Aberrant methylation of PSD disturbs Rac1-mediated immune responses governing neutrophil chemotaxis and apoptosis in ulcerative colitis-associated carcinogenesis.

PubMed

Kato, Takaharu; Suzuki, Koichi; Okada, Shinichiro; Kamiyama, Hidenori; Maeda, Takafumi; Saito, Masaaki; Koizumi, Kei; Miyaki, Yuichiro; Konishi, Fumio

2012-04-01

We previously reported that the Pleckstrin and Sec7 domain-containing (PSD) gene is preferentially methylated in patients with ulcerative colitis (UC) who developed colorectal cancer (CRC), and is implicated in UC-associated carcinogenesis through its inhibition of apoptosis. This study aimed to determine the potential effect of PSD methylation on its downstream molecule, Ras-related C3 botulinum toxin substrate 1 (Rac1), which governs neutrophil chemotaxis and apoptosis signaling. PSD was knocked down in a normal human fibroblast cell line (HNDF) and a neutrophil-like cell line (HL-60). Both NHDF and HL-60 cells exhibited numerous filamentous-actin (F-actin) rich membrane extensions, resulting in the activation of Rac1; this activation was hampered by PSD silencing. Lipopolysaccharide, a reactive oxygen species (ROS) inducer, stimulated NHDF cells to release ROS and activated caspase‑3/7 in the presence of neutrophils, which was inhibited by PSD knockdown. Migration assays demonstrated that chemotaxis of HL-60 cells was affected by PSD silencing in NHDF cells. Tissue sections from 6 UC patients with CRC and 15 UC patients without CRC were examined. To verify Rac1-mediated chemotaxis in tissue sections, we evaluated the grade of neutrophil infiltration by histological assessment and assessed F-actin and PSD expression by immunohistochemistry. Neutrophil infiltration, F-actin and PSD expression were significantly decreased in specimens from UC patients with PSD methylation compared with those without. Decreased levels of F-actin expression were observed in colorectal mucosa, as well as in infiltrating cells with PSD methylation. PSD expression was preferentially inhibited in colorectal mucosa by PSD methylation, whereas PSD expression was rarely observed in infiltrating cells, regardless of PSD methylation status. These data indicate that aberrant methylation of PSD occurs in UC-associated colorectal mucosa, enabling circumvention of Rac1-mediated immune responses governing neutrophil chemotaxis and apoptosis, and thus plays a pivotal role in the mechanisms underlying UC-associated carcinogenesis.

40 CFR 124.41 - Definitions applicable to PSD permits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

40 CFR 124.41 - Definitions applicable to PSD permits.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

40 CFR 124.41 - Definitions applicable to PSD permits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

40 CFR 124.41 - Definitions applicable to PSD permits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

40 CFR 124.41 - Definitions applicable to PSD permits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression

PubMed Central

Nelson, Christopher D.; Kim, Myung Jong; Hsin, Honor; Chen, Yelin

2013-01-01

Activity of glycogen synthase kinase-3β (GSK-3β) is required for long-term depression (LTD) via molecular mechanisms that are incompletely understood. Here, we report that PSD-95, a major scaffold protein of the postsynaptic density (PSD) that promotes synaptic strength, is phosphorylated on threonine-19 (T19) by GSK-3β. In cultured rat hippocampal neurons, phosphorylation of T19 increases rapidly with chemical LTD and is attenuated by pharmacologic or genetic suppression of GSK-3β. In organotypic rat hippocampal slices, we find that a nonphosphorylatable PSD-95 mutant (T19A) tagged with photoactivatable green fluorescent protein (PAGFP) shows enhanced stability in dendritic spines versus wild-type PSD-95, whereas the phosphomimetic mutant (PSD-95-T19D) is more readily dispersed. Further, overexpression of PSD-95-T19A, but not WT-PSD-95, impairs AMPA receptor internalization and the induction of LTD. These data indicate that phosphorylation on T19 by GSK-3β destabilizes PSD-95 within the PSD and is a critical step for AMPA receptor mobilization and LTD. PMID:23864697

Provider self-disclosure during contraceptive counseling.

PubMed

McLean, Merritt; Steinauer, Jody; Schmittdiel, Julie; Chan, Pamela; Dehlendorf, Christine

2017-02-01

Provider self-disclosure (PSD) - defined as providers making statements regarding personal information to patients - has not been well characterized in the context of contraceptive counseling. In this study, we describe the incidence, content and context of contraceptive PSD. This mixed methods analysis used data from the Provider-Patient Contraceptive Counseling study, for which 349 family planning patients were recruited from 2009 to 2012 from six clinics in the San Francisco Bay Area. Audio-recordings from their visits were analyzed for the presence or absence of PSD, and those visits with evidence of PSD were analyzed using qualitative methods. The associations of patient and provider demographics and patient satisfaction measures, obtained from survey data, with PSD were analyzed using bivariable and multivariable analyses. Thirty-seven percent of providers showed evidence of PSD during at least one visit, and PSD occurred in 9% of clinic visits. Fifty-four percent of PSD statements were about intrauterine devices. About half of PSD statements occurred prior to the final selection of the contraceptive method and appeared to influence the choice of method. In post-visit surveys, all patients who reported receiving PSD considered it to be appropriate, and patient-reported PSD was not statistically associated with measures of patient satisfaction. This study provides some support for the appropriateness of PSD during family planning encounters, at least as practiced during the sampled visits. Further research could explore whether this counseling strategy has an impact on patients' ability to identify the best contraceptive methods for them. In this study, PSD did not have a demonstrated negative effect on the provider-patient relationship. In almost half of visits, PSD appeared to influence patients' choice of a method; whether this influence is beneficial needs further research. Copyright © 2017 Elsevier Inc. All rights reserved.

75 FR 75658 - Approval and Promulgation of Implementation Plans; Alaska: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-06

... Significant Deterioration (PSD) program to reflect changes to the Federal PSD program relating to the... update Alaska's PSD program to reflect changes to the Federal PSD program that would authorize the State of Alaska to regulate GHGs under its PSD program and establish appropriate emission thresholds for...

Differential localization of SAP102 and PSD-95 is revealed in hippocampal spines using super-resolution light microscopy.

PubMed

Zheng, Chan-Ying; Wang, Ya-Xia; Kachar, Bechara; Petralia, Ronald S

2011-01-01

Synapse-associated protein 102 (SAP102) and postsynaptic density 95 (PSD-95) are two major cytoskeleton proteins in the postsynaptic density (PSD). Both of them belong to the membrane-associated guanylate kinase (MAGUK) family, which clusters and anchors glutamate receptors and other proteins at synapses. In our previous study, we found that SAP102 and PSD-95 have different distributions, using combined light/electron microscopy (LM/EM) methods.1 Here, we double labeled endogenous SAP102 and PSD-95 in mature hippocampal neurons, and then took images by two different kinds of super resolution microscopy-Stimulated Emission Depletion microscopy (STED) and DeltaVision OMX 3D super resolution microscopy. We found that our 2D and 3D super resolution data were consistent with our previous LM/EM data, showing significant differences in the localization of SAP102 and PSD-95 in spines: SAP102 is distributed in both the PSD and cytoplasm of spines, while PSD-95 is concentrated only in the PSD area. These results indicate functional differences between SAP102 and PSD-95 in synaptic organization and plasticity.

Loss of PSD-95 Enrichment is not a Prerequisite for Spine Retraction

PubMed Central

Woods, Georgia F.; Oh, Won Chan; Boudewyn, Lauren C.; Mikula, Sarah K.; Zito, Karen

2011-01-01

Changes in neuronal structure are thought to underlie long-term behavioral modifications associated with learning and memory. In particular, considerable evidence implicates the destabilization and retraction of dendritic spines along with the loss of spine synapses as an important cellular mechanism for refining brain circuits, yet the molecular mechanisms regulating spine elimination remain ill-defined. The postsynaptic density protein, PSD-95, is highly enriched in dendritic spines and has been associated with spine stability. Because spines with low levels of PSD-95 are more dynamic, and the recruitment of PSD-95 to nascent spines has been associated with spine stabilization, we hypothesized that loss of PSD-95 enrichment would be a prerequisite for spine retraction. To test this hypothesis, we used dual-color time-lapse two-photon microscopy to monitor rat hippocampal pyramidal neurons co-transfected with PSD-95-GFP and DsRed-Express, and we analyzed the relationship between PSD-95-GFP enrichment and spine morphological changes. Consistent with our hypothesis, we found that the majority of spines that retracted were relatively unenriched for PSD-95-GFP. However, in the subset of PSD-95-GFP-enriched spines that retracted, spine shrinkage and loss of PSD-95-GFP were tightly coupled, suggesting that loss of PSD-95-GFP enrichment did not precede spine retraction. Moreover, we found that in some instances spine retraction resulted in a significant enrichment of PSD-95-GFP on the dendritic shaft. Our data support a model of spine retraction in which loss of PSD-95 enrichment is not required prior to the destabilization of spines. PMID:21865455

Structural analysis of the PSD-95 cluster by electron tomography and CEMOVIS: a proposal for the application of the genetically encoded metallothionein tag.

PubMed

Hirabayashi, Ai; Fukunaga, Yuko; Miyazawa, Atsuo

2014-06-01

Postsynaptic density-95 (PSD-95) accumulates at excitatory postsynapses and plays important roles in the clustering and anchoring of numerous proteins at the PSD. However, a detailed ultrastructural analysis of clusters exclusively consisting of PSD-95 has never been performed. Here, we employed a genetically encoded tag, three tandem repeats of metallothionein (3MT), to study the structure of PSD-95 clusters in cells by electron tomography and cryo-electron microscopy of vitreous sections. We also performed conventional transmission electron microscopy (TEM). Cultured hippocampal neurons expressing a fusion protein of PSD-95 coupled to 3MT (PDS-95-3MT) were incubated with CdCl2 to result in the formation of Cd-bound PSD-95-3MT. Two types of electron-dense deposits composed of Cd-bound PSD-95-3MT were observed in these cells by TEM, as reported previously. Electron tomography revealed the presence of membrane-shaped structures representing PSD-95 clusters at the PSD and an ellipsoidal structure located in the non-synaptic cytoplasm. By TEM, the PSD-95 clusters appeared to be composed of a number of dense cores. In frozen hydrated sections, these dense cores were also found beneath the postsynaptic membrane. Taken together, our findings suggest that dense cores of PSD-95 aggregate to form the larger clusters present in the PSD and the non-synaptic cytoplasm. © The Author 2014. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cdk5 regulates PSD-95 ubiquitination in neurons

PubMed Central

Bianchetta, Michael J.; Lam, TuKiet T.; Jones, Stephen N.; Morabito, Maria A.

2011-01-01

The kinase Cdk5 and its activator p35 have been implicated in drug addiction, neurodegenerative diseases such as Alzheimer’s, learning and memory, and synapse maturation and plasticity. However the molecular mechanisms by which Cdk5 regulates synaptic plasticity are still unclear. PSD-95 is a major postsynaptic scaffolding protein of glutamatergic synapses that regulates synaptic strength and plasticity. PSD-95 is ubiquitinated by the Ubiquitin E3 Ligase Mdm2, and rapid and transient PSD-95 ubiquitination has been implicated in NMDA receptor-induced AMPA receptor endocytosis. Here we demonstrate that genetic or pharmacological reduction of Cdk5 activity increases the interaction of Mdm2 with PSD-95 and enhances PSD-95 ubiquitination without affecting PSD-95 protein levels in vivo in mice, suggesting a non-proteolytic function of ubiquitinated PSD-95 at synapses. We show that PSD-95 ubiquitination correlates with increased interaction with β-adaptin, a subunit of the clathrin adaptor protein complex AP-2. This interaction is increased by genetic reduction of Cdk5 activity or NMDA receptor stimulation and is dependent on Mdm2. Together these results support a function for Cdk5 in regulating PSD-95 ubiqutination and its interaction with AP-2 and suggest a mechanism by which PSD-95 may regulate NMDA receptor-induced AMPA receptor endocytosis. PMID:21849563

Interactions and phosphorylation of postsynaptic density 93 (PSD-93) by extracellular signal-regulated kinase (ERK).

PubMed

Guo, Ming-Lei; Xue, Bing; Jin, Dao-Zhong; Mao, Li-Min; Wang, John Q

2012-07-17

Postsynaptic density 93 (PSD-93) is a protein enriched at postsynaptic sites. As a key scaffolding protein, PSD-93 forms complexes with the clustering of various synaptic proteins to construct postsynaptic signaling networks and control synaptic transmission. Extracellular signal-regulated kinase (ERK) is a prototypic member of a serine/threonine protein kinase family known as mitogen-activated protein kinase (MAPK). This kinase, especially ERK2 isoform, noticeably resides in peripheral structures of neurons, such as dendritic spines and postsynaptic density areas, in addition to its distribution in the cytoplasm and nucleus, although little is known about specific substrates of ERK at synaptic sites. In this study, we found that synaptic PSD-93 is a direct target of ERK. This was demonstrated by direct protein-protein interactions between purified ERK2 and PSD-93 in vitro. The accurate ERK2-binding region seems to locate at an N-terminal region of PSD-93. In adult rat striatal neurons in vivo, native ERK from synaptosomal fractions also associated with PSD-93. In phosphorylation assays, active ERK2 phosphorylated PSD-93. An accurate phosphorylation site was identified at a serine site (S323). In striatal neurons, immunoprecipitated PSD-93 showed basal phosphorylation at an ERK-sensitive site. Our data provide evidence supporting PSD-93 as a new substrate of the synaptic species of ERK. ERK2 possesses the ability to interact with PSD-93 and phosphorylate PSD-93 at a specific site. Published by Elsevier B.V.

40 CFR 124.19 - Appeal of RCRA, UIC, NPDES, and PSD Permits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Appeal of RCRA, UIC, NPDES, and PSD..., and PSD Permits. (a) Within 30 days after a RCRA, UIC, NPDES, or PSD final permit decision (or a... may also decide on its own initiative to review any condition of any RCRA, UIC, NPDES, or PSD permit...

40 CFR 124.19 - Appeal of RCRA, UIC, NPDES, and PSD Permits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Appeal of RCRA, UIC, NPDES, and PSD..., and PSD Permits. (a) Within 30 days after a RCRA, UIC, NPDES, or PSD final permit decision (or a... may also decide on its own initiative to review any condition of any RCRA, UIC, NPDES, or PSD permit...

40 CFR 124.19 - Appeal of RCRA, UIC, NPDES, and PSD Permits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Appeal of RCRA, UIC, NPDES, and PSD..., and PSD Permits. (a) Within 30 days after a RCRA, UIC, NPDES, or PSD final permit decision (or a... may also decide on its own initiative to review any condition of any RCRA, UIC, NPDES, or PSD permit...

Relationship between 5-HTTLPR polymorphism and post-stroke depression.

PubMed

Guo, W Y; Zhang, Z H; Mu, J L; Liu, D; Zhao, L; Yao, Z Y; Song, J G

2016-02-19

Post-stroke depression (PSD) is a mental illness characterized by subjective feelings of depression, cognitive dysfunction, and decreased interest. The serotoninergic system is involved in the pathogenesis of depressive disorders and is regulated by the serotonin transporter gene. The serotonin transporter-linked polymorphic region (5-HTTLPR) has been examined as a factor associated with depression and other mental disorders. This study was performed to explore the relationship between 5-HTTLPR and PSD in a Han Chinese population. In total, 199 patients with PSD and 202 unrelated non-PSD patients were recruited from psychiatric hospitals. Depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. Blood samples were collected from all patients for 5-HTTLPR genotyping. Genotype and allele frequencies were compared between the two groups. SS genotype frequency was significantly higher in the PSD group than in the non-PSD group. LL genotype frequency was significantly higher in the non-PSD group than in the PSD group (P < 0.01). This study describes a positive association between 5-HTTLPR and PSD in a Han Chinese population and provides genetic evidence to support the genetic susceptibility of PSD.

Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95.

PubMed

Vallejo, Daniela; Codocedo, Juan F; Inestrosa, Nibaldo C

2017-04-01

The postsynaptic density (PSD) consists of a lattice-like array of interacting proteins that organizes and stabilizes synaptic receptors, ion channels, structural proteins, and signaling molecules required for normal synaptic transmission and synaptic function. The scaffolding and hub protein postsynaptic density protein-95 (PSD-95) is a major element of central chemical synapses and interacts with glutamate receptors, cell adhesion molecules, and cytoskeletal elements. In fact, PSD-95 can regulate basal synaptic stability as well as the activity-dependent structural plasticity of the PSD and, therefore, of the excitatory chemical synapse. Several studies have shown that PSD-95 is highly enriched at excitatory synapses and have identified multiple protein structural domains and protein-protein interactions that mediate PSD-95 function and trafficking to the postsynaptic region. PSD-95 is also a target of several signaling pathways that induce posttranslational modifications, including palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation; these modifications determine the synaptic stability and function of PSD-95 and thus regulate the fates of individual dendritic spines in the nervous system. In the present work, we review the posttranslational modifications that regulate the synaptic localization of PSD-95 and describe their functional consequences. We also explore the signaling pathways that induce such changes.

A metabonomic investigation on the biochemical perturbation in post-stroke patients with depressive disorder (PSD).

PubMed

Ding, Xinghua; Liu, Ruoxu; Li, Wenkai; Ni, Hengjia; Liu, Yong; Wu, Dandan; Yang, Shuguang; Liu, Jing; Xiao, Bo; Liu, Shaojun

2016-04-01

A metabonomics study based on GC/MS and multivariate statistical analysis was performed involving 28 post stroke depressed (PSD) patients, 27 post-stroke non-depressed (PSND) patients and 33 healthy subjects to investigate the biochemical perturbation in their plasma samples. The outcome of this study showed that there was distinctive metabolic profile for PSD patients. Seven sentinel metabolites showed marked perturbations in PSD patients' blood. The introduction of metabonomics approach may provide a novel metabonomic insight about PSD and the sentinel metabolites for classifying PSD.

Assessment of peak skin dose in interventional cardiology: A comparison between Gafchromic film and dosimetric software em.dose.

PubMed

Greffier, J; Van Ngoc Ty, C; Bonniaud, G; Moliner, G; Ledermann, B; Schmutz, L; Cornillet, L; Cayla, G; Beregi, J P; Pereira, F

2017-06-01

To compare the use of a dose mapping software to Gafchromic film measurement for a simplified peak skin dose (PSD) estimation in interventional cardiology procedure. The study was conducted on a total of 40 cardiac procedures (20 complex coronary angioplasty of chronic total occlusion (CTO) and 20 coronary angiography and coronary angioplasty (CA-PTCA)) conducted between January 2014 to December 2015. PSD measurement (PSD Film ) was obtained by placing XR-RV3 Gafchromic under the patient's back for each procedure. PSD (PSD em.dose ) was computed with the software em.dose©. The calculation was performed on the dose metrics collected from the private dose report of each procedure. Two calculation methods (method A: fluoroscopic kerma equally spread on cine acquisition and B: fluoroscopic kerma is added to one air Kerma cine acquisition that contributes to the PSD) were used to calculate the fluoroscopic dose contribution as fluoroscopic data were not recorded in our interventional room. Statistical analyses were carried out to compare PSD Film and PSD em.dose . The PSD Film median (1st quartile; 3rd quartile) was 0.251(0.190;0.336)Gy for CA-PTCA and 1.453(0.767;2.011)Gy for CTO. For method-A, the PSD em.dose was 0.248(0.182;0.369)Gy for CA-PTCA and 1.601(0.892;2.178)Gy for CTO, and 0.267(0.223;0.446)Gy and 1.75 (0.912;2.584)Gy for method-B, respectively. For the two methods, the correlation between PSD Film and PSD em.dose was strong. For all cardiology procedures investigated, the mean deviation between PSD Film and PSD em.dose was 3.4±21.1% for method-A and 17.3%±23.9% for method-B. The dose mapping software is convenient to calculate peak skin dose in interventional cardiology. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice

PubMed Central

2012-01-01

Background Postsynaptic density (PSD)-95-like membrane-associated guanylate kinases (PSD-MAGUKs) are scaffold proteins in PSDs that cluster signaling molecules near NMDA receptors. PSD-MAGUKs share a common domain structure, including three PDZ (PDZ1/2/3) domains in their N-terminus. While multiple domains enable the PSD-MAGUKs to bind various ligands, the contribution of each PDZ domain to synaptic organization and function is not fully understood. Here, we focused on the PDZ1/2 domains of PSD-95 that bind NMDA-type receptors, and studied the specific roles of the ligand binding of these domains in the assembly of PSD proteins, synaptic properties of hippocampal neurons, and behavior, using ligand binding-deficient PSD-95 cDNA knockin (KI) mice. Results The KI mice showed decreased accumulation of mutant PSD-95, PSD-93 and AMPA receptor subunits in the PSD fraction of the hippocampus. In the hippocampal CA1 region of young KI mice, basal synaptic efficacy was reduced and long-term potentiation (LTP) was enhanced with intact long-term depression. In adult KI mice, there was no significant change in the magnitude of LTP in CA1, but robustly enhanced LTP was induced at the medial perforant path-dentate gyrus synapses, suggesting that PSD-95 has an age- and subregion-dependent role. In a battery of behavioral tests, KI mice showed markedly abnormal anxiety-like behavior, impaired spatial reference and working memory, and impaired remote memory and pattern separation in fear conditioning test. Conclusions These findings reveal that PSD-95 including its ligand binding of the PDZ1/2 domains controls the synaptic clustering of PSD-MAGUKs and AMPA receptors, which may have an essential role in regulating hippocampal synaptic transmission, plasticity, and hippocampus-dependent behavior. PMID:23268962

Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice.

PubMed

Nagura, Hitoshi; Ishikawa, Yasuyuki; Kobayashi, Katsunori; Takao, Keizo; Tanaka, Tomo; Nishikawa, Kouki; Tamura, Hideki; Shiosaka, Sadao; Suzuki, Hidenori; Miyakawa, Tsuyoshi; Fujiyoshi, Yoshinori; Doi, Tomoko

2012-12-26

Postsynaptic density (PSD)-95-like membrane-associated guanylate kinases (PSD-MAGUKs) are scaffold proteins in PSDs that cluster signaling molecules near NMDA receptors. PSD-MAGUKs share a common domain structure, including three PDZ (PDZ1/2/3) domains in their N-terminus. While multiple domains enable the PSD-MAGUKs to bind various ligands, the contribution of each PDZ domain to synaptic organization and function is not fully understood. Here, we focused on the PDZ1/2 domains of PSD-95 that bind NMDA-type receptors, and studied the specific roles of the ligand binding of these domains in the assembly of PSD proteins, synaptic properties of hippocampal neurons, and behavior, using ligand binding-deficient PSD-95 cDNA knockin (KI) mice. The KI mice showed decreased accumulation of mutant PSD-95, PSD-93 and AMPA receptor subunits in the PSD fraction of the hippocampus. In the hippocampal CA1 region of young KI mice, basal synaptic efficacy was reduced and long-term potentiation (LTP) was enhanced with intact long-term depression. In adult KI mice, there was no significant change in the magnitude of LTP in CA1, but robustly enhanced LTP was induced at the medial perforant path-dentate gyrus synapses, suggesting that PSD-95 has an age- and subregion-dependent role. In a battery of behavioral tests, KI mice showed markedly abnormal anxiety-like behavior, impaired spatial reference and working memory, and impaired remote memory and pattern separation in fear conditioning test. These findings reveal that PSD-95 including its ligand binding of the PDZ1/2 domains controls the synaptic clustering of PSD-MAGUKs and AMPA receptors, which may have an essential role in regulating hippocampal synaptic transmission, plasticity, and hippocampus-dependent behavior.

Effects of recruitment, growth, and exploitation on walleye population size structure in northern Wisconsin lakes

USGS Publications Warehouse

Hansen, Michael J.; Nate, Nancy A.

2014-01-01

We evaluated the dynamics of walleye Sander vitreus population size structure, as indexed by the proportional size distribution (PSD) of quality-length fish, in Escanaba Lake during 1967–2003 and in 204 other lakes in northern Wisconsin during 1990–2011. We estimated PSD from angler-caught walleyes in Escanaba Lake and from spring electrofishing in 204 other lakes, and then related PSD to annual estimates of recruitment to age-3, length at age 3, and annual angling exploitation rate. In Escanaba Lake during 1967–2003, annual estimates of PSD were highly dynamic, growth (positively) explained 35% of PSD variation, recruitment explained only 3% of PSD variation, and exploitation explained only 7% of PSD variation. In 204 other northern Wisconsin lakes during 1990–2011, PSD varied widely among lakes, recruitment (negatively) explained 29% of PSD variation, growth (positively) explained 21% of PSD variation, and exploitation explained only 4% of PSD variation. We conclude that population size structure was most strongly driven by recruitment and growth, rather than exploitation, in northern Wisconsin walleye populations. Studies of other species over wide spatial and temporal ranges of recruitment, growth, and mortality are needed to determine which dynamic rate most strongly influences population size structure of other species. Our findings indicate a need to be cautious about assuming exploitation is a strong driver of walleye population size structure.

40 CFR 52.1519 - Identification of plan-conditional approval.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Air Act (CAA) elements 110(a)(2)(A), (C) only as it relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (E)(ii), and (J) only as it relates to the PSD program. This conditional... relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (E)(ii), and (J) only as it...

40 CFR 52.1519 - Identification of plan-conditional approval.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Air Act (CAA) elements 110(a)(2)(A), (C) only as it relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (E)(ii), and (J) only as it relates to the PSD program. This conditional... relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (E)(ii), and (J) only as it...

Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs.

PubMed

Zhu, Jinwei; Zhou, Qingqing; Shang, Yuan; Li, Hao; Peng, Mengjuan; Ke, Xiao; Weng, Zhuangfeng; Zhang, Rongguang; Huang, Xuhui; Li, Shawn S C; Feng, Guoping; Lu, Youming; Zhang, Mingjie

2017-12-26

The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2.

PubMed

Zheng, Sika; Gray, Erin E; Chawla, Geetanjali; Porse, Bo Torben; O'Dell, Thomas J; Black, Douglas L

2012-01-15

Postsynaptic density protein 95 (PSD-95) is essential for synaptic maturation and plasticity. Although its synaptic regulation has been widely studied, the control of PSD-95 cellular expression is not understood. We found that Psd-95 was controlled post-transcriptionally during neural development. Psd-95 was transcribed early in mouse embryonic brain, but most of its product transcripts were degraded. The polypyrimidine tract binding proteins PTBP1 and PTBP2 repressed Psd-95 (also known as Dlg4) exon 18 splicing, leading to premature translation termination and nonsense-mediated mRNA decay. The loss of first PTBP1 and then of PTBP2 during embryonic development allowed splicing of exon 18 and expression of PSD-95 late in neuronal maturation. Re-expression of PTBP1 or PTBP2 in differentiated neurons inhibited PSD-95 expression and impaired the development of glutamatergic synapses. Thus, expression of PSD-95 during early neural development is controlled at the RNA level by two PTB proteins whose sequential downregulation is necessary for synapse maturation.

Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95.

PubMed

Hafner, Anne-Sophie; Penn, Andrew C; Grillo-Bosch, Dolors; Retailleau, Natacha; Poujol, Christel; Philippat, Amandine; Coussen, Françoise; Sainlos, Matthieu; Opazo, Patricio; Choquet, Daniel

2015-04-22

PSD-95 is a prominent organizer of the postsynaptic density (PSD) that can present a filamentous orientation perpendicular to the plasma membrane. Interactions between PSD-95 and transmembrane proteins might be particularly sensitive to this orientation, as "long" cytoplasmic tails might be required to reach deeper PSD-95 domains. Extension/retraction of transmembrane protein C-tails offer a new way of regulating binding to PSD-95. Using stargazin as a model, we found that enhancing the apparent length of stargazin C-tail through phosphorylation or by an artificial linker was sufficient to potentiate binding to PSD-95, AMPAR anchoring, and synaptic transmission. A linear extension of stargazin C-tail facilitates binding to PSD-95 by preferentially engaging interaction with the farthest located PDZ domains regarding to the plasma membrane, which present a greater affinity for the stargazin PDZ-domain-binding motif. Our study reveals that the concerted orientation of the stargazin C-tail and PSD-95 is a major determinant of synaptic strength. Copyright © 2015 Elsevier Inc. All rights reserved.

Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Aβ and tau pathology in transgenic mouse models of Alzheimer's disease.

PubMed

Shao, Charles Y; Mirra, Suzanne S; Sait, Hameetha B R; Sacktor, Todd C; Sigurdsson, Einar M

2011-09-01

Impairment of synaptic plasticity underlies memory dysfunction in Alzheimer's disease (AD). Molecules involved in this plasticity such as PSD-95, a major postsynaptic scaffold protein at excitatory synapses, may play an important role in AD pathogenesis. We examined the distribution of PSD-95 in transgenic mice of amyloidopathy (5XFAD) and tauopathy (JNPL3) as well as in AD brains using double-labeling immunofluorescence and confocal microscopy. In wild type control mice, PSD-95 primarily labeled neuropil with distinct distribution in hippocampal apical dendrites. In 3-month-old 5XFAD mice, PSD-95 distribution was similar to that of wild type mice despite significant Aβ deposition. However, in 6-month-old 5XFAD mice, PSD-95 immunoreactivity in apical dendrites markedly decreased and prominent immunoreactivity was noted in neuronal soma in CA1 neurons. Similarly, PSD-95 immunoreactivity disappeared from apical dendrites and accumulated in neuronal soma in 14-month-old, but not in 3-month-old, JNPL3 mice. In AD brains, PSD-95 accumulated in Hirano bodies in hippocampal neurons. Our findings support the notion that either Aβ or tau can induce reduction of PSD-95 in excitatory synapses in hippocampus. Furthermore, this PSD-95 reduction is not an early event but occurs as the pathologies advance. Thus, the time-dependent PSD-95 reduction from synapses and accumulation in neuronal soma in transgenic mice and Hirano bodies in AD may mark postsynaptic degeneration that underlies long-term functional deficits.

Interaction partners of PSD-93 studied by X-ray crystallography and fluorescence polarization spectroscopy.

PubMed

Fiorentini, Monica; Bach, Anders; Strømgaard, Kristian; Kastrup, Jette S; Gajhede, Michael

2013-04-01

PSD-93 (chapsyn-110, DLG2) is a member of the family of membrane-associated guanylate kinase (MAGUK) proteins. The MAGUK proteins are involved in receptor localization and signalling pathways. The best characterized MAGUK protein, PSD-95, is known to be involved in NMDA receptor signalling via its PDZ domains. The PDZ domains of PSD-95 and PSD-93 are structurally very similar, but relatively little is known about the function of PSD-93. PSD-93 has been suggested to interact with GluD2 from the family of ionotropic glutamate receptors. Here, the interactions of four residues (GTSI) representing the extreme C-terminus of GluD2 with PSD-93 PDZ1 have been investigated in the crystalline phase. Two different binding modes of these residues were observed, suggesting that the peptide is not tightly bound to PSD-93 PDZ1. In accordance, the two N-terminal PSD-93 PDZ domains show no appreciable binding affinity for a GluD2-derived C-terminal octapeptide, whereas micromolar affinity was observed for a GluN2B-derived C-terminal octapeptide. This indicates that if present, the interactions between GluD2 and PSD-93 involve more than the extreme terminus of the receptor. In contrast, the tumour-suppressor protein SCRIB PDZ3 shows low micromolar affinity towards the GluD2-derived octapeptide, which is in agreement with previous findings using high-throughput assays.

40 CFR 52.530 - Significant deterioration of air quality.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Air Resource Management that establishes prevention of significant deterioration (PSD) applicability...-emitting sources and issue GHG PSD permits. FDEP's December 19, 2013 SIP revision also includes a GHG PSD Permit Transition Plan which governs the transition from EPA administering GHG PSD permitting...

Development of Software to Model AXAF-I Image Quality

NASA Technical Reports Server (NTRS)

Geary, Joseph; Hawkins, Lamar; Ahmad, Anees; Gong, Qian

1997-01-01

This report describes work conducted on Delivery Order 181 between October 1996 through June 1997. During this period software was written to: compute axial PSD's from RDOS AXAF-I mirror surface maps; plot axial surface errors and compute PSD's from HDOS "Big 8" axial scans; plot PSD's from FITS format PSD files; plot band-limited RMS vs axial and azimuthal position for multiple PSD files; combine and organize PSD's from multiple mirror surface measurements formatted as input to GRAZTRACE; modify GRAZTRACE to read FITS formatted PSD files; evaluate AXAF-I test results; improve and expand the capabilities of the GT x-ray mirror analysis package. During this period work began on a more user-friendly manual for the GT program, and improvements were made to the on-line help manual.

[The relationship between acute inflammatory cytokines, nerve function defect, daily living ability and PSD].

PubMed

Li, Ping; Zhang, Qiao-Lian; Li, Shuang-Ying

2017-02-08

To investigate the correlation between poststroke depression (PSD) and serum levels of inflammatory cytokines, neurologic impairment, daily life ability in patients with acute cerebral infarction at different time. Two hundreds and eighty patients who admitted to our hospital with a diagnosis of acute infarction excluded the patients mismatch conditions were evaluated by Hamilton depres-sion rating scale (HDRS) to diagnose PSD respectively at admission and 3 months after stroke. Serum inflammatory cytokines high-sensitivity C-reactive protein(hs-CRP), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were determined. NIH stroke scale(NIHSS) and Barthel index for daily life ability were used to evaluate nerve functions. Then we analyzed the correlation between PSD and serum inflammatory cytokines, correlation between PSD and functional impairment and daily life ability at different time. Logistic regression was performed to ana-lyze the risk factors of PSD. The PSD incidence was higher in recovery stage than that in acute stage, but there was no difference. Serum inflammatory cytokines were higher in PSD group at admission than that in non-PSD group. The NIHSS score and Barthel index in PSD group were different from those in non-group at acute and recovery stage. The OR score was 1.765, 1.646, 1.817, 1.188 and 2.015 respec-tively to TNF-α, IL-6 and Barthel index in the acute phase and to NIHSS and Barthel index in recovery stage. The pathogenesis of PSD at different courses of stroke is not same. TNF-α, IL-6 and Barthel index are the independent risk factors of PSD in acute phase, so do NIHSS score and Barthel index in recovery period.

Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome

PubMed Central

Ifrim, Marius F.; Williams, Kathryn R.

2015-01-01

Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3′UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3′UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS. PMID:25948262

Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome.

PubMed

Ifrim, Marius F; Williams, Kathryn R; Bassell, Gary J

2015-05-06

Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3'UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3'UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS. Copyright © 2015 the authors 0270-6474/15/357116-15$15.00/0.

SU-E-T-167: Characterization of In-House Plastic Scintillator Detectors Array for Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, T; Liu, H; Dimofte, A

Purpose: To characterize basic performance of plastic scintillator detectors (PSD) array designed for dosimetry of radiation therapy. Methods: An in-house PSD array has been developed by placing single point PSD into customized 2D holder. Each point PSD is a plastic scintillating fiber-based detector designed for highly accurate measurement of small radiotherapy fields used in patient plan verification and machine commissioning and QA procedures. A parallel fiber without PSD is used for Cerenkov separation by subtracting from PSD readings. Cerenkov separation was confirmed by optical spectroscopy. Alternative Cerenkov separation approaches are also investigated. The optical signal was converted to electronic signalmore » with a photodiode and then subsequently amplified. We measured its dosimetry performance, including percentage depth dose and output factor, and compared with reference ion chamber measurements. The PSD array is then placed along the radiation beam for multiple point dose measurement, representing subsets of PDD measurements, or perpendicular to the beam for profile measurements. Results: The dosimetry results of PSD point measurements agree well with reference ion chamber measurements. For percentage depth dose, the maximal differences between PSD and ion chamber results are 3.5% and 2.7% for 6MV and 15MV beams, respectively. For the output factors, PSD measurements are within 3% from ion chamber results. PDD and profile measurement with PSD array are also performed. Conclusions: The current design of multichannel PSD array is feasible for the dosimetry measurement in radiation therapy. Dose distribution along or perpendicular to the beam path could be measured. It might as well be used as range verification in proton therapy.A PS hollow fiber detector will be investigated to eliminate the Cerenkov radiation effect so that all 32 channels can be used.« less

Detergent-dependent separation of postsynaptic density, membrane rafts and other subsynaptic structures from the synaptic plasma membrane of rat forebrain.

PubMed

Zhao, LiYing; Sakagami, Hiroyuki; Suzuki, Tatsuo

2014-10-01

We systematically investigated the purification process of post-synaptic density (PSD) and post-synaptic membrane rafts (PSRs) from the rat forebrain synaptic plasma membranes by examining the components and the structures of the materials obtained after the treatment of synaptic plasma membranes with TX-100, n-octyl β-d-glucoside (OG) or 3-([3-cholamidopropyl]dimethylammonio)-2-hydroxy-1-propanesulfonate (CHAPSO). These three detergents exhibited distinct separation profiles for the synaptic subdomains. Type I and type II PSD proteins displayed mutually exclusive distribution. After TX-100 treatment, type I PSD was recovered in two fractions: a pellet and an insoluble fraction 8, which contained partially broken PSD-PSR complexes. Conventional PSD was suggested to be a mixture of these two PSD pools and did not contain type II PSD. An association of type I PSD with PSRs was identified in the TX-100 treatment, and those with type II PSD in the OG and CHAPSO treatments. An association of GABA receptors with gephyrin was easily dissociated. OG at a high concentration solubilized the type I PSD proteins. CHAPSO treatment resulted in a variety of distinct fractions, which contained certain novel structures. Two different pools of GluA, either PSD or possibly raft-associated, were identified in the OG and CHAPSO treatments. These results are useful in advancing our understanding of the structural organization of synapses at the molecular level. We systematically investigated the purification process of post-synaptic density (PSD) and synaptic membrane rafts by examining the structures obtained after treatment of the SPMs with TX-100, n-octyl β-d-glucoside or CHAPSO. Differential distribution of type I and type II PSD, synaptic membrane rafts, and other novel subdomains in the SPM give clues to understand the structural organization of synapses at the molecular level. © 2014 International Society for Neurochemistry.

Power Spectral Density Specification and Analysis of Large Optical Surfaces

NASA Technical Reports Server (NTRS)

Sidick, Erkin

2009-01-01

The 2-dimensional Power Spectral Density (PSD) can be used to characterize the mid- and the high-spatial frequency components of the surface height errors of an optical surface. We found it necessary to have a complete, easy-to-use approach for specifying and evaluating the PSD characteristics of large optical surfaces, an approach that allows one to specify the surface quality of a large optical surface based on simulated results using a PSD function and to evaluate the measured surface profile data of the same optic in comparison with those predicted by the simulations during the specification-derivation process. This paper provides a complete mathematical description of PSD error, and proposes a new approach in which a 2-dimentional (2D) PSD is converted into a 1-dimentional (1D) one by azimuthally averaging the 2D-PSD. The 1D-PSD calculated this way has the same unit and the same profile as the original PSD function, thus allows one to compare the two with each other directly.

76 FR 31241 - Prevention of Significant Deterioration (PSD) Program; Massachusetts; Announcing Delegation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

... Deterioration (PSD) Program; Massachusetts; Announcing Delegation Agreement Between EPA and Massachusetts... authority to implement and enforce the Federal Prevention of Significant Deterioration (PSD) program to the MassDEP. Therefore, effective that date, MassDEP is the implementing authority for the PSD program in...

75 FR 59081 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-27

... Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations AGENCY: Environmental Protection... the prevention of significant deterioration (PSD) construction permit program under the Federal Clean... potentially subject to the PSD construction permit program. On July 16, 2010, Michigan submitted revisions...

Identification of PSD-95 Depalmitoylating Enzymes.

PubMed

Yokoi, Norihiko; Fukata, Yuko; Sekiya, Atsushi; Murakami, Tatsuro; Kobayashi, Kenta; Fukata, Masaki

2016-06-15

Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering and regulation of AMPA receptor function. However, molecular mechanisms for palmitate cycling on PSD-95 remain incompletely understood, as PSD-95 depalmitoylating enzymes remain unknown. Here, we isolated 38 mouse or rat serine hydrolases and found that a subset specifically depalmitoylated PSD-95 in heterologous cells. These enzymes showed distinct substrate specificity. α/β-Hydrolase domain-containing protein 17 members (ABHD17A, 17B, and 17C), showing the strongest depalmitoylating activity to PSD-95, showed different localization from other candidates in rat hippocampal neurons, and were distributed to recycling endosomes, the dendritic plasma membrane, and the synaptic fraction. Expression of ABHD17 in neurons selectively reduced PSD-95 palmitoylation and synaptic clustering of PSD-95 and AMPA receptors. Furthermore, taking advantage of the acyl-PEGyl exchange gel shift (APEGS) method, we quantitatively monitored the palmitoylation stoichiometry and the depalmitoylation kinetics of representative synaptic proteins, PSD-95, GluA1, GluN2A, mGluR5, Gαq, and HRas. Unexpectedly, palmitate on all of them did not turn over in neurons. Uniquely, most of the PSD-95 population underwent rapid palmitoylation cycles, and palmitate cycling on PSD-95 decelerated accompanied by its increased stoichiometry as synapses developed, probably contributing to postsynaptic receptor consolidation. Finally, inhibition of ABHD17 expression dramatically delayed the kinetics of PSD-95 depalmitoylation. This study suggests that local palmitoylation machinery composed of synaptic DHHC palmitoylating enzymes and ABHD17 finely controls the amount of synaptic PSD-95 and synaptic function. Protein palmitoylation, the most common lipid modification, dynamically regulates neuronal protein localization and function. Its unique reversibility is conferred by DHHC-type palmitoyl acyl transferases (palmitoylating enzymes) and still controversial palmitoyl-protein thioesterases (depalmitoylating enzymes). Here, we identified the membrane-anchored serine hydrolases, ABHD17A, 17B, and 17C, as the physiological PSD-95 depalmitoylating enzymes that regulate PSD-95 palmitoylation cycles in neurons. This study describes the first direct evidence for the neuronal depalmitoylating enzyme and provides a new aspect of the dynamic regulatory mechanisms of synaptic development and synaptic plasticity. In addition, our established APEGS assay, which provides unbiased and quantitative information about the palmitoylation state and dynamics, revealed the distinct regulatory mechanisms for synaptic palmitoylation. Copyright © 2016 Yokoi, Fukata et al.

Identification of PSD-95 Depalmitoylating Enzymes

PubMed Central

Yokoi, Norihiko; Sekiya, Atsushi; Murakami, Tatsuro; Kobayashi, Kenta

2016-01-01

Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering and regulation of AMPA receptor function. However, molecular mechanisms for palmitate cycling on PSD-95 remain incompletely understood, as PSD-95 depalmitoylating enzymes remain unknown. Here, we isolated 38 mouse or rat serine hydrolases and found that a subset specifically depalmitoylated PSD-95 in heterologous cells. These enzymes showed distinct substrate specificity. α/β-Hydrolase domain-containing protein 17 members (ABHD17A, 17B, and 17C), showing the strongest depalmitoylating activity to PSD-95, showed different localization from other candidates in rat hippocampal neurons, and were distributed to recycling endosomes, the dendritic plasma membrane, and the synaptic fraction. Expression of ABHD17 in neurons selectively reduced PSD-95 palmitoylation and synaptic clustering of PSD-95 and AMPA receptors. Furthermore, taking advantage of the acyl-PEGyl exchange gel shift (APEGS) method, we quantitatively monitored the palmitoylation stoichiometry and the depalmitoylation kinetics of representative synaptic proteins, PSD-95, GluA1, GluN2A, mGluR5, Gαq, and HRas. Unexpectedly, palmitate on all of them did not turn over in neurons. Uniquely, most of the PSD-95 population underwent rapid palmitoylation cycles, and palmitate cycling on PSD-95 decelerated accompanied by its increased stoichiometry as synapses developed, probably contributing to postsynaptic receptor consolidation. Finally, inhibition of ABHD17 expression dramatically delayed the kinetics of PSD-95 depalmitoylation. This study suggests that local palmitoylation machinery composed of synaptic DHHC palmitoylating enzymes and ABHD17 finely controls the amount of synaptic PSD-95 and synaptic function. SIGNIFICANCE STATEMENT Protein palmitoylation, the most common lipid modification, dynamically regulates neuronal protein localization and function. Its unique reversibility is conferred by DHHC-type palmitoyl acyl transferases (palmitoylating enzymes) and still controversial palmitoyl-protein thioesterases (depalmitoylating enzymes). Here, we identified the membrane-anchored serine hydrolases, ABHD17A, 17B, and 17C, as the physiological PSD-95 depalmitoylating enzymes that regulate PSD-95 palmitoylation cycles in neurons. This study describes the first direct evidence for the neuronal depalmitoylating enzyme and provides a new aspect of the dynamic regulatory mechanisms of synaptic development and synaptic plasticity. In addition, our established APEGS assay, which provides unbiased and quantitative information about the palmitoylation state and dynamics, revealed the distinct regulatory mechanisms for synaptic palmitoylation. PMID:27307232

The relationship between PSD-95 clustering and spine stability in vivo.

PubMed

Cane, Michele; Maco, Bohumil; Knott, Graham; Holtmaat, Anthony

2014-02-05

The appearance and disappearance of dendritic spines, accompanied by synapse formation and elimination may underlie the experience-dependent reorganization of cortical circuits. The exact temporal relationship between spine and synapse formation in vivo remains unclear, as does the extent to which synapse formation enhances the stability of newly formed spines and whether transient spines produce synapses. We used in utero electroporation of DsRedExpress- and eGFP-tagged postsynaptic density protein 95 (PSD-95) to investigate the relationship between spine and PSD stability in mouse neocortical L2/3 pyramidal cells in vivo. Similar to previous studies, spines and synapses appeared and disappeared, even in naive animals. Cytosolic spine volumes and PSD-95-eGFP levels in spines covaried over time, suggesting that the strength of many individual synapses continuously changes in the adult neocortex. The minority of newly formed spines acquired PSD-95-eGFP puncta. Spines that failed to acquire a PSD rarely survived for more than a day. Although PSD-95-eGFP accumulation was associated with increased spine lifetimes, most new spines with a PSD did not convert into persistent spines. This indicates that transient spines may serve to produce short-lived synaptic contacts. Persistent spines that were destined to disappear showed, on average, reduced PSD-95-eGFP levels well before the actual pruning event. Altogether, our data indicate that the PSD size relates to spine stability in vivo.

TrkB and protein kinase Mζ regulate synaptic localization of PSD-95 in developing cortex.

PubMed

Yoshii, Akira; Murata, Yasunobu; Kim, Jihye; Zhang, Chao; Shokat, Kevan M; Constantine-Paton, Martha

2011-08-17

Postsynaptic density 95 (PSD-95), the major scaffold at excitatory synapses, is critical for synapse maturation and learning. In rodents, eye opening, the onset of pattern vision, triggers a rapid movement of PSD-95 from visual neuron somata to synapses. We showed previously that the PI3 kinase-Akt pathway downstream of BDNF/TrkB signaling stimulates synaptic delivery of PSD-95 via vesicular transport. However, vesicular transport requires PSD-95 palmitoylation to attach it to a lipid membrane. Also, PSD-95 insertion at synapses is known to require this lipid modification. Here, we show that BDNF/TrkB signaling is also necessary for PSD-95 palmitoylation and its transport to synapses in mouse visual cortical layer 2/3 neurons. However, palmitoylation of PSD-95 requires the activation of another pathway downstream of BDNF/TrkB, namely, signaling through phospholipase Cγ and the brain-specific PKC variant protein kinase M ζ (PKMζ). We find that PKMζ selectively regulates phosphorylation of the palmitoylation enzyme ZDHHC8. Inhibition of PKMζ results in a reduction of synaptic PSD-95 accumulation in vivo, which can be rescued by overexpressing ZDHHC8. Therefore, TrkB and PKMζ, two critical regulators of synaptic plasticity, facilitate PSD-95 targeting to synapses. These results also indicate that palmitoylation can be regulated by a trophic factor. Our findings have implications for neurodevelopmental disorders as well as aging brains.

TrkB and PKMζ regulate synaptic localization of PSD-95 in developing cortex

PubMed Central

Yoshii, Akira; Murata, Yasunobu; Kim, Jihye; Zhang, Chao; Shokat, Kevan M.; Constantine-Paton, Martha

2011-01-01

Post-synaptic density 95 (PSD-95), the major scaffold at excitatory synapses, is critical for synapse maturation and learning. In rodents, eye opening, the onset of pattern vision, triggers a rapid movement of PSD-95 from visual neuron somata to synapses. We previously showed that the PI3 kinase-Akt pathway downstream of BDNF/TrkB signaling stimulates synaptic delivery of PSD-95 via vesicular transport. However, vesicular transport requires PSD-95 palmitoylation to attach it to a lipid membrane. Also PSD-95 insertion at synapses is known to require this lipid modification. Here, we show that BDNF/TrkB signaling is also necessary for PSD-95 palmitoylation and its transport to synapses in mouse visual cortical layer 2/3 neurons. However, palmitoylation of PSD-95 requires the activation of another pathway downstream of BDNF/TrkB, namely signaling through PLCγ and the brain-specific PKC variant PKMζ. We find that PKMζ selectively regulates phosphorylation of the palmitoylation enzyme ZDHHC8. Inhibition of PKMζ results in a reduction of synaptic PSD-95 accumulation in vivo, which can be rescued by over-expression ZDHHC8. Therefore, TrkB and PKMζ, two critical regulators of synaptic plasticity, facilitate PSD-95 targeting to synapses. These results also indicate that palmitoylation can be regulated by a trophic factor. Our findings have implications for neurodevelopmental disorders as well as ageing brains. PMID:21849550

Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer's disease mice.

PubMed

Bustos, Fernando J; Ampuero, Estibaliz; Jury, Nur; Aguilar, Rodrigo; Falahi, Fahimeh; Toledo, Jorge; Ahumada, Juan; Lata, Jaclyn; Cubillos, Paula; Henríquez, Berta; Guerra, Miguel V; Stehberg, Jimmy; Neve, Rachael L; Inestrosa, Nibaldo C; Wyneken, Ursula; Fuenzalida, Marco; Härtel, Steffen; Sena-Esteves, Miguel; Varela-Nallar, Lorena; Rots, Marianne G; Montecino, Martin; van Zundert, Brigitte

2017-12-01

The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9). These epi-editors altered critical histone marks and subsequently Dlg4/PSD95 expression, which, importantly, impacted several hippocampal neuron plasticity processes. Intriguingly, transduction of the artificial transcription factor PSD95-VP64 rescued memory deficits in aged and Alzheimer's disease mice. Conclusively, this work validates PSD95 as a key player in memory and establishes epigenetic editing as a potential therapy to treat human neurological disorders. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats.

PubMed

Brianza-Padilla, Malinalli; Bonilla-Jaime, Herlinda; Almanza-Pérez, Julio César; López-López, Ana Laura; Sánchez-Muñoz, Fausto; Vázquez-Palacios, Gonzalo

2016-03-01

Sleep has a fundamental role in the regulation of energy balance, and it is an essential and natural process whose precise impacts on health and disease have not yet been fully elucidated. The aim of this study was to assess the consequences of different periods of paradoxical sleep deprivation (PSD) and recovery from PSD on lipid profile, oral glucose tolerance test (OGTT) results, and changes in insulin, corticosterone, ghrelin, and leptin concentrations. Three-month-old male Wistar rats weighing 250-350 g were submitted to 24, 96, or 192 h of PSD or 192 h of PSD with 480 h of recovery. The PSD was induced by the multiple platforms method. Subsequently, the animals were submitted to an OGTT. One day later, the animals were killed and the levels of triglycerides, total cholesterol, lipoproteins (low-density lipoprotein, very-low-density lipoprotein, and high-density lipoprotein), insulin, ghrelin, leptin, and corticosterone in plasma were quantified. There was a progressive decrease in body weight with increasing duration of PSD. The PSD induced basal hypoglycemia over all time periods evaluated. Evaluation of areas under the curve revealed progressive hypoglycemia only after 96 and 192 h of PSD. There was an increase in corticosterone levels after 192 h of PSD. We conclude that PSD induces alterations in metabolism that are reversed after a recovery period of 20 days.

Inferring Cirrus Size Distributions Through Satellite Remote Sensing and Microphysical Databases

NASA Technical Reports Server (NTRS)

Mitchell, David; D'Entremont, Robert P.; Lawson, R. Paul

2010-01-01

Since cirrus clouds have a substantial influence on the global energy balance that depends on their microphysical properties, climate models should strive to realistically characterize the cirrus ice particle size distribution (PSD), at least in a climatological sense. To date, the airborne in situ measurements of the cirrus PSD have contained large uncertainties due to errors in measuring small ice crystals (D<60 m). This paper presents a method to remotely estimate the concentration of the small ice crystals relative to the larger ones using the 11- and 12- m channels aboard several satellites. By understanding the underlying physics producing the emissivity difference between these channels, this emissivity difference can be used to infer the relative concentration of small ice crystals. This is facilitated by enlisting temperature-dependent characterizations of the PSD (i.e., PSD schemes) based on in situ measurements. An average cirrus emissivity relationship between 12 and 11 m is developed here using the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite instrument and is used to retrieve the PSD based on six different PSD schemes. The PSDs from the measurement-based PSD schemes are compared with corresponding retrieved PSDs to evaluate differences in small ice crystal concentrations. The retrieved PSDs generally had lower concentrations of small ice particles, with total number concentration independent of temperature. In addition, the temperature dependence of the PSD effective diameter De and fall speed Vf for these retrieved PSD schemes exhibited less variability relative to the unmodified PSD schemes. The reduced variability in the retrieved De and Vf was attributed to the lower concentrations of small ice crystals in the retrieved PSD.

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

40 CFR 52.1837 - Original identification of plan section.

Code of Federal Regulations, 2012 CFR

2012-07-01

... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

40 CFR 52.1837 - Original identification of plan section.

Code of Federal Regulations, 2014 CFR

2014-07-01

... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

40 CFR 52.1837 - Original identification of plan section.

Code of Federal Regulations, 2011 CFR

2011-07-01

... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

40 CFR 52.1837 - Original identification of plan section.

Code of Federal Regulations, 2013 CFR

2013-07-01

... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

76 FR 7546 - Proposed Information Collection; Comment Request; Prohibited Species Donation (PSD) Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-10

... Collection; Comment Request; Prohibited Species Donation (PSD) Program AGENCY: National Oceanic and... species donation (PSD) program for Pacific salmon and Pacific halibut has effectively reduced regulatory... distribution of salmon and halibut. The PSD program requires a collection-of-information so that NMFS can...

76 FR 81836 - Approval and Promulgation of Air Quality Implementation Plans; New Mexico; Albuquerque/Bernalillo...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... Significant Deterioration (PSD) program to establish appropriate emission thresholds for determining which new stationary sources and modification projects become subject to Albuquerque/Bernalillo County's PSD permitting..., New Mexico December 15, 2010 PSD SIP revision because the Agency has determined that this PSD SIP...

77 FR 36442 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-19

... Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations AGENCY: Environmental Protection... Significant Deterioration (PSD) construction permit program of State of Michigan's State Implementation Plan (SIP) to meet the Clean Air Act (CAA) requirements for PSD in Class I Areas attaining the National...

76 FR 26933 - Approval and Promulgation of Implementation Plans; Connecticut: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

... Significant Deterioration (PSD) program. First, the revision provides Connecticut with authority to issue PSD... determining which new stationary sources and modification projects become subject to Connecticut's PSD... required to apply its PSD program to GHG- emitting sources, and unless it does so (or unless EPA...

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

40 CFR 52.1837 - Original identification of plan section.

Code of Federal Regulations, 2010 CFR

2010-07-01

... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

75 FR 70254 - PSD and Title V Permitting Guidance for Greenhouse Gases

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OAR-2010-0841; FRL-9228-2] PSD and Title V Permitting..., ``PSD and Title V Permitting Guidance for Greenhouse Gases'' on its significant guidance Internet Web... guidance titled, ``PSD and Title V Permitting Guidance for Greenhouse Gases.'' This document has been...

On-orbit Status and Light Attenuation Behavior of the DAMPE-PSD

NASA Astrophysics Data System (ADS)

Li, Y.; Zhang, Y. P.; Zhang, Y. J.; Sun, Z. Y.; Yu, Y. H.; Dong, T. K.; Ma, P. X.; Wang, Y. P.; Yuan, Q.

2017-11-01

The DArk Matter Particle Explorer (DAMPE) is a high-resolution multi-purpose space-borne device for detecting the high-energy cosmic-rays like e±, γ-rays, protons, and heavy-ions, which was launched on 2015 December 17th. The Plastic Scintillator Detector (PSD) is the top-most sub-detector of DAMPE. The PSD is designed to measure the charge of incident high-energy particles, and to serve as a veto detector for discriminating γ-rays from the charged particles. In this paper, the on-orbit status of the PSD after launching in terms of high voltage (HV) and temperature stabilities is presented. The temperature and the HV variations of the PSD are less than 1°C and 0.5%, respectively. By using the on-orbit data, the attenuation lengths of PSD bars are obtained according to an empirical formula. A preliminary charge spectrum reconstructed from the X-layer of the PSD is obtained.

40 CFR 124.3 - Application for a permit.

Code of Federal Regulations, 2011 CFR

2011-07-01

... person who requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit....21 (PSD), and 122.1 (NPDES). Applications are not required for RCRA permits by rule (§ 270.60...), 144.31 (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits...

75 FR 19567 - Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-15

...-AP80 Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR... changed our interpretation of the PSD and nonattainment NSR regulations relating to the definition of... Historic Approach Under both the nonattainment NSR provisions of the CAA as well as the PSD provisions, a...

40 CFR 52.270 - Significant deterioration of air quality.

Code of Federal Regulations, 2013 CFR

2013-07-01

... applicable State plan for the State of California. (b) District PSD Plans. (1) The PSD rules for Sacramento... of PSD increments. (ii) Those projects which are major stationary sources or major modifications... 83-01, 5/6/83. (2) The PSD rules for North Coast Unified Air Quality Management District are approved...

40 CFR 124.3 - Application for a permit.

Code of Federal Regulations, 2012 CFR

2012-07-01

... person who requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit....21 (PSD), and 122.1 (NPDES). Applications are not required for RCRA permits by rule (§ 270.60...), 144.31 (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits...

Evaluating soybean breeding lines developed from differenct sources of resistance to phomopsis seed decay

USDA-ARS?s Scientific Manuscript database

Phomopsis seed decay (PSD) causes poor soybean seed quality worldwide. The primary causal agent of PSD is Phomopsis longicolla (syn. Diaporthe longicolla). Breeding for PSD-resistance is the most effective long-term strategy to control this disease. To develop soybean lines with resistance to PSD, m...

40 CFR 124.3 - Application for a permit.

Code of Federal Regulations, 2013 CFR

2013-07-01

... person who requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit....21 (PSD), and 122.1 (NPDES). Applications are not required for RCRA permits by rule (§ 270.60...), 144.31 (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits...

75 FR 55978 - Approval and Promulgation of Air Quality Implementation Plans; Texas; Revisions to the New Source...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

... Implementation Plan (SIP); Prevention of Significant Deterioration (PSD) AGENCY: Environmental Protection Agency... Texas PSD State Implementation Plan (SIP). EPA is approving a SIP revision submitted February 1, 2006... Texas PSD SIP; it merely approves reorganization and renumbering of the Texas PSD SIP rules. Further...

76 FR 30832 - Approval and Promulgation of Air Quality Implementation Plans; West Virginia; Permits for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-27

... for the prevention of significant deterioration (PSD) areas in West Virginia. This action will also add the Federally equivalent provisions to the rules for the PSD program as they pertain to... (CUs) to make the West Virginia PSD program consistent with the Federal PSD program. This action is...

40 CFR 52.270 - Significant deterioration of air quality.

Code of Federal Regulations, 2012 CFR

2012-07-01

... applicable State plan for the State of California. (b) District PSD Plans. (1) The PSD rules for Sacramento... of PSD increments. (ii) Those projects which are major stationary sources or major modifications... 83-01, 5/6/83. (2) The PSD rules for North Coast Unified Air Quality Management District are approved...

40 CFR 52.270 - Significant deterioration of air quality.

Code of Federal Regulations, 2011 CFR

2011-07-01

... applicable State plan for the State of California. (b) District PSD Plans. (1) The PSD rules for Sacramento... of PSD increments. (ii) Those projects which are major stationary sources or major modifications... 83-01, 5/6/83. (2) The PSD rules for North Coast Unified Air Quality Management District are approved...

40 CFR 124.3 - Application for a permit.

Code of Federal Regulations, 2010 CFR

2010-07-01

... person who requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit....21 (PSD), and 122.1 (NPDES). Applications are not required for RCRA permits by rule (§ 270.60...), 144.31 (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits...

76 FR 2589 - Approval and Promulgation of Implementation Plans; Mississippi: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-14

... clarify that the version of Mississippi's Prevention of Significant Deterioration (PSD) regulations... Mississippi's PSD regulations includes both a SIP revision approved by EPA on December 20, 2010, and a SIP... oxides (NO X ) as a precursor to ozone for PSD purposes) was included in the PSD rules that were...

77 FR 56124 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD and NSR Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

... Promulgation of Air Quality Implementation Plans; Michigan; PSD and NSR Regulations AGENCY: Environmental... the prevention of significant deterioration (PSD) construction permit program for the purpose of... approving Michigan's request to revise its SIP to add rule R. 336.2816 to be consistent with Federal PSD...

40 CFR 52.270 - Significant deterioration of air quality.

Code of Federal Regulations, 2014 CFR

2014-07-01

... applicable State plan for the State of California. (b) District PSD Plans. (1) The PSD rules for Sacramento... of PSD increments. (ii) Those projects which are major stationary sources or major modifications... 83-01, 5/6/83. (2) The PSD rules for North Coast Unified Air Quality Management District are approved...

Coxsackievirus and adenovirus receptor (CAR) mediates trafficking of acid sensing ion channel 3 (ASIC3) via PSD-95.

PubMed

Excoffon, Katherine J D A; Kolawole, Abimbola O; Kusama, Nobuyoshi; Gansemer, Nicholas D; Sharma, Priyanka; Hruska-Hageman, Alesia M; Petroff, Elena; Benson, Christopher J

2012-08-17

We have previously shown that the Coxsackievirus and adenovirus receptor (CAR) can interact with post-synaptic density 95 (PSD-95) and localize PSD-95 to cell-cell junctions. We have also shown that activity of the acid sensing ion channel (ASIC3), a H(+)-gated cation channel that plays a role in mechanosensation and pain signaling, is negatively modulated by PSD-95 through a PDZ-based interaction. We asked whether CAR and ASIC3 simultaneously interact with PSD-95, and if so, whether co-expression of these proteins alters their cellular distribution and localization. Results indicate that CAR and ASIC3 co-immunoprecipitate only when co-expressed with PSD-95. CAR also brings both PSD-95 and ASIC3 to the junctions of heterologous cells. Moreover, CAR rescues PSD-95-mediated inhibition of ASIC3 currents. These data suggest that, in addition to activity as a viral receptor and adhesion molecule, CAR can play a role in trafficking proteins, including ion channels, in a PDZ-based scaffolding complex. Copyright © 2012 Elsevier Inc. All rights reserved.

Ezh1 and Ezh2 differentially regulate PSD-95 gene transcription in developing hippocampal neurons.

PubMed

Henriquez, Berta; Bustos, Fernando J; Aguilar, Rodrigo; Becerra, Alvaro; Simon, Felipe; Montecino, Martin; van Zundert, Brigitte

2013-11-01

Polycomb Repressive Complex 2 (PRC2) mediates transcriptional silencing by catalyzing histone H3 lysine 27 trimethylation (H3K27me3), but its role in the maturation of postmitotic mammalian neurons remains largely unknown. We report that the PRC2 paralogs Ezh1 and Ezh2 are differentially expressed during hippocampal development. We show that depletion of Ezh2 leads to increased expression of PSD-95, a critical plasticity gene, and that reduced PSD-95 gene transcription is correlated with enrichment of Ezh2 at the PSD-95 gene promoter; however, the H3K27me3 epigenetic mark is not present at the PSD-95 gene promoter, likely due to the antagonizing effects of the H3S28P and H3K27Ac marks and the activity of the H3K27 demethylases JMJD3 and UTX. In contrast, increased PSD-95 gene transcription is accompanied by the presence of Ezh1 and elongation-engaged RNA Polymerase II complexes at the PSD-95 gene promoter, while knock-down of Ezh1 reduces PSD-95 transcription. These results indicate that Ezh1 and Ezh2 have antagonistic roles in regulating PSD-95 transcription. © 2013.

Race/ethnic Differences in Post-stroke Depression (PSD): Findings from the Stroke Warning Information and Faster Treatment (SWIFT) Study.

PubMed

Goldmann, Emily; Roberts, Eric T; Parikh, Nina S; Lord, Aaron S; Boden-Albala, Bernadette

2016-01-21

Post-stroke depression (PSD) is common and associated with poor stroke outcomes, but few studies have examined race/ethnic disparities in PSD. Given the paucity of work and inconsistent findings in this important area of research, our study aimed to examine race/ethnic differences in depression in a multi-ethnic cohort of stroke patients. Longitudinal. Prospective trial of a post-stroke educational intervention. 1,193 mild/moderate ischemic stroke/transient ischemic attack (TIA) patients. We used the Center for Epidemiologic Studies Depression (CES-D) Scale to assess subthreshold (CES-D score 8-15) and full (CES-D score ≥ 16) depression at one month ("early") and 12 months ("late") following stroke. Multinomial logistic regression analyses examined the association between race/ethnicity and early and late PSD separately. The prevalence of subthreshold and full PSD was 22.5% and 32.6% in the early period and 22.0% and 27.4% in the late period, respectively. Hispanics had 60% lower odds of early full PSD compared with non-Hispanic Whites after adjusting for other covariates (OR=.4, 95% CI: .2, .8). Race/ethnicity was not significantly associated with late PSD. Hispanic stroke patients had half the odds of PSD in early period compared with Whites, but no difference was found in the later period. Further studies comparing trajectories of PSD between race/ethnic groups may further our understanding of race/ethnic disparities in PSD and help identify effective interventions.

PSD-93 Attenuates Amyloid-β-Mediated Cognitive Dysfunction by Promoting the Catabolism of Amyloid-β.

PubMed

Yu, Linjie; Liu, Yi; Yang, Hui; Zhu, Xiaolei; Cao, Xiang; Gao, Jun; Zhao, Hui; Xu, Yun

2017-01-01

Amyloid-β (Aβ) is a key neuropathological hallmark of Alzheimer's disease (AD). Postsynaptic density protein 93 (PSD-93) is a key scaffolding protein enriched at postsynaptic sites. The aim of the present study was to examine whether PSD-93 overexpression could alleviate Aβ-induced cognitive dysfunction in APPswe/PS1dE9 (APP/PS1) mice by reducing Aβ levels in the brain. The level of PSD-93 was significantly decreased in the hippocampus of 6-month-old APP/PS1 mice compared with that in wild-type mice. Following lentivirus-mediated PSD-93 overexpression, cognitive function, synaptic function, and amyloid burden were investigated. The open field test, Morris water maze test, and fear condition test revealed that PSD-93 overexpression ameliorated spatial memory deficits in APP/PS1 mice. The facilitation of long-term potentiation induction was observed in APP/PS1 mice after PSD-93 overexpression. The expression of somatostatin receptor 4 (SSTR4) and neprilysin was increased, while the amyloid plaque load and Aβ levels were decreased in the brains of APP/PS1 mice. Moreover, PSD-93 interacted with SSTR4 and affected the level of SSTR4 on cell membrane, which was associated with the ubiquitination. Together, these findings suggest that PSD-93 attenuates spatial memory deficits and decreases amyloid levels in APP/PS1 mice, which might be associated with Aβ catabolism, and overexpression of PSD-93 might be a potential therapy for AD.

An Assessment of Common Approaches to Estimating Peak Skin Dose Resulting From Fluoroscopically Guided Interventions

NASA Astrophysics Data System (ADS)

Smith, Caleb Martin

Fluoroscopy guided procedures are increasing in complexity, and with that, Peak Skin Doses (PSD) that produce cutaneous radiation injury are a growing concern. Direct measurement of PSD is possible, but the decision to do so must be made in advance. PSD estimates and correctly monitoring their possible deterministic skin injuries are important to patient care. Three methods of indirect PSD estimation are examined for nine cases at MedStar Georgetown University Hospital. The aim of the study is to determine the magnitude of variation between these three methods for estimating the PSD. Method 1 (Fluoroscopy Time and Maximum Entrance Skin Exposure) was used at MedStar Georgetown University Hospital up until 2016. Methods 2 and 3 incorporate procedure information (Reference Point Air Kerma, Source-to-Patent distance, and Backscatter Factor) from DICOM (Digital Imaging and Communications in Medicine) tags into PSD estimates. Method 1 PSD estimates are vastly different, by as much as 136%, than those from Methods 2 and 3. Method 2 and 3 PSD estimates differ very little, 7.3% or less. Governing bodies have discounted Method 1 as a reliable dose metric because of its poor correlation with PSD. The accuracy of Method 2 is suitable to determine PSD and which dose band a patient fits so their injuries can be accurately monitored. Method 3, the most time intensive approach, should only be used in the case of a sentinel event where a full investigation is warranted.

The skin immune response of rainbow trout, Oncorhynchus mykiss (Walbaum), associated with puffy skin disease (PSD).

PubMed

Christie, Lyndsay; van Aerle, Ronny; Paley, Richard K; Verner-Jeffreys, David W; Tidbury, Hannah; Green, Matthew; Feist, Stephen W; Cano, Irene

2018-07-01

Puffy skin disease (PSD) is an emerging skin condition which affects rainbow trout, Oncorhynchus mykiss (Walbaum). The transmission pattern of PSD suggests an infectious aetiology, however, the actual causative infectious agent(s) remain(s) unknown. In the present study, the rainbow trout epidermal immune response to PSD was characterised. Skin samples from infected fish were analysed and classified as mild, moderate or severe PSD by gross pathology and histological assessment. The level of expression of 26 immune-associated genes including cytokines, immunoglobulins and cell markers were examined by TaqMan qPCR assays. A significant up-regulation of the gene expression of C3, lysozyme, IL-1β and T-bet and down-regulation of TGFβ and TLR3 was observed in PSD fish compared to control fish. MHCI gene expression was up-regulated only in severe PSD lesions. Histological examinations of the epidermis showed a significant increase in the number of eosinophil cells and dendritic melanocytes in PSD fish. In severe lesions, mild diffuse lymphocyte infiltration was observed. IgT and CD8 positive cells were detected locally in the skin of PSD fish by in situ hybridisation (ISH), however, the gene expression of those genes was not different from control fish. Total IgM in serum of diseased animals was not different from control fish, measured by a sandwich ELISA, nor was significant up regulation of IgM gene expression in PSD lesions observed. Taken together, these results show activation of the complement pathway, up-regulation of a Th17 type response and eosinophilia during PSD. This is typical of a response to extracellular pathogens (i.e. bacteria and parasites) and allergens, commonly associated with acute dermatitis. Copyright © 2018. Published by Elsevier Ltd.

Motor impairments, striatal degeneration, and altered dopamine-glutamate interplay in mice lacking PSD-95.

PubMed

Zhang, Jingping; Saur, Taixiang; Duke, Angela N; Grant, Seth G N; Platt, Donna M; Rowlett, James K; Isacson, Ole; Yao, Wei-Dong

2014-01-01

Excessive activation of the N-methyl-d-aspartate (NMDA) receptor and the neurotransmitter dopamine (DA) mediate neurotoxicity and neurodegeneration under many neurological conditions, including Huntington's disease (HD), an autosomal dominant neurodegenerative disease characterized by the preferential loss of medium spiny projection neurons (MSNs) in the striatum. PSD-95 is a major scaffolding protein in the postsynaptic density (PSD) of dendritic spines, where a classical role for PSD-95 is to stabilize glutamate receptors at sites of synaptic transmission. Our recent studies indicate that PSD-95 also interacts with the D1 DA receptor localized in spines and negatively regulates spine D1 signaling. Moreover, PSD-95 forms ternary protein complexes with D1 and NMDA receptors, and plays a role in limiting the reciprocal potentiation between both receptors from being escalated. These studies suggest a neuroprotective role for PSD-95. Here we show that mice lacking PSD-95, resulting from genetic deletion of the GK domain of PSD-95 (PSD-95-ΔGK mice), sporadically develop progressive neurological impairments characterized by hypolocomotion, limb clasping, and loss of DARPP-32-positive MSNs. Electrophysiological experiments indicated that NMDA receptors in mutant MSNs were overactive, suggested by larger, NMDA receptor-mediated miniature excitatory postsynaptic currents (EPSCs) and higher ratios of NMDA- to AMPA-mediated corticostriatal synaptic transmission. In addition, NMDA receptor currents in mutant cortical neurons were more sensitive to potentiation by the D1 receptor agonist SKF81297. Finally, repeated administration of the psychostimulant cocaine at a dose regimen not producing overt toxicity-related phenotypes in normal mice reliably converted asymptomatic mutant mice to clasping symptomatic mice. These results support the hypothesis that deletion of PSD-95 in mutant mice produces concomitant overactivation of both D1 and NMDA receptors that makes neurons more susceptible to NMDA excitotoxicity, causing neuronal damage and neurological impairments. Understanding PSD-95-dependent neuroprotective mechanisms may help elucidate processes underlying neurodegeneration in HD and other neurological disorders.

PSD-Zip70 Deficiency Causes Prefrontal Hypofunction Associated with Glutamatergic Synapse Maturation Defects by Dysregulation of Rap2 Activity.

PubMed

Mayanagi, Taira; Yasuda, Hiroki; Sobue, Kenji

2015-10-21

Dysregulation of synapse formation and plasticity is closely related to the pathophysiology of psychiatric and neurodevelopmental disorders. The prefrontal cortex (PFC) is particularly important for executive functions such as working memory, cognition, and emotional control, which are impaired in the disorders. PSD-Zip70 (Lzts1/FEZ1) is a postsynaptic density (PSD) protein predominantly expressed in the frontal cortex, olfactory bulb, striatum, and hippocampus. Here we found that PSD-Zip70 knock-out (PSD-Zip70KO) mice exhibit working memory and cognitive defects, and enhanced anxiety-like behaviors. These abnormal behaviors are caused by impaired glutamatergic synapse transmission accompanied by tiny-headed immature dendritic spines in the PFC, due to aberrant Rap2 activation, which has roles in synapse formation and plasticity. PSD-Zip70 modulates the Rap2 activity by interacting with SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) in the postsynapse. Furthermore, suppression of the aberrant Rap2 activation in the PFC rescued the behavioral defects in PSD-Zip70KO mice. Our data demonstrate a critical role for PSD-Zip70 in Rap2-dependent spine synapse development in the PFC and underscore the importance of this regulation in PFC-dependent behaviors. PSD-Zip70 deficiency causes behavioral defects in working memory and cognition, and enhanced anxiety due to prefrontal hypofunction. This study revealed that PSD-Zip70 plays essential roles in glutamatergic synapse maturation via modulation of the Rap2 activity in the PFC. PSD-Zip70 interacts with both SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) and modulates the Rap2 activity in postsynaptic sites. Our results provide a novel Rap2-specific regulatory mechanism in synaptic maturation involving PSD-Zip70. Copyright © 2015 the authors 0270-6474/15/3514327-14$15.00/0.

WE-E-18A-03: How Accurately Can the Peak Skin Dose in Fluoroscopy Be Determined Using Indirect Dose Metrics?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, A; Pasciak, A

Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that Result in skin reactions can be reached during these procedures. The purpose of this study was to assess the accuracy of different indirect dose estimates and to determine if PSD can be calculated within ±50% for embolization procedures. Methods: PSD were measured directly using radiochromic film for 41 consecutive embolization procedures. Indirect dose metrics from procedures were collected, including reference air kerma (RAK). Four different estimates of PSD were calculated and compared along with RAK to the measured PSD. The indirect estimates included a standard method,more » use of detailed information from the RDSR, and two simplified calculation methods. Indirect dosimetry was compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the indirect estimates were examined. Results: PSD calculated with the standard calculation method were within ±50% for all 41 procedures. This was also true for a simplified method using a single source-to-patient distance (SPD) for all calculations. RAK was within ±50% for all but one procedure. Cases for which RAK or calculated PSD exhibited large differences from the measured PSD were analyzed, and two causative factors were identified: ‘extreme’ SPD and large contributions to RAK from rotational angiography or runs acquired at large gantry angles. When calculated uncertainty limits [−12.8%, 10%] were applied to directly measured PSD, most indirect PSD estimates remained within ±50% of the measured PSD. Conclusions: Using indirect dose metrics, PSD can be determined within ±50% for embolization procedures, and usually to within ±35%. RAK can be used without modification to set notification limits and substantial radiation dose levels. These results can be extended to similar procedures, including vascular and interventional oncology. Film dosimetry is likely an unnecessary effort for these types of procedures.« less

40 CFR 52.181 - Significant deterioration of air quality.

Code of Federal Regulations, 2012 CFR

2012-07-01

...—submittal of the PSD Supplement Arkansas Plan of Implementation for Pollution Control (the “PSD Supplement... April 10, 1981); (2) June 3, 1988—submittal of revisions to the PSD Supplement (revised and adopted by the ACPCE on March 25, 1988); (3) June 19, 1990—submittal of revisions to the PSD Supplement (revised...

40 CFR 52.919 - Identification of plan-conditional approval.

Code of Federal Regulations, 2014 CFR

2014-07-01

... sections 110(a)(2)(C) and 110(a)(2)(J) as they both relate to Prevention of Significant Deterioration (PSD... requirements promulgated in the New Source Review (NSR) PM2.5 Rule related to the PM2.5 standard for their PSD... specific enforceable measures related the structural PSD requirements of the PSD and NNSR requirements...

40 CFR 52.379 - Control strategy: PM2.5.

Code of Federal Regulations, 2013 CFR

2013-07-01

... to CAA sections 110(a)(2)(A), (C) only as it related to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This conditional approval is contingent upon Connecticut taking... related to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This...

40 CFR 52.379 - Control strategy: PM2.5.

Code of Federal Regulations, 2014 CFR

2014-07-01

... to CAA sections 110(a)(2)(A), (C) only as it related to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This conditional approval is contingent upon Connecticut taking... related to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This...

40 CFR 52.181 - Significant deterioration of air quality.

Code of Federal Regulations, 2013 CFR

2013-07-01

...—submittal of the PSD Supplement Arkansas Plan of Implementation for Pollution Control (the “PSD Supplement... April 10, 1981); (2) June 3, 1988—submittal of revisions to the PSD Supplement (revised and adopted by the ACPCE on March 25, 1988); (3) June 19, 1990—submittal of revisions to the PSD Supplement (revised...

40 CFR 52.919 - Identification of plan-conditional approval.

Code of Federal Regulations, 2013 CFR

2013-07-01

... sections 110(a)(2)(C) and 110(a)(2)(J) as they both relate to Prevention of Significant Deterioration (PSD... requirements promulgated in the New Source Review (NSR) PM2.5 Rule related to the PM2.5 standard for their PSD... specific enforceable measures related the structural PSD requirements of the PSD and NNSR requirements...

40 CFR 124.3 - Application for a permit.

Code of Federal Regulations, 2014 CFR

2014-07-01

... requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit to the Director an application for each permit required under §§ 270.1 (RCRA), 144.1 (UIC), 40 CFR 52.21 (PSD... (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits) must...

40 CFR 52.181 - Significant deterioration of air quality.

Code of Federal Regulations, 2014 CFR

2014-07-01

...—submittal of the PSD Supplement Arkansas Plan of Implementation for Pollution Control (the “PSD Supplement... April 10, 1981); (2) June 3, 1988—submittal of revisions to the PSD Supplement (revised and adopted by the ACPCE on March 25, 1988); (3) June 19, 1990—submittal of revisions to the PSD Supplement (revised...

40 CFR 52.920 - Identification of plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Requirements—Other Sources 10/23/01 66 FR 53660 11/16/83 2.07 Public Notification for Title V, PSD, and Offset...) related to PSD requirements and 110(a)(2)(J) related to PSD requirements, EPA conditionally approved these...)(D)(i), With respect to sections 110(a)(2)(C) related to PSD requirements and 110(a)(2)(J) related to...

40 CFR 52.920 - Identification of plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Requirements—Other Sources 10/23/01 66 FR 53660 11/16/83 2.07 Public Notification for Title V, PSD, and Offset...) related to PSD requirements and 110(a)(2)(J) related to PSD requirements, EPA conditionally approved these...)(D)(i), With respect to sections 110(a)(2)(C) related to PSD requirements and 110(a)(2)(J) related to...

PSD95: A synaptic protein implicated in schizophrenia or autism?

PubMed

Coley, Austin A; Gao, Wen-Jun

2018-03-02

The molecular components of the postsynaptic density (PSD) in excitatory synapses of the brain are currently being investigated as one of the major etiologies of neurodevelopmental disorders such as schizophrenia (SCZ) and autism. Postsynaptic density protein-95 (PSD-95) is a major regulator of synaptic maturation by interacting, stabilizing and trafficking N-methyl-d-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic acid receptors (AMPARs) to the postsynaptic membrane. Recently, there has been overwhelming evidence that associates PSD-95 disruption with cognitive and learning deficits observed in SCZ and autism. For instance, recent genomic and sequencing studies of psychiatric patients highlight the aberrations at the PSD of glutamatergic synapses that include PSD-95 dysfunction. In animal studies, PSD-95 deficiency shows alterations in NMDA and AMPA-receptor composition and function in specific brain regions that may contribute to phenotypes observed in neuropsychiatric pathologies. In this review, we describe the role of PSD-95 as an essential scaffolding protein during synaptogenesis and neurodevelopment. More specifically, we discuss its interactions with NMDA receptor subunits that potentially affect glutamate transmission, and the formation of silent synapses during critical time points of neurodevelopment. Furthermore, we describe how PSD-95 may alter dendritic spine morphologies, thus regulating synaptic function that influences behavioral phenotypes in SCZ versus autism. Understanding the role of PSD-95 in the neuropathologies of SCZ and autism will give an insight of the cellular and molecular attributes in the disorders, thus providing treatment options in patients affected. Copyright © 2017 Elsevier Inc. All rights reserved.

Sick of inequality: gender and support for paid sick days.

PubMed

Lindemann, Danielle J; Houser, Linda; White, Karen

2015-01-01

The availability of paid sick days (PSD) is on the forefront of policy issues relating to women's health and well-being. Previous research regarding PSD and other forms of family-work balance legislation has linked access to paid time off from work for addressing one's own or another's health concerns to a range of health benefits for working women and their families. In general, public support for such policies is high, but little work has tested the extent to which support extends to PSD. Researchers have yet to engage in a rigorous statistical analysis of public opinion on PSD, including whether opinion varies by gender. Using data from a 2013 poll of adults in New Jersey (n = 925), we bridged this research gap by conducting the first multivariate analysis of public attitudes toward PSD. As expected, we found markedly high levels of support for PSD across all respondents, with a preponderance of most sociodemographic categories supporting proposed PSD legislation in New Jersey. We also found that gender was a strong predictor of support for PSD, with women significantly (odds ratio, 1.916; p ≤ .01) more likely than men to be in favor of such legislation. We discuss the implications of our findings for future work on PSD as well as for research concerning women, wellness, and work-life legislation more broadly. Published by Elsevier Inc.

40 CFR 52.1019 - Identification of plan-conditional approval.

Code of Federal Regulations, 2013 CFR

2013-07-01

...), (C) only as it relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This conditional approval is contingent upon... conditionally approved for CAA elements 110(a)(2)(A), (C) only as it relates to the PSD program, (D)(i)(II) only...

40 CFR 52.1019 - Identification of plan-conditional approval.

Code of Federal Regulations, 2014 CFR

2014-07-01

...), (C) only as it relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This conditional approval is contingent upon... conditionally approved for CAA elements 110(a)(2)(A), (C) only as it relates to the PSD program, (D)(i)(II) only...

40 CFR 124.19 - Appeal of RCRA, UIC, NPDES and PSD Permits.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Appeal of RCRA, UIC, NPDES and PSD... PSD Permits. (a) Petitioning for review of a permit decision. (1) Initiating an appeal. Appeal from a RCRA, UIC, NPDES, or PSD final permit decision issued under § 124.15 of this part, or a decision to...

40 CFR 124.19 - Appeal of RCRA, UIC, NPDES and PSD Permits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Appeal of RCRA, UIC, NPDES and PSD... PSD Permits. (a) Petitioning for review of a permit decision. (1) Initiating an appeal. Appeal from a RCRA, UIC, NPDES, or PSD final permit decision issued under § 124.15 of this part, or a decision to...

76 FR 142 - Notice of Prevention of Significant Deterioration Final Determination for Russell City Energy Center

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-03

... Deterioration (PSD) Permit issued to Russell City Energy Center, LLC by the Bay Area Air Quality Management... under authority of a PSD delegation agreement dated February 4, 2008, issued a PSD permit to Russell... Petitions for Review of the PSD decision with the EAB. The EAB issued an Order denying the Petitions for...

PKMζ is necessary and sufficient for synaptic clustering of PSD-95.

PubMed

Shao, Charles Y; Sondhi, Rachna; van de Nes, Paula S; Sacktor, Todd Charlton

2012-07-01

The persistent activity of protein kinase Mzeta (PKMζ), a brain-specific, constitutively active protein kinase C isoform, maintains synaptic long-term potentiation (LTP). Structural remodeling of the postsynaptic density is believed to contribute to the expression of LTP. We therefore examined the role of PKMζ in reconfiguring PSD-95, the major postsynaptic scaffolding protein at excitatory synapses. In primary cultures of hippocampal neurons, PKMζ activity was critical for increasing the size of PSD-95 clusters during chemical LTP (cLTP). Increasing PKMζ activity by overexpressing the kinase in hippocampal neurons was sufficient to increase PSD-95 cluster size, spine size, and postsynaptic AMPAR subunit GluA2. Overexpression of an inactive mutant of PKMζ did not increase PSD-95 clustering, and applications of the ζ-pseudosubstrate inhibitor ZIP reversed the PKMζ-mediated increases in PSD-95 clustering, indicating that the activity of PKMζ is necessary to induce and maintain the increased size of PSD-95 clusters. Thus the persistent activity of PKMζ is both necessary and sufficient for maintaining increases of PSD-95 clusters, providing a unified mechanism for long-term functional and structural modifications of synapses. Copyright © 2011 Wiley Periodicals, Inc.

Postsynaptic density protein (PSD)-95 expression is markedly decreased in the hippocampal CA1 region after experimental ischemia-reperfusion injury.

PubMed

Yan, Bing Chun; Park, Joon Ha; Ahn, Ji Hyeon; Lee, Jae-Chul; Won, Moo-Ho; Kang, Il-Jun

2013-07-15

Synaptic plasticity is important for functional recovery after cerebral ischemic injury. In the present study, we investigated chronological change in the immunoreactivity of PSD-95, a kind of postsynaptic density protein, in the hippocampus proper (CA1-3 regions) after 5 min of transient cerebral ischemia in gerbils. PSD-95 immunoreactivity was observed in MAP-2-immunoreactive dendrites in the CA1-3 regions of the sham group. The PSD-95 immunoreactivity was shown as beaded structure in the MAP-2-immunoreactive dendrites. However, PSD-95 immunoreactivity began to be dramatically decreased in MAP-2-immunoreactive dendrites in the CA1 region, not CA2-3 region, at early time after ischemia-reperfusion. At 5 days after ischemia-reperfusion, MAP-2 immunoreactivity almost disappeared in the ischemic CA1 region, and PSD-95 immunoreactivity was much lower than that in the sham group. In brief, PSD-95 immunoreactivity in the CA1 dendrites was markedly decreased at early time after ischemia-reperfusion. We suggest that decreased PSD-95 immunoreactivity in the ischemic CA1 region may lead to a deficit of postsynaptic plasticity in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling.

PubMed

Nikonenko, Irina; Boda, Bernadett; Steen, Sylvain; Knott, Graham; Welker, Egbert; Muller, Dominique

2008-12-15

Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation and organization remains unclear. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which PSD-95 regulates synaptogenesis. We find that PSD-95 overexpression affected spine morphology but also promoted the formation of multiinnervated spines (MISs) contacted by up to seven presynaptic terminals. The formation of multiple contacts was specifically prevented by deletion of the PDZ(2) domain of PSD-95, which interacts with nitric oxide (NO) synthase (NOS). Similarly, PSD-95 overexpression combined with small interfering RNA-mediated down-regulation or the pharmacological blockade of NOS prevented axon differentiation into varicosities and multisynapse formation. Conversely, treatment of hippocampal slices with an NO donor or cyclic guanosine monophosphate analogue induced MISs. NOS blockade also reduced spine and synapse density in developing hippocampal cultures. These results indicate that the postsynaptic site, through an NOS-PSD-95 interaction and NO signaling, promotes synapse formation with nearby axons.

PSD-95 alters microtubule dynamics via an association with EB3

PubMed Central

Sweet, Eric S.; Previtera, Michelle L.; Fernández, Jose R.; Charych, Erik I.; Tseng, Chia-Yi; Kwon, Munjin; Starovoytov, Valentin; Zheng, James Q.; Firestein, Bonnie L.

2011-01-01

Little is known about how the neuronal cytoskeleton is regulated when a dendrite decides whether to branch or not. Previously, we reported that postsynaptic density protein 95 (PSD-95) acts as a stop signal for dendrite branching. It is yet to be elucidated how PSD-95 affects the cytoskeleton and how this regulation relates to the dendritic arbor. Here, we show that the SH3 (src homology 3) domain of PSD-95 interacts with a proline-rich region within the microtubule end-binding protein EB3. Overexpression of PSD-95 or mutant EB3 results in a decreased lifetime of EB3 comets in dendrites. In line with these data, transfected rat neurons show that overexpression of PSD-95 results in less organized microtubules at dendritic branch points and decreased dendritogensis. The interaction between PSD-95 and EB3 elucidates a function for a novel region of EB3 and provides a new and important mechanism for the regulation of microtubules in determining dendritic morphology. PMID:21248129

How accurately can the peak skin dose in fluoroscopy be determined using indirect dose metrics?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, A. Kyle, E-mail: kyle.jones@mdanderson.org; Ensor, Joe E.; Pasciak, Alexander S.

Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that result in skin reactions can be reached during these procedures. There is no consensus as to whether or not indirect skin dosimetry is sufficiently accurate for fluoroscopically-guided interventions. However, measuring PSD with film is difficult and the decision to do so must be madea priori. The purpose of this study was to assess the accuracy of different types of indirect dose estimates and to determine if PSD can be calculated within ±50% using indirect dose metrics for embolization procedures. Methods: PSD were measured directly using radiochromicmore » film for 41 consecutive embolization procedures at two sites. Indirect dose metrics from the procedures were collected, including reference air kerma. Four different estimates of PSD were calculated from the indirect dose metrics and compared along with reference air kerma to the measured PSD for each case. The four indirect estimates included a standard calculation method, the use of detailed information from the radiation dose structured report, and two simplified calculation methods based on the standard method. Indirect dosimetry results were compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the different indirect estimates were examined. Results: When using the standard calculation method, calculated PSD were within ±35% for all 41 procedures studied. Calculated PSD were within ±50% for a simplified method using a single source-to-patient distance for all calculations. Reference air kerma was within ±50% for all but one procedure. Cases for which reference air kerma or calculated PSD exhibited large (±35%) differences from the measured PSD were analyzed, and two main causative factors were identified: unusually small or large source-to-patient distances and large contributions to reference air kerma from cone beam computed tomography or acquisition runs acquired at large primary gantry angles. When calculated uncertainty limits [−12.8%, 10%] were applied to directly measured PSD, most indirect PSD estimates remained within ±50% of the measured PSD. Conclusions: Using indirect dose metrics, PSD can be determined within ±35% for embolization procedures. Reference air kerma can be used without modification to set notification limits and substantial radiation dose levels, provided the displayed reference air kerma is accurate. These results can reasonably be extended to similar procedures, including vascular and interventional oncology. Considering these results, film dosimetry is likely an unnecessary effort for these types of procedures when indirect dose metrics are available.« less

Neural complexity in patients with poststroke depression: A resting EEG study.

PubMed

Zhang, Ying; Wang, Chunfang; Sun, Changcheng; Zhang, Xi; Wang, Yongjun; Qi, Hongzhi; He, Feng; Zhao, Xin; Wan, Baikun; Du, Jingang; Ming, Dong

2015-12-01

Poststroke depression (PSD) is one of the most common emotional disorders affecting post-stroke patients. However, the neurophysiological mechanism remains elusive. This study was aimed to study the relationship between complexity of neural electrical activity and PSD. Resting state eye-closed electroencephalogram (EEG) signals of 16 electrodes were recorded in 21 ischemic poststroke depression (PSD) patients, 22 ischemic poststroke non-depression (PSND) patients and 15 healthy controls (CONT). Lempel-Ziv Complexity (LZC) was used to evaluate changes in EEG complexity in PSD patients. Statistical analysis was performed to explore difference among different groups and electrodes. Correlation between the severity of depression (HDRS) and EEG complexity was determined with pearson correlation coefficients. Receiver operating characteristic (ROC) and binary logistic regression analysis were conducted to estimate the discriminating ability of LZC for PSD in specificity, sensitivity and accuracy. PSD patients showed lower neural complexity compared with PSND and CONT subjects in the whole brain regions. There was no significant difference among different brain regions, and no interactions between group and electrodes. None of the LZC significantly correlated with overall depression severity or differentiated symptom severity of 7 items in PSD patients, but in stroke patients, significant correlation was found between HDRS and LZC in the whole brain regions, especially in frontal and temporal. LZC parameters used for PSD recognition possessed more than 85% in specificity, sensitivity and accuracy, suggesting the feasibility of LZC to serve as screening indicators for PSD. Increased slow wave rhythms were found in PSD patients and clearly correlation was confirmed between neuronal complexity and spectral power of the four EEG rhythms. Lesion location of stroke patients in the study distributed in different brain regions, and most of the PSD patients were mild or moderate in depressive severity. Compared with conventional spectral analysis, complexity of neural activity using LZC was more sensitive and stationary in the measurement of abnormal brain activity in PSD patients and may offer a potential approach to facilitate clinical screening of this disease. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

PSD-95 regulates CRFR1 localization, trafficking and β-arrestin2 recruitment.

PubMed

Dunn, Henry A; Chahal, Harpreet S; Caetano, Fabiana A; Holmes, Kevin D; Yuan, George Y; Parikh, Ruchi; Heit, Bryan; Ferguson, Stephen S G

2016-05-01

Corticotropin-releasing factor (CRF) is a neuropeptide commonly associated with the hypothalamic-pituitary adrenal axis stress response. Upon release, CRF activates two G protein-coupled receptors (GPCRs): CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2). Although both receptors contribute to mood regulation, CRFR1 antagonists have demonstrated anxiolytic and antidepressant-like properties that may be exploited in the generation of new pharmacological interventions for mental illnesses. Previous studies have demonstrated CRFR1 capable of heterologously sensitizing serotonin 2A receptor (5-HT2AR) signaling: another GPCR implicated in psychiatric disease. Interestingly, this phenomenon was dependent on Postsynaptic density 95 (PSD-95)/Disc Large/Zona Occludens (PDZ) interactions on the distal carboxyl termini of both receptors. In the current study, we demonstrate that endogenous PSD-95 can be co-immunoprecipitated with CRFR1 from cortical brain homogenate, and this interaction appears to be primarily via the PDZ-binding motif. Additionally, PSD-95 colocalizes with CRFR1 within the dendritic projections of cultured mouse neurons in a PDZ-binding motif-dependent manner. In HEK 293 cells, PSD-95 overexpression inhibited CRFR1 endocytosis, whereas PSD-95 shRNA knockdown enhanced CRFR1 endocytosis. Although PSD-95 does not appear to play a significant role in CRF-mediated cAMP or ERK1/2 signaling, PSD-95 was demonstrated to suppress β-arrestin2 recruitment: providing a potential mechanism for PSD-95's inhibition of endocytosis. In revisiting previously documented heterologous sensitization, PSD-95 shRNA knockdown did not prevent CRFR1-mediated enhancement of 5-HT2AR signaling. In conclusion, we have identified and characterized a novel functional relationship between CRFR1 and PSD-95 that may have implications in the design of new treatment strategies for mental illness. Copyright © 2016 Elsevier Inc. All rights reserved.

Durable fear memories require PSD-95

PubMed Central

Fitzgerald, Paul J.; Pinard, Courtney R.; Camp, Marguerite C.; Feyder, Michael; Sah, Anupam; Bergstrom, Hadley; Graybeal, Carolyn; Liu, Yan; Schlüter, Oliver; Grant, Seth G.N.; Singewald, Nicolas; Xu, Weifeng; Holmes, Andrew

2014-01-01

Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. While overly persistent fear memories underlie anxiety disorders such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Post-synaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Employing a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95GK), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown approaches. We show that PSD-95 is dispensable for the formation and expression of recent fear memories, but essential for the formation of precise and flexible fear memories and for the maintenance of memories at remote time points. The failure of PSD-95GK mice to retrieve remote cued fear memories was associated with hypoactivation of the infralimbic cortex (IL) (not anterior cingulate (ACC) or prelimbic cortex), reduced IL single-unit firing and bursting, and attenuated IL gamma and theta oscillations. Adeno-associated PSD-95 virus-mediated knockdown in the IL, not ACC, was sufficient to impair recent fear extinction and remote fear memory, and remodel IL dendritic spines. Collectively, these data identify PSD-95 in the IL as a critical mechanism supporting the durability of fear memories over time. These preclinical findings have implications for developing novel approaches to treating trauma-based anxiety disorders that target the weakening of overly persistent fear memories. PMID:25510511

Durable fear memories require PSD-95.

PubMed

Fitzgerald, P J; Pinard, C R; Camp, M C; Feyder, M; Sah, A; Bergstrom, H C; Graybeal, C; Liu, Y; Schlüter, O M; Grant, S G; Singewald, N; Xu, W; Holmes, A

2015-07-01

Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. Although overly persistent fear memories underlie anxiety disorders, such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Postsynaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Using a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95(GK)), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown (KD) approaches. We show that PSD-95 is dispensable for the formation and expression of recent fear memories, but essential for the formation of precise and flexible fear memories and for the maintenance of memories at remote time points. The failure of PSD-95(GK) mice to retrieve remote cued fear memory was associated with hypoactivation of the infralimbic (IL) cortex (but not the anterior cingulate cortex (ACC) or prelimbic cortex), reduced IL single-unit firing and bursting, and attenuated IL gamma and theta oscillations. Adeno-associated virus-mediated PSD-95 KD in the IL, but not the ACC, was sufficient to impair recent fear extinction and remote fear memory, and remodel IL dendritic spines. Collectively, these data identify PSD-95 in the IL as a critical mechanism supporting the durability of fear memories over time. These preclinical findings have implications for developing novel approaches to treating trauma-based anxiety disorders that target the weakening of overly persistent fear memories.

Pima County Department of Environmental Quality PSD Delegation Agreement

EPA Pesticide Factsheets

This delegation agreement is for the entire Prevention of Significant Deterioration (PSD) program. This allows Pima County Air Quality District (Pima County ACQD) to issue PSD permits using 40 CFR 52.21

Protection relay of phase-shifting device with thyristor switch for high voltage power transmission lines

NASA Astrophysics Data System (ADS)

Lachugin, V. F.; Panfilov, D. I.; Akhmetov, I. M.; Astashev, M. G.; Shevelev, A. V.

2014-12-01

Problems of functioning of differential current protection systems of phase shifting devices (PSD) with mechanically changed coefficient of transformation of shunt transformer are analyzed. Requirements for devices of protection of PSD with thyristor switch are formulated. Based on use of nonlinear models of series-wound and shunt transformers of PSD modes of operation of major protection during PSD, switching to zero load operation and to operation under load and during short circuit operation were studied for testing PSD with failures. Use of the principle of duplicating by devices of differential current protection (with realization of functions of breaking) of failures of separate pares of PSD with thyristor switch was substantiated. To ensure protection sensitivity to the shunt transformer winding short circuit, in particular, to a short circuit that is not implemented in the current differential protection for PSD with mechanical switch, the differential current protection reacting to the amount of primary ampere-turns of high-voltage and low-voltage winding of this transformer was designed. Studies have shown that the use of differential current cutoff instead of overcurrent protection for the shunt transformer wndings allows one to provide the sensitivity during thyristor failure with the formation of a short circuit. The results of simulation mode for the PSD with switch thyristor designed to be installed as switching point of Voskhod-Tatarskaya-Barabinsk 220 kV transmission line point out the efficiency of the developed solutions that ensure reliable functioning of the PSD.

Perturbing NR2B-PSD-95 interaction relieves neuropathic pain by inactivating CaMKII-CREB signaling.

PubMed

Xu, Fangxia; Zhao, Xin; Liu, Lin; Song, Jia; Zhu, Yingjun; Chu, Shuaishuai; Shao, Xueming; Li, Xiuxiu; Ma, Zhengliang; Gu, Xiaoping

2017-09-06

Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting. A mimetic peptide Myr-NR2B9c was injected intrathecally to disrupt the interaction between PSD-95 and NR2B and detected by coimmunoprecipitation. Chronic dorsal root ganglia compression surgery induced thermal hyperalgesia and mechanical allodynia, and upregulated pain-related proteins such as phospho-NR2B, PSD-95, CaMKII, and CREB expressions in the spinal cord. Myr-NR2B9c disrupted the interaction between NR2B-containing NMDARs and PSD-95 in the spinal cord. Intrathecal administration of Myr-NR2B9c attenuated neuropathic pain behaviors and downregulated the expressions of phospho-NR2B, PSD-95, CaMKII, and CREB in the spinal cord. The present study indicates that dissociation of NR2B-containing NMDARs from PSD-95 inactivates CaMKII and CREB signaling and relieves pain.

PSD-93 deletion inhibits Fyn-mediated phosphorylation of NR2B and protects against focal cerebral ischemia.

PubMed

Zhang, Meijuan; Li, Qingjie; Chen, Ling; Li, Jie; Zhang, Xin; Chen, Xiang; Zhang, Qingxiu; Shao, Yuan; Xu, Yun

2014-08-01

Modification of N-methyl-d-aspartate receptor (NMDAR)-mediated excitotoxicity appears to be a potential target in the treatment of ischemic stroke. Postsynaptic density protein-93 (PSD-93) specifically binds the C-terminal tails of the NMDAR, which is critical to couple NMDAR activity to specific intracellular signaling. This study is to investigate whether PSD-93 disruption displays neuroprotection in a focal ischemic stroke model of adult mice and, if it does, to explore possible mechanisms. It was found that, following middle cerebral artery occlusion (MCAO), PSD-93 knockout (KO) mice manifested significant reductions in infarcted volume, neurological deficits and number of degenerated neurons. PSD-93 deletion also reduced cultured cortical neuronal death caused by glucose and oxygen deprivation (OGD). Ischemic long term potentiation (i-LTP) could not be induced in the PSD-93 KO group and wild type (WT) groups pretreated with either AP-5 (NMDAR inhibitor) or PP2 (Src family inhibitor). PSD-93 KO decreased the phosphorylation of the NR2B at Tyr1472 and the interaction between NR2B and Fyn after MCAO. Together, our study demonstrated that PSD-93 KO confers profound neuroprotection against ischemic brain injury, which probably links to the inhibitory effect on Fyn-mediated phosphorylation of NR2B caused by PSD-93 deletion. These findings may provide a novel avenue for the treatment of ischemic stroke. Copyright © 2014 Elsevier Inc. All rights reserved.

Winter precipitation particle size distribution measurement by Multi-Angle Snowflake Camera

NASA Astrophysics Data System (ADS)

Huang, Gwo-Jong; Kleinkort, Cameron; Bringi, V. N.; Notaroš, Branislav M.

2017-12-01

From the radar meteorology viewpoint, the most important properties for quantitative precipitation estimation of winter events are 3D shape, size, and mass of precipitation particles, as well as the particle size distribution (PSD). In order to measure these properties precisely, optical instruments may be the best choice. The Multi-Angle Snowflake Camera (MASC) is a relatively new instrument equipped with three high-resolution cameras to capture the winter precipitation particle images from three non-parallel angles, in addition to measuring the particle fall speed using two pairs of infrared motion sensors. However, the results from the MASC so far are usually presented as monthly or seasonally, and particle sizes are given as histograms, no previous studies have used the MASC for a single storm study, and no researchers use MASC to measure the PSD. We propose the methodology for obtaining the winter precipitation PSD measured by the MASC, and present and discuss the development, implementation, and application of the new technique for PSD computation based on MASC images. Overall, this is the first study of the MASC-based PSD. We present PSD MASC experiments and results for segments of two snow events to demonstrate the performance of our PSD algorithm. The results show that the self-consistency of the MASC measured single-camera PSDs is good. To cross-validate PSD measurements, we compare MASC mean PSD (averaged over three cameras) with the collocated 2D Video Disdrometer, and observe good agreements of the two sets of results.

PSD-95 regulates synaptic kainate receptors at mouse hippocampal mossy fiber-CA3 synapses.

PubMed

Suzuki, Etsuko; Kamiya, Haruyuki

2016-06-01

Kainate-type glutamate receptors (KARs) are the third class of ionotropic glutamate receptors whose activation leads to the unique roles in regulating synaptic transmission and circuit functions. In contrast to AMPA receptors (AMPARs), little is known about the mechanism of synaptic localization of KARs. PSD-95, a major scaffold protein of the postsynaptic density, is a candidate molecule that regulates the synaptic KARs. Although PSD-95 was shown to bind directly to KARs subunits, it has not been tested whether PSD-95 regulates synaptic KARs in intact synapses. Using PSD-95 knockout mice, we directly investigated the role of PSD-95 in the KARs-mediated components of synaptic transmission at hippocampal mossy fiber-CA3 synapse, one of the synapses with the highest density of KARs. Mossy fiber EPSCs consist of AMPA receptor (AMPAR)-mediated fast component and KAR-mediated slower component, and the ratio was significantly reduced in PSD-95 knockout mice. The size of KARs-mediated field EPSP reduced in comparison with the size of the fiber volley. Analysis of KARs-mediated miniature EPSCs also suggested reduced synaptic KARs. All the evidence supports critical roles of PSD-95 in regulating synaptic KARs. Copyright © 2015 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

The effect of particle size distribution on the design of urban stormwater control measures

USGS Publications Warehouse

Selbig, William R.; Fienen, Michael N.; Horwatich, Judy A.; Bannerman, Roger T.

2016-01-01

An urban pollutant loading model was used to demonstrate how incorrect assumptions on the particle size distribution (PSD) in urban runoff can alter the design characteristics of stormwater control measures (SCMs) used to remove solids in stormwater. Field-measured PSD, although highly variable, is generally coarser than the widely-accepted PSD characterized by the Nationwide Urban Runoff Program (NURP). PSDs can be predicted based on environmental surrogate data. There were no appreciable differences in predicted PSD when grouped by season. Model simulations of a wet detention pond and catch basin showed a much smaller surface area is needed to achieve the same level of solids removal using the median value of field-measured PSD as compared to NURP PSD. Therefore, SCMs that used the NURP PSD in the design process could be unnecessarily oversized. The median of measured PSDs, although more site-specific than NURP PSDs, could still misrepresent the efficiency of an SCM because it may not adequately capture the variability of individual runoff events. Future pollutant loading models may account for this variability through regression with environmental surrogates, but until then, without proper site characterization, the adoption of a single PSD to represent all runoff conditions may result in SCMs that are under- or over-sized, rendering them ineffective or unnecessarily costly.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wurtz, R.; Kaplan, A.

Pulse shape discrimination (PSD) is a variety of statistical classifier. Fully-­realized statistical classifiers rely on a comprehensive set of tools for designing, building, and implementing. PSD advances rely on improvements to the implemented algorithm. PSD advances can be improved by using conventional statistical classifier or machine learning methods. This paper provides the reader with a glossary of classifier-­building elements and their functions in a fully-­designed and operational classifier framework that can be used to discover opportunities for improving PSD classifier projects. This paper recommends reporting the PSD classifier’s receiver operating characteristic (ROC) curve and its behavior at a gamma rejectionmore » rate (GRR) relevant for realistic applications.« less

PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling

PubMed Central

Nikonenko, Irina; Boda, Bernadett; Steen, Sylvain; Knott, Graham; Welker, Egbert; Muller, Dominique

2008-01-01

Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation and organization remains unclear. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which PSD-95 regulates synaptogenesis. We find that PSD-95 overexpression affected spine morphology but also promoted the formation of multiinnervated spines (MISs) contacted by up to seven presynaptic terminals. The formation of multiple contacts was specifically prevented by deletion of the PDZ2 domain of PSD-95, which interacts with nitric oxide (NO) synthase (NOS). Similarly, PSD-95 overexpression combined with small interfering RNA–mediated down-regulation or the pharmacological blockade of NOS prevented axon differentiation into varicosities and multisynapse formation. Conversely, treatment of hippocampal slices with an NO donor or cyclic guanosine monophosphate analogue induced MISs. NOS blockade also reduced spine and synapse density in developing hippocampal cultures. These results indicate that the postsynaptic site, through an NOS–PSD-95 interaction and NO signaling, promotes synapse formation with nearby axons. PMID:19075115

Setting up a proper power spectral density (PSD) and autocorrelation analysis for material and process characterization

NASA Astrophysics Data System (ADS)

Rutigliani, Vito; Lorusso, Gian Francesco; De Simone, Danilo; Lazzarino, Frederic; Rispens, Gijsbert; Papavieros, George; Gogolides, Evangelos; Constantoudis, Vassilios; Mack, Chris A.

2018-03-01

Power spectral density (PSD) analysis is playing more and more a critical role in the understanding of line-edge roughness (LER) and linewidth roughness (LWR) in a variety of applications across the industry. It is an essential step to get an unbiased LWR estimate, as well as an extremely useful tool for process and material characterization. However, PSD estimate can be affected by both random to systematic artifacts caused by image acquisition and measurement settings, which could irremediably alter its information content. In this paper, we report on the impact of various setting parameters (smoothing image processing filters, pixel size, and SEM noise levels) on the PSD estimate. We discuss also the use of PSD analysis tool in a variety of cases. Looking beyond the basic roughness estimate, we use PSD and autocorrelation analysis to characterize resist blur[1], as well as low and high frequency roughness contents and we apply this technique to guide the EUV material stack selection. Our results clearly indicate that, if properly used, PSD methodology is a very sensitive tool to investigate material and process variations

Live Imaging of Endogenous PSD-95 Using ENABLED: A Conditional Strategy to Fluorescently Label Endogenous Proteins

PubMed Central

Fortin, Dale A.; Tillo, Shane E.; Yang, Guang; Rah, Jong-Cheol; Melander, Joshua B.; Bai, Suxia; Soler-Cedeño, Omar; Qin, Maozhen; Zemelman, Boris V.; Guo, Caiying

2014-01-01

Stoichiometric labeling of endogenous synaptic proteins for high-contrast live-cell imaging in brain tissue remains challenging. Here, we describe a conditional mouse genetic strategy termed endogenous labeling via exon duplication (ENABLED), which can be used to fluorescently label endogenous proteins with near ideal properties in all neurons, a sparse subset of neurons, or specific neuronal subtypes. We used this method to label the postsynaptic density protein PSD-95 with mVenus without overexpression side effects. We demonstrated that mVenus-tagged PSD-95 is functionally equivalent to wild-type PSD-95 and that PSD-95 is present in nearly all dendritic spines in CA1 neurons. Within spines, while PSD-95 exhibited low mobility under basal conditions, its levels could be regulated by chronic changes in neuronal activity. Notably, labeled PSD-95 also allowed us to visualize and unambiguously examine otherwise-unidentifiable excitatory shaft synapses in aspiny neurons, such as parvalbumin-positive interneurons and dopaminergic neurons. Our results demonstrate that the ENABLED strategy provides a valuable new approach to study the dynamics of endogenous synaptic proteins in vivo. PMID:25505322

Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3.

PubMed

Hruska, Martin; Henderson, Nathan T; Xia, Nan L; Le Marchand, Sylvain J; Dalva, Matthew B

2015-11-01

Organization of signaling complexes at excitatory synapses by membrane-associated guanylate kinase (MAGUK) proteins regulates synapse development, plasticity, senescence and disease. Post-translational modification of MAGUK family proteins can drive their membrane localization, yet it is unclear how these intracellular proteins are targeted to sites of synaptic contact. Here we show using super-resolution imaging, biochemical approaches and in vivo models that the trans-synaptic organizing protein ephrin-B3 controls the synaptic localization and stability of PSD-95 and links these events to changes in neuronal activity via negative regulation of a newly identified mitogen-associated protein kinase (MAPK)-dependent phosphorylation site on ephrin-B3, Ser332. Unphosphorylated ephrin-B3 was enriched at synapses, and interacted directly with and stabilized PSD-95 at synapses. Activity-induced phosphorylation of Ser332 dispersed ephrin-B3 from synapses, prevented the interaction with PSD-95 and enhanced the turnover of PSD-95. Thus, ephrin-B3 specifies the synaptic localization of PSD-95 and likely links the synaptic stability of PSD-95 to changes in neuronal activity.

[Changes in facial nerve function, morphology and neurotrophic factor III expression following three types of facial nerve injury].

PubMed

Zhang, Lili; Wang, Haibo; Fan, Zhaomin; Han, Yuechen; Xu, Lei; Zhang, Haiyan

2011-01-01

To study the changes in facial nerve function, morphology and neurotrophic factor III (NT-3) expression following three types of facial nerve injury. Changes in facial nerve function (in terms of blink reflex (BF), vibrissae movement (VM) and position of nasal tip) were assessed in 45 rats in response to three types of facial nerve injury: partial section of the extratemporal segment (group one), partial section of the facial canal segment (group two) and complete transection of the facial canal segment lesion (group three). All facial nerves specimen were then cut into two parts at the site of the lesion after being taken from the lesion site on 1st, 7th, 21st post-surgery-days (PSD). Changes of morphology and NT-3 expression were evaluated using the improved trichrome stain and immunohistochemistry techniques ,respectively. Changes in facial nerve function: In group 1, all animals had no blink reflex (BF) and weak vibrissae movement (VM) at the 1st PSD; The blink reflex in 80% of the rats recovered partly and the vibrissae movement in 40% of the rats returned to normal at the 7th PSD; The facial nerve function in 600 of the rats was almost normal at the 21st PSD. In group 2, all left facial nerve paralyzed at the 1st PSD; The blink reflex partly recovered in 40% of the rats and the vibrissae movement was weak in 80% of the rats at the 7th PSD; 8000 of the rats'BF were almost normal and 40% of the rats' VM completely recovered at the 21st PSD. In group 3, The recovery couldn't happen at anytime. Changes in morphology: In group 1, the size of nerve fiber differed in facial canal segment and some of myelin sheath and axons degenerated at the 7th PSD; The fibres' degeneration turned into regeneration at the 21st PSD; In group 2, the morphologic changes in this group were familiar with the group 1 while the degenerated fibers were more and dispersed in transection at the 7th PSD; Regeneration of nerve fibers happened at the 21st PSD. In group 3, most of the fibers crumbled at the 7th PSD and no regeneration was seen at the 21st PSD. Changes in NT-3: Positive staining of NT-3 was largely observed in axons at the 7th PSD, although little NT-3 was seen in the normal fibers. Facial palsy of the rats in group 2 was more extensive than that in group 1 and their function partly recovers at the 21st PSD. The fibres' degeneration occurs not only dispersed throughout the injury site but also occurred throught the length of the nerve. NT-3 immunoreactivity increased in activated fibers after partial transection.

Practical Findings from Applying the PSD Model for Evaluating Software Design Specifications

NASA Astrophysics Data System (ADS)

Räisänen, Teppo; Lehto, Tuomas; Oinas-Kukkonen, Harri

This paper presents practical findings from applying the PSD model to evaluating the support for persuasive features in software design specifications for a mobile Internet device. On the one hand, our experiences suggest that the PSD model fits relatively well for evaluating design specifications. On the other hand, the model would benefit from more specific heuristics for evaluating each technique to avoid unnecessary subjectivity. Better distinction between the design principles in the social support category would also make the model easier to use. Practitioners who have no theoretical background can apply the PSD model to increase the persuasiveness of the systems they design. The greatest benefit of the PSD model for researchers designing new systems may be achieved when it is applied together with a sound theory, such as the Elaboration Likelihood Model. Using the ELM together with the PSD model, one may increase the chances for attitude change.

Properties of pattern standard deviation in open-angle glaucoma patients with hemi-optic neuropathy and bi-optic neuropathy.

PubMed

Heo, Dong Won; Kim, Kyoung Nam; Lee, Min Woo; Lee, Sung Bok; Kim, Chang-Sik

2017-01-01

To evaluate the properties of pattern standard deviation (PSD) according to localization of the glaucomatous optic neuropathy. We enrolled 242 eyes of 242 patients with primary open-angle glaucoma, with a best-corrected visual acuity ≥ 20/25, and no media opacity. Patients were examined via dilated fundus photography, spectral-domain optical coherence tomography, and Humphrey visual field examination, and divided into those with hemi-optic neuropathy (superior or inferior) and bi-optic neuropathy (both superior and inferior). We assessed the relationship between mean deviation (MD) and PSD. Using broken stick regression analysis, the tipping point was identified, i.e., the point at which MD became significantly associated with a paradoxical reversal of PSD. In 91 patients with hemi-optic neuropathy, PSD showed a strong correlation with MD (r = -0.973, β = -0.965, p < 0.001). The difference between MD and PSD ("-MD-PSD") was constant (mean, -0.32 dB; 95% confidence interval, -2.48~1.84 dB) regardless of visual field defect severity. However, in 151 patients with bi-optic neuropathy, a negative correlation was evident between "-MD-PSD" and MD (r2 = 0.907, p < 0.001). Overall, the MD tipping point was -14.0 dB, which was close to approximately 50% damage of the entire visual field (p < 0.001). Although a false decrease of PSD usually begins at approximately 50% visual field damage, in patients with hemi-optic neuropathy, the PSD shows no paradoxical decrease and shows a linear correlation with MD.

75 FR 56106 - Notice of Prevention of Significant Deterioration Final Determination for Power Holdings of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

... Deterioration (PSD) permit issued to Power Holdings of Illinois, LLC, by the Illinois Environmental Protection... under authority of a PSD delegation agreement, issued a PSD permit to Power Holdings of Illinois, LLC...

Visual-spatial learning impairments are associated with hippocampal PSD-95 protein dysregulation in a mouse model of fragile X syndrome.

PubMed

Gandhi, Réno M; Kogan, Cary S; Messier, Claude; Macleod, Lindsey S

2014-03-05

Fragile X syndrome is the most common cause of inherited intellectual disability and is caused by the lack of fragile X mental retardation protein (FMRP) expression. In-vitro findings in mice and post-mortem autopsies in humans are characterized by dendritic spine abnormalities in the absence of Fmrp/FMRP. Biochemical and electrophysiological studies have identified postsynaptic density protein (PSD)-95 as having an established role in dendritic morphology as well as a molecular target of Fmrp. How Fmrp affects the expression of PSD-95 following behavioral learning is unknown. In the current study, wild type controls and Fmr1 knockout mice were trained in a subset of the Hebb-Williams (H-W) mazes. Dorsal hippocampal PSD-95 protein levels relative to a stable cytoskeleton protein (β-tubulin) were measured. We report a significant upregulation of PSD-95 protein levels in wild type mice, whereas training-related protein increases were blunted in Fmr1 knockout mice. In addition, there was a significant negative correlation between mean total errors on the mazes and PSD-95 protein levels. The coefficient of determination indicated that the mean total errors on the H-W mazes accounted for 35% of the variance in PSD-95 protein levels. These novel findings suggest that reduced PSD-95-associated postsynaptic plasticity may contribute to the learning and memory deficits observed in human fragile X syndrome patients.

Clinical outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts: a large multicenter study.

PubMed

Yang, Dennis; Amin, Sunil; Gonzalez, Susana; Mullady, Daniel; Edmundowicz, Steven A; DeWitt, John M; Khashab, Mouen A; Wang, Andrew Y; Nagula, Satish; Buscaglia, Jonathan M; Bucobo, Juan Carlos; Wagh, Mihir S; Draganov, Peter V; Stevens, Tyler; Vargo, John J; Khara, Harshit S; Diehl, David L; Keswani, Rajesh N; Komanduri, Srinadh; Yachimski, Patrick S; Prabhu, Anoop; Kwon, Richard S; Watson, Rabindra R; Goodman, Adam J; Benias, Petros; Carr-Locke, David L; DiMaio, Christopher J

2017-02-01

Background and study aims  Data on clinical outcomes of endoscopic drainage of debris-free pseudocysts (PDF) versus pseudocysts containing solid debris (PSD) are very limited. The aims of this study were to compare treatment outcomes between patients with PDF vs. PSD undergoing endoscopic ultrasound (EUS)-guided drainage via transmural stents. Patients and methods  Retrospective review of 142 consecutive patients with pseudocysts who underwent EUS-guided transmural drainage (TM) from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TM technical success, treatment outcomes (symptomatic and radiologic resolution), need for endoscopic re-intervention at follow-up, and adverse events (AEs). Results  TM was performed in 90 patients with PDF and 52 with PSD. Technical success: PDF 87 (96.7 %) vs. PSD 51 (98.1 %). There was no difference in the rates for endoscopic re-intervention (5.5 % in PDF vs. 11.5 % in PSD; P =  0.33) or AEs (12.2 % in PDF vs. 19.2 % in PSD; P  = 0.33). Median long-term follow-up after stent removal was 297 days (interquartile range [IQR]: 59 - 424 days) for PDF and 326 days (IQR: 180 - 448 days) for PSD ( P  = 0.88). There was a higher rate of short-term radiologic resolution of PDF (45; 66.2 %) vs. PSD (21; 51.2 %) (OR = 0.30; 95 % CI: 0.13 - 0.72; P  = 0.009). There was no difference in long-term symptomatic resolution (PDF: 70.4 % vs. PSD: 66.7 %; P  = 0.72) or radiologic resolution (PDF: 68.9 % vs. PSD: 78.6 %; P  = 0.72) Conclusions  There was no difference in need for endoscopic re-intervention, AEs or long-term treatment outcomes in patients with PDF vs. PSD undergoing EUS-guided drainage with transmural stents. Based on these results, the presence of solid debris in pancreatic fluid collections does not appear to be associated with a poorer outcome.

40 CFR 52.1586 - Section 110(a)(2) infrastructure requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... and the 1997 and 2006 PM2.5 NAAQS are disapproved for the following sections 110(a)(2)(C) (PSD program only), (D)(i)(II) (PSD program only), (D)(ii), and (J) (PSD program only). These requirements are being...

40 CFR 52.1586 - Section 110(a)(2) infrastructure requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... and the 1997 and 2006 PM2.5 NAAQS are disapproved for the following sections 110(a)(2)(C) (PSD program only), (D)(i)(II) (PSD program only), (D)(ii), and (J) (PSD program only). These requirements are being...

Postsynaptic localization of PSD-95 is regulated by all three pathways downstream of TrkB signaling.

PubMed

Yoshii, Akira; Constantine-Paton, Martha

2014-01-01

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate synaptic plasticity. TrkB triggers three downstream signaling pathways; Phosphatidylinositol 3-kinase (PI3K), Phospholipase Cγ (PLCγ) and Mitogen activated protein kinases/Extracellular signal-regulated kinases (MAPK/ERK). We previously showed two distinct mechanisms whereby BDNF-TrkB pathway controls trafficking of PSD-95, which is the major scaffold at excitatory synapses and is critical for synapse maturation. BDNF activates the PI3K-Akt pathway and regulates synaptic delivery of PSD-95 via vesicular transport (Yoshii and Constantine-Paton, 2007). BDNF-TrkB signaling also triggers PSD-95 palmitoylation and its transport to synapses through the phosphorylation of the palmitoylation enzyme ZDHHC8 by a protein kinase C (PKC; Yoshii etal., 2011). The second study used PKC inhibitors chelerythrine as well as a synthetic zeta inhibitory peptide (ZIP) which was originally designed to block the brain-specific PKC isoform protein kinase Mϖ (PKMϖ). However, recent studies raise concerns about specificity of ZIP. Here, we assessed the contribution of TrkB and its three downstream pathways to the synaptic distribution of endogenous PSD-95 in cultured neurons using chemical and genetic interventions. We confirmed that TrkB, PLC, and PI3K were critical for the postsynaptic distribution of PSD-95. Furthermore, suppression of MAPK/ERK also disrupted PSD-95 expression. Next, we examined the contribution of PKC. While both chelerythrine and ZIP suppressed the postsynaptic localization of PSD-95, RNA interference for PKMϖ did not have a significant effect. This result suggests that the ZIP peptide, widely used as the "specific" PKMϖ antagonist by many investigators may block a PKC variant other than PKMϖ such as PKCλ/ι. Our results indicate that TrkB regulates postsynaptic localization of PSD-95 through all three downstream pathways, but also recommend further work to identify other PKC variants that regulate palmitoylation and synaptic localization of PSD-95.

Postsynaptic density 95 (PSD-95) serine 561 phosphorylation regulates a conformational switch and bidirectional dendritic spine structural plasticity.

PubMed

Wu, Qian; Sun, Miao; Bernard, Laura P; Zhang, Huaye

2017-09-29

Postsynaptic density 95 (PSD-95) is a major synaptic scaffolding protein that plays a key role in bidirectional synaptic plasticity, which is a process important for learning and memory. It is known that PSD-95 shows increased dynamics upon induction of plasticity. However, the underlying structural and functional changes in PSD-95 that mediate its role in plasticity remain unclear. Here we show that phosphorylation of PSD-95 at Ser-561 in its guanylate kinase (GK) domain, which is mediated by the partitioning-defective 1 (Par1) kinases, regulates a conformational switch and is important for bidirectional plasticity. Using a fluorescence resonance energy transfer (FRET) biosensor, we show that a phosphomimetic mutation of Ser-561 promotes an intramolecular interaction between GK and the nearby Src homology 3 (SH3) domain, leading to a closed conformation, whereas a non-phosphorylatable S561A mutation or inhibition of Par1 kinase activity decreases SH3-GK interaction, causing PSD-95 to adopt an open conformation. In addition, S561A mutation facilitates the interaction between PSD-95 and its binding partners. Fluorescence recovery after photobleaching imaging reveals that the S561A mutant shows increased stability, whereas the phosphomimetic S561D mutation increases PSD-95 dynamics at the synapse. Moreover, molecular replacement of endogenous PSD-95 with the S561A mutant blocks dendritic spine structural plasticity during chemical long-term potentiation and long-term depression. Endogenous Ser-561 phosphorylation is induced by synaptic NMDA receptor activation, and the SH3-GK domains exhibit a Ser-561 phosphorylation-dependent switch to a closed conformation during synaptic plasticity. Our results provide novel mechanistic insight into the regulation of PSD-95 in dendritic spine structural plasticity through phosphorylation-mediated regulation of protein dynamics and conformation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Live imaging of endogenous PSD-95 using ENABLED: a conditional strategy to fluorescently label endogenous proteins.

PubMed

Fortin, Dale A; Tillo, Shane E; Yang, Guang; Rah, Jong-Cheol; Melander, Joshua B; Bai, Suxia; Soler-Cedeño, Omar; Qin, Maozhen; Zemelman, Boris V; Guo, Caiying; Mao, Tianyi; Zhong, Haining

2014-12-10

Stoichiometric labeling of endogenous synaptic proteins for high-contrast live-cell imaging in brain tissue remains challenging. Here, we describe a conditional mouse genetic strategy termed endogenous labeling via exon duplication (ENABLED), which can be used to fluorescently label endogenous proteins with near ideal properties in all neurons, a sparse subset of neurons, or specific neuronal subtypes. We used this method to label the postsynaptic density protein PSD-95 with mVenus without overexpression side effects. We demonstrated that mVenus-tagged PSD-95 is functionally equivalent to wild-type PSD-95 and that PSD-95 is present in nearly all dendritic spines in CA1 neurons. Within spines, while PSD-95 exhibited low mobility under basal conditions, its levels could be regulated by chronic changes in neuronal activity. Notably, labeled PSD-95 also allowed us to visualize and unambiguously examine otherwise-unidentifiable excitatory shaft synapses in aspiny neurons, such as parvalbumin-positive interneurons and dopaminergic neurons. Our results demonstrate that the ENABLED strategy provides a valuable new approach to study the dynamics of endogenous synaptic proteins in vivo. Copyright © 2014 the authors 0270-6474/14/3416698-15$15.00/0.

Decoding power-spectral profiles from FMRI brain activities during naturalistic auditory experience.

PubMed

Hu, Xintao; Guo, Lei; Han, Junwei; Liu, Tianming

2017-02-01

Recent studies have demonstrated a close relationship between computational acoustic features and neural brain activities, and have largely advanced our understanding of auditory information processing in the human brain. Along this line, we proposed a multidisciplinary study to examine whether power spectral density (PSD) profiles can be decoded from brain activities during naturalistic auditory experience. The study was performed on a high resolution functional magnetic resonance imaging (fMRI) dataset acquired when participants freely listened to the audio-description of the movie "Forrest Gump". Representative PSD profiles existing in the audio-movie were identified by clustering the audio samples according to their PSD descriptors. Support vector machine (SVM) classifiers were trained to differentiate the representative PSD profiles using corresponding fMRI brain activities. Based on PSD profile decoding, we explored how the neural decodability correlated to power intensity and frequency deviants. Our experimental results demonstrated that PSD profiles can be reliably decoded from brain activities. We also suggested a sigmoidal relationship between the neural decodability and power intensity deviants of PSD profiles. Our study in addition substantiates the feasibility and advantage of naturalistic paradigm for studying neural encoding of complex auditory information.

Transcriptional response to deletion of the phosphatidylserine decarboxylase Psd1p in the yeast Saccharomyces cerevisiae.

PubMed

Gsell, Martina; Mascher, Gerald; Schuiki, Irmgard; Ploier, Birgit; Hrastnik, Claudia; Daum, Günther

2013-01-01

In the yeast, Saccharomyces cerevisiae, the synthesis of the essential phospholipid phosphatidylethanolamine (PE) is accomplished by a network of reactions which comprises four different pathways. The enzyme contributing most to PE formation is the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) which catalyzes conversion of phosphatidylserine (PS) to PE. To study the genome wide effect of an unbalanced cellular and mitochondrial PE level and in particular the contribution of Psd1p to this depletion we performed a DNA microarray analysis with a ∆psd1 deletion mutant. This approach revealed that 54 yeast genes were significantly up-regulated in the absence of PSD1 compared to wild type. Surprisingly, marked down-regulation of genes was not observed. A number of different cellular processes in different subcellular compartments were affected in a ∆psd1 mutant. Deletion mutants bearing defects in all 54 candidate genes, respectively, were analyzed for their growth phenotype and their phospholipid profile. Only three mutants, namely ∆gpm2, ∆gph1 and ∆rsb1, were affected in one of these parameters. The possible link of these mutations to PE deficiency and PSD1 deletion is discussed.

40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

Code of Federal Regulations, 2013 CFR

2013-07-01

... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

40 CFR 52.2219 - Conditional approval.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... EPA is conditionally approving TDEC's submittal with respect to the PSD requirements of CAA sections... enforceable provisions for PSD increments as detailed in TDEC's October 4, 2012, commitment letter. Tennessee... PSD increments as described in the State's letter of commitment. (d) Conditional Approval—Submittal...

New Variance-Reducing Methods for the PSD Analysis of Large Optical Surfaces

NASA Technical Reports Server (NTRS)

Sidick, Erkin

2010-01-01

Edge data of a measured surface map of a circular optic result in large variance or "spectral leakage" behavior in the corresponding Power Spectral Density (PSD) data. In this paper we present two new, alternative methods for reducing such variance in the PSD data by replacing the zeros outside the circular area of a surface map by non-zero values either obtained from a PSD fit (method 1) or taken from the inside of the circular area (method 2).

The Role of the Two-Pore Domain Potassium Channel TREK-1 in the Therapeutic Effects of Escitalopram in a Rat Model of Poststroke Depression.

PubMed

Lin, Dai-Hua; Zhang, Xiang-Rong; Ye, Dong-Qing; Xi, Guang-Jun; Hui, Jiao-Jie; Liu, Shan-Shan; Li, Lin-Jiang; Zhang, Zhi-Jun

2015-06-01

Poststroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. TREK-1, a two-pore-domain potassium channel, has been implicated in the pathogenesis of stroke and depression. The aim of this study was to investigate whether TREK-1 plays a role in the therapeutic effects of the selective serotonin reuptake inhibitor (SSRI) escitalopram in a rat PSD model. The whole-cell patch-clamp technique was performed to assess the effect of escitalopram on recombinant TREK-1 currents in HEK293 cells. The expression of TREK-1 mRNA and protein was measured in the hippocampus and prefrontal cortex (PFC), and neural stem cell (NSC) proliferation was detected in the hippocampal dentate gyrus (DG) in PSD rats after 3 weeks of escitalopram administration. Escitalopram reversibly inhibited TREK-1 currents in a concentration-dependent manner. Chronic treatment with escitalopram significantly reversed the reductions in weight gain, locomotor activity, and sucrose preference in PSD rats. The expressions of TREK-1 mRNA and protein were significantly increased in hippocampal CA1, CA3, DG, and PFC in PSD rats, with the exception of TREK-1 mRNA in hippocampal CA1. NSC proliferation was significantly decreased in hippocampal DG of PSD rats. Escitalopram significantly reversed the regional increases of TREK-1 expression and the reduction of hippocampal NSC proliferation in PSD rats. TREK-1 plays an important role in the therapeutic effects of the SSRI escitalopram in PSD model, making TREK-1 an attractive candidate molecule for further understanding the pathophysiology and treatment of PSD. © 2015 John Wiley & Sons Ltd.

PSD microscopy: a new technique for adaptive local scanning of microscale objects.

PubMed

Rahimi, Mehdi; Shen, Yantao

2017-01-01

A position-sensitive detector/device (PSD) is a sensor that is capable of tracking the location of a laser beam on its surface. PSDs are used in many scientific instruments and technical applications including but not limited to atomic force microscopy, human eye movement monitoring, mirrors or machine tool alignment, vibration analysis, beam position control and so on. This work intends to propose a new application using the PSD. That is a new microscopy system called scanning PSD microscopy. The working mechanism is about putting an object on the surface of the PSD and fast scanning its area with a laser beam. To achieve a high degree of accuracy and precision, a reliable framework was designed using the PSD. In this work, we first tried to improve the PSD reading and its measurement performance. This was done by minimizing the effects of noise, distortion and other disturbing parameters. After achieving a high degree of confidence, the microscopy system can be implemented based on the improved PSD measurement performance. Later to improve the scanning efficiency, we developed an adaptive local scanning system to scan the whole area of the PSD in a short matter of time. It was validated that our comprehensive and adaptive local scanning method can shorten the scanning time in order of hundreds of times in comparison with the traditional raster scanning without losing any important information about the scanned 2D objects. Methods are also introduced to scan very complicated objects with bifurcations and crossings. By incorporating all these methods, the new microscopy system is capable of scanning very complicated objects in the matter of a few seconds with a resolution that is in order of a few micrometers.

PSD-95 interacts with NBCn1 and enhances channel-like activity without affecting Na/HCO(3) cotransport.

PubMed

Lee, Soojung; Yang, Han Soo; Kim, Eunjin; Ju, Eun Ji; Kwon, Min Hyung; Dudley, R Kyle; Smith, Yoland; Yun, C Chris; Choi, Inyeong

2012-01-01

The sodium/bicarbonate transporter NBCn1 plays an essential role in intracellular pH regulation and transepithelial HCO(3)(-) movement in the body. NBCn1 also has sodium channel-like activity uncoupled to Na/HCO(3) cotransport. We previously reported that NBCn1 interacts with the postsynaptic density protein PSD-95 in the brain. Here, we elucidated the structural determinant and functional consequence of NBCn1/PSD-95 interaction. In rat hippocampal CA3 neurons, NBCn1 was localized to the postsynaptic membranes of both dendritic shafts and spines and occasionally to the presynaptic membranes. A GST/NBCn1 fusion protein containing the C-terminal 131 amino acids of NBCn1 pulled down PSD-95 from rat brain lysates, whereas GST/NBCn1-ΔETSL (deletion of the last four amino acids) and GST/NBCn2 (NCBE) lacking the same ETSL did not. NBCn1 and PSD-95 were coimmunoprecipitated in HEK 293 cells, and their interaction did not affect the efficacy of PSD-95 to bind to the NMDA receptor NR2A. PSD-95 has negligible effects on intracellular pH changes mediated by NBCn1 in HEK 293 cells and Xenopus oocytes. However, PSD-95 increased an ionic conductance produced by NBCn1 channel-like activity. This increase was abolished by NBCn1-ΔETSL or by the peptide containing the last 15 amino acids of NBCn1. Our data suggest that PSD-95 interacts with NBCn1 and increases its channel-like activity while negligibly affecting Na/HCO(3) cotransport. The possibility that the channel-like activity occurs via an intermolecular cavity of multimeric NBCn1 proteins is discussed. Copyright © 2012 S. Karger AG, Basel.

Small RNAs regulate the biocontrol property of fluorescent Pseudomonas strain Psd.

PubMed

Upadhyay, Anamika; Kochar, Mandira; Upadhyay, Ashutosh; Tripathy, Soumya; Rajam, Manchikatla Venkat; Srivastava, Sheela

2017-03-01

The production of biocontrol factors by Pseudomonads is reported to be controlled at the post-transcriptional level by the GacS/GacA signal transduction pathway. This involves RNA-binding translational repressor proteins, RsmA and RsmE, and the small regulatory RNAs (sRNAs) RsmX, RsmY, and RsmZ. While the former represses genes involved in secondary metabolite production, the latter relieves this repression at the end of exponential growth. We have studied the fluorescent Pseudomonas strain Psd, possessing good biocontrol potential, and confirmed the presence of rsmY and rsmZ by PCR amplification. Gene constructs for all the three small RNAs (RsmX, RsmY and RsmZ) carried on broad host-range plasmid, pME6032 were mobilized into strain Psd. Expression analysis of gacA in the recombinant strains over-expressing rsmX (Psd-pME7320), rsmY (Psd-pME6359) and rsmZ (Psd-pME6918) revealed a significant upregulation of the response regulator. Besides, a remarkable down-regulation of rsmA was also reported in all the strains. The variant strains were found to produce comparatively higher levels of phenazines. Indole acetic acid levels were higher to some extent, and strain Psd-pME6918 also showed elevated production of HCN. The tomato seedlings infected with Fusarium oxysporum and Verticillium dahliae in the presence of culture filtrate of the recombinant strains showed better plant protection response in comparison to the wild-type strain Psd. These results suggest that small RNAs are important determinants in regulation of the biocontrol property of strain Psd. Copyright © 2016 Elsevier GmbH. All rights reserved.

PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density

PubMed Central

Chen, Xiaobing; Levy, Jonathan M.; Hou, Austin; Winters, Christine; Azzam, Rita; Sousa, Alioscka A.; Leapman, Richard D.; Nicoll, Roger A.; Reese, Thomas S.

2015-01-01

The postsynaptic density (PSD)-95 family of membrane-associated guanylate kinases (MAGUKs) are major scaffolding proteins at the PSD in glutamatergic excitatory synapses, where they maintain and modulate synaptic strength. How MAGUKs underlie synaptic strength at the molecular level is still not well understood. Here, we explore the structural and functional roles of MAGUKs at hippocampal excitatory synapses by simultaneous knocking down PSD-95, PSD-93, and synapse-associated protein (SAP)102 and combining electrophysiology and transmission electron microscopic (TEM) tomography imaging to analyze the resulting changes. Acute MAGUK knockdown greatly reduces synaptic transmission mediated by α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) and N-methyl-d-aspartate receptors (NMDARs). This knockdown leads to a significant rise in the number of silent synapses, diminishes the size of PSDs without changes in pre- or postsynaptic membrane, and depletes the number of membrane-associated PSD-95–like vertical filaments and transmembrane structures, identified as AMPARs and NMDARs by EM tomography. The differential distribution of these receptor-like structures and dependence of their abundance on PSD size matches that of AMPARs and NMDARs in the hippocampal synapses. The loss of these structures following MAGUK knockdown tracks the reduction in postsynaptic AMPAR and NMDAR transmission, confirming the structural identities of these two types of receptors. These results demonstrate that MAGUKs are required for anchoring both types of glutamate receptors at the PSD and are consistent with a structural model where MAGUKs, corresponding to membrane-associated vertical filaments, are the essential structural proteins that anchor and organize both types of glutamate receptors and govern the overall molecular organization of the PSD. PMID:26604311

Identification of N-methyl-D-aspartic acid (NMDA) receptor subtype-specific binding sites that mediate direct interactions with scaffold protein PSD-95.

PubMed

Cousins, Sarah L; Stephenson, F Anne

2012-04-13

N-methyl-D-aspartate (NMDA) neurotransmitter receptors and the postsynaptic density-95 (PSD-95) membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins are integral components of post-synaptic macromolecular signaling complexes that serve to propagate glutamate responses intracellularly. Classically, NMDA receptor NR2 subunits associate with PSD-95 MAGUKs via a conserved ES(E/D)V amino acid sequence located at their C termini. We previously challenged this dogma to demonstrate a second non-ES(E/D)V PSD-95-binding site in both NMDA receptor NR2A and NR2B subunits. Here, using a combination of co-immunoprecipitations from transfected mammalian cells, yeast two-hybrid interaction assays, and glutathione S-transferase (GST) pulldown assays, we show that NR2A subunits interact directly with PSD-95 via the C-terminal ESDV motif and additionally via an Src homology 3 domain-binding motif that associates with the Src homology 3 domain of PSD-95. Peptide inhibition of co-immunoprecipitations of NR2A and PSD-95 demonstrates that both the ESDV and non-ESDV sites are required for association in native brain tissue. Furthermore, we refine the non-ESDV site within NR2B to residues 1149-1157. These findings provide a molecular basis for the differential association of NMDA receptor subtypes with PSD-95 MAGUK scaffold proteins. These selective interactions may contribute to the organization, lateral mobility, and ultimately the function of NMDA receptor subtypes at synapses. Furthermore, they provide a more general molecular mechanism by which the scaffold, PSD-95, may discriminate between potential interacting partner proteins.

Identification of N-Methyl-d-aspartic Acid (NMDA) Receptor Subtype-specific Binding Sites That Mediate Direct Interactions with Scaffold Protein PSD-95*

PubMed Central

Cousins, Sarah L.; Stephenson, F. Anne

2012-01-01

N-methyl-d-aspartate (NMDA) neurotransmitter receptors and the postsynaptic density-95 (PSD-95) membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins are integral components of post-synaptic macromolecular signaling complexes that serve to propagate glutamate responses intracellularly. Classically, NMDA receptor NR2 subunits associate with PSD-95 MAGUKs via a conserved ES(E/D)V amino acid sequence located at their C termini. We previously challenged this dogma to demonstrate a second non-ES(E/D)V PSD-95-binding site in both NMDA receptor NR2A and NR2B subunits. Here, using a combination of co-immunoprecipitations from transfected mammalian cells, yeast two-hybrid interaction assays, and glutathione S-transferase (GST) pulldown assays, we show that NR2A subunits interact directly with PSD-95 via the C-terminal ESDV motif and additionally via an Src homology 3 domain-binding motif that associates with the Src homology 3 domain of PSD-95. Peptide inhibition of co-immunoprecipitations of NR2A and PSD-95 demonstrates that both the ESDV and non-ESDV sites are required for association in native brain tissue. Furthermore, we refine the non-ESDV site within NR2B to residues 1149–1157. These findings provide a molecular basis for the differential association of NMDA receptor subtypes with PSD-95 MAGUK scaffold proteins. These selective interactions may contribute to the organization, lateral mobility, and ultimately the function of NMDA receptor subtypes at synapses. Furthermore, they provide a more general molecular mechanism by which the scaffold, PSD-95, may discriminate between potential interacting partner proteins. PMID:22375001

The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury.

PubMed

Zhang, Qingxiu; Cheng, Hongyu; Rong, Rong; Yang, Hui; Ji, Qiuhong; Li, Qingjie; Rong, Liangqun; Hu, Gang; Xu, Yun

2015-12-01

The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. RT-PCR was used to detect the mRNA expression of IL-6, IL-10, Cox-2, iNOS, and TNF-α4h following reperfusion. Infarct volume at different time points after I/R was analyzed using 2,3,5-triphenyl tetrazolium staining, and neurological damage score (neurological severity scores, NSS) was used to evaluate the effect of PSD-93 gene knockout on the MCAO-induced neurological injury. In WT mice, early I/R injury led to the increase in the mRNA expression of proinflammatory cytokines IL-6, Cox-2, iNOS, and TNF-α that coincided with the decrease in the expression of anti-inflammatory cytokine IL-10, as compared to the sham group (P < 0.05). This effect was markedly attenuated by depleting PSD-93 levels by gene knockout. As compared to sham group, in PSD-93 KO mice I/R4h led to downregulation of Cox-2 and iNOS expression, and increase in the mRNA levels of IL-10 (P < 0.05). In addition, following MCAO, PSD-93 KO mice exhibited improved NSS and reduced infarct volumes, as compared with WT animals. PSD-93 knockout may play a neuroprotective role by mediating the early release of inflammatory cytokines induced by cerebral ischemia.

PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density.

PubMed

Chen, Xiaobing; Levy, Jonathan M; Hou, Austin; Winters, Christine; Azzam, Rita; Sousa, Alioscka A; Leapman, Richard D; Nicoll, Roger A; Reese, Thomas S

2015-12-15

The postsynaptic density (PSD)-95 family of membrane-associated guanylate kinases (MAGUKs) are major scaffolding proteins at the PSD in glutamatergic excitatory synapses, where they maintain and modulate synaptic strength. How MAGUKs underlie synaptic strength at the molecular level is still not well understood. Here, we explore the structural and functional roles of MAGUKs at hippocampal excitatory synapses by simultaneous knocking down PSD-95, PSD-93, and synapse-associated protein (SAP)102 and combining electrophysiology and transmission electron microscopic (TEM) tomography imaging to analyze the resulting changes. Acute MAGUK knockdown greatly reduces synaptic transmission mediated by α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) and N-methyl-d-aspartate receptors (NMDARs). This knockdown leads to a significant rise in the number of silent synapses, diminishes the size of PSDs without changes in pre- or postsynaptic membrane, and depletes the number of membrane-associated PSD-95-like vertical filaments and transmembrane structures, identified as AMPARs and NMDARs by EM tomography. The differential distribution of these receptor-like structures and dependence of their abundance on PSD size matches that of AMPARs and NMDARs in the hippocampal synapses. The loss of these structures following MAGUK knockdown tracks the reduction in postsynaptic AMPAR and NMDAR transmission, confirming the structural identities of these two types of receptors. These results demonstrate that MAGUKs are required for anchoring both types of glutamate receptors at the PSD and are consistent with a structural model where MAGUKs, corresponding to membrane-associated vertical filaments, are the essential structural proteins that anchor and organize both types of glutamate receptors and govern the overall molecular organization of the PSD.

PSD-95 Interacts with NBCn1 and Enhances Channel-like Activity without Affecting Na/HCO3 Cotransport

PubMed Central

Lee, Soojung; Yang, Han Soo; Kim, Eunjin; Ju, Eun Ji; Kwon, Min Hyung; Dudley, R. Kyle; Smith, Yoland; Yun, C. Chris; Choi, Inyeong

2013-01-01

Background/Aims The sodium/bicarbonate transporter NBCn1 plays an essential role in intracellular pH regulation and transepithelial HCO3− movement in the body. NBCn1 also has sodium channel-like activity uncoupled to Na/HCO3 cotransport. We previously reported that NBCn1 interacts with the postsynaptic density protein PSD-95 in the brain. Here, we elucidated the structural determinant and functional consequence of NBCn1/PSD-95 interaction. Methods: Results In rat hippocampal CA3 neurons, NBCn1 was localized to the postsynaptic membranes of both dendritic shafts and spines and occasionally to the presynaptic membranes. A GST/NBCn1 fusion protein containing the C-terminal 131 amino acids of NBCn1 pulled down PSD-95 from rat brain lysates, whereas GST/NBCn1-ΔETSL (deletion of the last four amino acids) and GST/NBCn2 (NCBE) lacking the same ETSL did not. NBCn1 and PSD-95 were coimmunoprecipitated in HEK 293 cells, and their interaction did not affect the efficacy of PSD-95 to bind to the NMDA receptor NR2A. PSD-95 has negligible effects on intracellular pH changes mediated by NBCn1 in HEK 293 cells and Xenopus oocytes. However, PSD-95 increased an ionic conductance produced by NBCn1 channel-like activity. This increase was abolished by NBCn1-ΔETSL or by the peptide containing the last 15 amino acids of NBCn1. Conclusion Our data suggest that PSD-95 interacts with NBCn1 and increases its channel-like activity while negligibly affecting Na/HCO3 cotransport. The possibility that the channel-like activity occurs via an intermolecular cavity of multimeric NBCn1 proteins is discussed. PMID:23183381

G quadruplex RNA structures in PSD-95 mRNA: potential regulators of miR-125a seed binding site accessibility.

PubMed

Stefanovic, Snezana; Bassell, Gary J; Mihailescu, Mihaela Rita

2015-01-01

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability caused by the CGG trinucleotide expansion in the 3'-untranslated region of the FMR1 gene on the X chromosome, that silences the expression of the Fragile X mental retardation protein (FMRP). FMRP has been shown to bind to a G-rich region within the PSD-95 mRNA which encodes for the postsynaptic density protein 95 (PSD-95), and together with the microRNA miR-125a, to play an important role in the reversible inhibition of the PSD-95 mRNA translation in neurons. The loss of FMRP in Fmr1 KO mice disables this translation control in the production of the PSD-95 protein. Interestingly, the miR-125a binding site on PSD-95 mRNA is embedded in the G-rich region bound by FMRP and postulated to adopt one or more G quadruplex structures. In this study, we have used different biophysical techniques to validate and characterize the formation of parallel G quadruplex structures and binding of miR-125a to its complementary sequence located within the 3' UTR of PSD-95 mRNA. Our results indicate that the PSD-95 mRNA G-rich region folds into alternate G quadruplex conformations that coexist in equilibrium. miR-125a forms a stable complex with PSD-95 mRNA, as evident by characteristic Watson-Crick base-pairing that coexists with one of the G quadruplex forms, suggesting a novel mechanism for G quadruplex structures to regulate the access of miR-125a to its binding site. © 2014 Stefanovic et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

G quadruplex RNA structures in PSD-95 mRNA: potential regulators of miR-125a seed binding site accessibility

PubMed Central

Stefanovic, Snezana; Bassell, Gary J.

2015-01-01

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability caused by the CGG trinucleotide expansion in the 3′-untranslated region of the FMR1 gene on the X chromosome, that silences the expression of the Fragile X mental retardation protein (FMRP). FMRP has been shown to bind to a G-rich region within the PSD-95 mRNA which encodes for the postsynaptic density protein 95 (PSD-95), and together with the microRNA miR-125a, to play an important role in the reversible inhibition of the PSD-95 mRNA translation in neurons. The loss of FMRP in Fmr1 KO mice disables this translation control in the production of the PSD-95 protein. Interestingly, the miR-125a binding site on PSD-95 mRNA is embedded in the G-rich region bound by FMRP and postulated to adopt one or more G quadruplex structures. In this study, we have used different biophysical techniques to validate and characterize the formation of parallel G quadruplex structures and binding of miR-125a to its complementary sequence located within the 3′ UTR of PSD-95 mRNA. Our results indicate that the PSD-95 mRNA G-rich region folds into alternate G quadruplex conformations that coexist in equilibrium. miR-125a forms a stable complex with PSD-95 mRNA, as evident by characteristic Watson–Crick base-pairing that coexists with one of the G quadruplex forms, suggesting a novel mechanism for G quadruplex structures to regulate the access of miR-125a to its binding site. PMID:25406362

Peeling skin diseases: 21 cases from Turkey and a review of the literature.

PubMed

Köse, O; Safali, M; Koç, E; Arca, E; Açikgöz, G; Özmen, I; Yeniay, Y

2012-07-01

Peeling skin diseases (PSD) refer to a group of rare autosomal recessive dermatosis which are characterized by spontaneous, continual peeling of the skin. Three different clinical pictures can be distinguished: Inflammatory PSD also referred to as peeling skin syndrome (PSS) type B, non-inflammatory PSD also referred to as PSS type A, and localized forms i.e. acral type PSS. To characterize the clinical and histopathological features of PSD in Turkey. We retrospectively reviewed the medical records and clinical photographs of patients who were given diagnosis of PSD and conducted histopathological evaluation of skin biopsies to identify the site of cleavage. Also we evaluated the cases including age, gender, age onset, clinical and histological findings, family history, associated disorders and PSD type. Twenty-one patients with PSD were seen at Gulhane School of Medicine in Ankara between the years 1994 and 2010 in this retrospective study. All patients were men. Their ages were between 20 and 26 years (22.44±2.30, Mean age±SD). Of the patients, eight cases (40%) were type A, eight cases (40%) were type B, and five cases (20%) were acral type PSS. Eleven cases (52%) had parental consanguinity. Keratoderma, cheilitis, keratosis pilaris, melanonichia, clubbing, hyperhidrosis, onychodystrophy were observed in eight cases as an accompanying disorder. In this case series, PSD occurred rarely and also showed generally mild course of disease in Turkey and most likely related to consanguineous of marriages. Future investigations on PSD will contribute to our progressing alternative targets for pathogenesis-based therapy. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Reduced thalamic volume in men with antisocial personality disorder or schizophrenia and a history of serious violence and childhood abuse.

PubMed

Kumari, V; Gudjonsson, G H; Raghuvanshi, S; Barkataki, I; Taylor, P; Sumich, A; Das, K; Kuipers, E; Ffytche, D H; Das, M

2013-05-01

Violent behaviour has been associated with presence of certain mental disorders, most notably antisocial personality disorder (ASPD) and schizophrenia, childhood abuse, and multiple brain abnormalities. This study examined for the first time, to the authors' knowledge, the role of psychosocial deprivation (PSD), including childhood physical and sexual abuse, in structural brain volumes of violent individuals with ASPD or schizophrenia. Fifty-six men (26 with ASPD or schizophrenia and a history of serious violence, 30 non-violent) underwent magnetic resonance imaging and were assessed on PSD. Stereological volumetric brain ratings were examined for group differences and their association with PSD ratings. PSD-brain associations were examined further using voxel-based-morphometry. The findings revealed: reduced thalamic volume in psychosocially-deprived violent individuals, relative to non-deprived violent individuals and healthy controls; negative association between thalamic volume and abuse ratings (physical and sexual) in violent individuals; and trend-level negative associations between PSD and hippocampal and prefrontal volumes in non-violent individuals. The voxel-based-morphometry analysis detected a negative association between PSD and localised grey matter volumes in the left inferior frontal region across all individuals, and additionally in the left middle frontal and precentral gyri in non-violent individuals. Violent mentally-disordered individuals with PSD, relative to those with no or minimal PSD, suffer from an additional brain deficit, i.e., reduced thalamic volume; this may affect sensory information processing, and have implications for management, of these individuals. PSD may have a stronger relationship with volumetric loss of stress-linked regions, namely the frontal cortex, in non-violent individuals. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Evaluating Disease Severity in Chronic Pain Patients with and without Fibromyalgia: A Comparison of the Symptom Impact Questionnaire and the Polysymptomatic Distress Scale.

PubMed

Friend, Ronald; Bennett, Robert M

2015-12-01

To compare the relative effectiveness of the Polysymptomatic Distress Scale (PSD) with the Symptom Impact Questionnaire (SIQR), the disease-neutral revision of the updated Fibromyalgia Impact Questionnaire (FIQR), in their ability to assess disease activity in patients with rheumatic disorders both with and without fibromyalgia (FM). The study included 321 patients from 8 clinical practices with some 16 different chronic pain disorders. Disease severity was assessed by the Medical Outcomes Study Short Form-36 (SF-36). Univariate analyses were used to assess the magnitude of PSD and SIQR correlations with SF-36 subscales. Hierarchical stepwise regression was used to evaluate the unique contribution of the PSD and SIQR to the SF-36. Random forest regression probed the relative importance of the SIQR and PSD components as predictors of SF-36. The correlations with the SF-36 subscales were significantly higher for the SIQR (0.48 to 0.78) than the PSD (0.29 to 0.56; p < 0.001). Stepwise regression revealed that the SIQR was contributing additional unique variance on SF-36 subscales, which was not the case for the PSD. Random forest regression showed SIQR Function, Symptoms, and Global Impact subscales were more important predictors of SF-36 than the PSD. The single SIQR pain item contributed 55% of SF-36 pain variance compared to 23% with the 19-point WPI (the Widespread Pain Index component of PSD). The SIQR, the disease-neutral revision of the updated FIQ, has several important advantages over the PSD in the evaluation of disease severity in chronic pain disorders.

Digital pulse shape discrimination.

PubMed

Miller, L F; Preston, J; Pozzi, S; Flaska, M; Neal, J

2007-01-01

Pulse-shape discrimination (PSD) has been utilised for about 40 years as a method to obtain estimates for dose in mixed neutron and photon fields. Digitizers that operate close to GHz are currently available at a reasonable cost, and they can be used to directly sample signals from photomultiplier tubes. This permits one to perform digital PSD rather than the traditional, and well-established, analogoue techniques. One issue that complicates PSD for neutrons in mixed fields is that the light output characteristics of typical scintillators available for PSD, such as BC501A, vary as a function of energy deposited in the detector. This behaviour is more easily accommodated with digital processing of signals than with analogoue signal processing. Results illustrate the effectiveness of digital PSD.

Power-spectral-density relationship for retarded differential equations

NASA Technical Reports Server (NTRS)

Barker, L. K.

1974-01-01

The power spectral density (PSD) relationship between input and output of a set of linear differential-difference equations of the retarded type with real constant coefficients and delays is discussed. The form of the PSD relationship is identical with that applicable to unretarded equations. Since the PSD relationship is useful if and only if the system described by the equations is stable, the stability must be determined before applying the PSD relationship. Since it is sometimes difficult to determine the stability of retarded equations, such equations are often approximated by simpler forms. It is pointed out that some common approximations can lead to erroneous conclusions regarding the stability of a system and, therefore, to the possibility of obtaining PSD results which are not valid.

40 CFR 52.2134 - Original identification of plan section.

Code of Federal Regulations, 2012 CFR

2012-07-01

... for ozone nonattainment areas, PSD NOX increment regulations, and regulations listing the definition..., paragraph 4; covering PSD. These regulations were effective August 24, 1990, and submitted September 18... 4 covering PSD. These regulations were effective June 26, 1992, and submitted July 23, 1992. (ii...

40 CFR 52.2134 - Original identification of plan section.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for ozone nonattainment areas, PSD NOX increment regulations, and regulations listing the definition..., paragraph 4; covering PSD. These regulations were effective August 24, 1990, and submitted September 18... 4 covering PSD. These regulations were effective June 26, 1992, and submitted July 23, 1992. (ii...

40 CFR 52.2134 - Original identification of plan section.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for ozone nonattainment areas, PSD NOX increment regulations, and regulations listing the definition..., paragraph 4; covering PSD. These regulations were effective August 24, 1990, and submitted September 18... 4 covering PSD. These regulations were effective June 26, 1992, and submitted July 23, 1992. (ii...

40 CFR 52.2134 - Original identification of plan section.

Code of Federal Regulations, 2013 CFR

2013-07-01

... for ozone nonattainment areas, PSD NOX increment regulations, and regulations listing the definition..., paragraph 4; covering PSD. These regulations were effective August 24, 1990, and submitted September 18... 4 covering PSD. These regulations were effective June 26, 1992, and submitted July 23, 1992. (ii...

Agrobacterium tumefaciens-mediated transformation of the soybean pathogen Phomopsis longicolla

USDA-ARS?s Scientific Manuscript database

Phomopsis seed decay (PSD) of soybean is caused primarily by the fungal pathogen Phomopsis longicolla. PSD impairs seed germination, reduces seedling vigor, and can substantially reduce stand establishment. In hot and humid conditions, PSD can cause significant yield losses. Few studies have explore...

Evaluation of the membrane lipid selectivity of the pea defensin Psd1.

PubMed

Gonçalves, Sónia; Teixeira, Alexandre; Abade, João; de Medeiros, Luciano Neves; Kurtenbach, Eleonora; Santos, Nuno C

2012-05-01

Psd1, a 46 amino acid residues defensin isolated from the pea Pisum sativum seeds, exhibits anti-fungal activity by a poorly understood mechanism of action. In this work, the interaction of Psd1 with biomembrane model systems of different lipid compositions was assessed by fluorescence spectroscopy. Partition studies showed a marked lipid selectivity of this antimicrobial peptide (AMP) toward lipid membranes containing ergosterol (the main sterol in fungal membranes) or specific glycosphingolipid components, with partition coefficients (K(p)) reaching uncommonly high values of 10(6). By the opposite, Psd1 does not partition to cholesterol-enriched lipid bilayers, such as mammalian cell membranes. The Psd1 mutants His36Lys and Gly12Glu present a membrane affinity loss relative to the wild type. Fluorescence quenching data obtained using acrylamide and membrane probes further clarify the mechanism of action of this peptide at the molecular level, pointing out the potential therapeutic use of Psd1 as a natural antimycotic agent. Copyright © 2012 Elsevier B.V. All rights reserved.

Ca2+/calmodulin binding to PSD-95 mediates homeostatic synaptic scaling down.

PubMed

Chowdhury, Dhrubajyoti; Turner, Matthew; Patriarchi, Tommaso; Hergarden, Anne C; Anderson, David; Zhang, Yonghong; Sun, Junqing; Chen, Chao-Yin; Ames, James B; Hell, Johannes W

2018-01-04

Postsynaptic density protein-95 (PSD-95) localizes AMPA-type glutamate receptors (AMPARs) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPARs during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca 2+ influx, Ca 2+ /calmodulin (Ca 2+ /CaM) binding to the N-terminus of PSD-95 mediates postsynaptic loss of PSD-95 and AMPARs during homeostatic scaling down. Our NMR structural analysis identified E17 within the PSD-95 N-terminus as important for binding to Ca 2+ /CaM by interacting with R126 on CaM. Mutating E17 to R prevented homeostatic scaling down in primary hippocampal neurons, which is rescued via charge inversion by ectopic expression of CaM R 126E , as determined by analysis of miniature excitatory postsynaptic currents. Accordingly, increased binding of Ca 2+ /CaM to PSD-95 induced by a chronic increase in Ca 2+ influx is a critical molecular event in homeostatic downscaling of glutamatergic synaptic transmission. © 2017 The Authors.

Involvement of a putative substrate binding site in the biogenesis and assembly of phosphatidylserine decarboxylase 1 from Saccharomyces cerevisiae.

PubMed

Di Bartolomeo, Francesca; Doan, Kim Nguyen; Athenstaedt, Karin; Becker, Thomas; Daum, Günther

2017-07-01

In the yeast Saccharomyces cerevisiae, the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) produces the largest amount of cellular phosphatidylethanolamine (PE). Psd1p is synthesized as a larger precursor on cytosolic ribosomes and then imported into mitochondria in a three-step processing event leading to the formation of an α-subunit and a β-subunit. The α-subunit harbors a highly conserved motif, which was proposed to be involved in phosphatidylserine (PS) binding. Here, we present a molecular analysis of this consensus motif for the function of Psd1p by using Psd1p variants bearing either deletions or point mutations in this region. Our data show that mutations in this motif affect processing and stability of Psd1p, and consequently the enzyme's activity. Thus, we conclude that this consensus motif is essential for structural integrity and processing of Psd1p. Copyright © 2017 Elsevier B.V. All rights reserved.

Hadron calorimeter (PSD) with new photo-detectors (MPPC) in NA61 experiment at CERN

NASA Astrophysics Data System (ADS)

Golubeva, M.; Guber, F.; Ivashkin, A.; Izvestnyy, A.; Kurepin, A.; Morozov, S.; Petukhov, O.; Selyuzhenkov, I.; Svintsov, I.; Taranenko, A.

2017-01-01

The Projectile Spectator Detector (PSD) is a segmented hadron calorimeter used in NA61 experiment (CERN) to determine a collision centrality as well as an event plane orientation in nucleus-nucleus collisions. The main goal of the experiment includes studying the onset of de-confinement and searching for the critical point of strongly interacting matter. It is of crucial importance to have a precise characterization of the event class with the PSD for the analysis of event-by-event observables. The PSD has been already used for centrality selection on trigger level in measurements of Be+Be and Ar+Sc reactions at beam energies 13 - 158 AGeV and Pb+Pb reaction at beam energy 30 AGeV. In 2016, the central modules of PSD have been equipped with new Hamamatsu MPPC silicon photo-detectors in order to extend dynamic range for studying Pb+Pb reaction at the full energy range 13 - 158 AGeV. Results of the PSD response on proton and lead beams are presented.

Low Serum Levels of Uric Acid are Associated With Development of Poststroke Depression.

PubMed

Gu, Yingying; Han, Bin; Wang, Liping; Chang, Yaling; Zhu, Lin; Ren, Wenwei; Yan, Mengjiao; Zhang, Xiangyang; He, Jincai

2015-11-01

Poststroke depression (PSD) is a frequent complication of stroke that has been associated with poorer outcome of stroke patients. This study sought to examine the possible association between serum uric acid levels and the development of PSD.We recruited 196 patients with acute ischemic stroke and 100 healthy volunteers. Serum uric acid levels were tested by uricase-PAP method within 24 hr after admission. Neuropsychological evaluations were conducted at 3-month poststroke. The 17-item Hamilton Depression Scale was used to assess depressive symptoms. Diagnosis of PSD was made in accordance with DSM-IV criteria for depression. Multivariate analyses were conducted using logistic regression models.Fifty-six patients (28.6%) were diagnosed as having PSD at 3 months. PSD patients showed significantly lower levels of uric acid at baseline as compared to non-PSD patients (237.02 ± 43.43 vs 309.10 ± 67.44 μmol/L, t = -8.86, P < 0.001). In multivariate analyses, uric acid levels (≤239.0 and ≥328.1 μmol/L) were independently associated with the development of PSD (OR, 7.76; 95% confidence interval [CI], 2.56-23.47, P < 0.001 and OR, 0.05; 95% CI, 0.01-0.43, P = 0.01, respectively) after adjustment for possible variables.Serum uric acid levels at admission are found to be correlated with PSD and may predict its development at 3 months after stroke.

Effects of environmental enrichment and paradoxical sleep deprivation on open-field behavior of amphetamine-treated mice.

PubMed

Fukushiro, Daniela Fukue; Calzavara, Mariana Bendlin; Trombin, Thaís Fernanda; Lopez, Giorgia Batlle; Abílio, Vanessa Costhek; Andersen, Monica Levy; Tufik, Sergio; Frussa-Filho, Roberto

2007-11-23

Environmental enrichment or paradoxical sleep deprivation (PSD) has been shown to modify some responses elicited by drugs of abuse. The aims of the present study were to examine the effects of environmental enrichment and PSD, conducted separately or in association, on open-field behavior elicited by amphetamine (AMP) in mice. Male C57BL/6 mice were randomly assigned to live in either an enriched environmental condition (EC) or a standard environmental condition (SC) for 12 months since weaning. Some of the EC and SC mice were sleep deprived for 48 h, while others were maintained in their home-cages. Immediately after PSD or home-cage stay, the animals received an ip injection of saline, 2.5 mg/kg AMP or 5.0 mg/kg AMP. Fifteen minutes later, their open-field behavior was quantified. Whereas PSD enhanced total and peripheral locomotor activity of acutely AMP-treated mice, environmental enrichment presented only a trend toward enhancement. When PSD and environmental enrichment were combined, an increase in the total and peripheral locomotion frequencies of AMP-treated animals, similar to that observed after PSD, was revealed. In addition, PSD, environmental enrichment or their combination did not modify the effects of AMP on the other open-field behavioral parameters that were analyzed. The present findings demonstrate that some (but not all) of the behavioral effects caused by AMP acute administration can be similarly and specifically enhanced by both environmental enrichment and PSD in C57BL/6 mice.

40 CFR 52.2522 - Approval status.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Federal regulatory SIP requirements for PSD applicable as of the August 31, 2011 SIP revision submission..., October 1, 2009, October 26, 2011, and February 17, 2012 which address the PSD-related requirements set... February 17, 2012 submitted to meet the PSD-related infrastructure SIP obligations set forth at CAA...

40 CFR 124.1 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-07-01

... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

50 CFR 679.26 - Prohibited Species Donation Program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ALASKA Management Measures § 679.26 Prohibited Species Donation Program. (a) Authorized species. The PSD... maintain adequate funding for the distribution of fish under the PSD program. (vii) A copy of the applicant... received under the PSD program, including sufficient liability insurance to cover public interests relating...

40 CFR 124.1 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-07-01

... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

40 CFR 124.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

40 CFR 52.522 - Approval status.

Code of Federal Regulations, 2014 CFR

2014-07-01

... prevention of significant deterioration (PSD) requirements for the regulation of greenhouse gas emissions. EPA is disapproving FDEP's submittal with respect to the PSD requirements of CAA sections 110(a)(2)(C... related to PSD requirements for the regulation of greenhouse gas emissions. [45 FR 17143, Mar. 18, 1980...

Evaluating soybean cultivars for resistance to Phomopsis seed decay in Mississippi

USDA-ARS?s Scientific Manuscript database

Phomopsis seed decay (PSD) of soybean reduces seed quality, germination and seedling vigor. PSD has been problematic in most soybean production areas including Mississippi (MS). Planting resistant cultivars is one of the most effective means to control PSD. However, very few soybean cultivars resis...

40 CFR 124.1 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-07-01

... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

40 CFR 69.31 - New exemptions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... This exemption applies solely to the PSD major source baseline date and trigger date in the... applicable requirement that is triggered by, implemented or calculated from the PSD major source baseline... the Northern Mariana Islands, use January 13, 1997 as the PSD major source baseline date and trigger...

40 CFR 52.200 - Original identification of plan section.

Code of Federal Regulations, 2012 CFR

2012-07-01

... plan to incorporate Federal Prevention of Significant Deterioration (PSD) Regulations 40 CFR 52.21 by... Plan for Prevention of Significant Deterioration (PSD) of Air Quality Supplement Arkansas Plan of Implementation for Air Pollution Control (PSD nitrogen dioxide increments), as adopted on May 25, 1990, by the...

50 CFR 679.26 - Prohibited Species Donation Program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ALASKA Management Measures § 679.26 Prohibited Species Donation Program. (a) Authorized species. The PSD... maintain adequate funding for the distribution of fish under the PSD program. (vii) A copy of the applicant... received under the PSD program, including sufficient liability insurance to cover public interests relating...

50 CFR 679.26 - Prohibited Species Donation Program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ALASKA Management Measures § 679.26 Prohibited Species Donation Program. (a) Authorized species. The PSD... maintain adequate funding for the distribution of fish under the PSD program. (vii) A copy of the applicant... received under the PSD program, including sufficient liability insurance to cover public interests relating...

40 CFR 124.1 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-07-01

... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

50 CFR 679.26 - Prohibited Species Donation Program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ALASKA Management Measures § 679.26 Prohibited Species Donation Program. (a) Authorized species. The PSD... distribution of fish under the PSD program. (vii) A copy of the applicant's articles of incorporation and... full responsibility for the documentation and disposition of fish received under the PSD program...

40 CFR 52.200 - Original identification of plan section.

Code of Federal Regulations, 2014 CFR

2014-07-01

... plan to incorporate Federal Prevention of Significant Deterioration (PSD) Regulations 40 CFR 52.21 by... Plan for Prevention of Significant Deterioration (PSD) of Air Quality Supplement Arkansas Plan of Implementation for Air Pollution Control (PSD nitrogen dioxide increments), as adopted on May 25, 1990, by the...

40 CFR 52.200 - Original identification of plan section.

Code of Federal Regulations, 2013 CFR

2013-07-01

... plan to incorporate Federal Prevention of Significant Deterioration (PSD) Regulations 40 CFR 52.21 by... Plan for Prevention of Significant Deterioration (PSD) of Air Quality Supplement Arkansas Plan of Implementation for Air Pollution Control (PSD nitrogen dioxide increments), as adopted on May 25, 1990, by the...

EPA-MassDEP Prevention of Significant Deterioration (PSD) Delegation Agreement

EPA Pesticide Factsheets

In April 2011, an agreement for delegation of the federal PSD program was executed by EPA Region 1 to the MassDEP. This agreement sets forth the terms & conditions according to which the MassDEP agrees to implement and enforce the federal PSD regulations.

Pin1 Modulates the Synaptic Content of NMDA Receptors via Prolyl-Isomerization of PSD-95.

PubMed

Antonelli, Roberta; De Filippo, Roberto; Middei, Silvia; Stancheva, Stefka; Pastore, Beatrice; Ammassari-Teule, Martine; Barberis, Andrea; Cherubini, Enrico; Zacchi, Paola

2016-05-18

Phosphorylation of serine/threonine residues preceding a proline regulates the fate of its targets through postphosphorylation conformational changes catalyzed by the peptidyl-prolyl cis-/trans isomerase Pin1. By flipping the substrate between two different functional conformations, this enzyme exerts a fine-tuning of phosphorylation signals. Pin1 has been detected in dendritic spines and shafts where it regulates protein synthesis required to sustain the late phase of long-term potentiation (LTP). Here, we demonstrate that Pin1 residing in postsynaptic structures can interact with postsynaptic density protein-95 (PSD-95), a key scaffold protein that anchors NMDA receptors (NMDARs) in PSD via GluN2-type receptor subunits. Pin1 recruitment by PSD-95 occurs at specific serine-threonine/proline consensus motifs localized in the linker region connecting PDZ2 to PDZ3 domains. Upon binding, Pin1 triggers structural changes in PSD-95, thus negatively affecting its ability to interact with NMDARs. In electrophysiological experiments, larger NMDA-mediated synaptic currents, evoked in CA1 principal cells by Schaffer collateral stimulation, were detected in hippocampal slices obtained from Pin1(-/-) mice compared with controls. Similar results were obtained in cultured hippocampal cells expressing a PSD-95 mutant unable to undergo prolyl-isomerization, thus indicating that the action of Pin1 on PSD-95 is critical for this effect. In addition, an enhancement in spine density and size was detected in CA1 principal cells of Pin1(-/-) or in Thy-1GFP mice treated with the pharmacological inhibitor of Pin1 catalytic activity PiB.Our data indicate that Pin1 controls synaptic content of NMDARs via PSD-95 prolyl-isomerization and the expression of dendritic spines, both required for LTP maintenance. PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein at excitatory postsynaptic densities and a potent regulator of synaptic strength and plasticity. The activity of PSD-95 is tightly controlled by several post-translational mechanisms including proline-directed phosphorylation. This signaling cascade regulates the fate of its targets through postphosphorylation conformational modifications catalyzed by the peptidyl-prolyl cis-/trans isomerase Pin1. Here, we uncover a new role of Pin1 in glutamatergic signaling. By interacting with PSD-95, Pin1 dampens PSD-95 ability to complex with NMDARs, thus negatively affecting NMDAR signaling and spine morphology. Our findings further emphasize the emerging role of Pin1 as a key modulator of synaptic transmission. Copyright © 2016 the authors 0270-6474/16/365437-11$15.00/0.

75 FR 59179 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-27

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R05-OAR-2010-0657; FRL-9205-7] Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations AGENCY: Environmental Protection... requirements of the prevention of significant deterioration (PSD) construction permit program in Michigan...

40 CFR 52.343 - Significant deterioration of air quality.

Code of Federal Regulations, 2012 CFR

2012-07-01

... constructed prior to September 2, 1986 and which have not otherwise subjected themselves to Colorado's PSD permitting regulations after September 2, 1986, either through application to Colorado for a PSD permit (in the case of those sources which improperly constructed without obtaining a PSD permit) or through...

7 CFR 760.1301 - Administration.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Administrator” in this part), and will be carried out by FSA's Price Support Division (PSD) and Kansas City... PSD, KCMO, a State committee, or a county committee will preclude the Administrator, FSA, or a... determination made by PSD, KCMO, a State committee, or a county committee. (f) The Deputy Administrator may...

7 CFR 760.1301 - Administration.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Administrator” in this part), and will be carried out by FSA's Price Support Division (PSD) and Kansas City... PSD, KCMO, a State committee, or a county committee will preclude the Administrator, FSA, or a... determination made by PSD, KCMO, a State committee, or a county committee. (f) The Deputy Administrator may...

76 FR 27898 - Approval and Promulgation of Air Quality Implementation Plans; Virginia; Prevention of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... greenhouse gas (GHG) Prevention of Significant Deterioration (PSD) permitting provisions as promulgated on June 3, 2010 in the Tailoring Rule. The SIP revision modifies Virginia's PSD program to [[Page 27899... become subject to Virginia's PSD permitting requirements for their GHG emissions. EPA is approving...

7 CFR 760.1301 - Administration.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Administrator” in this part), and will be carried out by FSA's Price Support Division (PSD) and Kansas City... PSD, KCMO, a State committee, or a county committee will preclude the Administrator, FSA, or a... determination made by PSD, KCMO, a State committee, or a county committee. (f) The Deputy Administrator may...

76 FR 35380 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

... processing. The proposed SIP revision modifies Indiana's Prevention of Significant Deterioration (PSD... modification projects become subject to Indiana's PSD permitting requirements for their greenhouse gas (GHG... EPA regulations regarding PSD permitting for GHGs. DATES: Comments must be received on or before July...

7 CFR 760.1301 - Administration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Administrator” in this part), and will be carried out by FSA's Price Support Division (PSD) and Kansas City... PSD, KCMO, a State committee, or a county committee will preclude the Administrator, FSA, or a... determination made by PSD, KCMO, a State committee, or a county committee. (f) The Deputy Administrator may...

40 CFR 69.41 - New exemptions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Significant Deterioration of Air Quality (PSD) permit issued to HOVIC; and shall include as a minimum, the... purpose of implementing the ICS at nearby locations approved by EPA and specified in the PSD permit. The... the NAAQS. (e) HOVIC must comply with all fuel switching requirements, contained in HOVIC's PSD permit...

77 FR 11744 - Approval and Promulgation of Implementation Plans; Tennessee: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-28

... New Source Review (NSR) Prevention of Significant Deterioration (PSD) program. Specifically, the SIP... modification projects become subject to Tennessee's PSD permitting requirements for GHG emissions. This rule... thresholds in the Tennessee SIP for GHG PSD requirements. EPA is approving Tennessee's January 11, 2012, SIP...

78 FR 50360 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Infrastructure SIP...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... National Ambient Air Quality Standards; Indiana PSD; Indiana State Board Requirements AGENCY: Environmental... from Indiana addressing EPA's requirements for the prevention of significant deterioration (PSD... (PSD elements), or EPA-R05-OAR-2012-0988 (state board requirements), by one of the following methods: 1...

40 CFR 52.343 - Significant deterioration of air quality.

Code of Federal Regulations, 2014 CFR

2014-07-01

... constructed prior to September 2, 1986 and which have not otherwise subjected themselves to Colorado's PSD permitting regulations after September 2, 1986, either through application to Colorado for a PSD permit (in the case of those sources which improperly constructed without obtaining a PSD permit) or through...

76 FR 15852 - Approval and Promulgation of Implementation Plans; Nebraska: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-22

... significant deterioration (PSD) preconstruction permitting program. The first applies to revisions relating to permitting of greenhouse gas (GHG) emissions under the PSD program. The second applies to revisions..., includes two significant changes impacting the regulation of GHGs under Nebraska's PSD program. First, the...

77 FR 73316 - Approval of Air Quality Implementation Plans; California; Eastern Kern, Imperial, Placer, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

... adopt and implement a SIP- approved Prevention of Significant Deterioration (PSD) permit program. We are...--Prevention of Significant Deterioration (PSD) Permit Program, PCAPCD Rule 518--Prevention of Significant Deterioration (PSD) Permit Program, and YSAQMD Rule 3.24-- Prevention of Significant Deterioration. The approval...

76 FR 59334 - Approval and Promulgation of Air Quality Implementation Plans; New Mexico; Albuquerque/Bernalillo...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... Prevention of Significant Deterioration (PSD) program to establish appropriate emission thresholds for... County's PSD permitting requirements for their greenhouse gas (GHG) emissions. Due to the SIP Narrowing Rule, 75 FR 82536, starting on January 2, 2011, the approved Albuquerque/Bernalillo County SIP's PSD...

76 FR 9658 - Approval and Promulgation of Implementation Plans; Kansas: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... greenhouse gas (GHG) under Kansas's New Source Review (NSR) Prevention of Significant Deterioration (PSD) program. First, the SIP revision provides the State of Kansas with authority to issue PSD permits... stationary sources and modification projects become subject to Kansas's PSD permitting requirements for their...

76 FR 40303 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Modifications to Indiana...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

... Significant Deterioration (PSD) and Nonattainment New Source Review (NNSR) rules. The amendments include grammatical changes, corrections to numbering, addition of definitions consistent with Federal PSD and NNSR... Federal PSD and NNSR regulations. DATES: Comments must be received on or before August 8, 2011. ADDRESSES...

Final PSD Permit Extension Letter - Energy Answers Arecibo, LLC/Energy Answers Arecibo Puerto Rico Renewable Energy Project, PR

EPA Pesticide Factsheets

This page contains the Final PSD Permit Extension Letter for Energy Answers Arecibo Puerto Rico Renewable Energy Project, issued on April 10, 2017 and the EPA Public Announcement for Final PSD Permit Extension for Energy Answers Arecibo, PR.

40 CFR 69.41 - New exemptions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Significant Deterioration of Air Quality (PSD) permit issued to HOVIC; and shall include as a minimum, the... purpose of implementing the ICS at nearby locations approved by EPA and specified in the PSD permit. The... the NAAQS. (e) HOVIC must comply with all fuel switching requirements, contained in HOVIC's PSD permit...

75 FR 81863 - Approval and Promulgation of Implementation Plans; Alabama: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-29

... Deterioration (PSD) program. Specifically, the SIP revision establishes appropriate emission thresholds for determining which new stationary sources and modification projects become subject to Alabama's PSD permitting requirements for their GHG emissions. The change is necessary because without it, on January 2, 2011, PSD...

77 FR 58027 - Approval and Promulgation of Implementation Plans; Florida: New Source Review-Prevention of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-19

... revision modifies Florida's New Source Review (NSR) Prevention of Significant Deterioration (PSD) permitting regulations to adopt, into the Florida SIP, federal NSR PSD requirements for the fine particulate... Implementation Rule and the 2010 PM 2.5 PSD Increment, Significant Impact [[Page 58028

40 CFR 52.824 - Original identification of plan section.

Code of Federal Regulations, 2010 CFR

2010-07-01

... attainment and unclassified areas of the state (PSD) were submitted on March 9, 1987, by the Iowa Department... review/PSD regulations. (47) Revised Chapters 22 and 23 regulations pertaining to stack height credits..., incorporates by reference revised EPA PSD rules pertaining to NO X increments. (i) Incorporation by reference...

40 CFR 52.343 - Significant deterioration of air quality.

Code of Federal Regulations, 2013 CFR

2013-07-01

... constructed prior to September 2, 1986 and which have not otherwise subjected themselves to Colorado's PSD permitting regulations after September 2, 1986, either through application to Colorado for a PSD permit (in the case of those sources which improperly constructed without obtaining a PSD permit) or through...

40 CFR 52.343 - Significant deterioration of air quality.

Code of Federal Regulations, 2011 CFR

2011-07-01

... constructed prior to September 2, 1986 and which have not otherwise subjected themselves to Colorado's PSD permitting regulations after September 2, 1986, either through application to Colorado for a PSD permit (in the case of those sources which improperly constructed without obtaining a PSD permit) or through...

75 FR 14401 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R05-OAR-2007-1043; FRL-9129-6] Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations AGENCY: Environmental Protection... (CAA). The revisions consist of requirements of the prevention of significant deterioration (PSD...

40 CFR 69.41 - New exemptions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Significant Deterioration of Air Quality (PSD) permit issued to HOVIC; and shall include as a minimum, the... purpose of implementing the ICS at nearby locations approved by EPA and specified in the PSD permit. The... the NAAQS. (e) HOVIC must comply with all fuel switching requirements, contained in HOVIC's PSD permit...

Characterization and variability of particle size distributions in Hudson Bay, Canada

NASA Astrophysics Data System (ADS)

Xi, Hongyan; Larouche, Pierre; Tang, Shilin; Michel, Christine

2014-06-01

Particle size distribution (PSD) plays a significant role in many aspects of aquatic ecosystems, including phytoplankton dynamics, sediment fluxes, and optical scattering from particulates. As of yet, little is known on the variability of particle size distribution in marine ecosystems. In this study, we investigated the PSD properties and variability in Hudson Bay based on measurements from a laser diffractometer (LISST-100X Type-B) in concert with biogeochemical parameters collected during summer 2010. Results show that most power-law fitted PSD slopes ranged from 2.5 to 4.5, covering nearly the entire range observed for natural waters. Offshore waters showed a predominance of smaller particles while near the coast, the effect of riverine inputs on PSD were apparent. Particulate inorganic matter contributed more to total suspended matter in coastal waters leading to lower PSD slopes than offshore. The depth distribution of PSD slopes shows that larger particles were associated with the pycnocline. Below the pycnocline, smaller particles dominated the spectra. A comparison between a PSD slope-based method to derive phytoplankton size class (PSC) and pigment-based derived PSC showed the two methods agreed relatively well. This study provides valuable baseline information on particle size properties and phytoplankton composition estimates in a sub-arctic environment subject to rapid environmental change.

Early Growth Response 1 (Egr-1) Regulates N-Methyl-d-aspartate Receptor (NMDAR)-dependent Transcription of PSD-95 and α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor (AMPAR) Trafficking in Hippocampal Primary Neurons*

PubMed Central

Qin, Xike; Jiang, Yongjun; Tse, Yiu Chung; Wang, Yunling; Wong, Tak Pan; Paudel, Hemant K.

2015-01-01

The N-methyl-d-aspartate receptor (NMDAR) controls synaptic plasticity and memory function and is one of the major inducers of transcription factor Egr-1 in the hippocampus. However, how Egr-1 mediates the NMDAR signal in neurons has remained unclear. Here, we show that the hippocampus of mice lacking Egr-1 displays electrophysiology properties and ultrastructure that are similar to mice overexpressing PSD-95, a major scaffolding protein of postsynaptic density involved in synapse formation, synaptic plasticity, and synaptic targeting of AMPA receptors (AMPARs), which mediate the vast majority of excitatory transmission in the CNS. We demonstrate that Egr-1 is a transcription repressor of the PSD-95 gene and is recruited to the PSD-95 promoter in response to NMDAR activation. Knockdown of Egr-1 in rat hippocampal primary neurons blocks NMDAR-induced PSD-95 down-regulation and AMPAR endocytosis. Likewise, overexpression of Egr-1 in rat hippocampal primary neurons causes reduction in PSD-95 protein level and promotes AMPAR endocytosis. Our data indicate that Egr-1 is involved in NMDAR-mediated PSD-95 down-regulation and AMPAR endocytosis, a process important in the expression of long term depression. PMID:26475861

Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission

PubMed Central

Krüger, Juliane M.; Favaro, Plinio D.; Liu, Mingna; Kitlińska, Agata; Huang, Xiaojie; Raabe, Monika; Akad, Derya S.; Liu, Yanling; Urlaub, Henning; Dong, Yan; Xu, Weifeng

2013-01-01

In the postsynaptic density of glutamatergic synapses, the discs large (DLG)-membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins coordinates a multiplicity of signaling pathways to maintain and regulate synaptic transmission. Postsynaptic density-93 (PSD-93) is the most variable paralog in this family; it exists in six different N-terminal isoforms. Probably because of the structural and functional variability of these isoforms, the synaptic role of PSD-93 remains controversial. To accurately characterize the synaptic role of PSD-93, we quantified the expression of all six isoforms in the mouse hippocampus and examined them individually in hippocampal synapses. Using molecular manipulations, including overexpression, gene knockdown, PSD-93 knock-out mice combined with biochemical assays, and slice electrophysiology both in rat and mice, we demonstrate that PSD-93 is required at different developmental synaptic states to maintain the strength of excitatory synaptic transmission. This strength is differentially regulated by the six isoforms of PSD-93, including regulations of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-active and inactive synapses, and activity-dependent modulations. Collectively, these results demonstrate that alternative combinations of N-terminal PSD-93 isoforms and DLG-MAGUK paralogs can fine-tune signaling scaffolds to adjust synaptic needs to regulate synaptic transmission. PMID:24068818

Spinal serum-inducible and glucocorticoid-inducible kinase 1 mediates neuropathic pain via kalirin and downstream PSD-95-dependent NR2B phosphorylation in rats.

PubMed

Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuan; Hsieh, Ming-Chun; Lin, Tzer-Bin

2013-03-20

The coupling of the spinal postsynaptic density-95 (PSD-95) with the glutamatergic N-methyl-d-aspartate receptor NR2B subunit and the subsequent NR2B phosphorylation contribute to pain-related plasticity. Increasing evidence reveals that kalirin, a Rho-guanine nucleotide exchange factor, modulates PSD-95-NR2B-dependent neuroplasticity. Our laboratory recently demonstrated that serum-inducible and glucocorticoid-inducible kinase 1 (SGK1) participates in inflammation-associated pain hypersensitivity by modulating spinal glutamatergic neurotransmission. Because kalirin is one of the proteins in PSD that is highly phosphorylated by various kinases, we tested whether kalirin could be a downstream target of spinal SGK1 that participates in neuropathic pain development via regulation of the PSD-95-NR2B coupling-dependent phosphorylation of NR2B. We observed that spinal nerve ligation (SNL, L5) in male Sprague Dawley rats resulted in behavioral allodynia, which was associated with phosphorylated SGK1 (pSGK1), kalirin, and phosphorylated NR2B (pNR2B) expression and an increase in pSGK1-kalirin-PSD-95-pNR2B coprecipitation in the ipsilateral dorsal horn (L4-L5). SNL-enhanced kalirin immunofluorescence was coincident with pSGK1, PSD-95, and pNR2B immunoreactivity. Small-interfering RNA (siRNA) that targeted spinal kalirin mRNA expression (10 μg, 10 μl; i.t.) reduced SNL-induced allodynia, kalirin and pNR2B expression, as well as kalirin-PSD-95 and PSD-95-pNR2B coupling and costaining without affecting SGK1 phosphorylation. Daily administration of GSK-650394 (an SGK1 antagonist; 100 nm, 10 μl, i.t.) not only exhibited effects similar to the kalirin mRNA-targeting siRNA but also attenuated pSGK1-kalirin costaining and SGK1-kalirin coupling. We suggest that nerve injury could induce spinal SGK1 phosphorylation that subsequently interacts with and upregulates kalirin to participate in neuropathic pain development via PSD-95-NR2B coupling-dependent NR2B phosphorylation.

IB-11PSEUDO-PROGRESSION (PsdPg) IS A HARBINGER OF A MORE EFFECTIVE ANTI-TUMOR RESPONSE

PubMed Central

Sturla, Lisa; Donahue, John; Machan, Jason; Delamonte, Suzanne; Jeyapalan, Suriya

2014-01-01

BACKGROUND: PsdPg is the increased contrast enhancement, high choline/creatine ratio and increased perfusion observed in the residual tumor bed of high-grade glioma patients after completion of temozolomide/radiation. It resolves within 3-6 months and incidence ranges from 10 - 31%. Though correlated with longer patient survival, its pathological basis is unclear. We used a cytokine/chemokine focused approach to compare the tumor microenvironment in pre- and post-treatment tumor tissue from patients with PsdPg to patients with true progression (TP). METHODS: We obtained pre-treatment formalin fixed paraffin embedded (FFPE) tissue from 35 GBM patients and post-treatment FFPE tissue from five patients with PsdPg and TP. A quantitative PCR array and custom Quantigene 2.0 multiplex was used to quantify gene expression corresponding to major cytokines/chemokines. An 18-gene signature was used to determine the macrophage polarization score (cumulative M2-associated cytokine expression - cumulative M1-associated cytokine expression). Immunohistochemistry (IHC) was used to confirm significantly different targets at the protein level. RESULTS: IHC revealed 7-fold higher B-cell infiltration in TP patients as compared to patients with PsdPg (p = 0.003). Macrophage and T-cell infiltration were not significantly different between the two groups. Nevertheless, the cytokines associated with macrophage polarization indicated pro-tumorigenic (M2) polarization in TP patients while PsdPg patients exhibited classical anti-tumorigenic (M1) polarization. TP patients had a 10-fold higher M2 score (p = 0.03) compared to PsdPg patients. The M1 score of tissue from PsdPg patients post-treatment was 25-fold higher than their pre-treatment tissue (p = 0.01). Analysis of a 7-gene signature associated with natural killer (NK) cell recruitment and activation showed a 8-fold higher expression in pre-treatment tissue from PsdPg patients compared to TP patients (p = 0.009) suggesting that NK cells, which are mediators of anti-tumor immunity, play an important role in pseudo-progression. CONCLUSIONS: These data suggest a more effective anti-tumor immune response in PsdPg patients, which may explain their longer overall survival.

The association of different types of cerebral infarction with post-stroke depression and cognitive impairment.

PubMed

Tu, Jun; Wang, Ling-Xiao; Wen, Hong-Feng; Xu, Yi-Cheng; Wang, Pei-Fu

2018-06-01

The aim of this study was to investigate post-stroke depression (PSD) and cognitive impairments in patients with different types of cerebral infarction.A total of 110 patients with cerebral infarction treated in our hospital from January 2015 to February 2016 were included in present study. Forty-seven patients were PSD patients and 63 patients were non-PSD patients. The Hamilton Depression Rating Scale (HAMD) and Mini-Mental State Examination (MMSE) were employed to assess depression and cognition of patientsAmong PSD patients, the proportion of patients with partial anterior circulation infarction (PACI, 68.75%) was significantly higher than patients with lacunar circulation infarction (LACI, 29.17%) and posterior circulation infarction (POCI, 26.67%) (P < .05). No significant difference was found in PSD patients with LACI and POCI (P > .05). The MMSE score of patients with PACI (18.05 ± 2.61) was lower than patients with POCI and LACI (P < .05), however, no significant difference was found in patients with LACI and POCI (P > 0.05). The incidences of cognitive impairment in patients with PACI, LACI, and POCI were 12.50%, 14.58%, and 13.33%, respectively. The MMSE score of PSD patients (21.23 ± 2.12) was significantly lower than non-PSD patients (P < .05).Compared with LACI and POCI patients, PACI patients had a higher incidence of PSD and impaired cognitive functions. In addition, affective disorders such as depression may be correlated with cognitive impairment in patients with cerebral infarction.

Bidirectional control of postsynaptic density-95 (PSD-95) clustering by Huntingtin.

PubMed

Parsons, Matthew P; Kang, Rujun; Buren, Caodu; Dau, Alejandro; Southwell, Amber L; Doty, Crystal N; Sanders, Shaun S; Hayden, Michael R; Raymond, Lynn A

2014-02-07

Huntington disease is associated with early alterations in corticostriatal synaptic function that precede cell death, and it is postulated that ameliorating such changes may delay clinical onset and/or prevent neurodegeneration. Although many of these synaptic alterations are thought to be attributable to a toxic gain of function of the mutant huntingtin protein, the role that nonpathogenic huntingtin (HTT) plays in synaptic function is relatively unexplored. Here, we compare the immunocytochemical localization of a major postsynaptic scaffolding protein, PSD-95, in striatal neurons from WT mice and mice overexpressing HTT with 18 glutamine repeats (YAC18, nonpathogenic). We found that HTT overexpression resulted in a palmitoylation- and BDNF-dependent increase in PSD-95 clustering at synaptic sites in striatal spiny projection neurons (SPNs) co-cultured with cortical neurons. Surprisingly, the latter effect was mediated presynaptically, as HTT overexpression in cortical neurons alone was sufficient to increase PSD-95 clustering in the postsynaptic SPNs. In contrast, antisense oligonucleotide knockdown of HTT in WT co-cultures resulted in a significant reduction of PSD-95 clustering in SPNs. Notably, despite these bidirectional changes in PSD-95 clustering, we did not observe an alteration in basal electrophysiological measures of AMPA and NMDA receptors. Thus, unlike in previous studies in the hippocampus, enhanced or decreased PSD-95 clustering alone was insufficient to drive AMPA or NMDA receptors into or out of SPN synapses. In all, our results demonstrate that nonpathogenic HTT can indeed influence synaptic protein localization and uncover a novel role of HTT in PSD-95 distribution.

Bidirectional Control of Postsynaptic Density-95 (PSD-95) Clustering by Huntingtin*

PubMed Central

Parsons, Matthew P.; Kang, Rujun; Buren, Caodu; Dau, Alejandro; Southwell, Amber L.; Doty, Crystal N.; Sanders, Shaun S.; Hayden, Michael R.; Raymond, Lynn A.

2014-01-01

Huntington disease is associated with early alterations in corticostriatal synaptic function that precede cell death, and it is postulated that ameliorating such changes may delay clinical onset and/or prevent neurodegeneration. Although many of these synaptic alterations are thought to be attributable to a toxic gain of function of the mutant huntingtin protein, the role that nonpathogenic huntingtin (HTT) plays in synaptic function is relatively unexplored. Here, we compare the immunocytochemical localization of a major postsynaptic scaffolding protein, PSD-95, in striatal neurons from WT mice and mice overexpressing HTT with 18 glutamine repeats (YAC18, nonpathogenic). We found that HTT overexpression resulted in a palmitoylation- and BDNF-dependent increase in PSD-95 clustering at synaptic sites in striatal spiny projection neurons (SPNs) co-cultured with cortical neurons. Surprisingly, the latter effect was mediated presynaptically, as HTT overexpression in cortical neurons alone was sufficient to increase PSD-95 clustering in the postsynaptic SPNs. In contrast, antisense oligonucleotide knockdown of HTT in WT co-cultures resulted in a significant reduction of PSD-95 clustering in SPNs. Notably, despite these bidirectional changes in PSD-95 clustering, we did not observe an alteration in basal electrophysiological measures of AMPA and NMDA receptors. Thus, unlike in previous studies in the hippocampus, enhanced or decreased PSD-95 clustering alone was insufficient to drive AMPA or NMDA receptors into or out of SPN synapses. In all, our results demonstrate that nonpathogenic HTT can indeed influence synaptic protein localization and uncover a novel role of HTT in PSD-95 distribution. PMID:24347167

Hysteresis in suspended sediment to turbidity relations due to changing particle size distributions

USGS Publications Warehouse

Landers, Mark N.; Sturm, Terry W.

2013-01-01

Turbidity (T) is the most ubiquitous of surrogate technologies used to estimate suspended-sediment concentration (SSC). The effects of sediment size on turbidity are well documented; however, effects from changes in particle size distributions (PSD) are rarely evaluated. Hysteresis in relations of SSC-to-turbidity (SSC~T) for single stormflow events was observed and quantified for a data set of 195 concurrent measurements of SSC, turbidity, discharge, velocity, and volumetric PSD collected during five stormflows in 2009–2010 on Yellow River at Gees Mill Road in metropolitan Atlanta, Georgia. Regressions of SSC-normalized turbidity (T/SSC) on concurrently measured PSD percentiles show an inverse, exponential influence of particle size on turbidity that is not constant across the size range of the PSD. The majority of the influence of PSD on T/SSC is from particles of fine-silt and smaller sizes (finer than 16 microns). This study shows that small changes in the often assumed stability of the PSD are significant to SSC~T relations. Changes of only 5 microns in the fine silt and smaller size fractions of suspended sediment PSD can produce hysteresis in the SSC~T rating that can increase error and produce bias. Observed SSC~T hysteresis may be an indicator of changes in sediment properties during stormflows and of potential changes in sediment sources. Trends in the PSD time series indicate that sediment transport is capacity-limited for sand-sized sediment in the channel and supply-limited for fine silt and smaller sediment from the hillslope.

Impairment of male reproductive function after sleep deprivation.

PubMed

Alvarenga, Tathiana A; Hirotsu, Camila; Mazaro-Costa, Renata; Tufik, Sergio; Andersen, Monica L

2015-05-01

To evaluate the influence of sleep loss on sexual behavior, hormone levels, sperm parameters, and testis-specific gene expression in male rats. Experimental research. Animal laboratory. Male adult Wistar-Hannover rats. Sexually experienced rats were subjected to paradoxic sleep deprivation (PSD) for 96 hours or sleep restriction (SR) for 21 days or kept in their home cage as control (CTRL). Sexual behavior, hormone levels, sperm parameters and expression of stress and nitric oxide-related genes were evaluated. PSD significantly decreased sexual behavior compared with the CTRL group, whereas SR had no effect. The PSD group had significantly lower testosterone levels than the CTRL group. Both PSD and SR groups had lower sperm viabilities than the CTRL group. The decrease in the number of live sperm compared with the CTRL group was larger in the PSD group than in the SR group. Regarding testicular gene expression, both PSD and SR led to an increase of iNOS and hydroxysteroid 11β-dehydrogenase 1 expressions compared with the CTRL group. These changes were more pronounced in the PSD group. A significant increase in endothelial nitric oxide synthase expression was observed in the PSD groups compared with the CTRL group. No changes were observed in dimethylarginine dimethylaminohydrolase 1 and casein kinase 2β-polypeptide expressions. Sleep loss can promote marked changes in the male reproductive system of rats, particularly affecting spermatic function in part by interfering in the testicular nitric oxide pathway. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

76 FR 59899 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

... Significant Deterioration (PSD) program to establish appropriate emission thresholds for determining which new... emissions above the thresholds established in the PSD regulations. DATES: This final rule is effective on... of GHG, and that do not limit PSD applicability to GHGs to the higher thresholds in the Tailoring...

75 FR 82246 - Action To Ensure Authority To Issue Permits Under the Prevention of Significant Deterioration...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-30

... Deterioration (PSD) program to sources of greenhouse gases (GHGs). This action will ensure that a permitting authority--EPA--is available in these states as of January 2, 2011, when PSD becomes applicable to GHG-emitting sources, to issue preconstruction PSD permits and thereby facilitate construction or expansion...

40 CFR 52.2522 - Approval status.

Code of Federal Regulations, 2013 CFR

2013-07-01

... requirements for PSD applicable as of the August 31, 2011 SIP revision submission date, EPA is acknowledging... February 17, 2012 which address the PSD-related requirements set forth in CAA section 110(a)(2)(D)(i)(II..., 2007, April 3, 2008, October 1, 2009, October 26, 2011, and February 17, 2012 submitted to meet the PSD...

78 FR 40968 - Notice of Extension of Deadline to Commence Construction Under Clean Air Act Prevention of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-09

...'') has extended the Prevention of Significant Deterioration (``PSD'') permit deadline for commencing construction for a final Clean Air Act PSD permit that authorizes Avenal Power Center, LLC (``APC'') to...: EPA's PSD permit for the AEP became effective on August 18, 2011, and included a deadline for...

78 FR 2354 - Approval and Promulgation of Air Quality Implementation Plans; Arkansas; Prevention of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-11

...) Prevention of Significant Deterioration (PSD) program updates the Arkansas SIP to incorporate by reference (IBR) requirements for the Federal PSD permitting program under EPA's November 29, 2005 Phase 2 8-hour Ozone Implementation rule. The November 6, 2012 proposed SIP revision to the Arkansas NSR PSD program...

Assessment of soybean breeding lines for resistance to Phomopsis seed decay from field trials in Stoneville, Mississippi

USDA-ARS?s Scientific Manuscript database

Phomopsis seed decay (PSD) is one of the most important seed diseases in soybean. A fungal pathogen, Phomopsis longicolla (syn. Diaporthe longicolla), is the primary causal agent of PSD. Planting PSD-resistant soybean cultivars is the most effective strategy to manage this disease. However, few comm...

40 CFR 52.1773 - Conditional approval.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Deterioration (PSD) infrastructure requirements for the 1997 annual and 2006 24-hour fine particulate matter... to the PM2.5 standard for their PSD program and committing to providing the necessary SIP revision to... PM2.5 Rule (including PM2.5 PSD Increment-SILs-SMC, as it relates to PM2.5 increments to meet the...

40 CFR 52.1773 - Conditional approval.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Deterioration (PSD) infrastructure requirements for the 1997 annual and 2006 24-hour fine particulate matter... to the PM2.5 standard for their PSD program and committing to providing the necessary SIP revision to... PM2.5 Rule (including PM2.5 PSD Increment-SILs-SMC, as it relates to PM2.5 increments to meet the...

40 CFR 52.1620 - Identification of plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

... prohibit interference with maintenance and PSD measures in any other state. Interstate transport for the... interference with maintenance and PSD measures in any other state. Sunland Park 1997 8-Hour Ozone Maintenance... other states' programs for PSD for the 1997 and 2008 Ozone and the 1997 and 2006 PM2.5 NAAQS Bernalillo...

76 FR 7116 - Approval and Promulgation of Implementation Plans; Alaska: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-09

... revision updates Alaska's Prevention of Significant Deterioration (PSD) program to reflect changes to the Federal PSD program relating to the permitting of greenhouse gas (GHG) emissions. DATES: This action is... Federal PSD program as of August 2, 2010 relating to the permitting of GHGs. In the proposal, EPA made the...

78 FR 54602 - Approval and Promulgation of State Implementation Plans; Utah: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-05

... Prevention of Significant Deterioration (PSD) program and other SIP provisions. These revisions were...'s regulations with the GHG emission thresholds established in EPA's ``PSD and Title V Greenhouse Gas... to approve the GHG (as it relates to the PSD program) revisions because the Agency has determined...

76 FR 49708 - Approval and Promulgation of Implementation Plans; Iowa: Prevention of Significant Deterioration...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-11

... regulation of Greenhouse Gases (GHGs) under Iowa's Prevention of Significant Deterioration (PSD) program..., 2010. It is intended to align Iowa's regulations with the ``PSD and Title V Greenhouse Gas Tailoring... the Clean Air Act (CAA or Act) and EPA regulations regarding PSD permitting for GHGs. DATES: Comments...

75 FR 56027 - Approval and Promulgation of Air Quality Implementation Plans; Texas; Revisions to the New Source...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

... Implementation Plan (SIP); Prevention of Significant Deterioration (PSD) AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: EPA is proposing to approve revisions to the Texas PSD State... revision submitted July 16, 2010. This action makes no significant changes to the Texas PSD SIP; it merely...

Evaluating soybean germplasm and commercial varieties for resistance to Phomopsis seed decay

USDA-ARS?s Scientific Manuscript database

Soybean Phomopsis seed decay (PSD) is the major cause of poor seed quality in most soybean production areas of the United States. Very few soybean cultivars currently available for planting in the US have resistance to PSD. To identify new sources of resistance to PSD, a multistate and multiyear res...

76 FR 20907 - Approval and Promulgation of Air Quality Implementation Plans; New Mexico; Prevention of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

... revision modifies New Mexico's Prevention of Significant Deterioration (PSD) program to establish... subject to New Mexico's PSD permitting requirements for their greenhouse gas (GHG) emissions. Due to the SIP Narrowing Rule, 75 FR 82536, starting on January 2, 2011, the approved New Mexico SIP's PSD...

75 FR 27191 - Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR): Aggregation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-14

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts 51 and 52 [EPA-HQ-OAR-2003-0064, FRL-9151-3] RIN 2060-AP80 Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR... of the Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR...

78 FR 19596 - Approval and Promulgation of Air Quality Implementation Plans; Arkansas; Prevention of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

...) Prevention of Significant Deterioration (PSD) program updates the Arkansas SIP to incorporate by reference (IBR) requirements for the federal PSD permitting program under EPA's November 29, 2005 Phase 2 8-hour Ozone Implementation rule. The November 6, 2012, SIP revision to the Arkansas NSR PSD program provides...

76 FR 26192 - Revisions to the California State Implementation Plan, Northern Sonoma County Air Pollution...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-06

...-approved Prevention of Significant Deterioration (PSD) permit programs. These revisions update the definitions used in the districts' PSD permit programs. DATES: This rule is effective on July 5, 2011 without... Deterioration (PSD) permit program. Both the NSCAPCD and MCAQMD are currently designated as attainment or...

76 FR 40242 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Modifications to Indiana...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

... Deterioration (PSD) and Nonattainment New Source Review (NNSR) rules. The amendments include grammatical changes, corrections to numbering, addition of definitions consistent with Federal PSD and NNSR regulations, and... revisions to EPA for approval on November 24, 2010. They are consistent with the current Federal PSD and...

75 FR 70140 - Approval and Promulgation of Implementation Plans; New York Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... Significant Deterioration of Air Quality (PSD) and Nonattainment New Source Review (NNSR) State regulations. These revisions create a new New York State PSD regulation program and modify the existing New York... EPA is taking no action at this time on the PSD permitting threshold provisions to the extent that...

Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development.

PubMed

Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

2013-05-28

The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5-PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5-PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders.

Anchoring and Synaptic stability of PSD-95 is driven by ephrin-B3

PubMed Central

Hruska, Martin; Henderson, Nathan T.; Xia, Nan L.; Le Marchand, Sylvain J.; Dalva, Matthew B.

2015-01-01

Summary Organization of signaling complexes at excitatory synapses by Membrane Associated Guanylate Kinase (MAGUK) proteins regulates synapse development, plasticity, senescence, and disease. Post-translational modification of MAGUK family proteins can drive their membrane localization, yet it is unclear how these intracellular proteins are targeted to sites of synaptic contact. Here we show using super-resolution imaging, biochemical approaches, and in vivo models that the trans-synaptic organizing protein, ephrin-B3, controls the synaptic localization and stability of PSD-95 and links these events to changes in neuronal activity via negative regulation of a novel MAPK-dependent phosphorylation site on ephrin-B3 (S332). Unphosphorylated ephrin-B3 is enriched at synapses, interacts directly with and stabilizes PSD-95 at synapses. Activity induced phosphorylation of S332 disperses ephrin-B3 from synapses, prevents the interaction with, and enhances the turnover of PSD-95. Thus, ephrin-B3 specifies the synaptic localization of PSD-95 and likely links the synaptic stability of PSD-95 to changes in neuronal activity. PMID:26479588

A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density

PubMed Central

Walkup, Ward G; Mastro, Tara L; Schenker, Leslie T; Vielmetter, Jost; Hu, Rebecca; Iancu, Ariella; Reghunathan, Meera; Bannon, Barry Dylan; Kennedy, Mary B

2016-01-01

SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold, which would free PDZ domains for occupancy by other proteins. Finally, we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP. DOI: http://dx.doi.org/10.7554/eLife.16813.001 PMID:27623146

A Statitstical Study of Energetic Electron Phase Space Density with RBSP and BD-IES Data

NASA Astrophysics Data System (ADS)

Chen, X.; Zong, Q.; Zhou, X.; Zou, H.; Wang, Y.

2017-12-01

We present a statistical study of energetic electron phase space density (PSD) with combined observations from the Magnetic Electron Ion Spectrometer (MagEIS) instruments onboard the Van Allen Probes and the Image Electron Spectrometer (BD-IES) onboard an inclined geosynchronous orbit satellite. The electron PSD as a function of the adiabatic invariants is derived using one year data (Nov. 2015 to Oct. 2016) of these instruments. The orbits of the satellites cover a wide range of L-shells, allowing for the distribution of electron PSD throughout the radiation belt (L* 1 to 10). A persistent peak of energetic electron ( 30 to 1000 MeV/G) PSD is unambiguously identified at L* 5.5, which may help to understand the role of local acceleration and radial diffusion in the dynamics of energetic electrons. In addition, the electron PSD shows a power-law distribution with the exponent varying from about -2 to -4 depending on L*. The variance of electron PSD during storm and substorm activities indicating by SYMH and AE indices are also discussed.

Palmitoylation-dependent CDKL5–PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development

PubMed Central

Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

2013-01-01

The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5–PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5–PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders. PMID:23671101

Immunolocalization of NR1, NR2A, and PSD-95 in rat hippocampal subregions during postnatal development.

PubMed

Ling, Wei; Chang, Lirong; Song, Yizhi; Lu, Tao; Jiang, Yuhua; Li, Youxiang; Wu, Yan

2012-05-01

Although the expression of NMDARs and synaptic-associated proteins has been widely studied, the temporospatial distribution of NMDAR subunits and synaptic proteins in different hippocampal subregions during postnatal development still lacks detailed information, and the relationship between NR1 or NR2 subunits and PSD-95 family proteins is controversial. In this study, we used immunofluorescent staining to assess NR1 or NR2A and PSD-95 expressions and the relationship between them in CA1, CA3, and DG of rat hippocampus on postnatal (P) days: P0, P4, P7, P10, P14, P21, P28, P56. The results showed that from P0 to P56, NR1, NR2A, and PSD-95 expressions increased gradually, and the time points of their expression peak differed in CA1, CA3, and DG during postnatal development. Interestingly, although the expression of PSD-95 was positively correlated to both NR1 and NR2A, the NR1 and PSD-95 coexpressed puncta were greatest in CA3, while NR2A and PSD-95 coexpressed puncta were greatest in CA1, compared to other subregions. Surprisingly, at P21, among different strata of CA1, the area of highest expression of NR2A was dramatically changed from stratum pyramidale to stratum polymorphum and stratum moleculare, and returned to stratum pyramidale gradually on the later observed days again, indicating that P21 may be one critical timepoint during postnatal development in CA1. The specific temporospatial distribution pattern of NR1, NR2A, and PSD-95 might be related to the different physiological functions during postnatal development. Discovering the alteration of the relationship between PSD-95 and NMDAR subunits expression may be helpful for understanding mechanisms and therapy of neurodegenerative diseases. Copyright © 2011 Elsevier GmbH. All rights reserved.

A preliminary examination of the validity and reliability of a new brief rating scale for symptom domains of psychosis: Brief Evaluation of Psychosis Symptom Domains (BE-PSD).

PubMed

Takeuchi, Hiroyoshi; Fervaha, Gagan; Lee, Jimmy; Agid, Ofer; Remington, Gary

2016-09-01

Brief assessments have the potential to be widely adopted as outcome measures in research but also routine clinical practice. Existing brief rating scales that assess symptoms of schizophrenia or psychosis have a number of limitations including inability to capture five symptom domains of psychosis and a lack of clearly defined operational anchor points for scoring. We developed a new brief rating scale for five symptom domains of psychosis with clearly defined operational anchor points - the Brief Evaluation of Psychosis Symptom Domains (BE-PSD). To examine the psychometric properties of the BE-PSD, fifty patients with schizophrenia or schizoaffective disorder were included in this preliminary cross-sectional study. To test the convergent and discriminant validity of the BE-PSD, correlational analyses were employed using the consensus Positive and Negative Syndrome Scale (PANSS) five-factor model. To examine the inter-rater reliability of the BE-PSD, single measures intraclass correlation coefficients (ICCs) were calculated for 11 patients. The BE-PSD domain scores demonstrated high convergent validity with the corresponding PANSS factor score (rs = 0.81-0.93) as well as good discriminant validity, as evidenced by lower correlations with the other PANSS factors (rs = 0.23-0.62). The BE-PSD also demonstrated excellent inter-rater reliability for each of the domain scores and the total scores (ICC(2,1) = 0.79-0.96). The present preliminary study found the BE-PSD measure to be valid and reliable; however, further studies are needed to establish the psychometric properties of the BE-PSD because of the limitations such as the small sample size and lacking data on test-retest reliability or sensitivity to change. Copyright © 2016 Elsevier Ltd. All rights reserved.

SU-F-P-44: A Direct Estimate of Peak Skin Dose for Interventional Fluoroscopy Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weir, V; Zhang, J

Purpose: There is an increasing demand for medical physicist to calculate peak skin dose (PSD) for interventional fluoroscopy procedures. The dose information (Dose-Area-Product and Air Kerma) displayed in the console cannot directly be used for this purpose. Our clinical experience shows that the use of the existing methods may overestimate or underestimate PSD. This study attempts to develop a direct estimate of PSD from the displayed dose metrics. Methods: An anthropomorphic torso phantom was used for dose measurements for a common fluoroscopic procedure. Entrance skin doses were measured with a Piranha solid state point detector placed on the table surfacemore » below the torso phantom. An initial “reference dose rate” (RE) measurement was conducted by comparing the displayed dose rate (mGy/min) to the dose rate measured. The distance from table top to focal spot was taken as the reference distance (RD at the RE. Table height was then adjusted. The displayed air kerma and DAP were recorded and sent to three physicists to estimate PSD. An inverse square correction was applied to correct displayed air kerma at various table heights. The PSD estimated by physicists and the PSD by the proposed method were then compared with the measurements. The estimated DAPs were compared to displayed DAP readings (mGycm2). Results: The difference between estimated PSD by the proposed method and direct measurements was less than 5%. For the same set of data, the estimated PSD by each of three physicists is different from measurements by ±52%. The DAP calculated by the proposed method and displayed DAP readings in the console is less than 20% at various table heights. Conclusion: PSD may be simply estimated from displayed air kerma or DAP if the distance between table top and tube focal spot or if x-ray beam area on table top is available.« less

Investigation of pore size and energy distributions by statistical physics formalism applied to agriculture products

NASA Astrophysics Data System (ADS)

Aouaini, Fatma; Knani, Salah; Yahia, Manel Ben; Bahloul, Neila; Ben Lamine, Abdelmottaleb; Kechaou, Nabil

2015-12-01

In this paper, we present a new investigation that allows determining the pore size distribution (PSD) in a porous medium. This PSD is achieved by using the desorption isotherms of four varieties of olive leaves. This is by the means of statistical physics formalism and Kelvin's law. The results are compared with those obtained with scanning electron microscopy. The effect of temperature on the distribution function of pores has been studied. The influence of each parameter on the PSD is interpreted. A similar function of adsorption energy distribution, AED, is deduced from the PSD.

DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy

PubMed Central

Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

2017-01-01

Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95–nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95–nNOS interactions in MHE. PMID:28932186

Early Growth Response 1 (Egr-1) Regulates N-Methyl-d-aspartate Receptor (NMDAR)-dependent Transcription of PSD-95 and α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor (AMPAR) Trafficking in Hippocampal Primary Neurons.

PubMed

Qin, Xike; Jiang, Yongjun; Tse, Yiu Chung; Wang, Yunling; Wong, Tak Pan; Paudel, Hemant K

2015-12-04

The N-methyl-d-aspartate receptor (NMDAR) controls synaptic plasticity and memory function and is one of the major inducers of transcription factor Egr-1 in the hippocampus. However, how Egr-1 mediates the NMDAR signal in neurons has remained unclear. Here, we show that the hippocampus of mice lacking Egr-1 displays electrophysiology properties and ultrastructure that are similar to mice overexpressing PSD-95, a major scaffolding protein of postsynaptic density involved in synapse formation, synaptic plasticity, and synaptic targeting of AMPA receptors (AMPARs), which mediate the vast majority of excitatory transmission in the CNS. We demonstrate that Egr-1 is a transcription repressor of the PSD-95 gene and is recruited to the PSD-95 promoter in response to NMDAR activation. Knockdown of Egr-1 in rat hippocampal primary neurons blocks NMDAR-induced PSD-95 down-regulation and AMPAR endocytosis. Likewise, overexpression of Egr-1 in rat hippocampal primary neurons causes reduction in PSD-95 protein level and promotes AMPAR endocytosis. Our data indicate that Egr-1 is involved in NMDAR-mediated PSD-95 down-regulation and AMPAR endocytosis, a process important in the expression of long term depression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A framework to understand the variations of PSD-95 expression in brain aging and in Alzheimer's disease.

PubMed

Savioz, Armand; Leuba, Geneviève; Vallet, Philippe G

2014-11-01

The postsynaptic density protein PSD-95 is a major element of synapses. PSD-95 is involved in aging, Alzheimer's disease (AD) and numerous psychiatric disorders. However, contradictory data about PSD-95 expression in aging and AD have been reported. Indeed in AD versus control brains PSD-95 varies according to regions, increasing in the frontal cortex, at least in a primary stage, and decreasing in the temporal cortex. In contrast, in transgenic mouse models of aging and AD PSD-95 expression is decreased, in behaviorally aged impaired versus unimpaired rodents it can decrease or increase and finally, it is increased in rodents grown in enriched environments. Different factors explain these contradictory results in both animals and humans, among others concomitant psychiatric endophenotypes, such as depression. The possible involvement of PSD-95 in reactive and/or compensatory mechanisms during AD progression is underscored, at least before the occurrence of important synaptic elimination. Thus, in AD but not in AD transgenic mice, enhanced expression might precede the diminution commonly observed in advanced aging. A two-compartments cell model, separating events taking place in cell bodies and synapses, is presented. Overall these data suggest that AD research will progress by untangling pathological from protective events, a prerequisite for effective therapeutic strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

Multitiered and Cooperative Surveillance of Mitochondrial Phosphatidylserine Decarboxylase 1.

PubMed

Ogunbona, Oluwaseun B; Onguka, Ouma; Calzada, Elizabeth; Claypool, Steven M

2017-09-01

Phosphatidylserine decarboxylase 1 (Psd1p), an ancient enzyme that converts phosphatidylserine to phosphatidylethanolamine in the inner mitochondrial membrane, must undergo an autocatalytic self-processing event to gain activity. Autocatalysis severs the protein into a large membrane-anchored β subunit that noncovalently associates with the small α subunit on the intermembrane space side of the inner membrane. Here, we determined that a temperature sensitive ( ts ) PSD1 allele is autocatalytically impaired and that its fidelity is closely monitored throughout its life cycle by multiple mitochondrial quality control proteases. Interestingly, the proteases involved in resolving misfolded Psd1 ts vary depending on its autocatalytic status. Specifically, the degradation of a Psd1 ts precursor unable to undergo autocatalysis requires the unprecedented cooperative and sequential actions of two inner membrane proteases, Oma1p and Yme1p. In contrast, upon heat exposure postautocatalysis, Psd1 ts β subunits accumulate in protein aggregates that are resolved by Yme1p acting alone, while the released α subunit is degraded in parallel by an unidentified protease. Importantly, the stability of endogenous Psd1p is also influenced by Yme1p. We conclude that Psd1p, the key enzyme required for the mitochondrial pathway of phosphatidylethanolamine production, is closely monitored at several levels and by multiple mitochondrial quality control mechanisms present in the intermembrane space. Copyright © 2017 American Society for Microbiology.

DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy.

PubMed

Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

2017-01-01

Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95-nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95-nNOS interactions in MHE.

40 CFR 124.6 - Draft permits.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

76 FR 2581 - Action To Ensure Authority To Issue Permits Under the Prevention of Significant Deterioration...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-14

... or Act) Prevention of Significant Deterioration (PSD) program to sources of greenhouse gases (GHGs... issue preconstruction PSD permits to GHG- emitting sources. This action is related to EPA's recent final rule, the GHG PSD SIP Call, published on December 13, 2010, in which EPA made a finding of substantial...

40 CFR 124.6 - Draft permits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

77 FR 58032 - Approval and Promulgation of Implementation Plans; New Mexico; Albuquerque/Bernalillo County...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-19

... prevention of significant deterioration (PSD) measures required in the SIP of any other state, with regard to... modify the PSD SIP to include nitrogen oxides (NO X ) as an ozone precursor. EPA is approving revisions to the Albuquerque/Bernalillo County PSD SIP that identify the PM 2.5 precursors and establish...

40 CFR 124.6 - Draft permits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

78 FR 6818 - Notice of Issuance of Prevention of Significant Deterioration Modification and Part 71 Operating...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

..., EPA issued a Modification to a Prevention of Significant Deterioration (PSD) permit to NRG Backup..., Minnesota. The modified PSD permit changes the required interval of nitrogen oxide performance testing for... comment period, which ended on October 19, 2012, EPA received a comment on the modified draft PSD permit...

40 CFR 124.6 - Draft permits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

77 FR 65305 - Approval of Air Quality Implementation Plans; California; San Joaquin Valley Unified Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-26

... incorporates District Rule 2410-- Prevention of Significant Deterioration (PSD)--into the California SIP to establish a PSD permit program for pre-construction review of certain new and modified major stationary... provides an adequate PSD permitting program as required by section 110 and part C of title I of the CAA...

77 FR 62200 - Approval and Promulgation of Implementation Plans; New Mexico; Revisions to the New Source Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

... Plan (SIP); Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NNSR... approve revisions to the New Mexico SIP to update the New Mexico NNSR and PSD SIP permitting programs.... New Mexico submitted the PSD and NNSR SIP permitting revisions in two SIP submittals on June 11, 2009...

40 CFR 124.6 - Draft permits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

Measuring the Unmeasurable: Upholding Rigor in Quantitative Studies of Personal and Social Development in Outdoor Adventure Education

ERIC Educational Resources Information Center

Scrutton, Roger; Beames, Simon

2015-01-01

Outdoor adventure education (OAE) has a long history of being credited with the personal and social development (PSD) of its participants. PSD is notoriously difficult to measure quantitatively, yet stakeholders demand statistical evidence that given approaches to eliciting PSD are effective in their methods. Rightly or wrongly, many stakeholders…

The utility of presacral drainage in penetrating rectal injuries in adult and pediatric patients.

PubMed

Savoie, Kate B; Beazley, Thomas M; Cleveland, Brent; Khaneki, Sina; Markel, Troy A; Hammer, Peter M; Savage, Stephanie; Williams, Regan F

2017-11-01

With changing weaponry associated with injuries in civilian trauma, there is no clinical census on the utility of presacral drainage (PSD) in penetrating rectal injuries (PRIs), particularly in pediatric patients. Patients with PRI from July 2004-June 2014 treated at two free-standing children's hospitals and two adult level 1 trauma centers were compared by age (pediatric patients ≤16 years) and PSD. A stratified analysis was performed based on age. The primary outcome was pelvic/presacral abscess. We identified 81 patients with PRI; 19 pediatric, 62 adult. Forty patients had PSD; only three pediatric patients had a drain. Adult patients were more likely to have sustained gunshot wounds (84%), whereas pediatric patients were more likely to sustain impalement injuries (59%). Pediatric patients were more likely to have distal extraperitoneal injuries (56% versus 27% in adults, P = 0.03). PSD was more common in adult patients (59% versus 14%, P = 0.0004), African-Americans (71% versus 11% Caucasian, P < 0.01), and those sustaining gun shot wounds (63% versus 18% impalement, P < 0.01); only race remained significant in stratified analysis for both adult and pediatric patients. There were three cases of pelvic/presacral abscess, all in the adult patients (P = 0.31); one patient with PSD and two without PSD (P = 0.58). In stratified analysis, there were no differences in any infectious complication between those with and without PSD. Pelvic/presacral abscess is a rare complication of PRI, especially in pediatric patients. PSD is not associated with decreased rates of infectious complications and may not be necessary in the treatment of PRI. Copyright © 2017 Elsevier Inc. All rights reserved.

Decrease in neuronal nicotinic acetylcholine receptor subunit and PSD-93 transcript levels in the male mouse MPG after cavernous nerve injury or explant culture.

PubMed

Girard, Beatrice M; Merriam, Laura A; Tompkins, John D; Vizzard, Margaret A; Parsons, Rodney L

2013-11-15

Quantitative real-time PCR was used to test whether cavernous nerve injury leads to a decrease in major pelvic ganglia (MPG) neuronal nicotinic ACh receptor (nAChR) subunit and postsynaptic density (PSD)-93 transcript levels. Subunits α3, β4, and α7, commonly expressed in the MPG, were selected for analysis. After 72 h in explant culture, MPG transcript levels for α3, β4, α7, and PSD-93 were significantly depressed. Three days after cavernous nerve axotomy or crush in vivo, transcript levels for α3, β4, and PSD-93, but not for α7, were significantly depressed. Three days after dissection of the cavernous nerve free of underlying tissue and application of a 5-mm lateral stretch (manipulation), transcript levels for α3 and PSD-93 were also significantly decreased. Seven days after all three surgical procedures, α3 transcript levels remained depressed, but PSD-93 transcript levels were still decreased only after axotomy or nerve crush. At 30 days postsurgery, transcript levels for the nAChR subunits and PSD-93 had recovered. ACh-induced currents were significantly smaller in MPG neurons dissociated from 3-day explant cultured ganglia than from those recorded in neurons dissociated from acutely isolated ganglia; this observation provides direct evidence showing that a decrease in nAChR function was coincident with a decrease in nAChR subunit transcript levels. We conclude that a downregulation of nAChR subunit and PSD-93 expression after cavernous nerve injury, or even manipulation, could interrupt synaptic transmission within the MPG and thus contribute to the loss of neural control of urogenital organs after pelvic surgeries.

Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity

PubMed Central

Ma, Qi; Ruan, Hongyu; Peng, Lisheng; Zhang, Mingjie; Gack, Michaela U.

2017-01-01

Ubiquitination-directed proteasomal degradation of synaptic proteins, presumably mediated by lysine 48 (K48) of ubiquitin, is a key mechanism in synapse and neural circuit remodeling. However, more than half of polyubiquitin (polyUb) species in the mammalian brain are estimated to be non-K48; among them, the most abundant is Lys 63 (K63)-linked polyUb chains that do not tag substrates for degradation but rather modify their properties and activity. Virtually nothing is known about the role of these nonproteolytic polyUb chains at the synapse. Here we report that K63-polyUb chains play a significant role in postsynaptic protein scaffolding and synaptic strength and plasticity. We found that the postsynaptic scaffold PSD-95 (postsynaptic density protein 95) undergoes K63 polyubiquitination, which markedly modifies PSD-95’s scaffolding potentials, enables its synaptic targeting, and promotes synapse maturation and efficacy. TNF receptor-associated factor 6 (TRAF6) is identified as a direct E3 ligase for PSD-95, which, together with the E2 complex Ubc13/Uev1a, assembles K63-chains on PSD-95. In contrast, CYLD (cylindromatosis tumor-suppressor protein), a K63-specific deubiquitinase enriched in postsynaptic densities, cleaves K63-chains from PSD-95. We found that neuronal activity exerts potent control of global and synaptic K63-polyUb levels and, through NMDA receptors, drives rapid, CYLD-mediated PSD-95 deubiquitination, mobilizing and depleting PSD-95 from synapses. Silencing CYLD in hippocampal neurons abolishes NMDA-induced chemical long-term depression. Our results unveil a previously unsuspected role for nonproteolytic polyUb chains in the synapse and illustrate a mechanism by which a PSD-associated K63-linkage–specific ubiquitin machinery acts on a major postsynaptic scaffold to regulate synapse organization, function, and plasticity. PMID:28973854

Hot-spot model for accretion disc variability as random process. II. Mathematics of the power-spectrum break frequency

NASA Astrophysics Data System (ADS)

Pecháček, T.; Goosmann, R. W.; Karas, V.; Czerny, B.; Dovčiak, M.

2013-08-01

Context. We study some general properties of accretion disc variability in the context of stationary random processes. In particular, we are interested in mathematical constraints that can be imposed on the functional form of the Fourier power-spectrum density (PSD) that exhibits a multiply broken shape and several local maxima. Aims: We develop a methodology for determining the regions of the model parameter space that can in principle reproduce a PSD shape with a given number and position of local peaks and breaks of the PSD slope. Given the vast space of possible parameters, it is an important requirement that the method is fast in estimating the PSD shape for a given parameter set of the model. Methods: We generated and discuss the theoretical PSD profiles of a shot-noise-type random process with exponentially decaying flares. Then we determined conditions under which one, two, or more breaks or local maxima occur in the PSD. We calculated positions of these features and determined the changing slope of the model PSD. Furthermore, we considered the influence of the modulation by the orbital motion for a variability pattern assumed to result from an orbiting-spot model. Results: We suggest that our general methodology can be useful for describing non-monotonic PSD profiles (such as the trend seen, on different scales, in exemplary cases of the high-mass X-ray binary Cygnus X-1 and the narrow-line Seyfert galaxy Ark 564). We adopt a model where these power spectra are reproduced as a superposition of several Lorentzians with varying amplitudes in the X-ray-band light curve. Our general approach can help in constraining the model parameters and in determining which parts of the parameter space are accessible under various circumstances.

Chemical Compensation of Mitochondrial Phospholipid Depletion in Yeast and Animal Models of Parkinson’s Disease

PubMed Central

Wang, Shaoxiao; Zhang, Siyuan; Xu, Chuan; Barron, Addie; Galiano, Floyd; Patel, Dhaval; Lee, Yong Joo; Caldwell, Guy A.; Caldwell, Kim A.

2016-01-01

We have been investigating the role that phosphatidylethanolamine (PE) and phosphatidylcholine (PC) content plays in modulating the solubility of the Parkinson’s disease protein alpha-synuclein (α-syn) using Saccharomyces cerevisiae and Caenorhabditis elegans. One enzyme that synthesizes PE is the conserved enzyme phosphatidylserine decarboxylase (Psd1/yeast; PSD-1/worms), which is lodged in the inner mitochondrial membrane. We previously found that decreasing the level of PE due to knockdown of Psd1/psd-1 affects the homeostasis of α-syn in vivo. In S. cerevisiae, the co-occurrence of low PE and α-syn in psd1Δ cells triggers mitochondrial defects, stress in the endoplasmic reticulum, misprocessing of glycosylphosphatidylinositol-anchored proteins, and a 3-fold increase in the level of α-syn. The goal of this study was to identify drugs that rescue this phenotype. We screened the Prestwick library of 1121 Food and Drug Administration-approved drugs using psd1Δ + α-syn cells and identified cyclosporin A, meclofenoxate hydrochloride, and sulfaphenazole as putative protective compounds. The protective activity of these drugs was corroborated using C. elegans in which α-syn is expressed specifically in the dopaminergic neurons, with psd-1 depleted by RNAi. Worm populations were examined for dopaminergic neuron survival following psd-1 knockdown. Exposure to cyclosporine, meclofenoxate, and sulfaphenazole significantly enhanced survival at day 7 in α-syn-expressing worm populations whereby 50–55% of the populations displayed normal neurons, compared to only 10–15% of untreated animals. We also found that all three drugs rescued worms expressing α-syn in dopaminergic neurons that were deficient in the phospholipid cardiolipin following cardiolipin synthase (crls-1) depletion by RNAi. We discuss how these drugs might block α-syn pathology in dopaminergic neurons. PMID:27736935

A low cost PSD-based monocular motion capture system

NASA Astrophysics Data System (ADS)

Ryu, Young Kee; Oh, Choonsuk

2007-10-01

This paper describes a monocular PSD-based motion capture sensor to employ with commercial video game systems such as Microsoft's XBOX and Sony's Playstation II. The system is compact, low-cost, and only requires a one-time calibration at the factory. The system includes a PSD(Position Sensitive Detector) and active infrared (IR) LED markers that are placed on the object to be tracked. The PSD sensor is placed in the focal plane of a wide-angle lens. The micro-controller calculates the 3D position of the markers using only the measured intensity and the 2D position on the PSD. A series of experiments were performed to evaluate the performance of our prototype system. From the experimental results we see that the proposed system has the advantages of the compact size, the low cost, the easy installation, and the high frame rates to be suitable for high speed motion tracking in games.

Vibration Measurement Method of a String in Transversal Motion by Using a PSD.

PubMed

Yang, Che-Hua; Wu, Tai-Chieh

2017-07-17

A position sensitive detector (PSD) is frequently used for the measurement of a one-dimensional position along a line or a two-dimensional position on a plane, but is more often used for measuring static or quasi-static positions. Along with its quick response when measuring short time-spans in the micro-second realm, a PSD is also capable of detecting the dynamic positions of moving objects. In this paper, theoretical modeling and experiments are conducted to explore the frequency characteristics of a vibrating string while moving transversely across a one-dimensional PSD. The theoretical predictions are supported by the experiments. When the string vibrates at its natural frequency while moving transversely, the PSD will detect two frequencies near this natural frequency; one frequency is higher than the natural frequency and the other is lower. Deviations in these two frequencies, which differ from the string's natural frequency, increase while the speed of motion increases.

40 CFR 52.875 - Original identification of plan section.

Code of Federal Regulations, 2014 CFR

2014-07-01

... applicable to stationary sources subject to prevention of significant deterioration (PSD) permit requirements... interim stack height policy for each PSD permit issued until such time as EPA revises its general stack... submitted rule revisions to K.A.R. 28-19-17, the PSD rule; to K.A.R. 28-19-19, the CEM rule; and to K.A.R...

40 CFR 52.1620 - Identification of plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

... maintenance and PSD measures in any other state. Interstate transport for the 1997 ozone and PM2.5 NAAQS New Mexico 9/17/2007 11/26/2010, 75 FR 72688 Revisions to prohibit interference with maintenance and PSD... for PSD for the 1997 and 2008 Ozone and the 1997 and 2006 PM2.5 NAAQS Bernalillo County 8/16/2010 8/19...

40 CFR 52.2479 - Contents of the federally approved, State submitted implementation plan.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-087 Prevention of significant deterioration (PSD) [02/19/91] 173-405-091 Special studies [02/19/91] 2... deterioration (PSD) [02/19/91] 173-410-100 Special studies [02/19/91] 2.2.415 WAC 173-415 Primary Aluminum...] 173-415-051 Prevention of significant deterioration (PSD) [02/19/91] 173-415-060 Monitoring and...

76 FR 55799 - Approval of Clean Air Act Prevention of Significant Deterioration Permit Issued to Avenal Power...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-09

... Deterioration (PSD) permit application submitted by Avenal Power Center, LLC to authorize construction of the Avenal Energy Project. DATES: The EPA's PSD permit for the Avenal Energy Project became effective and...: The EPA issued a PSD permit on May 27, 2011, to Avenal Power Center, LLC for the Avenal Energy Project...

40 CFR 52.875 - Original identification of plan section.

Code of Federal Regulations, 2012 CFR

2012-07-01

... applicable to stationary sources subject to prevention of significant deterioration (PSD) permit requirements... interim stack height policy for each PSD permit issued until such time as EPA revises its general stack... submitted rule revisions to K.A.R. 28-19-17, the PSD rule; to K.A.R. 28-19-19, the CEM rule; and to K.A.R...

40 CFR 52.2479 - Contents of the federally approved, State submitted implementation plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-087 Prevention of significant deterioration (PSD) [02/19/91] 173-405-091 Special studies [02/19/91] 2... deterioration (PSD) [02/19/91] 173-410-100 Special studies [02/19/91] 2.2.415 WAC 173-415 Primary Aluminum...] 173-415-051 Prevention of significant deterioration (PSD) [02/19/91] 173-415-060 Monitoring and...

78 FR 4339 - Approval and Promulgation of Implementation Plans; New Mexico; Revisions to the New Source Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-22

... Plan (SIP); Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NNSR... revisions to the New Mexico SIP to update the New Mexico NNSR and PSD SIP permitting programs consistent... submitted the PSD and NNSR SIP permitting revisions in two SIP submittals on June 11, 2009 and May 23, 2011...

40 CFR 52.875 - Original identification of plan section.

Code of Federal Regulations, 2013 CFR

2013-07-01

... applicable to stationary sources subject to prevention of significant deterioration (PSD) permit requirements... interim stack height policy for each PSD permit issued until such time as EPA revises its general stack... submitted rule revisions to K.A.R. 28-19-17, the PSD rule; to K.A.R. 28-19-19, the CEM rule; and to K.A.R...

40 CFR 52.875 - Original identification of plan section.

Code of Federal Regulations, 2011 CFR

2011-07-01

... applicable to stationary sources subject to prevention of significant deterioration (PSD) permit requirements... interim stack height policy for each PSD permit issued until such time as EPA revises its general stack... submitted rule revisions to K.A.R. 28-19-17, the PSD rule; to K.A.R. 28-19-19, the CEM rule; and to K.A.R...

Participatory System Dynamics Modeling: Increasing Stakeholder Engagement and Precision to Improve Implementation Planning in Systems.

PubMed

Zimmerman, Lindsey; Lounsbury, David W; Rosen, Craig S; Kimerling, Rachel; Trafton, Jodie A; Lindley, Steven E

2016-11-01

Implementation planning typically incorporates stakeholder input. Quality improvement efforts provide data-based feedback regarding progress. Participatory system dynamics modeling (PSD) triangulates stakeholder expertise, data and simulation of implementation plans prior to attempting change. Frontline staff in one VA outpatient mental health system used PSD to examine policy and procedural "mechanisms" they believe underlie local capacity to implement evidence-based psychotherapies (EBPs) for PTSD and depression. We piloted the PSD process, simulating implementation plans to improve EBP reach. Findings indicate PSD is a feasible, useful strategy for building stakeholder consensus, and may save time and effort as compared to trial-and-error EBP implementation planning.

Shear strength and microstructure of polydisperse packings: The effect of size span and shape of particle size distribution.

PubMed

Azéma, Emilien; Linero, Sandra; Estrada, Nicolas; Lizcano, Arcesio

2017-08-01

By means of extensive contact dynamics simulations, we analyzed the effect of particle size distribution (PSD) on the strength and microstructure of sheared granular materials composed of frictional disks. The PSDs are built by means of a normalized β function, which allows the systematic investigation of the effects of both, the size span (from almost monodisperse to highly polydisperse) and the shape of the PSD (from linear to pronouncedly curved). We show that the shear strength is independent of the size span, which substantiates previous results obtained for uniform distributions by packing fraction. Notably, the shear strength is also independent of the shape of the PSD, as shown previously for systems composed of frictionless disks. In contrast, the packing fraction increases with the size span, but decreases with more pronounced PSD curvature. At the microscale, we analyzed the connectivity and anisotropies of the contacts and forces networks. We show that the invariance of the shear strength with the PSD is due to a compensation mechanism which involves both geometrical sources of anisotropy. In particular, contact orientation anisotropy decreases with the size span and increases with PSD curvature, while the branch length anisotropy behaves inversely.

Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke.

PubMed

Luo, Chun-Xia; Lin, Yu-Hui; Qian, Xiao-Dan; Tang, Ying; Zhou, Hai-Hui; Jin, Xing; Ni, Huan-Yu; Zhang, Feng-Yun; Qin, Cheng; Li, Fei; Zhang, Yu; Wu, Hai-Yin; Chang, Lei; Zhu, Dong-Ya

2014-10-01

Stroke is a major public health concern. The lack of effective therapies heightens the need for new therapeutic targets. Mammalian brain has the ability to rewire itself to restore lost functionalities. Promoting regenerative repair, including neurogenesis and dendritic remodeling, may offer a new therapeutic strategy for the treatment of stroke. Here, we report that interaction of neuronal nitric oxide synthase (nNOS) with the protein postsynaptic density-95 (PSD-95) negatively controls regenerative repair after stroke in rats. Dissociating nNOS-PSD-95 coupling in neurons promotes neuronal differentiation of neural stem cells (NSCs), facilitates the migration of newborn cells into the injured area, and enhances neurite growth of newborn neurons and dendritic spine formation of mature neurons in the ischemic brain of rats. More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of regenerative repair in rats. Histone deacetylase 2 in NSCs may mediate the role of nNOS-PSD-95 association. Thus, nNOS-PSD-95 can serve as a target for regenerative repair after stroke. Copyright © 2014 the authors 0270-6474/14/3413535-14$15.00/0.

The magnetic structure and palaeomagnetic recording fidelity of sub-micron greigite (Fe3S4)

NASA Astrophysics Data System (ADS)

Valdez-Grijalva, Miguel A.; Nagy, Lesleis; Muxworthy, Adrian R.; Williams, Wyn; Fabian, Karl

2018-02-01

We present the results of a finite-element micromagnetic model of 30nm to 300nm greigite (Fe3S4) grains with a variety of equant morphologies. This grain size range covers the magnetic single-domain (SD) to pseudo single-domain (PSD) transition, and possibly also the PSD to multi-domain (MD) transition. The SD-PSD threshold d0 is determined to be 50nm ≤d0 ≤ 56nm depending on grain shape. The nudged elastic-band method was used to determine the room temperature energy barriers between stable states and thus the blocking volumes. It is found that, in the absence of interparticle magnetostatic interactions, the magnetisation of equant SD greigite is not stable on a geological scale and only PSD grains ≥ 70nm can be expected to carry a stable magnetisation over billion-year timescales, i.e., all non-interacting SD particles are essentially superparamagnetic. We further identify a mechanism for the PSD to multi-domain (MD) transition, which is of a continuous nature from PSD nucleation up to 300nm, when structures typical of MD behaviour like closure domains begin to form.

PSD-95 promotes the stabilization of young synaptic contacts.

PubMed

Taft, Christine E; Turrigiano, Gina G

2014-01-05

Maintaining a population of stable synaptic connections is probably of critical importance for the preservation of memories and functional circuitry, but the molecular dynamics that underlie synapse stabilization is poorly understood. Here, we use simultaneous time-lapse imaging of post synaptic density-95 (PSD-95) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) to investigate the dynamics of protein composition at axodendritic (AD) contacts. Our data reveal that this composition is highly dynamic, with both proteins moving into and out of the same synapse independently, so that synapses cycle rapidly between states in which they are enriched for none, one or both proteins. We assessed how PSD-95 and CaMKII interact at stable and transient AD sites and found that both phospho-CaMKII and PSD-95 are present more often at stable than labile contacts. Finally, we found that synaptic contacts are more stable in older neurons, and this process can be mimicked in younger neurons by overexpression of PSD-95. Taken together, these data show that synaptic protein composition is highly variable over a time-scale of hours, and that PSD-95 is probably a key synaptic protein that promotes synapse stability.

Determinants of Psychosocial Difficulties Experienced by Persons with Brain Disorders: Towards a ‘Horizontal Epidemiology’ Approach

PubMed Central

Sabariego, Carla; Coenen, Michaela; Ballert, Carolina; Cabello, Maria; Leonardi, Matilde; Anczewska, Marta; Pitkänen, Tuuli; Raggi, Alberto; Mellor, Blanca; Covelli, Venusia; Świtaj, Piotr; Levola, Jonna; Schiavolin, Silvia; Chrostek, Anna; Bickenbach, Jerome; Chatterji, Somnath; Cieza, Alarcos

2015-01-01

Background Persons with brain disorders experience significant psychosocial difficulties (PSD) in daily life, e.g. problems with managing daily routine or emotional lability, and the level of the PSD depends on social, physical and political environments, and psychologic-personal determinants. Our objective is to determine a brief set of environmental and psychologic-personal factors that are shared determinants of PSD among persons with different brain disorders. Methods Cross-sectional study, convenience sample of persons with either dementia, stroke, multiple sclerosis, epilepsy, migraine, depression, schizophrenia, substance dependence or Parkinson’s disease. Random forest regression and classical linear regression were used in the analyses. Results 722 subjects were interviewed in four European countries. The brief set of determinants encompasses presence of comorbidities, health status appraisal, stressful life events, personality changes, adaptation, self-esteem, self-worth, built environment, weather, and health problems in the family. Conclusions The identified brief set of common determinants of PSD can be used to support the implementation of cross-cutting interventions, social actions and policy tools to lower PSD experienced by persons with brain disorders. This set complements a recently proposed reliable and valid direct metric of PSD for brain disorders called PARADISE24. PMID:26675663

Spinal SIRPα1-SHP2 interaction regulates spinal nerve ligation-induced neuropathic pain via PSD-95-dependent NR2B activation in rats.

PubMed

Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuang; Hsieh, Ming-Chun; Lin, Tzer-Bin

2012-05-01

The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. Nerve ligation induced allodynia, SIRPα1, SHP2, phosphorylated SHP2 (pSHP2), and phosphorylated NR2B (pNR2B) expression, and SHP2-PSD-95, pSHP2-PSD-95, PSD-95-NR2B, and PSD-95-pNR2B coimmunoprecipitation in the ipsilateral dorsal horn. In allodynic rats, injury-induced SHP2 immunoreactivity was localized in the ipsilateral dorsal horn neurons and coincident with PSD-95 and NR2B immunoreactivity. SIRPα1 silencing using small interfering RNA (siRNA; 1, 3, or 5μg/rat for 7days) prevented injury-induced allodynia and the associated changes in protein expression, phosphorylation, and coimmunoprecipitation. Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Diabetes mellitus is associated with late-onset post-stroke depression.

PubMed

Zhang, Yu; He, Ji-Rong; Liang, Huai-Bin; Lu, Wen-Jing; Yang, Guo-Yuan; Liu, Jian-Rong; Zeng, Li-Li

2017-10-15

To explore the associated factors of late-onset post-stroke depression (PSD). A total of 251 patients with acute ischemic stroke were recruited. The evaluation of depression was performed 2 weeks after ischemia. 206 patients showing no depression in 2 weeks were followed up. They were divided into late-onset PSD group and non-depressed group by clinical interview with Hamilton depression scale score 3 months after stroke. On the first day following hospitalization, the clinical data including age, gender, educational level and vascular risk factors were recorded. The severity, etiological subtype and location of stroke were evaluated. The inflammatory mediators, glucose and lipid levels were recorded on the day of admission. The association between clinical factors and late-onset PSD was explored by logistic regression analysis. The ROC analysis was performed to evaluate the predicting power of the clinical factors. 187 of 206 patients completed the assessment 3 months after stroke. 19 (10.16%) patients were diagnosed as late onset PSD. Diabetes mellitus was an independent risk factor for late-onset PSD (OR 2.675, p = 0.047). ROC analysis demonstrated that glucose and HbA1C could predict late-onset PSD with specificity of 84.4%. The sample of our study was small. The results should be further confirmed in a larger cohort of patients with acute ischemic stroke. The acute ischemic stroke patients with diabetes mellitus were more tendered to suffer late-onset PSD. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders

PubMed Central

Redle, Erin; Vannest, Jennifer; Maloney, Thomas; Tsevat, Rebecca K.; Eikenberry, Sarah; Lewis, Barbara; Shriberg, Lawrence D.; Tkach, Jean; Holland, Scott K.

2014-01-01

Children with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. Methods This case-control study included 12 children with PSD (mean age 7.42 years, 4 female) and 12 controls (mean age 7.44 years, 4 female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. Results Children with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. Conclusions Over-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD. PMID:25481413

The Glutamatergic Aspects of Schizophrenia Molecular Pathophysiology: Role of the Postsynaptic Density, and Implications for Treatment

PubMed Central

Iasevoli, Felice; Tomasetti, Carmine; Buonaguro, Elisabetta F.; de Bartolomeis, Andrea

2014-01-01

Schizophrenia is one of the most debilitating psychiatric diseases with a lifetime prevalence of approximately 1%. Although the specific molecular underpinnings of schizophrenia are still unknown, evidence has long linked its pathophysiology to postsynaptic abnormalities. The postsynaptic density (PSD) is among the molecular structures suggested to be potentially involved in schizophrenia. More specifically, the PSD is an electron-dense thickening of glutamatergic synapses, including ionotropic and metabotropic glutamate receptors, cytoskeletal and scaffolding proteins, and adhesion and signaling molecules. Being implicated in the postsynaptic signaling of multiple neurotransmitter systems, mostly dopamine and glutamate, the PSD constitutes an ideal candidate for studying dopamine-glutamate disturbances in schizophrenia. Recent evidence suggests that some PSD proteins, such as PSD-95, Shank, and Homer are implicated in severe behavioral disorders, including schizophrenia. These findings, further corroborated by genetic and animal studies of schizophrenia, offer new insights for the development of pharmacological strategies able to overcome the limitations in terms of efficacy and side effects of current schizophrenia treatment. Indeed, PSD proteins are now being considered as potential molecular targets against this devastating illness. The current paper reviews the most recent hypotheses on the molecular mechanisms underlying schizophrenia pathophysiology. First, we review glutamatergic dysfunctions in schizophrenia and we provide an update on postsynaptic molecules involvement in schizophrenia pathophysiology by addressing both human and animal studies. Finally, the possibility that PSD proteins may represent potential targets for new molecular interventions in psychosis will be discussed. PMID:24851087

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dosemeci, Ayse, E-mail: dosemeca@mail.nih.gov; Thein, Soe; Yang, Yijung

Highlights: Black-Right-Pointing-Pointer CYLD is a deubiquitinase specific for lysine63-linked polyubiquitins. Black-Right-Pointing-Pointer Presence of CYLD in PSDs is established by biochemistry and immunoEM. Black-Right-Pointing-Pointer CYLD accumulates on PSDs upon depolarization of neurons. Black-Right-Pointing-Pointer Accumulation of CYLD at PSDs may regulate trafficking/degradation of synaptic proteins. -- Abstract: Polyubiquitin chains on proteins flag them for distinct fates depending on the type of polyubiquitin linkage. While lysine48-linked polyubiquitination directs proteins to proteasomal degradation, lysine63-linked polyubiquitination promotes different protein trafficking and is involved in autophagy. Here we show that postsynaptic density (PSD) fractions from adult rat brain contain deubiquitinase activity that targets both lysine48 andmore » lysine63-linked polyubiquitins. Comparison of PSD fractions with parent subcellular fractions by Western immunoblotting reveals that CYLD, a deubiquitinase specific for lysine63-linked polyubiquitins, is highly enriched in the PSD fraction. Electron microscopic examination of hippocampal neurons in culture under basal conditions shows immunogold label for CYLD at the PSD complex in approximately one in four synapses. Following depolarization by exposure to high K+, the proportion of CYLD-labeled PSDs as well as the labeling intensity of CYLD at the PSD increased by more than eighty percent, indicating that neuronal activity promotes accumulation of CYLD at the PSD. An increase in postsynaptic CYLD following activity would promote removal of lysine63-polyubiquitins from PSD proteins and thus could regulate their trafficking and prevent their autophagic degradation.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gagnon, Jean-Christophe; Theriault, Dany; Guillot, Mathieu

Purpose: To compare the performance of plastic scintillation detectors (PSD) for quality assurance (QA) in stereotactic radiosurgery conditions to a microion-chamber (IC), Gafchromic EBT2 films, 60 008 shielded photon diode (SD) and unshielded diodes (UD), and assess a new 2D crosshair array prototype adapted to small field dosimetry. Methods: The PSD consists of a 1 mm diameter by 1 mm long scintillating fiber (BCF-60, Saint-Gobain, Inc.) coupled to a polymethyl-methacrylate optical fiber (Eska premier, Mitsubishi Rayon Co., Ltd., Tokyo, Japan). Output factors (S{sub c,p}) for apertures used in radiosurgery ranging from 4 to 40 mm in diameter have been measured.more » The PSD crosshair array (PSDCA) is a water equivalent device made up of 49 PSDs contained in a 1.63 cm radius area. Dose profiles measurements were taken for radiosurgery fields using the PSDCA and were compared to other dosimeters. Moreover, a typical stereotactic radiosurgery treatment using four noncoplanar arcs was delivered on a spherical phantom in which UD, IC, or PSD was placed. Using the Xknife planning system (Integra Radionics Burlington, MA), 15 Gy was prescribed at the isocenter, where each detector was positioned. Results: Output Factors measured by the PSD have a mean difference of 1.3% with Gafchromic EBT2 when normalized to a 10 x 10 cm{sup 2} field, and 1.0% when compared with UD measurements normalized to the 35 mm diameter cone. Dose profiles taken with the PSD crosshair array agreed with other single detectors dose profiles in spite of the presence of the 49 PSDs. Gamma values comparing 1D dose profiles obtained with PSD crosshair array with Gafchromic EBT2 and UD measured profiles shows 98.3% and 100.0%, respectively, of detector passing the gamma acceptance criteria of 0.3 mm and 2%. The dose measured by the PSD for a complete stereotactic radiosurgery treatment is comparable to the planned dose corrected for its SD-based S{sub c,p} within 1.4% and 0.7% for 5 and 35 mm diameter cone, respectively. Furthermore, volume averaging of the IC can be observed for the 5 mm aperture where it differs by as much as 9.1% compared to the PSD measurement. The angular dependency of the UD is also observed, unveiled by an under-response around 2.5% of both 5 and 35 mm apertures. Conclusions: Output Factors and dose profiles measurements performed, respectively, with the PSD and the PSDCA were in agreement with those obtained with the UD and EBT2 films. For stereotactic radiosurgery treatment verification, the PSD gives accurate results compared to the planning system and the IC once the latter is corrected to compensate for the averaging effect of the IC. The PSD provides precise results when used as a single detector or in a dense array, resulting in a great potential for stereotactic radiosurgery QA measurements.« less

77 FR 64237 - Notice of Approval of Clean Air Act Prevention of Significant Deterioration Permit Issued to the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-19

... Air Act Prevention of Significant Deterioration (PSD) permit for the City of Palmdale (City) for the construction of the Palmdale Hybrid Power Project (PHPP). DATES: EPA Region 9 issued a final PSD permit... decision can obtain them at http://www.epa.gov/eab/ . A copy of the PSD permit is also available at http...

Structural Origins of Scintillation: Metal Organic Frameworks as a Nanolaboratory

DTIC Science & Technology

2016-06-01

scintillation response and thus the ability to perform neutron/gamma particle discrimination via pulse-shape discrimination ( PSD ). Unfortunately, the...defined an alternative approach towards particle discrimination that addresses the limitations of conventional PSD organic scintillators. This approach...discrimination ( PSD ), for which the prompt component of the scintillation response is quenched for high specific energy loss (dE/dX) particles such as protons

Impairment of TrkB-PSD-95 Signaling in Angelman Syndrome

PubMed Central

Cao, Cong; Rioult-Pedotti, Mengia S.; Migani, Paolo; Yu, Crystal J.; Tiwari, Rakesh; Parang, Keykavous; Spaller, Mark R.; Goebel, Dennis J.; Marshall, John

2013-01-01

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) TrkB receptor signaling, which is known to be essential for both the induction and maintenance of LTP. We report that TrkB signaling in the AS mouse is defective, and show that reduction of Arc expression to control levels rescues the signaling deficits. Moreover, the association of the postsynaptic density protein PSD-95 with TrkB is critical for intact BDNF signaling, and elevated levels of Arc were found to impede PSD-95/TrkB association. In Ube3A deficient mice, the BDNF-induced recruitment of PSD-95, as well as PLCγ and Grb2-associated binder 1 (Gab1) with TrkB receptors was attenuated, resulting in reduced activation of PLCγ-α-calcium/calmodulin-dependent protein kinase II (CaMKII) and PI3K-Akt, but leaving the extracellular signal-regulated kinase (Erk) pathway intact. A bridged cyclic peptide (CN2097), shown by nuclear magnetic resonance (NMR) studies to uniquely bind the PDZ1 domain of PSD-95 with high affinity, decreased the interaction of Arc with PSD-95 to restore BDNF-induced TrkB/PSD-95 complex formation, signaling, and facilitate the induction of LTP in AS mice. We propose that the failure of TrkB receptor signaling at synapses in AS is directly linked to elevated levels of Arc associated with PSD-95 and PSD-95 PDZ-ligands may represent a promising approach to reverse cognitive dysfunction. PMID:23424281

Impairment of TrkB-PSD-95 signaling in Angelman syndrome.

PubMed

Cao, Cong; Rioult-Pedotti, Mengia S; Migani, Paolo; Yu, Crystal J; Tiwari, Rakesh; Parang, Keykavous; Spaller, Mark R; Goebel, Dennis J; Marshall, John

2013-01-01

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) TrkB receptor signaling, which is known to be essential for both the induction and maintenance of LTP. We report that TrkB signaling in the AS mouse is defective, and show that reduction of Arc expression to control levels rescues the signaling deficits. Moreover, the association of the postsynaptic density protein PSD-95 with TrkB is critical for intact BDNF signaling, and elevated levels of Arc were found to impede PSD-95/TrkB association. In Ube3A deficient mice, the BDNF-induced recruitment of PSD-95, as well as PLCγ and Grb2-associated binder 1 (Gab1) with TrkB receptors was attenuated, resulting in reduced activation of PLCγ-α-calcium/calmodulin-dependent protein kinase II (CaMKII) and PI3K-Akt, but leaving the extracellular signal-regulated kinase (Erk) pathway intact. A bridged cyclic peptide (CN2097), shown by nuclear magnetic resonance (NMR) studies to uniquely bind the PDZ1 domain of PSD-95 with high affinity, decreased the interaction of Arc with PSD-95 to restore BDNF-induced TrkB/PSD-95 complex formation, signaling, and facilitate the induction of LTP in AS mice. We propose that the failure of TrkB receptor signaling at synapses in AS is directly linked to elevated levels of Arc associated with PSD-95 and PSD-95 PDZ-ligands may represent a promising approach to reverse cognitive dysfunction.

[Role of phosphorylation of MARCKS-PSD in the secretion of MUC5AC induced by cold temperatures in human airway epithelial cells].

PubMed

Li, Minchao; Perelman, Juliy M; Zhou, Xiangdong

2012-05-01

To construct phosphorylation sites domain (PSD) mutant of myristoylated alaninerich C kinase substrate (MARCKS) and explore the role of transient receptor potential melastatin 8 cation channels (TRPM8) and MARCKS in cold-induced synthesis and exocytosis of mucin (MUC) 5AC. Human placental cDNA was used as a template to amplify the full coding region of MARCKS cDNA by PCR. Ser159, Ser 163, Ser 167, Ser 170 in the PSD were mutated to aspartic acids by an overlap PCR method. The resultant PSD mutant cDNA and the wild-type MARCKS cDNA were each subcloned into a mammalian expression vector pcDNA3.0. Recombinant constructs were confirmed by restriction enzyme digestion analysis and DNA sequencing. In intervention experiments, cells were pretreated with the TRPM8 channel antagonist BCTC and transfected with MARCKS-PSD mutant cDNA, and thereafter cold stimulation was applied. The levels of MUC5AC were measured by immunofluorescence and ELISA to clarify the roles of TRPM8 and PSD mutant on the synthesis and secretion of MUC5AC induced by cold, respectively. Restriction enzyme digestion analysis and DNA sequencing revealed that the pcDNA3.0- MARCKS and pcDNA3.0-MARCKS-PSD mutants were successfully constructed. The levels of intracellular and secreted MUC5AC of cold treated group were significantly higher than those of control group (P<0.05). BCTC attenuated the cold-induced synthesis and secretion of MUC5AC when compared with cold treated group (P<0.05). Transfection of 16HBE cells with the MARCKS-PSD mutant cDNA resulted in significant inhibition of mucin secretion in response to cold, and significantly higher level of intracellular MUC5AC than that of control group (P<0.01), whereas transfection with the vector DNA or the wild-type MARCKS cDNA had no effect on the mucin synthesis and secretion in response to cold (P>0.05). TRPM8 and phosphorylation of MARCKS-PSD mediates the cold-induced exocytosis of MUC5AC by airway epithelial cells.

Vibration Measurement Method of a String in Transversal Motion by Using a PSD

PubMed Central

Yang, Che-Hua; Wu, Tai-Chieh

2017-01-01

A position sensitive detector (PSD) is frequently used for the measurement of a one-dimensional position along a line or a two-dimensional position on a plane, but is more often used for measuring static or quasi-static positions. Along with its quick response when measuring short time-spans in the micro-second realm, a PSD is also capable of detecting the dynamic positions of moving objects. In this paper, theoretical modeling and experiments are conducted to explore the frequency characteristics of a vibrating string while moving transversely across a one-dimensional PSD. The theoretical predictions are supported by the experiments. When the string vibrates at its natural frequency while moving transversely, the PSD will detect two frequencies near this natural frequency; one frequency is higher than the natural frequency and the other is lower. Deviations in these two frequencies, which differ from the string’s natural frequency, increase while the speed of motion increases. PMID:28714915

Dlgap1 knockout mice exhibit alterations of the postsynaptic density and selective reductions in sociability.

PubMed

Coba, M P; Ramaker, M J; Ho, E V; Thompson, S L; Komiyama, N H; Grant, S G N; Knowles, J A; Dulawa, S C

2018-02-02

The scaffold protein DLGAP1 is localized at the post-synaptic density (PSD) of glutamatergic neurons and is a component of supramolecular protein complexes organized by PSD95. Gain-of-function variants of DLGAP1 have been associated with obsessive-compulsive disorder (OCD), while haploinsufficient variants have been linked to autism spectrum disorder (ASD) and schizophrenia in human genetic studies. We tested male and female Dlgap1 wild type (WT), heterozygous (HT), and knockout (KO) mice in a battery of behavioral tests: open field, dig, splash, prepulse inhibition, forced swim, nest building, social approach, and sucrose preference. We also used biochemical approaches to examine the role of DLGAP1 in the organization of PSD protein complexes. Dlgap1 KO mice were most notable for disruption of protein interactions in the PSD, and deficits in sociability. Other behavioral measures were largely unaffected. Our data suggest that Dlgap1 knockout leads to PSD disruption and reduced sociability, consistent with reports of DLGAP1 haploinsufficient variants in schizophrenia and ASD.

Smart particles for noble drug delivery system.

PubMed

Park, Cheolyoung; Kim, Jihoon; Jang, Seunghyun; Woo, Hee-Gweon; Ko, Young Chun; Sohn, Honglae

2010-05-01

Optically encoded smart particles were prepared for noble drug delivery materials. Distributed Bragg reflector (DBR) porous silicon (PSi) was generated by applying a computer-generated pseudo-square wave current waveform. This DBR PSi film was lifted off from the Si substrate and thermally oxidized to convert PSi to porous silicon dioxide (PSD). DBR PSD film was derivatized with 20(S)-Camptothecin (CPT) and fractured by ultrasono-method to give smart particles. DBR PSD smart particles exhibited a sharp photonic band gap in the optical reflectivity spectrum. Optical characteristic of PSD smart particles retained DBR photonic property in aqueous buffer solution. The release of CPT and change of reflection wavelength were measured by UV-vis and reflectance spectrometer, respectively. The intensity of differential peak from reflection resonances of the smart particles was increased with a drug release. The blue shift of reflection peak resulted in the decrease of refractive index of PSD smart particles during the drug release. The concentration of released drug exhibited an linear relationship with a release time.

Poststroke Depression: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

PubMed

Towfighi, Amytis; Ovbiagele, Bruce; El Husseini, Nada; Hackett, Maree L; Jorge, Ricardo E; Kissela, Brett M; Mitchell, Pamela H; Skolarus, Lesli E; Whooley, Mary A; Williams, Linda S

2017-02-01

Poststroke depression (PSD) is common, affecting approximately one third of stroke survivors at any one time after stroke. Individuals with PSD are at a higher risk for suboptimal recovery, recurrent vascular events, poor quality of life, and mortality. Although PSD is prevalent, uncertainty remains regarding predisposing risk factors and optimal strategies for prevention and treatment. This is the first scientific statement from the American Heart Association on the topic of PSD. Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee and the American Heart Association's Manuscript Oversight Committee. Members were assigned topics relevant to their areas of expertise and reviewed appropriate literature, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion. This multispecialty statement provides a comprehensive review of the current evidence and gaps in current knowledge of the epidemiology, pathophysiology, outcomes, management, and prevention of PSD, and provides implications for clinical practice. © 2016 American Heart Association, Inc.

Mathematical Model and Calibration Procedure of a PSD Sensor Used in Local Positioning Systems.

PubMed

Rodríguez-Navarro, David; Lázaro-Galilea, José Luis; Bravo-Muñoz, Ignacio; Gardel-Vicente, Alfredo; Domingo-Perez, Francisco; Tsirigotis, Georgios

2016-09-15

Here, we propose a mathematical model and a calibration procedure for a PSD (position sensitive device) sensor equipped with an optical system, to enable accurate measurement of the angle of arrival of one or more beams of light emitted by infrared (IR) transmitters located at distances of between 4 and 6 m. To achieve this objective, it was necessary to characterize the intrinsic parameters that model the system and obtain their values. This first approach was based on a pin-hole model, to which system nonlinearities were added, and this was used to model the points obtained with the nA currents provided by the PSD. In addition, we analyzed the main sources of error, including PSD sensor signal noise, gain factor imbalances and PSD sensor distortion. The results indicated that the proposed model and method provided satisfactory calibration and yielded precise parameter values, enabling accurate measurement of the angle of arrival with a low degree of error, as evidenced by the experimental results.

Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions.

PubMed

Pedersen, Søren W; Albertsen, Louise; Moran, Griffin E; Levesque, Brié; Pedersen, Stine B; Bartels, Lina; Wapenaar, Hannah; Ye, Fei; Zhang, Mingjie; Bowen, Mark E; Strømgaard, Kristian

2017-09-15

The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effect of phosphorylation on PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids at four positions within the PDZ domains and examined the effects on interactions with a large set of binding partners. We observed complex effects on affinity. Most notably, phosphorylation at Y397 induced a significant increase in affinity for stargazin, as confirmed by NMR and single molecule FRET. Additionally, we compared the effects of phosphorylation to phosphomimetic mutations, which revealed that phosphomimetics are ineffective substitutes for tyrosine phosphorylation. Our strategy to generate site-specifically phosphorylated PDZ domains provides a detailed understanding of the role of phosphorylation in the regulation of PSD-95 interactions.

Simulation results of Pulse Shape Discrimination (PSD) for background reduction in INTEGRAL Spectrometer (SPI) germanium detectors

NASA Technical Reports Server (NTRS)

Slassi-Sennou, S. A.; Boggs, S. E.; Feffer, P. T.; Lin, R. P.

1997-01-01

Pulse Shape Discrimination (PSD) for background reduction will be used in the INTErnational Gamma Ray Astrophysics Laboratory (INTEGRAL) imaging spectrometer (SPI) to improve the sensitivity from 200 keV to 2 MeV. The observation of significant astrophysical gamma ray lines in this energy range is expected, where the dominant component of the background is the beta(sup -) decay in the Ge detectors due to the activation of Ge nuclei by cosmic rays. The sensitivity of the SPI will be improved by rejecting beta(sup -) decay events while retaining photon events. The PSD technique will distinguish between single and multiple site events. Simulation results of PSD for INTEGRAL-type Ge detectors using a numerical model for pulse shape generation are presented. The model was shown to agree with the experimental results for a narrow inner bore closed end cylindrical detector. Using PSD, a sensitivity improvement factor of the order of 2.4 at 0.8 MeV is expected.

USING LEAKED POWER TO MEASURE INTRINSIC AGN POWER SPECTRA OF RED-NOISE TIME SERIES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, S. F.; Xue, Y. Q., E-mail: zshifu@mail.ustc.edu.cn, E-mail: xuey@ustc.edu.cn

Fluxes emitted at different wavebands from active galactic nuclei (AGNs) fluctuate at both long and short timescales. The variation can typically be characterized by a broadband power spectrum, which exhibits a red-noise process at high frequencies. The standard method of estimating the power spectral density (PSD) of AGN variability is easily affected by systematic biases such as red-noise leakage and aliasing, in particular when the observation spans a relatively short period and is gapped. Focusing on the high-frequency PSD that is strongly distorted due to red-noise leakage and usually not significantly affected by aliasing, we develop a novel and observablemore » normalized leakage spectrum (NLS), which sensitively describes the effects of leaked red-noise power on the PSD at different temporal frequencies. Using Monte Carlo simulations, we demonstrate how an AGN underlying PSD sensitively determines the NLS when there is severe red-noise leakage, and thereby how the NLS can be used to effectively constrain the underlying PSD.« less

Singular value decomposition based impulsive noise reduction in multi-frequency phase-sensitive demodulation of electrical impedance tomography

NASA Astrophysics Data System (ADS)

Hao, Zhenhua; Cui, Ziqiang; Yue, Shihong; Wang, Huaxiang

2018-06-01

As an important means in electrical impedance tomography (EIT), multi-frequency phase-sensitive demodulation (PSD) can be viewed as a matched filter for measurement signals and as an optimal linear filter in the case of Gaussian-type noise. However, the additive noise usually possesses impulsive noise characteristics, so it is a challenging task to reduce the impulsive noise in multi-frequency PSD effectively. In this paper, an approach for impulsive noise reduction in multi-frequency PSD of EIT is presented. Instead of linear filters, a singular value decomposition filter is employed as the pre-stage filtering module prior to PSD, which has advantages of zero phase shift, little distortion, and a high signal-to-noise ratio (SNR) in digital signal processing. Simulation and experimental results demonstrated that the proposed method can effectively eliminate the influence of impulsive noise in multi-frequency PSD, and it was capable of achieving a higher SNR and smaller demodulation error.

Stabilization of Particle Discrimination Efficiencies for Neutron Spectrum Unfolding With Organic Scintillators

NASA Astrophysics Data System (ADS)

Lawrence, Chris C.; Polack, J. K.; Febbraro, Michael; Kolata, J. J.; Flaska, Marek; Pozzi, S. A.; Becchetti, F. D.

2017-02-01

The literature discussing pulse-shape discrimination (PSD) in organic scintillators dates back several decades. However, little has been written about PSD techniques that are optimized for neutron spectrum unfolding. Variation in n-γ misclassification rates and in γ/n ratio of incident fields can distort the neutron pulse-height response of scintillators and these distortions can in turn cause large errors in unfolded spectra. New applications in arms-control verification call for detection of lower-energy neutrons, for which PSD is particularly problematic. In this article, we propose techniques for removing distortions on pulse-height response that result from the merging of PSD distributions in the low-pulse-height region. These techniques take advantage of the repeatable shapes of PSD distributions that are governed by the counting statistics of scintillation-photon populations. We validate the proposed techniques using accelerator-based time-of-flight measurements and then demonstrate them by unfolding the Watt spectrum from measurement with a 252Cf neutron source.

40 CFR 52.1031 - EPA-approved Maine regulations.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... 100 5/7/79 1/3/80 45 FR 6784 (c)(10) PSD Plan Only. 100 Definitions Regulations 12/24/79 2/19/80 45 FR...) Adopts PSD increments based on PM10, in place of increments based on TSP. 111 Petroleum Liquid Storage... for PM10. 115 Emission License Regulation. 5/7/79 1/30/80 45 FR 6784 (c)(10) PSD 12/24/79 2/19/80 45...

Simulated and Real Sheet-of-Light 3D Object Scanning Using a-Si:H Thin Film PSD Arrays.

PubMed

Contreras, Javier; Tornero, Josep; Ferreira, Isabel; Martins, Rodrigo; Gomes, Luis; Fortunato, Elvira

2015-11-30

A MATLAB/SIMULINK software simulation model (structure and component blocks) has been constructed in order to view and analyze the potential of the PSD (Position Sensitive Detector) array concept technology before it is further expanded or developed. This simulation allows changing most of its parameters, such as the number of elements in the PSD array, the direction of vision, the viewing/scanning angle, the object rotation, translation, sample/scan/simulation time, etc. In addition, results show for the first time the possibility of scanning an object in 3D when using an a-Si:H thin film 128 PSD array sensor and hardware/software system. Moreover, this sensor technology is able to perform these scans and render 3D objects at high speeds and high resolutions when using a sheet-of-light laser within a triangulation platform. As shown by the simulation, a substantial enhancement in 3D object profile image quality and realism can be achieved by increasing the number of elements of the PSD array sensor as well as by achieving an optimal position response from the sensor since clearly the definition of the 3D object profile depends on the correct and accurate position response of each detector as well as on the size of the PSD array.

Puffy skin disease (PSD) in rainbow trout, Oncorhynchus mykiss (Walbaum): a case definition.

PubMed

Maddocks, C E; Nolan, E T; Feist, S W; Crumlish, M; Richards, R H; Williams, C F

2015-07-01

Puffy skin disease (PSD) is a disease that causes skin pathology in rainbow trout, Oncorhynchus mykiss (Walbaum). Incidence of PSD in UK fish farms and fisheries has increased sharply in the last decade, with growing concern from both industry sectors. This paper provides the first comprehensive case definition of PSD, combining clinical and pathological observations of diseased rainbow trout from both fish farms and fisheries. The defining features of PSD, as summarized in the case definition, were focal lateral flank skin lesions that appeared as cutaneous swelling with pigment loss and petechiae. These were associated with lethargy, poor body condition, inappetance and low level mortality. Epidermal hyperplasia and spongiosis, oedema of the dermis stratum spongiosum and a mild diffuse inflammatory cellularity were typical in histopathology of skin. A specific pathogen or aetiology was not identified. Prevalence and severity of skin lesions was greatest during late summer and autumn, with the highest prevalence being 95%. Atypical lesions seen in winter and spring were suggestive of clinical resolution. PSD holds important implications for both trout aquaculture and still water trout fisheries. This case definition will aid future diagnosis, help avoid confusion with other skin conditions and promote prompt and consistent reporting. © 2014 John Wiley & Sons Ltd.

PDZ Ligand Binding-Induced Conformational Coupling of the PDZ-SH3-GK Tandems in PSD-95 Family MAGUKs.

PubMed

Zeng, Menglong; Ye, Fei; Xu, Jia; Zhang, Mingjie

2018-01-05

Discs large (DLG) MAGUKs are abundantly expressed in glutamatergic synapses, crucial for synaptic transmission, and plasticity by anchoring various postsynaptic components including glutamate receptors, downstream scaffold proteins and signaling enzymes. Different DLG members have shared structures and functions, but also contain unique features. How DLG family proteins function individually and cooperatively is largely unknown. Here, we report that PSD-95 PDZ3 directly couples with SH3-GK tandem in a PDZ ligand binding-dependent manner, and the coupling can promote PSD-95 dimerization and multimerization. Aided by sortase-mediated protein ligation and selectively labeling, we elucidated the PDZ3/SH3-GK conformational coupling mechanism using NMR spectroscopy. We further demonstrated that PSD-93, but not SAP102, can also undergo PDZ3 ligand binding-induced conformational coupling with SH3-GK and form homo-oligomers. Interestingly, PSD-95 and PSD-93 can also form ligand binding-induced hetero-oligomers, suggesting a cooperative assembly mechanism for the mega-N-methyl-d-aspartate receptor synaptic signaling complex. Finally, we provide evidence showing that ligand binding-induced conformational coupling between PDZ and SH3-GK is a common feature for other MAGUKs including CASK and PALS1. Copyright © 2017 Elsevier Ltd. All rights reserved.

In-Flight Vibration Environment of the NASA F-15B Flight Test Fixture

NASA Technical Reports Server (NTRS)

Corda, Stephen; Franz, Russell J.; Blanton, James N.; Vachon, M. Jake; DeBoer, James B.

2002-01-01

Flight vibration data are analyzed for the NASA F-15B/Flight Test Fixture II test bed. Understanding the in-flight vibration environment benefits design and integration of experiments on the test bed. The power spectral density (PSD) of accelerometer flight data is analyzed to quantify the in-flight vibration environment from a frequency of 15 Hz to 1325 Hz. These accelerometer data are analyzed for typical flight conditions and maneuvers. The vibration data are compared to flight-qualification random vibration test standards. The PSD levels in the lateral axis generally are greater than in the longitudinal and vertical axes and decrease with increasing frequency. At frequencies less than approximately 40 Hz, the highest PSD levels occur during takeoff and landing. Peaks in the PSD data for the test fixture occur at approximately 65, 85, 105-110, 200, 500, and 1000 Hz. The pitch-pulse and 2-g turn maneuvers produce PSD peaks at 115 Hz. For cruise conditions, the PSD level of the 85-Hz peak is greatest for transonic flight at Mach 0.9. From 400 Hz to 1325 Hz, the takeoff phase has the highest random vibration levels. The flight-measured vibration levels generally are substantially lower than the random vibration test curve.

Neutron/gamma pulse shape discrimination (PSD) in plastic scintillators with digital PSD electronics

NASA Astrophysics Data System (ADS)

Hutcheson, Anthony L.; Simonson, Duane L.; Christophersen, Marc; Phlips, Bernard F.; Charipar, Nicholas A.; Piqué, Alberto

2013-05-01

Pulse shape discrimination (PSD) is a common method to distinguish between pulses produced by gamma rays and neutrons in scintillator detectors. This technique takes advantage of the property of many scintillators that excitations by recoil protons and electrons produce pulses with different characteristic shapes. Unfortunately, many scintillating materials with good PSD properties have other, undesirable properties such as flammability, toxicity, low availability, high cost, and/or limited size. In contrast, plastic scintillator detectors are relatively low-cost, and easily handled and mass-produced. Recent studies have demonstrated efficient PSD in plastic scintillators using a high concentration of fluorescent dyes. To further investigate the PSD properties of such systems, mixed plastic scintillator samples were produced and tested. The addition of up to 30 wt. % diphenyloxazole (DPO) and other chromophores in polyvinyltoluene (PVT) results in efficient detection with commercial detectors. These plastic scintillators are produced in large diameters up to 4 inches by melt blending directly in a container suitable for in-line detector use. This allows recycling and reuse of materials while varying the compositions. This strategy also avoids additional sample handling and polishing steps required when using removable molds. In this presentation, results will be presented for different mixed-plastic compositions and compared with known scintillating materials

Characterization and genetic mapping of a Photoperiod-sensitive dwarf 1 locus in rice (Oryza sativa L.).

PubMed

Li, Riqing; Xia, Jixing; Xu, Yiwei; Zhao, Xiucai; Liu, Yao-Guang; Chen, Yuanling

2014-01-01

Plant height is an important agronomic trait for crop architecture and yield. Most known factors determining plant height function in gibberellin or brassinosteroid biosynthesis or signal transduction. Here, we report a japonica rice (Oryza sativa ssp. japonica) dominant dwarf mutant, Photoperiod-sensitive dwarf 1 (Psd1). The Psd1 mutant showed impaired cell division and elongation, and a severe dwarf phenotype under long-day conditions, but nearly normal growth in short-day. The plant height of Psd1 mutant could not be rescued by gibberellin or brassinosteroid treatment. Genetic analysis with R1 and F2 populations determined that Psd1 phenotype was controlled by a single dominant locus. Linkage analysis with 101 tall F2 plants grown in a long-day season, which were derived from a cross between Psd1 and an indica cultivar, located Psd1 locus on chromosome 1. Further fine-mapping with 1017 tall F2 plants determined this locus on an 11.5-kb region. Sequencing analysis of this region detected a mutation site in a gene encoding a putative lipid transfer protein; the mutation produces a truncated C-terminus of the protein. This study establishes the genetic foundation for understanding the molecular mechanisms regulating plant cell division and elongation mediated by interaction between genetic and environmental factors.

Nanoscale segregation of actin nucleation and elongation factors determines dendritic spine protrusion

PubMed Central

Chazeau, Anaël; Mehidi, Amine; Nair, Deepak; Gautier, Jérémie J; Leduc, Cécile; Chamma, Ingrid; Kage, Frieda; Kechkar, Adel; Thoumine, Olivier; Rottner, Klemens; Choquet, Daniel; Gautreau, Alexis; Sibarita, Jean-Baptiste; Giannone, Grégory

2014-01-01

Actin dynamics drive morphological remodeling of neuronal dendritic spines and changes in synaptic transmission. Yet, the spatiotemporal coordination of actin regulators in spines is unknown. Using single protein tracking and super-resolution imaging, we revealed the nanoscale organization and dynamics of branched F-actin regulators in spines. Branched F-actin nucleation occurs at the PSD vicinity, while elongation occurs at the tip of finger-like protrusions. This spatial segregation differs from lamellipodia where both branched F-actin nucleation and elongation occur at protrusion tips. The PSD is a persistent confinement zone for IRSp53 and the WAVE complex, an activator of the Arp2/3 complex. In contrast, filament elongators like VASP and formin-like protein-2 move outwards from the PSD with protrusion tips. Accordingly, Arp2/3 complexes associated with F-actin are immobile and surround the PSD. Arp2/3 and Rac1 GTPase converge to the PSD, respectively, by cytosolic and free-diffusion on the membrane. Enhanced Rac1 activation and Shank3 over-expression, both associated with spine enlargement, induce delocalization of the WAVE complex from the PSD. Thus, the specific localization of branched F-actin regulators in spines might be reorganized during spine morphological remodeling often associated with synaptic plasticity. PMID:25293574

Endonasal Operative Corridor Expansion by Sphenoidal Pneumosinus Dilatans in Tuberculum Sellae Meningiomas.

PubMed

Raheja, Amol; Karsy, Michael; Eli, Ilyas; Guan, Jian; Couldwell, William T

2017-10-01

A retrospective cohort study of patients with tuberculum sellae meningioma (TSM)-associated sphenoidal pneumosinus dilatans (PSD) over a recent epoch was evaluated using a propensity-matched morphometric analysis. A total of 38 patients with TSM and sphenoidal PSD were identified and matched by age and sex to 32 patients without tumors (controls). Overall, no significant difference between test and control groups was noted in sphenoid sinus size or other parameters; however, significantly greater mean distances from the posterior margin of the planum sphenoidale to the diaphragma sella (0.76 ± 0.23 vs. 1.03 ± 0.27, respectively; P = 0.0001) and angle between the planum sphenoidale to anterior face of sella turcica (113.41 ± 10.58 vs. 123.21 ± 12.55, respectively; P = 0.001) were seen in patients with TSM and PSD, suggestive of a selective expansion of the tuberculum sellae region. TSM/sphenoid sinus morphologies were divided into 3 types (A, B, and C) based on the extent of tumor and sinus morphology. There was progressive increase in tumor volume and anteroposterior sinus diameter from sphenoidal PSD types A-C, which influenced selection of surgical approach. This study suggests that TSM-associated sphenoidal PSD leads to more selective splaying of the tuberculum sellae region rather than cumulative increase in sinus volume. This may lead to operative corridor expansion for endonasal access to TSM associated with sphenoidal PSD. A radiologic classification scheme for sphenoidal PSD associated with TSM is suggested that may aid surgical decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petrik, Nikolay G.; Henderson, Michael A.; Kimmel, Gregory A.

Angle-resolved photon stimulated desorption (PSD) combined with infrared reflection-adsorption spectroscopy and temperature programmed desorption reveal two distinct channels in the photochemistry of acetone on rutile TiO₂(110) surface. During UV irradiation of co-adsorbed oxygen and acetone molecules, methyl radicals (CH₃) are ejected in two different directions: i) normal to the surface and ii) off-normal at ~±66° to the surface normal in the azimuth (i.e. perpendicular to the rows of bridging oxygen and Ti atoms). Both components are relatively narrow and non-cosine, indicating non-thermal evolution of CH₃ radicals. The direction of the “off-normal” PSD component is consistent with orientation of the C–CH₃more » bonds in the n²-acetone diolate—a photoactive form of acetone chemisorption on the oxidized TiO₂(110) surface proposed earlier from experimental and theoretical studies. The direction of the “normal” PSD component requires an orientation of a C–CH₃ bond which is not consistent with the n²-acetone diolate structure. The angular distribution of the CH₃ PSD depends on the acetone coverage. The “off-normal” PSD component dominates at lower acetone coverage (< 0.2 ML), but does not increase at higher coverages in accord with the acetone diolate peak intensity in the infrared reflection-absorption spectra. The “normal” PSD component grows with the acetone coverage up to 0.6 ML. The newly discovered “normal” PSD channel is tentatively assigned to a photo-produced n²- acetone enolate as a potential precursor based on the H/D exchange experiments« less

Predictivity of Early Depressive Symptoms for Post-Stroke Depression.

PubMed

Lewin-Richter, A; Volz, M; Jöbges, M; Werheid, K

2015-08-01

Depression is a frequent complication after stroke. However, little is known about the predictive value of early self-reported depressive symptoms (DS) for later development of post-stroke depression (PSD) 6 months after discharge. Using a prospective longitudinal design, we investigated the prevalence of DS and examined their predictive value for depressive disorders 6 months after stroke while statistically controlling major established PSD risk factors. During inpatient rehabilitation, 96 stroke patients were screened for DS. After 6 months, 71 patients were attainable for a follow-up. DS was assessed using the 15-item Geriatric Depression Scale (GDS-15). At follow-up a telephone interview that included the Structured Clinical Interview for Psychiatric Disorders (SCID), which is based on DSM-IV criteria, and the GDS-15 was conducted. Patients with major depression (MD) at the follow-up were considered to have PSD. Regression analyses were conducted to examine the influence of early DS on PSD after 6 months while controlling for age, premorbid depression, and functional and cognitive impairments. The percentage of patients who scored above the GDS-15 cut-off for clinically relevant DS increased significantly, from 37% to 44%, after 6 months. According to the SCID, 27% of stroke patients fulfilled the criteria for MD, and another 16% fulfilled those for minor depression. Logistic regression showed that DS at baseline significantly predicted PSD at follow-up (odds ratio: 1.43; 95% CI: 1.15-1.8). Self-reported DS during inpatient rehabilitation are predictive for PSD 6 months after discharge. Assessment of early DS contributes to identifying stroke patients at risk for PSD, thereby facilitating prevention and treatment.

Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders.

PubMed

Redle, Erin; Vannest, Jennifer; Maloney, Thomas; Tsevat, Rebecca K; Eikenberry, Sarah; Lewis, Barbara; Shriberg, Lawrence D; Tkach, Jean; Holland, Scott K

2015-02-09

Children with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. This case-control study included 12 children with PSD (mean age 7.42 years, four female) and 12 controls (mean age 7.44 years, four female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. Children with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. Over-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD. Copyright © 2014 Elsevier B.V. All rights reserved.

Paid sick days and stay-at-home behavior for influenza

PubMed Central

Piper, Kaitlin; Youk, Ada; James, A. Everette

2017-01-01

Access to paid sick days (PSD) differs by workplace size, race/ethnicity, gender, and income in the United States. It is not known to what extent decisions to stay home from work when sick with infectious illnesses such as influenza depend on PSD access, and whether access impacts certain demographic groups more than others. We examined demographic and workplace characteristics (including access to PSD) associated with employees’ decisions to stay home from work for their own or a child’s illness. Linking the 2009 Medical Expenditure Panel Survey (MEPS) consolidated data file to the medical conditions file, we used multivariate Poisson regression models with robust variance estimates to identify factors associated with missed work for an employee’s own or a child’s illness/injury, influenza-like-illness (ILI), and influenza. Controlling for gender, race/ethnicity, education, and income, access to PSD was associated with a higher probability of staying home for an employee’s own illness/injury, ILI, or influenza, and for a child’s illness/injury. Hispanic ethnicity was associated with a lower prevalence of staying home for the employee’s own or a child’s illness compared to non-Hispanic Whites. Access to PSD was associated with a significantly greater increase in the probability of staying home among Hispanics than among non-Hispanic Whites. Women had a significantly higher probability of staying home for their child’s illness compared to men, suggesting that women remain the primary caregivers for ill children. Our results indicate that PSD access is important to encourage employees to stay home from work when sick with ILI or influenza. Also, PSD access may be important to enable stay-at-home behavior among Hispanics. We conclude that access to PSD is likely to reduce the spread of disease in workplaces by increasing the rate at which sick employees stay home from work, and reduce the economic burden of staying home on minorities, women, and families. PMID:28151940

Paid sick days and stay-at-home behavior for influenza.

PubMed

Piper, Kaitlin; Youk, Ada; James, A Everette; Kumar, Supriya

2017-01-01

Access to paid sick days (PSD) differs by workplace size, race/ethnicity, gender, and income in the United States. It is not known to what extent decisions to stay home from work when sick with infectious illnesses such as influenza depend on PSD access, and whether access impacts certain demographic groups more than others. We examined demographic and workplace characteristics (including access to PSD) associated with employees' decisions to stay home from work for their own or a child's illness. Linking the 2009 Medical Expenditure Panel Survey (MEPS) consolidated data file to the medical conditions file, we used multivariate Poisson regression models with robust variance estimates to identify factors associated with missed work for an employee's own or a child's illness/injury, influenza-like-illness (ILI), and influenza. Controlling for gender, race/ethnicity, education, and income, access to PSD was associated with a higher probability of staying home for an employee's own illness/injury, ILI, or influenza, and for a child's illness/injury. Hispanic ethnicity was associated with a lower prevalence of staying home for the employee's own or a child's illness compared to non-Hispanic Whites. Access to PSD was associated with a significantly greater increase in the probability of staying home among Hispanics than among non-Hispanic Whites. Women had a significantly higher probability of staying home for their child's illness compared to men, suggesting that women remain the primary caregivers for ill children. Our results indicate that PSD access is important to encourage employees to stay home from work when sick with ILI or influenza. Also, PSD access may be important to enable stay-at-home behavior among Hispanics. We conclude that access to PSD is likely to reduce the spread of disease in workplaces by increasing the rate at which sick employees stay home from work, and reduce the economic burden of staying home on minorities, women, and families.

Post-synaptic Density-95 (PSD-95) Binding Capacity of G-protein-coupled Receptor 30 (GPR30), an Estrogen Receptor That Can Be Identified in Hippocampal Dendritic Spines*

PubMed Central

Akama, Keith T.; Thompson, Louisa I.; Milner, Teresa A.; McEwen, Bruce S.

2013-01-01

The estrogen 17β-estradiol (E2) modulates dendritic spine plasticity in the cornu ammonis 1 (CA1) region of the hippocampus, and GPR30 (G-protein coupled estrogen receptor 1 (GPER1)) is an estrogen-sensitive G-protein-coupled receptor (GPCR) that is expressed in the mammalian brain and in specific subregions that are responsive to E2, including the hippocampus. The subcellular localization of hippocampal GPR30, however, remains unclear. Here, we demonstrate that GPR30 immunoreactivity is detected in dendritic spines of rat CA1 hippocampal neurons in vivo and that GPR30 protein can be found in rat brain synaptosomes. GPR30 immunoreactivity is identified at the post-synaptic density (PSD) and in the adjacent peri-synaptic zone, and GPR30 can associate with the spine scaffolding protein PSD-95 both in vitro and in vivo. This PSD-95 binding capacity of GPR30 is specific and determined by the receptor C-terminal tail that is both necessary and sufficient for PSD-95 interaction. The interaction with PSD-95 functions to increase GPR30 protein levels residing at the plasma membrane surface. GPR30 associates with the N-terminal tandem pair of PDZ domains in PSD-95, suggesting that PSD-95 may be involved in clustering GPR30 with other receptors in the hippocampus. We demonstrate that GPR30 has the potential to associate with additional post-synaptic GPCRs, including the membrane progestin receptor, the corticotropin releasing hormone receptor, and the 5HT1a serotonin receptor. These data demonstrate that GPR30 is well positioned in the dendritic spine compartment to integrate E2 sensitivity directly onto multiple inputs on synaptic activity and might begin to provide a molecular explanation as to how E2 modulates dendritic spine plasticity. PMID:23300088

Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled receptor 30 (GPR30), an estrogen receptor that can be identified in hippocampal dendritic spines.

PubMed

Akama, Keith T; Thompson, Louisa I; Milner, Teresa A; McEwen, Bruce S

2013-03-01

The estrogen 17β-estradiol (E2) modulates dendritic spine plasticity in the cornu ammonis 1 (CA1) region of the hippocampus, and GPR30 (G-protein coupled estrogen receptor 1 (GPER1)) is an estrogen-sensitive G-protein-coupled receptor (GPCR) that is expressed in the mammalian brain and in specific subregions that are responsive to E2, including the hippocampus. The subcellular localization of hippocampal GPR30, however, remains unclear. Here, we demonstrate that GPR30 immunoreactivity is detected in dendritic spines of rat CA1 hippocampal neurons in vivo and that GPR30 protein can be found in rat brain synaptosomes. GPR30 immunoreactivity is identified at the post-synaptic density (PSD) and in the adjacent peri-synaptic zone, and GPR30 can associate with the spine scaffolding protein PSD-95 both in vitro and in vivo. This PSD-95 binding capacity of GPR30 is specific and determined by the receptor C-terminal tail that is both necessary and sufficient for PSD-95 interaction. The interaction with PSD-95 functions to increase GPR30 protein levels residing at the plasma membrane surface. GPR30 associates with the N-terminal tandem pair of PDZ domains in PSD-95, suggesting that PSD-95 may be involved in clustering GPR30 with other receptors in the hippocampus. We demonstrate that GPR30 has the potential to associate with additional post-synaptic GPCRs, including the membrane progestin receptor, the corticotropin releasing hormone receptor, and the 5HT1a serotonin receptor. These data demonstrate that GPR30 is well positioned in the dendritic spine compartment to integrate E2 sensitivity directly onto multiple inputs on synaptic activity and might begin to provide a molecular explanation as to how E2 modulates dendritic spine plasticity.

76 FR 54410 - Approval and Promulgation of Air Quality Implementation Plans; Commonwealth of Pennsylvania...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

...), (G), (H), (J), (K), (L), and (M), or portions thereof; and the following infrastructure elements for the 2006 PM 2.5 NAAQS: 110(a)(2)(A), (B), (C), (D), (E), (F), (G), (H), (J), (K), (L), and (M), or..., K, L, M. G, H, J , K, L, M. December 7, 2007 D(i)(II)PSD D(i)(II)PSD. June 6, 2008 C, D(i)(II)PSD, J...

Measurement of particle size distribution in mammalian cells in vitro by use of polarized light spectroscopy

NASA Astrophysics Data System (ADS)

Bartlett, Matthew; Huang, George; Larcom, Lyndon; Jiang, Huabei

2004-02-01

We demonstrate the feasibility of measuring the particle size distribution (PSD) of internal cell structures in vitro. We use polarized light spectroscopy to probe the internal morphology of mammalian breast cancer (MCF7) and cervical cancer (Siha) cells. We find that graphing the least-squared error versus the scatterer size provides insight into cell scattering. A nonlinear optimization scheme is used to determine the PSD iteratively. The results suggest that 2-μm particles (possibly the mitochondria) contribute most to the scattering. Other subcellular structures, such as the nucleoli and the nucleus, may also contribute significantly. We reconstruct the PSD of the mitochondria, as verified by optical microscopy. We also demonstrate the angle dependence of the PSD.

Particle size distribution control of Pt particles used for particle gun

NASA Astrophysics Data System (ADS)

Ichiji, M.; Akiba, H.; Nagao, H.; Hirasawa, I.

2017-07-01

The purpose of this study is particle size distribution (PSD) control of submicron sized Pt particles used for particle gun. In this report, simple reaction crystallization is conducted by mixing H2PtCl6 and ascorbic acid. Without the additive, obtained Pt particles have broad PSD and reproducibility of experiment is low. With seeding, Pt particles have narrow PSD and reproducibility improved. Additionally, mean particle diameter of 100-700 nm is controlled by changing seeding amount. Obtained particles are successfully characterized as Pt by XRD results. Moreover, XRD spectra indicate that obtained particles are polycrystals. These experimental results suggest that seeding consumed nucleation, as most nuclei attached on the seed surface. This mechanism virtually restricted nucleation to have narrow PSD can be obtained.

Technical Note: Evaluation of plastic scintillator detector for small field stereotactic patient-specific quality assurance.

PubMed

Qin, Yujiao; Gardner, Stephen J; Kim, Joshua; Huang, Yimei; Wen, Ning; Doemer, Anthony; Chetty, Indrin J

2017-10-01

To evaluate the performance of a commercial plastic scintillator detector (PSD) for small-field stereotactic patient-specific quality assurance (QA) measurements using flattening-filter-free beam. A total of 10 spherical targets [volume range: (0.03 cc-2 cc)] were planned with two techniques: (a) dynamic conformal arc (DCA-10 plans) and (b) volumetric modulated arc therapy (VMAT-10 plans). All plans were generated using Varian Eclipse treatment planning system, and AcurosXB v.13 algorithm in 1.0 mm grid size. Additionally, 14 previously treated cranial and spine SRS plans were evaluated [6 DCA, 8 VMAT, volume range: (0.04 cc-119.02 cc)]. Plan modulation was quantified via two metrics: MU per prescription dose (MU/Rx) and Average Leaf Pair Opening (ALPO). QA was performed on the Varian Edge linear accelerator equipped with HDMLC. Three detectors were used: (a) PinPoint ion chamber (PTW; active volume 0.015 cc), (b) Exradin W1 PSD (Standard Imaging; active volume 0.002 cc), and (c) Gafchromic EBT3 film (Ashland). PinPoint chamber and PSD were positioned perpendicular to beam axis in a Lucy phantom (Standard Imaging); films were placed horizontally capturing the coronal plane. PSD, film, and PinPoint chamber measured average differences of 1.00 ± 1.54%, 1.30 ± 1.69%, and -0.66 ± 2.36%, respectively, compared to AcurosXB dose calculation. As the target volume decreased, PinPoint chamber measured lower doses (maximum -5.07% at 0.07 cc target), while PSD and film measured higher doses (2.87% and 2.54% at 0.03 cc target) than AcurosXB. Film agreed with the benchmark detector PSD by an average difference of 0.31 ± 1.20%, but suffered from larger uncertainty; PinPoint chamber underestimated dose by more than 4% for targets smaller than 0.2 cc. Taking PSD as the measurement standard, DCA plans achieved good QA results across all volumes studied, with an average of -0.07 ± 0.89%; for VMAT plans, PSD measured consistently higher dose (1.95 ± 1.36%) than AcurosXB. Correlation study revealed that plan modulation quantified by both MU/Rx and ALPO correlated significantly with QA results. Among all three detectors, PSD demonstrated superior performances in plans with small fields and heavy modulation. High consistency and low uncertainty made PSD a suitable detector for clinical routine SRS QA. PinPoint chamber should be avoided for targets smaller than 0.2 cc; film dosimetry can be utilized with careful evaluation of its uncertainty bracket. Compared to PSD measurements, AcurosXB calculation demonstrated high accuracy for nonmodulated small fields. The positive correlation between plan modulation and QA discrepancy calls for our attention for clinical SRS plans with high modulation. © 2017 American Association of Physicists in Medicine.

SU-G-TeP2-08: Evaluation of Plastic Scintillator Detector for Small Field Stereotactic Patient-Specific Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Y; Gardner, S; Huang, Y

Purpose: To evaluate the performance of a commercial plastic scintillator detector (PSD) for small-field stereotactic patient-specific quality assurance using flattening-filter-free (FFF) beams. Methods: A total of ten spherical targets (volume range:[0.03cc–2cc]) were planned using Dynamic Conformal Arc(DCA-10 plans) and Volumetric Modulated Arc Therapy(VMAT-10 plans) techniques in Eclipse(AAA v.11, 1mm dose calculation grid size). Additionally, 15 previously-treated cranial and spine SRS plans were evaluated (6 DCA, 9 VMAT, volume range:[0.04cc–119.02cc]). All measurements were acquired using Varian Edge equipped with HDMLC. Three detectors were used: PinPoint ion chamber (PTW;active volume 0.015cc), Exradin W1 PSD (Standard Imaging;active volume 0.002cc), and Gafchromic EBT3 filmmore » (Ashland). PinPoint and PSD were positioned perpendicular to beam axis in a Lucy phantom (Standard Imaging). Films were placed at isocenter in solid water. Calibration films were delivered for absolute dose analysis. Results: For large spherical targets(>1.5cc) with DCA, all detectors agreed within 1% of AAA calculations. As target volume decreased, PSD measured higher doses than AAA (maximum difference: 3.3% at 0.03cc target), while PinPoint chamber measured lower doses (maximum difference:-3.8% at 0.03cc target). Inter-detector differences between pinpoint and PSD increased with decreasing target size; differences>5% were observed for targets<0.09cc. Similar trends for inter-detector behavior were observed for clinical plans. For target sizes<0.08cc, PSD measured>5% higher dose than PinPoint chamber (maximum difference: 9.25% at 0.04cc target). Film demonstrated agreement of −0.19±1.47% with PSD for all spherical targets, and agreement within −0.98±2.25% for all 15 clinical targets. Unlike DCA, VMAT plans did not show improved AAA-to-detector agreements for large targets. Conclusion: For all targets, the PSD measurements agreed with film within 1.0%, on average. For small volume targets (<0.10cc), PSD agreed with film but measured significantly higher doses (>5%) compared with the pin point ion chamber. The plastic scintillator detector appears to be suitable for accurate measurements of small SRS targets.« less

The role of PSD-95 in the rearrangement of Kv1.3 channels to the immunological synapse.

PubMed

Szilágyi, Orsolya; Boratkó, Anita; Panyi, György; Hajdu, Péter

2013-09-01

Establishment of the immunological synapse (IS) between T lymphocytes and antigen-presenting cells is a key step in the adaptive immune response. Several proteins accumulate in the IS, such as the Kv1.3 potassium channel; however, the mechanism of this translocation is unknown. PSD-95 and SAP97 are adaptor proteins that regulate the polarized cell surface expression and localization of Kv1 channels in neurons. We investigated whether these proteins affect the redistribution of Kv1.3 into the IS in non-excitable human T cells. We show here that PSD-95 and SAP97 are expressed in Jurkat and interact with the C terminus of Kv1.3. Disruption of the interaction between PSD-95 or SAP97 and Kv1.3 in Jurkat was realized by the expression of a C-terminal truncated Kv1.3, which lacks the binding domain for these proteins, or by the knockdown of the expression of PSD-95 or SAP97 using specific shRNA. Expression of the truncated Kv1.3 or knockdown of PSD-95, but not the knockdown of SAP97, inhibited the recruitment of Kv1.3 into the IS; the fraction of cells showing polarized Kv1.3 expression upon engagement in an IS was significantly lower than in control cells expressing the full-length Kv1.3, and the rearrangement of Kv1.3 did not show time dependence. In contrast, Jurkat cells expressing the full-length channel showed marked time dependence in the recruitment into the IS peaking at 1 min after the conjugation of the cells. These results demonstrate that PSD-95 participates in the targeting of Kv1.3 into the IS, implying its important role in human T-cell activation.

Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia

PubMed Central

Catts, Vibeke Sørensen; Derminio, Dominique Suzanne; Hahn, Chang-Gyu; Weickert, Cynthia Shannon

2015-01-01

Background: There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Our group recently identified a decrease in total NR1 mRNA and protein expression in the dorsolateral prefrontal cortex in a case-control study of individuals with schizophrenia (n=37/group). The NR1 subunit is critical to NMDA receptor function at the postsynaptic density, a cellular structure rich in the scaffolding protein, PSD-95. The extent to which the NMDA receptor NR1 subunit is altered at the site of action, in the postsynaptic density, is not clear. Aims: To extend our previous results by measuring levels of NR1 and PSD-95 protein in postsynaptic density-enriched fractions of prefrontal cortex from the same individuals in the case-control study noted above. Methods: Postsynaptic density-enriched fractions were isolated from fresh-frozen prefrontal cortex (BA10) and subjected to western blot analysis for NR1 and PSD-95. Results: We found a 20% decrease in NR1 protein (t(66)=−2.874, P=0.006) and a 30% decrease in PSD-95 protein (t(63)=−2.668, P=0.010) in postsynaptic density-enriched fractions from individuals with schizophrenia relative to unaffected controls. Conclusions: Individuals with schizophrenia have less NR1 protein, and therefore potentially fewer functional NMDA receptors, at the postsynaptic density. The associated decrease in PSD-95 protein at the postsynaptic density suggests that not only are glutamate receptors compromised in individuals with schizophrenia, but the overall spine architecture and downstream signaling supported by PSD-95 may also be deficient. PMID:27336043

Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of the MAGUK GK domain.

PubMed

Xia, Yitian; Shang, Yuan; Zhang, Rongguang; Zhu, Jinwei

2017-08-10

The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodelling, which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), although the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing. In the present study, we determine the crystal structure of PSD-95 GK in complex with the MAP1A peptide at 2.6-Å resolution. The complex structure reveals that, unlike a linear and elongated conformation in the phosphor-peptide/GK complexes, the MAP1A peptide adopts a unique conformation with a stretch of hydrophobic residues far from each other in the primary sequence clustering and interacting with the 'hydrophobic site' of PSD-95 GK and a highly conserved aspartic acid of MAP1A (D2117) mimicking the phosphor-serine/threonine in binding to the 'phosphor-site' of PSD-95 GK. We demonstrate that the MAP1A peptide may undergo a conformational transition upon binding to PSD-95 GK. Further structural comparison of known DLG GK-mediated complexes reveals the target recognition specificity and versatility of DLG GKs. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Proteomic analysis of PSD-93 knockout mice following the induction of ischemic cerebral injury.

PubMed

Rong, Rong; Yang, Hui; Rong, Liangqun; Wei, Xiue; Li, Qingjie; Liu, Xiaomei; Gao, Hong; Xu, Yun; Zhang, Qingxiu

2016-03-01

Postsynaptic density protein-93 (PSD-93) is enriched in the postsynaptic density and is involved in N-methyl-d-aspartate receptor (NMDAR) triggered neurotoxicity through PSD-93/NMDAR/nNOS signaling pathway. In the present study, we found that PSD-93 deficiency reduced infarcted volume and neurological deficits induced by transient middle cerebral artery occlusion (tMCAO) in the mice. To identify novel targets of PSD-93 related neurotoxicity, we applied isobaric tags for relative and absolute quantitative (iTRAQ) labeling and combined this labeling with on-line two-dimensional LC/MS/MS technology to elucidate the changes in protein expression in PSD-93 knockout mice following tMCAO. The proteomic data set consisted of 1892 proteins. Compared to control group, differences in expression levels in ischemic group >1.5-fold and <0.66-fold were considered as differential expression. A total of 104 unique proteins with differential abundance levels were identified, among which 17 proteins were selected for further validation. Gene ontology analysis using UniProt database revealed that these differentially expressed proteins are involved in diverse function such as synaptic transmission, neuronal neurotransmitter and ion transport, modification of organelle membrane components. Moreover, network analysis revealed that the interacting proteins were involved in the transport of synaptic vesicles, the integrity of synaptic membranes and the activation of the ionotropic glutamate receptors NMDAR1 and NMDAR2B. Finally, RT-PCR and Western blot analysis showed that SynGAP, syntaxin-1A, protein kinase C β, and voltage-dependent L-type calcium channels were inhibited by ischemia-reperfusion. Identification of these proteins provides valuable clues to elucidate the mechanisms underlying the actions of PSD-93 in ischemia-reperfusion induced neurotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression of the postsynaptic scaffold PSD-95 and development of synaptic physiology during giant terminal formation in the auditory brainstem of the chicken.

PubMed

Goyer, David; Fensky, Luisa; Hilverling, Anna Maria; Kurth, Stefanie; Kuenzel, Thomas

2015-05-01

In the avian nucleus magnocellularis (NM) endbulb of Held giant synapses develop from temporary bouton terminals. The molecular regulation of this process is not well understood. Furthermore, it is unknown how the postsynaptic specialization of the endbulb synapses develops. We therefore analysed expression of the postsynaptic scaffold protein PSD-95 during the transition from bouton-to-endbulb synapses. PSD-95 has been implicated in the regulation of the strength of glutamatergic synapses and could accordingly be of functional relevance for giant synapse formation. PSD-95 protein was expressed at synaptic sites in embryonic chicken auditory brainstem and upregulated between embryonic days (E)12 and E16. We applied immunofluorescence staining and confocal microscopy to quantify pre-and postsynaptic protein signals during bouton-to-endbulb transition. Giant terminal formation progressed along the tonotopic axis in NM, but was absent in low-frequency NM. We found a tonotopic gradient of postsynaptic PSD-95 signals in NM. Furthermore, PSD-95 immunosignals showed the greatest increase between E12 and E15, temporally preceding the bouton-to-endbulb transition. We then applied whole-cell electrophysiology to measure synaptic currents elicited by synaptic terminals during bouton-to-endbulb transition. With progressing endbulb formation postsynaptic currents rose more rapidly and synapses were less susceptible to short-term depression, but currents were not different in amplitude or decay-time constant. We conclude that development of presynaptic specializations follows postsynaptic development and speculate that the early PSD-95 increase could play a functional role in endbulb formation. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia.

PubMed

Catts, Vibeke Sørensen; Derminio, Dominique Suzanne; Hahn, Chang-Gyu; Weickert, Cynthia Shannon

2015-01-01

There is converging evidence of involvement of N-methyl-d-aspartate (NMDA) receptor hypofunction in the pathophysiology of schizophrenia. Our group recently identified a decrease in total NR1 mRNA and protein expression in the dorsolateral prefrontal cortex in a case-control study of individuals with schizophrenia (n=37/group). The NR1 subunit is critical to NMDA receptor function at the postsynaptic density, a cellular structure rich in the scaffolding protein, PSD-95. The extent to which the NMDA receptor NR1 subunit is altered at the site of action, in the postsynaptic density, is not clear. To extend our previous results by measuring levels of NR1 and PSD-95 protein in postsynaptic density-enriched fractions of prefrontal cortex from the same individuals in the case-control study noted above. Postsynaptic density-enriched fractions were isolated from fresh-frozen prefrontal cortex (BA10) and subjected to western blot analysis for NR1 and PSD-95. We found a 20% decrease in NR1 protein (t(66)=-2.874, P=0.006) and a 30% decrease in PSD-95 protein (t(63)=-2.668, P=0.010) in postsynaptic density-enriched fractions from individuals with schizophrenia relative to unaffected controls. Individuals with schizophrenia have less NR1 protein, and therefore potentially fewer functional NMDA receptors, at the postsynaptic density. The associated decrease in PSD-95 protein at the postsynaptic density suggests that not only are glutamate receptors compromised in individuals with schizophrenia, but the overall spine architecture and downstream signaling supported by PSD-95 may also be deficient.

Effect of complex aerobic physical exercise on PSD-95 in the hippocampus and on cognitive function in juvenile mice

NASA Astrophysics Data System (ADS)

Satriani, W. H.; Redjeki, S.; Kartinah, N. T.

2017-08-01

Increased neuroplasticity induced by complex aerobic physical exercise is associated with improved cognitive function in adult mice. Increased cognitive function is assumed to be based on increased synapse formation. One of the regions of the brain that is important in cognitive function is the hippocampus, which plays a role in memory formation. Post synaptic density-95 (PSD-95) is an adhesion protein of the post-synaptic density scaffolding that is essential to synaptic stabilization. As we age, the PSD-95 molecule matures the synapses needed for the formation of the basic circuitry of the nervous system in the brain. However, during the growth period, synapse elimination is higher than its formation. This study aims to determine whether complex aerobic exercise can improve cognitive function and PSD-95 levels in the hippocampus of juvenile mice during their growth stage. The mice performed complex aerobic exercise starting at five weeks of age and continuing for seven weeks with a gradual increase of 8 m/min. At eight weeks it was increased to 10 m/min. The exercise was done for five days of each week. The subjects of the study were tested for cognition one week before being sacrificed (at 12 weeks). The PSD-95 in the hippocampus was measured with ELISA. The results showed that there was a significant difference in cognitive function, where p < 0.05, between the group that was given complex aerobic exercise and a control group that did not. However, the PSD-95 levels did not differ significantly between the two groups. The results of this study indicate that early complex aerobic exercise can improve cognitive ability in adulthood but does not increase the levels of PSD-95 in adults.

Power spectral density of a single Brownian trajectory: what one can and cannot learn from it

NASA Astrophysics Data System (ADS)

Krapf, Diego; Marinari, Enzo; Metzler, Ralf; Oshanin, Gleb; Xu, Xinran; Squarcini, Alessio

2018-02-01

The power spectral density (PSD) of any time-dependent stochastic process X t is a meaningful feature of its spectral content. In its text-book definition, the PSD is the Fourier transform of the covariance function of X t over an infinitely large observation time T, that is, it is defined as an ensemble-averaged property taken in the limit T\\to ∞ . A legitimate question is what information on the PSD can be reliably obtained from single-trajectory experiments, if one goes beyond the standard definition and analyzes the PSD of a single trajectory recorded for a finite observation time T. In quest for this answer, for a d-dimensional Brownian motion (BM) we calculate the probability density function of a single-trajectory PSD for arbitrary frequency f, finite observation time T and arbitrary number k of projections of the trajectory on different axes. We show analytically that the scaling exponent for the frequency-dependence of the PSD specific to an ensemble of BM trajectories can be already obtained from a single trajectory, while the numerical amplitude in the relation between the ensemble-averaged and single-trajectory PSDs is a fluctuating property which varies from realization to realization. The distribution of this amplitude is calculated exactly and is discussed in detail. Our results are confirmed by numerical simulations and single-particle tracking experiments, with remarkably good agreement. In addition we consider a truncated Wiener representation of BM, and the case of a discrete-time lattice random walk. We highlight some differences in the behavior of a single-trajectory PSD for BM and for the two latter situations. The framework developed herein will allow for meaningful physical analysis of experimental stochastic trajectories.

Studying the protein organization of the postsynaptic density by a novel solid phase- and chemical cross-linking-based technology.

PubMed

Liu, Szu-Heng; Cheng, Huei-Hsuan; Huang, San-Yuan; Yiu, Pei-Chun; Chang, Yen-Chung

2006-06-01

Agarose beads carrying a cleavable, fluorescent, and photoreactive cross-linking reagent on the surface were synthesized and used to selectively pull out the proteins lining the surface of supramolecules. A quantitative comparison of the abundances of various proteins in the sample pulled out by the beads from supramolecules with their original abundances could provide information on the spatial arrangement of these proteins in the supramolecule. The usefulness of these synthetic beads was successfully verified by trials using a synthetic protein complex consisting of three layers of different proteins on glass coverslips. By using these beads, we determined the interior or superficial locations of five major and 19 minor constituent proteins in the postsynaptic density (PSD), a large protein complex and the landmark structure of asymmetric synapses in the mammalian central nervous system. The results indicate that alpha,beta-tubulins, dynein heavy chain, microtubule-associated protein 2, spectrin, neurofilament H and M subunits, an hsp70 protein, alpha-internexin, dynamin, and PSD-95 protein reside in the interior of the PSD. Dynein intermediate chain, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors, kainate receptors, N-cadherin, beta-catenin, N-ethylmaleimide-sensitive factor, an hsc70 protein, and actin reside on the surface of the PSD. The results further suggest that the N-methyl-d-aspartate receptors and the alpha-subunits of calcium/calmodulin-dependent protein kinase II are likely to reside on the surface of the PSD although with unique local protein organizations. Based on our results and the known interactions between various PSD proteins from data mining, a model for the molecular organization of the PSD is proposed.

Subclinical keratoconus detection by pattern analysis of corneal and epithelial thickness maps with optical coherence tomography

PubMed Central

Li, Yan; Chamberlain, Winston; Tan, Ou; Brass, Robert; Weiss, Jack L.; Huang, David

2016-01-01

PURPOSE To screen for subclinical keratoconus by analyzing corneal, epithelial, and stromal thickness map patterns with Fourier-domain optical coherence tomography (OCT). SETTING Four centers in the United States. DESIGN Cross-sectional observational study. METHODS Eyes of normal subjects, subclinical keratoconus eyes, and the topographically normal eye of a unilateral keratoconus patient were studied. Corneas were scanned using a 26 000 Hz Fourier-domain OCT system (RTVue). Normal subjects were divided into training and evaluation groups. Corneal, epithelial, and stromal thickness maps and derived diagnostic indices, including pattern standard deviation (PSD) variables and pachymetric map–based keratoconus risk scores were calculated from the OCT data. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the diagnostic accuracy of the indices. RESULTS The study comprised 150 eyes of 83 normal subjects, 50 subclinical keratoconus eyes of 32 patients, and 1 topographically normal eye of a unilateral keratoconus patient. Subclinical keratoconus was characterized by inferotemporal thinning of the cornea, epithelium, and stroma. The PSD values for corneal (P < .001), epithelial (P < .001), and stromal (P = .049) thickness maps were all significantly higher in subclinical keratoconic eyes than in the normal group. The diagnostic accuracy was significantly higher for PSD variables (pachymetric PSD, AUC = 0.941; epithelial PSD, AUC = 0.985; stromal PSD, AUC = 0.924) than for the pachymetric map–based keratoconus risk score (AUC = 0.735). CONCLUSIONS High-resolution Fourier-domain OCT could map corneal, epithelial, and stromal thicknesses. Corneal and sublayer thickness changes in subclinical keratoconus could be detected with high accuracy using PSD variables. These new diagnostic variables might be useful in the detection of early keratoconus. PMID:27026454

Event-based total suspended sediment particle size distribution model

NASA Astrophysics Data System (ADS)

Thompson, Jennifer; Sattar, Ahmed M. A.; Gharabaghi, Bahram; Warner, Richard C.

2016-05-01

One of the most challenging modelling tasks in hydrology is prediction of the total suspended sediment particle size distribution (TSS-PSD) in stormwater runoff generated from exposed soil surfaces at active construction sites and surface mining operations. The main objective of this study is to employ gene expression programming (GEP) and artificial neural networks (ANN) to develop a new model with the ability to more accurately predict the TSS-PSD by taking advantage of both event-specific and site-specific factors in the model. To compile the data for this study, laboratory scale experiments using rainfall simulators were conducted on fourteen different soils to obtain TSS-PSD. This data is supplemented with field data from three construction sites in Ontario over a period of two years to capture the effect of transport and deposition within the site. The combined data sets provide a wide range of key overlooked site-specific and storm event-specific factors. Both parent soil and TSS-PSD in runoff are quantified by fitting each to a lognormal distribution. Compared to existing regression models, the developed model more accurately predicted the TSS-PSD using a more comprehensive list of key model input parameters. Employment of the new model will increase the efficiency of deployment of required best management practices, designed based on TSS-PSD, to minimize potential adverse effects of construction site runoff on aquatic life in the receiving watercourses.

Particle-size distribution (PSD) of pulverized hair: A quantitative approach of milling efficiency and its correlation with drug extraction efficiency.

PubMed

Chagas, Aline Garcia da Rosa; Spinelli, Eliani; Fiaux, Sorele Batista; Barreto, Adriana da Silva; Rodrigues, Silvana Vianna

2017-08-01

Different types of hair were submitted to different milling procedures and their resulting powders were analyzed by scanning electron microscopy (SEM) and laser diffraction (LD). SEM results were qualitative whereas LD results were quantitative and accurately characterized the hair powders through their particle size distribution (PSD). Different types of hair were submitted to an optimized milling conditions and their PSD was quite similar. A good correlation was obtained between PSD results and ketamine concentration in a hair sample analyzed by LC-MS/MS. Hair samples were frozen in liquid nitrogen for 5min and pulverized at 25Hz for 10min, resulting in 61% of particles <104μm and 39% from 104 to 1000μm. Doing so, a 359% increment on ketamine concentration was obtained for an authentic sample extracted after pulverization comparing with the same sample cut in 1mm fragments. When milling time was extended to 25min, >90% of particles were <60μm and an additional increment of 52.4% in ketamine content was obtained. PSD is a key feature on analysis of pulverized hair as it can affect the method recovery and reproducibility. In addition, PSD is an important issue on sample retesting and quality control procedures. Copyright © 2017 Elsevier B.V. All rights reserved.

Osseointegration of titanium implants functionalised with phosphoserine-tethered poly(epsilon-lysine) dendrons: a comparative study with traditional surface treatments in sheep.

PubMed

Stübinger, Stefan; Nuss, Katja; Bürki, Alexander; Mosch, Isabel; le Sidler, Miché; Meikle, Steve T; von Rechenberg, Brigitte; Santin, Matteo

2015-02-01

The aim of this study was to analyse the osseointegrative potential of phosphoserine-tethered dendrons when applied as surface functionalisation molecules on titanium implants in a sheep model after 2 and 8 weeks of implantation. Uncoated and dendron-coated implants were implanted in six sheep. Sandblasted and etched (SE) or porous additive manufactured (AM) implants with and without additional dendron functionalisation (SE-PSD; AM-PSD) were placed in the pelvic bone. Three implants per group were examined histologically and six implants were tested biomechanically. After 2 and 8 weeks the bone-to-implant contact (BIC) total values of SE implants (43.7±12.2; 53.3±9.0%) and SE-PSD (46.7±4.5; 61.7±4.9%) as well as AM implants (20.49±5.1; 43.9±9.7%) and AM-PSD implants (19.7±3.5; 48.3±15.6%) showed no statistically significant differences. For SE-PSD and AM-PSD a separate analysis of only the cancellous BIC demonstrated a statistically significant difference after 2 and 8 weeks. Biomechanical findings proved the overall increased stability of the porous implants after 8 weeks. Overall, the great effect of implant macro design on osseointegration was further supported by additional phosphoserine-tethered dendrons for SE and AM implants.

Precise-spike-driven synaptic plasticity: learning hetero-association of spatiotemporal spike patterns.

PubMed

Yu, Qiang; Tang, Huajin; Tan, Kay Chen; Li, Haizhou

2013-01-01

A new learning rule (Precise-Spike-Driven (PSD) Synaptic Plasticity) is proposed for processing and memorizing spatiotemporal patterns. PSD is a supervised learning rule that is analytically derived from the traditional Widrow-Hoff rule and can be used to train neurons to associate an input spatiotemporal spike pattern with a desired spike train. Synaptic adaptation is driven by the error between the desired and the actual output spikes, with positive errors causing long-term potentiation and negative errors causing long-term depression. The amount of modification is proportional to an eligibility trace that is triggered by afferent spikes. The PSD rule is both computationally efficient and biologically plausible. The properties of this learning rule are investigated extensively through experimental simulations, including its learning performance, its generality to different neuron models, its robustness against noisy conditions, its memory capacity, and the effects of its learning parameters. Experimental results show that the PSD rule is capable of spatiotemporal pattern classification, and can even outperform a well studied benchmark algorithm with the proposed relative confidence criterion. The PSD rule is further validated on a practical example of an optical character recognition problem. The results again show that it can achieve a good recognition performance with a proper encoding. Finally, a detailed discussion is provided about the PSD rule and several related algorithms including tempotron, SPAN, Chronotron and ReSuMe.

Precise-Spike-Driven Synaptic Plasticity: Learning Hetero-Association of Spatiotemporal Spike Patterns

PubMed Central

Yu, Qiang; Tang, Huajin; Tan, Kay Chen; Li, Haizhou

2013-01-01

A new learning rule (Precise-Spike-Driven (PSD) Synaptic Plasticity) is proposed for processing and memorizing spatiotemporal patterns. PSD is a supervised learning rule that is analytically derived from the traditional Widrow-Hoff rule and can be used to train neurons to associate an input spatiotemporal spike pattern with a desired spike train. Synaptic adaptation is driven by the error between the desired and the actual output spikes, with positive errors causing long-term potentiation and negative errors causing long-term depression. The amount of modification is proportional to an eligibility trace that is triggered by afferent spikes. The PSD rule is both computationally efficient and biologically plausible. The properties of this learning rule are investigated extensively through experimental simulations, including its learning performance, its generality to different neuron models, its robustness against noisy conditions, its memory capacity, and the effects of its learning parameters. Experimental results show that the PSD rule is capable of spatiotemporal pattern classification, and can even outperform a well studied benchmark algorithm with the proposed relative confidence criterion. The PSD rule is further validated on a practical example of an optical character recognition problem. The results again show that it can achieve a good recognition performance with a proper encoding. Finally, a detailed discussion is provided about the PSD rule and several related algorithms including tempotron, SPAN, Chronotron and ReSuMe. PMID:24223789

Efficacy of Cognitive Rehabilitation Therapy on Poststroke Depression among Survivors of First Stroke Attack in Ibadan, Nigeria.

PubMed

Olukolade, Olugbemi; Osinowo, Helen O

2017-01-01

Poststroke depression (PSD) is a common complication after stroke. There is no adequate treatment for PSD. This study examined efficacy of cognitive rehabilitation therapy (CRT) in the treatment of PSD among stroke survivors. An experimental design, 30 participants with poststroke depression were randomly assigned into 3 groups of cognitive rehabilitation therapy (CRT), psychoeducation (PE), and the control group (CG). CRT consisted of nine sessions with three-phased sessions focusing on activity stimulation, negative thoughts, and people contacts, PE consisted of nine sessions focusing on knowledge on stroke and poststroke depression, and the CG group was on the waiting list. The BDI scale was used for assessing PSD at posttest. There was a significant difference in the efficacy of CRT, PE, and the CG on PSD, with CRT-CG mean difference of -9.4 ± 3.11 and PE-CG 1.0 ± 3.83. Furthermore, stress was not a confounding variable on the efficacy of CRT. The type of therapy significantly influenced PSD at posttest, with the CRT having greater mean reduction to CG (-11.1 ± 3.1) than PE to the CG (3.0 ± 3.8). Cognitive rehabilitation therapy significantly reduced poststroke depression. Hence, it should be integrated as an adjunct treatment of poststroke depression.

PAUSED encodes the Arabidopsis exportin-t ortholog.

PubMed

Hunter, Christine A; Aukerman, Milo J; Sun, Hui; Fokina, Maria; Poethig, R Scott

2003-08-01

Los1p/exportin-t (XPOT) mediates the nuclear export of tRNAs in yeast and mammals. The requirements for this transport pathway are unclear, however, because los1 mutations do not affect yeast growth, and the phenotype of XPOT mutations in mammals is unknown. Here, we show that PAUSED (PSD) is the Arabidopsis ortholog of LOS1/XPOT and is capable of rescuing the tRNA export defect of los1 in Brewer's yeast (Saccharomyces cerevisiae), suggesting that its function has been conserved. Putative null alleles of PSD disrupt the initiation of the shoot apical meristem and delay leaf initiation after germination, the emergence of the radicle and lateral roots, and the transition to flowering. Plants doubly mutant for psd and hasty, the Arabidopsis ortholog of exportin 5, are viable but have a more severe phenotype than either single mutant. These results suggest that PSD plays a role in tRNA export in Arabidopsis, but that at least one-and perhaps several-additional tRNA export pathways also exist. The PSD transcript is broadly expressed during development and is alternatively spliced in the 3'-untranslated region. No temporal or spatial difference in the abundance of different splice forms was observed. We propose that the mutant phenotype of psd reflects defects in developmental events and cell/tissue types that require elevated levels of protein synthesis and are therefore acutely sensitive to a reduction in tRNA export.

Effects of Dimeric PSD-95 Inhibition on Excitotoxic Cell Death and Outcome After Controlled Cortical Impact in Rats.

PubMed

Sommer, Jens Bak; Bach, Anders; Malá, Hana; Gynther, Mikko; Bjerre, Ann-Sofie; Gram, Marie Gajhede; Marschner, Linda; Strømgaard, Kristian; Mogensen, Jesper; Pickering, Darryl S

2017-12-01

Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were investigated in order to assess uptake of the drug into the central nervous system of rats. After a controlled cortical impact rats were randomized to receive a single injection of either saline or two different doses of UCCB01-144 (10 or 20 mg/kg IV) immediately after injury. Spatial learning and memory were assessed in a water maze at 2 weeks post-trauma, and at 4 weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects of PSD-95 inhibitors in TBI are discussed.

Technical Note: Out‐of‐field dose measurement at near surface with plastic scintillator detector

PubMed Central

Bourgouin, Alexandra; Varfalvy, Nicolas

2016-01-01

Out‐of‐field dose depends on multiple factors, making peripheral dosimetry complex. Only a few dosimeters have the required features for measuring peripheral dose. Plastic scintillator dosimeters (PSDs) offer numerous dosimetric advantages as required for out‐of‐field dosimetry. The purpose of this study is to determine the potential of using PSD as a surface peripheral dosimeter. Measurements were performed with a parallel‐plate ion chamber, a small volume ion chamber, and with a PSD. Lateral‐dose measurements (LDM) at 0.5 cm depth and depth‐dose curve (PDD) were made and compared to the dose calculation provided by a treatment planning system (TPS). This study shows that a PSD can measure a dose as low as 0.51±0.17cGy for photon beam and 0.58±0.20cGy for electron beam with a difference of 0.2 and 0.1 cGy compared to a parallel‐plate ion chamber. This study demonstrates the potential of using PSD as an out‐of‐field dosimeter since measurements with PSD avoid averaging over a too‐large depth, at 1 mm diameter, and can make precise measurement at very low dose. Also, electronic equilibrium is easier to reach with PSD due to its small sensitive volume and its water equivalence. PACS number(s): 87.55.N, 87.55.km PMID:27685131

Partial sleep deprivation by environmental noise increases food intake and body weight in obesity resistant rats

PubMed Central

Mavanji, Vijayakumar; Teske, Jennifer A.; Billington, Charles J.; Kotz, Catherine M.

2012-01-01

Objective Sleep-restriction in humans increases risk for obesity, but previous rodent studies show weight loss following sleep deprivation, possibly due to stressful-methods used to prevent sleep. Obesity-resistant (OR) rats exhibit consolidated-sleep and resistance to weight-gain. We hypothesized that sleep disruption by a less-stressful method would increase body weight, and examined effect of partial sleep deprivation (PSD) on body weight in OR and Sprague-Dawley (SD) rats. Design and Methods OR and SD rats (n=12/group) were implanted with transmitters to record sleep/wake. After baseline recording, six SD and six OR rats underwent 8 h PSD during light-phase for 9 d. Sleep was reduced using recordings of random noise. Sleep/wake states were scored as wakefulness (W), slow-wave-sleep (SWS) and rapid-eye-movement-sleep (REMS). Total number of transitions between stages, SWS-delta-power, food intake and body weight were documented. Results Exposure to noise decreased SWS and REMS time, while increasing W time. Sleep-deprivation increased number of transitions between stages and SWS-delta-power. Further, PSD during the rest phase increased recovery-sleep during active phase. The PSD SD and OR rats had greater food intake and body weight compared to controls Conclusions PSD by less-stressful means increases body weight in rats. Also, PSD during rest phase increases active period sleep. PMID:23666828

Development of a novel multi-point plastic scintillation detector with a single optical transmission line for radiation dose measurement*

PubMed Central

Therriault-Proulx, François; Archambault, Louis; Beaulieu, Luc; Beddar, Sam

2013-01-01

Purpose The goal of this study was to develop a novel multi-point plastic scintillation detector (mPSD) capable of measuring the dose accurately at multiple positions simultaneously using a single optical transmission line. Methods A 2-point mPSD used a band-pass approach that included splitters, color filters, and an EMCCD camera. The 3-point mPSD was based on a new full-spectrum approach, in which a spectrograph was coupled to a CCD camera. Irradiations of the mPSDs and of an ion chamber were performed with a 6-MV photon beam at various depths and lateral positions in a water tank. Results For the 2-point mPSD, the average relative differences between mPSD and ion chamber measurements for the depth-dose were 2.4±1.6% and 1.3±0.8% for BCF-60 and BCF-12, respectively. For the 3-point mPSD, the average relative differences over all conditions were 2.3±1.1%, 1.6±0.4%, and 0.32±0.19% for BCF-60, BCF-12, and BCF-10, respectively. Conclusions This study demonstrates the practical feasibility of mPSDs. This type of detector could be very useful for pre-treatment quality assurance applications as well as an accurate tool for real-time in vivo dosimetry. PMID:23060069

Partial sleep deprivation by environmental noise increases food intake and body weight in obesity-resistant rats.

PubMed

Mavanji, Vijayakumar; Teske, Jennifer A; Billington, Charles J; Kotz, Catherine M

2013-07-01

Sleep restriction in humans increases risk for obesity, but previous rodent studies show weight loss following sleep deprivation, possibly due to stressful methods used to prevent sleep. Obesity-resistant (OR) rats exhibit consolidated-sleep and resistance to weight gain. It was hypothesized that sleep disruption by a less-stressful method would increase body weight, and the effect of partial sleep deprivation (PSD) on body weight in OR and Sprague-Dawley (SD) rats was examined. OR and SD rats (n = 12/group) were implanted with transmitters to record sleep/wake. After baseline recording, six SD and six OR rats underwent 8 h PSD during light phase for 9 days. Sleep was reduced using recordings of random noise. Sleep/wake states were scored as wakefulness (W), slow-wave-sleep (SWS), and rapid-eye-movement-sleep (REMS). Total number of transitions between stages, SWS-delta-power, food intake, and body weight were documented. Exposure to noise decreased SWS and REMS time, while increasing W time. Sleep-deprivation increased the number of transitions between stages and SWS-delta-power. Further, PSD during the rest phase increased recovery sleep during the active phase. The PSD SD and OR rats had greater food intake and body weight compared to controls PSD by less-stressful means increases body weight in rats. Also, PSD during the rest phase increases active period sleep. Copyright © 2012 The Obesity Society.

Physicochemical stability, pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process.

PubMed

Shanmugam, Srinivasan; Park, Jae-Hyun; Chi, Sang-Cheol; Yong, Chul Soon; Choi, Han-Gon; Woo, Jong Soo

2011-06-01

To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process. Physicochemical stability was performed in accelerated (40°C 70 ± 5% RH) and stress (60°C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.v. administration of PTX equivalent to 6 and 12 mg/kg formulations. Physical stability of PSD showed excellent stability with no recrystallization of the amorphous form. Chemical stability of PSD in terms of % PTX remaining was 98.2 ± 0.6% at 6 months and 97.9 ± 0.3% at 4 weeks of accelerated and stress conditions, respectively. The PK study showed a nonlinear increase in AUC with increasing dose, that is, 100% increase in dose (from 6 to 12 mg/kg) resulted in 405.90% increase in AUC. Unlike PK study, the organ distribution study of PTX from PSD showed linear relationship with dose escalation. The order of organ distribution of PTX from highest to lowest for both PSD and Taxol® was liver>kidney>lung>brain. This study demonstrated excellent physicochemical stability with insight information on the PK and biodistribution of PTX from PSD prepared by SAS process.

40 CFR 52.931 - Significant deterioration of air quality.

Code of Federal Regulations, 2013 CFR

2013-07-01

... approval of Kentucky's Regulation for Prevention of Significant Deterioration (PSD), Visibility Monitoring... Deterioration (PSD), Visibility Monitoring, and Visibility New Source Review in Attainment Areas. (b) The...

40 CFR 52.931 - Significant deterioration of air quality.

Code of Federal Regulations, 2014 CFR

2014-07-01

... approval of Kentucky's Regulation for Prevention of Significant Deterioration (PSD), Visibility Monitoring... Deterioration (PSD), Visibility Monitoring, and Visibility New Source Review in Attainment Areas. (b) The...

40 CFR 52.931 - Significant deterioration of air quality.

Code of Federal Regulations, 2012 CFR

2012-07-01

... approval of Kentucky's Regulation for Prevention of Significant Deterioration (PSD), Visibility Monitoring... Deterioration (PSD), Visibility Monitoring, and Visibility New Source Review in Attainment Areas. (b) The...

40 CFR 52.931 - Significant deterioration of air quality.

Code of Federal Regulations, 2011 CFR

2011-07-01

... approval of Kentucky's Regulation for Prevention of Significant Deterioration (PSD), Visibility Monitoring... Deterioration (PSD), Visibility Monitoring, and Visibility New Source Review in Attainment Areas. (b) The...

Spectral Study of Measles Epidemics: The Dependence of Spectral Gradient on the Population Size of the Community

NASA Astrophysics Data System (ADS)

Sumi, Ayako; Olsen, Lars Folke; Ohtomo, Norio; Tanaka, Yukio; Sawamura, Sadashi

2003-02-01

We have carried out spectral analysis of measles notifications in several communities in Denmark, UK and USA. The results confirm that each power spectral density (PSD) shows exponential characteristics, which are universally observed in the PSD for time series generated from nonlinear dynamical system. The exponential gradient increases with the population size. For almost all communities, many spectral lines observed in each PSD can be fully assigned to linear combinations of several fundamental periods, suggesting that the measles data are substantially noise-free. The optimum least squares fitting curve calculated using these fundamental periods essentially reproduces an underlying variation of the measles data, and an extension of the curve can be used to predict measles epidemics. For the communities with large population sizes, some PSD patterns obtained from segment time series analysis show a close resemblance to the PSD patterns at the initial stages of a period-doubling bifurcation process for the so-called susceptible/exposed/infectious/recovered (SEIR) model with seasonal forcing. The meaning of the relationship between the exponential gradient and the population size is discussed.

Quantitative characterization of surface topography using spectral analysis

NASA Astrophysics Data System (ADS)

Jacobs, Tevis D. B.; Junge, Till; Pastewka, Lars

2017-03-01

Roughness determines many functional properties of surfaces, such as adhesion, friction, and (thermal and electrical) contact conductance. Recent analytical models and simulations enable quantitative prediction of these properties from knowledge of the power spectral density (PSD) of the surface topography. The utility of the PSD is that it contains statistical information that is unbiased by the particular scan size and pixel resolution chosen by the researcher. In this article, we first review the mathematical definition of the PSD, including the one- and two-dimensional cases, and common variations of each. We then discuss strategies for reconstructing an accurate PSD of a surface using topography measurements at different size scales. Finally, we discuss detecting and mitigating artifacts at the smallest scales, and computing upper/lower bounds on functional properties obtained from models. We accompany our discussion with virtual measurements on computer-generated surfaces. This discussion summarizes how to analyze topography measurements to reconstruct a reliable PSD. Analytical models demonstrate the potential for tuning functional properties by rationally tailoring surface topography—however, this potential can only be achieved through the accurate, quantitative reconstruction of the PSDs of real-world surfaces.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tao-Cheng, Jung-Hwa; Yang, Yijung; Bayer, K. Ulrich

Highlights: • NMDA-induces accumulation of Shank at the postsynaptic density. • Shank accumulation is preferential to the distal region of the postsynaptic density. • Shank accumulation is mediated by CaMKII. - Abstract: Shank is a specialized scaffold protein present in high abundance at the postsynaptic density (PSD). Using pre-embedding immunogold electron microscopy on cultured hippocampal neurons, we had previously demonstrated further accumulation of Shank at the PSD under excitatory conditions. Here, using the same experimental protocol, we demonstrate that a cell permeable CaMKII inhibitor, tatCN21, blocks NMDA-induced accumulation of Shank at the PSD. Furthermore we show that NMDA application changesmore » the distribution pattern of Shank at the PSD, promoting a 7–10 nm shift in the median distance of Shank labels away from the postsynaptic membrane. Inhibition of CaMKII with tatCN21 also blocks this shift in the distribution of Shank. Altogether these results imply that upon activation of NMDA receptors, CaMKII mediates accumulation of Shank, preferentially at the distal regions of the PSD complex extending toward the cytoplasm.« less

Fractal Theory and Field Cover Experiments: Implications for the Fractal Characteristics and Radon Diffusion Behavior of Soils and Rocks.

PubMed

Tan, Wanyu; Li, Yongmei; Tan, Kaixuan; Duan, Xianzhe; Liu, Dong; Liu, Zehua

2016-12-01

Radon diffusion and transport through different media is a complex process affected by many factors. In this study, the fractal theories and field covering experiments were used to study the fractal characteristics of particle size distribution (PSD) of six kinds of geotechnical materials (e.g., waste rock, sand, laterite, kaolin, mixture of sand and laterite, and mixture of waste rock and laterite) and their effects on radon diffusion. In addition, the radon diffusion coefficient and diffusion length were calculated. Moreover, new formulas for estimating diffusion coefficient and diffusion length functional of fractal dimension d of PSD were proposed. These results demonstrate the following points: (1) the fractal dimension d of the PSD can be used to characterize the property of soils and rocks in the studies of radon diffusion behavior; (2) the diffusion coefficient and diffusion length decrease with increasing fractal dimension of PSD; and (3) the effectiveness of final covers in reducing radon exhalation of uranium tailings impoundments can be evaluated on the basis of the fractal dimension of PSD of materials.

Age-Associated Changes in the Spectral and Statistical Parameters of Surface Electromyogram of Tibialis Anterior.

PubMed

Siddiqi, Ariba; Arjunan, Sridhar Poosapadi; Kumar, Dinesh Kant

2016-01-01

Age-related neuromuscular change of Tibialis Anterior (TA) is a leading cause of muscle strength decline among the elderly. This study has established the baseline for age-associated changes in sEMG of TA at different levels of voluntary contraction. We have investigated the use of Gaussianity and maximal power of the power spectral density (PSD) as suitable features to identify age-associated changes in the surface electromyogram (sEMG). Eighteen younger (20-30 years) and 18 older (60-85 years) cohorts completed two trials of isometric dorsiflexion at four different force levels between 10% and 50% of the maximal voluntary contraction. Gaussianity and maximal power of the PSD of sEMG were determined. Results show a significant increase in sEMG's maximal power of the PSD and Gaussianity with increase in force for both cohorts. It was also observed that older cohorts had higher maximal power of the PSD and lower Gaussianity. These age-related differences observed in the PSD and Gaussianity could be due to motor unit remodelling. This can be useful for noninvasive tracking of age-associated neuromuscular changes.

40 CFR 52.344 - Visibility protection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... industrial source categories regulated by the NSR and PSD regulations which have previously been approved by EPA. However, Colorado's NSR and PSD regulations have been disapproved for certain sources as listed...

40 CFR 52.344 - Visibility protection.

Code of Federal Regulations, 2014 CFR

2014-07-01

... industrial source categories regulated by the NSR and PSD regulations which have previously been approved by EPA. However, Colorado's NSR and PSD regulations have been disapproved for certain sources as listed...

40 CFR 52.976 - Review of new sources and modification.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the preconstruction requirements for the prevention of significant deterioration (PSD) of air quality... requirements for the prevention of significant deterioration (PSD) of air quality and the Administrator's...

40 CFR 52.976 - Review of new sources and modification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the preconstruction requirements for the prevention of significant deterioration (PSD) of air quality... requirements for the prevention of significant deterioration (PSD) of air quality and the Administrator's...

40 CFR 52.976 - Review of new sources and modification.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the preconstruction requirements for the prevention of significant deterioration (PSD) of air quality... requirements for the prevention of significant deterioration (PSD) of air quality and the Administrator's...

40 CFR 52.344 - Visibility protection.

Code of Federal Regulations, 2010 CFR

2010-07-01

... industrial source categories regulated by the NSR and PSD regulations which have previously been approved by EPA. However, Colorado's NSR and PSD regulations have been disapproved for certain sources as listed...

40 CFR 52.976 - Review of new sources and modification.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the preconstruction requirements for the prevention of significant deterioration (PSD) of air quality... requirements for the prevention of significant deterioration (PSD) of air quality and the Administrator's...

40 CFR 52.344 - Visibility protection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... industrial source categories regulated by the NSR and PSD regulations which have previously been approved by EPA. However, Colorado's NSR and PSD regulations have been disapproved for certain sources as listed...

40 CFR 52.976 - Review of new sources and modification.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the preconstruction requirements for the prevention of significant deterioration (PSD) of air quality... requirements for the prevention of significant deterioration (PSD) of air quality and the Administrator's...

40 CFR 52.344 - Visibility protection.

Code of Federal Regulations, 2012 CFR

2012-07-01

... industrial source categories regulated by the NSR and PSD regulations which have previously been approved by EPA. However, Colorado's NSR and PSD regulations have been disapproved for certain sources as listed...

40 CFR 52.2381 - EPA-approved Vermont State regulations.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-fired boilers. 3/24/79 1/30/80 45 FR 6781 (c)(9) Related to PSD. 11/4/79 2/19/80 45 FR 10775 (c)(10) All... FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For NSR Plan. Section 5-406Required air modeling 3/24/79 1/30/80 45 FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For...

40 CFR 52.2381 - EPA-approved Vermont State regulations.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-fired boilers. 3/24/79 1/30/80 45 FR 6781 (c)(9) Related to PSD. 11/4/79 2/19/80 45 FR 10775 (c)(10) All... FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For NSR Plan. Section 5-406Required air modeling 3/24/79 1/30/80 45 FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For...

40 CFR 52.2381 - EPA-approved Vermont State regulations.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-fired boilers. 3/24/79 1/30/80 45 FR 6781 (c)(9) Related to PSD. 11/4/79 2/19/80 45 FR 10775 (c)(10) All... FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For NSR Plan. Section 5-406Required air modeling 3/24/79 1/30/80 45 FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For...

40 CFR 52.2381 - EPA-approved Vermont State regulations.

Code of Federal Regulations, 2013 CFR

2013-07-01

...-fired boilers. 3/24/79 1/30/80 45 FR 6781 (c)(9) Related to PSD. 11/4/79 2/19/80 45 FR 10775 (c)(10) All... FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For NSR Plan. Section 5-406Required air modeling 3/24/79 1/30/80 45 FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For...

40 CFR 52.2381 - EPA-approved Vermont State regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-fired boilers. 3/24/79 1/30/80 45 FR 6781 (c)(9) Related to PSD. 11/4/79 2/19/80 45 FR 10775 (c)(10) All... FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For NSR Plan. Section 5-406Required air modeling 3/24/79 1/30/80 45 FR 6781 (c)(9) For PSD Plan. 3/24/79 2/19/80 45 FR 10775 (c)(10) For...

Pancreas-sparing duodenectomy for trauma.

PubMed

Yadav, T D; Kaushik, R

2004-01-01

The application of pancreas sparing duodenectomy (PSD) in extensive duodenal trauma has not been fully explored. We report 3 caes of duodenal trauma in whom PSD was performed successfully and with good results.

40 CFR 52.2058 - Prevention of significant air quality deterioration.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Pennsylvania Environmental Resources on October 28, 1983. All PSD permit applications and requests for... Pennsylvania Environmental Resources on October 28, 1983. All PSD permit applications and requests for...

Single-Centre Experience of Off-Pump Multi-Vessel Coronary Artery Bypass Grafting Using Proximal Suture Device.

PubMed

Ohira, Suguru; Doi, Kiyoshi; Numata, Satoshi; Yamazaki, Sachiko; Itatani, Keiichi; Kawajiri, Hidetake; Morimoto, Kazuki; Yaku, Hitoshi

2017-10-01

To investigate the results of off-pump coronary artery grafting (OPCAB) with the proximal suture device (PSD) regarding postoperative stroke and graft patency. The PSD was used in 376 patients (32.0%), aorta-no-touch OPCAB was performed in 523 patients (45.2%), on-pump beating coronary artery bypass surgery (CABG) (on-beat group) in 125 patients (10.6%) including 51 conversions (conversion rate: 5.4%), and CABG with aortic clamp use (clamp group) in 152 patients. In the PSD group, Enclose II was used in 267 patients (71.0%). The hospital mortality rate was 1.95%. There was no early stroke in the OPCAB group, whereas the early-stroke rate was 0.8% in the on-beat group and 2.6% in the clamp group. The incidences of stroke at one month were: PSD group, 1.6%; no-touch group, 1.1%; on-beat group, 1.6%; and clamp group, 4.6% (p=0.014). The rates of complete revascularisation were higher in the PSD and clamp groups (94.7 and 94.0%, respectively) compared with the no-touch and on-beat groups (81.5 and 84.9%, respectively; p<0.001). The vein graft patency rates were comparable between the PSD and clamp groups. In multiple logistic regression analysis, OPCAB using the PSD did not increase the risk of stroke compared with the no-touch group (adjusted odds ratio [AOR]: 1.40; p=0.594) or on-beat group (AOR: 0.99; p=0.206), but reduced the risk of stroke compared with the clamp group (AOR: 0.19; p=0.005). Off-pump coronary artery grafting using the PSD was a safe and effective procedure. It led to lower incidences of postoperative stroke and excellent rates of graft patency and complete revascularisation compared with conventional CABG. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

D-Serine and Serine Racemase Are Associated with PSD-95 and Glutamatergic Synapse Stability

PubMed Central

Lin, Hong; Jacobi, Ariel A.; Anderson, Stewart A.; Lynch, David R.

2016-01-01

D-serine is an endogenous coagonist at the glycine site of synaptic NMDA receptors (NMDARs), synthesized by serine racemase (SR) through conversion of L-serine. It is crucial for synaptic plasticity and is implicated in schizophrenia. Our previous studies demonstrated specific loss of SR, D-serine-responsive synaptic NMDARs, and glutamatergic synapses in cortical neurons lacking α7 nicotinic acetylcholine receptors, which promotes glutamatergic synapse formation and maturation during development. We thus hypothesize that D-serine and SR (D-serine/SR) are associated with glutamatergic synaptic development. Using morphological and molecular studies in cortical neuronal cultures, we demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development. Endogenous D-serine and SR colocalize with PSD-95, but not presynaptic vesicular glutamate transporter 1 (VGLUT1), in glutamatergic synapses of cultured cortical neurons. Low-density astrocytes in cortical neuronal cultures lack SR expression but contain enriched D-serine in large vesicle-like structures, suggesting possible synthesis of D-serine in postsynaptic neurons and storage in astrocytes. More interestingly, endogenous D-serine and SR colocalize with PSD-95 in the postsynaptic terminals of glutamatergic synapses during early and late synaptic development, implicating involvement of D-serine/SR in glutamatergic synaptic development. Exogenous application of D-serine enhances the interactions of SR with PSD-95 and NR1, and increases the number of VGLUT1- and PSD-95-positive glutamatergic synapses, suggesting that exogenous D-serine enhances postsynaptic SR/PSD-95 signaling and stabilizes glutamatergic synapses during cortical synaptic development. This is blocked by NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5) and 7-chlorokynurenic acid (7-CK), a specific antagonist at the glycine site of NMDARs, demonstrating that D-serine effects are mediated through postsynaptic NMDARs. Conversely, exogenous application of glycine has no such effects, suggesting D-serine, rather than glycine, modulates postsynaptic events. Taken together, our findings demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development, implicating D-serine/SR as regulators of cortical synaptic and circuit development. PMID:26941605

D-Serine and Serine Racemase Are Associated with PSD-95 and Glutamatergic Synapse Stability.

PubMed

Lin, Hong; Jacobi, Ariel A; Anderson, Stewart A; Lynch, David R

2016-01-01

D-serine is an endogenous coagonist at the glycine site of synaptic NMDA receptors (NMDARs), synthesized by serine racemase (SR) through conversion of L-serine. It is crucial for synaptic plasticity and is implicated in schizophrenia. Our previous studies demonstrated specific loss of SR, D-serine-responsive synaptic NMDARs, and glutamatergic synapses in cortical neurons lacking α7 nicotinic acetylcholine receptors, which promotes glutamatergic synapse formation and maturation during development. We thus hypothesize that D-serine and SR (D-serine/SR) are associated with glutamatergic synaptic development. Using morphological and molecular studies in cortical neuronal cultures, we demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development. Endogenous D-serine and SR colocalize with PSD-95, but not presynaptic vesicular glutamate transporter 1 (VGLUT1), in glutamatergic synapses of cultured cortical neurons. Low-density astrocytes in cortical neuronal cultures lack SR expression but contain enriched D-serine in large vesicle-like structures, suggesting possible synthesis of D-serine in postsynaptic neurons and storage in astrocytes. More interestingly, endogenous D-serine and SR colocalize with PSD-95 in the postsynaptic terminals of glutamatergic synapses during early and late synaptic development, implicating involvement of D-serine/SR in glutamatergic synaptic development. Exogenous application of D-serine enhances the interactions of SR with PSD-95 and NR1, and increases the number of VGLUT1- and PSD-95-positive glutamatergic synapses, suggesting that exogenous D-serine enhances postsynaptic SR/PSD-95 signaling and stabilizes glutamatergic synapses during cortical synaptic development. This is blocked by NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5) and 7-chlorokynurenic acid (7-CK), a specific antagonist at the glycine site of NMDARs, demonstrating that D-serine effects are mediated through postsynaptic NMDARs. Conversely, exogenous application of glycine has no such effects, suggesting D-serine, rather than glycine, modulates postsynaptic events. Taken together, our findings demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development, implicating D-serine/SR as regulators of cortical synaptic and circuit development.

Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice.

PubMed

Greifzu, Franziska; Parthier, Daniel; Goetze, Bianka; Schlüter, Oliver M; Löwel, Siegrid

2016-01-01

Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of cortical plasticity, namely the long-range influence on V1-plasticity after an S1-lesion.

Intrathecal injection of the peptide myr-NR2B9c attenuates bone cancer pain via perturbing N-methyl-D-aspartate receptor-PSD-95 protein interactions in mice.

PubMed

Liu, Yue; Cui, Xinlong; Sun, Yu-E; Yang, Xuli; Ni, Kun; Zhou, Yu; Ma, Zhengliang; Gu, Xiaoping

2014-06-01

N-methyl-D-aspartate receptor (NMDARs)-dependent central sensitization plays an important role in cancer pain. Binding of NMDAR subunit 2B (NR2B) by postsynaptic density protein-95 (PSD-95) can couple NMDAR activity to intracellular enzymes, such as neuronal nitric oxide synthase (nNOS), facilitate downstream signaling pathways, and modulate NMDAR stability, contributing to synaptic plasticity. In this study, we investigated whether perturbing the specific interaction between spinal NR2B-containing NMDAR and PSD-95, using a peptide-mimetic strategy, could attenuate bone cancer-related pain behaviors. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer-related pain behaviors. Western blotting was applied to examine the expression of spinal phospho-Tyr1472 NR2B, nNOS, and PSD-95. We further investigated the effects of intrathecal injection of the mimetic peptide Myr-NR2B9c, which competitively disrupts the interaction between PSD-95 and NR2B, on nociceptive behaviors and on the upregulation of phospho-Tyr1472 NR2B, nNOS, and PSD-95 associated with bone cancer pain in the spinal cord. Inoculation of osteosarcoma cells induced progressive bone cancer pain and resulted in a significant upregulation of phospho-Tyr1472 NR2B, nNOS, and PSD-95. Intrathecal administration of Myr-NR2B9c attenuated bone cancer-evoked mechanical allodynia, thermal hyperalgesia, and reduced spinal phospho-Tyr1472 NR2B, nNOS, and PSD-95 expression. Intrathecal administration of Myr-NR2B9c reduced bone cancer pain. Internalization of spinal NR2B and dissociation NR2B-containing NMDARs activation from downstream nNOS signaling may contribute to the analgesic effects of Myr-NR2B9c. This approach may circumvent the negative consequences associated with blocking NMDARs, and may be a novel strategy for the treatment of bone cancer pain.

Testing relativistic electron acceleration mechanisms

NASA Astrophysics Data System (ADS)

Green, Janet Carol

2002-09-01

This dissertation tests models of relativistic electron acceleration in the earth's outer radiation belt. The models fall into two categories: external and internal. External acceleration models transport and accelerate electrons from a source region in the outer magnetosphere to the inner magnetosphere. Internal acceleration models accelerate a population of electrons already present in the inner magnetosphere. In this dissertation, we test one specific external acceleration mechanism, perform a general test that differentiates between internal and external acceleration models, and test one promising internal acceleration model. We test the models using Polar-HIST data that we transform into electron phase space density (PSD) as a function of adiabatic invariants. We test the ultra low frequency (ULF) wave enhanced radial diffusion external acceleration mechanism by looking for a causal relationship between increased wave power and increased electron PSD at three L* values. One event with increased wave power at two L* values and no subsequent PSD increase does not support the model suggesting that ULF wave power alone is not sufficient to cause an electron response. Excessive loss of electrons and the duration of wave power do not explain the lack of a PSD enhancement at low L*. We differentiate between internal and external acceleration mechanisms by examining the radial profile of electron PSD. We observe PSD profiles that depend on local time. Nightside profiles are highly dependent on the magnetic field model used to calculate PSD as a function of adiabatic invariants and are not reliable. Dayside PSD profiles are more robust and consistent with internal acceleration of electrons. We test one internal acceleration model, the whistler/electromagnetic ion cyclotron wave model, by comparing observed pitch angle distributions to those predicted by the model using a superposed epoch analysis. The observations show pitch angle distributions corresponding to electrons with energy >=4.0 MeV becoming more peaked at 90° during the storm recovery phase. The observation is consistent with but does not confirm the model. Our tests indicate that relativistic electrons are accelerated by an internal source acceleration mechanism but we do not identify a unique mechanism.

Comparisons of Particulate Size Distributions from Multiple Combustion Strategies

NASA Astrophysics Data System (ADS)

Zhang, Yizhou

In this study, a comparison of particle size distribution (PSD) measurements from eight different combustion strategies was conducted at four different load-speed points. The PSDs were measured using a scanning mobility particle sizer (SMPS) together with a condensation particle counter (CPC). To study the influence of volatile particles, PSD measurements were performed with and without a volatile particle remover (thermodenuder, TD) at both low and high dilution ratios. The common engine platform utilized in the experiment helps to eliminate the influence of background particulate and ensures similarity in dilution conditions. The results show a large number of volatile particles were present under LDR sample conditions for most of the operating conditions. The use of a TD, especially when coupled with HDR, was demonstrated to be effective at removing volatile particles and provided consistent measurements across all combustion strategies. The PSD comparison showed that gasoline premixed combustion strategies such as HCCI and GCI generally have low PSD magnitudes for particle sizes greater than the Particle Measurement Programme (PMP) cutoff diameter (23 nm), and the PSDs were highly nuclei-mode particle dominated. The strategies using diesel as the only fuel (DLTC and CDC) generally showed the highest particle number emissions for particles larger than 23 nm and had accumulation-mode particle dominated PSDs. A consistent correlation between the increase of the direct-injection of diesel fuel and a higher fraction of accumulation-mode particles was observed over all combustion strategies. A DI fuel substitution study and injector nozzle geometry study were conducted to better understand the correlation between PSD shape and DI fueling. It was found that DI fuel properties has a clear impact on PSD behavior for CDC and NG DPI. Fuel with lower density and lower sooting tendency led to a nuclei-mode particle dominated PSD shape. For NG RCCI, accumulation-mode particle concentration was found to be insensitive to DI fuel properties. Similar PSD behavior of increased nuclei-mode particle fraction was also observed when a smaller orifice nozzle was used for CDC and NG DPI operation. For NG DPI, a reduction of DI fuel fraction generally led to a reduction in accumulation-mode particles.

An assembly of proteins and lipid domains regulates transport of phosphatidylserine to phosphatidylserine decarboxylase 2 in Saccharomyces cerevisiae.

PubMed

Riekhof, Wayne R; Wu, Wen-I; Jones, Jennifer L; Nikrad, Mrinalini; Chan, Mallory M; Loewen, Christopher J R; Voelker, Dennis R

2014-02-28

Saccharomyces cerevisiae uses multiple biosynthetic pathways for the synthesis of phosphatidylethanolamine. One route involves the synthesis of phosphatidylserine (PtdSer) in the endoplasmic reticulum (ER), the transport of this lipid to endosomes, and decarboxylation by PtdSer decarboxylase 2 (Psd2p) to produce phosphatidylethanolamine. Several proteins and protein motifs are known to be required for PtdSer transport to occur, namely the Sec14p homolog PstB2p/Pdr17p; a PtdIns 4-kinase, Stt4p; and a C2 domain of Psd2p. The focus of this work is on defining the protein-protein and protein-lipid interactions of these components. PstB2p interacts with a protein encoded by the uncharacterized gene YPL272C, which we name Pbi1p (PstB2p-interacting 1). PstB2p, Psd2, and Pbi1p were shown to be lipid-binding proteins specific for phosphatidic acid. Pbi1p also interacts with the ER-localized Scs2p, a binding determinant for several peripheral ER proteins. A complex between Psd2p and PstB2p was also detected, and this interaction was facilitated by a cryptic C2 domain at the extreme N terminus of Psd2p (C2-1) as well the previously characterized C2 domain of Psd2p (C2-2). The predicted N-terminal helical region of PstB2p was necessary and sufficient for promoting the interaction with both Psd2p and Pbi1p. Taken together, these results support a model for PtdSer transport involving the docking of a PtdSer donor membrane with an acceptor via specific protein-protein and protein-lipid interactions. Specifically, our model predicts that this process involves an acceptor membrane complex containing the C2 domains of Psd2p, PstB2p, and Pbi1p that ligate to Scs2p and phosphatidic acid present in the donor membrane, forming a zone of apposition that facilitates PtdSer transfer.

Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice

PubMed Central

Greifzu, Franziska; Parthier, Daniel; Goetze, Bianka; Schlüter, Oliver M.; Löwel, Siegrid

2016-01-01

Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of cortical plasticity, namely the long-range influence on V1-plasticity after an S1-lesion. PMID:26930616

What does it mean to be pseudo single domain? Demystifying the PSD state

NASA Astrophysics Data System (ADS)

Lascu, I.; Harrison, R. J.; Einsle, J. F.; Ball, M.

2016-12-01

Until recently, non-interacting stable single domain grains were thought to be the sole reliable paleomagnetic recorders. However most natural samples contain so-called "non-ideal" paleomagnetic recorders, which are either interacting single domain particles, or magnetic grains larger than single domain grains, but smaller than proper multi domain grains, which are poor paleomagnetic recorders. The grain size range for these recorders, which for magnetite comprises grains from 100 nm to a few μm in size, is known as the pseudo single domain (PSD) state. Natural samples containing abundant PSD grains have been shown time and again to reliably record thermomagnetic remanent magnetizations that are stable over billions of years. Here we attempt to shed new light on the PSD state by investigating obsidian varieties found at Glass Butte, Oregon, which present the opportunity to study simple cases of magnetic grains encapsulated in volcanic glass. We do this by combining rock magnetism, scanning electron microscopy (SEM) nanotomography, and finite-element micromagnetic modeling. Using rock magnetism we have identified PSD signatures in these samples via their fingerprint in first-order reversal curve (FORC) diagrams. Tomographic reconstructions obtained by stacking SEM images acquired via sequential milling through sample volumes of a few tens of cubic μm reveal the presence of abundant grains that span the PSD grain size interval. These grains have a variety of shapes, from simple ellipsoidal particles, to more complex morphologies attained through the coalescence of neighboring grains during crystallization, to intricate "rolling snowball" morphologies in larger grains that contain appendices formed as a result of particle growth in a dynamic environment as the flowing lava cooled. Micromagnetic modeling of the simplest morphologies reveals that these grains are in single vortex states, with the remanence controlled by irregularities in grain morphology. Coalesced grains present extreme cases of shape anisotropy, which will control the remanence. The remanence of the largest grains is controlled by the collection of PSD states from areas of the grain with pronounced shape anisotropy. Finally, micromagnetic modeling of realistic grain shapes allows the understanding of PSD signatures in FORC diagrams.

Puffy Skin Disease Is an Emerging Transmissible Condition in Rainbow Trout Oncorhynchus mykiss Walbaum

PubMed Central

Cano, Irene; Verner-Jeffreys, David W.; van Aerle, Ronny; Paley, Richard K.; Peeler, Edmund J.; Green, Matthew; Rimmer, Georgina S. E.; Savage, Jacqueline; Joiner, Claire L.; Bayley, Amanda E.; Mewett, Jason; Hulland, Jonathan; Feist, Stephen W.

2016-01-01

The transmission of puffy skin disease (PSD) to rainbow trout Oncorhynchus mykiss Walbaum was tested in the laboratory by conducting co-habitation challenges with puffy skin (PS)-affected fish (Trojans) collected from the field. Two separate challenges were conducted using Trojans sourced from two different sites and diploid (first trial) or triploid (second trial) naïve fish. PSD-specific clinical signs were observed in both groups of naïve fish, with 66% of the fish sampled during the challenges showing signs of varying severity. The first clinical features of PSD were presented as white oval skin patches on one or both flanks 15–21 days post-challenge (dpc). The extent of the lesions ranged from 10 to 90% of the body surface, depending on the severity of the lesion. Both the severity and number of affected fish increased during the challenge. Macroscopically, oedema of the skin and multifocal petechial haemorrhaging were observed towards the end of the trials. Abnormal fish behaviour consisting of “flashing” and excessive mucous production was noted from 15 dpc onwards. Fish with severe PSD lesions also displayed inappetence and associated emaciation. Rodlet cells were observed in 41% of the fresh skin scrapes analysed from the second trial. Histologically epidermal oedema was observed in 31% of the naive fish showing gross pathology, with additional 12% displaying epidermal hyperplasia, mostly observed at the end of the challenge. Other concomitant features of the PSD lesions in challenged fish were epithelial erosion and sloughing, and occasionally mild or focal inflammation. No consistent pathology of internal organs was observed. The parasites Ichthyophthirius multifiliis and Ichthyobodo necator were observed in skin samples of a proportion of naïve challenged fish and in Trojans but not in control fish. The presence of these and other known fish pathogens in the skin of PSD-fish was confirmed by high-throughput sequencing analysis. In summary, we have demonstrated that PSD is a transmissible condition. However, even though a number of known fish pathogens were identified in the skin tissues of PSD-fish, the actual causative infectious agent(s) remain(s) unknown. PMID:27391648

40 CFR 49.151 - Program overview.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PSD increment violation. (5) If an AQIA is submitted, the reviewing authority determines that the new or modified source will not cause or contribute to a NAAQS or PSD increment violation. (6) The...

40 CFR 49.151 - Program overview.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PSD increment violation. (5) If an AQIA is submitted, the reviewing authority determines that the new or modified source will not cause or contribute to a NAAQS or PSD increment violation. (6) The...

40 CFR 124.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 271.2 (RCRA), the definitions below apply to this part, except for PSD permits which are governed by... Administrator delegates authority to the Environmental Appeals Board to issue final decisions in RCRA, PSD, UIC...

40 CFR 49.151 - Program overview.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PSD increment violation. (5) If an AQIA is submitted, the reviewing authority determines that the new or modified source will not cause or contribute to a NAAQS or PSD increment violation. (6) The...

40 CFR 124.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 271.2 (RCRA), the definitions below apply to this part, except for PSD permits which are governed by... Administrator delegates authority to the Environmental Appeals Board to issue final decisions in RCRA, PSD, UIC...

40 CFR 124.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 271.2 (RCRA), the definitions below apply to this part, except for PSD permits which are governed by... Administrator delegates authority to the Environmental Appeals Board to issue final decisions in RCRA, PSD, UIC...

40 CFR 124.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 271.2 (RCRA), the definitions below apply to this part, except for PSD permits which are governed by... Administrator delegates authority to the Environmental Appeals Board to issue final decisions in RCRA, PSD, UIC...

40 CFR 124.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 271.2 (RCRA), the definitions below apply to this part, except for PSD permits which are governed by... Administrator delegates authority to the Environmental Appeals Board to issue final decisions in RCRA, PSD, UIC...

40 CFR 69.32 - Title V conditional exemption.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (PSD) increments. (2) CNMI may conduct air emissions modeling, using EPA guidelines, for power plants... determine whether existing power plants cause or contribute to violation of the NAAQS and PSD increments in...

40 CFR 69.32 - Title V conditional exemption.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (PSD) increments. (2) CNMI may conduct air emissions modeling, using EPA guidelines, for power plants... determine whether existing power plants cause or contribute to violation of the NAAQS and PSD increments in...

40 CFR 52.1634 - Significant deterioration of air quality.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Significant Deterioration (PSD) and its Supplemental document, is approved as meeting the requirements of part... satisfying the conditions of EPA's conditional approval of the State's PSD program on February 27, 1987 (52...

40 CFR 52.1634 - Significant deterioration of air quality.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Significant Deterioration (PSD) and its Supplemental document, is approved as meeting the requirements of part... satisfying the conditions of EPA's conditional approval of the State's PSD program on February 27, 1987 (52...

40 CFR 69.32 - Title V conditional exemption.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (PSD) increments. (2) CNMI may conduct air emissions modeling, using EPA guidelines, for power plants... determine whether existing power plants cause or contribute to violation of the NAAQS and PSD increments in...

40 CFR 69.32 - Title V conditional exemption.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (PSD) increments. (2) CNMI may conduct air emissions modeling, using EPA guidelines, for power plants... determine whether existing power plants cause or contribute to violation of the NAAQS and PSD increments in...

40 CFR 52.2303 - Significant deterioration of air quality.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Environmental Quality on April 20, 2011 and submitted on May 19, 2011) to address PSD permitting requirements... Prevention of Significant Deterioration (PSD) Supplement document, submitted October 26, 1987 (as adopted by...

40 CFR 52.1634 - Significant deterioration of air quality.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Significant Deterioration (PSD) and its Supplemental document, is approved as meeting the requirements of part... satisfying the conditions of EPA's conditional approval of the State's PSD program on February 27, 1987 (52...

Neutron-gamma discrimination via PSD plastic scintillator and SiPMs

NASA Astrophysics Data System (ADS)

Taggart, M. P.; Payne, C.; Sellin, P. J.

2016-10-01

The reduction in availability and inevitable increase in cost of traditional neutron detectors based on the 3He neutron capture reaction has resulted in a concerted effort to seek out new techniques and detection media to meet the needs of national nuclear security. Traditionally, the alternative has been provided through pulse shape discrimination (PSD) using liquid scintillators. However, these are not without their own inherent issues, primarily concerning user safety and ongoing maintenance. A potential system devised to separate neutron and gamma ray pulses utilising the PSD technique takes advantage of recent improvements in silicon photomultiplier (SiPM) technology and the development of plastic scintillators exhibiting the PSD phenomena. In this paper we present the current iteration of this ongoing work having achieved a Figure of Merit (FoM) of 1.39 at 1.5 MeVee.

Recent developments in plastic scintillators with pulse shape discrimination

NASA Astrophysics Data System (ADS)

Zaitseva, N. P.; Glenn, A. M.; Mabe, A. N.; Carman, M. L.; Hurlbut, C. R.; Inman, J. W.; Payne, S. A.

2018-05-01

The paper reports results of studies conducted to improve scintillation performance of plastic scintillators capable of neutron/gamma pulse-shape discrimination (PSD). Compositional modifications made with the polymer matrix improved physical stability, allowing for increased loads of the primary dye that, in combination with selected secondary dyes, provided enhanced PSD especially important for the lower energy ranges. Additional measurements were made with a newly-introduced PSD plastic EJ-276, that replaces the first commercially produced EJ-299. Comparative studies conducted with the new materials and EJ-309 liquids at large scale (up to 10 cm) show that current plastics may provide scintillation and PSD performance sufficient for the replacement of liquid scintillators. Comparison to stilbene single crystals compliments the information about the status of the solid-state materials recently developed for fast neutron detection applications.

Enhanced Characterization of Niobium Surface Topography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Xu, Hui Tian, Charles Reece, Michael Kelley

2011-12-01

Surface topography characterization is a continuing issue for the Superconducting Radio Frequency (SRF) particle accelerator community. Efforts are underway to both to improve surface topography, and its characterization and analysis using various techniques. In measurement of topography, Power Spectral Density (PSD) is a promising method to quantify typical surface parameters and develop scale-specific interpretations. PSD can also be used to indicate how chemical processes modifiesy the roughnesstopography at different scales. However, generating an accurate and meaningful topographic PSD of an SRF surface requires careful analysis and optimization. In this report, polycrystalline surfaces with different process histories are sampled with AFMmore » and stylus/white light interferometer profilometryers and analyzed to indicate trace topography evolution at different scales. evolving during etching or polishing. Moreover, Aan optimized PSD analysis protocol will be offered to serve the SRF surface characterization needs is presented.« less

A PSD (position sensing device) to map the shift and tilt of the SRT secondary mirror

NASA Astrophysics Data System (ADS)

Pisanu, Tonino; Buffa, Franco; Concu, Raimondo; Marongiu, Pasqualino; Pili, Mauro; Poppi, Sergio; Serra, Giampaolo; Urru, Enrico; Vargiu, Gianpaolo

2014-07-01

The Sardinia Radio Telescope (SRT) Metrology team has started to install the initial group of devices on the new 64 meters radio-telescope. These devices will be devoted for the realization of the antenna deformation control system: an electronic inclinometer able to monitor the alidade deformations and a Position Sensing Device (PSD) able to map the secondary mirror (M2) displacements and tilts. The inclinometer is used to map the rail conditions, the azimuthal axis inclination and the thermal effects on the alidade structure. The PSD will be used to measure the secondary mirror displacements induced by the gravity and by the thermal deformations that produce shifts and tilts with respect to it s ideal optical alignment. The PSD will be traced by a laser diode installed on a mechanically stable position inside the vertex room. Preliminarly we decided to characterize excursion range of M2, in order to know if the PSD measuring range of about +/- 10 mm is enough for our purposes. We designed, built and tested an optical measuring device, based on commercial CMOS with a wider measurement range of +/- 40 mm and with a resolution of around 0.1 mm. After a laboratory characterization at the 23 meters real distance, the PSD and the laser have been installed in the antenna. In this paper we show the results of the measurements performed by moving the antenna in elevation.

PAUSED Encodes the Arabidopsis Exportin-t Ortholog1

PubMed Central

Hunter, Christine A.; Aukerman, Milo J.; Sun, Hui; Fokina, Maria; Poethig, R. Scott

2003-01-01

Los1p/exportin-t (XPOT) mediates the nuclear export of tRNAs in yeast and mammals. The requirements for this transport pathway are unclear, however, because los1 mutations do not affect yeast growth, and the phenotype of XPOT mutations in mammals is unknown. Here, we show that PAUSED (PSD) is the Arabidopsis ortholog of LOS1/XPOT and is capable of rescuing the tRNA export defect of los1 in Brewer's yeast (Saccharomyces cerevisiae), suggesting that its function has been conserved. Putative null alleles of PSD disrupt the initiation of the shoot apical meristem and delay leaf initiation after germination, the emergence of the radicle and lateral roots, and the transition to flowering. Plants doubly mutant for psd and hasty, the Arabidopsis ortholog of exportin 5, are viable but have a more severe phenotype than either single mutant. These results suggest that PSD plays a role in tRNA export in Arabidopsis, but that at least one—and perhaps several—additional tRNA export pathways also exist. The PSD transcript is broadly expressed during development and is alternatively spliced in the 3′-untranslated region. No temporal or spatial difference in the abundance of different splice forms was observed. We propose that the mutant phenotype of psd reflects defects in developmental events and cell/tissue types that require elevated levels of protein synthesis and are therefore acutely sensitive to a reduction in tRNA export. PMID:12913168

Novel method of detecting movement of the interference fringes using one-dimensional PSD.

PubMed

Wang, Qi; Xia, Ji; Liu, Xu; Zhao, Yong

2015-06-02

In this paper, a method of using a one-dimensional position-sensitive detector (PSD) by replacing charge-coupled device (CCD) to measure the movement of the interference fringes is presented first, and its feasibility is demonstrated through an experimental setup based on the principle of centroid detection. Firstly, the centroid position of the interference fringes in a fiber Mach-Zehnder (M-Z) interferometer is solved in theory, showing it has a higher resolution and sensitivity. According to the physical characteristics and principles of PSD, a simulation of the interference fringe's phase difference in fiber M-Z interferometers and PSD output is carried out. Comparing the simulation results with the relationship between phase differences and centroid positions in fiber M-Z interferometers, the conclusion that the output of interference fringes by PSD is still the centroid position is obtained. Based on massive measurements, the best resolution of the system is achieved with 5.15, 625 μm. Finally, the detection system is evaluated through setup error analysis and an ultra-narrow-band filter structure. The filter structure is configured with a one-dimensional photonic crystal containing positive and negative refraction material, which can eliminate background light in the PSD detection experiment. This detection system has a simple structure, good stability, high precision and easily performs remote measurements, which makes it potentially useful in material small deformation tests, refractivity measurements of optical media and optical wave front detection.

Resolving the Origin of Pseudo-Single Domain Magnetic Behavior

NASA Astrophysics Data System (ADS)

Roberts, Andrew P.; Almeida, Trevor P.; Church, Nathan S.; Harrison, Richard J.; Heslop, David; Li, Yiliang; Li, Jinhua; Muxworthy, Adrian R.; Williams, Wyn; Zhao, Xiang

2017-12-01

The term "pseudo-single domain" (PSD) has been used to describe the transitional state in rock magnetism that spans the particle size range between the single domain (SD) and multidomain (MD) states. The particle size range for the stable SD state in the most commonly occurring terrestrial magnetic mineral, magnetite, is so narrow ( 20-75 nm) that it is widely considered that much of the paleomagnetic record of interest is carried by PSD rather than stable SD particles. The PSD concept has, thus, become the dominant explanation for the magnetization associated with a major fraction of particles that record paleomagnetic signals throughout geological time. In this paper, we argue that in contrast to the SD and MD states, the term PSD does not describe the relevant physical processes, which have been documented extensively using three-dimensional micromagnetic modeling and by parallel research in material science and solid-state physics. We also argue that features attributed to PSD behavior can be explained by nucleation of a single magnetic vortex immediately above the maximum stable SD transition size. With increasing particle size, multiple vortices, antivortices, and domain walls can nucleate, which produce variable cancellation of magnetic moments and a gradual transition into the MD state. Thus, while the term PSD describes a well-known transitional state, it fails to describe adequately the physics of the relevant processes. We recommend that use of this term should be discontinued in favor of "vortex state," which spans a range of behaviors associated with magnetic vortices.

Performance of soil particle-size distribution models for describing deposited soils adjacent to constructed dams in the China Loess Plateau

NASA Astrophysics Data System (ADS)

Zhao, Pei; Shao, Ming-an; Horton, Robert

2011-02-01

Soil particle-size distributions (PSD) have been used to estimate soil hydraulic properties. Various parametric PSD models have been proposed to describe the soil PSD from sparse experimental data. It is important to determine which PSD model best represents specific soils. Fourteen PSD models were examined in order to determine the best model for representing the deposited soils adjacent to dams in the China Loess Plateau; these were: Skaggs (S-1, S-2, and S-3), fractal (FR), Jaky (J), Lima and Silva (LS), Morgan (M), Gompertz (G), logarithm (L), exponential (E), log-exponential (LE), Weibull (W), van Genuchten type (VG) as well as Fredlund (F) models. Four-hundred and eighty samples were obtained from soils deposited in the Liudaogou catchment. The coefficient of determination (R 2), the Akaike's information criterion (AIC), and the modified AIC (mAIC) were used. Based upon R 2 and AIC, the three- and four-parameter models were both good at describing the PSDs of deposited soils, and the LE, FR, and E models were the poorest. However, the mAIC in conjunction with R 2 and AIC results indicated that the W model was optimum for describing PSD of the deposited soils for emphasizing the effect of parameter number. This analysis was also helpful for finding out which model is the best one. Our results are applicable to the China Loess Plateau.

Association of Membrane Rafts and Postsynaptic Density: Proteomics, Biochemical, and Ultrastructural Analyses

PubMed Central

Suzuki, Tatsuo; Zhang, Jingping; Miyazawa, Shoko; Liu, Qian; Farzan, Michael R.; Yao, Wei-Dong

2011-01-01

Postsynaptic membrane rafts are believed to play important roles in synaptic signaling, plasticity, and maintenance. However, their molecular identities remain elusive. Further, how they interact with the well-established signaling specialization, the postsynaptic density (PSD), is poorly understood. We previously detected a number of conventional PSD proteins in detergent-resistant membranes (DRMs). Here, we have performed LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry) analyses on postsynaptic membrane rafts and PSDs. Our comparative analysis identified an extensive overlap of protein components in the two structures. This overlapping could be explained, at least partly, by a physical association of the two structures. Meanwhile, a significant number of proteins displayed biased distributions to either rafts or PSDs, suggesting distinct roles for the two postsynaptic specializations. Using biochemical and electron microscopic methods, we directly detected membrane raft-PSD complexes. In vitro reconstitution experiments indicated that the formation of raft-PSD complexes was not due to the artificial reconstruction of once-solubilized membrane components and PSD structures, supporting that these complexes occurred in vivo. Taking together, our results provide evidence that postsynaptic membrane rafts and PSDs may be physically associated. Such association could be important in postsynaptic signal integration, synaptic function, and maintenance. PMID:21797867

Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation and mGluR signaling

PubMed Central

Muddashetty, Ravi S.; Nalavadi, Vijayalaxmi C.; Gross, Christina; Yao, Xiaodi; Xing, Lei; Laur, Oskar; Warren, Stephen T.; Bassell, Gary J.

2011-01-01

Summary The molecular mechanism how RISC and microRNAs selectively and reversibly regulate mRNA translation in response to receptor signaling is unknown but could provide a means for temporal and spatial control of translation. Here we show that miR-125a targeting PSD-95 mRNA allows reversible inhibition of translation and regulation by mGluR signaling. Inhibition of miR-125a increased PSD-95 levels in dendrites and altered dendritic spine morphology. Bidirectional control of PSD-95 expression depends on miR-125a and FMRP phosphorylation status. miR-125a levels at synapses and its association with AGO2 is reduced in Fmr1 KO. FMRP phosphorylation promotes the formation of an AGO2-miR-125a inhibitory complex on PSD-95 mRNA, whereas mGluR signaling of translation requires FMRP dephosphorylation and release of AGO2 from the mRNA. These findings reveal a novel mechanism whereby FMRP phosphorylation provides a reversible switch for AGO2 and microRNA to selectively regulate mRNA translation at synapses in response to receptor activation. PMID:21658607

Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval.

PubMed

Li, Jun; Han, Zhou; Cao, Bo; Cai, Cheng-Yun; Lin, Yu-Hui; Li, Fei; Wu, Hai-Ying; Chang, Lei; Luo, Chun-Xia; Zhu, Dong-Ya

2017-11-04

Granule cells in the dentate gyrus regenerate constantly in adult hippocampus and then integrate into neural circuits in the hippocampus thereby providing the neural basis for learning and memory. Promoting the neurogenesis in the hippocampus facilitates learning and memory such as spatial learning, object identification, and extinction learning. The interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) is reported to negatively regulate neurogenesis in brain, so we hypothesized that disrupting this interaction might facilitate the neurogenesis in the dentate gyrus (DG) and thus enhance the extinction memory retrieval of fear learning. We found that uncoupling the nNOS-PSD-95 complex in remote contextual fear condition promoted both neuronal proliferation and survival in the DG, contributing to an enhanced retrieval of the extinction memory. Moreover, the nNOS-PSD-95 uncoupling-induced neurogenesis may be mediated by the extracellular signal-regulated kinase (ERK) as the phosphorylation level of ERK1/2 was increased after uncoupling. These findings suggest that the nNOS-PSD-95 complex may serve as a novel target for the treatment of post-traumatic stress disorder (PTSD). Copyright © 2017 Elsevier Inc. All rights reserved.

Calibration of phoswich-based lung counting system using realistic chest phantom.

PubMed

Manohari, M; Mathiyarasu, R; Rajagopal, V; Meenakshisundaram, V; Indira, R

2011-03-01

A phoswich detector, housed inside a low background steel room, coupled with a state-of-art pulse shape discrimination (PSD) electronics is recently established at Radiological Safety Division of IGCAR for in vivo monitoring of actinides. The various parameters of PSD electronics were optimised to achieve efficient background reduction in low-energy regions. The PSD with optimised parameters has reduced steel room background from 9.5 to 0.28 cps in the 17 keV region and 5.8 to 0.3 cps in the 60 keV region. The Figure of Merit for the timing spectrum of the system is 3.0. The true signal loss due to PSD was found to be less than 2 %. The phoswich system was calibrated with Lawrence Livermore National Laboratory realistic chest phantom loaded with (241)Am activity tagged lung set. Calibration factors for varying chest wall composition and chest wall thickness in terms of muscle equivalent chest wall thickness were established. (241)Am activity in the JAERI phantom which was received as a part of IAEA inter-comparison exercise was estimated. This paper presents the optimisation of PSD electronics and the salient results of the calibration.

Age-Associated Changes in the Spectral and Statistical Parameters of Surface Electromyogram of Tibialis Anterior

PubMed Central

2016-01-01

Age-related neuromuscular change of Tibialis Anterior (TA) is a leading cause of muscle strength decline among the elderly. This study has established the baseline for age-associated changes in sEMG of TA at different levels of voluntary contraction. We have investigated the use of Gaussianity and maximal power of the power spectral density (PSD) as suitable features to identify age-associated changes in the surface electromyogram (sEMG). Eighteen younger (20–30 years) and 18 older (60–85 years) cohorts completed two trials of isometric dorsiflexion at four different force levels between 10% and 50% of the maximal voluntary contraction. Gaussianity and maximal power of the PSD of sEMG were determined. Results show a significant increase in sEMG's maximal power of the PSD and Gaussianity with increase in force for both cohorts. It was also observed that older cohorts had higher maximal power of the PSD and lower Gaussianity. These age-related differences observed in the PSD and Gaussianity could be due to motor unit remodelling. This can be useful for noninvasive tracking of age-associated neuromuscular changes. PMID:27610379

Optimal design of waveform digitisers for both energy resolution and pulse shape discrimination

NASA Astrophysics Data System (ADS)

Cang, Jirong; Xue, Tao; Zeng, Ming; Zeng, Zhi; Ma, Hao; Cheng, Jianping; Liu, Yinong

2018-04-01

Fast digitisers and digital pulse processing have been widely used for spectral application and pulse shape discrimination (PSD) owing to their advantages in terms of compactness, higher trigger rates, offline analysis, etc. Meanwhile, the noise of readout electronics is usually trivial for organic, plastic, or liquid scintillator with PSD ability because of their poor intrinsic energy resolution. However, LaBr3(Ce) has been widely used for its excellent energy resolution and has been proven to have PSD ability for alpha/gamma particles. Therefore, designing a digital acquisition system for such scintillators as LaBr3(Ce) with both optimal energy resolution and promising PSD ability is worthwhile. Several experimental research studies about the choice of digitiser properties for liquid scintillators have already been conducted in terms of the sampling rate and vertical resolution. Quantitative analysis on the influence of waveform digitisers, that is, fast amplifier (optional), sampling rates, and vertical resolution, on both applications is still lacking. The present paper provides quantitative analysis of these factors and, hence, general rules about the optimal design of digitisers for both energy resolution and PSD application according to the noise analysis of time-variant gated charge integration.

40 CFR 60.754 - Test methods and procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... calculating emissions for PSD purposes, the owner or operator of each MSW landfill subject to the provisions of this subpart shall estimate the NMOC emission rate for comparison to the PSD major source and...

40 CFR 60.754 - Test methods and procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... calculating emissions for PSD purposes, the owner or operator of each MSW landfill subject to the provisions of this subpart shall estimate the NMOC emission rate for comparison to the PSD major source and...

40 CFR 60.754 - Test methods and procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... calculating emissions for PSD purposes, the owner or operator of each MSW landfill subject to the provisions of this subpart shall estimate the NMOC emission rate for comparison to the PSD major source and...

40 CFR 144.31 - Application for a permit; authorization by permit.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (PSD) program under the Clean Air Act. (2) Name, mailing address, and location of the facility for... under SDWA. (iii) NPDES program under CWA. (iv) Prevention of Significant Deterioration (PSD) program...

40 CFR 52.2630 - Prevention of significant deterioration of air quality.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., including Supplement A, in all PSD permit application reviews. The Division will utilize any future revisions to the Guideline in PSD permitting reviews as revisions become effective. [44 FR 51979, Sept. 6...

40 CFR 81.300 - Scope.

Code of Federal Regulations, 2011 CFR

2011-07-01

... air quality (PSD). With respect to areas identified as “Rest of State” it should be assumed that such reference comprises a single area designation for PSD baseline area purposes. However, for PM-10, the use of...

40 CFR 81.300 - Scope.

Code of Federal Regulations, 2012 CFR

2012-07-01

... air quality (PSD). With respect to areas identified as “Rest of State” it should be assumed that such reference comprises a single area designation for PSD baseline area purposes. However, for PM-10, the use of...

40 CFR 52.2630 - Prevention of significant deterioration of air quality.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., including Supplement A, in all PSD permit application reviews. The Division will utilize any future revisions to the Guideline in PSD permitting reviews as revisions become effective. [44 FR 51979, Sept. 6...

40 CFR 52.2630 - Prevention of significant deterioration of air quality.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., including Supplement A, in all PSD permit application reviews. The Division will utilize any future revisions to the Guideline in PSD permitting reviews as revisions become effective. [44 FR 51979, Sept. 6...

40 CFR 81.300 - Scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... air quality (PSD). With respect to areas identified as “Rest of State” it should be assumed that such reference comprises a single area designation for PSD baseline area purposes. However, for PM-10, the use of...

40 CFR 52.2630 - Prevention of significant deterioration of air quality.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., including Supplement A, in all PSD permit application reviews. The Division will utilize any future revisions to the Guideline in PSD permitting reviews as revisions become effective. [44 FR 51979, Sept. 6...

40 CFR 60.754 - Test methods and procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... calculating emissions for PSD purposes, the owner or operator of each MSW landfill subject to the provisions of this subpart shall estimate the NMOC emission rate for comparison to the PSD major source and...

40 CFR 60.754 - Test methods and procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... calculating emissions for PSD purposes, the owner or operator of each MSW landfill subject to the provisions of this subpart shall estimate the NMOC emission rate for comparison to the PSD major source and...

Draft PSD Guidance for Impacts of the North County Resource Recovery PSD Remand

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

PSD Applicability for a PSD-Avoidance Permit Action for Intermet Corporation's Archer Creek Facility

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Plastic scintillators with efficient neutron/gamma pulse shape discrimination

NASA Astrophysics Data System (ADS)

Zaitseva, Natalia; Rupert, Benjamin L.; PaweŁczak, Iwona; Glenn, Andrew; Martinez, H. Paul; Carman, Leslie; Faust, Michelle; Cherepy, Nerine; Payne, Stephen

2012-03-01

A possibility of manufacturing plastic scintillators with efficient neutron/gamma pulse shape discrimination (PSD) is demonstrated using a system of a polyvinyltoluene (PVT) polymer matrix loaded with a scintillating dye, 2,5-diphenyloxazole (PPO). Similarities and differences of conditions leading to the rise of PSD in liquid and solid organic scintillators are discussed based on the classical model of excited state interaction and delayed light formation. First characterization results are presented to show that PSD in plastic scintillators can be of the similar magnitude or even higher than in standard commercial liquid scintillators.

Lambda-cyhalothrin disrupts the up-regulation effect of 17β-estradiol on post-synaptic density 95 protein expression via estrogen receptor α-dependent Akt pathway.

PubMed

Wang, Qunan; Xia, Xin; Deng, Xiaomei; Li, Nian; Wu, Daji; Zhang, Long; Yang, Chengwei; Tao, Fangbiao; Zhou, Jiangning

2016-03-01

Lambda-cyhalothrin (LCT), one of the type II pyrethroids, has been widely used throughout the world. The estrogenic effect of LCT to increase cell proliferation has been well established. However, whether the estrogenic effect of LCT will influence neurodevelopment has not been investigated. In addition, 17β-Estradiol (E2) plays a crucial role in neurodevelopment and induces an increase in synaptic proteins. The post-synaptic density 95 (PSD95) protein, which is involved in the development of the structure and function of new spines and localized with estrogen receptor α (ERα) at the post-synaptic density (PSD), was detected in our study by using hippocampal neuron cell line HT22. We found that LCT up-regulated PSD95 and ERα expression, estrogen receptor (ER) antagonist ICI182,780 and phosphatidylinositol-4; 5-bisphosphate 3-kinase (PI3K) inhibitor LY294,002 blocked this effect. In addition, LCT disrupted the promotion effect of E2 on PSD95. To investigate whether the observed changes are caused by ERα-dependent signaling activation, we next detected the effects of LCT on the ERα-mediated PI3K-Protein kinase B (PKB/Akt)-eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) pathway. There existed an activation of Akt and the downstream factor 4E-BP1 after LCT treatment. In addition, LCT could disrupt the activation effect of E2 on the Akt pathway. However, no changes in cAMP response element-binding protein (CREB) activation and PSD95 messenger ribonucleic acid (mRNA) were observed. Our findings demonstrated that LCT could increase the PSD95 protein level via the ERα-dependent Akt pathway, and LCT might disrupt the up-regulation effect of E2 on PSD95 protein expression via this signaling pathway. Copyright © 2015. Published by Elsevier B.V.

[The role of BDNF pathway in lambda-cyhalothrin disrupting the promotion of 17β-Estradiol on Post-synaptic Density 95 protein expression in HT22 cell].

PubMed

Li, N; Wang, Q N; Wu, D J; Yang, C W; Luo, B B

2016-07-20

Objective: To explore the effect of BDNF pathway on lambda-cyhalothrin interfering estrogen promoting the expression of PSD95 in hippocampus neurons. Methods: HT22 cell line were used to, treating with lambda-cyhalothrin (LCT, 50 μmol/L) , 17β-Estradiol (E2, 10 nmol/L) , LCT (50 μmol/L) +TrkB FC (20 μg/ml) , E2 (10 nmol/L) +TrkB FC (20 μg/ml) , LCT (50 μmol/L) +ICI182 780 (1 μmol/L) , E2 (10 nmol/L) + ICI182 780 (1 μmol/L) , LCT (50 μmol/L) +E2 (10 nmol/L) for 24 h. MTT kit was used to detect cell viability. Post-synaptic Density 95 protein expression was measured by western blot. ELISA assay was used to detect the level of brain derived neurotrophic factor (BDNF) of culture supernatant and cell. Results: Campared to Sham, LCT or E2 could promote the expression of PSD95 LCT+ICI could reduce the expresion of BDNF ( P <0.05) , campared to LCT, LCT+TrkB FC could reduce the expression of PSD95 and LCT+ICI cound reduce the expresion of BDNF ( P <0.05) , campared to E2, E2+TrkB FC could reduce the expression of PSD95 and E 2 +ICI could reduce the expression of BDNF ( P <0.05) , campared to E2, LCT+ E2 could reduce the expression of PSD95 and BDNF ( P <0.05) . Conclusion: BDNF pathway plays a key role in E2 promoting the expression of PSD95 in neural cells. Although LCT alone has a similar effect on E2. LCT could disrupt the promotion of E2 on PSD95 expression via BDNF pathway.

The Relationship between Frontal Lobe Lesions, Course of Post-Stroke Depression, and 1-year Prognosis in Patients with First-Ever Ischemic Stroke

PubMed Central

Shi, Yu-Zhi; Xiang, Yu-Tao; Wu, Shuo-Lin; Zhang, Ning; Zhou, Juan; Bai, Ying; Wang, Shuo; Wang, Yi-Long; Zhao, Xing-Quan; Ungvari, Gabor S.; Chiu, Helen F. K.; Wang, Yong-Jun; Wang, Chun-Xue

2014-01-01

Background and Purpose Most studies on post-stroke depression (PSD) have focused on a certain time point after stroke instead of the time course of PSD. The aim of this study was to determine the relationship between frontal lobe lesions, course of PSD over a year following the stroke onset, and the 1-year prognosis in patients with first-ever ischemic stroke. Methods A total of 1067 patients from the prospective cohort study on the incidence and outcome of patients with post stroke depression in China who were diagnosed with first-ever ischemic stroke and attended 4 follow-up visits at 14±2 days, 3 months, 6 months, and 1 year after stroke onset, were enrolled in the study. PSD was diagnosed according to DSM-IV. The course of PSD was divided into the following two categories: persistent/recurrent depression and no/transient depression. Patients with any ischemic lesion responsible for the indexed stroke event located in the frontal lobe were defined as patients with frontal lobe lesions. Modified Rankin Scale (mRS) ≥2 at 1-year was considered to be poor prognosis. Results There were 109 patients with and 958 patients without frontal lobe lesions that formed the frontal lobe (FL) and no-frontal lobe (NFL) groups, respectively. After adjusting for confounding variables, frontal lobe lesion was significantly associated with persistent/recurrent PSD (OR 2.025, 95%CI 1.039–3.949). Overall, 32.7% of patients in the FL group had poor prognosis at 1- year compared with 22.7% in the NFL group (P = 0.021). Compared with no/transient depression, persistent/recurrent depression was found to be an independent predictor of poor prognosis at 1-year both in FL and NFL groups. Conclusions Long-term and periodical screening, evaluation and treatment are needed for PSD after the onset of ischemic stroke, particularly for patients with frontal lobe infarction. PMID:25003990

Pathological reorganization of NMDA receptors subunits and postsynaptic protein PSD-95 distribution in Alzheimer's disease.

PubMed

Leuba, Genevieve; Vernay, Andre; Kraftsik, Rudolf; Tardif, Eric; Riederer, Beat Michel; Savioz, Armand

2014-01-01

In Alzheimer's disease (AD), synaptic alterations play a major role and are often correlated with cognitive changes. In order to better understand synaptic modifications, we compared alterations in NMDA receptors and postsynaptic protein PSD-95 expression in the entorhinal cortex (EC) and frontal cortex (FC; area 9) of AD and control brains. We combined immunohistochemical and image analysis methods to quantify on consecutive sections the distribution of PSD-95 and NMDA receptors GluN1, GluN2A and GluN2B in EC and FC from 25 AD and control cases. The density of stained receptors was analyzed using multivariate statistical methods to assess the effect of neurodegeneration. In both regions, the number of neuronal profiles immunostained for GluN1 receptors subunit and PSD-95 protein was significantly increased in AD compared to controls (3-6 fold), while the number of neuronal profiles stained for GluN2A and GluN2B receptors subunits was on the contrary decreased (3-4 fold). The increase in marked neuronal profiles was more prominent in a cortical band corresponding to layers 3 to 5 with large pyramidal cells. Neurons positive for GluN1 or PSD-95 staining were often found in the same localization on consecutive sections and they were also reactive for the anti-tau antibody AD2, indicating a neurodegenerative process. Differences in the density of immunoreactive puncta representing neuropile were not statistically significant. Altogether these data indicate that GluN1 and PSD-95 accumulate in the neuronal perikarya, but this is not the case for GluN2A and GluN2B, while the neuropile compartment is less subject to modifications. Thus, important variations in the pattern of distribution of the NMDA receptors subunits and PSD-95 represent a marker in AD and by impairing the neuronal network, contribute to functional deterioration.

Data Series Subtraction with Unknown and Unmodeled Background Noise

NASA Technical Reports Server (NTRS)

Vitale, Stefano; Congedo, Giuseppe; Dolesi, Rita; Ferroni, Valerio; Hueller, Mauro; Vetrugno, Daniele; Weber, William Joseph; Audley, Heather; Danzmann, Karsten; Diepholz, Ingo;

Ovarian steroids increase PSD-95 expression and dendritic spines in the dorsal raphe of ovariectomized macaques.

PubMed

Rivera, Heidi M; Bethea, Cynthia L

2013-12-01

Estradiol (E) and progesterone (P) promote spinogenesis in several brain areas. Intracellular signaling cascades that promote spinogenesis involve RhoGTPases, glutamate signaling and synapse assembly. We found that in serotonin neurons, E ± P administration increases (a) gene and protein expression of RhoGTPases, (b) gene expression of glutamate receptors, and (c) gene expression of pivotal synapse assembly proteins. Therefore, in this study we determined whether structural changes in dendritic spines in the dorsal raphe follow the observed changes in gene and protein expression. Dendritic spines were examined with immunogold silver staining of a spine marker protein, postsynaptic density-95 (PSD-95) and with Golgi staining. In the PSD-95 study, adult Ovx monkeys received placebo, E, P, or E + P for 1 month (n = 3/group). Sections were immunostained for PSD-95 and the number of PSD-95-positive puncta was determined with stereology. E, P, and E + P treatment significantly increased the total number of PSD-95-positive puncta (ANOVA, P = 0.04). In the golgi study, adult Ovx monkeys received placebo, E or E + P for 1 month (n = 3-4) and the midbrain was golgi-stained. A total of 80 neurons were analyzed with Neurolucida software. There was a significant difference in spine density that depended on branch order (two-way ANOVA). E + P treatment significantly increased spine density in higher-order (3°-5°) dendritic branches relative to Ovx group (Bonferroni, P < 0.05). In summary, E + P leads to the elaboration of dendritic spines on dorsal raphe neurons. The ability of E to induce PSD-95, but not actual spines, suggests either a sampling or time lag issue. Increased spinogenesis on serotonin dendrites would facilitate excitatory glutamatergic input and, in turn, increase serotonin neurotransmission throughout the brain. Copyright © 2013 Wiley Periodicals, Inc.

Melatonin improves neuroplasticity by upregulating the growth-associated protein-43 (GAP-43) and NMDAR postsynaptic density-95 (PSD-95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long-term recovery period.

PubMed

Juan, Wei-Sheng; Huang, Sheng-Yang; Chang, Che-Chao; Hung, Yu-Chang; Lin, Yu-Wen; Chen, Tsung-Ying; Lee, Ai-Hua; Lee, Ai-Chiang; Wu, Tian-Shung; Lee, E-Jian

2014-03-01

Recent evidence shows that the NMDAR postsynaptic density-95 (PSD-95), growth-associated protein-43 (GAP-43), and matrix metalloproteinase-9 (MMP-9) protein enhance neuroplasticity at the subacute stage of stroke. Here, we evaluated whether melatonin would modulate the PSD-95, GAP-43, and MMP-9 proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to experimental stroke. Adult male Sprague-Dawley rats were treated with melatonin (5 mg/kg) or vehicle at reperfusion onset after transient occlusion of the right middle cerebral artery (tMCAO) for 90 min. Animals were euthanized for Western immunoblot analyses for the PSD-95 and GAP-43 proteins and gelatin zymography for the MMP-9 activity at 7 days postinsult. Another set of animals was sacrificed for histologic and Golgi-Cox-impregnated sections at 28 days postinsult. In cultured neurons exposed to glutamate excitotoxicity, melatonin significantly upregulated the GAP-43 and PSD-95 expressions and improved dendritic aborizations (P<0.05, respectively). Relative to controls, melatonin-treated stroke animals caused a significant improvement in GAP-43 and PSD-95 expressions as well as the MMP-9 activity in the ischemic brain (P<0.05). Consequently, melatonin also significantly promoted the dendritic spine density and reduced infarction in the ischemic brain, and improved neurobehaviors as well at 28 days postinsult (P<0.05, respectively). Together, melatonin upregulates GAP-43, PSD-95, and MMP-9 proteins, which likely accounts for its actions to improve neuroplasticity in cultured neurons exposed to glutamate excitotoxicity and to enhance long-term neuroprotection, neuroplasticity, and brain remodeling in stroke rats. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The relationship between frontal lobe lesions, course of post-stroke depression, and 1-year prognosis in patients with first-ever ischemic stroke.

PubMed

Shi, Yu-Zhi; Xiang, Yu-Tao; Wu, Shuo-Lin; Zhang, Ning; Zhou, Juan; Bai, Ying; Wang, Shuo; Wang, Yi-Long; Zhao, Xing-Quan; Ungvari, Gabor S; Chiu, Helen F K; Wang, Yong-Jun; Wang, Chun-Xue

2014-01-01

Most studies on post-stroke depression (PSD) have focused on a certain time point after stroke instead of the time course of PSD. The aim of this study was to determine the relationship between frontal lobe lesions, course of PSD over a year following the stroke onset, and the 1-year prognosis in patients with first-ever ischemic stroke. A total of 1067 patients from the prospective cohort study on the incidence and outcome of patients with post stroke depression in China who were diagnosed with first-ever ischemic stroke and attended 4 follow-up visits at 14±2 days, 3 months, 6 months, and 1 year after stroke onset, were enrolled in the study. PSD was diagnosed according to DSM-IV. The course of PSD was divided into the following two categories: persistent/recurrent depression and no/transient depression. Patients with any ischemic lesion responsible for the indexed stroke event located in the frontal lobe were defined as patients with frontal lobe lesions. Modified Rankin Scale (mRS) ≥2 at 1-year was considered to be poor prognosis. There were 109 patients with and 958 patients without frontal lobe lesions that formed the frontal lobe (FL) and no-frontal lobe (NFL) groups, respectively. After adjusting for confounding variables, frontal lobe lesion was significantly associated with persistent/recurrent PSD (OR 2.025, 95%CI 1.039-3.949). Overall, 32.7% of patients in the FL group had poor prognosis at 1- year compared with 22.7% in the NFL group (P = 0.021). Compared with no/transient depression, persistent/recurrent depression was found to be an independent predictor of poor prognosis at 1-year both in FL and NFL groups. Long-term and periodical screening, evaluation and treatment are needed for PSD after the onset of ischemic stroke, particularly for patients with frontal lobe infarction.

THE LONGEST TIMESCALE X-RAY VARIABILITY REVEALS EVIDENCE FOR ACTIVE GALACTIC NUCLEI IN THE HIGH ACCRETION STATE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Youhong, E-mail: youhong.zhang@mail.tsinghua.edu.cn

2011-01-01

The All Sky Monitor (ASM) on board the Rossi X-ray Timing Explorer has continuously monitored a number of active galactic nuclei (AGNs) with similar sampling rates for 14 years, from 1996 January to 2009 December. Utilizing the archival ASM data of 27 AGNs, we calculate the normalized excess variances of the 300-day binned X-ray light curves on the longest timescale (between 300 days and 14 years) explored so far. The observed variance appears to be independent of AGN black-hole mass and bolometric luminosity. According to the scaling relation of black-hole mass (and bolometric luminosity) from galactic black hole X-ray binariesmore » (GBHs) to AGNs, the break timescales that correspond to the break frequencies detected in the power spectral density (PSD) of our AGNs are larger than the binsize (300 days) of the ASM light curves. As a result, the singly broken power-law (soft-state) PSD predicts the variance to be independent of mass and luminosity. Nevertheless, the doubly broken power-law (hard-state) PSD predicts, with the widely accepted ratio of the two break frequencies, that the variance increases with increasing mass and decreases with increasing luminosity. Therefore, the independence of the observed variance on mass and luminosity suggests that AGNs should have soft-state PSDs. Taking into account the scaling of the break timescale with mass and luminosity synchronously, the observed variances are also more consistent with the soft-state than the hard-state PSD predictions. With the averaged variance of AGNs and the soft-state PSD assumption, we obtain a universal PSD amplitude of 0.030 {+-} 0.022. By analogy with the GBH PSDs in the high/soft state, the longest timescale variability supports the standpoint that AGNs are scaled-up GBHs in the high accretion state, as already implied by the direct PSD analysis.« less

40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

Code of Federal Regulations, 2014 CFR

2014-07-01

... not be the cause for any Prevention of Significant Deterioration (PSD) increment to be exceeded, then... quality standards or cause any PSD increment to be exceeded, then EPA shall so inform the State of its...

40 CFR 52.1679 - EPA-approved New York State regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... approval; no action taken on provisions that may require PSD permits for sources of greenhouse gas (GHG) emissions with emissions below the thresholds identified in EPA's final PSD and Title V GHG Tailoring Rule...

40 CFR 144.31 - Application for a permit; authorization by permit.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Significant Deterioration (PSD) program under the Clean Air Act. (2) Name, mailing address, and location of... (PSD) program under the Clean Air Act. (v) Nonattainment program under the Clean Air Act. (vi) National...

40 CFR 52.27 - Protection of visibility from sources in attainment areas.

Code of Federal Regulations, 2012 CFR

2012-07-01

... quality standards for such pollutants, and where a State PSD program has been approved as part of the... Act, in the prevention of significant deterioration (PSD) program approved as part of the applicable...

40 CFR 144.31 - Application for a permit; authorization by permit.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Significant Deterioration (PSD) program under the Clean Air Act. (2) Name, mailing address, and location of... (PSD) program under the Clean Air Act. (v) Nonattainment program under the Clean Air Act. (vi) National...

40 CFR 52.27 - Protection of visibility from sources in attainment areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... quality standards for such pollutants, and where a State PSD program has been approved as part of the... Act, in the prevention of significant deterioration (PSD) program approved as part of the applicable...

40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

Code of Federal Regulations, 2010 CFR

2010-07-01

... not be the cause for any Prevention of Significant Deterioration (PSD) increment to be exceeded, then... quality standards or cause any PSD increment to be exceeded, then EPA shall so inform the State of its...

40 CFR 144.31 - Application for a permit; authorization by permit.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Significant Deterioration (PSD) program under the Clean Air Act. (2) Name, mailing address, and location of... (PSD) program under the Clean Air Act. (v) Nonattainment program under the Clean Air Act. (vi) National...

40 CFR 52.27 - Protection of visibility from sources in attainment areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

... quality standards for such pollutants, and where a State PSD program has been approved as part of the... Act, in the prevention of significant deterioration (PSD) program approved as part of the applicable...

40 CFR 52.27 - Protection of visibility from sources in attainment areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

... quality standards for such pollutants, and where a State PSD program has been approved as part of the... Act, in the prevention of significant deterioration (PSD) program approved as part of the applicable...

40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

Code of Federal Regulations, 2013 CFR

2013-07-01

... not be the cause for any Prevention of Significant Deterioration (PSD) increment to be exceeded, then... quality standards or cause any PSD increment to be exceeded, then EPA shall so inform the State of its...

40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

Code of Federal Regulations, 2011 CFR

2011-07-01

... not be the cause for any Prevention of Significant Deterioration (PSD) increment to be exceeded, then... quality standards or cause any PSD increment to be exceeded, then EPA shall so inform the State of its...

40 CFR 144.31 - Application for a permit; authorization by permit.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Significant Deterioration (PSD) program under the Clean Air Act. (2) Name, mailing address, and location of... (PSD) program under the Clean Air Act. (v) Nonattainment program under the Clean Air Act. (vi) National...

40 CFR 52.27 - Protection of visibility from sources in attainment areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... quality standards for such pollutants, and where a State PSD program has been approved as part of the... Act, in the prevention of significant deterioration (PSD) program approved as part of the applicable...

40 CFR 52.1601 - Control strategy and regulations: Sulfur oxides.

Code of Federal Regulations, 2012 CFR

2012-07-01

... not be the cause for any Prevention of Significant Deterioration (PSD) increment to be exceeded, then... quality standards or cause any PSD increment to be exceeded, then EPA shall so inform the State of its...

The polarity protein partitioning-defective 1 (PAR-1) regulates dendritic spine morphogenesis through phosphorylating postsynaptic density protein 95 (PSD-95).

PubMed

Wu, Qian; DiBona, Victoria L; Bernard, Laura P; Zhang, Huaye

2012-08-31

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95.

Particle-size distribution models for the conversion of Chinese data to FAO/USDA system.

PubMed

Shangguan, Wei; Dai, YongJiu; García-Gutiérrez, Carlos; Yuan, Hua

2014-01-01

We investigated eleven particle-size distribution (PSD) models to determine the appropriate models for describing the PSDs of 16349 Chinese soil samples. These data are based on three soil texture classification schemes, including one ISSS (International Society of Soil Science) scheme with four data points and two Katschinski's schemes with five and six data points, respectively. The adjusted coefficient of determination r (2), Akaike's information criterion (AIC), and geometric mean error ratio (GMER) were used to evaluate the model performance. The soil data were converted to the USDA (United States Department of Agriculture) standard using PSD models and the fractal concept. The performance of PSD models was affected by soil texture and classification of fraction schemes. The performance of PSD models also varied with clay content of soils. The Anderson, Fredlund, modified logistic growth, Skaggs, and Weilbull models were the best.

Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation.

PubMed

Vercruysse, J; Burggraeve, A; Fonteyne, M; Cappuyns, P; Delaet, U; Van Assche, I; De Beer, T; Remon, J P; Vervaet, C

2015-02-01

Twin screw granulation (TSG) has been reported by different research groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution (PSD), resulting in suboptimal flow properties. The aim of the current study was to evaluate the impact of granulator screw configuration on the PSD of granules produced by TSG. Experiments were performed using a 25 mm co-rotating twin screw granulator, being part of the ConsiGma™-25 system (a fully continuous from-powder-to-tablet manufacturing line from GEA Pharma Systems). Besides the screw elements conventionally used for TSG (conveying and kneading elements), alternative designs of screw elements (tooth-mixing-elements (TME), screw mixing elements (SME) and cutters) were investigated using an α-lactose monohydrate formulation granulated with distilled water. Granulation with only conveying elements resulted in wide and multimodal PSD. Using kneading elements, the width of the PSD could be partially narrowed and the liquid distribution was more homogeneous. However, still a significant fraction of oversized agglomerates was obtained. Implementing additional kneading elements or cutters in the final section of the screw configuration was not beneficial. Furthermore, granulation with only TME or SME had limited impact on the width of the PSD. Promising results were obtained by combining kneading elements with SME, as for these configurations the PSD was narrower and shifted to the size fractions suitable for tableting. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of the dimeric PSD-95 inhibitor UCCB01-144 on functional recovery after fimbria-fornix transection in rats.

PubMed

Sommer, Jens Bak; Bach, Anders; Malá, Hana; Strømgaard, Kristian; Mogensen, Jesper; Pickering, Darryl S

2017-10-01

Pharmacological inhibition of PSD-95 is a promising therapeutic strategy in the treatment of stroke, and positive effects of monomeric and dimeric PSD-95 inhibitors have been reported in numerous studies. However, whether therapeutic effects will generalize to other types of acute brain injury such as traumatic brain injury (TBI), which has pathophysiological mechanisms in common with stroke, is currently uncertain. We have previously found a lack of neuroprotective effects of dimeric PSD-95 inhibitors in the controlled cortical impact model of TBI in rats. However, as no single animal model is currently able to mimic the complex and heterogeneous pathophysiology of TBI, it is necessary to assess treatment effects across a range of models. In this preliminary study we investigated the neuroprotective abilities of the dimeric PSD-95 inhibitor UCCB01-144 after fimbria-fornix (FF) transection in rats. UCCB01-144 or saline was injected into the lateral tail vein of rats immediately after sham surgery or FF-transection, and effects on spatial delayed alternation in a T-maze were assessed over a 28-day period. Task acquisition was significantly impaired in FF-transected animals, but there were no significant effects of UCCB01-144 on spatial delayed alternation after FF-transection or sham surgery, although decelerated learning curves were seen after treatment with UCCB01-144 in FF-transected animals. The results of the present study are consistent with previous research showing a lack of neuroprotective effects of PSD-95 inhibition in experimental models of TBI. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, H; Lin, H; Darafsheh, A

Purpose: To characterize basic performance of plastic scintillator detectors (PSD) designed for dosimetry of radiation therapy. Methods: The Exradin W1 Scintillator is a plastic scintillating fiber-based detector designed for highly accurate measurement of small radiotherapy fields used in patient plan verification and machine commissioning and QA procedures. The Cerenkov emissions were corrected using spectral separation. The optical signal was converted to electronic signal with a photodiode. We measured its dosimetry performance, including percentage depth dose, output factor, dose and dose rate linear response. We compared the dosimetry results with reference ion chamber measurements. Results: The dosimetry results of PSD agreemore » well with reference ion chamber measurements. For percentage depth dose, the differences between PSD and ion chamber results are on average 1.7±1.1% and 0.8±0.8% with a maximum of 3.5% and 2.7% for 6MV and 15MV beams, respectively. For the output factors, PSD measurements are within 2% from ion chamber results. The dose linear response is within 1% when dose is larger than 20 MU for both 6 MV and 15 MV. The dose rate linear response is within 1% for the entire dose rate used (100 MU/min to 600MU/min). Conclusions: The current design of PSD is feasible for the dosimtry measurement in radiation therapy. This combination of PSD and photodiode system could be extended to multichannel array detection of dose distribution. It might as well be used as range verification in proton therapy. The work is partially supported by: DOD (W81XWH-09-2-0174) and American Cancer Society (IRG-78-002-28)« less

Targeting protein-protein interactions with trimeric ligands: high affinity inhibitors of the MAGUK protein family.

PubMed

Nissen, Klaus B; Haugaard-Kedström, Linda M; Wilbek, Theis S; Nielsen, Line S; Åberg, Emma; Kristensen, Anders S; Bach, Anders; Jemth, Per; Strømgaard, Kristian

2015-01-01

PDZ domains in general, and those of PSD-95 in particular, are emerging as promising drug targets for diseases such as ischemic stroke. We have previously shown that dimeric ligands that simultaneously target PDZ1 and PDZ2 of PSD-95 are highly potent inhibitors of PSD-95. However, PSD-95 and the related MAGUK proteins contain three consecutive PDZ domains, hence we envisioned that targeting all three PDZ domains simultaneously would lead to more potent and potentially more specific interactions with the MAGUK proteins. Here we describe the design, synthesis and characterization of a series of trimeric ligands targeting all three PDZ domains of PSD-95 and the related MAGUK proteins, PSD-93, SAP-97 and SAP-102. Using our dimeric ligands targeting the PDZ1-2 tandem as starting point, we designed novel trimeric ligands by introducing a PDZ3-binding peptide moiety via a cysteine-derivatized NPEG linker. The trimeric ligands generally displayed increased affinities compared to the dimeric ligands in fluorescence polarization binding experiments and optimized trimeric ligands showed low nanomolar inhibition towards the four MAGUK proteins, thus being the most potent inhibitors described. Kinetic experiments using stopped-flow spectrometry showed that the increase in affinity is caused by a decrease in the dissociation rate of the trimeric ligand as compared to the dimeric ligands, likely reflecting the lower probability of simultaneous dissociation of all three PDZ ligands. Thus, we have provided novel inhibitors of the MAGUK proteins with exceptionally high affinity, which can be used to further elucidate the therapeutic potential of these proteins.

Validation of fibromyalgia survey questionnaire and polysymptomatic distress scale in a Persian population.

PubMed

Bidari, Ali; Ghavidel-Parsa, Banafsheh; Amir Maafi, Alireza; Montazeri, Ali; Ghalehbaghi, Babak; Hassankhani, Amir; Aarabi, Yasaman; Haghdoost, Afrooz

2015-12-01

The aim of this study was to assess validity of the fibromyalgia survey questionnaire (FSQ) and polysymptomatic distress scale (PSD) in an Iranian population. We also sought to classify the severity levels of fibromyalgia (FM) symptoms according to the PSD scale. Participants were divided into FM and non-FM chronic pain disorder groups according to expert physician diagnosis. Patients in both groups answered to Persian-translated version of FSQ, fibromyalgia impact questionnaire (FIQ) and Short-Form-12 (SF-12). Both 1990 ACR criteria and FSDC were assessed in participates of two groups. Internal consistency and construct validity were evaluated. There was good internal consistency measured by Cronbach's alpha (0.814 for FSQ). FSQ and its subscales correlated significantly with FIQ scores and SF-12 subscales, indicating acceptable construct validity. The concordance rates of FSQ with 1990 ACR criteria and expert diagnosis were 61.2 and 75.7, respectively (convergence validity). The mean score of PSD and its components in FM group were significantly more than in control groups (discriminative validity). Using lower PSD score cutoff (≥8.5) for the diagnosis of fibromyalgia appeared to be the most effective approach in our population. ROC analysis of the PSD scores revealed 8.5-11.5, 11.5-15 and more than 15, respectively, as a mild, moderate and severe FM. Persian version of FSQ was a valid instrument for application in survey research among Iranian patients with chronic pain disorders. The current study revealed that PSD could be used as a valid tool for assessment of symptoms intensity regardless of fibromyalgia diagnosis.

76 FR 26224 - Revisions to the California State Implementation Plan, Northern Sonoma County Air Pollution...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-06

... Significant Deterioration (PSD) permit programs. These proposed revisions update the definitions used in the districts' PSD permit programs. DATES: Any comments on this proposal must arrive by June 6, 2011. ADDRESSES...

40 CFR 124.4 - Consolidation of permit processing.

Code of Federal Regulations, 2011 CFR

2011-07-01

... consolidate processing a PSD permit with any other permit under paragraph (a) or (b) of this section when to do so would delay issuance of the PSD permit more than one year from the effective date of the...

40 CFR 124.4 - Consolidation of permit processing.

Code of Federal Regulations, 2012 CFR

2012-07-01

... consolidate processing a PSD permit with any other permit under paragraph (a) or (b) of this section when to do so would delay issuance of the PSD permit more than one year from the effective date of the...

40 CFR 124.4 - Consolidation of permit processing.

Code of Federal Regulations, 2013 CFR

2013-07-01

... consolidate processing a PSD permit with any other permit under paragraph (a) or (b) of this section when to do so would delay issuance of the PSD permit more than one year from the effective date of the...

40 CFR 124.4 - Consolidation of permit processing.

Code of Federal Regulations, 2010 CFR

2010-07-01

... consolidate processing a PSD permit with any other permit under paragraph (a) or (b) of this section when to do so would delay issuance of the PSD permit more than one year from the effective date of the...

40 CFR 124.4 - Consolidation of permit processing.

Code of Federal Regulations, 2014 CFR

2014-07-01

... processing a PSD permit with any other permit under paragraph (a) or (b) of this section when to do so would delay issuance of the PSD permit more than one year from the effective date of the application under...