PIF5 negatively regulate anthocyanin biosynthesis under red light in Arabidopsis seedlings.

Science.gov (United States)

Liu, Zhongjuan; Zhang, Yongqiang; Wang, Jianfeng; Li, Ping; Zhao, Chengzhou; Chen, Yadi; Bi, Yurong

2015-09-01

Light is an important environmental factor inducing anthocyanin accumulation in plants. Phytochrome-interacting factors (PIFs) have been shown to be a family of bHLH transcription factors involved in light signaling in Arabidopsis. Red light effectively increased anthocyanin accumulation in wild-type Col-0, whereas the effects were enhanced in pif4 and pif5 mutants but impaired in overexpression lines PIF4OX and PIF5OX, indicating that PIF4 and PIF5 are both negative regulators for red light-induced anthocyanin accumulation. Consistently, transcript levels of several genes involved in anthocyanin biosynthesis and regulatory pathway, including CHS, F3'H, DFR, LDOX, PAP1 and TT8, were significantly enhanced in mutants pif4 and pif5 but decreased in PIF4OX and PIF5OX compared to in Col-0, indicating that PIF4 and PIF5 are transcriptional repressor of these gene. Transient expression assays revealed that PIF4 and PIF5 could repress red light-induced promoter activities of F3'H and DFR in Arabidopsis protoplasts. Furthermore, chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) test and electrophoretic mobility shift assay (EMSA) showed that PIF5 could directly bind to G-box motifs present in the promoter of DFR. Taken together, these results suggest that PIF4 and PIF5 negatively regulate red light-induced anthocyanin accumulation through transcriptional repression of the anthocyanin biosynthetic genes in Arabidopsis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Smart conjugated polymer nanocarrier for healthy weight loss by negative feedback regulation of lipase activity

Science.gov (United States)

Chen, Yu-Lei; Zhu, Sha; Zhang, Lei; Feng, Pei-Jian; Yao, Xi-Kuang; Qian, Cheng-Gen; Zhang, Can; Jiang, Xi-Qun; Shen, Qun-Dong

2016-02-01

Healthy weight loss represents a real challenge when obesity is increasing in prevalence. Herein, we report a conjugated polymer nanocarrier for smart deactivation of lipase and thus balancing calorie intake. After oral administration, the nanocarrier is sensitive to lipase in the digestive tract and releases orlistat, which deactivates the enzyme and inhibits fat digestion. It also creates negative feedback to control the release of itself. The nanocarrier smartly regulates activity of the lipase cyclically varied between high and low levels. In spite of high fat diet intervention, obese mice receiving a single dose of the nanocarrier lose weight over eight days, whereas a control group continues the tendency to gain weight. Daily intragastric administration of the nanocarrier leads to lower weight of livers or fat pads, smaller adipocyte size, and lower total cholesterol level than that of the control group. Near-infrared fluorescence of the nanocarrier reveals its biodistribution.Healthy weight loss represents a real challenge when obesity is increasing in prevalence. Herein, we report a conjugated polymer nanocarrier for smart deactivation of lipase and thus balancing calorie intake. After oral administration, the nanocarrier is sensitive to lipase in the digestive tract and releases orlistat, which deactivates the enzyme and inhibits fat digestion. It also creates negative feedback to control the release of itself. The nanocarrier smartly regulates activity of the lipase cyclically varied between high and low levels. In spite of high fat diet intervention, obese mice receiving a single dose of the nanocarrier lose weight over eight days, whereas a control group continues the tendency to gain weight. Daily intragastric administration of the nanocarrier leads to lower weight of livers or fat pads, smaller adipocyte size, and lower total cholesterol level than that of the control group. Near-infrared fluorescence of the nanocarrier reveals its biodistribution

47 CFR 76.981 - Negative option billing.

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2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Negative option billing. 76.981 Section 76.981 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Rate Regulation § 76.981 Negative option billing. (a) A cable operator...

Neural predictors of emotional inertia in daily life.

Science.gov (United States)

Waugh, Christian E; Shing, Elaine Z; Avery, Bradley M; Jung, Youngkyoo; Whitlow, Christopher T; Maldjian, Joseph A

2017-09-01

Assessing emotional dynamics in the brain offers insight into the fundamental neural and psychological mechanisms underlying emotion. One such dynamic is emotional inertia-the influence of one's emotional state at one time point on one's emotional state at a subsequent time point. Emotion inertia reflects emotional rigidity and poor emotion regulation as evidenced by its relationship to depression and neuroticism. In this study, we assessed changes in cerebral blood flow (CBF) from before to after an emotional task and used these changes to predict stress, positive and negative emotional inertia in daily life events. Cerebral blood flow changes in the lateral prefrontal cortex (lPFC) predicted decreased non-specific emotional inertia, suggesting that the lPFC may feature a general inhibitory mechanism responsible for limiting the impact that an emotional state from one event has on the emotional state of a subsequent event. CBF changes in the ventromedial prefrontal cortex and lateral occipital cortex were associated with positive emotional inertia and negative/stress inertia, respectively. These data advance the blossoming literature on the temporal dynamics of emotion in the brain and on the use of neural indices to predict mental health-relevant behavior in daily life. © The Author (2017). Published by Oxford University Press.

The effects of superimposed tilt and lower body negative pressure on anterior and posterior cerebral circulations.

Science.gov (United States)

Tymko, Michael M; Rickards, Caroline A; Skow, Rachel J; Ingram-Cotton, Nathan C; Howatt, Michael K; Day, Trevor A

2016-09-01

Steady-state tilt has no effect on cerebrovascular reactivity to increases in the partial pressure of end-tidal carbon dioxide (PETCO2). However, the anterior and posterior cerebral circulations may respond differently to a variety of stimuli that alter central blood volume, including lower body negative pressure (LBNP). Little is known about the superimposed effects of head-up tilt (HUT; decreased central blood volume and intracranial pressure) and head-down tilt (HDT; increased central blood volume and intracranial pressure), and LBNP on cerebral blood flow (CBF) responses. We hypothesized that (a) cerebral blood velocity (CBV; an index of CBF) responses during LBNP would not change with HUT and HDT, and (b) CBV in the anterior cerebral circulation would decrease to a greater extent compared to posterior CBV during LBNP when controlling PETCO2 In 13 male participants, we measured CBV in the anterior (middle cerebral artery, MCAv) and posterior (posterior cerebral artery, PCAv) cerebral circulations using transcranial Doppler ultrasound during LBNP stress (-50 mmHg) in three body positions (45°HUT, supine, 45°HDT). PETCO2 was measured continuously and maintained at constant levels during LBNP through coached breathing. Our main findings were that (a) steady-state tilt had no effect on CBV responses during LBNP in both the MCA (P = 0.077) and PCA (P = 0.583), and (b) despite controlling for PETCO2, both the MCAv and PCAv decreased by the same magnitude during LBNP in HUT (P = 0.348), supine (P = 0.694), and HDT (P = 0.407). Here, we demonstrate that there are no differences in anterior and posterior circulations in response to LBNP in different body positions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

The correlation of the thalamic lesions on MRI with cerebral cortical blood flow in patients with lacunar infarction

International Nuclear Information System (INIS)

Nabatame, Hidehiko; Nakamura, Kazuo; Matsuda, Minoru; Fujimoto, Naoki; Fukuyama, Hidenao.

1995-01-01

We performed MRI and measured cerebral blood flow (CBF) using 123 I-IMP SPECT microsphere model in twenty three right-handed patients with lacunar infarction. Twelve of 23 patients showed chronic deterioration of dysarthria and gait disturbance. The mental function of the patients was evaluated by the Mini-Mental State (MMS) examination. The area of high intensity on T2-weighted images was quantitatively analyzed in the cerebral white matter (WM), lenticular nucleus (LN) and thalamus (THA). The score of MMS was positively correlated with the local CBF in the bilateral frontal, parietal, temporal and occipital cortices (p<0.05). Also, the area of high intensity in the left THA showed a significant negative correlation with local CBF of the bilateral frontal, parietal, temporal and occipital cortices (p<0.001). The high intensity areas of the bilateral LN, right WM and right THA had a significant but weaker negative correlation with local CBF of some cortices. These findings suggest that thalamic lesions on the dominant side play an important role in the reduction of cortical blood flow and the deterioration of mental functions in patients with lacunar infarction. (author)

Study on effects of an atypical antipsychotic, risperidone on regional cerebral blood flow with 99mTc-HMPAO SPECT in drug-naive and unmedicated schizophrenic patients

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Koiwa, Daisuke

2003-01-01

To examine the underlying mechanisms of intracerebral or clinical actions of the atypical antipsychotic, risperidone (RIS), the effects of RIS on absolute regional cerebral blood flows (rCBFs) measured with 99mTc-HMPAO SPECT and correlations between the rCBFs and psychotic symptoms assessed with positive and negative syndrome scale (PANSS) were investigated in 10 drug-naive and unmedicated schizophrenic patients with acute hallucinatory and delusional state. Both the SPECT and PANSS were repeated before and after oral 2-week administration of RIS 3 mg/day in all of the 10 patients and after subsequent 2-week administration of RIS 4-6 mg/day in half of the patients. The rCBF values were significantly decreased in the left precentral gyrus alone after the low dose of RIS 3 mg/day in comparison with before the RIS dose. The rCBF values were significantly decreased in the right cingulate, postcentral, inferior parietal gyri and the left inferior temporal gyrus after the high dose of RIS 4-6 mg/day in comparison with before the low dose of RIS 3 mg/day. The psychiatric assessment with PANSS showed an improvement of positive and negative symptoms after the low RIS dose and still more after the high RIS dose. Statistical analyses on relationships between the rCBF values and PANSS scores before and after the low RIS dose showed a positive correlation between the rCBF values in the right middle temporal gyrus and hallucinations (mainly auditory hallucination). These results suggest that chronic RIS administration dose-dependently produces a decrease of rCBF in the cerebral cortex in the manner that the low dose decreases rCBF in a few restricted cortical regions, while the high dose induces the rCBF reduction in more widespread cortical regions. The RIS-induced rCBF decrease in the cerebral cortex is considered to be attributable to a secondary inactivation in the cerebral cortex due to D 2 dopamine receptor blockade of RIS in the striatum through the cortico

7 CFR 996.11 - Negative aflatoxin content.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Negative aflatoxin content. 996.11 Section 996.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... aflatoxin content. Negative aflatoxin content means 15 parts per billion (ppb) or less for peanuts that have...

Amyloid burden and sleep blood pressure in amnestic mild cognitive impairment

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Tarumi, Takashi; Harris, Thomas S.; Hill, Candace; German, Zohre; Riley, Jonathan; Turner, Marcel; Womack, Kyle B.; Kerwin, Diana R.; Monson, Nancy L.; Stowe, Ann M.; Mathews, Dana; Cullum, C. Munro

2015-01-01

Objective: To determine whether cortical β-amyloid (Aβ) deposition is associated with circadian blood pressure (BP) profiles and dynamic cerebral blood flow (CBF) regulation in patients with amnestic mild cognitive impairment (aMCI). Methods: Forty participants with aMCI were included in this study. Cortical Aβ depositions were measured by 18F-florbetapir PET and expressed as the standardized uptake value ratio (SUVR) relative to the cerebellum. Circadian BP profiles were measured by 24-hour ambulatory monitoring during awake and sleep periods. The dipping status of sleep BP (i.e., the percent changes from the awake BP) was calculated and dichotomized into the dipper (≥10%) and nondipper (<10%) groups. Dynamic CBF regulation was assessed by a transfer function analysis between beat-to-beat changes in BP and CBF velocity measured from the middle cerebral artery during a repeated sit-stand maneuver. Results: Age was positively correlated with a greater Aβ deposition in the posterior cingulate, precuneus, and mean cortex. Accounting for the age effect, attenuated reductions in sleep systolic BP were associated with higher levels of posterior cingulate SUVR. Consistently, the nondippers exhibited a higher SUVR in the posterior cingulate than the dippers. Transfer function gain between changes in BP and CBF velocity was diminished in the nondippers, and moreover those individuals with a lower gain exhibited a higher SUVR in the posterior cingulate. Conclusions: Attenuated reductions in sleep BP are associated with a greater Aβ burden in the posterior cingulate and altered dynamic CBF regulation in patients with aMCI. PMID:26537049

Neural correlates of preparatory and regulatory control over positive and negative emotion.

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Seo, Dongju; Olman, Cheryl A; Haut, Kristen M; Sinha, Rajita; MacDonald, Angus W; Patrick, Christopher J

2014-04-01

This study used functional magnetic resonance imaging to investigate brain activation during preparatory and regulatory control while participants (N = 24) were instructed either to simply view or decrease their emotional response to, pleasant, neutral or unpleasant pictures. A main effect of emotional valence on brain activity was found in the right precentral gyrus, with greater activation during positive than negative emotion regulation. A main effect of regulation phase was evident in the bilateral anterior prefrontal cortex (PFC), precuneus, posterior cingulate cortex, right putamen and temporal and occipital lobes, with greater activity in these regions during preparatory than regulatory control. A valence X regulation interaction was evident in regions of ventromedial PFC and anterior cingulate cortex, reflecting greater activation while regulating negative than positive emotion, but only during active emotion regulation (not preparation). Conjunction analyses revealed common brain regions involved in differing types of emotion regulation including selected areas of left lateral PFC, inferior parietal lobe, temporal lobe, right cerebellum and bilateral dorsomedial PFC. The right lateral PFC was additionally activated during the modulation of both positive and negative valence. Findings demonstrate significant modulation of brain activity during both preparation for, and active regulation of positive and negative emotional states.

Analysis of the interaction between human RITA and Drosophila Suppressor of Hairless.

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Brockmann, Birgit; Mastel, Helena; Oswald, Franz; Maier, Dieter

2014-12-01

Notch signalling mediates intercellular communication, which is effected by the transcription factor CSL, an acronym for vertebrate CBF1/RBP-J, Drosophila Suppressor of Hairless [Su(H)] and C. elegans Lag1. Nuclear import of CBF1/RBP-J depends on co-activators and co-repressors, whereas the export relies on RITA. RITA is a tubulin and CBF1/RBP-J binding protein acting as a negative regulator of Notch signalling in vertebrates. RITA protein is highly conserved in eumatazoa, but no Drosophila homologue was yet identified. In this work, the activity of human RITA in the fly was addressed. To this end, we generated transgenic flies that allow a tissue specific induction of human RITA, which was demonstrated by Western blotting and in fly tissues. Unexpectedly, overexpression of RITA during fly development had little phenotypic consequences, even when overexpressed simultaneously with either Su(H) or the Notch antagonist Hairless. We demonstrate the in vivo binding of human RITA to Su(H) and to tubulin by co-immune precipitation. Moreover, RITA and tubulin co-localized to some degree in several Drosophila tissues. Overall our data show that human RITA, albeit binding to Drosophila Su(H) and tubulin, cannot influence the Notch signalling pathway in the fly, suggesting that a nuclear export mechanism of Su(H), if existent in Drosophila, does not depend on RITA. © 2015 The Authors.

Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse

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Masayuki Tanaka

2016-07-01

Full Text Available Thrombin-activated protease-activated receptor (PAR-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR. Direct exposure of the cells to thrombin dramatically attenuated the cell proliferation without causing cell damage. This thrombin-induced attenuation was almost completely abolished by the PAR antagonist RWJ 56110, as well as by dabigatran and 4-(2-aminoethylbenzenesulfonyl fluoride (AEBSF, which are selective and non-selective thrombin inhibitors, respectively. Expectedly, the PAR-1 agonist peptide (AP SFLLR-NH2 also attenuated the cell proliferation. The cell proliferation was not affected by the PAR-1 negative control peptide RLLFT-NH2, which is an inactive peptide for PAR-1. Independently, we determined the effect of in vivo treatment with AEBSF or AP on hippocampal neurogenesis in the adult mouse. The administration of AEBSF, but not that of AP, significantly increased the number of newly-generated cells in the hippocampal subgranular zone. These data suggest that PAR-1 negatively regulated adult neurogenesis in the hippocampus by inhibiting the proliferative activity of the NPCs.

Chrysanthemum WRKY gene CmWRKY17 negatively regulates salt stress tolerance in transgenic chrysanthemum and Arabidopsis plants.

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Li, Peiling; Song, Aiping; Gao, Chunyan; Wang, Linxiao; Wang, Yinjie; Sun, Jing; Jiang, Jiafu; Chen, Fadi; Chen, Sumei

2015-08-01

CmWRKY17 was induced by salinity in chrysanthemum, and it might negatively regulate salt stress in transgenic plants as a transcriptional repressor. WRKY transcription factors play roles as positive or negative regulators in response to various stresses in plants. In this study, CmWRKY17 was isolated from chrysanthemum (Chrysanthemum morifolium). The gene encodes a 227-amino acid protein and belongs to the group II WRKY family, but has an atypical WRKY domain with the sequence WKKYGEK. Our data indicated that CmWRKY17 was localized to the nucleus in onion epidermal cells. CmWRKY17 showed no transcriptional activation in yeast; furthermore, luminescence assay clearly suggested that CmWRKY17 functions as a transcriptional repressor. DNA-binding assay showed that CmWRKY17 can bind to W-box. The expression of CmWRKY17 was induced by salinity in chrysanthemum, and a higher expression level was observed in the stem and leaf compared with that in the root, disk florets, and ray florets. Overexpression of CmWRKY17 in chrysanthemum and Arabidopsis increased the sensitivity to salinity stress. The activities of superoxide dismutase and peroxidase and proline content in the leaf were significantly lower in transgenic chrysanthemum than those in the wild type under salinity stress, whereas electrical conductivity was increased in transgenic plants. Expression of the stress-related genes AtRD29, AtDREB2B, AtSOS1, AtSOS2, AtSOS3, and AtNHX1 was reduced in the CmWRKY17 transgenic Arabidopsis compared with that in the wild-type Col-0. Collectively, these data suggest that CmWRKY17 may increase the salinity sensitivity in plants as a transcriptional repressor.

The effect of isovolemic hemodilution with oxycyte, a perfluorocarbon emulsion, on cerebral blood flow in rats.

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Zhong-jin Yang

Full Text Available BACKGROUND: Cerebral blood flow (CBF is auto-regulated to meet the brain's metabolic requirements. Oxycyte is a perfluorocarbon emulsion that acts as a highly effective oxygen carrier compared to blood. The aim of this study is to determine the effects of Oxycyte on regional CBF (rCBF, by evaluating the effects of stepwise isovolemic hemodilution with Oxycyte on CBF. METHODOLOGY: Male rats were intubated and ventilated with 100% O(2 under isoflurane anesthesia. The regional (striatum CBF (rCBF was measured with a laser doppler flowmeter (LDF. Stepwise isovolemic hemodilution was performed by withdrawing 4ml of blood and substituting the same volume of 5% albumin or 2 ml Oxycyte plus 2 ml albumin at 20-minute intervals until the hematocrit (Hct values reached 5%. PRINCIPAL FINDINGS: In the albumin-treated group, rCBF progressively increased to approximately twice its baseline level (208+/-30% when Hct levels were less than 10%. In the Oxycyte-treated group on the other hand, rCBF increased by significantly smaller increments, and this group's mean rCBF was only slightly higher than baseline (118+/-18% when Hct levels were less than 10%. Similarly, in the albumin-treated group, rCBF started to increase when hemodilution with albumin caused the CaO(2 to decrease below 17.5 ml/dl. Thereafter, the increase in rCBF was accompanied by a nearly proportional decrease in the CaO(2 level. In the Oxycyte-treated group, the increase in rCBF was significantly smaller than in the albumin-treated group when the CaO(2 level dropped below 10 ml/dl (142+/-20% vs. 186+/-26%, and rCBF returned to almost baseline levels (106+/-15 when the CaO(2 level was below 7 ml/dl. CONCLUSIONS/SIGNIFICANCE: Hemodilution with Oxycyte was accompanied with higher CaO(2 and PO(2 than control group treated with albumin alone. This effect may be partially responsible for maintaining relatively constant CBF and not allowing the elevated blood flow that was observed with albumin.

Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

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Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

2018-05-16

Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

Exercise Activates p53 and Negatively Regulates IGF-1 Pathway in Epidermis within a Skin Cancer Model.

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Yu, Miao; King, Brenee; Ewert, Emily; Su, Xiaoyu; Mardiyati, Nur; Zhao, Zhihui; Wang, Weiqun

2016-01-01

Exercise has been previously reported to lower cancer risk through reducing circulating IGF-1 and IGF-1-dependent signaling in a mouse skin cancer model. This study aims to investigate the underlying mechanisms by which exercise may down-regulate the IGF-1 pathway via p53 and p53-related regulators in the skin epidermis. Female SENCAR mice were pair-fed an AIN-93 diet with or without 10-week treadmill exercise at 20 m/min, 60 min/day and 5 days/week. Animals were topically treated with TPA 2 hours before sacrifice and the target proteins in the epidermis were analyzed by both immunohistochemistry and Western blot. Under TPA or vehicle treatment, MDM2 expression was significantly reduced in exercised mice when compared with sedentary control. Meanwhile, p53 was significantly elevated. In addition, p53-transcriptioned proteins, i.e., p21, IGFBP-3, and PTEN, increased in response to exercise. There was a synergy effect between exercise and TPA on the decreased MDM2 and increased p53, but not p53-transcripted proteins. Taken together, exercise appeared to activate p53, resulting in enhanced expression of p21, IGFBP-3, and PTEN that might induce a negative regulation of IGF-1 pathway and thus contribute to the observed cancer prevention by exercise in this skin cancer model.

Age Differences in Affective and Cardiovascular Responses to a Negative Social Interaction: The Role of Goals, Appraisals, and Emotion Regulation

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Luong, Gloria; Charles, Susan T.

2014-01-01

Older adults often report less affective reactivity to interpersonal tensions than younger individuals, but few studies have directly investigated mechanisms explaining this effect. The current study examined whether older adults’ differential endorsement of goals, appraisals, and emotion regulation strategies (i.e., conflict avoidance/de-escalation, self-distraction) during a controlled negative social interaction may explain age differences in affective and cardiovascular responses to the conflict discussion. Participants (N=159; 80 younger adults, 79 older adults) discussed hypothetical dilemmas with disagreeable confederates. Throughout the laboratory session, participants’ subjective emotional experience, blood pressure, and pulse rate were assessed. Older adults generally exhibited less reactivity (negative affect reactivity, diastolic blood pressure reactivity, and pulse rate reactivity) to the task, and more pronounced positive and negative affect recovery following the task, than did younger adults. Older adults appraised the task as more enjoyable and the confederate as more likeable, and more strongly endorsed goals to perform well on the task, which mediated age differences in negative affect reactivity, pulse rate reactivity, and positive affect recovery (i.e., increases in post-task positive affect), respectively. In addition, younger adults showed increased negative affect reactivity with greater use of self-distraction, whereas older adults did not. Together, findings suggest that older adults respond less negatively to unpleasant social interactions than younger adults, and these responses are explained in part by older adults’ pursuit of different motivational goals, less threatening appraisals of the social interaction, and more effective use of self-distraction, compared to younger adults. PMID:24773101

TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis.

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Sun, Honghong; Gong, Shunyou; Carmody, Ruaidhri J; Hilliard, Anja; Li, Li; Sun, Jing; Kong, Li; Xu, Lingyun; Hilliard, Brendan; Hu, Shimin; Shen, Hao; Yang, Xiaolu; Chen, Youhai H

2008-05-02

Immune homeostasis is essential for the normal functioning of the immune system, and its breakdown leads to fatal inflammatory diseases. We report here the identification of a member of the tumor necrosis factor-alpha-induced protein-8 (TNFAIP8) family, designated TIPE2, that is required for maintaining immune homeostasis. TIPE2 is preferentially expressed in lymphoid tissues, and its deletion in mice leads to multiorgan inflammation, splenomegaly, and premature death. TIPE2-deficient animals are hypersensitive to septic shock, and TIPE2-deficient cells are hyper-responsive to Toll-like receptor (TLR) and T cell receptor (TCR) activation. Importantly, TIPE2 binds to caspase-8 and inhibits activating protein-1 and nuclear factor-kappaB activation while promoting Fas-induced apoptosis. Inhibiting caspase-8 significantly blocks the hyper-responsiveness of TIPE2-deficient cells. These results establish that TIPE2 is an essential negative regulator of TLR and TCR function, and its selective expression in the immune system prevents hyperresponsiveness and maintains immune homeostasis.

Ethanol negatively regulates hepatic differentiation of hESC by inhibition of the MAPK/ERK signaling pathway in vitro.

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Wei Gao

Full Text Available Alcohol insult triggers complex events in the liver, promoting fibrogenic/inflammatory signals and in more advanced cases, aberrant matrix deposition. It is well accepted that the regenerative capacity of the adult liver is impaired during alcohol injury. The liver progenitor/stem cells have been shown to play an important role in liver regeneration -in response to various chronic injuries; however, the effects of alcohol on stem cell differentiation in the liver are not well understood.We employed hepatic progenitor cells derived from hESCs to study the impact of ethanol on hepatocyte differentiation by exposure of these progenitor cells to ethanol during hepatocyte differentiation.We found that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitor cells in a dose-dependent manner. There was also a moderate cell cycle arrest at G1/S checkpoint in the ethanol treated cells, which is associated with a reduced level of cyclin D1 in these cells. Ethanol treatment specifically inhibited the activation of the ERK but not JNK nor the p38 MAP signaling pathway. At the same time, the WNT signaling pathway was also reduced in the cells exposed to ethanol. Upon evaluating the effects of the inhibitors of these two signaling pathways, we determined that the Erk inhibitor replicated the effects of ethanol on the hepatocyte differentiation and attenuated the WNT/β-catenin signaling, however, inhibitors of WNT only partially replicated the effects of ethanol on the hepatocyte differentiation.Our results demonstrated that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitors through inhibiting the MAPK/ERK signaling pathway, and subsequently attenuating the WNT signaling pathway. Thus, our finding provides a novel insight into the mechanism by which alcohol regulates cell fate selection of hESC-derived hepatic progenitor cells, and the identified pathways may provide therapeutic targets

Arabidopsis ETO1 specifically interacts with and negatively regulates type 2 1-aminocyclopropane-1-carboxylate synthases

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Saito Koji

2005-08-01

Full Text Available Abstract Background In Arabidopsis, ETO1 (ETHYLENE-OVERPRODUCER1 is a negative regulator of ethylene evolution by interacting with AtACS5, an isoform of the rate-limiting enzyme, 1-aminocyclopropane-1-carboxylate synthases (ACC synthase or ACS, in ethylene biosynthetic pathway. ETO1 directly inhibits the enzymatic activity of AtACS5. In addition, a specific interaction between ETO1 and AtCUL3, a constituent of a new type of E3 ubiquitin ligase complex, suggests the molecular mechanism in promoting AtACS5 degradation by the proteasome-dependent pathway. Because orthologous sequences to ETO1 are found in many plant species including tomato, we transformed tomato with Arabidopsis ETO1 to evaluate its ability to suppress ethylene production in tomato fruits. Results Transgenic tomato lines that overexpress Arabidopsis ETO1 (ETO1-OE did not show a significant delay of fruit ripening. So, we performed yeast two-hybrid assays to investigate potential heterologous interaction between ETO1 and three isozymes of ACC synthases from tomato. In the yeast two-hybrid system, ETO1 interacts with LE-ACS3 as well as AtACS5 but not with LE-ACS2 or LE-ACS4, two major isozymes whose gene expression is induced markedly in ripening fruits. According to the classification of ACC synthases, which is based on the C-terminal amino acid sequences, both LE-ACS3 and AtACS5 are categorized as type 2 isozymes and possess a consensus C-terminal sequence. In contrast, LE-ACS2 and LE-ACS4 are type 1 and type 3 isozymes, respectively, both of which do not possess this specific C-terminal sequence. Yeast two-hybrid analysis using chimeric constructs between LE-ACS2 and LE-ACS3 revealed that the type-2-ACS-specific C-terminal tail is required for interaction with ETO1. When treated with auxin to induce LE-ACS3, seedlings of ETO1-OE produced less ethylene than the wild type, despite comparable expression of the LE-ACS3 gene in the wild type. Conclusion These results suggest that ETO1

PGC-1-related coactivator (PRC) negatively regulates endothelial adhesion of monocytes via inhibition of NF κB activity

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Chengye, Zhan; Daixing, Zhou, E-mail: dxzhou7246@hotmail.com; Qiang, Zhong; Shusheng, Li

2013-09-13

Highlights: •First time to display that LPS downregulate the expression of PRC. •First time to show that PRC inhibits the induction of VCAM-1 and E-selectin. •First time to show that PRC inhibit monocytes attachment to endothelial cells. •First time to display that PRC inhibits transcriptional activity of NF-κB. •PRC protects the respiration rate and suppresses the glycolysis rate against LPS. -- Abstract: PGC-1-related coactivator (PRC) is a growth-regulated transcriptional cofactor known to activate many of the nuclear genes specifying mitochondrial respiratory function. Endothelial dysfunction is a prominent feature found in many inflammatory diseases. Adhesion molecules, such as VCAM-1, mediate the attachment of monocytes to endothelial cells, thereby playing an important role in endothelial inflammation. The effects of PRC in regards to endothelial inflammation remain unknown. In this study, our findings show that PRC can be inhibited by the inflammatory cytokine LPS in cultured human umbilical vein endothelial cells (HUVECs). In the presence of LPS, the expression of endothelial cell adhesion molecular, such as VCAM1 and E-selectin, is found to be increased. These effects can be negated by overexpression of PRC. Importantly, monocyte adhesion to endothelial cells caused by LPS is significantly attenuated by PRC. In addition, overexpression of PRC protects mitochondrial metabolic function and suppresses the rate of glycolysis against LPS. It is also found that overexpression of PRC decreases the transcriptional activity of NF-κB. These findings suggest that PRC is a negative regulator of endothelial inflammation.

New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

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Venkat, Poornima; Chopp, Michael; Chen, Jieli

2016-06-30

The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow.

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Lee, Dooyoung; Kim, Jiyeon; Beste, Michael T; Koretzky, Gary A; Hammer, Daniel A

2012-06-01

T lymphocyte arrest within microvasculature is an essential process in immune surveillance and the adaptive immune response. Integrins and chemokines coordinately regulate when and where T cells stop under flow via chemokine-triggered inside-out activation of integrins. Diacylglycerol kinases (DGKs) regulate the levels of diacylglycerol (DAG) which in turn determine the activation of guanine nucleotide exchange factors (GEFs) and Ras proximity 1 (Rap1) molecules crucial to the activation of integrin lymphocyte function-associated antigen 1 (LFA-1). However, how the level of DGK regulates chemokine-stimulated LFA-1-mediated T cell arrest under flow is unknown. Using a combination of experiment and computational modeling, we demonstrate that DGKζ is a crucial regulator of CXCL12-triggered T cell arrest on surfaces presenting inter-cellular adhesion molecule 1 (ICAM-1). Using flow chamber assays, we found that the deficiency of DGKζ in T cells significantly increased firm arrest to ICAM-1-coated substrates and shortened the time to stop without altering the rolling velocity. These results suggest that DGKζ levels affect LFA-1-mediated T cell firm arrest, but not P-selectin-mediated rolling during CXCL12 stimulation. We accurately simulated the role of DGKζ in firm arrest of T cells computationally using an Integrated-Signaling Adhesive Dynamics (ISAD). In the absence of DGK catalytic reaction, the model cells rolled for a significantly shorter time before arrest, compared to when DGK molecules were present. Predictions of our model for T cell arrest quantitatively match experimental results. Overall these results demonstrate that DGKζ is a negative regulator of CXCL12-triggered inside-out activation of LFA-1 and firm adhesion of T cells under shear flow.

Application of SPECT to psychiatry

International Nuclear Information System (INIS)

Matsuda, Hiroshi

1999-01-01

Brain perfusion SPECT using 99m Tc-ethyl-cysteinate dimer ( 99m Tc-ECD) was applied to psychiatric diseases with aid of statistical parametric mapping (SPM) for analysis of data. To evaluate influence of aging on brain perfusion, noninvasive measurements of cerebral blood flow using 99m Tc-ECD were performed in 53 normal volunteers, age 18 to 87 years old. Mean cerebral blood flow (mCBF) was 43.9±5.0 ml/100 g/min and showed weak negative correlation with aging (r=0.451). Perisylvian cerebral cortices and medial frontal areas including anterior cingulate gyri showed greater negative correlation than other areas. These findings suggest the necessity of age-matched control regional CBF (rCBF) data to investigate rCBF abnormality in patients. Four drug-naive schizophrenic patients showed flow decrease in bilateral frontal and superior temporal areas and a left infero-posterior temporal area. Haloperidol administration induced flow decrease in bilateral frontal and left parietal areas, while flow increase in bilateral striatal and right hippocampal areas. Ten aged depressive patients showed flow decrease in bilateral frontal and left temporo-parietal areas. Even after remission patients showed flow decrease in the left frontal area as compared with normal subjects. Remission induced flow increase in the right frontal, right parietal, and right orbitofrontal areas compared with depression. These results suggest that CBF measurements using 99m Tc-ECD were useful for objective evaluation of regional abnormality in brain function in psychiatric diseases. (author)

Regional cerebral blood flow and anxiety: a correlation study in neurologically normal patients

International Nuclear Information System (INIS)

Rodriguez, G.; Cogorno, P.; Gris, A.; Marenco, S.; Mesiti, C.; Nobili, F.; Rosadini, G.

1989-01-01

Regional CBF (rCBF) was evaluated by the 133 Xe inhalation method in 60 neurologically normal patients (30 men and 30 women) and hemispheric and regional values were correlated with anxiety measurements collected by a self-rating questionnaire before and after the examination. Statistically significant negative correlations between rCBF and anxiety measures were found. rCBF reduction for high anxiety levels is in line with results previously reported by others and could be related to lower performance levels for moderately high anxiety scores as those reported in the present population. This could perhaps be explained by rearrangement of flow from cortical zones to deeper areas of the brain, classically known to be implicated in the control of emotions. However, these results should be interpreted cautiously, since they were obtained in patients and not in normal subjects

PRKCI negatively regulates autophagy via PIK3CA/AKT–MTOR signaling

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Qu, Liujing; Li, Ge; Xia, Dan; Hongdu, Beiqi; Xu, Chentong; Lin, Xin [Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Sciences Center, Beijing (China); Peking University Center for Human Disease Genomics, Peking University, Beijing (China); Chen, Yingyu, E-mail: yingyu_chen@bjmu.edu.cn [Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Sciences Center, Beijing (China); Peking University Center for Human Disease Genomics, Peking University, Beijing (China)

2016-02-05

The atypical protein kinase C isoform PRKC iota (PRKCI) plays a key role in cell proliferation, differentiation, and carcinogenesis, and it has been shown to be a human oncogene. Here, we show that PRKCI overexpression in U2OS cells impaired functional autophagy in normal or cell stress conditions, as characterized by decreased levels of light chain 3B-II protein (LC3B-II) and weakened degradation of endogenous and exogenous autophagic substrates. Conversely, PRKCI knockdown by small interference RNA resulted in opposite effects. Additionally, we identified two novel PRKCI mutants, PRKCI{sup L485M} and PRKCI{sup P560R}, which induced autophagy and exhibited dominant negative effects. Further studies indicated that PRKCI knockdown–mediated autophagy was associated with the inactivation of phosphatidylinositol 3-kinase alpha/AKT–mammalian target of rapamycin (PIK3CA/AKT–MTOR) signaling. These data underscore the importance of PRKCI in the regulation of autophagy. Moreover, the finding may be useful in treating PRKCI-overexpressing carcinomas that are characterized by increased levels of autophagy. - Highlights: • The atypical protein kinase C iota isoform (PRKCI) is a human oncogene. • PRKCI overexpression impairs functional autophagy in U2OS cells. • It reduces LC3B-II levels and weakens SQSTM1 and polyQ80 aggregate degradation. • PRKCI knockdown has the opposite effect. • The effect of PRKCI knockdown is related to PIK3CA/AKT–MTOR signaling inactivation.

The Wheat Mediator Subunit TaMED25 Interacts with the Transcription Factor TaEIL1 to Negatively Regulate Disease Resistance against Powdery Mildew.

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Liu, Jie; Zhang, Tianren; Jia, Jizeng; Sun, Jiaqiang

2016-03-01

Powdery mildew, caused by the biotrophic fungal pathogen Blumeria graminis f. sp. tritici, is a major limitation for the production of bread wheat (Triticum aestivum). However, to date, the transcriptional regulation of bread wheat defense against powdery mildew remains largely unknown. Here, we report the function and molecular mechanism of the bread wheat Mediator subunit 25 (TaMED25) in regulating the bread wheat immune response signaling pathway. Three homoalleles of TaMED25 from bread wheat were identified and mapped to chromosomes 5A, 5B, and 5D, respectively. We show that knockdown of TaMED25 by barley stripe mosaic virus-induced gene silencing reduced bread wheat susceptibility to the powdery mildew fungus during the compatible plant-pathogen interaction. Moreover, our results indicate that MED25 may play a conserved role in regulating bread wheat and barley (Hordeum vulgare) susceptibility to powdery mildew. Similarly, bread wheat ETHYLENE INSENSITIVE3-LIKE1 (TaEIL1), an ortholog of Arabidopsis (Arabidopsis thaliana) ETHYLENE INSENSITIVE3, negatively regulates bread wheat resistance against powdery mildew. Using various approaches, we demonstrate that the conserved activator-interacting domain of TaMED25 interacts physically with the separate amino- and carboxyl-terminal regions of TaEIL1, contributing to the transcriptional activation activity of TaEIL1. Furthermore, we show that TaMED25 and TaEIL1 synergistically activate ETHYLENE RESPONSE FACTOR1 (TaERF1) transcription to modulate bread wheat basal disease resistance to B. graminis f. sp. tritici by repressing the expression of pathogenesis-related genes and deterring the accumulation of reactive oxygen species. Collectively, we identify the TaMED25-TaEIL1-TaERF1 signaling module as a negative regulator of bread wheat resistance to powdery mildew. © 2016 American Society of Plant Biologists. All Rights Reserved.

SNF1-related protein kinases 2 are negatively regulated by a plant-specific calcium sensor.

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Bucholc, Maria; Ciesielski, Arkadiusz; Goch, Grażyna; Anielska-Mazur, Anna; Kulik, Anna; Krzywińska, Ewa; Dobrowolska, Grażyna

2011-02-04

SNF1-related protein kinases 2 (SnRK2s) are plant-specific enzymes involved in environmental stress signaling and abscisic acid-regulated plant development. Here, we report that SnRK2s interact with and are regulated by a plant-specific calcium-binding protein. We screened a Nicotiana plumbaginifolia Matchmaker cDNA library for proteins interacting with Nicotiana tabacum osmotic stress-activated protein kinase (NtOSAK), a member of the SnRK2 family. A putative EF-hand calcium-binding protein was identified as a molecular partner of NtOSAK. To determine whether the identified protein interacts only with NtOSAK or with other SnRK2s as well, we studied the interaction of an Arabidopsis thaliana orthologue of the calcium-binding protein with selected Arabidopsis SnRK2s using a two-hybrid system. All kinases studied interacted with the protein. The interactions were confirmed by bimolecular fluorescence complementation assay, indicating that the binding occurs in planta, exclusively in the cytoplasm. Calcium binding properties of the protein were analyzed by fluorescence spectroscopy using Tb(3+) as a spectroscopic probe. The calcium binding constant, determined by the protein fluorescence titration, was 2.5 ± 0.9 × 10(5) M(-1). The CD spectrum indicated that the secondary structure of the protein changes significantly in the presence of calcium, suggesting its possible function as a calcium sensor in plant cells. In vitro studies revealed that the activity of SnRK2 kinases analyzed is inhibited in a calcium-dependent manner by the identified calcium sensor, which we named SCS (SnRK2-interacting calcium sensor). Our results suggest that SCS is involved in response to abscisic acid during seed germination most probably by negative regulation of SnRK2s activity.

Arterial spin-labeling MR imaging of cerebral hemorrhages

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Noguchi, Tomoyuki [Department of Radiology, National Center for Global Health and Medicine, Tokyo (Japan); Saga University, Department of Radiology, Faculty of Medicine and Graduate School of Medicine, Saga (Japan); Nishihara, Masashi; Egashira, Yoshiaki; Azama, Shinya; Hirai, Tetsuyoshi; Kitano, Isao; Irie, Hiroyuki [Saga University, Department of Radiology, Faculty of Medicine and Graduate School of Medicine, Saga (Japan); Yakushiji, Yusuke [Saga University, Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Saga (Japan); Kawashima, Masatou [Saga University, Department of Neurosurgery, Faculty of Medicine and Graduate School of Medicine, Saga (Japan)

2015-11-15

The purpose of this study is to identify the characteristics of brain perfusion measured by arterial spin-labeling magnetic resonance imaging (ASL-MRI) in cerebral hemorrhages. Brain blood flow values (CBF-ASL values) for cerebral and cerebellar hemispheres and segmented cerebral regions were measured by ASL-MRI in 19 putaminal hemorrhage patients and 20 thalamic hemorrhage patients in acute or subacute stages. We assessed the lateralities of CBF-ASL values and the relationships between CBF-ASL values and other imaging findings and clinical manifestations. Both the 19 putaminal hemorrhage patients and the 20 thalamic hemorrhage patients had significantly low CBF-ASL values of the contralateral cerebellum in subacute stage, suggesting that ASL-MRI might delineate crossed cerebellar diaschisis (CCD). Ipsilateral low CBF-ASL values were observed in frontal lobes and thalami with a putaminal hemorrhage and lentiform nuclei, temporal lobes, and parietal lobes with a thalamic hemorrhage, suggesting that ASL-MRI showed the ipsilateral cerebral diaschisis (ICD). In the putaminal hemorrhage patients, the hematoma volume negatively affected both the bilateral cerebellar and cerebral hemispheric CBF-ASL values. In the thalamic hemorrhage patients, a concomitant intraventricular hemorrhage caused low cerebral hemispheric CBF-ASL values. The use of ASL-MRI is sensitive to the perfusion abnormalities and could thus be helpful to estimate functional abnormalities in cerebral hemorrhage patients. (orig.)

Arterial spin-labeling MR imaging of cerebral hemorrhages

International Nuclear Information System (INIS)

Noguchi, Tomoyuki; Nishihara, Masashi; Egashira, Yoshiaki; Azama, Shinya; Hirai, Tetsuyoshi; Kitano, Isao; Irie, Hiroyuki; Yakushiji, Yusuke; Kawashima, Masatou

2015-01-01

The purpose of this study is to identify the characteristics of brain perfusion measured by arterial spin-labeling magnetic resonance imaging (ASL-MRI) in cerebral hemorrhages. Brain blood flow values (CBF-ASL values) for cerebral and cerebellar hemispheres and segmented cerebral regions were measured by ASL-MRI in 19 putaminal hemorrhage patients and 20 thalamic hemorrhage patients in acute or subacute stages. We assessed the lateralities of CBF-ASL values and the relationships between CBF-ASL values and other imaging findings and clinical manifestations. Both the 19 putaminal hemorrhage patients and the 20 thalamic hemorrhage patients had significantly low CBF-ASL values of the contralateral cerebellum in subacute stage, suggesting that ASL-MRI might delineate crossed cerebellar diaschisis (CCD). Ipsilateral low CBF-ASL values were observed in frontal lobes and thalami with a putaminal hemorrhage and lentiform nuclei, temporal lobes, and parietal lobes with a thalamic hemorrhage, suggesting that ASL-MRI showed the ipsilateral cerebral diaschisis (ICD). In the putaminal hemorrhage patients, the hematoma volume negatively affected both the bilateral cerebellar and cerebral hemispheric CBF-ASL values. In the thalamic hemorrhage patients, a concomitant intraventricular hemorrhage caused low cerebral hemispheric CBF-ASL values. The use of ASL-MRI is sensitive to the perfusion abnormalities and could thus be helpful to estimate functional abnormalities in cerebral hemorrhage patients. (orig.)

Negative Effects of Antimonopoly Regulation on the Russian Electric Power Industry

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Elena NEPRINTSEVA

2017-07-01

Full Text Available With the antimonopoly regulation in the domestic economy getting more stringent an analysis of the current measures of antimonopoly regulation in terms of their efficiency is now becoming ever more relevant. The aim of the study - analyze how the measures of antimonopoly regulation affect competitive relationships in the electric power industry. The following methods have been used in this work: empirical method, cause-effect method and scientific abstraction method. The article sets out an analysis of the antimonopoly regulation measures that the antimonopoly authority applies. It also provides an assessment of consequences that follow from such methods being applied for the promotion of competitive relationships on the market of electric power and capacity. A conclusion has been reached that the antimonopoly regulation measures being applied impede the progress of competitive relationships on the market of electric power and capacity. The continuing process of reformation in electric power industry aims to liberalize relationships in the area of electric power production. Yet, as a result of this process, generating capacities are becoming increasingly more concentrated mainly around state companies. This is mainly caused by the lack of certainty regarding the results of the industry reformation and a more stringent state regulation over the last years of the reforms. At the same time, for the purposes of limiting the market force, measures of antimonopoly regulation are being applied to generating companies. Such measures have an adverse effect on competitive relationships and stimulate further concentration.

Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

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Penrose, Harrison; Heller, Sandra; Cable, Chloe [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Makboul, Rania [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Pathology Department, Assiut University, Assiut (Egypt); Chadalawada, Gita; Chen, Ying [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Crawford, Susan E. [Department of Pathology, Saint Louis University School of Medicine, 1402 South Grand Blvd, Saint Louis, MO 63104 (United States); Savkovic, Suzana D., E-mail: ssavkovi@tulane.edu [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States)

2016-01-15

The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

International Nuclear Information System (INIS)

Penrose, Harrison; Heller, Sandra; Cable, Chloe; Makboul, Rania; Chadalawada, Gita; Chen, Ying; Crawford, Susan E.; Savkovic, Suzana D.

2016-01-01

The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

TRIM30α Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING.

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Yanming Wang

2015-06-01

Full Text Available Uncontrolled immune responses to intracellular DNA have been shown to induce autoimmune diseases. Homeostasis regulation of immune responses to cytosolic DNA is critical for limiting the risk of autoimmunity and survival of the host. Here, we report that the E3 ubiquitin ligase tripartite motif protein 30α (TRIM30α was induced by herpes simplex virus type 1 (HSV-1 infection in dendritic cells (DCs. Knockdown or genetic ablation of TRIM30α augmented the type I IFNs and interleukin-6 response to intracellular DNA and DNA viruses. Trim30α-deficient mice were more resistant to infection by DNA viruses. Biochemical analyses showed that TRIM30α interacted with the stimulator of interferon genes (STING, which is a critical regulator of the DNA-sensing response. Overexpression of TRIM30α promoted the degradation of STING via K48-linked ubiquitination at Lys275 through a proteasome-dependent pathway. These findings indicate that E3 ligase TRIM30α is an important negative-feedback regulator of innate immune responses to DNA viruses by targeting STING.

bHLH003, bHLH013 and bHLH017 are new targets of JAZ repressors negatively regulating JA responses.

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Sandra Fonseca

Full Text Available Cell reprogramming in response to jasmonates requires a tight control of transcription that is achieved by the activity of JA-related transcription factors (TFs. Among them, MYC2, MYC3 and MYC4 have been described as activators of JA responses. Here we characterized the function of bHLH003, bHLH013 and bHLH017 that conform a phylogenetic clade closely related to MYC2, MYC3 and MYC4. We found that these bHLHs form homo- and heterodimers and also interact with JAZ repressors in vitro and in vivo. Phenotypic analysis of JA-regulated processes, including root and rosette growth, anthocyanin accumulation, chlorophyll loss and resistance to Pseudomonas syringae, on mutants and overexpression lines, suggested that these bHLHs are repressors of JA responses. bHLH003, bHLH013 and bHLH017 are mainly nuclear proteins and bind DNA with similar specificity to that of MYC2, MYC3 and MYC4, but lack a conserved activation domain, suggesting that repression is achieved by competition for the same cis-regulatory elements. Moreover, expression of bHLH017 is induced by JA and depends on MYC2, suggesting a negative feed-back regulation of the activity of positive JA-related TFs. Our results suggest that the competition between positive and negative TFs determines the output of JA-dependent transcriptional activation.

BRUTUS and its paralogs, BTS LIKE1 and BTS LIKE2, encode important negative regulators of the iron deficiency response in Arabidopsis thaliana.

Science.gov (United States)

Hindt, Maria N; Akmakjian, Garo Z; Pivarski, Kara L; Punshon, Tracy; Baxter, Ivan; Salt, David E; Guerinot, Mary Lou

2017-07-19

Iron (Fe) is required for plant health, but it can also be toxic when present in excess. Therefore, Fe levels must be tightly controlled. The Arabidopsis thaliana E3 ligase BRUTUS (BTS) is involved in the negative regulation of the Fe deficiency response and we show here that the two A. thaliana BTS paralogs, BTS LIKE1 (BTSL1) and BTS LIKE2 (BTSL2) encode proteins that act redundantly as negative regulators of the Fe deficiency response. Loss of both of these E3 ligases enhances tolerance to Fe deficiency. We further generated a triple mutant with loss of both BTS paralogs and a partial loss of BTS expression that exhibits even greater tolerance to Fe-deficient conditions and increased Fe accumulation without any resulting Fe toxicity effects. Finally, we identified a mutant carrying a novel missense mutation of BTS that exhibits an Fe deficiency response in the root when grown under both Fe-deficient and Fe-sufficient conditions, leading to Fe toxicity when plants are grown under Fe-sufficient conditions.

fundTPL-2 – ERK1/2 Signaling Promotes Host Resistance against Intracellular Bacterial Infection by Negative Regulation of Type I Interferon Production3

Science.gov (United States)

McNab, Finlay W.; Ewbank, John; Rajsbaum, Ricardo; Stavropoulos, Evangelos; Martirosyan, Anna; Redford, Paul S.; Wu, Xuemei; Graham, Christine M.; Saraiva, Margarida; Tsichlis, Philip; Chaussabel, Damien; Ley, Steven C.; O’Garra, Anne

2013-01-01

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of mortality and morbidity worldwide, causing approximately 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL-12, IL-1 and TNF-α, as well as IFN-γ and CD4+ Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I interferon have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL-10 is known to inhibit the immune response to Mtb in murine models through the negative regulation of key pro-inflammatory cytokines and the subsequent Th1 response. We show here, using a combination of transcriptomic analysis, genetics and pharmacological inhibitors that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I interferon production. The TPL-2-ERK1/2 signalling pathway regulated production by macrophages of several cytokines important in the immune response to Mtb as well as regulating induction of a large number of additional genes, many in a type I IFN dependent manner. In the absence of TPL-2 in vivo, excess type I interferon promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I interferon may promote susceptibility to this important disease. PMID:23842752

Loss of PTB or negative regulation of Notch mRNA reveals distinct zones of Notch and actin protein accumulation in Drosophila embryo.

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Cedric S Wesley

Full Text Available Polypyrimidine Tract Binding (PTB protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1 the Notch mRNA is a potential target of PTB, (2 PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3 the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions.

Loss of PTB or Negative Regulation of Notch mRNA Reveals Distinct Zones of Notch and Actin Protein Accumulation in Drosophila Embryo

Science.gov (United States)

Wesley, Cedric S.; Guo, Heng; Chaudhry, Kanita A.; Thali, Markus J.; Yin, Jerry C.; Clason, Todd; Wesley, Umadevi V.

2011-01-01

Polypyrimidine Tract Binding (PTB) protein is a regulator of mRNA processing and translation. Genetic screens and studies of wing and bristle development during the post-embryonic stages of Drosophila suggest that it is a negative regulator of the Notch pathway. How PTB regulates the Notch pathway is unknown. Our studies of Drosophila embryogenesis indicate that (1) the Notch mRNA is a potential target of PTB, (2) PTB and Notch functions in the dorso-lateral regions of the Drosophila embryo are linked to actin regulation but not their functions in the ventral region, and (3) the actin-related Notch activity in the dorso-lateral regions might require a Notch activity at or near the cell surface that is different from the nuclear Notch activity involved in cell fate specification in the ventral region. These data raise the possibility that the Drosophila embryo is divided into zones of different PTB and Notch activities based on whether or not they are linked to actin regulation. They also provide clues to the almost forgotten role of Notch in cell adhesion and reveal a role for the Notch pathway in cell fusions. PMID:21750738

Functional response of cerebral blood flow induced by somatosensory stimulation in rats with subarachnoid hemorrhage

Science.gov (United States)

Li, Zhiguo; Huang, Qin; Liu, Peng; Li, Pengcheng; Ma, Lianting; Lu, Jinling

2015-09-01

Subarachnoid hemorrhage (SAH) is often accompanied by cerebral vasospasm (CVS), which is the phenomenon of narrowing of large cerebral arteries, and then can produce delayed ischemic neurological deficit (DIND) such as lateralized sensory dysfunction. CVS was regarded as a major contributor to DIND in patients with SAH. However, therapy for preventing vasospasm after SAH to improve the outcomes may not work all the time. It is important to find answers to the relationship between CVS and DIND after SAH. How local cerebral blood flow (CBF) is regulated during functional activation after SAH still remains poorly understood, whereas, the regulation of CBF may play an important role in weakening the impact of CVS on cortex function. Therefore, it is worthwhile to evaluate the functional response of CBF in the activated cortex in an SAH animal model. Most evaluation of the effect of SAH is presently carried out by neurological behavioral scales. The functional imaging of cortical activation during sensory stimulation may help to reflect the function of the somatosensory cortex more locally than the behavioral scales do. We investigated the functional response of CBF in the somatosensory cortex induced by an electrical stimulation to contralateral forepaw via laser speckle imaging in a rat SAH model. Nineteen Sprague-Dawley rats from two groups (control group, n=10 and SAH group, n=9) were studied. SAH was induced in rats by double injection of autologous blood into the cisterna magna after CSF aspiration. The same surgical procedure was applied in the control group without CSF aspiration or blood injection. Significant CVS was found in the SAH group. Meanwhile, we observed a delayed peak of CBF response in rats with SAH compared with those in the control group, whereas no significant difference was found in magnitude, duration, and areas under curve of relative CBF changes between the two groups. The results suggest that the regulation function of local CBF during

Lysophosphatidic acid receptor-5 negatively regulates cellular responses in mouse fibroblast 3T3 cells

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Dong, Yan; Hirane, Miku; Araki, Mutsumi [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Tsujiuchi, Toshifumi, E-mail: ttujiuch@life.kindai.ac.jp [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)

2014-04-04

Highlights: • LPA{sub 5} inhibits the cell growth and motile activities of 3T3 cells. • LPA{sub 5} suppresses the cell motile activities stimulated by hydrogen peroxide in 3T3 cells. • Enhancement of LPA{sub 5} on the cell motile activities inhibited by LPA{sub 1} in 3T3 cells. • The expression and activation of Mmp-9 were inhibited by LPA{sub 5} in 3T3 cells. • LPA signaling via LPA{sub 5} acts as a negative regulator of cellular responses in 3T3 cells. - Abstract: Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors (LPA{sub 1}–LPA{sub 6}) mediates a variety of biological functions, including cell migration. Recently, we have reported that LPA{sub 1} inhibited the cell motile activities of mouse fibroblast 3T3 cells. In the present study, to evaluate a role of LPA{sub 5} in cellular responses, Lpar5 knockdown (3T3-L5) cells were generated from 3T3 cells. In cell proliferation assays, LPA markedly stimulated the cell proliferation activities of 3T3-L5 cells, compared with control cells. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3-L5 cells were significantly higher than those of control cells. The activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. 3T3-L5 cells stimulated the activation of Mmp-2, correlating with the expression levels of Mmp-2 gene. Moreover, to assess the co-effects of LPA{sub 1} and LPA{sub 5} on cell motile activities, Lpar5 knockdown (3T3a1-L5) cells were also established from Lpar1 over-expressing (3T3a1) cells. 3T3a1-L5 cells increased the cell motile activities of 3T3a1 cells, while the cell motile activities of 3T3a1 cells were significantly lower than those of control cells. These results suggest that LPA{sub 5} may act as a negative regulator of cellular responses in mouse fibroblast 3T3 cells, similar to the case for LPA{sub 1}.

Lysophosphatidic acid receptor-5 negatively regulates cellular responses in mouse fibroblast 3T3 cells