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Sample records for pcp based simulacao

  1. PCP

    MedlinePlus

    ... Right Sport for You Healthy School Lunch Planner PCP KidsHealth > For Teens > PCP Print A A A ... Quit? Avoiding PCP en español PCP What Is PCP? PCP, or phencyclidine, is a dangerous drug that ...

  2. PCP-based mice models of schizophrenia: differential behavioral, neurochemical and cellular effects of acute and subchronic treatments.

    PubMed

    Castañé, Anna; Santana, Noemí; Artigas, Francesc

    2015-11-01

    N-methyl-D-aspartate receptor (NMDA-R) hypofunction has been proposed to account for the pathophysiology of schizophrenia. Thus, NMDA-R blockade has been used to model schizophrenia in experimental animals. Acute and repeated treatments have been successfully tested; however, long-term exposure to NMDA-R antagonists more likely resembles the core symptoms of the illness. To explore whether schizophrenia-related behaviors are differentially induced by acute and subchronic phencyclidine (PCP) treatment in mice and to examine the neurobiological bases of these differences. Subchronic PCP induced a sensitization of acute locomotor effects. Spontaneous alternation in a T-maze and novel object recognition performance were impaired after subchronic but not acute PCP, suggesting a deficit in working memory. On the contrary, reversal learning and immobility in the tail suspension test were unaffected. Subchronic PCP significantly reduced basal dopamine but not serotonin output in medial prefrontal cortex (mPFC) and markedly decreased the expression of tyrosine hydroxylase in the ventral tegmental area. Finally, acute and subchronic PCP treatments evoked a different pattern of c-fos expression. At 1 h post-treatment, acute PCP increased c-fos expression in many cortical regions, striatum, thalamus, hippocampus, and dorsal raphe. However, the increased c-fos expression produced by subchronic PCP was restricted to the retrosplenial cortex, thalamus, hippocampus, and supramammillary nucleus. Four days after the last PCP injection, c-fos expression was still increased in the hippocampus of subchronic PCP-treated mice. Acute and subchronic PCP administration differently affects neuronal activity in brain regions relevant to schizophrenia, which could account for their different behavioral effects.

  3. Remarkable catalytic activity of dinitrogen-bridged dimolybdenum complexes bearing NHC-based PCP-pincer ligands toward nitrogen fixation

    PubMed Central

    Eizawa, Aya; Arashiba, Kazuya; Tanaka, Hiromasa; Kuriyama, Shogo; Matsuo, Yuki; Nakajima, Kazunari; Yoshizawa, Kazunari; Nishibayashi, Yoshiaki

    2017-01-01

    Intensive efforts for the transformation of dinitrogen using transition metal–dinitrogen complexes as catalysts under mild reaction conditions have been made. However, limited systems have succeeded in the catalytic formation of ammonia. Here we show that newly designed and prepared dinitrogen-bridged dimolybdenum complexes bearing N-heterocyclic carbene- and phosphine-based PCP-pincer ligands [{Mo(N2)2(PCP)}2(μ-N2)] (1) work as so far the most effective catalysts towards the formation of ammonia from dinitrogen under ambient reaction conditions, where up to 230 equiv. of ammonia are produced based on the catalyst. DFT calculations on 1 reveal that the PCP-pincer ligand serves as not only a strong σ-donor but also a π-acceptor. These electronic properties are responsible for a solid connection between the molybdenum centre and the pincer ligand, leading to the enhanced catalytic activity for nitrogen fixation. PMID:28374835

  4. Remarkable catalytic activity of dinitrogen-bridged dimolybdenum complexes bearing NHC-based PCP-pincer ligands toward nitrogen fixation.

    PubMed

    Eizawa, Aya; Arashiba, Kazuya; Tanaka, Hiromasa; Kuriyama, Shogo; Matsuo, Yuki; Nakajima, Kazunari; Yoshizawa, Kazunari; Nishibayashi, Yoshiaki

    2017-04-04

    Intensive efforts for the transformation of dinitrogen using transition metal-dinitrogen complexes as catalysts under mild reaction conditions have been made. However, limited systems have succeeded in the catalytic formation of ammonia. Here we show that newly designed and prepared dinitrogen-bridged dimolybdenum complexes bearing N-heterocyclic carbene- and phosphine-based PCP-pincer ligands [{Mo(N2)2(PCP)}2(μ-N2)] (1) work as so far the most effective catalysts towards the formation of ammonia from dinitrogen under ambient reaction conditions, where up to 230 equiv. of ammonia are produced based on the catalyst. DFT calculations on 1 reveal that the PCP-pincer ligand serves as not only a strong σ-donor but also a π-acceptor. These electronic properties are responsible for a solid connection between the molybdenum centre and the pincer ligand, leading to the enhanced catalytic activity for nitrogen fixation.

  5. Remarkable catalytic activity of dinitrogen-bridged dimolybdenum complexes bearing NHC-based PCP-pincer ligands toward nitrogen fixation

    NASA Astrophysics Data System (ADS)

    Eizawa, Aya; Arashiba, Kazuya; Tanaka, Hiromasa; Kuriyama, Shogo; Matsuo, Yuki; Nakajima, Kazunari; Yoshizawa, Kazunari; Nishibayashi, Yoshiaki

    2017-04-01

    Intensive efforts for the transformation of dinitrogen using transition metal-dinitrogen complexes as catalysts under mild reaction conditions have been made. However, limited systems have succeeded in the catalytic formation of ammonia. Here we show that newly designed and prepared dinitrogen-bridged dimolybdenum complexes bearing N-heterocyclic carbene- and phosphine-based PCP-pincer ligands [{Mo(N2)2(PCP)}2(μ-N2)] (1) work as so far the most effective catalysts towards the formation of ammonia from dinitrogen under ambient reaction conditions, where up to 230 equiv. of ammonia are produced based on the catalyst. DFT calculations on 1 reveal that the PCP-pincer ligand serves as not only a strong σ-donor but also a π-acceptor. These electronic properties are responsible for a solid connection between the molybdenum centre and the pincer ligand, leading to the enhanced catalytic activity for nitrogen fixation.

  6. Substance use - phencyclidine (PCP)

    MedlinePlus

    PCP; Substance abuse - phencyclidine; Drug abuse - phencyclidine; Drug use - phencyclidine ... PA: Elsevier; 2016:chap 50. National Institute on Drug Abuse. Research report series: Hallucinogens and dissociative drugs. Updated ...

  7. PCP (phencyclidine): an update.

    PubMed

    Garey, R E

    1979-01-01

    The steady rise in the promiscuous use of phencyclidine (PCP) as a "recreational" drug has recently gained nationwide attention because of the numerous violent and/or bizarre incidents caused by the use of this drug. Because the media often exaggerate reports of bizarre and violent behavior to make a "good" story, the potential PCP user may be tempted to ignore the media warnings. In the case of PCP, however exaggerated the story, a real danger does exist. So, despite numerous newspaper, radio and television warnings about the possible consequences of PCP use and abuse, the incidence of toxic reactions continues to climb. In many cases PCP is sold as other drugs, particularly THC, and in various colored capsules, tablets, liquids and crystals which may explain the increased usage despite the numerous warnings against its use. The advances in laboratory techniques and chemical processess have enabled the clandestine chemist to prepare relatively pure PCP and thus eliminate many of the toxic side effects due to impurities in the drug. In addition, 30 or more psychoactive PCP analogues have been developed and are starting to make an appearance on the street. PCP is perhaps the most potent psychotomimetic compound known at the present time and is capable of inducing a psychosis which is clinically indistinguishable from schizophrenia. The psychosis-producing effects of PCP are the most common toxic effects seen in hospital emergency rooms; but as the amount of PCP taken and/or the simultaneous involvement of other drugs, particularly barbiturates, occurs, severe medical problems (e.g., coma, seizures, respiratory arrest) begin to appear. Death from high doses of PCP or PCP plus other drugs does occur, but the principal cause of death from PCP abuse is due to trauma, homicide or suicide (usually of the bizarre or violent form). Young adult males, persons predisposed to mental illness and naive drug users appear to be the most susceptible to the adverse effects of PCP

  8. PCP Use among Adolescents.

    ERIC Educational Resources Information Center

    Young, Thomas J.

    1987-01-01

    This article, aimed at professionals in the field of adolescent psychology, briefly reviews the use of phencyclidine (PCP), its pharmacology, clinical effects, diagnosis, treatment, and prevention. (Author/BN)

  9. PCP Use among Adolescents.

    ERIC Educational Resources Information Center

    Young, Thomas J.

    1987-01-01

    This article, aimed at professionals in the field of adolescent psychology, briefly reviews the use of phencyclidine (PCP), its pharmacology, clinical effects, diagnosis, treatment, and prevention. (Author/BN)

  10. PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent

    SciTech Connect

    Tamminga, C.A.; Tanimoto, K.; Kuo, S.; Chase, T.N.; Contreras, P.C.; Rice, K.C.; Jackson, A.E.; O'Donohue, T.L.

    1987-01-01

    The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with (/sup 14/C)-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor.

  11. Pneumocystis jiroveci pneumonia (PCP) in patients receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast cancer: incidence and risk factors.

    PubMed

    Waks, Adrienne G; Tolaney, Sara M; Galar, Alicia; Arnaout, Amal; Porter, Julie B; Marty, Francisco M; Winer, Eric P; Hammond, Sarah P; Baden, Lindsey R

    2015-11-01

    Opportunistic infection with Pneumocystis jiroveci pneumonia (PCP) has not been recognized as a significant complication of early-stage breast cancer treatment. However, we have observed an increase in PCP incidence among patients receiving chemotherapy for early-stage breast cancer. Herein we identify risk factors for and calculate incidence of PCP in this population. We identified all cases of PCP at Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH) from 1/1/2000 to 12/31/2013 in patients with stage I-III breast cancer treated with an adriamycin/cyclophosphamide (AC)-containing regimen. Nineteen cases of PCP in non-metastatic breast cancer patients were identified. All patients with PCP were diagnosed after receipt of either three or four cycles of AC chemotherapy on a dose-dense schedule. Patients who developed PCP were treated with median 16.4 mg prednisone equivalents/day as nausea prophylaxis for a median 64 days. The overall incidence of PCP among 2057 patients treated with neoadjuvant or adjuvant dose-dense AC for three or more cycles was 0.6 % (95 % confidence interval 0.3-1.0 %). No PCP was diagnosed in 1001 patients treated with non-dose-dense AC. There was one death from PCP. Women receiving dose-dense AC chemotherapy for early-stage breast cancer are at risk for PCP. Administering the same chemotherapy and corticosteroid dose over an 8-week versus 12-week non-dose-dense schedule appears to have created a novel infectious vulnerability. Replacing dexamethasone with alternative anti-emetics may mitigate this risk.

  12. Treatment of PCP addiction and PCP addiction-related behavior

    DOEpatents

    Dewey, Stephen L.; Brodie, Jonathan D.; Ashby, Jr., Charles R.

    2002-01-01

    The present invention provides a method for changing addiction-related behavior of a mammal suffering from addiction to phencyclidine (PCP). The method includes administering to the mammal an effective amount of gamma vinylGABA (GVG) or a pharmaceutically acceptable salt thereof, or an enantiomer or a racemic mixture thereof, wherein the effective amount is sufficient to diminish, inhibit or eliminate behavior associated with craving or use of PCP.

  13. PCP

    MedlinePlus

    ... their surroundings. It can also distort a user's perceptions of sight, sound, and reality — the drug is known for giving users a false sense of strength, power, and invincibility. Higher doses of ...

  14. The PCP SYS IV Management System: Implementation and Training Overview.

    ERIC Educational Resources Information Center

    Silver, Dorothy Z.; Clapp, Elizabeth J.

    This is the final paper in a series of three on SYS IV, a computer-based management system developed by the PLATO Curriculum Project (PCP) which tests students, routes students to lessons, stores detailed records of online student activity, and keeps summary records of student activities. An introduction describes how the system simultaneously…

  15. The PCP SYS IV Management System: Educational Overview.

    ERIC Educational Resources Information Center

    Siegel, Martin A.; Davis, Dennis M.

    This paper describes the structure and function of the SYS IV PLATO Curriculum Project's (PCP) computer-based management system and justifies the system design. A consideration of features most critical in the design of management systems provides the context for a discussion of specific SYS IV features, which include its ability to deliver any…

  16. Pneumocystis Pneumonia and the Rheumatologist: Which Patients Are At Risk and How Can PCP Be Prevented?

    PubMed

    Wolfe, Rachel M; Peacock, James E

    2017-06-01

    Immunosuppressive therapy for connective tissue diseases (CTDs) is steadily becoming more intense. The resultant impairment in cell-mediated immunity has been accompanied by an increasing risk for opportunistic infection (OI). Pneumocystis pneumonia (PCP) has been recognized as an OI in patients with CTDs, but specific risk factors and precise indications for PCP prophylaxis remain poorly defined. This review was undertaken to update information on the risk of PCP in patients with CTDs and to examine current guidelines for PCP prophylaxis in this population. Data on the occurrence of PCP and indications for prophylaxis in patients with CTDs is sparse. Large systematic reviews did not incorporate patients with CTD secondary to the lack of randomized control trials. Upon reviewing guidelines published since 2015, prophylaxis for PCP is recommended only for patients with ANCA-positive vasculitis, specifically granulomatosis with polyangiitis (GPA), who are undergoing intense induction therapy. Evidence-based recommendations for the prophylaxis of PCP in patients with CTDs cannot be provided. There is expert consensus that PCP prophylaxis is warranted in patients with GPA undergoing induction therapy. Prophylaxis should perhaps also be considered for other CTD patients who are receiving similar intense immunosuppressive therapy especially if they are lymphopenic or have a low CD4 count.

  17. PCP IMMUMOASSAY TECHNOLOGIES - INNOVATIVE TECHNOLOGY EVALUATION REPORT

    EPA Science Inventory

    Three enzyme-linked immunosorbent assay technologies for pentachlorophenol (PCP) testing in soil and water were evaluated. Penta RISc Test Systems (formerly ENSYS, Inc.), EnviroGard™ PCP Immunoassay Test Kit (Millipore Corp.), and Pentachlorophenol RaPID Assay (formerly Ohmicron ...

  18. PCP IMMUMOASSAY TECHNOLOGIES - INNOVATIVE TECHNOLOGY EVALUATION REPORT

    EPA Science Inventory

    Three enzyme-linked immunosorbent assay technologies for pentachlorophenol (PCP) testing in soil and water were evaluated. Penta RISc Test Systems (formerly ENSYS, Inc.), EnviroGard™ PCP Immunoassay Test Kit (Millipore Corp.), and Pentachlorophenol RaPID Assay (formerly Ohmicron ...

  19. PCP copolymers grafted with RGD enhance the rates of RGD-PCP micelles internalized into cells.

    PubMed

    Chung, Tze-Wen; Tyan, Yu-Chang; Yang, Jean-Dean

    2010-01-01

    RGD-PCP copolymers were fabricated by grafting Arg-Gly-Asp (RGD) peptide to poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCP) copolymers and the rate of internalization of RGD-PCP micelles by PC 12 cells were examined. Increasing intensity of the absorbance of amine groups in FT-IR spectra of RGD-PCP copolymers compared with those of PCP copolymers indicated the presence of RGD in new copolymers. Moreover, the grafting efficiency and molar ratio of RGD peptides to PCP copolymers were 88.2% and 0.45, respectively, analysed with HPLC. The RGD-PCP copolymers self-assemble to micelles at the critical micelle concentration (CMC) of 0.018 wt% (178 mg L(-1)) and with a mean diameter of 90 nm using a dynamic light-scattering (DLS) analyser. Interestingly, the internalization of DPH-loaded RGD-PCP micelles into PC 12 cells is much faster (e.g. within 5 min) than that of PCP micelles. The new RGD-PCP micelles may potentially be used in cellular drug delivery.

  20. Pathway Controlled Penetration (PcP)

    SciTech Connect

    Knight, Earl E.; Rougier, Esteban; Zubelewicz, Aleksander

    2012-08-29

    The technical approach employs advanced computational simulation tools to demonstrate how current assets can destroy RWK-RFI-12-0001's HDBT, a tunnel complex with two portals built into the base of a granite mountain. The granite over layer is assumed to be 60 meters thick over both portals and 80 meters over the facility's mission space. Key S&T is the completed development of a highly innovative viscoplastic fracture material model, 3D parallel gas-fracture capabilities into FDEM, and a stochastic handling of the material properties. Phase I - Develop and validate code simulation tools: (1) develop, incorporate and validate AZ-Frac material model for granite; and (2) Develop and incorporate gas-driven-fracture modeling into LANL's FDEM MUNROU code; (3) Develop and incorporate stochastic features into FDEM modeling. Phase II - Conduct PcP analysis on above HDBT: (1) Acquire HDBT design data, develop simulation model; and (2) Evaluate and select most promising defeat alternative. Phase III - Deliver code, train Service target analysts, and conduct simulations against real world HDBTs. PcP uses advanced computer simulations to enhance HDBT functional defeat efforts. Newly developed material models that account for fractural energy coupled with the finite discrete element methodology (FDEM) will provide targeting packages that will create penetration avenues for current or future lethality options. This novel computational approach requires full 3D geologic and structure characterization as well as significant high performance computing capabilities. The goal is to distinctively alter the targeting paradigm by leveraging critical DoD assets along with insitu geologic strata. In other words, assets will utilize underground rock structure to their benefit by creating rubbilization zones that will allow pathway controlled penetration.

  1. What's a Primary Care Physician (PCP)?

    MedlinePlus

    ... and the Internet What's a Primary Care Physician (PCP)? KidsHealth > For Parents > What's a Primary Care Physician ( ... getting the right amount of exercise. Types of PCPs Different types of PCPs treat kids and teens. ...

  2. Remediation System Evaluation, Havertown PCP Superfund Site

    EPA Pesticide Factsheets

    The Havertown PCP site is located in Havertown, Haverford Township, Delaware County, in southeastern Pennsylvania. The site contamination was first discovered in 1962 when the Pennsylvania State Department of Health became aware of contaminants in ...

  3. Anatomical study of posterior clinoid process (PCP) and its clinical meanings.

    PubMed

    Cheng, Ye; Chen, Yong; Zhou, Zijian; Zhu, Jiajing; Feng, Yan; Zhao, Gang

    2015-03-01

    The aim of this study is to provide a new and comprehensive anatomic study of the posterior clinoid process (PCP) as well as data for PCP location to guide the surgeons in endoscopic surgery. Computed tomography angiography images of 120 PCPs and structures around them in adults were reviewed. The measurement was on coronal, sagittal, and axial planes after multiplanar reconstruction. The length, width, and thickness were accessed for the best understanding of the feature of PCP. The distance from the base of the PCP and the middle lowest point of the sellar floor was measured to find the position of the PCP during the transphenoid approach. PCP varies in width and thickness in different portions of it and is closely related to the internal carotid artery and posterior communicating artery, which makes it an important landmark during surgery. The shape of PCP is various, and the analysis of its relationship to the important structures around it is of great value. In addition, the preoperative radiological evaluation plays a major role in patients considered for endoscopic sinus surgery. Detailed preoperative analysis of the anatomy of the sphenoid sinus and its boundaries is crucial in facilitating entry to the pituitary fossa and reducing intraoperative complications.

  4. Concentrations of pentachlorophenol (PCP) in fish and shrimp in Jiangsu Province, China.

    PubMed

    Ge, Jiachun; Pan, Jianling; Fei, Zhiliang; Wu, Guanghong; Giesy, John P

    2007-08-01

    Pentachlorophenol (PCP) concentrations were determined in 55 samples of fish, shrimp, crabs, frogs and turtles collected in Jiangsu Province and 55 freshwater shrimp samples collected from the Huiming Fish Market, Nanjing, China between 2003 and 2004. PCP concentrations ranged from less than the method detection limit (MDL: 0.5 microg/kg ww) to 61 microg/kg ww, with a mean of 5.2 microg/kg ww in 55 samples collected across Jiangsu Province and a mean of 0.5 microg/kg ww for freshwater shrimp collected from the Huiming Fish Market. Concentrations of PCP in common carp (Carassius auratus) were significantly greater than concentrations of PCP in other species from all of the areas studied. Grass carp (Ctenopharyngodon idella) contained the second greatest concentrations and crustacean species contained the least concentrations. Concentrations of PCP were greater in samples collected from Southern Jiangsu than those collected from other areas of Jiangsu Province. Concentrations of PCP in the freshwater shrimp (Macrobrachium nipponense) from the Huiming Fish Market were greater in March and September than those collected in June and December. Based on the allowable daily intake (ADI) set by the US National Academy of Science, current concentrations of PCP measured in aquatic products from Jiangsu Province presented minimus health risks to humans.

  5. Field analytical screening program: PCP method. Innovative technology evaluation report. Report for 1 July-31 August 1993

    SciTech Connect

    Hess, E.; Hamilton, D.

    1995-08-01

    This innovative technology evaluation report (ITER) presents information on the demonstration of the U.S. Environmental Protection Agency (EPA) Region 7 Superfund Field Analytical Screening Program (FASP) method for determining pentachlorophenol (PCP) contamination in soil and water. This method was demonstrated in Norrisville, North Carolina, in August 1993. The FASP PCP Method was developed by the EPA Superfund Branch for use at Superfund sites. The method uses a gas chromatograph (GC) equipped with a megabore capillary column and either a flame ionization detector (FID) or an electron capture detector (ECD). Gas chromatography is an EPA-approved method for determining PCP concentrations in soil, water, and waste samples. The FASP PCP Method is an abbrevaited, modified version of approved methods. Soil and water samples require extraction before GC analysis. To remove interferences caused by petroleum hydrocarbons, an acid-base partition cleanup step is used during the FASP PCP Method.

  6. What's a Primary Care Physician (PCP)?

    MedlinePlus

    ... the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to ... care. The best preventive care means forming a relationship with a PCP you like and trust, taking your child for scheduled checkups and vaccines , and following the ...

  7. FIELD ANALYTICAL SCREENING PROGRAM: PCP METHOD - INNOVATIVE TECHNOLOGY EVALUATION REPORT

    EPA Science Inventory

    The Field Analytical Screening Program (FASP) pentachlorophenol (PCP) method uses a gas chromatograph (GC) equipped with a megabore capillary column and flame ionization detector (FID) and electron capture detector (ECD) to identify and quantify PCP. The FASP PCP method is design...

  8. FIELD ANALYTICAL SCREENING PROGRAM: PCP METHOD - INNOVATIVE TECHNOLOGY EVALUATION REPORT

    EPA Science Inventory

    The Field Analytical Screening Program (FASP) pentachlorophenol (PCP) method uses a gas chromatograph (GC) equipped with a megabore capillary column and flame ionization detector (FID) and electron capture detector (ECD) to identify and quantify PCP. The FASP PCP method is design...

  9. PCP prophylaxis with use of corticosteroids by neurologists.

    PubMed

    Kelly, Dearbhla M; Cronin, Simon

    2014-04-01

    Pneumocystis jirovecii pneumonia (PCP) is increasingly reported in patients without HIV. Corticosteroids are a major risk factor, with up to 90% of patients receiving corticosteroid treatment prior to the development of PCP. In view of this, many specialties now prescribe PCP prophylaxis to patients receiving prolonged or high-dose glucocorticoid regimens. Neurologists frequently prescribe corticosteroids but may not be as aware of the risk for PCP. Here, we review the evidence for routine PCP prophylaxis among regular glucocorticoid users and ask what guidance there is on the subject for neurologists.

  10. Planar cell polarity (PCP) proteins and spermatogenesis.

    PubMed

    Chen, Haiqi; Cheng, C Yan

    2016-11-01

    In adult mammalian testes, spermatogenesis is comprised of several discrete cellular events that work in tandem to support the transformation and differentiation of diploid spermatogonia to haploid spermatids in the seminiferous epithelium during the seminiferous epithelial cycle. These include: self-renewal of spermatogonial stem cells via mitosis and their transformation into differentiated spermatogonia, meiosis I/II, spermiogenesis and the release of sperms at spermiation. Studies have shown that these cellular events are under precise and coordinated controls of multiple proteins and signaling pathways. These events are also regulated by polarity proteins that are known to confer classical apico-basal (A/B) polarity in other epithelia. Furthermore, spermatid development is likely supported by planar cell polarity (PCP) proteins since polarized spermatids are aligned across the plane of seminiferous epithelium in an orderly fashion, analogous to hair cells in the cochlea of the inner ear. Thus, the maximal number of spermatids can be packed and supported by a fixed population of differentiated Sertoli cells in the limited space of the seminiferous epithelium in adult testes. In this review, we briefly summarize recent findings regarding the role of PCP proteins in the testis. This information should be helpful in future studies to better understand the role of PCP proteins in spermatogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. A Systematic Review and Meta-Analysis of the Data Behind Current Recommendations for Corticosteroids in Non-HIV-Related PCP: Knowing When You Are on Shaky Foundations.

    PubMed

    Injean, Patil; Eells, Samantha J; Wu, Hoover; McElroy, Imani; Gregson, Aric L; McKinnell, James A

    2017-03-01

    Randomized trials show a mortality benefit to adjunctive corticosteroids for human immunodeficiency virus (HIV)-related Pneumocystis jiroveci pneumonia (HIV-PCP). Guidelines for non-HIV PCP (NH-PCP) recommend adjunctive corticosteroids based on expert opinion. We conducted a systematic review and meta-analysis characterizing adjunctive corticosteroids for NH-PCP. We searched MEDLINE from 1966 through 2015. Data on clinical outcomes from NH-PCP were extracted with a standardized instrument. Heterogeneity was assessed with the I(2) index. Pooled odds ratios and 95% confidence interval were calculated using a fixed effects model. Our search yielded 5044 abstracts, 277 articles were chosen for full review, and 6 articles described outcomes in moderate to severe NH-PCP. Studies were limited by variable definitions, treatment selection bias, concomitant infections and small sample size. Individual studies reported shorter intensive care unit stay and duration of mechanical ventilation of patients given adjunctive corticosteroids. There was no association between corticosteroids and survival in NH-PCP (odds ratio, 0.66; 95% confidence interval, 0.38-1.15; P = 0.14). The literature does not support an association between adjunctive corticosteroids and survival from NH-PCP but data are limited and findings should not be considered conclusive. Further research with improved methodology is needed to better understand the role of adjunctive corticosteroids for NH-PCP.

  12. A Systematic Review and Meta-Analysis of the Data Behind Current Recommendations for Corticosteroids in Non–HIV-Related PCP: Knowing When You Are on Shaky Foundations

    PubMed Central

    Injean, Patil; Eells, Samantha J.; Wu, Hoover; McElroy, Imani; Gregson, Aric L.; McKinnell, James A.

    2017-01-01

    Background Randomized trials show a mortality benefit to adjunctive corticosteroids for human immunodeficiency virus (HIV)-related Pneumocystis jiroveci pneumonia (HIV-PCP). Guidelines for non-HIV PCP (NH-PCP) recommend adjunctive corticosteroids based on expert opinion. We conducted a systematic review and meta-analysis characterizing adjunctive corticosteroids for NH-PCP. Methods We searched MEDLINE from 1966 through 2015. Data on clinical outcomes from NH-PCP were extracted with a standardized instrument. Heterogeneity was assessed with the I2 index. Pooled odds ratios and 95% confidence interval were calculated using a fixed effects model. Results Our search yielded 5044 abstracts, 277 articles were chosen for full review, and 6 articles described outcomes in moderate to severe NH-PCP. Studies were limited by variable definitions, treatment selection bias, concomitant infections and small sample size. Individual studies reported shorter intensive care unit stay and duration of mechanical ventilation of patients given adjunctive corticosteroids. There was no association between corticosteroids and survival in NH-PCP (odds ratio, 0.66; 95% confidence interval, 0.38-1.15; P = 0.14). Conclusions The literature does not support an association between adjunctive corticosteroids and survival from NH-PCP but data are limited and findings should not be considered conclusive. Further research with improved methodology is needed to better understand the role of adjunctive corticosteroids for NH-PCP. PMID:28361121

  13. The pentachlorophenol-dehalogenating Desulfitobacterium hafniense strain PCP-1

    PubMed Central

    Villemur, Richard

    2013-01-01

    In this report, a complete description of Desulfitobacterium hafniense strain PCP-1 is presented. The D. hafniense strain PCP-1 was isolated from a methanogenic consortium for its capacity to dehalogenate pentachlorophenol (PCP) into 3-chlorophenol. This strain is also capable of dehalogenating several other chloroaromatic compounds and tetrachloroethene into trichloroethene. Four gene loci encoding putative chlorophenol-reductive dehalogenases (CprA2 to CprA5) were detected, and the products of two of these loci have been demonstrated to dechlorinate different chlorinated phenols. Strain PCP-1 was used in laboratory-scale bioprocesses to degrade PCP present in contaminated environments. Desulfitobacterium hafniense PCP-1 is an excellent candidate for the development of efficient bioprocesses to degrade organohalide compounds. PMID:23479749

  14. The pentachlorophenol-dehalogenating Desulfitobacterium hafniense strain PCP-1.

    PubMed

    Villemur, Richard

    2013-04-19

    In this report, a complete description of Desulfitobacterium hafniense strain PCP-1 is presented. The D. hafniense strain PCP-1 was isolated from a methanogenic consortium for its capacity to dehalogenate pentachlorophenol (PCP) into 3-chlorophenol. This strain is also capable of dehalogenating several other chloroaromatic compounds and tetrachloroethene into trichloroethene. Four gene loci encoding putative chlorophenol-reductive dehalogenases (CprA2 to CprA5) were detected, and the products of two of these loci have been demonstrated to dechlorinate different chlorinated phenols. Strain PCP-1 was used in laboratory-scale bioprocesses to degrade PCP present in contaminated environments. Desulfitobacterium hafniense PCP-1 is an excellent candidate for the development of efficient bioprocesses to degrade organohalide compounds.

  15. The plane facts of PCP in the CNS.

    PubMed

    Goodrich, Lisa V

    2008-10-09

    Planar cell polarity (PCP) pathways have been defined by their ability to direct the development of obviously polarized cellular architectures. Recent studies indicate that PCP pathways also regulate aspects of cell morphology that are not restricted to the plane of the epithelium. In the developing nervous system, PCP-mediated changes in the cytoskeleton are fundamental to neuronal migration, neuronal polarity, axon guidance, and dendritic arborization, highlighting the importance of "planar polarity" genes for defining the shape of a neuron in all dimensions.

  16. PCP-ML: protein characterization package for machine learning.

    PubMed

    Eickholt, Jesse; Wang, Zheng

    2014-11-18

    Machine Learning (ML) has a number of demonstrated applications in protein prediction tasks such as protein structure prediction. To speed further development of machine learning based tools and their release to the community, we have developed a package which characterizes several aspects of a protein commonly used for protein prediction tasks with machine learning. A number of software libraries and modules exist for handling protein related data. The package we present in this work, PCP-ML, is unique in its small footprint and emphasis on machine learning. Its primary focus is on characterizing various aspects of a protein through sets of numerical data. The generated data can then be used with machine learning tools and/or techniques. PCP-ML is very flexible in how the generated data is formatted and as a result is compatible with a variety of existing machine learning packages. Given its small size, it can be directly packaged and distributed with community developed tools for protein prediction tasks. Source code and example programs are available under a BSD license at http://mlid.cps.cmich.edu/eickh1jl/tools/PCPML/. The package is implemented in C++ and accessible as a Python module.

  17. Electrochemical mineralization of pentachlorophenol (PCP) by Ti/SnO2-Sb electrodes.

    PubMed

    Niu, Junfeng; Bao, Yueping; Li, Yang; Chai, Zhen

    2013-09-01

    Electrochemical degradation of pentachlorophenol (PCP) in aqueous solution was investigated over Ti/SnO2-Sb electrodes prepared by sol-gel method. X-ray diffraction (XRD), scanning electron microscopy (SEM) and electrochemical measurements were used to characterize the physicochemical properties of the electrodes. The electrochemical degradation of PCP followed pseudo-first-order kinetics. The main influencing factors, including the types of supporting electrolyte (i.e., NaClO4, Na2SO4, Na2SO3, NaNO3, and NaNO2), initial concentrations of PCP (5-1000mgL(-1)), pH values (3.0-11.0), and current densities (5-40mAcm(-2)) were evaluated. The degradation and mineralization ratios of 100mgL(-1) of PCP achieved >99.8% and 83.0% after 30min electrolysis with a 10mmolL(-1) Na2SO4 at a current density of 10mAcm(-2), respectively. The corresponding half-life time (t1/2) was 3.94min. The degradation pathways that were involved in dechlorination, protons generation, and mineralization processes were proposed based on the determination of total organic carbon, chloride, and intermediate products (i.e., low chlorinated phenol and some organic acids). The toxicity of PCP and its intermediates could be reduced effectively by electrolysis. These results showed that electrochemical technique could achieve a significant mineralization rate in a short time (<30min), which provided an efficient way for PCP elimination from wastewater. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Dinuclear PCP pincer complexes from Lewis acidic [Pd(OTf)(PCP)] and basic [Pd(4-Spy)(PCP)] (OTf = triflate; 4-Spy = 4-pyridinethiolate; PCP = (-)CH(CH(2)CH(2)PPh(2))(2)).

    PubMed

    Neo, Kian Eang; Huynh, Han Vinh; Koh, Lip Lin; Henderson, William; Hor, T S Andy

    2007-12-28

    The Lewis acidic pincer with a labile triflate ligand, viz. [Pd(OTf)(PCP)] (PCP = (-)CH(CH(2)CH(2)PPh(2))(2)) was prepared from [PdCl(PCP)] with AgOTf. It reacts readily with neutral bidentate ligands [L = 4,4'-bipyridine (4,4'-bpy) and 1,1'-bis(diphenylphosphino)ferrocene (dppf)] to give dinuclear PCP pincers [{Pd(PCP)}(2)(micro-L)][OTf](2) (L = 4,4'-bpy, 2; dppf,3). [PdCl(PCP)] also reacts with 4-mercaptopyridine in the presence of KOH to give a Lewis basic pincer with a free pyridine functional group [Pd(4-Spy)(PCP)]4. Its metalloligand character is exemplified by the isolation of an asymmetric dinuclear double-pincer complex [{Pd(PCP)}(2)(micro-4-Spy)][PF(6)] 6 bridged by an ambidentate pyridinethiolato ligand. Complexes 1, 2, 3, 4 and 6 have been characterized by single-crystal X-ray diffraction analyses.

  19. The Social, Behavioral, and Health Effects of Phencyclidine (PCP) Use.

    ERIC Educational Resources Information Center

    Sharp, Jeffrey G.; Graeven, David B.

    1981-01-01

    The perceived social, behavioral, and health effects of phencyclidine (PCP) use among a sample of 200 users were studied. Results suggest that chronic PCP use has a destructive impact upon developmental processes by disrupting education and employment, impairing close relationships, contributing to criminal status, and otherwise impairing mental…

  20. The immunotoxic effects of dual exposure to PCP and TCDD.

    PubMed

    Chen, Hsiu-Min; Lee, Yu-Hsuan; Chen, Rong-Jane; Chiu, Hui-Wen; Wang, Bour-Jr; Wang, Ying-Jan

    2013-11-25

    Pentachlorophenol (PCP) was a commonly used fungicide, herbicide, insecticide, and bactericide in industrial, agricultural, and domestic settings; however, it was also contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). It has been reported that technical grade PCP had immunosuppressive effects and that the immune system was the major target of PCDD/PCDFs toxicity. Although the immune response after exposure to PCP or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been studied, the toxic effects of exposure to both PCP and TCDD have not yet been reported. The aim of this study was to evaluate the effects on immune cells from mice intraperitoneally immunized with OVA and subsequently treated with PCP or TCDD alone or in combination by gavage. The animals were terminated on day 7 and 14, and the spleen and plasma samples were collected for immunotoxicity evaluation. The numbers and populations of splenocytes, T cell-derived cytokines produced by splenocytes, splenocyte-generated cytotoxicity and OVA-specific antibodies in plasma were investigated. Our results indicate that the spleen/body weight ratio and splenocyte number was reduced by TCDD alone; in addition, this reduction was enhanced when TCDD was combined with PCP. Exposure to TCDD alone or in conjunction with PCP suppressed many ovalbumin (OVA)-stimulated cytokines, including IL-2, IFN-γ, IL-4, IL-5, and IL-10. Furthermore, the immunoglobulins IgG and IgM were suppressed in mice administered by PCP alone, but the suppressive effects were greater in mice treated with TCDD alone or in combination with PCP. Co-exposure to PCP and TCDD resulted in an antagonistic effect on TCDD-induced suppression of IFN-γ and IL-10. Our results demonstrate that PCP alone is immunotoxic, regardless of the presence of TCDD. PCP led to mild changes in cytokine secretion, and it compromised splenocyte-generated cytotoxicity and IgM and IgG antibody production on day 7. The finding

  1. Negative schizophrenic symptomatology and the PCP (phencyclidine) model of schizophrenia.

    PubMed

    Javitt, D C

    1987-01-01

    Amphetamine induced psychosis has for the past 30 years provided a useful model for the study of schizophrenia. The amphetamine model, however, has been shown to have a number of shortcomings including an inability to model the deficit symptoms of schizophrenia. PCP (phencyclidine) has been shown to be capable of inducing a schizophreniform psychosis consisting of both productive and defict symptomatology. PCP induced psychosis, therefore, may provide a useful model of schizophrenia. This paper reviews the literature concerning the PCP model of schizophrenia and provides some independent confirmation of the ability of PCP to modulate mesocortical dopaminergic activity. Since PCP appears to mediate its CNS effects via a subclass of glutamate receptors, a possible glutamate theory of schizophrenia is proposed.

  2. From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs.

    PubMed

    Morris, Hamilton; Wallach, Jason

    2014-01-01

    PCP or phencyclidine was discovered in 1956 and soon became a popular street drug. Dissociatives including PCP, ketamine, and dextromethorphan have been used non-medically for their mind-altering effects for over 60 years. Many of these compounds have also been used clinically and in legitimate research. At least 14 derivatives of PCP were sold for non-medical and illict use from the late 1960s until the 1990s. With the advent of the Internet, the drug market underwent a dramatic evolution. While initially gray-market chemical vendors offering dextromethorphan and ketamine thrived, most recently the market has shifted to legal high and online-based research chemical vendors. Starting with the first dissociative research chemical, 4-MeO-PCP in 2008, the dissociative research chemical market has rapidly evolved and currently comprises at least 12 dissociatives, almost half of which were unknown in the scientific literature prior to their introduction. Several of these, including methoxetamine, have reached widespread use internationally. A historical account of non-medical use of over 30 dissociative compounds was compiled from a diverse collection of sources. The first complete portrait of this underground market is presented along with the relevant legal, technological, and scientific developments which have driven its evolution. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Predictors of PCP, OH-PCBs, PCBs and chlorinated pesticides in a general female Norwegian population.

    PubMed

    Rylander, Charlotta; Lund, Eiliv; Frøyland, Livar; Sandanger, Torkjel M

    2012-08-01

    The aims of the current study were to assess plasma concentrations and predictors of halogenated phenolic compounds (HPCs), polychlorinated biphenyls (PCBs) and chlorinated pesticides in a representative group of postmenopausal Norwegian women (n=311, mean age: 56 years). In addition to delivering a blood sample, the participants had also filled out a detailed questionnaire regarding their current health status, use of medication and dietary habits, etc. The association between a large number of dietary variables, lifestyle factors and plasma concentration of organic pollutants were investigated using multivariate statistics. Within the current study group, p,p'-DDE (median: 903 ng/L w.w.) and pentachlorophenol (PCP, median: 711 ng/L w.w.) were the dominating compounds on a wet weight basis and were present in considerable higher concentrations than the PCBs, the hydroxylated PCBs (OH-PCBs) and the remaining chlorinated pesticides. Of the PCBs, PCB 153 was detected in highest concentrations, whereas 4-OH-PCB187 was present in highest concentration of the selected OH-PCBs. The ratio of ΣOH-PCB to ΣPCB varied between 0.06 and 0.77 ng/L and were significantly lower in individuals with higher ΣPCB concentration. PCP did not co-vary with the other contaminants, indicating a different route of exposure. No clear food cluster was positively associated with PCP exposure; however intake of marine food was negatively linked to PCP concentration and age and being a non-smoker were positive predictors of PCP. The other investigated contaminants co-varied and were positively associated with age, plasma concentrations of marine derived omega-3 fatty acids and a traditional Norwegian fish and bread based diet. The difference in contaminant concentration between high, medium and low consumers of total marine food were however marginal for the dominating PCBs and chlorinated pesticides. The current results indicate however that marine food in itself could be a source of some of

  4. PCP prevention--more cases of resistance to sulfa drugs.

    PubMed

    1998-09-01

    Three studies that are highlighted suggest that PCP-causing microbes are developing resistance to Bactrim/Septra (B/S), the drug of choice for preventing the life-threatening complications caused by PCP, toxoplasmosis, and bacterial pneumonia. While resistance does not appear to be happening on a large scale, it is a concern because no other drug has the same beneficial effects of B/S. Research is needed for simple, low-toxicity treatments and prophylactic drugs for PCP, before resistance becomes a common problem.

  5. Identification of differential hepatic proteins in rare minnow (Gobiocypris rarus) exposed to pentachlorophenol (PCP) by proteomic analysis.

    PubMed

    Fang, Yanjun; Gao, Xianjun; Zha, Jinmiao; Ning, Baoan; Li, Xiaoli; Gao, Zhixian; Chao, Fuhuan

    2010-11-10

    Pentachlorophenol (PCP) is a ubiquitous contaminant that has been shown to lead to hepatoxicity and is implicated in the incidence of liver tumors in human. A number of previous studies have described the toxic effects of PCP based on conventional toxicological indices. However, little evidence on protein levels is available at present. For further understanding of mechanisms of action and identifying the potential protein biomarkers for PCP exposure, two-dimensional electrophoresis coupled with mass spectrometry has been used to identify proteins differentially expressed in the livers of rare minnow (Gobiocypris rarus) following PCP exposure of 0.5, 5, 50 μg/L. After comparison of the protein profiles from treated and control groups, 39 protein spots were found altered in abundance (>2-fold) from male and female PCP-treated groups. Matrix-assisted laser desorption/ionization (MALDI) tandem time-of-flight mass spectrometry (TOF/MS) analysis allowed the unambiguous identification, and 18 protein spots were identified successfully, 12 proteins in females and 6 proteins in males, respectively. These proteins were involved in transport, metabolism, response to oxidative stress and other biological processes. Of these proteins, four differentially expressed mRNA encoding proteins underwent quantitative analysis by quantitative real-time PCR (QRT-PCR). The consistent and discrepant results between mRNA and protein levels suggested that complicated regulatory mechanisms of gene expression were implicated in the response to PCP exposure. In addition, marked gender differences in response to PCP have been described from the comparison of the male and female liver protein profiles. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. HNU-HANBY PCP IMMUNOASSAY TEST KIT - INNOVATIVE TECHNOLOGY EVALUATION REPORT

    EPA Science Inventory

    The HNU-Hanby pentachlorophenol (PCP) test kit rapidly analyzes for PCP in soil samples. The test kit can only detect those PCP carriers that contain aromatic compounds. The test kit estimates PCP concentrations in soil samples indirectly by measuring petroleum hydrocarbon carrie...

  7. HNU-HANBY PCP IMMUNOASSAY TEST KIT - INNOVATIVE TECHNOLOGY EVALUATION REPORT

    EPA Science Inventory

    The HNU-Hanby pentachlorophenol (PCP) test kit rapidly analyzes for PCP in soil samples. The test kit can only detect those PCP carriers that contain aromatic compounds. The test kit estimates PCP concentrations in soil samples indirectly by measuring petroleum hydrocarbon carrie...

  8. Benzo annulated cycloheptatriene PCP pincer iridium complexes.

    PubMed

    Leis, Wolfgang; Wernitz, Sophie; Reichart, Benedikt; Ruckerbauer, David; Wielandt, Johannes Wolfram; Mayer, Hermann A

    2014-08-28

    The benzo annulated cycloheptatriene PCP pincer ligand was prepared in five steps. Treatment of with Ir(CO)3Cl gave the meridional cyclometalated chlorohydrido carbonyl iridium complexes which differ in their arrangement of the H, Cl, and CO ligands around iridium. Storing in THF led to isomerization processes. Hydrogen shifts from the sp(3)-CH carbon bound to iridium into the ligand backbone produced the three isomers . Reductive elimination of HCl from these complexes resulted in the square planar Ir(i) carbonyl complexes . Abstraction of the hydrogen from the sp(3)-CH-Ir fragment could be achieved either by treatment of with Ph3CBF4 or by the elimination of H2 which is initiated by CF3SO3H. The mass spectrometric characterisation of using fast atom bombardment reveals a complex fragmentation pattern. These different "fragment" ions were further investigated by electro-spray ionisation (tandem) mass spectrometry in high and low resolution. The identified compounds were attributed to structures by DFT calculations.

  9. Use of haloperidol in PCP-intoxicated individuals.

    PubMed

    MacNeal, James J; Cone, David C; Sinha, Vinnita; Tomassoni, Anthony J

    2012-11-01

    Emergency medical workers often experience violence while performing their job functions. Phencyclidine (PCP)-intoxicated patients are often violent and difficult to control physically. A chemical restraint is frequently needed to assist in protecting both patients and staff from agitated persons. This study evaluated haloperidol as a chemical restraint in PCP-intoxicated patients. This is a retrospective case series of all PCP-positive patients who received haloperidol for behavioral control from April 2008 to April 2011 at a single large (944 bed), urban, tertiary-care hospital. All patients receiving haloperidol and having a toxicology screen positive for PCP were identified using an electronic medical record. Identified cases were then manually reviewed by investigators for adverse events. Subjects included 59 adult patients who were acutely agitated requiring chemical restraint or sedation with haloperidol, and who tested positive for PCP. There were 20 females and 39 males, ranging in age from 19 to 54 years. Patients received haloperidol via the PO, IM, or IV routes in doses ranging from 1 to 10 mg. There were two adverse events (mild hypoxia and mild hypotension) found during chart review; neither were serious nor required change in patient disposition. In this study, haloperidol does not seem to cause harm when used in the management of PCP-intoxicated patients. Caution must always be exercised in the use of chemical restraint; further prospective study is warranted.

  10. Tuning PCP-Ir complexes: the impact of an N-heterocyclic olefin.

    PubMed

    Iglesias, Manuel; Iturmendi, Amaia; Sanz Miguel, Pablo J; Polo, Victor; Pérez-Torrente, Jesús J; Oro, Luis A

    2015-08-11

    A new PCP-type ligand based on an N-heterocyclic olefin (NHO) scaffold has been prepared. The flexibility of this ligand, which is able to adopt facial coordination modes in Ir(I) or meridional in Ir(III) complexes, can be attributed to the dual nature (ylide-olefin) of the NHO scaffold. This results in a rare case of olefin "slippage" that is supported by X-ray crystallography and DFT calculations.

  11. [The host community of a child with food allergies: the personalized care project (PCP)].

    PubMed

    Rancé, F

    2010-12-01

    The personalized care project (PCP) can manage allergic emergencies that may occur during school hours. Other objectives are to facilitate academic achievement, social and professional integration of children and adolescents with chronic illness such as food allergy, by promoting education through certain changes. The PCP is derived from official files including Circular N(o) 2003-135 of September 8 and the inter-ministerial circular of 25 June 2001. The family must request a protocol with the host school principal or school head. Then, the doctor of Education organizes the drafting of the document based on information provided by the physician (or allergist). Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  12. Developing a qPCR method to quantify AhR-PCP-DNA complex for detection of environmental trace-level PCP.

    PubMed

    Zhao, Xiaoxiang; Pang, Xiaoqian; Chaisuwan, Nuanapa

    2011-07-01

    Pentachlorophenol (PCP), a widely-used aseptic or biocide, is known as an environmental toxicant involved in endocrine disruption even at a trace level. In order to reliably and efficiently quantify environmental trace-quantity PCP, this study developed a novel PCP detection method using the aryl hydrocarbon receptor (AhR) and fluorescence quantitative PCR (qPCR). DNA probe with AhR binding sites was synthesized by PCR before added into AhR-PCP complex. After AhR-PCP-DNA complex was digested with exonuclease, copy number of DNA probe was determined using fluorescence qPCR. To calculate PCP concentration in samples, a standard curve (PCP concentration versus Ct value) was constructed and the detection range was 10(-13) to 10(-9) M. PCP detection limit was 0.0089 ppt for the AhR-PCP-DNA complex assay and 8.8780 ppm for high performance liquid chromatography, demonstrating that the method developed in this study is more sensitive. These results suggest that AhR-PCP-DNA complex method may be successfully applicable in detection and quantification of environmental trace-level PCP.

  13. Central phencyclidine (PCP) receptor binding is glutamate dependent: evidence for a PCP/excitatory amino acid receptor (EAAR) complex

    SciTech Connect

    Loo, P.; Braunwalder, A.; Lehmann, J.; Williams, M.

    1986-03-01

    PCP and other dissociative anesthetica block the increase in neuronal firing rate evoked by the EAAR agonist, N-methyl-Daspartate. NMDA and other EAAs such as glutamate (glu) have not been previously shown to affect PCP ligand binding. In the present study, using once washed rat forebrain membranes, 10 ..mu..M-glu was found to increase the binding of (/sup 3/H)TCP, a PCP analog, to defined PCP recognition sites by 20%. Removal of glu and aspartate (asp) by extensive washing decreased TCP binding by 75-90%. In these membranes, 10 ..mu..M L-glu increased TCP binding 3-fold. This effect was stereospecific and evoked by other EAAs with the order of activity, L-glu > D-asp > L- asp > NMDA > D-glu > quisqualate. Kainate, GABA, NE, DA, 5-HT, 2-chloroadenosine, oxotremorine and histamine had no effect on TCP binding at concentrations up to 100 ..mu..M. The effects of L-glu were attenuated by the NMDA-type receptor antagonist, 2-amino-7--phosphonoheptanoate (AP7; 10 ..mu..M-1 mM). These findings indicate that EAAS facilitate TCP binding, possibly through NMDA-type receptors. The observed interaction between the PCP receptor and EAARs may reflect the existence of a macromolecular receptor complex similar to that demonstrated for the benzodiazepines and GABA.

  14. Regulation of PCP by the Fat signaling pathway

    PubMed Central

    Matis, Maja; Axelrod, Jeffrey D.

    2013-01-01

    Planar cell polarity (PCP) in epithelia, orthogonal to the apical–basal axis, is essential for numerous developmental events and physiological functions. Drosophila model systems have been at the forefront of studies revealing insights into mechanisms regulating PCP and have revealed distinct signaling modules. One of these, involving the atypical cadherins Fat and Dachsous and the ectokinase Four-jointed, appears to link the direction of cell polarization to the tissue axes. We discuss models for the function of this signaling module as well as several unanswered questions that may guide future investigations. PMID:24142873

  15. Female PCP-using jail detainees: proneness to violence and gender differences.

    PubMed

    Fishbein, D H

    1996-01-01

    Previous studies indicate that PCP users have different characteristics from other drug users and that female PCP use is more common than use among males. Furthermore, there is evidence that those who respond to PCP with violence may differ from those who do not. This study attempted to examine comprehensively the psychological, behavioral, and background factors among female jail inmates that may contribute to a PCP preference and subjects' perception of various behavioral states while using PCP. Female PCP users were further examined relative to male PCP users to differentiate them on the basis of these perceptual factors. A distinction was further made between females and males prone to PCP-induced violence and those who do not become violent with respect to the above psychological and behavioral measures. Our results showed differences between male and female PCP users that are discrepant with the assumption that men and women perceive similar drug-related experiences. In particular, female PCP using subjects reported more dysphoria and aggressiveness when not using PCP, while male subjects were more likely to report aggressive behavior and dysphoria under the influence. Overall, these results suggest that males who prefer PCP may be self-stimulating and females who prefer PCP may be attempting to self-medicate.

  16. Cell polarity and planar cell polarity (PCP) in spermatogenesis.

    PubMed

    Chen, Haiqi; Mruk, Dolores D; Lui, Wing-Yee; Wong, Chris K C; Lee, Will M; Cheng, C Yan

    2017-09-28

    In adult mammalian testes, spermatids, most notably step 17-19 spermatids in stage IV-VIII tubules, are aligned with their heads pointing toward the basement membrane and their tails toward the tubule lumen. On the other hand, these polarized spermatids also align across the plane of seminiferous epithelium, mimicking planar cell polarity (PCP) found in other hair cells in cochlea (inner ear). This orderly alignment of developing spermatids during spermiogenesis is important to support spermatogenesis, such that the maximal number of developing spermatids can be packed and supported by a fixed population of differentiated Sertoli cells in the limited space of the seminiferous epithelium in adult testes. In this review, we provide emerging evidence to demonstrate spermatid PCP in the seminiferous epithelium to support spermatogenesis. We also review findings in the field regarding the biology of spermatid cellular polarity (e.g., head-tail polarity and apico-basal polarity) and its inter-relationship to spermatid PCP. Furthermore, we also provide a hypothetical concept on the importance of PCP proteins in endocytic vesicle-mediated protein trafficking events to support spermatogenesis through protein endocytosis and recycling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. WASHING STUDIES FOR PCP AND CREOSOTE-CONTAMINATED SOIL

    EPA Science Inventory

    The Environmental Protection Agency has conducted a series of bench-scale and pilot-scale studies to evaluate the feasibility of washing pentachlorophenol (PCP) and creosote from the soil at an abandoned wood-treatment Superfund site in Pensacola, FL. The high sand content and lo...

  18. The PCP SYS IV Management System: Technical Overview.

    ERIC Educational Resources Information Center

    Bryan, John T.; Felty, J. Michael

    This paper is the second in a three-part series on SYS IV, an instructional management system developed by the PLATO Curriculum Project (PCP) that incorporates some of the features of the previous SYS systems. Focus is primarily on the new features that make the system unique. Following a brief background section explaining the purpose of SYS IV,…

  19. WASHING STUDIES FOR PCP AND CREOSOTE-CONTAMINATED SOIL

    EPA Science Inventory

    The Environmental Protection Agency has conducted a series of bench-scale and pilot-scale studies to evaluate the feasibility of washing pentachlorophenol (PCP) and creosote from the soil at an abandoned wood-treatment Superfund site in Pensacola, FL. The high sand content and lo...

  20. The PCP SYS IV Management System: Technical Overview.

    ERIC Educational Resources Information Center

    Bryan, John T.; Felty, J. Michael

    This paper is the second in a three-part series on SYS IV, an instructional management system developed by the PLATO Curriculum Project (PCP) that incorporates some of the features of the previous SYS systems. Focus is primarily on the new features that make the system unique. Following a brief background section explaining the purpose of SYS IV,…

  1. Pentachlorophenol (PCP) dechlorination in horizontal-flow anaerobic immobilized biomass (HAIB) reactors.

    PubMed

    Damianovic, M H R Z; Moraes, E M; Zaiat, M; Foresti, E

    2009-10-01

    This study verifies the potential applicability of horizontal-flow anaerobic immobilized biomass (HAIB) reactors to pentachlorophenol (PCP) dechlorination. Two bench-scale HAIB reactors (R1 and R2) were filled with cubic polyurethane foam matrices containing immobilized anaerobic sludge. The reactors were then continuously fed with synthetic wastewater consisting of PCP, glucose, acetic acid, and formic acid as co-substrates for PCP anaerobic degradation. Before being immobilized in polyurethane foam matrices, the biomass was exposed to wastewater containing PCP in reactors fed at a semi-continuous rate of 2.0 microg PCP g(-1) VS. The applied PCP loading rate was increased from 0.05 to 2.59 mg PCP l(-1)day(-1) for R1, and from 0.06 to 4.15 mg PCP l(-1)day(-1) for R2. The organic loading rates (OLR) were 1.1 and 1.7 kg COD m(-3)day(-1) at hydraulic retention times (HRT) of 24h for R1 and 18 h for R2. Under such conditions, chemical oxygen demand (COD) removal efficiencies of up to 98% were achieved in the HAIB reactors. Both reactors exhibited the ability to remove 97% of the loaded PCP. Dichlorophenol (DCP) was the primary chlorophenol detected in the effluent. The adsorption of PCP and metabolites formed during PCP degradation in the packed bed was negligible for PCP removal efficiency.

  2. Adaptive response of trivial activated sludge towards toxic effect of oNP, PCP and combination oNP/PCP

    SciTech Connect

    Topalova, Y.; Dimkov, R. . Faculty of Biology); Kozuharov, D. )

    1999-01-01

    The reaction of the real aerobic activated sludge taken from the Sofia Waste Water Treatment Plant (SWWTP) and treated with the xenobiotics pentachlorphenol (PCP) (0.16 mMol), ortho-nitrophenol (oNP) (0.58 mMol) and with a combination of PCP (0.08 mMol), oNP (0.29 mMol) has been investigated in a model detoxification process. The adaptive changes are studied in the microbial structure level and at the level of changes in the qualitative and quantitative parameters of the macro-organisms in the activated sludge (consuments of 1 and 2 level). The presence of several different taxonomic groups has been shown by other researchers to be essential in the detoxification process. The quantitative changes in these taxonomic and physiological groups of micro-organisms are studied. The number of micro-organisms from Pseudomonas, Acinetobacter and the bacteria from the xenobiotic-catabolizing complex considerably increased with the individual and the combined effect of the xenobiotics oNP, PCP and oNP PCP. At the same time the toxic shock leads to a remarkable reduction of NH[sub 3] releasing, nitrifying bacteria and those from family Enterobacteriaceae. It is ascertained that the number of Ciliata, Flagellata apochromata, Oligochaeta and Rotatoria is strongly decreased in the series of samples treated with xenobiotics. The leading role of micro-organisms in the real detoxification of hazardous pollutants was experimentally confirmed by research.

  3. Response of compost maturity and microbial community composition to pentachlorophenol (PCP)-contaminated soil during composting.

    PubMed

    Zeng, Guangming; Yu, Zhen; Chen, Yaoning; Zhang, Jiachao; Li, Hui; Yu, Man; Zhao, Mingjie

    2011-05-01

    Two composting piles were prepared by adding to a mixture of rice straw, vegetables and bran: (i) raw soil free from pentachlorophenol (PCP) contamination (pile A) and (ii) PCP-contaminated soil (pile B). It was shown by the results that compost maturity characterized by water soluble carbon (WSC), TOC/TN ratio, germination index (GI) and dehydrogenase activity (DA) was significantly affected by PCP exposure, which resulted in an inferior degree of maturity for pile B. DGGE analysis revealed an inhibited effect of PCP on compost microbial abundance. The bacteria community shifts were mainly consistent with composting factors such as temperature, pH, moisture content and substrates. By contrast, the fungal communities were more sensitive to PCP contamination due to the significant correlation between fungal community shifts and PCP removal. Therefore, the different microbial community compositions for properly evaluating the degree of maturity and PCP contamination were suggested. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Effects of Subchronic Phencyclidine (PCP) Treatment on Social Behaviors, and Operant Discrimination and Reversal Learning in C57BL/6J Mice

    PubMed Central

    Brigman, Jonathan L.; Ihne, Jessica; Saksida, Lisa M.; Bussey, Timothy J.; Holmes, Andrew

    2008-01-01

    Subchronic treatment with the psychotomimetic phencyclidine (PCP) has been proposed as a rodent model of the negative and cognitive/executive symptoms of schizophrenia. There has, however, been a paucity of studies on this model in mice, despite the growing use of the mouse as a subject in genetic and molecular studies of schizophrenia. In the present study, we evaluated the effects of subchronic PCP treatment (5 mg/kg twice daily × 7 days, followed by 7 days withdrawal) in C57BL/6J mice on (1) social behaviors using a sociability/social novelty-preference paradigm, and (2) pairwise visual discrimination and reversal learning using a touchscreen-based operant system. Results showed that mice subchronically treated with PCP made more visits to (but did not spend more time with) a social stimulus relative to an inanimate one, and made more visits and spent more time investigating a novel social stimulus over a familiar one. Subchronic PCP treatment did not significantly affect behavior in either the discrimination or reversal learning tasks. These data encourage further analysis of the potential utility of mouse subchronic PCP treatment for modeling the social withdrawal component of schizophrenia. They also indicate that the treatment regimen employed was insufficient to impair our measures of discrimination and reversal learning in the C57BL/6J strain. Further work will be needed to identify alternative methods (e.g., repeated cycles of subchronic PCP treatment, use of different mouse strains) that reliably produce discrimination and/or reversal impairment, as well as other cognitive/executive measures that are sensitive to chronic PCP treatment in mice. PMID:19255630

  5. Constraining PCP Violating Varying Alpha Theory through Laboratory Experiments

    SciTech Connect

    Maity, Debaprasad; Chen, Pisin; /NCTS, Taipei /Taiwan, Natl. Taiwan U. /KIPAC, Menlo Park /SLAC

    2012-06-06

    In this report we have studied the implication of a parity and charge-parity (PCP) violating interaction in varying alpha theory. Due to this interaction, the state of photon polarization can change when it passes through a strong background magnetic field. We have calculated the optical rotation and ellipticity of the plane of polarization of an electromagnetic wave and tested our results against different laboratory experiments. Our model contains a PCP violating parameter {beta} and a scale of alpha variation {omega}. By analyzing the laboratory experimental data, we found the most stringent constraints on our model parameters to be 1 {le} {omega} {le} 10{sup 13} GeV{sup 2} and -0.5 {le} {beta} {le} 0.5. We also found that with the existing experimental input parameters it is very difficult to detect the ellipticity in the near future.

  6. Washing studies for PCP and creosote-contaminated soil

    SciTech Connect

    Tobia, R.J.; Camacho, J.M.; Augustin, P.; Griffiths, R.A.; Frederick, R.M.

    1994-01-01

    The Environmental Protection Agency has conducted a series of bench-scale and pilot-scale studies to evaluate the feasibility of washing pentachlorophenol (PCP) and creosote from the soil at an abandoned wood-treatment Superfund site in Pensacola, FL. The high sand content and low silt/fines content of the soil made soil washing a promising alternative to incineration. The bench-scale tests confirmed the feasibility of washing the PCP and the carcinogenic creosote compounds from the soil using a nonionic surfactant at the pH of nine to ten and a water temperature of approximately 120 F. The target concentrations for total creosote were not achieved, but the results were sufficiently close to warrant further testing. The pilot-scale tests using the EPA's mobile Volume Reduction Unit produced residual PCP, carcinogenic creosote, and total creosote levels below the target levels. The tests also produced comparison data on the effects of surfactant concentration, pH, temperature, and liquid:solid ratio. (Copyright (c) 1994 Elsevier Science B.V.)

  7. Pharmacological specificity of some psychotomimetic and antipsychotic agents for the sigma and PCP binding sites

    SciTech Connect

    Itzhak, Y.

    1988-01-01

    The pharmacological specificity of representative psychotomimetic agents such a phencyclidine (PCP) analogs, opiate benzomorphans and several antipsychotic agents was assessed for the sigma and PCP binding sites. In a series of binding experiments, in rat brain membranes, sigma and PCP binding sites were labeled with (/sup 3/H)-1-(1-(3-hydroxyphenyl) cyclohexyl) piperidine ((/sup 3/H)PCP-3-OH), (+)(/sup 3/H)-N-allylnormetazocine ((+)(/sup 3/H)SKF 10047) and (+) (/sup 3/H)-3-(3-hydroxy-phenyl)-N-(1-propyl) piperidine and ((+)(/sup 3/H)-3-PPP). PCP analogs inhibit potently high affinity (/sup 3/H)PCP-3-OH binding and (+)(/sup 3/H)SKF 10047 binding, moderately the low affinity binding component of (/sup 3/H)PCP-3-OH and very weakly (+) (/sup 3/H)-3-PPP binding. (+)SKF 10047 and cyclazocine are potent to moderate inhibitors of (+)(/sup 3/H)SKF 10047, high affinity (/sup 3/H)PCP-3-OH and (+)(/sup 3/H)-3-PCP-3-OH binding. The antipsychotic agents display high affinity for (+)(/sup 3/H)-3-PPP binding sites, moderate affinity for (+)(/sup 3/H)SKF 10047 sites and have no effect on either the high or low affinity (/sup 3/H)PCP-3-OH binding. 20 references, 3 figures, 2 tables.

  8. (1-3)-beta-D-glucan in association with lactate dehydrogenase as biomarkers of Pneumocystis pneumonia (PcP) in HIV-infected patients.

    PubMed

    Esteves, F; Lee, C-H; de Sousa, B; Badura, R; Seringa, M; Fernandes, C; Gaspar, J F; Antunes, F; Matos, O

    2014-07-01

    Pneumocystis pneumonia (PcP) is a major HIV-related illness caused by Pneumocystis jirovecii. Definitive diagnosis of PcP requires microscopic detection of P. jirovecii in pulmonary specimens. The objective of this study was to evaluate the usefulness of two serum markers in the diagnosis of PcP. Serum levels of (1-3)-beta-d-glucan (BG) and lactate dehydrogenase (LDH) were investigated in 100 HIV-positive adult patients and 50 healthy blood donors. PcP cases were confirmed using indirect immunofluorescence with monoclonal anti-Pneumocystis antibodies and nested-PCR to amplify the large subunit mitochondrial rRNA gene of P. jirovecii in pulmonary specimens. BG and LDH levels in serum were measured using quantitative microplate-based assays. BG and LDH positive sera were statistically associated with PcP cases (P ≤ 0.001). Sensitivity, specificity, positive/negative predictive values (PPV/NPV), and positive/negative likelihood ratios (PLR/NLR) were 91.3 %, 61.3 %, 85.1 %, 79.2 %, 2.359, and 0.142, respectively, for the BG kit assay, and 91.3 %, 35.5 %, 75.9 %, 64.7 %, 1.415 and 0.245, respectively, for the LDH test. Serologic markers levels combined with the clinical diagnostic criteria for PcP were evaluated for their usefulness in diagnosis of PcP. The most promising cutoff levels for diagnosis of PcP were determined to be 400 pg/ml of BG and 350 U/l of LDH, which combined with clinical data presented 92.8 % sensitivity, 83.9 % specificity, 92.8 % PPV, 83.9 % NPV, 5.764 PLR and 0.086 NLR (P < 0.001). This study confirmed that BG is a reliable indicator for detecting P. jirovecii infection. The combination between BG/LDH levels and clinical data is a promising alternative approach for PcP diagnosis.

  9. The balance of prickle/spiny-legs isoforms controls the amount of coupling between core and fat PCP systems.

    PubMed

    Merkel, Matthias; Sagner, Andreas; Gruber, Franz Sebastian; Etournay, Raphael; Blasse, Corinna; Myers, Eugene; Eaton, Suzanne; Jülicher, Frank

    2014-09-22

    The conserved Fat and Core planar cell polarity (PCP) pathways work together to specify tissue-wide orientation of hairs and ridges in the Drosophila wing. Their components form intracellularly polarized complexes at adherens junctions that couple the polarity of adjacent cells and form global patterns. How Fat and Core PCP systems interact is not understood. Some studies suggest that Fat PCP directly orients patterns formed by Core PCP components. Others implicate oriented tissue remodeling in specifying Core PCP patterns. We use genetics, quantitative image analysis, and physical modeling to study Fat and Core PCP interactions during wing development. We show their patterns change during morphogenesis, undergoing phases of coupling and uncoupling that are regulated by antagonistic Core PCP protein isoforms Prickle and Spiny-legs. Evolving patterns of Core PCP are hysteretic: the early Core PCP pattern is modified by tissue flows and then by coupling to Fat PCP, producing sequential patterns that guide hairs and then ridges. Our data quantitatively account for altered hair and ridge polarity patterns in PCP mutants. Premature coupling between Fat and Core PCP explains altered polarity patterns in pk mutants. In other Core PCP mutants, hair polarity patterns are guided directly by Fat PCP. When both systems fail, hairs still align locally and obey signals associated with veins. Temporally regulated coupling between the Fat and Core PCP systems enables a single tissue to develop sequential polarity patterns that orient distinct morphological structures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Appetite for danger - genetic potential for PCP degradation at historically polluted groundwater sites

    NASA Astrophysics Data System (ADS)

    Mikkonen, Anu; Yläranta, Kati; Tiirola, Marja; Romantschuk, Martin; Sinkkonen, Aki

    2016-04-01

    Pentachlorophenol (PCP) is a priority pollutant of exclusively anthropogenic origin. Formerly used commonly in timber preservatives, PCP has persisted at polluted groundwater sites decades after its use was banned, typically as the last detectable contaminant component. Notorious for its toxicity and poor biodegradability, little is known about the genetic potential and pathways for PCP degradation in the environment. The only fully characterized mineralization pathway is initiated by the enzyme coded by chromosomal pcpB gene, previously detected in PCP degrading Sphingomonadaceae bacteria isolated at two continents. However, there is no information about the abundance or diversity of any PCP degradation related gene at contaminated sites in situ. Our aim was to assess whether pcpB and/or sphingomonads seem to play a role in in situ degradation of PCP, by studying whether pcpB i) is detectable at chlorophenol-polluted groundwater sediments, ii) responds to PCP concentration changes, and iii) shows correlation with the abundance of sphingomonads or a specific sphingomonad genus. Novel protocols for quantification and profiling of pcpB, with primers covering full known diversity, were developed and tested at two sites in Finland with well-documented long-term chlorophenol contamination history: Kärkölä and Pursiala. High throughput sequencing complemented characterization of the total bacterial community and pcpB gene pool. The relative abundance of pcpB in bacterial community was associated with spatial variability in groundwater PCP concentration in Pursiala, and with temporal differences in groundwater PCP concentration in Kärkölä. T-RFLP fingerprinting results indicated and Ion Torrent PGM and Sanger sequencing confirmed the presence of a single phylotype of pcpB at both geographically distant, historically contaminated sites, matching the one detected previously in Canadian bioreactor clones and Kärkölä bioreactor isolates. Sphingomonad abundance

  11. Ag/AgO Nanoparticles Grown via Time Dependent Double Mechanism in a 2D Layered Ni-PCP and Their Antibacterial Efficacy

    PubMed Central

    Agarwal, Rashmi A.; Gupta, Neeraj K.; Singh, Rajan; Nigam, Shivansh; Ateeq, Bushra

    2017-01-01

    A simple synthesis route for growth of Ag/AgO nanoparticles (NPs) in large quantitative yields with narrow size distribution from a functional, non-activated, Ni (II) based highly flexible porous coordination polymer (PCP) as a template has been demonstrated. This template is a stable storage media for the NPs larger than the pore diameters of the PCP. From EPR study it was concluded that NPs were synthesized via two mechanisms i.e. acid formation and the redox activity of the framework. Size range of Ag/AgO NPs is sensitive to choice of solvent and reaction time. Direct use of Ag/AgO@Ni-PCP shows influential growth inhibition towards Escherichia coli and the pathogen Salmonella typhimurium at extremely low concentrations. The pristine template shows no cytotoxic activity, even though it contains Ni nodes in the framework. PMID:28322256

  12. Ag/AgO Nanoparticles Grown via Time Dependent Double Mechanism in a 2D Layered Ni-PCP and Their Antibacterial Efficacy

    NASA Astrophysics Data System (ADS)

    Agarwal, Rashmi A.; Gupta, Neeraj K.; Singh, Rajan; Nigam, Shivansh; Ateeq, Bushra

    2017-03-01

    A simple synthesis route for growth of Ag/AgO nanoparticles (NPs) in large quantitative yields with narrow size distribution from a functional, non-activated, Ni (II) based highly flexible porous coordination polymer (PCP) as a template has been demonstrated. This template is a stable storage media for the NPs larger than the pore diameters of the PCP. From EPR study it was concluded that NPs were synthesized via two mechanisms i.e. acid formation and the redox activity of the framework. Size range of Ag/AgO NPs is sensitive to choice of solvent and reaction time. Direct use of Ag/AgO@Ni-PCP shows influential growth inhibition towards Escherichia coli and the pathogen Salmonella typhimurium at extremely low concentrations. The pristine template shows no cytotoxic activity, even though it contains Ni nodes in the framework.

  13. Controlling a toxic shock of pentachlorophenol (PCP) to anaerobic digestion using activated carbon addition.

    PubMed

    Xiao, Yeyuan; De Araujo, Cecilia; Sze, Chun Chau; Stuckey, David C

    2015-04-01

    Several powdered and granular activated carbons (PACs and GACs) were tested for adsorption of pentachlorophenol (PCP) in bench-scale anaerobic digestion reactors to control the toxicity of PCP to acetoclastic methanogenesis. Results showed that the adsorption capacities of PAC were reduced by 21-54%, depending on the PAC addition time, in the presence of the methanogenic sludge compared to the controls without sludge. As a preventive measure, PAC at a low dose of 20% (mass ratio to the VSS) added 24 h prior to, or simultaneously with, the addition of PCP could completely eliminate the toxic effects of PCP. At the same dose, PAC also enabled methanogenesis to recover immediately after the sludge had been exposed to PCP for 24h. GAC was not effective in enabling the recovery of methanogenesis due to its slow adsorption kinetics; however, at a dose of 80% it could partially ameliorate the toxic shock of PCP. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Adsorption of PolyCarboxylate Poly(ethylene glycol) (PCP) esters on Montmorillonite (Mmt): effect of exchangeable cations (Na+, Mg2+ and Ca2+) and PCP molecular structure.

    PubMed

    Ait-Akbour, Rachid; Boustingorry, Pascal; Leroux, Fabrice; Leising, Frédéric; Taviot-Guého, Christine

    2015-01-01

    This study deals with the adsorption of PolyCarboxylate Poly(ethylene glycol) esters (PCP) superplasticizers on Na-, Mg- and Ca-saturated Montmorillonite (Mmt) clays. The interactions have been examined through different experimental methods: adsorption isotherms, zeta potential measurements and sedimentation experiments. It was found that PCP adsorption depends both on the architecture of PCP molecules and the nature of cation located on the interlayer exchange sites of the Montmorillonite. Whatever the PCP, a larger amount was adsorbed on Na-Mont than on Mg-Mont or Ca-Mont. This indicates the occurrence of two adsorption mechanisms: (i) a superficial adsorption via electrostatic interactions between the carboxylate groups of PCP and positively charged sites on clay surfaces, (ii) intercalation of ether units of the PCP grafts in the interlayer space by displacement of water molecules coordinated to the exchangeable cations. Furthermore, despite the weak negative values of the zeta potential, the addition of PCP promotes the stability of the suspensions which is attributed to steric repulsion acting between particles. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Risk factors for Pneumocystis jiroveci pneumonia (PcP) in renal transplant recipients.

    PubMed

    Eitner, Frank; Hauser, Ingeborg A; Rettkowski, Olaf; Rath, Thomas; Lopau, Kai; Pliquett, Rainer U; Fiedler, Roman; Guba, Markus; Hilgers, Ralf-Dieter; Floege, Jürgen; Fischereder, Michael

    2011-06-01

    Pneumocystis jiroveci pneumonia (PcP) is a potentially life-threatening complication in renal transplant recipients with increased reports during the past few years. Individual risk factors for susceptibility to PcP are incompletely understood. We retrospectively analysed 60 cases of confirmed PcP, diagnosed in six German transplant centres between 2004 and 2008, as well as 60 matched controls. Compared with controls, PcP cases revealed the following significant differences: PcP cases had a poorer renal function (eGFR 31 vs. 42 mL/min in controls), more biopsy-proven rejections (18 vs. 5 patients), more frequent treatment with mycophenolate mofetil (53 vs. 44 patients) and less frequent treatment with interleukin-2 receptor antagonist (20 vs. 32 patients). According to centre policy, in those years, none of the patients or controls had received PcP prophylaxis after transplantation. Of the 60 patients with PcP, 30% developed the disease after the currently recommended duration of prophylactic treatment, 27% died in the course of the disease and 45% required treatment in the ICU. Our case-control study reveals a novel risk profile for PcP. Renal transplant recipients with more pronounced renal insufficiency following rejection episodes and treated with intensified immunosuppression are at particular risk for PcP.

  16. Non-precious metal complexes with an anionic PCP pincer architecture.

    PubMed

    Murugesan, Sathiyamoorthy; Kirchner, Karl

    2016-01-14

    This perspective article provides an overview of the advancements in the field of non-precious metal complexes featuring anionic PCP pincer ligands with the inclusion of aliphatic systems. It covers research from the beginning in 1976 until late 2015 and provides a summary of key developments in this area, which is, to date, limited to the metals nickel, cobalt, iron, and molybdenum. While the research in nickel PCP complexes is already quite extensive, the chemistry of cobalt, iron, and molybdenum PCP complexes is comparatively sparse. With other non-precious metals such as copper, manganese, chromium or vanadium no PCP complexes are known as yet. In the case of nickel PCP complexes already many catalytic applications such as Suzuki-Miyaura coupling, C-S cross coupling, Kharasch and Michael additions, hydrosilylation of aldehydes and ketones, cyanomethylation of aldehydes, and hydroamination of nitriles were reported. While iron PCP complexes were found to be active catalysts for the hydrosilylation of aldehydes and ketones as well as the dehydrogenation of ammonia-borane, cobalt PCP complexes were not applied to any catalytic reactions. Surprisingly, only one molybdenum PCP complex is reported, which was capable of cleaving dinitrogen to give a nitride complex. This perspective underlines that the combination of cheap and abundant metals such as nickel, cobalt, and iron with PCP pincer ligands may result in the development of novel, versatile, and efficient catalysts for atom-efficient catalytic reactions.

  17. [FTIR study of adsorption of PCP on hematite surface].

    PubMed

    Fang, Ji-Min; Li, Shan-Hu; Gong, Wen-Qi; Sun, Zhen-Ya; Yang, Hong-Gang

    2009-02-01

    The adsorption of pentachlorophenol on hematite was studied through adsorption experiments and FTIR analysis. The pH adsorption isotherms of pentachlorophenol onto hematite were obtained by the static state experiments. The largest adsorption quantity occurred at about pH 6. The adsorption quantity at pH 8.5 of the isoelectric point of hematite was about 31% of the largest adsorption quantity. Fourier transform infrared (FTIR) spectroscopy was used to analyse the change of hematite before and after PCP adsorption, and the species of PCP on hematite. It was discovered that: (1) the typical peak at 565 cm(-1) of the Fe-O bond in alpha-Fe2O3 did not change before and after adsorption, and the adsorption occurred on the surface of hematite. (2) At pH 6.0, the stretching vibration peak at 3 438 cm(-1) due to the hydrogen bond formed between O-H on the surface of alpha-Fe2O3 and water molecules shifted to 3 417 cm(-1). The bending vibration peak of H-O-H+ on the surface at 1 643 cm(-1) was weakened because of complex reaction. The peak owing to Fe-OH bond was displaced from 1 050-1 100 cm(-1) to 950 cm(-1) with increased intensity. The C-O bond stretching vibration peak of PCP was displaced from 1 215 to 1 122 cm(-1). The main interaction between PCP and hematite was static electric interaction. (3) At pH 8.5, the stretching vibration peak of the hydrogen bond formed between O-H on the surface of alpha-Fe2O3 and water molecules was displaced from 3 438 to 3 428 cm(-1). The bending vibration peak at 1 643 cm(-1) was obviously weakened because of the hydrogen bonding. The H-O-H+ bending vibration peak at 1 050-1 100 cm(-1) was displaced to 947 cm(-1) with obviously increased intensity, indicating that the interaction was mainly through hydrogen bond.

  18. A density functional theory for vapor-liquid interfaces using the PCP-SAFT equation of state.

    PubMed

    Gross, Joachim

    2009-11-28

    A Helmholtz energy functional for inhomogeneous fluid phases based on the perturbed-chain polar statistical associating fluid theory (PCP-SAFT) equation of state is proposed. The model is supplemented with a capillary wave contribution to the surface tension to account for long-wavelength fluctuations of a vapor-liquid interface. The functional for the dispersive attraction is based on a nonlocal perturbation theory for chain fluids and the difference of the perturbation theory to the dispersion term of the PCP-SAFT equation of state is treated with a local density approximation. This approach suggested by Gloor et al. [Fluid Phase Equilib. 194, 521 (2002)] leads to full compatibility with the PCP-SAFT equation of state. Several levels of approximation are compared for the nonlocal functional of the dispersive attractions. A first-order non-mean-field description is found to be superior to a mean-field treatment, whereas the inclusion of a second-order perturbation term does not contribute significantly to the results. The proposed functional gives excellent results for the surface tension of nonpolar or only moderately polar fluids, such as alkanes, aromatic substances, ethers, and ethanoates. A local density approximation for the polar interactions is sufficient for carbon dioxide as a strongly quadrupolar compound. The surface tension of acetone, as an archetype dipolar fluid, is overestimated, suggesting that a nonisotropic orientational distribution function across an interface should for strong dipolar substances be accounted for.

  19. Retinal ON Bipolar Cells Express a New PCP2 Splice Variant That Accelerates the Light Response

    PubMed Central

    Sulaiman, Pyroja; Feddersen, Rod M.; Liu, Jian; Smith, Robert G.; Vardi, Noga

    2008-01-01

    PCP2, a member of the GoLoco domain-containing family, is present exclusively in cerebellar Purkinje cells and retinal ON bipolar cells. Its function in these tissues is unknown. Biochemical and expression system studies suggest that PCP2 is a guanine nucleotide dissociation inhibitor, although a guanine nucleotide exchange factor has also been suggested. Here, we studied the function of PCP2 in ON bipolar cells because their light response depends on Gαo1, which is known to interact with PCP2. We identified a new splice variant of PCP2 (Ret-PCP2) and localized it to rod bipolar and ON cone bipolar cells. Electroretinogram recordings from PCP2-null mice showed a normal a-wave but a slower falling phase of the b-wave (generated by the activity of ON bipolar cells) relative to the wild type. Whole-cell recordings from rod bipolar cells showed, both under Ames medium and after blocking GABAA/C and glycine receptors, that PCP2-null rod bipolar cells were more depolarized than wild-type cells with greater inward current when clamped to −60 mV. Also under both conditions, the rise time of the response to intense light was slower by 28% (Ames) and 44% (inhibitory blockers) in the null cells. Under Ames medium, we also observed >30% longer decay time in the PCP2-null rod bipolar cells. We conclude that PCP2 facilitates cation channels closure in the dark, shortens the rise time of the light response directly, and accelerates the decay time indirectly via the inhibitory network. These data can most easily be explained if PCP2 serves as a guanine nucleotide exchange factor. PMID:18768681

  20. PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues

    PubMed Central

    Felizola, Saulo J. A.; Nakamura, Yasuhiro; Ono, Yoshikiyo; Kitamura, Kanako; Kikuchi, Kumi; Onodera, Yoshiaki; Ise, Kazue; Takase, Kei; Sugawara, Akira; Hattangady, Namita; Rainey, William E.; Satoh, Fumitoshi; Sasano, Hironobu

    2014-01-01

    Purkinje cell protein 4 (PCP4) is a calmodulin (CaM) binding protein that accelerates calcium association and dissociation with CaM. It has been previously detected in aldosterone-producing adenomas (APA) but details on its expression and function in adrenocortical tissues have remained unknown. Therefore, we performed the immunohistochemical analysis of PCP4 in the following tissues: normal adrenal (NA; n=15), APA (n=15), cortisol producing adenomas (CPA; n=15) and idiopathic hyperaldosteronism cases (IHA; n=5). APA samples (n=45) were also submitted to quantitative RT-PCR (qPCR) of PCP4, CYP11B1, and CYP11B2, as well as DNA sequencing for KCNJ5 mutations. Transient transfection analysis using PCP4 siRNA was also performed in H295R adrenocortical carcinoma cells, following ELISA analysis, and CYP11B2 luciferase assays were also performed after PCP4 vector transfection in order to study the regulation of PCP4 protein expression. In our findings, PCP4 immunoreactivity was predominantly detected in APA and in the zona glomerulosa (ZG) of NA and IHA. In APA, the mRNA levels of PCP4 were significantly correlated with those of CYP11B2 (P<0.0001) and were significantly higher in cases with KCNJ5 mutation than wild-type (P=0.005). Following PCP4 vector transfection, CYP11B2 luciferase reporter activity was significantly higher than controls in the presence of angiotensin-II. Knockdown of PCP4 resulted in a significant decrease in CYP11B2 mRNA levels (P=0.012) and aldosterone production (P=0.011). Our results indicate that PCP4 is a regulator of aldosterone production in normal, hyperplastic and neoplastic human adrenocortical cells. PMID:24403568

  1. Sensorimotor enhancement in mouse mutants lacking the Purkinje cell-specific Gi/o modulator, Pcp2(L7)

    PubMed Central

    Iscru, Emilia; Serinagaoglu, Yelda; Schilling, Karl; Tian, Jinbin; Bowers-Kidder, Stephanie L.; Zhang, Rui; Morgan, James I.; DeVries, A. Courtney; Nelson, Randy J.; Zhu, Michael X.; Oberdick, John

    2009-01-01

    Pcp2(L7) is a GoLoco domain protein specifically and abundantly expressed in cerebellar Purkinje cells. It has been hypothesized to “tune” Gi/o-coupled receptor modulation of physiological effectors, including the P-type Ca2+ channel. We have analyzed a mouse mutant in which the Pcp2(L7) gene was inactivated and find significant anatomical, behavioral and electrophysiological changes. Anatomically, we observed mild cerebellar hypoplasia. Behaviorally, the mutants were altered in modalities atypical for a traditional cerebellar mutant, and oddly, all of these changes could be considered functional enhancements. This includes increased asymptotic performance in gross motor learning, increased rate of acquisition in tone-conditioned fear, and enhanced pre-pulse inhibition of the acoustic startle response. Electrophysiological analysis of Purkinje cells in the mutants reveals depression of the complex spike waveform that may underlie the behavioral changes. Based on these observations we suggest that the Pcp2(L7) protein acts as a sensorimotor damper that modulates time- and sense-dependent changes in motor responses. PMID:18930827

  2. Sensorimotor enhancement in mouse mutants lacking the Purkinje cell-specific Gi/o modulator, Pcp2(L7).

    PubMed

    Iscru, Emilia; Serinagaoglu, Yelda; Schilling, Karl; Tian, Jinbin; Bowers-Kidder, Stephanie L; Zhang, Rui; Morgan, James I; DeVries, A Courtney; Nelson, Randy J; Zhu, Michael X; Oberdick, John

    2009-01-01

    Pcp2(L7) is a GoLoco domain protein specifically and abundantly expressed in cerebellar Purkinje cells. It has been hypothesized to "tune" G(i/o)-coupled receptor modulation of physiological effectors, including the P-type Ca(2+) channel. We have analyzed a mouse mutant in which the Pcp2(L7) gene was inactivated and find significant anatomical, behavioral and electrophysiological changes. Anatomically, we observed mild cerebellar hypoplasia. Behaviorally, the mutants were altered in modalities atypical for a traditional cerebellar mutant, and oddly, all of these changes could be considered functional enhancements. This includes increased asymptotic performance in gross motor learning, increased rate of acquisition in tone-conditioned fear, and enhanced pre-pulse inhibition of the acoustic startle response. Electrophysiological analysis of Purkinje cells in the mutants reveals depression of the complex spike waveform that may underlie the behavioral changes. Based on these observations we suggest that the Pcp2(L7) protein acts as a sensorimotor damper that modulates time- and sense-dependent changes in motor responses.

  3. DEMONSTRATION BULLETIN: HNU-HANBY PCP IMMUNOASSAY TEST KIT - HNU - SYSTEMS, INC.

    EPA Science Inventory

    The HNU-Hanby test kit rapidly analyzes for petroleum hydrocarbons in soil and water samples. The test kit can be used to estimate pentachlorophenol (PCP) concentrations in samples when the carrier solvent is a petroleum hydrocarbon. The test kit estimates PCP concentrations in ...

  4. Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase.

    PubMed

    Carroll, Marilyn E; Kohl, Emily A; Johnson, Krista M; LaNasa, Rachel M

    2013-06-01

    In previous studies with male and female rhesus monkeys, withdrawal of access to oral phencyclidine (PCP) self-administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females, and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer impulsive choice for SACC increased during PCP withdrawal more in males than females. The goal of the present study was to examine the effect of PCP (0.25 or 0.5 mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle. In component 1, PCP and water were available from two drinking spouts for 1.5 h sessions under concurrent FR 16 schedules. In component 2, a SACC solution was available for 45 min under a DD schedule. Monkeys had a choice of one immediate SACC delivery (0.6 ml) or six delayed SACC deliveries, and the delay was increased by 1 s after a response on the delayed lever and decreased by 1 s after a response on the immediate lever. There was then a 10-day water substitution phase, or PCP withdrawal, that occurred during the mid-follicular phase (days 7-11) or the late luteal phase (days 24-28) of the menstrual cycle. Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases. PCP deliveries were higher during the luteal (vs follicular) phase. Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration. PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys.

  5. Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase

    PubMed Central

    Carroll, Marilyn E.; Kohl, Emily A.; Johnson, Krista M.; LaNasa, Rachel M.

    2013-01-01

    Background In previous studies with male and female rhesus monkeys withdrawal of access to oral phencyclidine (PCP) self administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer. Impulsive choice for SACC increased during PCP withdrawal more than females. Objectives The goal of the present study was to examine the effect of PCP (0.25 or 0.5 mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle. Materials and methods In Component 1 PCP and water were available from 2 drinking spouts for 1.5 h sessions under concurrent FR 16 schedules. In Component 2 a SACC solution was available for 45 min under a DD schedule. Monkeys had a choice of one immediate SACC delivery (0.6 ml) or 6 delayed SACC deliveries, and the delay was increased by 1 sec after a response on the delayed lever and decreased by 1 sec after a response on the immediate lever. There was then a 10-day water substitution phase, or PCP-withdrawal, that occurred during the mid-folllicular phase (Days 7–11) or the late-luteal (Days 24–28) phase of the menstrual cycle. Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases. Results PCP deliveries were higher during the luteal vs the follicular phase. Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration. Conclusions PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys. PMID:23344553

  6. Phencyclidine (PCP) produces sexually dimorphic effects on voluntary sucrose consumption and elevated plus maze behavior.

    PubMed

    Turgeon, Sarah M; Anderson, Nicole; O'Loughlin, Kerry

    2010-04-01

    Previous research in our laboratory indicates that the psychotomimetic drug phencyclidine (PCP) reduces voluntary sucrose consumption in male rats, potentially modeling the schizophrenic symptom of anhedonia. Given reports from the clinical literature that schizophrenia has a later age of onset and more favorable outcome in females, PCP might be expected to have sexually dimorphic effects in animal models of schizophrenia such as PCP-induced decreases in voluntary sucrose consumption. Young adult (66 days old) and adult (109 days old) male and female rats were trained to drink sucrose during a 30 min/day presentation protocol. On the day prior to the test day, animals were treated with PCP (15 mg/kg) or saline four hours after the onset of the sucrose presentation (20 h prior to the sucrose on the test day). PCP decreased sucrose consumption on the test day similarly in adult males and females, although females also showed decreased water consumption. In young animals, PCP decreased sucrose consumption in males but not in females. These results are consistent with the prediction that females will be less sensitive to the schizophrenia-like behavioral effects of PCP. In a separate study, the same animals were tested in an elevated plus maze one to two months after testing for voluntary sucrose consumption. Significant sex x drug interaction effects on a number of measures in the elevated plus maze indicated that prior exposure to PCP had an anxiolytic effect in females and an anxiogenic effect in males. While unexpected, this finding indicates an additional sexually dimorphic effect of PCP on behavior and its potential relevance to the PCP model of schizophrenia is discussed. 2010 Elsevier Inc. All rights reserved.

  7. ErbB signaling antagonist ameliorates behavioral deficit induced by phencyclidine (PCP) in mice, without affecting metabolic syndrome markers.

    PubMed

    Tadmor, Hagar; Golani, Idit; Doron, Ravid; Kremer, Ilana; Shamir, Alon

    2017-08-14

    Schizophrenia is a severe syndrome that affects about 1% of the world population. Since the mid-1950s, antipsychotics have been used to treat schizophrenia with preference for treating positive symptoms; however, their tolerance level is low, there are numerous side effects, and only some patients respond to the treatment. Antipsychotic medications that are more effective, better tolerated, and with fewer adverse effects are urgently needed. Given the accumulating evidence of the role filled by the ErbB signaling network in the biology of the dopamine, GABA, and glutamate systems, and in the etiology of schizophrenia, we hypothesized that the ErbB network is a candidate for development of a novel agent through which various symptoms of schizophrenia and other psychiatric disorders might be treated. Herein, we studied, in mice, the capability of blocking the ErbB signaling, in comparison with the atypical antipsychotic drug clozapine, to counter schizophrenia-like behavior induced by acute and sub-chronic phencyclidine (PCP), and determined whether inhibition of the ErbB networks induced weight gain and affected social and exploratory behavior, and metabolic syndrome markers. We demonstrated that administration of the pan-ErbB inhibitor JNJ28871063 (JNJ) reduced the level of activity in the open field induced by an acute injection of PCP. Moreover, the ability of JNJ to attenuate the effect of PCP is as effective as clozapine. In addition and like clozapine, JNJ normalized social behavior impairment induced by sub-chronic PCP and stress. Adult JNJ-treated mice displayed normal sociability and exploratory behavior, and their serum cholesterol, LDL, and HDL levels were lower than in the saline-treated mice. Sub-chronic treatment did not affect weight gain, glucose levels, and the activity of hepatic enzymes catalase and SOD. These data suggest that treatment with JNJ attenuates abnormal behaviors induced by PCP, and has similar effects as the antipsychotic drug

  8. Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model

    PubMed Central

    Sershen, Henry; Hashim, Audrey; Dunlop, David S.; Suckow, Raymond F.; Cooper, Tom B.; Javitt, Daniel C.

    2016-01-01

    Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D-amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D-serine. In the present study we further evaluated the effect of DAAO inhibitors 5-chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D-serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol®) was tested with D-serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor sodium benzoate (NaB) (400 mg/kg), and NaB plus D-serine also significantly reduced PCP-induced locomotor activity, but without affecting plasma or brain D-serine level

  9. Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model.

    PubMed

    Sershen, Henry; Hashim, Audrey; Dunlop, David S; Suckow, Raymond F; Cooper, Tom B; Javitt, Daniel C

    2016-02-01

    Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D-amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D-serine. In the present study we further evaluated the effect of DAAO inhibitors 5-chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D-serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol(®)) was tested with D-serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor NaB (400 mg/kg), and NaB plus D-serine also significantly reduced PCP-induced locomotor activity, but without affecting plasma or brain D-serine level, arguing against a DAAO

  10. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... involving marijuana, cocaine, amphetamines, or PCP? 40.137 Section 40.137 Transportation Office of the... results involving marijuana, cocaine, amphetamines, or PCP? (a) As the MRO, you must verify a confirmed positive test result for marijuana, cocaine, amphetamines, and/or PCP unless the employee presents a...

  11. Fatal Intoxication Involving 3-MeO-PCP: A Case Report and Validated Method.

    PubMed

    Bakota, Erica; Arndt, Crystal; Romoser, Amelia A; Wilson, Stephen K

    2016-09-01

    We present in this case report a validated method for accurate quantitative analysis of 3-methoxy phencyclidine (3-MeO-PCP) to determine postmortem blood concentrations of this PCP analog. A 29-year-old male with a history of illicit drug use was found unresponsive in his bed with a bag of white powder next to him. Resuscitation efforts were unsuccessful and the individual was pronounced dead 9 minutes after arrival to the hospital. Initial ELISA screening suggested the presence of PCP in the decedent's blood. However, confirmatory testing revealed no detectable PCP. Instead, a large peak corresponding to a m/z 274.218 species with retention time similar to PCP was present on a LC-TOF-MS drug screen, suggesting a possible PCP analog. This mass corresponds specifically to a methoxy-PCP analog, several of which are available for purchase online. Standards for 3-MeO-PCP and 4-MeO-PCP were obtained and injected on the same instrument. Although the 3- and 4-MeO-PCP analogs have identical masses and retention times, they are still distinguishable through their mass spectra. The peak from the decedent's sample matched both the mass spectrum and the retention time of 3-MeO-PCP. A quantitative LC-MS-MS method was subsequently developed and validated for casework. Analysis using this method revealed a concentration of 139 ± 41 µg/L 3-MeO-PCP in the decedent's blood. Diphenhydramine (4.1 ± 0.7 mg/L), marijuana metabolite (presumptive positive, confirmation not performed) and a small amount of amphetamine (<0.10 mg/L) were also found in the decedent's blood. The cause of death was determined to be combined 3-MeO-PCP, diphenhydramine and amphetamine toxicity. The manner of death was certified as an accident. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. The Drosophila Homologue of the Amyloid Precursor Protein Is a Conserved Modulator of Wnt PCP Signaling

    PubMed Central

    Soldano, Alessia; Okray, Zeynep; Janovska, Pavlina; Tmejová, Kateřina; Reynaud, Elodie; Claeys, Annelies; Yan, Jiekun; Atak, Zeynep Kalender; De Strooper, Bart; Dura, Jean-Maurice; Bryja, Vítězslav; Hassan, Bassem A.

    2013-01-01

    Wnt Planar Cell Polarity (PCP) signaling is a universal regulator of polarity in epithelial cells, but it regulates axon outgrowth in neurons, suggesting the existence of axonal modulators of Wnt-PCP activity. The Amyloid precursor proteins (APPs) are intensely investigated because of their link to Alzheimer's disease (AD). APP's in vivo function in the brain and the mechanisms underlying it remain unclear and controversial. Drosophila possesses a single APP homologue called APP Like, or APPL. APPL is expressed in all neurons throughout development, but has no established function in neuronal development. We therefore investigated the role of Drosophila APPL during brain development. We find that APPL is involved in the development of the Mushroom Body αβ neurons and, in particular, is required cell-autonomously for the β-axons and non-cell autonomously for the α-axons growth. Moreover, we find that APPL is a modulator of the Wnt-PCP pathway required for axonal outgrowth, but not cell polarity. Molecularly, both human APP and fly APPL form complexes with PCP receptors, thus suggesting that APPs are part of the membrane protein complex upstream of PCP signaling. Moreover, we show that APPL regulates PCP pathway activation by modulating the phosphorylation of the Wnt adaptor protein Dishevelled (Dsh) by Abelson kinase (Abl). Taken together our data suggest that APPL is the first example of a modulator of the Wnt-PCP pathway specifically required for axon outgrowth. PMID:23690751

  13. The Drosophila homologue of the amyloid precursor protein is a conserved modulator of Wnt PCP signaling.

    PubMed

    Soldano, Alessia; Okray, Zeynep; Janovska, Pavlina; Tmejová, Kateřina; Reynaud, Elodie; Claeys, Annelies; Yan, Jiekun; Atak, Zeynep Kalender; De Strooper, Bart; Dura, Jean-Maurice; Bryja, Vítězslav; Hassan, Bassem A

    2013-01-01

    Wnt Planar Cell Polarity (PCP) signaling is a universal regulator of polarity in epithelial cells, but it regulates axon outgrowth in neurons, suggesting the existence of axonal modulators of Wnt-PCP activity. The Amyloid precursor proteins (APPs) are intensely investigated because of their link to Alzheimer's disease (AD). APP's in vivo function in the brain and the mechanisms underlying it remain unclear and controversial. Drosophila possesses a single APP homologue called APP Like, or APPL. APPL is expressed in all neurons throughout development, but has no established function in neuronal development. We therefore investigated the role of Drosophila APPL during brain development. We find that APPL is involved in the development of the Mushroom Body αβ neurons and, in particular, is required cell-autonomously for the β-axons and non-cell autonomously for the α-axons growth. Moreover, we find that APPL is a modulator of the Wnt-PCP pathway required for axonal outgrowth, but not cell polarity. Molecularly, both human APP and fly APPL form complexes with PCP receptors, thus suggesting that APPs are part of the membrane protein complex upstream of PCP signaling. Moreover, we show that APPL regulates PCP pathway activation by modulating the phosphorylation of the Wnt adaptor protein Dishevelled (Dsh) by Abelson kinase (Abl). Taken together our data suggest that APPL is the first example of a modulator of the Wnt-PCP pathway specifically required for axon outgrowth.

  14. The role of P2X7 receptors in a rodent PCP-induced schizophrenia model.

    PubMed

    Koványi, Bence; Csölle, Cecilia; Calovi, Stefano; Hanuska, Adrienn; Kató, Erzsébet; Köles, László; Bhattacharya, Anindya; Haller, József; Sperlágh, Beáta

    2016-11-08

    P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7-/-), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated. The selective P2X7 receptor antagonist JNJ-47965567 partly replicated the effect of gene deficiency on PCP-induced behavioral changes and counteracted PCP-induced social withdrawal. We also show that PCP treatment upregulates and increases the functional responsiveness of P2X7Rs in the prefrontal cortex of young adult animals. The amplitude of NMDA evoked currents recorded from layer V pyramidal neurons of cortical slices were slightly decreased by both genetic deletion of P2rx7 and by JNJ-47965567. PCP induced alterations in mRNA expression encoding schizophrenia-related genes, such as NR2A, NR2B, neuregulin 1, NR1 and GABA α1 subunit were absent in the PFC of young adult P2rx7-/- animals. Our findings point to P2X7R as a potential therapeutic target in schizophrenia.

  15. Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking.

    PubMed

    Gault, William J; Olguin, Patricio; Weber, Ursula; Mlodzik, Marek

    2012-03-05

    Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and function. Polarized vesicle trafficking has emerged as a fundamental mechanism by which protein and membrane can be targeted to discrete subcellular domains to promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling orchestrates cytoskeletal polarization and drives morphogenetic changes in such contexts as the vertebrate body axis and external Drosophila melanogaster tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been identified, the interplay between the vesicle trafficking machinery and downstream terminal PCP-directed processes is less established. In this paper, we show that Drosophila CK1-γ/gilgamesh (gish) regulates the PCP-associated process of trichome formation through effects on Rab11-mediated vesicle recycling. Although the core Fz/PCP proteins dictate prehair formation broadly, CK1-γ/gish restricts nucleation to a single site. Moreover, CK1-γ/gish works in parallel with the Fz/PCP effector multiple wing hairs, which restricts prehair formation along the perpendicular axis to Gish. Our findings suggest that polarized Rab11-mediated vesicle trafficking regulated by CK1-γ is required for PCP-directed processes.

  16. Interaction between phencyclidine (PCP) and GABA-ergic drugs: clinical implications.

    PubMed

    Menon, M K; Clark, W G; Vivonia, C

    1980-01-01

    Pretreatment (IP) of mice with (-) baclofen, muscimol, 4,5,6,7-tetrahydroisoxazolo (S,4-c) pyridin-3-ol hydrate (THIP), aminooxyacetic acid (AOAA) or gamma-acetylenic GABA caused a dose-dependent inhibition of thelocomotor stimulant effect of phencyclidine (PCP, 8 mg/kg). Although (-) baclofen was found to be the most effective PCP antagonist, its (+) isomer was inactive. The maximum blocking effect of AOAA was seen in animals treated 3 and 6 hr earlier. Except for gamma-acetylenic GABA, none of these drugs significantly blocked the locomotor stimulant effect of d-amphetamine (3 mg/kg, IP). Diazepam reduced d-amphetamine response, but failed to influence PCP-induced stimulation. The locomotor stimulant effect of PCP, unlike that of d-amphetamine, may be the result of a specific GABA antagonistic effect at certain dopamine-rich areas of the brain. It seems that (-) baclofen may prove to be useful in the management of PCP intoxication. Administration of higher doses of PCP (20 and 50 mg/kg) in mice pretreated with (-) baclofen resulted in the development of surgical anesthesia manifested as the loss of a) righting reflex, b) pain sensation and c) corneal reflex. The duration of the general anesthetic response was found to be a function of the doses of both (-) baclofen and PCP. The possible use of (-) baclofen as an adjuvant to general anesthetic is discussed.

  17. Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking

    PubMed Central

    Gault, William J.; Olguin, Patricio; Weber, Ursula

    2012-01-01

    Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and function. Polarized vesicle trafficking has emerged as a fundamental mechanism by which protein and membrane can be targeted to discrete subcellular domains to promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling orchestrates cytoskeletal polarization and drives morphogenetic changes in such contexts as the vertebrate body axis and external Drosophila melanogaster tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been identified, the interplay between the vesicle trafficking machinery and downstream terminal PCP-directed processes is less established. In this paper, we show that Drosophila CK1-γ/gilgamesh (gish) regulates the PCP-associated process of trichome formation through effects on Rab11-mediated vesicle recycling. Although the core Fz/PCP proteins dictate prehair formation broadly, CK1-γ/gish restricts nucleation to a single site. Moreover, CK1-γ/gish works in parallel with the Fz/PCP effector multiple wing hairs, which restricts prehair formation along the perpendicular axis to Gish. Our findings suggest that polarized Rab11-mediated vesicle trafficking regulated by CK1-γ is required for PCP-directed processes. PMID:22391037

  18. Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation.

    PubMed

    Wang, Jianbo; Hamblet, Natasha S; Mark, Sharayne; Dickinson, Mary E; Brinkman, Brendan C; Segil, Neil; Fraser, Scott E; Chen, Ping; Wallingford, John B; Wynshaw-Boris, Anthony

    2006-05-01

    The planar cell polarity (PCP) pathway is conserved throughout evolution, but it mediates distinct developmental processes. In Drosophila, members of the PCP pathway localize in a polarized fashion to specify the cellular polarity within the plane of the epithelium, perpendicular to the apicobasal axis of the cell. In Xenopus and zebrafish, several homologs of the components of the fly PCP pathway control convergent extension. We have shown previously that mammalian PCP homologs regulate both cell polarity and polarized extension in the cochlea in the mouse. Here we show, using mice with null mutations in two mammalian Dishevelled homologs, Dvl1 and Dvl2, that during neurulation a homologous mammalian PCP pathway regulates concomitant lengthening and narrowing of the neural plate, a morphogenetic process defined as convergent extension. Dvl2 genetically interacts with Loop-tail, a point mutation in the mammalian PCP gene Vangl2, during neurulation. By generating Dvl2 BAC (bacterial artificial chromosome) transgenes and introducing different domain deletions and a point mutation identical to the dsh1 allele in fly, we further demonstrated a high degree of conservation between Dvl function in mammalian convergent extension and the PCP pathway in fly. In the neuroepithelium of neurulating embryos, Dvl2 shows DEP domain-dependent membrane localization, a pre-requisite for its involvement in convergent extension. Intriguing, the Loop-tail mutation that disrupts both convergent extension in the neuroepithelium and PCP in the cochlea does not disrupt Dvl2 membrane distribution in the neuroepithelium, in contrast to its drastic effect on Dvl2 localization in the cochlea. These results are discussed in light of recent models on PCP and convergent extension.

  19. Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation

    PubMed Central

    Wang, Jianbo; Hamblet, Natasha S.; Mark, Sharayne; Dickinson, Mary E.; Brinkman, Brendan C.; Segil, Neil; Fraser, Scott E.; Chen, Ping; Wallingford, John B.; Wynshaw-Boris, Anthony

    2014-01-01

    The planar cell polarity (PCP) pathway is conserved throughout evolution, but it mediates distinct developmental processes. In Drosophila, members of the PCP pathway localize in a polarized fashion to specify the cellular polarity within the plane of the epithelium, perpendicular to the apicobasal axis of the cell. In Xenopus and zebrafish, several homologs of the components of the fly PCP pathway control convergent extension. We have shown previously that mammalian PCP homologs regulate both cell polarity and polarized extension in the cochlea in the mouse. Here we show, using mice with null mutations in two mammalian Dishevelled homologs, Dvl1 and Dvl2, that during neurulation a homologous mammalian PCP pathway regulates concomitant lengthening and narrowing of the neural plate, a morphogenetic process defined as convergent extension. Dvl2 genetically interacts with Loop-tail, a point mutation in the mammalian PCP gene Vangl2, during neurulation. By generating Dvl2 BAC (bacterial artificial chromosome) transgenes and introducing different domain deletions and a point mutation identical to the dsh1 allele in fly, we further demonstrated a high degree of conservation between Dvl function in mammalian convergent extension and the PCP pathway in fly. In the neuroepithelium of neurulating embryos, Dvl2 shows DEP domain-dependent membrane localization, a pre-requisite for its involvement in convergent extension. Intriguing, the Loop-tail mutation that disrupts both convergent extension in the neuroepithelium and PCP in the cochlea does not disrupt Dvl2 membrane distribution in the neuroepithelium, in contrast to its drastic effect on Dvl2 localization in the cochlea. These results are discussed in light of recent models on PCP and convergent extension. PMID:16571627

  20. Bioremediation of PCP and creosote contaminated soil using white-rot fungus Phanerochaete sordida

    SciTech Connect

    Patel, D.M.; Barkley, N.

    1995-11-01

    The ability of white-rot fungus to deplete pentachlorophenol (PCP) and polynuclear aromatic hydrocarbons (PAHs) from soil, which was contaminated with commercial wood preservatives, was demonstrated in a field study. Inoculation of soil containing 968 {micro}g of PCP g{sup {minus}1} and 1,420 {micro}g of total PAHs g{sup {minus}1} with Phanerochaete sordida resulted in an overall decrease of 71% of PCP and 59% of total PAHs in the soil in 20 weeks. Over the same period, in soil containing 855 {micro}g of PCP g{sup {minus}1} and 1,050 {micro}g of total PAHs g{sup {minus}1} which was amended with sterile spawn (i.e., not containing P. sordida) material, an overall decrease of 69% of PCP and 66% of total PAHs was observed. And, in soil containing 746 {micro}g of PCP g{sup {minus}1} and 1,100 {micro}g of total PAHs g{sup {minus}1}, which was neither inoculated with P. sordida nor amended with the sterile spawn material, an overall decrease of 14% of PCP and 65% of total PAHs was observed. Results indicate that the degradation rates and percent reductions of PCP and PAHs in the inoculated and the amended soils were statistically the same. Percent reductions and degradation rates of PCP and the 4- and 5-ring PAHs in the inoculated and amended soils were significantly higher than in the nonamended soil. In contrast, reductions and degradation rates of 2- and 3-ring PAHs in the nonamended soil were significantly higher than in either the inoculated or amended soils. Overall reductions in total PAHs in the three soils were statistically identical.

  1. Phencyclidine analog use in Sweden--intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project.

    PubMed

    Bäckberg, Matilda; Beck, Olof; Helander, Anders

    2015-11-01

    3-Methoxy-phencyclidine (3-MeO-PCP) and 4-methoxy-phencyclidine (4-MeO-PCP) are analogs of and drug substitutes for the dissociative substance PCP ("Angel dust"), a recreational drug that was most popular in the 1970s. In Sweden, use of methoxylated PCP analogs was noted starting in mid-2013, according to statistics from the Poisons Information Centre. The objective of this case series was to present clinical and bioanalytical data from analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP within the STRIDA project. Observational case series of consecutive patients with self-reported or suspected exposure to new psychoactive substances (NPS) and who require hospital care. Blood and urine samples were collected from intoxicated patients presenting at emergency departments (ED) or intensive care units (ICU) all over Sweden. NPS analysis was performed by multicomponent liquid chromatographic-tandem mass spectrometric (LC-MS/MS) and LC-high-resolution MS (LC-HRMS) methods. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. The Poisons Information Centre registered its first call related to methoxylated PCP analogs in July 2013, while analytically confirmed cases first appeared in October 2013. From July 2013 to March 2015, 1243 cases of suspected NPS intoxication originating from ED or ICU were enrolled in the STRIDA project. During the 21-month period, 56 (4.5%) patients tested positive for 3-MeO-PCP and 11 (0.9%) for 4-MeO-PCP; 8 of these cases involved both substances. The 59 patients were aged 14-55 (median: 26) years and 51 (86%) were men. Co-exposure to other NPSs and/or classical drugs of abuse was common with only 7 cases (12%) indicated to be 3-MeO-PCP single-substance intoxications; prominent clinical signs seen in the latter cases were hypertension (systolic blood pressure ≥ 140 mmHg; 7 cases), tachycardia (≥ 100/min; 5 cases), and altered mental

  2. Metaphit, an isothiocyanate analog of PCP, induces audiogenic seizures in mice.

    PubMed

    Debler, E A; Lipovac, M N; Lajtha, A; Zlokovic, B V; Jacobson, A E; Rice, K C; Reith, M E

    1989-06-08

    Metaphit induces audiogenic seizures in mice. The most severe clonic/tonic seizures occur 18-24 h after metaphit administration. After 48 h the incidence of the seizure episodes begin to diminish. These audiogenic seizures can be prevented by the administration of either PCP or MK-801 24 h after metaphit and 30 min prior to audio stimulation. These seizures may be due to a modulation of the PCP recognition site by metaphit which results in an enhanced probability that the NMDA/PCP ion channels are open.

  3. PCP-induced deficits in murine nest building activity: employment of an ethological rodent behavior to mimic negative-like symptoms of schizophrenia.

    PubMed

    Pedersen, Christian Spang; Sørensen, Dorte Bratbo; Parachikova, Anna I; Plath, Niels

    2014-10-15

    Schizophrenia is a severe psychiatric disorder characterized by three symptom domains, positive (hallucinations, obsession), negative (social withdrawal, apathy, self-neglect) and cognitive (impairment in attention, memory and executive function). Whereas current medication ameliorates positive symptomatology, negative symptoms as well as cognitive dysfunctions remain untreated. The development of improved therapies for negative symptoms has proven particularly difficult, in part due to the inability of mimicking these in rodents. Here, we address the predictive validity of combining an ethologically well preserved behavior in rodents, namely nest building activity, with an established animal model of schizophrenia, the sub-chronic PCP model, for negative symptoms. Decline in rodent nesting activity has been suggested to mirror domains of negative symptoms of schizophrenia, including social withdrawal, anhedonia and self-neglect, whereas repeated treatment with the NMDAR antagonist PCP induces and exacerbates schizophrenia-like symptoms in rodents and human subjects. Using a back-translational approach of pharmacological validation, we tested the effects of two agents targeting the nicotinic α7 receptor (EVP-6124 and TC-5619) that were reported to exert some beneficial effect on negative symptoms in schizophrenic patients. Sub-chronic PCP treatment resulted in a significant nest building deficit in mice and treatment with EVP-6124 and TC-5619 reversed this PCP-induced deficit. In contrast, the atypical antipsychotic drug risperidone remained ineffective in this assay. In addition, EVP-6124, TC-5619 and risperidone were tested in the Social Interaction Test (SIT), an assay suggested to address negative-like symptoms. Results obtained in SIT were comparable to results in the nest building test (NEST). Based on these findings, we propose nest building in combination with the sub-chronic PCP model as a novel approach to assess negative-like symptoms of schizophrenia

  4. Impulsivity as a behavioral measure of withdrawal of orally delivered PCP and nondrug rewards in male and female monkeys.

    PubMed

    Carroll, Marilyn E; Mach, Jami L; La Nasa, Rachel M; Newman, Jennifer L

    2009-11-01

    Withdrawal of phencyclidine (PCP), ethanol (ETOH), and other drugs reduces operant responding maintained by food. Experiment 1 examined the effects of withdrawing daily short access (2 h) to drug on impulsivity for saccharin (SACC) using a delay discounting task and comparing male and female rhesus monkeys. Experiment 2 examined the effects of withdrawing a nondrug substance (e.g., food or SACC) on impulsivity for PCP. In experiment 1, either PCP or ETOH was available daily with water for 2 h under a fixed ratio 16 (FR 16) or FR 8 schedule, respectively. In a second component, SACC was available for 45 min under a delay discounting schedule. Next, water was substituted, and drug access was then restored. In experiment 2, PCP was available under a delay discounting schedule during food satiation or restriction or during concurrent SACC vs water access. In experiment 1, withdrawal of 0.5 mg/ml PCP increased impulsivity for SACC, but not SACC intake, in males and females. During 16% ETOH access, impulsivity for SACC was elevated compared to baseline water access, and it returned to baseline levels during ETOH withdrawal. In experiment 2, food restriction resulted in increased PCP intake in males and females and increases in impulsivity for PCP that were greater in males than in females. SACC withdrawal had no effect on impulsivity for PCP or PCP intake. Withdrawal of PCP and reduced food access increased impulsivity for SACC or PCP, respectively. Impulsivity is a sensitive indicator of drug dependence.

  5. DEMONSTRATION BULLETIN: FIELD ANALYTICAL SCREENING PROGRAM: PCP METHOD - U.S. ENVIRONMENTAL PROTECTION AGENCY

    EPA Science Inventory

    The Superfund Innovative Technology Evaluation (SITE) Program evaluates new technologies to assess their effectiveness. This bulletin summarizes results from the 1993 SITE demonstration of the Field Analytical Screening Program (FASP) Pentachlorophenol (PCP) Method to determine P...

  6. Choosing a Primary Health Care Provider (PCP): A Guide for Young Women

    MedlinePlus

    ... Conditions Nutrition & Fitness Emotional Health Choosing a Primary Health Care Provider (PCP): General Information Posted under Health Guides . ... needs. How do I find the names of health care providers? You should first make a list of ...

  7. Damped propagation of cell polarization explains distinct PCP phenotypes of epithelial patterning

    PubMed Central

    Zhu, Hao; Owen, Markus R.

    2013-01-01

    During epithelial patterning in metazoans cells are polarized in the plane of a tissue, a process referred to as planar cell polarity (PCP). Interactions between a few molecules produce distinct phenotypes in diverse tissues in animals from flies to humans and make PCP tightly associated with tissue and organ growth control. An interesting question is whether these phenotypes share common traits. Previous computational models revealed how PCP signalling determines cell polarization in some specific contexts. We have developed a computational model, examined PCP signalling in varied molecular contexts, and revealed how details of molecular interactions and differences in molecular contexts affect the direction, speed, and propagation of cell polarization. The main finding is that damped propagation of cell polarization can generate rich variances in phenotypes of domineering non-autonomy and error correction in different contexts. These results impressively demonstrate how simple molecular interactions cause distinct, yet inherently analogous, developmental patterning. PMID:23995897

  8. Choosing a Primary Health Care Provider (PCP): A Guide for Young Men

    MedlinePlus

    ... Conditions Nutrition & Fitness Emotional Health Choosing a Primary Health Care Provider (PCP): General Information Posted under Health Guides . ... needs. How do I find the names of health care providers? Here are some ways to find a ...

  9. LOW COST SOLIDIFICATION/STABILIZATION TREATMENT FOR SOILS CONTAMINATED WITH DIOXIN, PCP, AND CREOSOTE

    EPA Science Inventory

    The USEPA's National Risk Management Research Laboratory condcuted successful treatability tests of innovative solidification/stablization (S/S) formulations to treat soils contaminated with dioxins, pentachlorophenol (PCP), and creosote from four wood preserving sites. For one o...

  10. LOW COST SOLIDIFICATION/STABILIZATION TREATMENT FOR SOILS CONTAMINATED WITH DIOXIN, PCP AND CREOSOTE

    EPA Science Inventory

    The USEPA's NRMRL conducted successful treatability tests of innovative solidification/stabilization (S/S) formulations to treat soils contaminated with dioxins, pentachlorophenol (PCP), and creosote from four wood preserving sites. Formulations developed during these studies wer...

  11. The PCP pathway regulates Baz planar distribution in epithelial cells

    PubMed Central

    Aigouy, Benoit; Le Bivic, André

    2016-01-01

    The localisation of apico-basal polarity proteins along the Z-axis of epithelial cells is well understood while their distribution in the plane of the epithelium is poorly characterised. Here we provide a systematic description of the planar localisation of apico-basal polarity proteins in the Drosophila ommatidial epithelium. We show that the adherens junction proteins Shotgun and Armadillo, as well as the baso-lateral complexes, are bilateral, i.e. present on both sides of cell interfaces. In contrast, we report that other key adherens junction proteins, Bazooka and the myosin regulatory light chain (Spaghetti squash) are unilateral, i.e. present on one side of cell interfaces. Furthermore, we demonstrate that planar cell polarity (PCP) and not the apical determinants Crumbs and Par-6 control Bazooka unilaterality in cone cells. Altogether, our work unravels an unexpected organisation and combination of apico-basal, cytoskeletal and planar polarity proteins that is different on either side of cell-cell interfaces and unique for the different contacts of the same cell. PMID:27624969

  12. The involvement of PCP proteins in radial cell intercalations during Xenopus embryonic development.

    PubMed

    Ossipova, Olga; Chu, Chih-Wen; Fillatre, Jonathan; Brott, Barbara K; Itoh, Keiji; Sokol, Sergei Y

    2015-12-15

    The planar cell polarity (PCP) pathway orients cells in diverse epithelial tissues in Drosophila and vertebrate embryos and has been implicated in many human congenital defects and diseases, such as ciliopathies, polycystic kidney disease and malignant cancers. During vertebrate gastrulation and neurulation, PCP signaling is required for convergent extension movements, which are primarily driven by mediolateral cell intercalations, whereas the role for PCP signaling in radial cell intercalations has been unclear. In this study, we examine the function of the core PCP proteins Vangl2, Prickle3 (Pk3) and Disheveled in the ectodermal cells, which undergo radial intercalations during Xenopus gastrulation and neurulation. In the epidermis, multiciliated cell (MCC) progenitors originate in the inner layer, but subsequently migrate to the embryo surface during neurulation. We find that the Vangl2/Pk protein complexes are enriched at the apical domain of intercalating MCCs and are essential for the MCC intercalatory behavior. Addressing the underlying mechanism, we identified KIF13B, as a motor protein that binds Disheveled. KIF13B is required for MCC intercalation and acts synergistically with Vangl2 and Disheveled, indicating that it may mediate microtubule-dependent trafficking of PCP proteins necessary for cell shape regulation. In the neural plate, the Vangl2/Pk complexes were also concentrated near the outermost surface of deep layer cells, suggesting a general role for PCP in radial intercalation. Consistent with this hypothesis, the ectodermal tissues deficient in Vangl2 or Disheveled functions contained more cell layers than normal tissues. We propose that PCP signaling is essential for both mediolateral and radial cell intercalations during vertebrate morphogenesis. These expanded roles underscore the significance of vertebrate PCP proteins as factors contributing to a number of diseases, including neural tube defects, tumor metastases, and various genetic

  13. Wnt/PCP signaling controls intracellular position of MTOCs during gastrulation convergence and extension movements.

    PubMed

    Sepich, Diane S; Usmani, Mohsinah; Pawlicki, Staci; Solnica-Krezel, Lila

    2011-02-01

    During vertebrate gastrulation, convergence and extension cell movements are coordinated with the anteroposterior and mediolateral embryonic axes. Wnt planar cell polarity (Wnt/PCP) signaling polarizes the motile behaviors of cells with respect to the anteroposterior embryonic axis. Understanding how Wnt/PCP signaling mediates convergence and extension (C&E) movements requires analysis of the mechanisms employed to alter cell morphology and behavior with respect to embryonic polarity. Here, we examine the interactions between the microtubule cytoskeleton and Wnt/PCP signaling during zebrafish gastrulation. First, we assessed the location of the centrosome/microtubule organizing center (MTOC) relative to the cell nucleus and the body axes, as a marker of cell polarity. The intracellular position of MTOCs was polarized, perpendicular to the plane of the germ layers, independently of Wnt/PCP signaling. In addition, this position became biased posteriorly and medially within the plane of the germ layers at the transition from mid- to late gastrulation and from slow to fast C&E movements. This depends on intact Wnt/PCP signaling through Knypek (Glypican4/6) and Dishevelled components. Second, we tested whether microtubules are required for planar cell polarization. Once the planar cell polarity is established, microtubules are not required for accumulation of Prickle at the anterior cell edge. However, microtubules are needed for cell-cell contacts and initiation of its anterior localization. Reciprocal interactions occur between Wnt/PCP signaling and microtubule cytoskeleton during C&E gastrulation movements. Wnt/PCP signaling influences the polarity of the microtubule cytoskeleton and, conversely, microtubules are required for the asymmetric distribution of Wnt/PCP pathway components.

  14. The involvement of PCP proteins in radial cell intercalations during Xenopus embryonic development

    PubMed Central

    Ossipova, Olga; Chu, Chih-Wen; Fillatre, Jonathan; Brott, Barbara K.; Itoh, Keiji; Sokol, Sergei Y.

    2015-01-01

    The planar cell polarity (PCP) pathway orients cells in diverse epithelial tissues in Drosophila and vertebrate embryos and has been implicated in many human congenital defects and diseases, such as ciliopathies, polycystic kidney disease and malignant cancers. During vertebrate gastrulation and neurulation, PCP signaling is required for convergent extension movements, which are primarily driven by mediolateral cell intercalations, whereas the role for PCP signaling in radial cell intercalations has been unclear. In this study, we examine the function of the core PCP proteins Vangl2, Prickle3 (Pk3) and Disheveled in the ectodermal cells, which undergo radial intercalations during Xenopus gastrulation and neurulation. In the epidermis, multiciliated cell (MCC) progenitors originate in the inner layer, but subsequently migrate to the embryo surface during neurulation. We find that the Vangl2/Pk protein complexes are enriched at the apical domain of intercalating MCCs and are essential for the MCC intercalatory behavior. Addressing the underlying mechanism, we identified KIF13B, as a motor protein that binds Disheveled. KIF13B is required for MCC intercalation and acts synergistically with Vangl2 and Disheveled, indicating that it may mediate microtubule-dependent trafficking of PCP proteins necessary for cell shape regulation. In the neural plate, the Vangl2/Pk complexes were also concentrated near the outermost surface of deep layer cells, suggesting a general role for PCP in radial intercalation. Consistent with this hypothesis, the ectodermal tissues deficient in Vangl2 or Disheveled functions contained more cell layers than normal tissues. We propose that PCP signaling is essential for both mediolateral and radial cell intercalations during vertebrate morphogenesis. These expanded roles underscore the significance of vertebrate PCP proteins as factors contributing to a number of diseases, including neural tube defects, tumor metastases, and various genetic

  15. Combover/CG10732, a novel PCP effector for Drosophila wing hair formation.

    PubMed

    Fagan, Jeremy K; Dollar, Gretchen; Lu, Qiuheng; Barnett, Austen; Pechuan Jorge, Joaquin; Schlosser, Andreas; Pfleger, Cathie; Adler, Paul; Jenny, Andreas

    2014-01-01

    The polarization of cells is essential for the proper functioning of most organs. Planar Cell Polarity (PCP), the polarization within the plane of an epithelium, is perpendicular to apical-basal polarity and established by the non-canonical Wnt/Fz-PCP signaling pathway. Within each tissue, downstream PCP effectors link the signal to tissue specific readouts such as stereocilia orientation in the inner ear and hair follicle orientation in vertebrates or the polarization of ommatidia and wing hairs in Drosophila melanogaster. Specific PCP effectors in the wing such as Multiple wing hairs (Mwh) and Rho Kinase (Rok) are required to position the hair at the correct position and to prevent ectopic actin hairs. In a genome-wide screen in vitro, we identified Combover (Cmb)/CG10732 as a novel Rho kinase substrate. Overexpression of Cmb causes the formation of a multiple hair cell phenotype (MHC), similar to loss of rok and mwh. This MHC phenotype is dominantly enhanced by removal of rok or of other members of the PCP effector gene family. Furthermore, we show that Cmb physically interacts with Mwh, and cmb null mutants suppress the MHC phenotype of mwh alleles. Our data indicate that Cmb is a novel PCP effector that promotes to wing hair formation, a function that is antagonized by Mwh.

  16. Effect of a NAPL on migration of PCP in soil columns

    SciTech Connect

    Wang, J.; Wang, J.M.; Banerji, S.K.

    1995-12-31

    Pentachlorophenol (PCP) is a widely used wood-treating chemical that is applied to wood under pressure in the form of concentrated solution in solvents that are nonaqueous phase liquids (NAPL). As a result, any spill at a wood-treating site using PCP results in soil contamination with PCP in the presence of a NAPL. Hence, a study of migration of PCP was conducted in presence of kerosene as a NAPL in unsaturated soils. Addition of kerosene to soil caused a change in the effective size of soil particles; the porosity, pore velocity, and dispersion coefficients, all changed (as measured by bromide breakthrough) in soil columns contaminated with kerosene. Moisture content of soil was found to be a key parameter determining the residual NAPL content in the soils. PCP/kerosene breakthrough experiments showed that the organic phase penetrated deeper and faster into soils with higher moisture content, and the residual kerosene acted as a sorptive phase that retarded the migration of PCP.

  17. Combover/CG10732, a Novel PCP Effector for Drosophila Wing Hair Formation

    PubMed Central

    Fagan, Jeremy K.; Dollar, Gretchen; Lu, Qiuheng; Barnett, Austen; Pechuan Jorge, Joaquin; Schlosser, Andreas; Pfleger, Cathie; Adler, Paul; Jenny, Andreas

    2014-01-01

    The polarization of cells is essential for the proper functioning of most organs. Planar Cell Polarity (PCP), the polarization within the plane of an epithelium, is perpendicular to apical-basal polarity and established by the non-canonical Wnt/Fz-PCP signaling pathway. Within each tissue, downstream PCP effectors link the signal to tissue specific readouts such as stereocilia orientation in the inner ear and hair follicle orientation in vertebrates or the polarization of ommatidia and wing hairs in Drosophila melanogaster. Specific PCP effectors in the wing such as Multiple wing hairs (Mwh) and Rho Kinase (Rok) are required to position the hair at the correct position and to prevent ectopic actin hairs. In a genome-wide screen in vitro, we identified Combover (Cmb)/CG10732 as a novel Rho kinase substrate. Overexpression of Cmb causes the formation of a multiple hair cell phenotype (MHC), similar to loss of rok and mwh. This MHC phenotype is dominantly enhanced by removal of rok or of other members of the PCP effector gene family. Furthermore, we show that Cmb physically interacts with Mwh, and cmb null mutants suppress the MHC phenotype of mwh alleles. Our data indicate that Cmb is a novel PCP effector that promotes to wing hair formation, a function that is antagonized by Mwh. PMID:25207969

  18. Synthesis, Structure, and Reactivity of Co(II) and Ni(II) PCP Pincer Borohydride Complexes.

    PubMed

    Murugesan, Sathiyamoorthy; Stöger, Berthold; Weil, Matthias; Veiros, Luis F; Kirchner, Karl

    2015-04-13

    The 15e square-planar complexes [Co(PCP(Me)-iPr)Cl] (2a) and [Co(PCP-tBu)Cl] (2b), respectively, react readily with NaBH4 to afford complexes [Co(PCP(Me)-iPr)(η(2)-BH4)] (4a) and [Co(PCP-tBu)(η(2)-BH4)] (4b) in high yields, as confirmed by IR spectroscopy, X-ray crystallography, and elemental analysis. The borohydride ligand is symmetrically bound to the cobalt center in η(2)-fashion. These compounds are paramagnetic with effective magnetic moments of 2.0(1) and 2.1(1) μB consistent with a d(7) low-spin system corresponding to one unpaired electron. None of these complexes reacted with CO2 to give formate complexes. For structural and reactivity comparisons, we prepared the analogous Ni(II) borohydride complex [Ni(PCP(Me)-iPr)(η(2)-BH4)] (5) via two different synthetic routes. One utilizes [Ni(PCP(Me)-iPr)Cl] (3) and NaBH4, the second one makes use of the hydride complex [Ni(PCP(Me)-iPr)H] (6) and BH3·THF. In both cases, 5 is obtained in high yields. In contrast to 4a and 4b, the borohydride ligand is asymmetrically bound to the nickel center but still in an η(2)-mode. [Ni(PCP(Me)-iPr)(η(2)-BH4)] (5) loses readily BH3 at elevated temperatures in the presence of NEt3 to form 6. Complexes 5 and 6 are both diamagnetic and were characterized by a combination of (1)H, (13)C{(1)H}, and (31)P{(1)H} NMR, IR spectroscopy, and elemental analysis. Additionally, the structure of these compounds was established by X-ray crystallography. Complexes 5 and 6 react with CO2 to give the formate complex [Ni(PCP(Me)-iPr)(OC(C=O)H] (7). The extrusion of BH3 from [Co(PCP(Me)-iPr)(η(2)-BH4)] (4a) and [Ni(PCP(Me)-iPr)(η(2)-BH4)] (5) with the aid of NH3 to yield the respective hydride complexes [Co(PCP(Me)-iPr)H] and [Ni(PCP(Me)-iPr)H] (6) and BH3NH3 was investigated by DFT calculations showing that formation of the Ni hydride is thermodynamically favorable, whereas the formation of the Co(II) hydride, in agreement with the experiment, is unfavorable. The electronic structures and

  19. Postnatal Phencyclidine (PCP) as a Neurodevelopmental Animal Model of Schizophrenia Pathophysiology and Symptomatology: A Review.

    PubMed

    Grayson, B; Barnes, S A; Markou, A; Piercy, C; Podda, G; Neill, J C

    Cognitive dysfunction and negative symptoms of schizophrenia remain an unmet clinical need. Therefore, it is essential that new treatments and approaches are developed to recover the cognitive and social impairments that are seen in patients with schizophrenia. These may only be discovered through the use of carefully validated, aetiologically relevant and translational animal models. With recent renewed interest in the neurodevelopmental hypothesis of schizophrenia, postnatal administration of N-methyl-D-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) has been proposed as a model that can mimic aspects of schizophrenia pathophysiology. The purpose of the current review is to examine the validity of this model and compare it with the adult subchronic PCP model. We review the ability of postnatal PCP administration to produce behaviours (specifically cognitive deficits) and neuropathology of relevance to schizophrenia and their subsequent reversal by pharmacological treatments. We review studies investigating effects of postnatal PCP on cognitive domains in schizophrenia in rats. Morris water maze and delayed spontaneous alternation tasks have been used for working memory, attentional set-shifting for executive function, social novelty discrimination for selective attention and prepulse inhibition of acoustic startle for sensorimotor gating. In addition, we review studies on locomotor activity and neuropathology. We also include two studies using dual hit models incorporating postnatal PCP and two studies on social behaviour deficits following postnatal PCP. Overall, the evidence we provide supports the use of postnatal PCP to model cognitive and neuropathological disturbances of relevance to schizophrenia. To date, there is a lack of evidence to support a significant advantage of postnatal PCP over the adult subchronic PCP model and full advantage has not been taken of its neurodevelopmental component. When thoroughly characterised, it is likely

  20. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients.

    PubMed

    Stern, Anat; Green, Hefziba; Paul, Mical; Vidal, Liat; Leibovici, Leonard

    2014-10-01

    Pneumocystis pneumonia (PCP) is a disease affecting immunocompromised patients. PCP among these patients is associated with significant morbidity and mortality. To assess the effectiveness of PCP prophylaxis among non-HIV immunocompromised patients; and to define the type of immunocompromised patient for whom evidence suggests a benefit for PCP prophylaxis. Electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE and EMBASE (to March 2014), LILACS (to March 2014), relevant conference proceedings; and references of identified trials. Randomised controlled trials (RCTs) or quasi-RCTs comparing prophylaxis with an antibiotic effective against PCP versus placebo, no intervention, or antibiotic(s) with no activity against PCP; and trials comparing different antibiotics effective against PCP among immunocompromised non-HIV patients. We only included trials in which Pneumocystis infections were available as an outcome. Two review authors independently assessed risk of bias in each trial and extracted data from the included trials. We contacted authors of the included trials to obtain missing data. The primary outcome was documented PCP infections. Risk ratios (RR) with 95% confidence intervals (CI) were estimated and pooled using the random-effects model. Thirteen trials performed between the years 1974 and 2008 were included, involving 1412 patients. Four trials included 520 children with acute lymphoblastic leukemia and the remaining trials included adults with acute leukemia, solid organ transplantation or autologous bone marrow transplantation. Compared to no treatment or treatment with fluoroquinolones (inactive against Pneumocystis), there was an 85% reduction in the occurrence of PCP in patients receiving prophylaxis with trimethoprim/sulfamethoxazole, RR of 0.15 (95% CI 0.04 to 0.62; 10 trials, 1000 patients). The evidence was graded as moderate due to possible risk of bias. PCP

  1. Role of PCP referral and weight loss in the Hopkins POWER trial.

    PubMed

    Tseng, Eva; Wang, Nae-Yuh; Clark, Jeanne M; Appel, Lawrence J; Bennett, Wendy L

    2015-01-01

    Primary care providers (PCPs) play an important role in identifying and counseling obese patients to lose weight, but it is unknown whether PCP referral of patients into a weight loss intervention is associated with greater weight loss. The objectives are to determine if PCP referral is associated with greater 1) weight loss, 2) end of study patient-provider relationship quality, and 3) satisfaction and participation rates in the intervention. 415 obese patients enrolled in the Hopkins POWER trial from six primary care practices in the Baltimore area. We conducted a secondary analysis of results from the trial using longitudinal mixed-effects model and generalized linear model, adjusting for clinic, sex, age, and race. The primary outcome was absolute weight change from baseline to 24 months. Secondary outcomes were patient-provider relationship quality and satisfaction and participation rates in the intervention. Participants in both PCP and non-PCP referral groups lost a similar amount of weight from baseline to 24 months. PCP referral was not significantly associated with percentage of completed coach contacts, web logins, and satisfaction with trial, but was associated with higher end of study patient-provider relationship quality (p = 0.007). Our study represents the first of its kind to examine the role of PCP referral of patients into a weight loss trial. While we did not find evidence that PCP referral is associated with increased weight loss, further research is needed to determine how PCPs can use their relationship with patients to promote weight loss and enhance intervention effects.

  2. The role of P2X7 receptors in a rodent PCP-induced schizophrenia model

    PubMed Central

    Koványi, Bence; Csölle, Cecilia; Calovi, Stefano; Hanuska, Adrienn; Kató, Erzsébet; Köles, László; Bhattacharya, Anindya; Haller, József; Sperlágh, Beáta

    2016-01-01

    P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7−/−), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated. The selective P2X7 receptor antagonist JNJ-47965567 partly replicated the effect of gene deficiency on PCP-induced behavioral changes and counteracted PCP-induced social withdrawal. We also show that PCP treatment upregulates and increases the functional responsiveness of P2X7Rs in the prefrontal cortex of young adult animals. The amplitude of NMDA evoked currents recorded from layer V pyramidal neurons of cortical slices were slightly decreased by both genetic deletion of P2rx7 and by JNJ-47965567. PCP induced alterations in mRNA expression encoding schizophrenia-related genes, such as NR2A, NR2B, neuregulin 1, NR1 and GABA α1 subunit were absent in the PFC of young adult P2rx7−/− animals. Our findings point to P2X7R as a potential therapeutic target in schizophrenia. PMID:27824163

  3. PCP can enhance dendritic cells to present the HBsAg peptide.

    PubMed

    Tang, Shang-hong; Gao, Liu-cun; Zhang, Zhi-yong; Li, Yun-ming; Bi, Qian; Song, Cao-jun; Yang, Gui-tao

    2011-02-01

    To investigate the influence of paraclorophenol (pCP) on dendritic cells loading and presenting HBsAg from peripheral blood monocytes of healthy volunteers identified as hepatitis B vaccine nonresponders. The density gradient centrifugation was performed to isolate mononuclear cells from 10 hepatitis B vaccine nonresponders. The adherent monocytes were incubated with HBsAg adding rhGM-CSF and rhIL-4 in the presence of absence of pCP for 7 days. Then the supernatant was collected for ELISA assays. The culture medium system without pCP was used as negative control and without pCP or HBsAG was named blank control. the matured DCs were co-incubated with autologous T lymphocytes for 72h and the supernatant was also collected for ELISA assays. In the presence of pCP, the level of IL-12 in supernate (265.68± 16.21) ng/L was significantly higher than the negative control (168.76±10.01) ng/L (P<0.05) and blank control (87±5.79)ng/L (P<0.05); after co-incubated with autologous T lymphocytes for 3 days, the level of IFN-γ with pCP (773.04±32.73) mg/L was also significantly higher than the negative control (573.59±26.11) mg/L (P<0.05) ans blank control (362.81±24.27)mg/L (P<0.05). pCP can effectively enhance the dendritic cells loading and presenting HBsAg from peripheral blood monocytes of healthy volunteers identified as hepatitis B vaccine nonresponders, which also can dramatically increase te autologous T lymphocytes response.7

  4. Structures of the inducer-binding domain of pentachlorophenol-degrading gene regulator PcpR from Sphingobium chlorophenolicum.

    PubMed

    Hayes, Robert P; Moural, Timothy W; Lewis, Kevin M; Onofrei, David; Xun, Luying; Kang, ChulHee

    2014-11-12

    PcpR is a LysR-type transcription factor from Sphingobium chlorophenolicum L-1 that is responsible for the activation of several genes involved in polychlorophenol degradation. PcpR responds to several polychlorophenols in vivo. Here, we report the crystal structures of the inducer-binding domain of PcpR in the apo-form and binary complexes with pentachlorophenol (PCP) and 2,4,6-trichlorophenol (2,4,6-TCP). Both X-ray crystal structures and isothermal titration calorimetry data indicated the association of two PCP molecules per PcpR, but only one 2,4,6-TCP molecule. The hydrophobic nature and hydrogen bonds of one binding cavity allowed the tight association of both PCP (Kd = 110 nM) and 2,4,6-TCP (Kd = 22.8 nM). However, the other cavity was unique to PCP with much weaker affinity (Kd = 70 μM) and thus its significance was not clear. Neither phenol nor benzoic acid displayed any significant affinity to PcpR, indicating a role of chlorine substitution in ligand specificity. When PcpR is compared with TcpR, a LysR-type regulator controlling the expression of 2,4,6-trichlorophenol degradation in Cupriavidus necator JMP134, most of the residues constituting the two inducer-binding cavities of PcpR are different, except for their general hydrophobic nature. The finding concurs that PcpR uses various polychlorophenols as long as it includes 2,4,6-trichlorophenol, as inducers; whereas TcpR is only responsive to 2,4,6-trichlorophenol.

  5. Structures of the Inducer-Binding Domain of Pentachlorophenol-Degrading Gene Regulator PcpR from Sphingobium chlorophenolicum

    PubMed Central

    Hayes, Robert P.; Moural, Timothy W.; Lewis, Kevin M.; Onofrei, David; Xun, Luying; Kang, ChulHee

    2014-01-01

    PcpR is a LysR-type transcription factor from Sphingobium chlorophenolicum L-1 that is responsible for the activation of several genes involved in polychlorophenol degradation. PcpR responds to several polychlorophenols in vivo. Here, we report the crystal structures of the inducer-binding domain of PcpR in the apo-form and binary complexes with pentachlorophenol (PCP) and 2,4,6-trichlorophenol (2,4,6-TCP). Both X-ray crystal structures and isothermal titration calorimetry data indicated the association of two PCP molecules per PcpR, but only one 2,4,6-TCP molecule. The hydrophobic nature and hydrogen bonds of one binding cavity allowed the tight association of both PCP (Kd = 110 nM) and 2,4,6-TCP (Kd = 22.8 nM). However, the other cavity was unique to PCP with much weaker affinity (Kd = 70 μM) and thus its significance was not clear. Neither phenol nor benzoic acid displayed any significant affinity to PcpR, indicating a role of chlorine substitution in ligand specificity. When PcpR is compared with TcpR, a LysR-type regulator controlling the expression of 2,4,6-trichlorophenol degradation in Cupriavidus necator JMP134, most of the residues constituting the two inducer-binding cavities of PcpR are different, except for their general hydrophobic nature. The finding concurs that PcpR uses various polychlorophenols as long as it includes 2,4,6-trichlorophenol, as inducers; whereas TcpR is only responsive to 2,4,6-trichlorophenol. PMID:25397598

  6. The primary care provider (PCP)-cancer specialist relationship: A systematic review and mixed-methods meta-synthesis.

    PubMed

    Dossett, Lesly A; Hudson, Janella N; Morris, Arden M; Lee, M Catherine; Roetzheim, Richard G; Fetters, Michael D; Quinn, Gwendolyn P

    2017-03-01

    Although they are critical to models of coordinated care, the relationship and communication between primary care providers (PCPs) and cancer specialists throughout the cancer continuum are poorly understood. By using predefined search terms, the authors conducted a systematic review of the literature in 3 databases to examine the relationship and communication between PCPs and cancer specialists. Among 301 articles identified, 35 met all inclusion criteria and were reviewed in-depth. Findings from qualitative, quantitative, and disaggregated mixed-methods studies were integrated using meta-synthesis. Six themes were identified and incorporated into a preliminary conceptual model of the PCP-cancer specialist relationship: 1) poor and delayed communication between PCPs and cancer specialists, 2) cancer specialists' endorsement of a specialist-based model of care, 3) PCPs' belief that they play an important role in the cancer continuum, 4) PCPs' willingness to participate in the cancer continuum, 5) cancer specialists' and PCPs' uncertainty regarding the PCP's oncology knowledge/experience, and 6) discrepancies between PCPs and cancer specialists regarding roles. These data indicate a pervasive need for improved communication, delineation, and coordination of responsibilities between PCPs and cancer specialists. Future interventions aimed at these deficiencies may improve patient and physician satisfaction and cancer care coordination. CA Cancer J Clin 2017;67:156-169. © 2016 American Cancer Society.

  7. Phytoremediation efficiency of a pcp-contaminated soil using four plant species as mono- and mixed cultures.

    PubMed

    Hechmi, Nejla; Aissa, Nadhira Ben; Abdenaceur, Hassen; Jedidi, Naceur

    2014-01-01

    Bioremediation of soil polluted by pentachlorophenol (PCP) is of great importance due to the persistence and carcinogenic properties of PCP. Phytoremediation has long been recognized as a promising approach for removal of PCP from soil. The present study was conducted to investigate the capability of four plant species; white clover, ryegrass, alfalfa, and rapeseed grown alone and in combination to remediate pentachlorophenol contaminated soil. After 60 days cultivation, white clover, raygrass, alfalfa, and rapeseed all significantly enhanced the degradation of PCP in soils. Alfalfa showed highest efficiency for the removal of PCP in single cropping flowed by rapeseed and ryegrass. Mixed cropping significantly enhanced the remediation efficiencies as compared to single cropping; about 89.84% of PCP was removed by mixed cropping of rapeseed and alfalfa, and 72.01% of PCP by mixed cropping of rape and white clover. Mixed cropping of rapeseed with alfalfa was however far better for the remediation of soil PCP than single cropping. An evaluation of soil biological activities as a monitoring mechanism for the bioremediation process of a PCP-contaminated soil was made using measurements of microbial counts and dehydrogenase activity.

  8. Synthesis of PCP-supported nickel complexes and their reactivity with carbon dioxide.

    PubMed

    Schmeier, Timothy J; Nova, Ainara; Hazari, Nilay; Maseras, Feliu

    2012-05-29

    The Ni amide and hydroxide complexes [(PCP)Ni(NH(2))] (2; PCP=bis-2,6-di-tert-butylphosphinomethylbenzene) and [(PCP)Ni(OH)] (3) were prepared by treatment of [(PCP)NiCl] (1) with NaNH(2) or NaOH, respectively. The conditions for the formation of 3 from 1 and NaOH were harsh (2 weeks in THF at reflux) and a more facile synthetic route involved protonation of 2 with H(2)O, to generate 3 and ammonia. Similarly the basic amide in 2 was protonated with a variety of other weak acids to form the complexes [(PCP)Ni(2-Me-imidazole)] (4), [(PCP)Ni(dimethylmalonate)] (5), [(PCP)Ni(oxazole)] (6), and [(PCP)Ni(CCPh)] (7), respectively. The hydroxide compound 3, could also be used as a Ni precursor and treatment of 3 with TMSCN (TMS=trimethylsilyl) or TMSN(3) generated [(PCP)Ni(CN)] (8) or [(PCP)Ni(N(3))] (9), respectively. Compounds 3-7, and 9 were characterized by X-ray crystallography. Although 3, 4, 6, 7, and 9 are all four-coordinate complexes with a square-planar geometry around Ni, 5 is a pseudo-five-coordinate complex, with the dimethylmalonate ligand coordinated in an X-type fashion through one oxygen atom, and weakly as an L-type ligand through another oxygen atom. Complexes 2-9 were all reacted with carbon dioxide. Compounds 2-4 underwent facile reaction at low temperature to form the κ(1)-O carboxylate products [(PCP)Ni{OC(O)NH(2)}] (10), [(PCP)Ni{OC(O)OH}] (11), and [(PCP)Ni{OC(O)-2-Me-imidazole}] (12), respectively. Compounds 10 and 11 were characterized by X-ray crystallography. No reaction was observed between 5-9 and carbon dioxide, even at elevated temperatures. DFT calculations were performed to model the thermodynamics for the insertion of carbon dioxide into 2-9 to form a κ(1)-O carboxylate product and understand the pathways for carbon dioxide insertion into 2, 3, 6, and 7. The computed free energies indicate that carbon dioxide insertion into 2 and 3 is thermodynamically favorable, insertion into 8 and 9 is significantly uphill, insertion into 5 and 7

  9. Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

    PubMed

    Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

    2014-09-01

    A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Transcriptional changes induced by in vivo exposure to pentachlorophenol (PCP) in Chironomus riparius (Diptera) aquatic larvae.

    PubMed

    Morales, Mónica; Martínez-Paz, Pedro; Martín, Raquel; Planelló, Rosario; Urien, Josune; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2014-12-01

    Pentachlorophenol (PCP) has been extensively used worldwide as a pesticide and biocide and is frequently detected in the aquatic environment. In the present work, the toxicity of PCP was investigated in Chironomus riparius aquatic larvae. The effects following short- and long-term exposures were evaluated at the molecular level by analyzing changes in the transcriptional profile of different endocrine genes, as well as in genes involved in the stress response and detoxification. Interestingly, although no differences were found after 12- and 24-h treatments, at 96-h exposures PCP was able to induce significant increases in transcripts from the ecdysone receptor gene (EcR), the early ecdysone-inducible E74 gene, the estrogen-related receptor gene (ERR), the Hsp70 gene and the CYP4G gene. In contrast, the Hsp27 gene appeared to be downregulated, while the ultraspiracle gene (usp) (insect ortholog of the retinoid X receptor) was not altered in any of the conditions assayed. Moreover, Glutathione-S-Transferase (GST) activity was not affected. The results obtained show the ability of PCP to modulate transcription of different biomarker genes from important cellular metabolic activities, which could be useful in genomic approaches to monitoring. In particular, the significant upregulation of hormonal genes represents the first evidence at the genomic level of the potential endocrine disruptive effects of PCP on aquatic invertebrates. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Sorption-desorption behavior of PCP on soil organic matter and clay minerals.

    PubMed

    Pu, Xunchi; Cutright, Teresa J

    2006-08-01

    Pentachlorophenol (PCP) contamination is a severe environmental problem due to its widespread occurrence, toxicity and recalcitrance. In order to gain a better understanding of the fate of PCP in soils, the role of the soil organic matter (SOM) and clay minerals in the PCP sorption-desorption was studied on two bulk field soils, two subsoils (i.e., SOM or clay-removed soil) and two artificial soils. The two field soils used were a silty loam from New Mexico (NM) containing 10% clay and a sandy-clay-loam from Colombia (CO) South America comprised of 18% clay minerals. The bulk CO soil containing kaolinite sorbed significantly less PCP than the NM soil. All soils depicted an apparent hysteresis during sorption. The CO bulk and subsoils desorbed 14-20% and 15-26% of the sorbed PCP respectively whereas the NM bulk and subsoils desorbed only 4-12% and 5-16%, respectively. Experiments conducted with pure clay and artificial soils indicated that the expandable clay minerals were key sorbent material. Additional studies to investigate the interaction between SOM and clay minerals are needed to fully understand sorptive phenomena.

  12. Use of EAF dust as heterogeneous catalyst in Fenton oxidation of PCP contaminated wastewaters.

    PubMed

    Mecozzi, R; Di Palma, L; Pilone, D; Cerboni, L

    2006-09-21

    In this study, chemical oxidation tests using H2O2 were performed on a solution contaminated with 100 mg l(-1) of pentachlorophenol (PCP). The effectiveness of electric arc furnace dust and hematite as heterogeneous catalysts was evaluated. Reactions were conducted at pH 2 for 24 h. Either H2O2 stabilized with KH2PO4 or un-stabilized H2O2 was used. Total organic carbon (T.O.C.) removal and chloride release from PCP molecule were monitored. Results showed that the maximum removal yields for electric arc furnace (EAF) dust (49.2% T.O.C., 56.7% Cl) were achieved when H2O2:PCP ratio was 10:1 and Fe:H2O2 = 1:5 for unstabilized H2O2 and when H2O2:PCP = 10:1 and Fe:H2O2 = 1:1 for stabilized H2O2 (48% T.O.C., 60.6% Cl). The maximum yield using hematite (45.2% T.O.C., 55.2% Cl) was obtained when H2O2:PCP ratio was 10:1 and Fe:H2O2 was 1:2. When EAF dust was used and Fe:H2O2 > 1:5, Cl release was higher than the one expected from T.O.C. removal.

  13. Complete anaerobic mineralization of pentachlorophenol (PCP) under continuous flow conditions by sequential combination of PCP-dechlorinating and phenol-degrading consortia.

    PubMed

    Li, Zhiling; Yang, Suyin; Inoue, Yasushi; Yoshida, Naoko; Katayama, Arata

    2010-12-01

    Complete mineralization of 50 µM of pentachlorophenol (PCP) was achieved anaerobically under continuous flow conditions using two columns connected in series with a hydraulic retention time of 14.2 days, showing the highest reported mineralization rate yet of 3.5 µM day(-1). The first column, when injected with a reductive PCP dechlorinating consortium, dechlorinated PCP to mainly phenol and traces of 3-chlorophenol (3-CP) using lactate supplied continuously as an electron donor. The second column, with an anaerobic phenol degrading consortium, decomposed phenol and 3-CP under iron-reducing conditions with substantial fermentative degradation of organic compounds. When 20 mM of lactate was introduced into the first column, the phenol degradation activity of the second column was lost in a short period of time, because the amorphous Fe(III) oxide (FeOOH) that had been packed in the column before use was depleted by lactate metabolites, such as acetate and propionate, flowing into the second column from the first column. The complete mineralization of PCP was maintained for a long period by reducing the lactate concentration to 4 mM, effectively extending the longevity of second-column activity with no depletion of FeOOH for more than 200 pore volumes (corresponding to 3,000 days). The carbon balance showed that 50 µM PCP and 4 mM lactate in the influent had transformed to CO(2) (81%) and CH(4) (3%) and had contributed to biomass growth (8%). A comparison of the microbial consortia introduced into the columns and those flowing out from the columns suggested that the introduced population did not flow out during the experiments, although the microbial composition of the phenol column was considered to be affected by the inflow of microbes from the PCP dechlorination column. These results suggest that a sequential combination of reductive dechlorinating and anaerobic oxidizing consortia is useful for anaerobic remediation of chlorinated aromatic compounds in

  14. Preparation and analytical characterization of 1-(1-phenylcyclohexyl)piperidine (PCP) and 1-(1-phenylcyclohexyl)pyrrolidine (PCPy) analogues.

    PubMed

    Wallach, Jason; De Paoli, Giorgia; Adejare, Adeboye; Brandt, Simon D

    2014-01-01

    Classic examples of psychoactive arylcycloalkylamines include ketamine and 1-(1-phenylcyclohexyl)piperidine (PCP) and many others serve as important structural templates for neuropharmacological research. The recent emergence of PCP analogues that can be obtained from internet retailers requires the implementation of appropriate monitoring strategies for harm reduction purposes. Access to analytical data plays a key part when encountering these substances, especially if reference material is not available. The present study describes the synthesis of three substituted 1-(1-phenylcyclohexyl)piperidines, (3-MeO-, 4-MeO- and 3-Me-PCP) and three substituted 1-(1-phenylcyclohexyl)pyrrolidine analogues (3-MeO-, 4-MeO- and 3-Me-PCPy). Analytical characterizations of all six arylcyclohexylamines and their primary 1-phenylcyclohexanamine intermediates included gas chromatography ion trap electron- and chemical ionization and high resolution mass spectrometry, liquid chromatography electrospray hybrid triple-quadrupole linear ion trap tandem mass spectrometry, infrared, diode array detection and (1) H and (13) C nuclear magnetic resonance (NMR) spectroscopy. Solvent (CDCl3 vs. d6 -DMSO) and protonation effects (free bases vs hydrochloride salts) were studied in order to investigate the impact on shifts and splitting patterns, for example, when attempting to assign separate axial and equatorial proton chemical shifts of NMR spectra. Differentiation between the isomeric 3-MeO-/4-MeO-PCP and PCPy analogues was feasible under mass spectral conditions. Gas chromatography analysis appeared to induce notable degradation of the 4-MeO-substituted analytes, especially when dealing with the HCl salts which led to the detection of the substituted 1-phenylcyclohex-1-ene nucleus. This phenomenon was observed to be less pronounced with the 3-MeO isomers, possibly due to the resonance properties of the para-methoxy group followed by more facile elimination of the amine. Copyright © 2013

  15. Distinct physiological and developmental properties of hippocampal CA2 subfield revealed by using anti-Purkinje cell protein 4 (PCP4) immunostaining

    PubMed Central

    San Antonio, Andrew; Liban, Kristopher; Ikrar, Taruna; Tsyganovskiy, Eugene; Xu, Xiangmin

    2014-01-01

    The hippocampal CA2 subfield was initially identified by Lorente de Nó as an anatomically distinct region based on its cytoarchitectural features. Although there is an enormous body of literature on other hippocampal subfields (CA1 and CA3), relatively little is known about the physiological and developmental properties of CA2. Here we report identification of the CA2 region in the mouse by immunostaining with a Purkinje cell protein 4 (PCP4) antibody, which effectively delineates CA3/CA2 and CA2/CA1 borders and agrees well with previous cytoarchitectural definitions of CA2. The PCP4 immunostaining–delineated CA2 neurons have distinguishable differences in cell morphology, physiology, and synaptic circuit connections compared with distal CA3 and proximal CA1 regions. The average somatic sizes of excitatory cells differ across CA1–3, with the smallest to largest somatic size being CA1PCP4 and other marker expressions, these neurons have less distinct neurophysiological and morphological properties. Developmental examination revealed that PCP4 immunostaining first appears at postnatal day 4–5 and becomes successively more refined around CA2 until reaching adult form by postnatal day 21. J. Comp. Neurol. J. Comp. Neurol. 522:1333–1354, 2014. © 2013 Wiley Periodicals, Inc. PMID:24166578

  16. Impact of electrokinetic remediation on microbial communities within PCP contaminated soil.

    PubMed

    Lear, G; Harbottle, M J; Sills, G; Knowles, C J; Semple, K T; Thompson, I P

    2007-03-01

    Electrokinetic techniques have been used to stimulate the removal of organic pollutants within soil, by directing contaminant migration to where remediation may be more easily achieved. The effect of this and other physical remediation techniques on the health of soil microbial communities has been poorly studied and indeed, largely ignored. This study reports the impact on soil microbial communities during the application of an electric field within ex situ laboratory soil microcosms contaminated with pentachlorophenol (PCP; 100mg kg(-1) oven dry soil). Electrokinetics reduced counts of culturable bacteria and fungi, soil microbial respiration and carbon substrate utilisation, especially close to the acidic anode where PCP accumulated (36d), perhaps exacerbated by the greater toxicity of PCP at lower soil pH. There is little doubt that a better awareness of the interactions between soil electrokinetic processes and microbial communities is key to improving the efficacy and sustainability of this remediation strategy.

  17. PCDD/PCDF behavior in low-temperature pyrolysis of PCP-contaminated sandy soil.

    PubMed

    Thuan, Ngo Thi; Dien, Nguyen Thanh; Chang, Moo Been

    2013-01-15

    This study investigates the behavior of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) formation, dechlorination and destruction in PCP-contaminated sandy soil by low-temperature thermal treatment. Experimental tests were carried out in a nitrogen atmosphere in the temperature range of 200-400 °C with a treatment time of 30 min. 70% of PCP removal from the soil was achieved, resulting in 1436±230 ng/kg, the highest PCDD/F formation at 250 °C; however, the highest toxic concentration was measured around 4.20±0.62 ng TEQ/kg at 300 °C with 80% PCP removal from the soil. Further analysis has revealed that OCDD is the most dominant congener that is supposed to be formed from the pyrolysis of PCP, while OCDF is the second prevailing congener, possibly due to pyrolysis of 2,3,4,5-TeCP being a main byproduct of PCP pyrolysis. Detection of less chlorinated dioxins and furans over 300 °C indicates the dechlorination of highly chlorinated dioxins and furans, especially octachlorinated dibenzo-p-dioxin (OCDD) at 350 °C and 400 °C. Desorption from soil was supposed as a main mechanism for the distribution of PCDD/Fs in the gaseous phase, and not much difference in dioxins and furan levels was observed at 350 °C and 400 °C in the gaseous phase. Therefore, 350 °C is the most appropriate temperature to remove most PCP and PCDD/Fs from soil, as well as to meet PCDD/F emission standards (0.1 ng I-TEQ/Nm(3)). Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Numerical simulation of a steam-injection pilot study for a PCP-contaminated aquifer.

    PubMed

    Tse, Ken K C; Liou, Tai-Sheng; Lo, Shang-Lien

    2006-07-01

    The following study was focused on the simulation of a steam-injection field pilottest conducted in our past research. The scope of research contained two main subjects: heat transfer and contaminant transport when steam was injected into a pentachlorophenol (PCP)-contaminated aquifer. Numerical simulation of the heat transfer during the field test showed that vertical permeability is more influential to the distribution of water temperature than the horizontal permeability. If the vertical permeability is relatively high, the steam in the aquifer has a higher tendency to migrate upward and cause the aquifer temperature to rise faster. The simulation results also showed that heat convection is very sensitive to the soil permeability. Therefore, high permeability media makes the effect of heat convection more important on applying the steam-injection method. Heat conduction dominates the heat transfer within the hot aqueous zone. However, the hot aqueous zone is relatively smaller than the steam zone when steam is injected into the aquifer. Therefore, heat conduction is not as important as heat convection within the steam zone, which is the same result observed in the field test. Specific heat of soil media is also a sensitive factor. A numerical simulator, T2VOC, was utilized to simulate the PCP transport in the aquifer when steam was injected into the aquifer. The results showed that the shape of PCP distribution was identical to that of steam. It illustrated thatthe steam carried PCP upward and laterally. The high vertical soil permeability causes the steam to migrate upward with PCP easily. A low partitioning coefficient allows PCP to be desorbed easier, also an important factor. A majority of the PCP in the soil was transferred to the aqueous phase as the water temperature increased, showing similar results to those observed in the field test. According to the sensitivity analysis, PCP transport is more sensitive to the vertical permeability than the

  19. Risk factors for mortality from pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis.

    PubMed

    Liu, Yao; Su, Lili; Jiang, Shu-Juan; Qu, Hui

    2017-08-29

    The number of patients with non-human immunodeficiency virus (HIV) related pneumocystis carinii pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We performed a meta-analysis to describe the clinical characteristics and factors associated with outcomes of PCP in HIV-negative patients. A total of 13 studies including 867 patients with non-HIV related PCP was included. The overall mortality for non-HIV patients with PCP was 30.6%. The most common underlying disorder for the development of PCP is hematological malignancies (29.1%), followed by autoimmune disease (20.1%), organ or bone marrow transplantation (14.0%), and solid tumors (6.0%). Risk factors associated with increased mortality rate including old age, female sex, longer time from onset of symptoms to diagnosis, respiratory failure, solid tumors, high lactate dehydrogenase, low serum albumin, bacterial, and aspergillus co-infection, etc (P < 0.05). Adjunctive corticosteroid and PCP prophylaxis was not shown to improve the outcome of PCP in non-HIV patients (P > 0.05). Our findings indicate that mortality in non-HIV patients with PCP is high. Improved knowledge about the prognostic factors may guide the early treatment.

  20. Cytotoxic effects of pentachlorophenol (PCP) and its metabolite tetrachlorohydroquinone (TCHQ) on liver cells are modulated by antioxidants.

    PubMed

    Pietsch, Constanze; Hollender, Juliane; Dorusch, Falk; Burkhardt-Holm, Patricia

    2014-08-01

    The worldwide distribution and high bioaccumulation potential of pentachlorophenol (PCP) in aquatic organisms imply a high toxicological impact in aquatic systems. Firstly, our investigations show that, similar to mammalian cell lines, PCP can be metabolized to tetrachlorohydroquinone (TCHQ) in the permanent cell line derived from rainbow trout liver cells (RTL-W1). Moreover, we demonstrate that PCP as well as its metabolite TCHQ is capable of influencing the viability of these cells. Three cell viability assays were performed to assess possible cellular targets of these substances. Thus, the cytotoxicity of the PCP-derivative TCHQ was shown for the first time in a fish cell line. Further investigations revealed the involvement of ROS in the cytotoxicity of PCP and its metabolite TCHQ. The observation of oxidative stress provides a plausible explanation for the increased cytotoxicity at higher concentrations especially for PCP and implies possible mechanisms underlying these observations. In addition, antioxidants such as ascorbic acid and quercetin modulate the detrimental effects of PCP and TCHQ whereby both compounds exacerbate the cytotoxic effects of high PCP and TCHQ concentrations.

  1. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... has a legitimate medical use. Use of a drug of abuse (e.g., heroin, PCP, marijuana) or any other... involving marijuana, cocaine, amphetamines, or PCP? 40.137 Section 40.137 Transportation Office of the... Medical Review Officers and the Verification Process § 40.137 On what basis does the MRO verify...

  2. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... has a legitimate medical use. Use of a drug of abuse (e.g., heroin, PCP, marijuana) or any other... involving marijuana, cocaine, amphetamines, or PCP? 40.137 Section 40.137 Transportation Office of the... Medical Review Officers and the Verification Process § 40.137 On what basis does the MRO verify...

  3. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... has a legitimate medical use. Use of a drug of abuse (e.g., heroin, PCP, marijuana) or any other... involving marijuana, cocaine, amphetamines, or PCP? 40.137 Section 40.137 Transportation Office of the... Medical Review Officers and the Verification Process § 40.137 On what basis does the MRO verify...

  4. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... has a legitimate medical use. Use of a drug of abuse (e.g., heroin, PCP, marijuana) or any other... involving marijuana, cocaine, amphetamines, or PCP? 40.137 Section 40.137 Transportation Office of the... Medical Review Officers and the Verification Process § 40.137 On what basis does the MRO verify...

  5. Brief exposure to methamphetamine (METH) and phencyclidine (PCP) during late development leads to long-term learning deficits in rats.

    PubMed

    White, Ilsun M; Minamoto, Takehiro; Odell, Joseph R; Mayhorn, Joseph; White, Wesley

    2009-04-17

    Exposure to methamphetamine (METH) and phencyclidine (PCP) during early development is thought to produce later behavioral deficits. We postulated that exposure to METH and PCP during later development would produce similar behavioral deficits, particularly learning deficits in adulthood. Wistar rats were treated with METH (9 mg/kg), PCP (9 mg/kg), or saline during later development, postnatal days (PD) 50-51, and subsequent behavioral changes were examined including: locomotor activity during the acute drug state (PD 50-51) and the post-drug phase (PD 50-80); social interaction on PD 54-80; and spatial discrimination and reversal in adulthood (after PD 90). METH and PCP differentially affected locomotion during the acute state, but not during the post-drug phase. METH decreased social interaction throughout tests two weeks after drug treatment, whereas PCP decreased social interaction only during the first 8 min of tests. Neither METH nor PCP impaired initial acquisition of spatial discrimination. However, reversal was significantly impaired by PCP, whereas METH produced a mild deficit, compared to controls. Our data provide evidence that exposure to PCP and METH during later development lead to enduring cognitive deficits in adulthood. Selective impairment of reversal may reflect neurological damage in the prefrontal cortex due to early exposure to drugs.

  6. PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia.

    PubMed

    Walker, Melissa M; Novak, Lea; Widener, Rebecca; Grubbs, James Aaron; King, Janice; Hale, Joanetha Y; Ochs, Martina M; Myers, Lisa E; Briles, David E; Deshane, Jessy

    2016-03-01

    We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TRAIL, and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells. The latter have been shown to facilitate the clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation, and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia.

  7. Developmental molecular and functional cerebellar alterations induced by PCP4/PEP19 overexpression: implications for Down syndrome.

    PubMed

    Mouton-Liger, François; Sahún, Ignasi; Collin, Thibault; Lopes Pereira, Patricia; Masini, Debora; Thomas, Sophie; Paly, Evelyne; Luilier, Sabrina; Même, Sandra; Jouhault, Quentin; Bennaï, Soumia; Beloeil, Jean-Claude; Bizot, Jean-Charles; Hérault, Yann; Dierssen, Mara; Créau, Nicole

    2014-03-01

    PCP4/PEP19 is a modulator of Ca(2+)-CaM signaling. In the brain, it is expressed in a very specific pattern in postmitotic neurons. In particular, Pcp4 is highly expressed in the Purkinje cell, the sole output neuron of the cerebellum. PCP4, located on human chromosome 21, is present in three copies in individuals with Down syndrome (DS). In a previous study using a transgenic mouse model (TgPCP4) to evaluate the consequences of 3 copies of this gene, we found that PCP4 overexpression induces precocious neuronal differentiation during mouse embryogenesis. Here, we report combined analyses of the cerebellum at postnatal stages (P14 and adult) in which we identified age-related molecular, electrophysiological, and behavioral alterations in the TgPCP4 mouse. While Pcp4 overexpression at P14 induces an earlier neuronal maturation, at adult stage it induces increase in cerebellar CaMK2alpha and in cerebellar LTD, as well as learning impairments. We therefore propose that PCP4 contributes significantly to the development of Down syndrome phenotypes through molecular and functional changes. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Anti-apoptotic effects of PCP4/PEP19 in human breast cancer cell lines: a novel oncotarget.

    PubMed

    Hamada, Taiji; Souda, Masakazu; Yoshimura, Takuya; Sasaguri, Shoko; Hatanaka, Kazuhito; Tasaki, Takashi; Yoshioka, Takako; Ohi, Yasuyo; Yamada, Sohsuke; Tsutsui, Masato; Umekita, Yoshihisa; Tanimoto, Akihide

    2014-08-15

    The PCP4/PEP19 is a calmodulin-binding anti-apoptotic peptide in neural cells but its potential role in human cancer has largely been unknown. We investigated the expression of PCP4/PEP19 in human breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 cells, and found that estrogen receptor (ER)-positive MCF-7 and ER-negative SK-BR-3 cells expressed PCP4/PEP19. In the MCF-7 cells, cell proliferation was estrogen-dependent, and PCP4/PEP19 expression was induced by estrogen. In both cell lines, PCP4/PEP19 knockdown induced apoptosis and slightly decreased Akt phosphorylation. Knockdown of calcium/calmodulin-dependent protein kinase kinase 1 (CaMKK1), resulting in decreased phospho-Akt(Thr308), enhanced apoptosis in SK-BR-3 but not in MCF-7 cells. CaMKK2 knockdown moderately decreased phospho-Akt(Thr308) and increased apoptosis in MCF-7 cells but not in SK-BR-3 cells. These data indicated that PCP4/PEP19 regulates apoptosis but exact mechanism is still unknown. PCP4/PEP19 can therefore potentially serve as independent oncotarget for therapy of PCP4/PEP19-positive breast cancers irrespective of ER expression.

  9. Anti-apoptotic Effects of PCP4/PEP19 in Human Breast Cancer Cell Lines: A Novel Oncotarget

    PubMed Central

    Hamada, Taiji; Souda, Masakazu; Yoshimura, Takuya; Sasaguri, Shoko; Hatanaka, Kazuhito; Tasaki, Takashi; Yoshioka, Takako; Ohi, Yasuyo; Yamada, Sohsuke; Tsutsui, Masato; Umekita, Yoshihisa; Tanimoto, Akihide

    2014-01-01

    The PCP4/PEP19 is a calmodulin-binding anti-apoptotic peptide in neural cells but its potential role in human cancer has largely been unknown. We investigated the expression of PCP4/PEP19 in human breast cancer cell lines MCF-7, SK-BR-3, and MDA-MB-231 cells, and found that estrogen receptor (ER)-positive MCF-7 and ER-negative SK-BR-3 cells expressed PCP4/PEP19. In the MCF-7 cells, cell proliferation was estrogen-dependent, and PCP4/PEP19 expression was induced by estrogen. In both cell lines, PCP4/PEP19 knockdown induced apoptosis and slightly decreased Akt phosphorylation. Knockdown of calcium/calmodulin-dependent protein kinase kinase 1 (CaMKK1), resulting in decreased phospho-AktThr308, enhanced apoptosis in SK-BR-3 but not in MCF-7 cells. CaMKK2 knockdown moderately decreased phospho-AktThr308 and increased apoptosis in MCF-7 cells but not in SK-BR-3 cells. These data indicated that PCP4/PEP19 regulates apoptosis but exact mechanism is still unknown. PCP4/PEP19 can therefore potentially serve as independent oncotarget for therapy of PCP4/PEP19-positive breast cancers irrespective of ER expression. PMID:25153723

  10. β-Hydrogen Elimination Reactions of Nickel and Palladium Methoxides Stabilised by PCP Pincer Ligands.

    PubMed

    Martínez-Prieto, Luis M; Ávila, Elena; Palma, Pilar; Álvarez, Eleuterio; Cámpora, Juan

    2015-06-26

    Nickel and palladium methoxides [((iPr)PCP)M-OMe], which contain the (iPr)PCP pincer ligand, decompose upon heating to give products of different kinds. The palladium derivative cleanly gives the dimeric Pd(0) complex [Pd(μ-(iPr)PCHP)]2 ((iPr)PCHP = 2,6-bis(diisopropylphosphinomethyl)phenyl) and formaldehyde. In contrast, decomposition of [((iPr)PCP)Ni-OMe] affords polynuclear carbonyl phosphine complexes. Both decomposition processes are initiated by β-hydrogen elimination (BHE), but the resulting [((iPr)PCP)M-H] hydrides undergo divergent reaction sequences that ultimately lead to the irreversible breakdown of the pincer units. Whereas the Pd hydride spontaneously experiences reductive C-H coupling, the decay of its Ni analogue is brought about by its reaction with formaldehyde released in the BHE step. Kinetic measurements showed that the BHE reaction is reversible and less favourable for Ni than for Pd for both kinetic and thermodynamic reasons. DFT calculations confirmed the main conclusions of the kinetic studies and provided further insight into the mechanisms of the decomposition reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. RESULTS OF A METHOD VERIFICATION STUDY FOR ANALYSES OF PCP IN SOIL

    EPA Science Inventory

    As a prelude to a field demonstration of the fungal treatment technology by the SITE Program, a field treatability study was performed to select optimal fungal species and loading rates.using the site-specific soil matrix contaminated with Wood preserving wastes: PCP and PAHS. ur...

  12. EXTRACTION OF PENTACHLOROPHENOL (PCP) FROM SOILS USING ENVIRONMENTALLY BENIGN ACID SOLUTIONS

    EPA Science Inventory

    The presence of organic contaminants like PCP in soil is a major environmental concern. Various remediation methods have been used of which soil washing is a common procedure. Many different solvents like surfactants, ionic liquids and cyclodextrins have been studied. the pres...

  13. Model for PCP contracts offers right incentives for Medicare, Medicaid providers.

    PubMed

    1999-10-01

    Consider this model for PCP contracting. Provider organizations in Medicare and Medicaid often structure arrangements with their primary care providers that set up the organizations--and the doctors--to fail. An actuary from Milliman & Robertson in Seattle illustrates how to establish the right kinds of incentives for PCPs.

  14. EXTRACTION OF PENTACHLOROPHENOL (PCP) FROM SOILS USING ENVIRONMENTALLY BENIGN ACID SOLUTIONS

    EPA Science Inventory

    The presence of organic contaminants like PCP in soil is a major environmental concern. Various remediation methods have been used of which soil washing is a common procedure. Many different solvents like surfactants, ionic liquids and cyclodextrins have been studied. the pres...

  15. RESULTS OF A METHOD VERIFICATION STUDY FOR ANALYSES OF PCP IN SOIL

    EPA Science Inventory

    As a prelude to a field demonstration of the fungal treatment technology by the SITE Program, a field treatability study was performed to select optimal fungal species and loading rates.using the site-specific soil matrix contaminated with Wood preserving wastes: PCP and PAHS. ur...

  16. INVESTIGATION OF THE POTENTIAL RELEASE OF POLYCHLORINATED DIOXINS AND FURANS FROM PCP-TREATED UTILITY POLES

    EPA Science Inventory

    The United States (US) Environmental Protection Agency (EPA) estimated that the use of technical grade pentachlorophenol (PCP) between 1970 and 1995 to treat wood was approximately 400,000 metric tons in the US, and that between 4,800 and 36,000 grams of 2,3,7,8-tetrachlorodiben...

  17. Human exposure to PCDDs and their precursors from heron and tern eggs in the Yangtze River Delta indicate PCP origin.

    PubMed

    Zhou, Yihui; Yin, Ge; Asplund, Lillemor; Stewart, Kathryn; Rantakokko, Panu; Bignert, Anders; Ruokojärvi, Päivi; Kiviranta, Hannu; Qiu, Yanling; Ma, Zhijun; Bergman, Åke

    2017-06-01

    Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are highly toxic to humans and wildlife. In the present study, PCDD/Fs were analyzed in the eggs of whiskered terns (Chlidonias hybrida), and genetically identified eggs from black-crowned night herons (Nycticorax nycticorax) sampled from two lakes in the Yangtze River Delta area, China. The median toxic equivalent (TEQ) of PCDD/Fs were 280 (range: 95-1500) and 400 (range: 220-1100) pg TEQ g(-1) lw (WHO, 1998 for birds) in the eggs of black-crowned night heron and whiskered tern, respectively. Compared to known sources, concentrations of PCDDs relative to the sum of PCDD/Fs in bird eggs, demonstrated high abundance of octachlorodibenzo-p-dioxin (OCDD), 1,2,3,4,6,7,8-heptaCDD and 1,2,3,6,7,8-hexaCDD indicating pentachlorophenol (PCP), and/or sodium pentachlorophenolate (Na-PCP) as significant sources of the PCDD/Fs. The presence of polychlorinated diphenyl ethers (PCDEs), hydroxylated and methoxylated polychlorinated diphenyl ethers (OH- and MeO-PCDEs, known impurities in PCP products), corroborates this hypothesis. Further, significant correlations were found between the predominant congener CDE-206, 3'-OH-CDE-207, 2'-MeO-CDE-206 and OCDD, indicating a common origin. Eggs from the two lakes are sometimes used for human consumption. The WHO health-based tolerable intake of PCDD/Fs is exceeded if eggs from the two lakes are consumed regularly on a weekly basis, particularly for children. The TEQs extensively exceed maximum levels for PCDD/Fs in hen eggs and egg products according to EU legislation (2.5 pg TEQ g(-1)lw). The results suggest immediate action should be taken to manage the contamination, and further studies evaluating the impacts of egg consumption from wild birds in China. Likewise, studies on dioxins and other POPs in common eggs need to be initiated around China. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. 3-MeO-PCP intoxication in two young men: First in vivo detection in Italy.

    PubMed

    Bertol, Elisabetta; Pascali, Jennifer; Palumbo, Diego; Catalani, Valeria; Di Milia, Maria Grazia; Fioravanti, Alessia; Mari, Francesco; Vaiano, Fabio

    2017-05-01

    3-MeO-PCP or 3-methoxyphencyclidine is a derivative of phencyclidine. It acts as a dissociative anesthetic and it has allegedly hallucinogenic and sedative effects. There are almost no documented intoxication cases and references about its pharmacology and toxicity in literature. This study presents two concomitant intoxication cases due to consumption of 3-MeO-PCP and alcohol. A 19 (A) and a 21 years old (B) men were brought to Santa Maria Nuova Hospital in a comatose state (Glasgow score 3). They showed respiratory acidosis, right anisocoria with mydriatic pupils and hypothermia. Toxicological screening was negative. They were intubated for 7-8h. Almost 24h after hospitalization they were still in a delirious and agitated status. The subjects declared a high alcohol consumption and ingestion of unknown pills. Blood and urine were collected upon their arrival to the Emergency Department and sent to our Forensic Toxicology Division. Blood alcohol content was 2.0g/L for subject A and 1,7g/L for subject B. The specimens were analyzed by means of GC-MS, revealing the presence of 3-MeO-PCP. A confirmation and quantification was carried out by means of a new and fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for new psychoactive substances (NPS) detection. The analysis was performed adding acetonitrile to the samples, the supernatant was dried and reconstituted with methanol. Mephedrone-D3 was used as internal standard. Acquisition was performed through multiple reaction monitoring (MRM) dynamic mode. The MRM transitions used for quantification of 3-MeO-PCP were: m/z 274→86, 121. 3-MeO-PCP was quantified in all the biological samples at the following concentrations: 350.0 (blood) and 6109.2 (urine) ng/mL for A; 180.1 (blood) and 3003.6 (urine) ng/mL for B. Taking into account the analytical results, we can suppose that the manifested symptoms were due to the consumption of 3-MeO-PCP in synergy with alcohol. Our report is the first

  19. Combinatorial signaling by the Frizzled/PCP and Egfr-pathways during planar cell polarity establishment in the Drosophila eye

    PubMed Central

    Weber, Ursula; Pataki, Csilla; Mihaly, Jozsef; Mlodzik, Marek

    2008-01-01

    Summary Frizzled (Fz)/PCP signaling regulates planar, vectorial orientation of cells or groups of cells within whole tissues. Although Fz/PCP signaling has been analyzed in several contexts, little is known about nuclear events acting downstream of Fz/PCP signaling in the R3/R4 cell fate decision in the Drosophila eye or in other contexts. Here we demonstrate a specific requirement for Egfr-signaling and the transcription factors Fos (AP-1), Yan and Pnt in PCP dependent R3/R4 specification. Loss and gain-of-function assays suggest that the transcription factors integrate input from Fz/PCP and Egfr-signaling and that the ETS factors Pnt and Yan cooperate with Fos (and Jun) in the PCP-specific R3/R4 determination. Our data indicate that Fos (either downstream of Fz/PCP signaling or parallel to it) and Yan are required in R3 to specify its fate (Fos) or inhibit R4 fate (Yan), and that Egfr-signaling is required in R4 via Pnt for its fate specification. Taken together with previous work establishing a Notch-dependent Su(H) function in R4, we conclude that Fos, Yan, Pnt, and Su(H) integrate Egfr, Fz, and Notch-signaling input in R3 or R4 to establish cell fate and ommatidial polarity. PMID:18291359

  20. The PCP effector Fuzzy controls cilial assembly and signaling by recruiting Rab8 and Dishevelled to the primary cilium.

    PubMed

    Zilber, Yulia; Babayeva, Sima; Seo, Jung Hwa; Liu, Jia Jia; Mootin, Steven; Torban, Elena

    2013-03-01

    The planar cell polarity (PCP) pathway controls multiple cellular processes during vertebrate development. Recently the PCP pathway was implicated in ciliogenesis and in ciliary function. The primary cilium is an apically projecting solitary organelle that is generated via polarized intracellular trafficking. Because it acts as a signaling nexus, defects in ciliogenesis or cilial function cause multiple congenital anomalies in vertebrates. Loss of the PCP effector Fuzzy affects PCP signaling and formation of primary cilia; however, the mechanisms underlying these processes are largely unknown. Here we report that Fuzzy localizes to the basal body and ciliary axoneme and is essential for ciliogenesis by delivering Rab8 to the basal body and primary cilium. Fuzzy appears to control subcellular localization of the core PCP protein Dishevelled, recruiting it to Rab8-positive vesicles and to the basal body and cilium. We show that loss of Fuzzy results in inhibition of PCP signaling and hyperactivation of the canonical WNT pathway. We propose a mechanism by which Fuzzy participates in ciliogenesis and affects both canonical WNT and PCP signaling.

  1. Effects of lamotrigine on PCP-evoked elevations in monoamine levels in the medial prefrontal cortex of freely moving rats.

    PubMed

    Quarta, Davide; Large, Charles H

    2011-12-01

    Lamotrigine is suggested to have potential as an add-on treatment for patients with schizophrenia. Supporting evidence comes from the efficacy of the drug in models of psychotic-like behaviour induced by N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP). These drugs enhance levels of the monoamines in the cortex, which may contribute to their psychotomimetic effects. The ability of lamotrigine to prevent these neurochemical changes has not been examined. We studied PCP-evoked overflow of noradrenaline, dopamine and serotonin in the medial prefrontal cortex of awake rats using microdialysis. Rats were administered lamotrigine or vehicle, followed by PCP. Locomotor activity was also recorded before and after drug treatment. Lamotrigine did not have an influence on basal levels of the monoamines, but significantly reduced PCP-evoked overflow of dopamine and serotonin; PCP-evoked overflow of noradrenaline was also reduced by lamotrigine, but not to a significant degree. In contrast, PCP-induced hyperactivity was unaffected by lamotrigine. It is concluded that lamotrigine can modify PCP-evoked monoamine overflow in the cortex, consistent with an ability to prevent the psychotomimetic effects of NMDA receptor antagonists in rodents and humans. The dissociation between monoamine overflow and locomotor activity suggests the involvement of different brain circuits; relevance to the treatment of schizophrenia is also discussed.

  2. The PCP effector Fuzzy controls cilial assembly and signaling by recruiting Rab8 and Dishevelled to the primary cilium

    PubMed Central

    Zilber, Yulia; Babayeva, Sima; Seo, Jung Hwa; Liu, Jia Jia; Mootin, Steven; Torban, Elena

    2013-01-01

    The planar cell polarity (PCP) pathway controls multiple cellular processes during vertebrate development. Recently the PCP pathway was implicated in ciliogenesis and in ciliary function. The primary cilium is an apically projecting solitary organelle that is generated via polarized intracellular trafficking. Because it acts as a signaling nexus, defects in ciliogenesis or cilial function cause multiple congenital anomalies in vertebrates. Loss of the PCP effector Fuzzy affects PCP signaling and formation of primary cilia; however, the mechanisms underlying these processes are largely unknown. Here we report that Fuzzy localizes to the basal body and ciliary axoneme and is essential for ciliogenesis by delivering Rab8 to the basal body and primary cilium. Fuzzy appears to control subcellular localization of the core PCP protein Dishevelled, recruiting it to Rab8-positive vesicles and to the basal body and cilium. We show that loss of Fuzzy results in inhibition of PCP signaling and hyperactivation of the canonical WNT pathway. We propose a mechanism by which Fuzzy participates in ciliogenesis and affects both canonical WNT and PCP signaling. PMID:23303251

  3. Secreted frizzled-related protein disrupts PCP in eye lens fiber cells that have polarised primary cilia

    PubMed Central

    Sugiyama, Yuki; Stump, Richard J. W.; Nguyen, Anke; Wen, Li; Chen, Yongjuan; Wang, Yanshu; Murdoch, Jennifer N.; Lovicu, Frank J.; McAvoy, John W.

    2009-01-01

    Planar cell polarity (PCP) signaling polarises cells along tissue axes. Although pathways involved are becoming better understood, outstanding issues include; (i) existence/identity of cues that orchestrate global polarisation in tissues, and (ii) the generality of the link between polarisation of primary cilia and asymmetric localisation of PCP proteins. Mammalian lenses are mainly comprised of epithelial-derived fiber cells. Concentrically arranged fibers are precisely aligned as they elongate along the anterior-posterior axis and orientate towards lens poles where they meet fibers from other segments to form characteristic sutures. We show that lens exhibits PCP, with each fiber cell having a apically situated cilium and in most cases this is polarised towards the anterior pole. Frizzled and other PCP proteins are also asymmetrically localised along the equatorial-anterior axis. Mutations in core PCP genes Van Gogh-like 2 and Celsr1 perturb oriented fiber alignment and suture formation. Suppression of the PCP pathway by overexpressing Sfrp2, shows that whilst local groups of fibers are often similarly oriented, they lack global orientation; consequently when local groups of fibers with different orientations meet they form multiple, small, ectopic suture-like configurations. This indicates that this extracellular inhibitor disrupts a global polarising signal that utilises a PCP-mediated mechanism to coordinate the global alignment and orientation of fibers to lens poles. PMID:19968984

  4. Reconstruction of microbial community structures as evidences for soil redox coupled reductive dechlorination of PCP in a mangrove soil.

    PubMed

    Xu, Yan; He, Yan; Tang, Xianjin; Brookes, Philip C; Xu, Jianming

    2017-10-15

    The aim was to investigate the influence of pentachlorophenol (PCP) on the soil microbial communities and the coupled mechanism between PCP reductive dechlorination and soil redox under anaerobic condition. Accordingly, a slurry incubation experiment was carried out in which bacterial and archaeal communities were detected by MiSeq amplicon sequencing. The original microbial community balance was gradually disrupted and new microbial structure was reconstructed subsequently through self-regulation and acclimation during PCP transformation, coupling with the changes of soil biogeochemical redox dynamics. The phylum Bacteroidetes predominated during the earlier PCP dechlorination period and then was progressively replaced by Proteobacteria and Firmicutes groups when PCP was mostly transformed into 2,3,4,5-TeCP and 3,4,5-TCP. Heatmap and hierarchical cluster analysis revealed the Clostridium-like, Geobacter-like and Dehalococcoides-like organisms enriched concurrently during PCP reductive dechlorination processes. The relative abundance changes of the redox-active microorganisms, together with their relevance to the corresponding biogeochemical redox processes, showed that PCP dechlorination, Fe(III) and SO4(2-) reduction, as well as methanogenesis were coupled terminal electron accepting processes. The combined analysis of the microbial function, the affinity for substrates (H2 and acetate) and the sensitivity for PCP toxicity by microorganisms might explain why electron transport chain has changed in soil biogeochemical redox process. Our study offers a comprehensive description of the impact of PCP on the soil microbial community structures, which could be very useful for understanding the regulation of soil nutrient and energy transfer during biogeochemical cycling processes in soils with significant inputs of exogenous pollutants. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration

    PubMed Central

    Moens, Cecilia B.

    2016-01-01

    The planar cell polarity (PCP) pathway is a cell-contact mediated mechanism for transmitting polarity information between neighboring cells. PCP “core components” (Vangl, Fz, Pk, Dsh, and Celsr) are essential for a number of cell migratory events including the posterior migration of facial branchiomotor neurons (FBMNs) in the plane of the hindbrain neuroepithelium in zebrafish and mice. While the mechanism by which PCP signaling polarizes static epithelial cells is well understood, how PCP signaling controls highly dynamic processes like neuronal migration remains an important outstanding question given that PCP components have been implicated in a range of directed cell movements, particularly during vertebrate development. Here, by systematically disrupting PCP signaling in a rhombomere-restricted manner we show that PCP signaling is required both within FBMNs and the hindbrain rhombomere 4 environment at the time when they initiate their migration. Correspondingly, we demonstrate planar polarized localization of PCP core components Vangl2 and Fzd3a in the hindbrain neuroepithelium, and transient localization of Vangl2 at the tips of retracting FBMN filopodia. Using high-resolution timelapse imaging of FBMNs in genetic chimeras we uncover opposing cell-autonomous and non-cell-autonomous functions for Fzd3a and Vangl2 in regulating FBMN protrusive activity. Within FBMNs, Fzd3a is required to stabilize filopodia while Vangl2 has an antagonistic, destabilizing role. However, in the migratory environment Fzd3a acts to destabilize FBMN filopodia while Vangl2 has a stabilizing role. Together, our findings suggest a model in which PCP signaling between the planar polarized neuroepithelial environment and FBMNs directs migration by the selective stabilization of FBMN filopodia. PMID:26990447

  6. PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration.

    PubMed

    Davey, Crystal F; Mathewson, Andrew W; Moens, Cecilia B

    2016-03-01

    The planar cell polarity (PCP) pathway is a cell-contact mediated mechanism for transmitting polarity information between neighboring cells. PCP "core components" (Vangl, Fz, Pk, Dsh, and Celsr) are essential for a number of cell migratory events including the posterior migration of facial branchiomotor neurons (FBMNs) in the plane of the hindbrain neuroepithelium in zebrafish and mice. While the mechanism by which PCP signaling polarizes static epithelial cells is well understood, how PCP signaling controls highly dynamic processes like neuronal migration remains an important outstanding question given that PCP components have been implicated in a range of directed cell movements, particularly during vertebrate development. Here, by systematically disrupting PCP signaling in a rhombomere-restricted manner we show that PCP signaling is required both within FBMNs and the hindbrain rhombomere 4 environment at the time when they initiate their migration. Correspondingly, we demonstrate planar polarized localization of PCP core components Vangl2 and Fzd3a in the hindbrain neuroepithelium, and transient localization of Vangl2 at the tips of retracting FBMN filopodia. Using high-resolution timelapse imaging of FBMNs in genetic chimeras we uncover opposing cell-autonomous and non-cell-autonomous functions for Fzd3a and Vangl2 in regulating FBMN protrusive activity. Within FBMNs, Fzd3a is required to stabilize filopodia while Vangl2 has an antagonistic, destabilizing role. However, in the migratory environment Fzd3a acts to destabilize FBMN filopodia while Vangl2 has a stabilizing role. Together, our findings suggest a model in which PCP signaling between the planar polarized neuroepithelial environment and FBMNs directs migration by the selective stabilization of FBMN filopodia.

  7. Measurement of an explosive behavior in the mouse, induced by MK-801, a PCP analogue.

    PubMed

    Deutsch, S I; Hitri, A

    1993-06-01

    MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor complex that binds with high-affinity to the phencyclidine (PCP) binding site, stimulated an outbred strain of NIH Swiss mice to display discrete episodes of explosive jumping behavior, designated as "popping." The episodes of this behavior were characterized with respect to their dose dependency, latency, and duration. The number of mice displaying this behavior increased with increasing doses of MK-801. The intensity of the popping behavior was sensitive to dose-dependent inhibition by haloperidol, a conventional antipsychotic medication, and clozapine, an atypical antipsychotic medication. In view of PCP's ability to precipitate a schizophreniform psychosis in humans, the behavior may serve as a useful preclinical paradigm for the screening of potentially novel antipsychotic medications.

  8. DEMONSTRATION BULLETIN: PCP IMMUNOASSAY TECHNOLOGIES - PENTA RISC BY ENSYS INC., PENTA RAPID BY OHMICRON CORP., ENVIROGARD BY MILLIPORE

    EPA Science Inventory

    The objectives of this demonstration were to test these field screening technologies for accuracy and precision in detecting Pentachlorophenol (PCP) levels in soil and water by comparing their results with those of a confirmatory laboratory. The three immunoassay technologies ...

  9. The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9

    SciTech Connect

    Haribaskar, Ramachandran; Puetz, Michael; Schupp, Birte; Skouloudaki, Kassiani; Bietenbeck, Andreas; Walz, Gerd; Schaefer, Tobias

    2009-09-11

    The planar cell polarity (PCP) pathway, a {beta}-catenin-independent branch of the Wnt signaling pathway, orients cells and their appendages with respect to the body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego, acts as a molecular switch that blocks {beta}-catenin-dependent and promotes {beta}-catenin-independent Wnt signaling. We report now that Diversin, containing several nuclear localization signals, translocates to the nucleus, where it interacts with the transcription factor AF9. Both Diversin and AF9 block canonical Wnt signaling; however, this occurs independently of each other, and does not require nuclear Diversin. In contrast, AF9 strongly augments the Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene expression in the nucleus, and this augmentation largely depends on the presence of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade translocate to the nucleus to participate in transcriptional regulation and PCP signaling.

  10. Wnt/PCP proteins regulate stereotyped axon branch extension in Drosophila

    PubMed Central

    Ng, Julian

    2012-01-01

    Branching morphology is a hallmark feature of axons and dendrites and is essential for neuronal connectivity. To understand how this develops, I analyzed the stereotyped pattern of Drosophila mushroom body (MB) neurons, which have single axons branches that extend dorsally and medially. I found that components of the Wnt/Planar Cell Polarity (PCP) pathway control MB axon branching. frizzled mutant animals showed a predominant loss of dorsal branch extension, whereas strabismus (also known as Van Gogh) mutants preferentially lost medial branches. Further results suggest that Frizzled and Strabismus act independently. Nonetheless, branching fates are determined by complex Wnt/PCP interactions, including interactions with Dishevelled and Prickle that function in a context-dependent manner. Branching decisions are MB-autonomous but non-cell-autonomous as mutant and non-mutant neurons regulate these decisions collectively. I found that Wnt/PCP components do not need to be asymmetrically localized to distinct branches to execute branching functions. However, Prickle axonal localization depends on Frizzled and Strabismus. PMID:22147954

  11. Desorptive behavior of pentachlorophenol (PCP) and phenanthrene in soil-water systems

    SciTech Connect

    Fall, C.; Chaouki, J.; Chavarie, C.

    2000-04-01

    Recent investigations have prompted the need for a better understanding of the complete desorptive behavior of hydrophobic organic compounds in soils. The present study evaluated the irreversibilities associated with the desorption of pentachlorophenol (PCP) and phenanthrene from different types of soils. The study also examined the influence of solid-liquid ratio of the current batch desorption tests, specifically the completeness and accuracy of data gathered for establishing isotherms. Results demonstrated that the desorption of PCP and phenanthrene from contaminated soils can lead to three different types of behavior: complete reversibility, partial reversibility, or total irreversibility. The equilibrium adsorption constant (K{sub d}) is identified as a key parameter that indirectly sets the extent of hysteresis during the reverse process of desorption. According to the data, irreversibility occurs more in soils with a large adsorption capacity, that is, when K{sub d} is approximately 50 mL/g or more in the case of the phenanthrene- and PCP-soil systems evaluated. Furthermore, to facilitate the desorption experiments overall, the study proposes selection criteria for the solid-liquid ratio of batch tests to allow for variations in the adsorption capacity of each soil.

  12. Reduction of pollutants in pulp paper mill effluent treated by PCP-degrading bacterial strains.

    PubMed

    Chandra, Ram; Raj, Abhay; Yadav, Sangeeta; Patel, Devendra Kumar

    2009-08-01

    Two PCP-degrading bacterial strains, Bacillus cereus (ITRC-S6) and Serratia marcescens (ITRC-S7) were used for the treatment of pulp and paper mill effluent at conditions; 1.0% glucose and 0.5% peptone at 30 +/- 1 degrees C at 120 rpm for 168 h of incubation. These two bacterial strains effectively reduced colour (45-52%), lignin (30-42%), BOD (40-70%), COD (50-60%), total phenol (32-40%) and PCP (85-90%) within 168 h of incubation. However, the highest reduction in colour (62%), lignin (54%), BOD (70%), COD (90%), total phenol (90%) and PCP (100%) was recorded by mixed culture treatment. The bacterial mechanism for the degradation of pulp and paper mill effluent may be explained by an increase in the cells biomass using added co-substrates resulting liberation of significant amount of chloride due to bacterial dechlorination of chlorolignins and chlorophenols this showed reduction in colour, lignin and toxicity in the effluent. Further, GC-MS analysis of ethyl acetate-extractable compounds from treated pulp paper mill effluent reinforces the bacterium capability for the degradation of lignin and pentachlorophenol, as many aromatic compounds such as 2-chlorophenol, 2, 4, 6-trichlorophenol and tetrachlorohydroquinone, 6-chlorohydroxyquinol and tetrachlorohydroquinone detected which were not present in the untreated effluent.

  13. Dechlorination of pentachlorophenol (PCP) in aqueous solution on novel Pd-loaded electrode modified with PPy-SDBS composite film.

    PubMed

    Sun, Zhirong; Wei, Xuefeng; Zhang, Huan; Hu, Xiang

    2015-03-01

    Pentachlorophenol (PCP) is a persistent pollutant and a suspected human carcinogen. It can be found in the air, water, and soil and enters the environment through evaporation from treated wood surfaces, industrial spills, and disposal at uncontrolled hazardous waste sites. Ecotoxicity of PCP necessitates the development of rapid and reliable remediation techniques. Electrocatalytic hydrogenolysis (ECH) has been proven as a promising method for detoxification of halogenated wastes, due to its rapid reaction rate, low apparatus cost, mild reaction conditions, and absence of secondary contaminants. Challenge for the application of ECH is to prepare a Pd-coated cathode with high stability, high catalytic activity, and low Pd loading level. In this work, Pd/polypyrrole-sodium dodecyl benzene sulfonate/meshed Ti (Pd/PPy-SDBS/Ti) electrode was prepared and was characterized by cyclic voltammetry, scanning electron microscopy, X-ray diffraction, and inductively coupled plasma-atomic emission spectrometry. Electrochemically reductive dechlorination of PCP on the Pd/PPy-SDBS/Ti electrode in aqueous solution was investigated. Pd microparticles were uniformly dispersed on PPy-SDBS film which was previously electrodeposited on the meshed Ti supporting electrode. The loading of Pd on the electrode was 0.72 mg cm(-2). Electrocatalytic dechlorination of PCP was performed in a two-compartment cell separated by cation-exchange membrane. The PCP removal on the Pd/PPy-SDBS/Ti electrode could reach 100 % within 70 min with dechlorination current 3 mA when PCP initial concentration was 10 mg L(-1) and initial pH was 2.4. Conversion of PCP on the Pd/PPy-SDBS/Ti electrode followed pseudo-first-order kinetics, and the apparent activation energy was 13.0 kJ mol(-1). The removal of PCP still kept 100 % after 70 min dechlorination when the Pd/PPy-SDBS/Ti cathode was reused ten times. The electrode exhibited promising dechlorination potential with high electrocatalytic activity, good stability

  14. A multiplexed nucleic acid microsystem for point-of-care detection of HIV co-infection with MTB and PCP.

    PubMed

    Xu, Lingjia; Kong, Jilie

    2013-12-15

    Many individuals infected with the human immunodeficiency virus (HIV), especially children in African countries, die of co-infections with Mycobacterium tuberculosis (MTB) (coinfection rate: 50%) or Pneumocystis carinii pneumonia (PCP) (coinfection rate: 81%). The present proposal describes a rapid, portable, low-cost, multiplexed point-of-care diagnostic technique for simultaneously detecting HIV, MTB, and PCP. This technique incorporates a creative micro-device (hardware) and a loop-mediated isothermal amplification strategy (software).

  15. Comparative effects of phencyclidine (PCP) and. delta. /sup 9/-tetrahydrocannabinol (THC) on glucose oxidation in the rat testis

    SciTech Connect

    Husain, S.; Bauer, V.

    1986-03-05

    Glucose and fructose are important fuels of cellular energetics in organs like testis and brain. The previous in-vitro studies indicated that THC may disrupt many gonadal functions by inhibiting energy metabolism in the testis. PCP is sold on the street as any one of a variety of psychoactive drugs. Most commonly it is misrepresented as THC. Therefore, to compare the effects of PCP and THC on glucose utilization, in-vitro radiorespirometric experiments were conducted in rat testicular tissues. The /sup 14/CO/sub 2/ production from 5.5 mM radiolabelled glucose was followed in the presence and absence of 0.2, 0.1, 0.05, 0.01, 0.005, 0.0025 mM PCP. PCP produced a dose-dependent biphasic effect, stimulating /sup 14/CO/sub 2/ production by 6.2, 17 and 5.8% and then inhibiting it by 13.2, 15.4 and 8.9% with respective concentrations of PCP. This is in contrast to THC which produced a dose-related inhibition of 15.2, 18.1, 20.1 and 25.3% in /sup 14/CO/sub 2/ production with 0.1, 0.2, 0.3 and 0.4 mM THC. These observations are significant due to the possible abuse of PCP together with THC either deliberately or by misrepresentation.

  16. Olanzapine Prevents the PCP-induced Reduction in the Neurite Outgrowth of Prefrontal Cortical Neurons via NRG1

    PubMed Central

    Zhang, Qingsheng; Yu, Yinghua; Huang, Xu-Feng

    2016-01-01

    Accumulating evidence suggests that reducing neurite outgrowth and synaptic plasticity plays a critical role in the pathology of cognitive deficits in schizophrenia. The N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) can induce symptoms of schizophrenia as well as reduce dendritic spine density and neurite growth. The antipsychotic drug olanzapine may improve these deficits. This study aimed to investigate: (1) if olanzapine prevents PCP-induced suppression of neurite outgrowth and synaptic protein expression; (2) if olanzapine affects the Akt-GSK3 signaling pathway; and (3) the role of neuregulin 1 (NRG1) in this process. Immunofluorescence revealed that PCP treatment for 24 hours reduces both neurite length (28.5%) and the number of neurite branches (35.6%) in primary prefrontal cortical neuron cultures. PCP reduced protein and mRNA expressions of synaptophysin (24.9% and 23.2%, respectively) and PSD95 (31.5% and 21.4%, respectively), and the protein expression of p-Akt (26.7%) and p-GSK3β (35.2%). Olanzapine co-treatment prevented these PCP-induced effects in normal neurons but not in neurons from NRG1-knockout mice. These results indicate that NRG1 mediates the preventive effects of olanzapine on the PCP-induced impairment of neurite outgrowth and synaptic protein expression. This study provides potential targets for interventions on improving the efficacy of olanzapine on preventing cognitive deficits in schizophrenia. PMID:26781398

  17. Olanzapine Prevents the PCP-induced Reduction in the Neurite Outgrowth of Prefrontal Cortical Neurons via NRG1.

    PubMed

    Zhang, Qingsheng; Yu, Yinghua; Huang, Xu-Feng

    2016-01-19

    Accumulating evidence suggests that reducing neurite outgrowth and synaptic plasticity plays a critical role in the pathology of cognitive deficits in schizophrenia. The N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) can induce symptoms of schizophrenia as well as reduce dendritic spine density and neurite growth. The antipsychotic drug olanzapine may improve these deficits. This study aimed to investigate: (1) if olanzapine prevents PCP-induced suppression of neurite outgrowth and synaptic protein expression; (2) if olanzapine affects the Akt-GSK3 signaling pathway; and (3) the role of neuregulin 1 (NRG1) in this process. Immunofluorescence revealed that PCP treatment for 24 hours reduces both neurite length (28.5%) and the number of neurite branches (35.6%) in primary prefrontal cortical neuron cultures. PCP reduced protein and mRNA expressions of synaptophysin (24.9% and 23.2%, respectively) and PSD95 (31.5% and 21.4%, respectively), and the protein expression of p-Akt (26.7%) and p-GSK3β (35.2%). Olanzapine co-treatment prevented these PCP-induced effects in normal neurons but not in neurons from NRG1-knockout mice. These results indicate that NRG1 mediates the preventive effects of olanzapine on the PCP-induced impairment of neurite outgrowth and synaptic protein expression. This study provides potential targets for interventions on improving the efficacy of olanzapine on preventing cognitive deficits in schizophrenia.

  18. A one-dimensional model of PCP signaling: polarized cell behavior in the notochord of the ascidian Ciona.

    PubMed

    Kourakis, Matthew J; Reeves, Wendy; Newman-Smith, Erin; Maury, Benoit; Abdul-Wajid, Sarah; Smith, William C

    2014-11-01

    Despite its importance in development and physiology the planar cell polarity (PCP) pathway remains one of the most enigmatic signaling mechanisms. The notochord of the ascidian Ciona provides a unique model for investigating the PCP pathway. Interestingly, the notochord appears to be the only embryonic structure in Ciona activating the PCP pathway. Moreover, the Ciona notochord as a single-file array of forty polarized cells is a uniquely tractable system for the study of polarization dynamics and the transmission of the PCP pathway. Here, we test models for propagation of a polarizing signal, interrogating temporal, spatial and signaling requirements. A simple cell-cell relay cascading through the entire length of the notochord is not supported; instead a more complex mechanism is revealed, with interactions influencing polarity between neighboring cells, but not distant ones. Mechanisms coordinating notochord-wide polarity remain elusive, but appear to entrain general (i.e., global) polarity even while local interactions remain important. However, this global polarizer does not appear to act as a localized, spatially-restricted determinant. Coordination of polarity along the long axis of the notochord requires the PCP pathway, a role we demonstrate is temporally distinct from this pathway's earlier role in convergent extension and intercalation. We also reveal polarity in the notochord to be dynamic: a cell's polarity state can be changed and then restored, underscoring the Ciona notochord's amenability for in vivo studies of PCP. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Bioremediation of a Chilean Andisol contaminated with pentachlorophenol (PCP) by solid substrate cultures of white-rot fungi.

    PubMed

    Rubilar, O; Tortella, G; Cea, M; Acevedo, F; Bustamante, M; Gianfreda, L; Diez, M C

    2011-02-01

    This study provides a first attempt investigation of a serie of studies on the ability of Anthracophyllum discolor, a recently isolated white-rot fungus from forest of southern Chile, for the treatment of soil contaminated with pentachlorophenol (PCP) to future research on potential applications in bioremediation process. Bioremediation of soil contaminated with PCP (250 and 350 mg kg⁻¹ soil) was investigated with A. discolor and compared with the reference strain Phanerochaete chrysosporium. Both strains were incorporated as free and immobilized in wheat grains, a lignocellulosic material previously selected among wheat straw, wheat grains and wood chips through the growth and colonization of A. discolor. Wheat grains showed a higher growth and colonization of A. discolor, increasing the production of manganese peroxidase (MnP) activity. Moreover, the application of white-rot fungi immobilized in wheat grains to the contaminated soil favored the fungus spread. In turn, with both fungal strains and at the two PCP concentrations a high PCP removal (70-85%) occurred as respect to that measured with the fungus as free mycelium (30-45%). Additionally, the use of wheat grains in soil allowed the proliferation of microorganisms PCP decomposers, showing a synergistic effect with A. discolor and P. chrysosporium and increasing the PCP removal in the soil.

  20. A one-dimensional model of PCP signaling: polarized cell behavior in the notochord of the ascidian Ciona

    PubMed Central

    Kourakis, Matthew J.; Reeves, Wendy; Newman-Smith, Erin; Maury, Benoit; Abdul-Wajid, Sarah; Smith, William C.

    2014-01-01

    Despite its importance in development and physiology the planar cell polarity (PCP) pathway remains one of the most enigmatic signaling mechanisms. The notochord of the ascidian Ciona provides a unique model for investigating the PCP pathway. Interestingly, the notochord appears to be the only embryonic structure in Ciona activating the PCP pathway. Moreover, the Ciona notochord as a single-file array of forty polarized cells is a uniquely tractable system for the study of polarization dynamics and the transmission of the PCP pathway. Here, we test models for propagation of a polarizing signal, interrogating temporal, spatial and signaling requirements. A simple cell-cell relay cascading through the entire length of the notochord is not supported; instead a more complex mechanism is revealed, with interactions influencing polarity between neighboring cells, but not distant ones. Mechanisms coordinating notochord-wide polarity remain elusive, but appear to entrain general (i.e., global) polarity even while local interactions remain important. However, this global polarizer does not appear to act as a localized, spatially-restricted determinant. Coordination of polarity along the long axis of the notochord requires the PCP pathway, a role we demonstrate is temporally distinct from this pathway’s earlier role in convergent extension and intercalation. We also reveal polarity in the notochord to be dynamic: a cell’s polarity state can be changed and then restored, underscoring the Ciona notochord’s amenability for in vivo studies of PCP. PMID:25173874

  1. Evidence for Natural Horizontal Transfer of the pcpB Gene in the Evolution of Polychlorophenol-Degrading Sphingomonads

    PubMed Central

    Tiirola, Marja A.; Wang, Hong; Paulin, Lars; Kulomaa, Markku S.

    2002-01-01

    The chlorophenol degradation pathway in Sphingobium chlorophenolicum is initiated by the pcpB gene product, pentachlorophenol-4-monooxygenase. The distribution of the gene was studied in a phylogenetically diverse group of polychlorophenol-degrading bacteria isolated from contaminated groundwater in Kärkölä, Finland. All the sphingomonads isolated were shown to share pcpB gene homologs with 98.9 to 100% sequence identity. The gene product was expressed when the strains were induced by 2,3,4,6-tetrachlorophenol. A comparative analysis of the 16S rDNA and pcpB gene trees suggested that a recent horizontal transfer of the pcpB gene was involved in the evolution of the catabolic pathway in the Kärkölä sphingomonads. The full-length Kärkölä pcpB gene allele had approximately 70% identity with the three pcpB genes previously sequenced from sphingomonads. It was very closely related to the environmental clones obtained from chlorophenol-enriched soil samples (M. Beaulieu, V. Becaert, L. Deschenes, and R. Villemur, Microbiol. Ecol. 40:345-355, 2000). The gene was not present in polychlorophenol-degrading nonsphingomonads isolated from the Kärkölä source. PMID:12200305

  2. A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway.

    PubMed

    Salašová, Alena; Yokota, Chika; Potěšil, David; Zdráhal, Zbyněk; Bryja, Vítězslav; Arenas, Ernest

    2017-07-11

    Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. Our study shows for the first time that LRRK2 activates the WNT/PCP

  3. Probing the core-mantle boundary beneath Europe and Western Eurasia: A detailed study using PcP

    NASA Astrophysics Data System (ADS)

    Gassner, Alexandra; Thomas, Christine; Krüger, Frank; Weber, Michael

    2015-09-01

    We use PcP (the core reflected P phase) recordings of deep earthquakes and nuclear explosions from the Gräfenberg (Germany) and NORSAR (Norway) arrays to investigate the core-mantle boundary region beneath Europe and western Eurasia. We find evidence for a previously unknown ultra-low velocity zone 600 km south-east of Moscow, located at the edge of a middle-size low shear- velocity region imaged in seismic tomography that is located beneath the Volga river region. The observed amplitude variations of PcP can be modelled by velocity reductions of P and S-waves of -5% and -15%, respectively, with a density increase of +15%. Travel time delays of pre-and postcursors are indicating a thickness of about 13 km for this ultra-low velocity region (ULVZ). However, our modelling also reveals highly ambiguous amplitude variations of PcP and a reflection off the top of the anomaly for various ULVZs and topography models. Accordingly, large velocity contrasts of up to -10% in VP and -20% in VS cannot be excluded. In general, the whole Volga river region shows a complex pattern of PcP amplitudes caused most likely by CMB undulations. Further PcP probes beneath Paris, Kiev and northern Italy indicate likely normal CMB conditions, whereas the samples below Finland and the Hungary-Slovakia border yield strongly amplified PcP signals suggesting strong CMB topography effects. We evaluate the amplitude behaviour of PcP as a function of distance and several ULVZ models using the 1D reflectivity and the 2D Gauss beam method. The influence of the velocity and density perturbations is analysed as well as the anomaly thickness, the dominant period of the source wavelet and interface topographies. Strong variation of the PcP amplitude are obtained as a function of distance and of the impedance contrast. We also consider two types of topographies: undulations atop the CMB in the presence of flat ULVZs and vice versa. Where a broad range of CMB topography dimensions lead to large PcP

  4. Evaluation of dissipation mechanisms by Lolium perenne L, and Raphanus sativus for pentachlorophenol (PCP) in copper co-contaminated soil.

    PubMed

    Lin, Qi; Wang, Zhaowei; Ma, Song; Chen, Yingxu

    2006-09-15

    Though phytoremediation is widely studied in remediation of metal contaminated soils or organic contaminated soils, little information is available regarding the effectiveness and processes of phytoremediation of sites co-contaminated with organic and metal pollutants. Sites co-contaminated with organic and metal pollutants are common and considered to be a more complex problem as the two components often cause a synergistic effect on cytotoxicity as measured both by growth inhibition and colony-forming ability. In this paper, the dissipation mechanisms for pentachlorophenol (PCP) in copper co-contaminated soil by Lolium perenne L, and Raphanus sativus was investigated in a greenhouse experiment by monitoring the growth response of plants, evaluating the removal efficiency of extractable PCP, differentiating PCP residuals in strongly and loosely adhering rhizosphere soils, and analyzing the microbial activity in the rhizosphere. In copper co-contaminated soil with the initial PCP concentration of 50 mg/kg, plants grew better with the increment of soil Cu level (0, 150, 300 mg/kg), which implied that combinations of inorganic and organic pollutants sometimes exerted antagonistic effects on plant cytotoxicity. The observed higher PCP dissipation in soil spiked with 50 mg/kg PCP in the presence of Cu and the less difference of PCP residual between strongly and loosely adhering soils further suggests the occurrence of Cu-PCP interaction and the enhanced degradation and mass flow are two possible explanations. In copper co-contaminated soil with the initial PCP concentration of 100 mg/kg, however, both plant growth and microbial activity were inhibited with the increment of soil Cu level. The lowered degrading activity of microorganisms and the reduced mass flow were probably responsible for the significantly lower levels of PCP dissipation in copper co-contaminated soil. These results showed that remediation of sites co-contaminated with organic and metal pollutants is

  5. Treatment technologies used for the removal of As, Cr, Cu, PCP and/or PCDD/F from contaminated soil: A review.

    PubMed

    Guemiza, Karima; Coudert, Lucie; Metahni, Sabrine; Mercier, Guy; Besner, Simon; Blais, Jean-François

    2017-07-05

    The contamination of soils by metals such as arsenic, chromium, copper and organic compounds such as pentachlorophenol (PCP) and dioxins and furans (PCDD/F) is a major problem in industrialized countries. Excavation followed by disposal in an appropriate landfilling is usually used site to manage these contaminated soils. Many researches have been conducted to develop physical, biological, thermal and chemical methods to allow the rehabilitation of contaminated sites. Thermal treatments including thermal desorption seemed to be the most appropriate methods, allowing the removal of more than 99.99% of organic contaminants but, they are ineffective for inorganic compounds. Biological treatments have been developed to remove inorganic and hydrophobic organic contaminants but their applications are limited to soils contaminated by easily biodegradable organic compounds. Among the physical technologies available, attrition is the most commonly used technique for the rehabilitation of soils contaminated by both organic and inorganic contaminants. Chemical processes using acids, bases, redox agents and surfactants seemed to be an interesting option to simultaneously extract organic and inorganic contaminants from soils. This paper will provide an overview of the recent developments in the field of decontamination technologies applicable for the removal of As, Cr, Cu, PCP and/or PCDD/F from contaminated soils. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP

    PubMed Central

    Wang, Ying; Naturale, Victor F.; Adler, Paul N.

    2017-01-01

    The Planar cell Polarity Effector (PPE) genes inturned, fuzzy, and fritz are downstream components in the frizzled/starry night signaling pathway, and their function is instructed by upstream Planar Cell Polarity (PCP) core genes such as frizzled and dishevelled. PPE proteins accumulate asymmetrically in wing cells and function in a protein complex mediated by direct interactions between In and Frtz and In and Fy. How the PCP proteins instruct the accumulation of PPE protein is unknown. We found a likely direct interaction between Dishevelled and Fritz and Dishevelled and Fuzzy that could play a role in this. We previously found that mild overexpression of frtz rescued a weak in allele. To determine if this was due to extra Frtz stabilizing mutant In or due to Frtz being able to bypass the need for In we generate a precise deletion of the inturned gene (inPD). We found that mild overexpression of Fritz partially rescued inPD, indicating that fritz has In independent activity in PCP. Previous studies of PPE proteins used fixed tissues, and did not provide any insights into the dynamic properties of PPE proteins. We used CRISPR/Cas9 genome editing technology to edit the fritz gene to add a green fluorescent protein tag. fritzmNeonGreen provides complete rescue activity and works well for in vivo imaging. Our data showed that Fritz is very dynamic in epidermal cells and preferentially distributed to discrete membrane subdomains (“puncta”). Surprisingly, we found it in stripes in developing bristles. PMID:28258110

  7. Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP.

    PubMed

    Wang, Ying; Naturale, Victor F; Adler, Paul N

    2017-04-03

    The Planar cell Polarity Effector (PPE) genes inturned, fuzzy, and fritz are downstream components in the frizzled/starry night signaling pathway, and their function is instructed by upstream Planar Cell Polarity (PCP) core genes such as frizzled and dishevelled PPE proteins accumulate asymmetrically in wing cells and function in a protein complex mediated by direct interactions between In and Frtz and In and Fy. How the PCP proteins instruct the accumulation of PPE protein is unknown. We found a likely direct interaction between Dishevelled and Fritz and Dishevelled and Fuzzy that could play a role in this. We previously found that mild overexpression of frtz rescued a weak in allele. To determine if this was due to extra Frtz stabilizing mutant In or due to Frtz being able to bypass the need for In we generate a precise deletion of the inturned gene (in(PD) ). We found that mild overexpression of Fritz partially rescued in(PD) , indicating that fritz has In independent activity in PCP. Previous studies of PPE proteins used fixed tissues, and did not provide any insights into the dynamic properties of PPE proteins. We used CRISPR/Cas9 genome editing technology to edit the fritz gene to add a green fluorescent protein tag. fritz(m)(NeonGreen) provides complete rescue activity and works well for in vivo imaging. Our data showed that Fritz is very dynamic in epidermal cells and preferentially distributed to discrete membrane subdomains ("puncta"). Surprisingly, we found it in stripes in developing bristles. Copyright © 2017 Wang et al.

  8. A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP.

    PubMed

    Johansson, Anna; Lindstedt, Daniel; Roman, Markus; Thelander, Gunilla; Nielsen, Elisabet I; Lennborn, Ulrica; Sandler, Håkan; Rubertsson, Sten; Ahlner, Johan; Kronstrand, Robert; Kugelberg, Fredrik C

    2017-06-01

    3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016. The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse. 3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry. In the clinical case, the concentration of 3-MeO-PCP was 0.14μg/g at admission, 0.08μg/g 2.5h after admission, 0.06μg/g 5h after admission and 0.04μg/g 17h after admission. The half-life of 3-MeO-PCP was estimated to 11h. In the autopsy cases, femoral blood concentrations ranged from 0.05μg/g to 0.38μg/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well. Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Core mantle boundary topography from short period PcP, PKP, and PKKP data

    NASA Astrophysics Data System (ADS)

    Sze, Edmond K. M.; van der Hilst, Robert D.

    2003-01-01

    We use a total of 839,369 PcP, PKPab, PKPbc, PKPdf, PKKPab, and PKKPbc residual travel times from [Bull. Seism. Soc. Am. 88 (1998) 722] grouped in 29,837 summary rays to constrain lateral variation in the depth to the core-mantle boundary (CMB). We assumed a homogeneous outer core, and the data were corrected for mantle structure and inner-core anisotropy. Inversions of separate data sets yield amplitude variations of up to 5 km for PcP, PKPab, PKPbc, and PKKP and 13 km for PKPdf. This is larger than the CMB undulations inferred in geodetic studies and, moreover, the PcP results are not readily consistent with the inferences from PKP and PKKP. Although the source-receiver ambiguity for the core-refracted phases can explain some of it, this discrepancy suggest that the travel-time residuals cannot be explained by topography alone. The wavespeed perturbations in the tomographic model used for the mantle corrections might be too small to fully account for the trade off between volumetric heterogeneity and CMB topography. In a second experiment we therefore re-applied corrections for mantle structure outside a basal 290 km-thick layer and inverted all data jointly for both CMB topography and volumetric heterogeneity within this layer. The resultant CMB model can explain PcP, PKP, and PKKP residuals and has approximately 0.2 km excess core ellipticity, which is in good agreement with inferences from free core nutation observations. Joint inversion yields a peak-to-peak amplitude of CMB topography of about 3 km, and the inversion yields velocity variations of ±5% in the basal layer. The latter suggests a strong trade-off between topography and volumetric heterogeneity, but uncertainty analyses suggest that the variation in core radius can be resolved. The spherical averages of all inverted topographic models suggest that the data are best fit if the actual CMB radius is 1.5 km less than in the Earth reference model used (i.e. the average outer core radius would be 3478

  10. Effect of phosphorus addition on the reductive transformation of pentachlorophenol (PCP) and iron reduction with microorganism involvement.

    PubMed

    Wang, Yongkui; Liu, Xianli; Huang, Jiexun; Xiao, Wensheng; Zhang, Jiaquan; Yin, Chunqin

    2017-04-25

    The transformation of phosphorus added to the soil environment has been proven to be influenced by the Fe biochemical process, which thereby may affect the transformation of organic chlorinated contaminants. However, the amount of related literatures regarding this topic is limited. This study aimed to determine the effects of phosphorus addition on pentachlorophenol (PCP) anaerobic transformation, iron reduction, and paddy soil microbial community structure. Results showed that the transformation of phosphorus, iron, and PCP were closely related to the microorganisms. Moreover, phosphorus addition significantly influenced PCP transformation and iron reduction, which promoted and inhibited these processes at low and high concentrations, respectively. Both the maximum reaction rate of PCP transformation and the maximum Fe(II) amount produced were obtained at 1 mmol/L phosphorus concentration. Among the various phosphorus species, dissolved P and NaOH-P considerably changed, whereas only slight changes were observed for the remaining phosphorus species. Microbial community structure analysis demonstrated that adding low concentration of phosphorus promoted the growth of Clostridium bowmanii, Clostridium hungatei, and Clostridium intestinale and Pseudomonas veronii. By contrast, high-concentration phosphorus inhibited growth of these microorganisms, similar to the curves of PCP transformation and iron reduction. These observations indicated that Clostridium and P. veronii, especially Clostridium, played a vital role in the transformation of related substances in the system. All these findings may serve as a reference for the complicated reactions among the multiple components of soils.

  11. Frizzled-Induced Van Gogh Phosphorylation by CK1ε Promotes Asymmetric Localization of Core PCP Factors in Drosophila.

    PubMed

    Kelly, Lindsay K; Wu, Jun; Yanfeng, Wang A; Mlodzik, Marek

    2016-07-12

    Epithelial tissues are polarized along two axes. In addition to apical-basal polarity, they are often polarized within the plane of the epithelium, so-called Planar Cell Polarity (PCP). PCP depends upon Wnt/Frizzled (Fz) signaling factors, including Fz itself and Van Gogh (Vang/Vangl). We sought to understand how Vang interaction with other core PCP factors affects Vang function. We find that Fz induces Vang phosphorylation in a cell-autonomous manner. Vang phosphorylation occurs on conserved N-terminal serine/threonine residues, is mediated by CK1ε/Dco, and is critical for polarized membrane localization of Vang and other PCP proteins. This regulatory mechanism does not require Fz signaling through Dishevelled and thus represents a cell-autonomous upstream interaction between Fz and Vang. Furthermore, this signaling event appears to be related to Wnt5a-mediated Vangl2 phosphorylation during mouse limb patterning and may thus be a general mechanism underlying Wnt-regulated PCP establishment. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. IFT88 plays a cilia- and PCP-independent role in controlling oriented cell divisions during vertebrate embryonic development.

    PubMed

    Borovina, Antonia; Ciruna, Brian

    2013-10-17

    The role for cilia in establishing planar cell polarity (PCP) is contentious. Although knockdown of genes known to function in ciliogenesis has been reported to cause PCP-related morphogenesis defects in zebrafish, genetic mutations affecting intraflagellar transport (IFT) do not show PCP phenotypes despite the requirement for IFT in cilia formation. This discrepancy has been attributed to off-target effects of antisense morpholino oligonucleotide (MO) injection, confounding maternal effects in zygotic mutant embryos, or an inability to distinguish between cilia-dependent versus cilia-independent protein functions. To determine the role of cilia in PCP, we generated maternal + zygotic IFT88 (MZift88) mutant zebrafish embryos, which never form cilia. We clearly demonstrate that cilia are not required to establish PCP. Rather, IFT88 plays a cilia-independent role in controlling oriented cell divisions at gastrulation and neurulation. Our results have important implications for the interpretation of cilia gene function in normal development and in disease. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Structural characterization of 2,6-dichloro-p-hydroquinone 1,2-dioxygenase (PcpA) from Sphingobium chlorophenolicum, a new type of aromatic ring-cleavage enzyme

    PubMed Central

    Hayes, Robert P.; Green, Abigail R.; Nissen, Mark S.; Lewis, Kevin M.; Xun, Luying; Kang, ChulHee

    2014-01-01

    Summary PcpA (2,6-dichloro-p-hydroquinone 1,2-dioxygenase) from Sphingobium chlorophenolicum, a non-haem Fe(II) dioxygenase capable of cleaving the aromatic ring of p-hydroquinone and its substituted variants, is a member of the recently discovered p-hydroquinone 1,2-dioxygenases. Here we report the 2.6 Å structure of PcpA, which consists of four βαβββ motifs, a hallmark of the vicinal oxygen chelate superfamily. The secondary co-ordination sphere of the Fe(II) centre forms an extensive hydrogen-bonding network with three solvent exposed residues, linking the catalytic Fe(II) to solvent. A tight hydrophobic pocket provides p-hydroquinones access to the Fe(II) centre. The p-hydroxyl group is essential for the substrate-binding, thus phenols and catechols, lacking a p-hydroxyl group, do not bind to PcpA. Site-directed mutagenesis and kinetic analysis confirm the critical catalytic role played by the highly conserved His10, Thr13, His226 and Arg259. Based on these results, we propose a general reaction mechanism for p-hydroquinone 1,2-dioxygenases. PMID:23489289

  14. Wood treating sites: Analysis of PCP and creosote using on-site mobile high hazard laboratory. Fact sheet

    SciTech Connect

    Not Available

    1992-12-01

    Laboratory Gas Chromatography/Mass Spectrometry (GC/MS) methods are normally employed to determine pentachlorophenol (PCP) and creosote contaminant levels in soil samples from hazardous waste sites. Laboratory GC/MS methods can be modified for field (on-site) use to provide timely results while maintaining high data quality. The U.S. Environmental Protection Agency's Environmental Response Team (U.S. EPA/ERT), through its Response Engineering and Analytical Contract (REAC), has developed field GC/MS methods to provide timely, reliable, and cost-effective PCP and creosote analyses needed by site managers to guide remediation and removal activities.

  15. PCP METHODOLOGY FOR DETERMINING DOSE RATES FOR SMALL GRAM QUANTITIES IN SHIPPING PACKAGINGS

    SciTech Connect

    Nathan, S.

    2011-08-23

    The Small Gram Quantity (SGQ) concept is based on the understanding that small amounts of hazardous materials, in this case radioactive materials, are significantly less hazardous than large amounts of the same materials. This study describes a methodology designed to estimate an SGQ for several neutron and gamma emitting isotopes that can be shipped in a package compliant with 10 CFR Part 71 external radiation level limits regulations. These regulations require packaging for the shipment of radioactive materials perform, under both normal and accident conditions, the essential functions of material containment, subcriticality, and maintain external radiation levels within regulatory limits. 10 CFR 71.33(b)(1)(2)&(3) state radioactive and fissile materials must be identified and their maximum quantity, chemical and physical forms be included in an application. Furthermore, the U.S. Federal Regulations require application contain an evaluation demonstrating the package (i.e., the packaging and its contents) satisfies the external radiation standards for all packages (10 CFR 71.31(2), 71.35(a), & 71.47). By placing the contents in a He leak-tight containment vessel, and limiting the mass to ensure subcriticality, the first two essential functions are readily met. Some isotopes emit sufficiently strong photon radiation that small amounts of material can yield a large external dose rate. Quantifying of the dose rate for a proposed content is a challenging issue for the SGQ approach. It is essential to quantify external radiation levels from several common gamma and neutron sources that can be safely placed in a specific packaging, to ensure compliance with federal regulations. The Packaging Certification Program (PCP) Methodology for Determining Dose Rate for Small Gram Quantities in Shipping Packagings described in this report provides bounding mass limits for a set of proposed SGQ isotopes. Methodology calculations were performed to estimate external radiation levels

  16. PcpA promotes higher levels of infection and modulates recruitment of myeloid-derived suppressor cells during pneumococcal pneumonia.1

    PubMed Central

    Walker, Melissa M.; Novak, Lea; Widener, Rebecca; Grubbs, James Aaron; King, Janice; Hale, Joanetha Y.; Ochs, Martina M.; Myers, Lisa E.; Briles, David E.; Deshane, Jessy

    2016-01-01

    We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, BAL and spleens of mice at 24-hrs post infection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12-hrs) in the focal-pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TNF-related apoptosis - inducing ligand (TRAIL) and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells (MDSCs). The latter have been shown to facilitate clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia. PMID:26829988

  17. Synthesis and Reactivity of Four- and Five-Coordinate Low-Spin Cobalt(II) PCP Pincer Complexes and Some Nickel(II) Analogues.

    PubMed

    Murugesan, Sathiyamoorthy; Stöger, Berthold; Carvalho, Maria Deus; Ferreira, Liliana P; Pittenauer, Ernst; Allmaier, Günter; Veiros, Luis F; Kirchner, Karl

    2014-11-10

    Anhydrous CoCl2 or [NiCl2(DME)] reacts with the ligand PCP(Me)-iPr (1) in the presence of nBuLi to afford the 15e and 16e square planar complexes [Co(PCP(Me)-iPr)Cl] (2) and [Ni(PCP(Me)-iPr)Cl] (3), respectively. Complex 2 is a paramagnetic d(7) low-spin complex, which is a useful precursor for a series of Co(I), Co(II), and Co(III) PCP complexes. Complex 2 reacts readily with CO and pyridine to afford the five-coordinate square-pyramidal 17e complexes [Co(PCP(Me)-iPr)(CO)Cl] (4) and [Co(PCP(Me)-iPr)(py)Cl] (5), respectively, while in the presence of Ag(+) and CO the cationic complex [Co(PCP(Me)-iPr)(CO)2](+) (6) is afforded. The effective magnetic moments μeff of all Co(II) complexes were derived from the temperature dependence of the inverse molar magnetic susceptibility by SQUID measurements and are in the range 1.9 to 2.4 μB. This is consistent with a d(7) low-spin configuration with some degree of spin-orbit coupling. Oxidation of 2 with CuCl2 affords the paramagnetic Co(III) PCP complex [Co(PCP(Me)-iPr)Cl2] (7), while the synthesis of the diamagnetic Co(I) complex [Co(PCP(Me)-iPr)(CO)2] (8) was achieved by stirring 2 in toluene with KC8 in the presence of CO. Finally, the cationic 16e Ni(II) PCP complex [Ni(PCP(Me)-iPr)(CO)](+) (10) was obtained by reacting complex 3 with 1 equiv of AgSbF6 in the presence of CO. The reactivity of CO addition to Co(I), Co(II), and Ni(II) PCP square planar complexes of the type [M(PCP(Me)-iPr)(CO)] (n) (n = +1, 0) was investigated by DFT calculations, showing that formation of the Co species, 6 and 8, is thermodynamically favorable, while Ni(II) maintains the 16e configuration since CO addition is unfavorable in this case. X-ray structures of most complexes are provided and discussed. A structural feature of interest is that the apical CO ligand in 4 deviates significantly from linearity, with a Co-C-O angle of 170.0(1)°. The DFT-calculated value is 172°, clearly showing that this is not a packing but an electronic effect.

  18. Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.

    PubMed

    Cui, Cheng; Chatterjee, Bishwanath; Lozito, Thomas P; Zhang, Zhen; Francis, Richard J; Yagi, Hisato; Swanhart, Lisa M; Sanker, Subramaniam; Francis, Deanne; Yu, Qing; San Agustin, Jovenal T; Puligilla, Chandrakala; Chatterjee, Tania; Tansey, Terry; Liu, Xiaoqin; Kelley, Matthew W; Spiliotis, Elias T; Kwiatkowski, Adam V; Tuan, Rocky; Pazour, Gregory J; Hukriede, Neil A; Lo, Cecilia W

    2013-11-01

    Planar cell polarity (PCP) regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin cytoskeleton to

  19. Wdpcp, a PCP Protein Required for Ciliogenesis, Regulates Directional Cell Migration and Cell Polarity by Direct Modulation of the Actin Cytoskeleton

    PubMed Central

    Cui, Cheng; Chatterjee, Bishwanath; Lozito, Thomas P.; Zhang, Zhen; Francis, Richard J.; Yagi, Hisato; Swanhart, Lisa M.; Sanker, Subramaniam; Francis, Deanne; Yu, Qing; San Agustin, Jovenal T.; Puligilla, Chandrakala; Chatterjee, Tania; Tansey, Terry; Liu, Xiaoqin; Kelley, Matthew W.; Spiliotis, Elias T.; Kwiatkowski, Adam V.; Tuan, Rocky; Pazour, Gregory J.; Hukriede, Neil A.; Lo, Cecilia W.

    2013-01-01

    Planar cell polarity (PCP) regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet–Biedl/Meckel–Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin cytoskeleton to

  20. Refractory acute respiratory failure due to Pneumocystis jiroveci (PCP) and Cytomegalovirus (CMV) pneumonitis: A case report and review of literature.

    PubMed

    Shah, Kairav; Cherabuddi, Kartikeya; Beal, Stacy G; Kalyatanda, Gautam

    2017-01-01

    Opportunistic infections with Pneumocystis jiroveci pneumonia (PCP) are common in patients with HIV (human immunodeficiency virus) and are encountered once the CD4 count decreases below 200 cells/mm3. Cytomegalovirus (CMV) tends to cause disease once the CD4 count drops below 50 cells/mm3. CMV pneumonitis is not common in this population. However, detecting its presence in broncho-alveolar lavage (BAL) fluid has been associated with increased morbidity and mortality. The role of antiviral therapy against CMV remains unclear. We report a newly diagnosed HIV patient with a CD4 count of 44 cells/mm3 presenting with acute respiratory failure secondary to PCP that failed to respond to 3 weeks of standard therapy with trimethoprim-sulfamethoxazole and corticosteroids. He was later diagnosed to have a CMV co-infection causing pneumonitis with BAL cytology findings showing CMV cytopathic effects and PCP. Plasma CMV DNA PCR was 17,424 copies/mL. He responded well after introduction of intravenous ganciclovir. The presence of histopathologic changes demonstrating viral cytopathic effects on BAL cytology along with a high plasma CMV DNA PCR should raise the specificity for diagnosing CMV pneumonitis. True PCP and CMV pneumonitis can occur, and the addition of antiviral therapy with ganciclovir may benefit such patients in the right clinical scenario.

  1. The Use of Fry (Embalming Fluid and PCP-Laced Cigarettes or Marijuana Sticks) among Crack Cocaine Smokers

    ERIC Educational Resources Information Center

    Peters, Ronald J.; Williams, Mark; Ross, Michael W.; Atkinson, John; McCurdy, Sherly A.

    2009-01-01

    Statistics show that the prevalence of crack cocaine use and embalming fluid and phencyclidine (PCP)-laced cigarettes or marijuana sticks, commonly referred to on the street as "fry" or "wet" is a problem; however, the relationship between these substances of abuse and concurrent polydrug use is unknown. In the present study, a…

  2. The Use of Fry (Embalming Fluid and PCP-Laced Cigarettes or Marijuana Sticks) among Crack Cocaine Smokers

    ERIC Educational Resources Information Center

    Peters, Ronald J.; Williams, Mark; Ross, Michael W.; Atkinson, John; McCurdy, Sherly A.

    2009-01-01

    Statistics show that the prevalence of crack cocaine use and embalming fluid and phencyclidine (PCP)-laced cigarettes or marijuana sticks, commonly referred to on the street as "fry" or "wet" is a problem; however, the relationship between these substances of abuse and concurrent polydrug use is unknown. In the present study, a…

  3. Increased PCP removal by Amylomyces rouxii transformants with heterologous Phanerochaete chrysosporium peroxidases supplementing their natural degradative pathway.

    PubMed

    Montiel-González, A M; Fernández, F J; Keer, N; Tomasini, A

    2009-08-01

    Fungal peroxidases and phenoloxidases are widely used in aromatic toxic compounds degradation. Peroxidases, such as lignin peroxidase and manganese peroxidase, as well as laccases are mainly produced by basidiomycetes and to a lower extent by other fungi, such as ascomycetes. Peroxidase-encoding genes have been described and homologous expression has been achieved in basidiomycetes. Heterologous expression has also been achieved in some non-producing peroxidase ascomycetes, like Penicillium and Aspergillus. In this work, heterologous expression of peroxidase-encoding genes, lignin peroxidase, and manganese peroxidase was achieved in a zygomycete producing only phenoloxidases (Amylomyces rouxii), aimed at coupling two different pathways used in nature for PCP removal in only one microbial strain. The ability of PCP removal was assayed with one of the obtained transformants, resulting in increased activity with respect to the ability of the parental strain cultured free of the inducer tyrosine (95% and 45%, respectively, of the initial PCP (12.5 mg L(-1)) in 120 h, or 100% and 49%, respectively, of the initial PCP after 144 h of liquid culture).

  4. A method for reducing the amount of PCP in wood with less detriment to protection against fungi

    NASA Astrophysics Data System (ADS)

    Rabia, Y. Ait; Haloui, A.; Vergnaud, J. M.

    1996-01-01

    Large pieces of wood were immersed in a solution of pentachlorophenol (PCP) in order to introduce this chemical into the wood, the chemical being able to protect the wood against fungi. A method was explored to reduce the cost of the operation by decreasing the amount of PCP and the time of absorption. It consists of creating high gradients of concentration of PCP in the wood with a high concentration on the surface. In order to evaluate the level of protection by the PCP, it is desirable to know the profiles of concentration of this chemical developed through the wood. Experiments were performed either by immersing wood samples in solutions of the chemical over given periods of time or by measuring the amount of chemical introduced in the wood. An analytical solution able to describe the process of absorption, with the diffusion through the anisotropic solid, was used. As a result, the profiles of concentration of the chemical developed throughout the wood sample were obtained. The use of dimensionless numbers makes the results more general, whatever the size of the wood sample.

  5. AMERICAN CREOSOTE SITE CASE STUDY: SOLIDIFICATION/STABILIZATION OF DIOXINS, PCP, AND CREOSOTE FOR $64 PER CUBIC YARD

    EPA Science Inventory

    This case study describes the development of solidification/stabilization (S/S) formulas and their application to rededicate the American Creosote site in Jackson, Tennessee. During 1998 and 1999, 45,000 cubic yards of soil contaminated with Creosote, PCP, and Dioxins were treat...

  6. Enhanced withdrawal from chickens of hexachlorobenzene (HCB) and pentachlorophenol (PCP) by colestipol, mineral oil, and/or restricted feeding

    SciTech Connect

    Polin, D.; Olson, B.; Bursian, S.; Lehning, E.

    1986-01-01

    Young chickens fed hexachlorobenzene (HCB) or pentachlorophenol (PCP) for 14 d at 10 ppm in the diet contained body burdens of 573 or 362 micrograms, respectively. These diets were withdrawn (d 0) and replaced for 21 d with diets containing 5% mineral oil (MO), or 5% colestipol (CO), a bile-acid-binding resin, or the chickens were restricted in feed intake to 50% of controls (50-RF), fed MO plus 50-RF, or CO plus 50-RF. Without any treatment during withdrawal, body burdens were reduced to 63% and 70% of the d 0 values for HCB and PCP, respectively. MO, CO, or 50-RF reduced body burdens of HCB to 37% of d 0 burdens, but the combination treatments with 50-RF reduced body burdens to 19% of d 0 values. PCP was at 35% of the d 0 burdens from 50-RF, while all other treatments had reduced body burdens to nondetectable amounts of less than 0.7 micrograms/bird by d 21 of withdrawal. Body fat was not reduced by mineral oil, but was reduced to some extent by CO, and was markedly reduced by 50-RF. 50-RF always reduced body burdens of PCP or HCB alone or in combination with MO or CO. These data are discussed in relationship to the nonbiliary excretion of xenobiotics.

  7. Cationic PCP iridaepoxide and carbene complexes for facile water elimination and activation processes.

    PubMed

    Doyle, Lauren E; Piers, Warren E; Bi, David W

    2017-03-13

    Iridaepoxide dihydride complexes of a PCP ligand bearing benzo[b]thiophene linkers are synthesized through ligand coopertive N2O and H2 activations. These neutral complexes also eliminate water at elevated temperatures to form the corresponding PCcarbeneP complexes which results in the formal hydrogenation of N2O to water. The synthesis of cationic iridaepoxide dihydride complexes are reported herein where the room temperature elimination of water is observed when a donating solvent is used. This supports a previously proposed mechanism for this water elimination where hydrides cis to the epoxide are required. Ir(i) and Ir(iii) cationic PCcarbeneP complexes are also synthesized through protonation and through O-H oxidation additions of water and phenol.

  8. The role of 5-HT1A receptors in phencyclidine (PCP)-induced novel object recognition (NOR) deficit in rats.

    PubMed

    Horiguchi, M; Meltzer, H Y

    2012-05-01

    Atypical antipsychotic drugs (APDs), many of which are direct or indirect serotonin (5-HT)(1A) agonists, and tandospirone, a 5-HT(1A) partial agonist, have been reported to improve cognition in schizophrenia. We tested the effect of 5-HT(1A) agonism, alone, and in combination with other psychotropic agents, including the atypical APD, lurasidone, in reversing the deficit in novel object recognition (NOR) induced by subchronic treatment with the non-competitive NMDA receptor antagonist, phencyclidine (PCP) (2 mg/kg, b.i.d., for 7 days). Subchronic treatment with PCP induced a persistent NOR deficit. Lurasidone (0.1 mg/kg), a potent 5-HT(1A) partial agonist, 5-HT(2A) antagonist, and weaker D(2) antagonist, tandospirone (0.6 mg/kg), and the selective post-synaptic 5-HT(1A) agonist, F15599 (0.16 mg/kg), ameliorated the subchronic PCP-induced-NOR deficit. The 5-HT(1A) antagonist, WAY100635 (0.6 mg/kg), blocked the ameliorating effects of tandospirone and lurasidone. The combination of sub-effective doses of tandospirone (0.2 mg/kg) and lurasidone (0.03 mg/kg) also reversed the PCP-induced NOR-deficit. Buspirone, a less potent partial 5-HT(1A) agonist than tandospirone, was less effective. Co-administration of tandospirone (0.2 mg/kg) and pimavanserin (3 mg/kg), a relatively selective 5-HT(2A) receptor inverse agonist, did not reverse the effect of sub-chronic PCP on NOR. The D(2) antagonist, haloperidol, blocked the ameliorating effect of tandospirone on the PCP-induced deficit in NOR. These results indicate that 5-HT(1A) agonism is adequate to ameliorate the PCP-induced impairment in NOR and suggest further study of utilizing the combination of a 5-HT(1A) agonist and an atypical APD to ameliorate some types of cognitive impairment in schizophrenia.

  9. The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye

    PubMed Central

    López-Escobar, Beatriz; Cano, David A.; Rojas, Anabel; de Felipe, Beatriz; Palma, Francisco; Sánchez-Alcázar, José A.; Henderson, Deborah; Ybot-González, Patricia

    2015-01-01

    Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1gt/gt and Daam1gt/+ embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1gt/+ mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos. PMID:25540130

  10. The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye.

    PubMed

    López-Escobar, Beatriz; Cano, David A; Rojas, Anabel; de Felipe, Beatriz; Palma, Francisco; Sánchez-Alcázar, José A; Henderson, Deborah; Ybot-González, Patricia

    2015-02-01

    Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1(gt/gt) and Daam1(gt/+) embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1(gt/+) mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos. © 2015. Published by The Company of Biologists Ltd.

  11. Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: possible involvement of the endocannabinoid system

    PubMed Central

    Seillier, Alexandre; Giuffrida, Andrea

    2015-01-01

    Previous studies have shown that social withdrawal in the phencyclidine (PCP) rat model of schizophrenia results from deficient endocannabinoid-induced activation of CB1 receptors. To understand the underlying cognitive mechanisms of the social deficit in PCP-treated rats, we examined the impact of pharmacological manipulation of the endocannabinoid system on sociability (i.e. social approach) and social novelty preference (which relies on social recognition). Control rats showed a clear preference for a “social” cage (i.e. unfamiliar stimulus rat placed under a wire mesh cage) versus an “empty” cage, and spent more time exploring a “novel” cage (i.e. new stimulus rat) versus a “familiar” cage. In contrast, rats receiving PCP (5 mg/kg, b.i.d. for 7 days, followed by a 7 day-washout period) showed intact sociability, but lacked social novelty preference. This PCP-induced deficit was due to increased activity at CB1 receptors as it was reversed by systemic administration of the CB1 antagonist AM251 (1 mg/kg). In agreement with this hypothesis, the cannabinoid agonist CP55,940 (0.003 – 0.03 mg/kg) dose-dependently suppressed social novelty preference in control animals without affecting sociability. Taken together, these data suggest that PCP-treated rats have a deficit in social cognition, possibly induced by increased stimulation of CB1 receptors. This deficit, however, is distinct from the social withdrawal previously observed in these animals, as the latter is due to deficient, rather than increased, CB1 stimulation. PMID:26706691

  12. Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: Possible involvement of the endocannabinoid system.

    PubMed

    Seillier, Alexandre; Giuffrida, Andrea

    2016-02-01

    Previous studies have shown that social withdrawal in the phencyclidine (PCP) rat model of schizophrenia results from deficient endocannabinoid-induced activation of CB1 receptors. To understand the underlying cognitive mechanisms of the social deficit in PCP-treated rats, we examined the impact of pharmacological manipulation of the endocannabinoid system on sociability (i.e. social approach) and social novelty preference (which relies on social recognition). Control rats showed a clear preference for a "social" cage (i.e. unfamiliar stimulus rat placed under a wire mesh cage) versus an "empty" cage, and spent more time exploring a "novel" cage (i.e. new stimulus rat) versus a "familiar" cage. In contrast, rats receiving PCP (5 mg/kg, b.i.d. for 7 days, followed by a 7 day-washout period) showed intact sociability, but lacked social novelty preference. This PCP-induced deficit was due to increased activity at CB1 receptors as it was reversed by systemic administration of the CB1 antagonist AM251 (1 mg/kg). In agreement with this hypothesis, the cannabinoid agonist CP55,940 (0.003-0.03 mg/kg) dose-dependently suppressed social novelty preference in control animals without affecting sociability. Taken together, these data suggest that PCP-treated rats have a deficit in social cognition, possibly induced by increased stimulation of CB1 receptors. This deficit, however, is distinct from the social withdrawal previously observed in these animals, as the latter is due to deficient, rather than increased, CB1 stimulation.

  13. Distinct neuronal activation patterns are associated with PCP-induced social withdrawal and its reversal by the endocannabinoid-enhancing drug URB597

    PubMed Central

    Matricon, Julien; Seillier, Alexandre; Giuffrida, Andrea

    2016-01-01

    The fatty acid amide hydrolase inhibitor, URB597, an endocannabinoid enhancing drug, reverses social withdrawal in the sub-chronic PCP rat model of schizophrenia, but reduces social interaction (SI) in controls. To identify the anatomical substrates associated with PCP-induced social withdrawal and the contrasting effects of URB597 on SI in PCP- versus saline-treated rats, we analyzed SI-induced c-Fos expression in 28 brain areas relevant to schizophrenia and/or social behavior following vehicle or URB597 administration. In saline-treated rats, SI was accompanied by changes in c-Fos expression in the infralimbic and orbitofrontal cortices, dorsomedial caudate putamen, ventrolateral nucleus of the septum, dorsolateral periaqueductal gray (dlPAG) and central amygdala. Except for the dlPAG, these changes were not observed in PCP-treated rats or in saline-treated rats receiving URB597. In the dorsomedial part of the bed nucleus of the stria terminalis (dmBNST), SI-induced c-Fos expression was observed only in PCP-treated rats. Interestingly, URB597 in PCP-treated rats restored a similar c-Fos expression pattern as observed in saline-treated rats: activation of the orbitofrontal cortex, inhibition of the central amygdala and suppression of activation of the dmBNST. These data suggest that orbitofrontal cortex, central amygdala and dmBNST play a critical role in the reversal of PCP-induced social withdrawal by URB597. PMID:27091613

  14. Chl- a triplet quenching by peridinin in H-PCP and organic solvent revealed by step-scan FTIR time-resolved spectroscopy

    NASA Astrophysics Data System (ADS)

    Bonetti, C.; Alexandre, M. T. A.; Hiller, R. G.; Kennis, J. T. M.; Grondelle, R. van

    2009-02-01

    Triplet-state dynamics in Chl- a/Per mixtures in organic solvent and in native H-PCP were studied by means of step-scan FTIR spectroscopy. A single decay component of 10 μs was observed for the H-PCP triplet, the spectrum of which closely matches the 13 μs component of A-PCP [Alexandre et al., Biophysical Journal 93 (2007) 2118-2128], implying that in H-PCP, as in A-PCP, the peridinin triplet state is shared with Chl- a. In a mixture of Chl- a and Per in THF, TEET from 3Chl- a to 3Per proceeds in 3.5 μs followed by 3Per decay in 7 μs. Using a target analysis procedure, 3Chl- a and 3Per infrared difference spectra were obtained. The specific carbonyl frequencies of 3Per and 3Chl- a in THF confirm our assignment of their co-existence in the infrared spectra of H-PCP and A-PCP.

  15. Hydrothermal alteration of CM carbonaceous chondrites: Implications of the identification of tochilinite as one type of meteoritic PCP

    NASA Technical Reports Server (NTRS)

    Zolensky, M. E.

    1984-01-01

    Poorly characterized phases (PCP's) constitute up to 30 volume percent of some CM carbonaceous chondrites, and are therefore an important key to an understanding of the physico-chemical conditions attending matrix evolution. An iron rich form of the terrestrial phase tochilinite was recently identified as a common type of PCP. Tochilinite has the general formula 6Fe(0.9)S.5(Mg,Fe)(OH)2 and consists of alternating machinawite (FeS) and brucite ((Mg,Fe)(OH)2) sheets, with iron vacancies in the sulfide sheets. In iron rich tochilinite, ferrous hydroxide, called amakinite, replaces brucite. If CM carbonaceous kchondrites have underdone hydrothermal alteration, iron rich tochilinite, at least, probably grew from aqueous solutions characterized by low FO2, high FS2, pH 10 to 12, and at a temperature at or below 170 C.

  16. Differences between adolescents and adults in the acute effects of PCP and ketamine and in sensitization following intermittent administration.

    PubMed

    Rocha, Angelica; Hart, Nigel; Trujillo, Keith A

    2017-06-01

    Adolescence is a phase of development during which many physiological and behavioral changes occur, including increased novelty seeking and risk taking. In humans, this is reflected in experimentation with drugs. Research demonstrates that drug use that begins during adolescence is more likely to lead to addiction than drug use that begins later in life. Despite this, relatively little is known of the effects of drugs in adolescence, and differences in response between adolescents and adults. PCP and ketamine are popular club drugs, both possessing rewarding properties that could lead to escalating use. Drug sensitization (or reverse tolerance), which refers to an increase in an effect of a drug following repeated use, has been linked with the development of drug cravings that is a hallmark of addiction. The current work investigated the acute response and the development of sensitization to PCP and ketamine in adolescent and adult rats. Periadolescent Sprague-Dawley rats (30days or 38days of age), and young adults (60days of age) received PCP (6mg/kg IP) or ketamine (20mg/kg IP) once every three days, for a total of five drug injections. Adolescents and adults showed a stimulant response to the first injection of either drug, however the response was considerably greater in the youngest adolescents and lowest in the adults. With repeated administration, adults showed a robust escalation in activity that was indicative of the development of sensitization. Adolescents showed a flatter trajectory, with similar high levels of activity following an acute treatment and after five drug treatments. The results demonstrate important distinctions between adolescents and adults in the acute and repeated effects of PCP and ketamine. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The change of organic matter in sewage sludge composting and its influence on the adsorption of pentachlorophenol (PCP).

    PubMed

    Liping, Lou; Defu, Liu; Huanyu, Chen; Fang, Chen; Yunfeng, He; Guangming, Tian

    2015-04-01

    Due to the abundance of organic matter in compost, the addition of compost to soil can promote the adsorption of pesticides. However, few studies have examined the influence of the composting duration on the organic matter (OM) transformation and adsorption capacity of the compost. In this study, a mixture of sewage sludge and straw was composted, and then the physicochemical properties of various OM were studied. Additionally, the sorption capacities of humic acid (HA), humin (HM), humic acid + humin, and fulvic acid (FA) + humic acid + humin extracted from composts of different stages toward pentachlorophenol (PCP) were compared. The sorption data can be well-described by the Freundlich model, and the sorption capacity of PCP on HM is the strongest of all organic components. After 120 days of composting, the sorption abilities of HA and HM increased by 54.76 and 36.73%, respectively, which corresponds with increases in the aromatization degree, BET specific area, and pore volume and with a decrease in acid functional groups. The sorption ability of HA and HM increased by 54.76 and 36.73% due to the increase of the aromatization degree. However, the sorption capacity of the compost decreased by 51.2%, which resulted from a decrease in total organic matter content and from the interaction between organic components in composts. This could be verified by the sequence of the sorption capacity: HM > HM + HA > HM + HA + FA > HA. The contribution of humus to the sorption of PCP onto compost is approximately 41 to 55%, and it increases with composting time. Therefore, it is possible that other components are present that affect the adsorption of PCP on composts.

  18. Disruption of PCP signaling causes limb morphogenesis and skeletal defects and may underlie Robinow syndrome and brachydactyly type B.

    PubMed

    Wang, Bing; Sinha, Tanvi; Jiao, Kai; Serra, Rosa; Wang, Jianbo

    2011-01-15

    Brachydactyly type B (BDB1) and Robinow syndrome (RRS) are two skeletal disorders caused by mutations in ROR2, a co-receptor of Wnt5a. Wnt5a/Ror2 can activate multiple branches of non-canonical Wnt signaling, but it is unclear which branch(es) mediates Wnt5a/Ror2 function in limb skeletal development. Here, we provide evidence implicating the planar cell polarity (PCP) pathway as the downstream component of Wnt5a in the limb. We show that a mutation in the mouse PCP gene Vangl2 causes digit defects resembling the clinical phenotypes in BDB1, including loss of phalanges. Halving the dosage of Wnt5a in Vangl2 mutants enhances the severity and penetrance of the digit defects and causes long bone defects reminiscent of RRS, suggesting that Wnt5a and Vangl2 function in the same pathway and disruption of PCP signaling may underlie both BDB1 and RRS. Consistent with a role for PCP signaling in tissue morphogenesis, mutation of Vangl2 alters the shape and dimensions of early limb buds: the width and thickness are increased, whereas the length is decreased. The digit pre-chondrogenic condensates also become wider, thicker and shorter. Interestingly, altered limb bud dimensions in Vangl2 mutants also affect limb growth by perturbing the signaling network that regulates the balance between Fgf and Bmp signaling. Halving the dosage of Bmp4 partially suppresses the loss of phalanges in Vangl2 mutants, supporting the hypothesis that an aberrant increase in Bmp signaling is the cause of the brachydactyly defect. These findings provide novel insight into the signaling mechanisms of Wnt5a/Ror2 and the pathogenesis in BDB1 and RRS.

  19. Sensitivity study of an OCDD environmental fate screening model in soils in the presence of PCP wood-preserving oil.

    PubMed

    Bulle, Cécile; Bertrand, François; Samson, Réjean; Deschênes, Louise

    2008-08-01

    In order to better understand the fate of polychloro dibenzo-p-dioxins and furans (PCDD/Fs) in soils around pentachlorophenol (PCP) treated poles, a model was developed to assess the influence of wood-preserving oil and PCP on the vertical migration of octachloro-dibenzo-p-dioxin (OCDD). Simulations were performed for three soil types: sand, clay and organic. OCDD fate was modeled in the absence of co-contaminant and in the presence of oil with or without 5% (w/w) PCP. A variance propagation study was conducted to evaluate the model sensitivity to a small variation in input parameters, to determine the uncertainty on the migration depth modeled for each soil, and to understand the variability of this migration observed between different soil types. The model predicts a different OCDD fate depending on the soil type with a significant migration in the case of sand and an absence of migration in the case of organic soil. No migration is predicted in the absence of co-contaminants and a migration depth of 7-600 cm is predicted in the presence of oil (with and without PCP). Model sensitivity also depends on the soil type: the predicted OCDD migration depth is, respectively, 22 cm+/-10 cm for organic soils, 71 cm+/-20 cm for clay and 566 cm+/-200 cm for sand after 60 days of emissions from a class 3, 12.2m long pole. Even if the input parameters have a significant uncertainty due to the lack of available data, the model results seem reliable as a first approximation to screen an eventual PCDD/F migration.

  20. Acute toxicity of chromate, DDT, PCP, TPBS, and zinc to Daphnia magna cultured in hard and soft water

    SciTech Connect

    Berglind, R.; Dave, G.

    1984-07-01

    The aim of this study was to compare the toxicity of five chemicals to water fleas (Daphnia magna) cultured in either hard to soft water. The toxicity tests were made in reconstituted waters and the five chemicals to be tested were, p,p'-DDT, pentachlorophenol (PCP), tetrapropylenbenzyl sulfonate (TPBS), potassium bichromate (K/sub 2/Cr/sub 2/O/sub 7/) and zincsulfate (ZnSO/sub 4/ x 7H/sub 2/O).

  1. AEG-1 activates Wnt/PCP signaling to promote metastasis in tongue squamous cell carcinoma.

    PubMed

    Pan, Yunping; Guo, Xu; Yang, Zheng; Chen, Shan; Lei, Yiyan; Lin, Millicent; Wang, Liantang; Feng, Chongjin; Ke, Zunfu

    2016-01-12

    Despite advances in therapy, survival among patients with locally advanced squamous cell carcinoma of tongue (TSCC) and cervical lymph node metastasis remains dismal. Here, we estimated the functional effect of AEG-1 on TSCC metastasis and explored the molecular mechanism by which AEG-1 stimulates epithelial-mesenchymal transition (EMT). We initially found that AEG-1 mRNA levels were much higher in metastatic TSCC than in non-metastatic TSCC and that AEG-1 expression strongly correlates with EMT status. Receiver operating characteristic analysis showed that the combined AEG-1 and EMT statuses are predictive of the survival rate among TSCC patients. In addition, AEG-1 knockdown inhibited EMT in cultured TSCC cell lines and in a xenograft-mouse model. Recombinant AEG-1 activated Wnt/PCP-Rho signaling, and its stimulatory effects on TSCC cell invasiveness and EMT were reversed by an anti-Wnt5a neutralizing antibody or by inhibition of Rac1 or ROCK. These results highlight the critical stimulatory effect of AEG-1 on cancer cell invasiveness and EMT and indicate that AEG-1 may be a useful prognostic biomarker for TSCC patients.

  2. THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

    PubMed

    Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

    2016-02-01

    Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach.

  3. PLD1 regulates Xenopus convergent extension movements by mediating Frizzled7 endocytosis for Wnt/PCP signal activation.

    PubMed

    Lee, Hyeyoon; Lee, Seung Joon; Kim, Gun-Hwa; Yeo, Inchul; Han, Jin-Kwan

    2016-03-01

    Phospholipase D (PLD) is involved in the regulation of receptor-associated signaling, cell movement, cell adhesion and endocytosis. However, its physiological role in vertebrate development remains poorly understood. In this study, we show that PLD1 is required for the convergent extension (CE) movements during Xenopus gastrulation by activating Wnt/PCP signaling. Xenopus PLD1 protein is specifically enriched in the dorsal region of Xenopus gastrula embryo and loss or gain-of-function of PLD1 induce defects in gastrulation and CE movements. These defective phenotypes are due to impaired regulation of Wnt/PCP signaling pathway. Biochemical and imaging analysis using Xenopus tissues reveal that PLD1 is required for Fz7 receptor endocytosis upon Wnt11 stimulation. Moreover, we show that Fz7 endocytosis depends on dynamin and regulation of GAP activity of dynamin by PLD1 via its PX domain is crucial for this process. Taken together, our results suggest that PLD1 acts as a new positive mediator of Wnt/PCP signaling by promoting Wnt11-induced Fz7 endocytosis for precise regulation of Xenopus CE movements.

  4. Exposures to the environmental toxicants pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) modify secretion of interleukin 1-beta (IL-1β) from human immune cells.

    PubMed

    Martin, Tamara J; Whalen, Margaret M

    2017-04-01

    Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) are environmental contaminants found in human blood. Previous studies have shown that PCP and DDT inhibit the lytic function of highly purified human natural killer (NK) lymphocytes and decrease the expression of several surface proteins on NK cells. Interleukin-1 βeta (IL-1β) is a cytokine produced by lymphocytes and monocytes, and anything that elevates its levels inappropriately can lead to chronic inflammation, which among other consequences can increase tumor development and invasiveness. Here, PCP and DDT were examined for their ability to alter secretion of IL-1β from immune cell preparations of various complexity: NK cells; monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCS); and PBMCs. Cells were exposed to concentrations of PCP ranging from 5 to 0.05 µM and DDT concentrations of 2.5-0.025 μM for 24, 48 h, and 6 days. Results showed that both PCP and DDT increased IL-1β secretion from all of the immune cell preparations. The specific concentrations of PCP and DDT that increased IL-1β secretion varied by donor. Immune cells from all donors showed compound-induced increases in IL-1β secretion at one or more concentration at one or more length of exposure. The mechanism of PCP stimulation of IL1-β secretion was also addressed, and it appears that the MAPKs, ERK1/2 and p38, may be utilized by PCP to stimulate secretion of IL-1β.

  5. Low prevalence of Pneumocystis pneumonia (PCP) but high prevalence of pneumocystis dihydropteroate synthase (dhps) gene mutations in HIV-infected persons in Uganda.

    PubMed

    Taylor, Steve M; Meshnick, Steven R; Worodria, William; Andama, Alfred; Cattamanchi, Adithya; Davis, J Lucian; Yoo, Samuel D; Byanyima, Patrick; Kaswabuli, Sylvia; Goodman, Carol D; Huang, Laurence

    2012-01-01

    Pneumocystis jirovecii pneumonia (PCP) is an important opportunistic infection in patients infected with HIV, but its burden is incompletely characterized in those areas of sub-Saharan Africa where HIV is prevalent. We explored the prevalence of both PCP in HIV-infected adults admitted with pneumonia to a tertiary-care hospital in Uganda and of putative P. jirovecii drug resistance by mutations in fungal dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr). In 129 consecutive patients with sputum smears negative for mycobacteria, 5 (3.9%) were diagnosed with PCP by microscopic examination of Giemsa-stained bronchoalveolar lavage fluid. Concordance was 100% between Giemsa stain and PCR (dhps and dhfr). PCP was more prevalent in patients newly-diagnosed with HIV (11.4%) than in patients with known HIV (1.1%; p = 0.007). Mortality at 2 months after discharge was 29% overall: 28% among PCP-negative patients, and 60% (3 of 5) among PCP-positive patients. In these 5 fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation. No non-synonymous dhfr mutations were detected. PCP is an important cause of pneumonia in patients newly-diagnosed with HIV in Uganda, is associated with high mortality, and putative molecular evidence of drug resistance is prevalent. Given the reliability of field diagnosis in our cohort, future studies in sub-Saharan Africa can investigate the clinical impact of these genotypes.

  6. Human Antibodies to PhtD, PcpA, and Ply Reduce Adherence to Human Lung Epithelial Cells and Murine Nasopharyngeal Colonization by Streptococcus pneumoniae

    PubMed Central

    Kaur, Ravinder; Surendran, Naveen; Ochs, Martina

    2014-01-01

    Streptococcus pneumoniae adherence to human epithelial cells (HECs) is the first step in pathogenesis leading to infections. We sought to determine the role of human antibodies against S. pneumoniae protein vaccine candidates PhtD, PcpA, and Ply in preventing adherence to lung HECs in vitro and mouse nasopharyngeal (NP) colonization in vivo. Human anti-PhtD, -PcpA, and -Ply antibodies were purified and Fab fragments generated. Fabs were used to test inhibition of adherence of TIGR4 and nonencapsulated strain RX1 to A549 lung HECs. The roles of individual proteins in adherence were tested using isogenic mutants of strain TIGR4. Anti-PhtD, -PcpA, and -Ply human antibodies were assessed for their ability to inhibit NP colonization in vivo by passive transfer of human antibody in a murine model. Human antibodies generated against PhtD and PcpA caused a decrease in adherence to A549 cells (P < 0.05). Anti-PhtD but not anti-PcpA antibodies showed a protective role against mouse NP colonization. To our surprise, anti-Ply antibodies also caused a significant (P < 0.05) reduction in S. pneumoniae colonization. Our results support the potential of PhtD, PcpA, and Ply protein vaccine candidates as alternatives to conjugate vaccines to prevent non-serotype-specific S. pneumoniae colonization and invasive infection. PMID:25245804

  7. Performance Contoured Programming: A Structure for Microcomputer-Based Teaching of Individuals with Severe Learning Difficulties.

    ERIC Educational Resources Information Center

    Ager, Alastair

    1986-01-01

    Suggests programming structures of computer assisted instruction for teaching severely learning disabled students be related to an established educational model. Use of performance contoured programming (PCP), based upon behavioral model of precision teaching, is discussed and contrasted with cognitive programming approaches. PCP applications and…

  8. Synthesis, Structure, and Reactivity of Co(II) and Ni(II) PCP Pincer Borohydride Complexes

    PubMed Central

    2015-01-01

    The 15e square-planar complexes [Co(PCPMe-iPr)Cl] (2a) and [Co(PCP-tBu)Cl] (2b), respectively, react readily with NaBH4 to afford complexes [Co(PCPMe-iPr)(η2-BH4)] (4a) and [Co(PCP-tBu)(η2-BH4)] (4b) in high yields, as confirmed by IR spectroscopy, X-ray crystallography, and elemental analysis. The borohydride ligand is symmetrically bound to the cobalt center in η2-fashion. These compounds are paramagnetic with effective magnetic moments of 2.0(1) and 2.1(1) μB consistent with a d7 low-spin system corresponding to one unpaired electron. None of these complexes reacted with CO2 to give formate complexes. For structural and reactivity comparisons, we prepared the analogous Ni(II) borohydride complex [Ni(PCPMe-iPr)(η2-BH4)] (5) via two different synthetic routes. One utilizes [Ni(PCPMe-iPr)Cl] (3) and NaBH4, the second one makes use of the hydride complex [Ni(PCPMe-iPr)H] (6) and BH3·THF. In both cases, 5 is obtained in high yields. In contrast to 4a and 4b, the borohydride ligand is asymmetrically bound to the nickel center but still in an η2-mode. [Ni(PCPMe-iPr)(η2-BH4)] (5) loses readily BH3 at elevated temperatures in the presence of NEt3 to form 6. Complexes 5 and 6 are both diamagnetic and were characterized by a combination of 1H, 13C{1H}, and 31P{1H} NMR, IR spectroscopy, and elemental analysis. Additionally, the structure of these compounds was established by X-ray crystallography. Complexes 5 and 6 react with CO2 to give the formate complex [Ni(PCPMe-iPr)(OC(C=O)H] (7). The extrusion of BH3 from [Co(PCPMe-iPr)(η2-BH4)] (4a) and [Ni(PCPMe-iPr)(η2-BH4)] (5) with the aid of NH3 to yield the respective hydride complexes [Co(PCPMe-iPr)H] and [Ni(PCPMe-iPr)H] (6) and BH3NH3 was investigated by DFT calculations showing that formation of the Ni hydride is thermodynamically favorable, whereas the formation of the Co(II) hydride, in agreement with the experiment, is unfavorable. The electronic structures and the bonding of the borohydride ligand in [Co

  9. Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats.

    PubMed

    Redrobe, John P; Elster, Lisbeth; Frederiksen, Kristen; Bundgaard, Christoffer; de Jong, Inge E M; Smith, Garrick P; Bruun, Anne Techau; Larsen, Peter H; Didriksen, Michael

    2012-06-01

    A growing body of evidence suggests that negative modulation of γ-aminobutyric acid (GABA) GABA(A) α5 receptors may be a promising strategy for the treatment of certain facets of cognitive impairment; however, selective modulators of GABA(A) α5 receptors have not yet been tested in "schizophrenia-relevant" cognitive assay/model systems in animals. The objectives of this study were to investigate the potential of RO4938581, a negative modulator of GABA(A) α5 receptors, and to attenuate cognitive impairments induced following sub-chronic (sub-PCP) and early postnatal PCP (neo-PCP) administration in the novel object recognition (NOR) and intra-extradimensional shift (ID/ED) paradigms in rats. Complementary in vitro, ex vivo and in vivo studies were performed to confirm negative modulatory activity of RO4938581 and to investigate animal model validity, concept validity and potential side effect issues, respectively. In vitro studies confirmed the reported negative modulatory activity of RO4938581, whilst immunohistochemical analyses revealed significantly reduced parvalbumin-positive cells in the prefrontal cortex of sub-PCP- and neo-PCP-treated rats. RO4938581 (1 mg/kg) ameliorated both sub-PCP- and neo-PCP-induced cognitive deficits in NOR and ID/ED performance, respectively. In contrast, QH-II-066 (1 and 3 mg/kg), a GABA(A) α5 receptor positive modulator, impaired cognitive performance in the NOR task when administered to vehicle-treated animals. Additional studies revealed that both RO4938581 (1 mg/kg) and QH-II-066 (1 and 3 mg/kg) attenuated amphetamine-induced hyperactivity in rats. Taken together, these novel findings suggest that negative modulation of GABA(A) α5 receptors may represent an attractive treatment option for the cognitive impairments, and potentially positive symptoms, associated with schizophrenia.

  10. Distinct neuronal activation patterns are associated with PCP-induced social withdrawal and its reversal by the endocannabinoid-enhancing drug URB597.

    PubMed

    Matricon, Julien; Seillier, Alexandre; Giuffrida, Andrea

    2016-09-01

    The fatty acid amide hydrolase inhibitor, URB597, an endocannabinoid enhancing drug, reverses social withdrawal in the sub-chronic PCP rat model of schizophrenia, but reduces social interaction (SI) in controls. To identify the anatomical substrates associated with PCP-induced social withdrawal and the contrasting effects of URB597 on SI in PCP- versus saline-treated rats, we analyzed SI-induced c-Fos expression in 28 brain areas relevant to schizophrenia and/or social behavior following vehicle or URB597 administration. In saline-treated rats, SI was accompanied by changes in c-Fos expression in the infralimbic and orbitofrontal cortices, dorsomedial caudate putamen, ventrolateral nucleus of the septum, dorsolateral periaqueductal gray (dlPAG) and central amygdala. Except for the dlPAG, these changes were not observed in PCP-treated rats or in saline-treated rats receiving URB597. In the dorsomedial part of the bed nucleus of the stria terminalis (dmBNST), SI-induced c-Fos expression was observed only in PCP-treated rats. Interestingly, URB597 in PCP-treated rats restored a similar c-Fos expression pattern as observed in saline-treated rats: activation of the orbitofrontal cortex, inhibition of the central amygdala and suppression of activation of the dmBNST. These data suggest that orbitofrontal cortex, central amygdala and dmBNST play a critical role in the reversal of PCP-induced social withdrawal by URB597. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  11. Differential Responses to Wnt and PCP Disruption Predict Expression and Developmental Function of Conserved and Novel Genes in a Cnidarian

    PubMed Central

    Lapébie, Pascal; Ruggiero, Antonella; Barreau, Carine; Chevalier, Sandra; Chang, Patrick; Dru, Philippe; Houliston, Evelyn; Momose, Tsuyoshi

    2014-01-01

    We have used Digital Gene Expression analysis to identify, without bilaterian bias, regulators of cnidarian embryonic patterning. Transcriptome comparison between un-manipulated Clytia early gastrula embryos and ones in which the key polarity regulator Wnt3 was inhibited using morpholino antisense oligonucleotides (Wnt3-MO) identified a set of significantly over and under-expressed transcripts. These code for candidate Wnt signaling modulators, orthologs of other transcription factors, secreted and transmembrane proteins known as developmental regulators in bilaterian models or previously uncharacterized, and also many cnidarian-restricted proteins. Comparisons between embryos injected with morpholinos targeting Wnt3 and its receptor Fz1 defined four transcript classes showing remarkable correlation with spatiotemporal expression profiles. Class 1 and 3 transcripts tended to show sustained expression at “oral” and “aboral” poles respectively of the developing planula larva, class 2 transcripts in cells ingressing into the endodermal region during gastrulation, while class 4 gene expression was repressed at the early gastrula stage. The preferential effect of Fz1-MO on expression of class 2 and 4 transcripts can be attributed to Planar Cell Polarity (PCP) disruption, since it was closely matched by morpholino knockdown of the specific PCP protein Strabismus. We conclude that endoderm and post gastrula-specific gene expression is particularly sensitive to PCP disruption while Wnt-/β-catenin signaling dominates gene regulation along the oral-aboral axis. Phenotype analysis using morpholinos targeting a subset of transcripts indicated developmental roles consistent with expression profiles for both conserved and cnidarian-restricted genes. Overall our unbiased screen allowed systematic identification of regionally expressed genes and provided functional support for a shared eumetazoan developmental regulatory gene set with both predicted and previously

  12. In vivo labeling of phencyclidine (PCP) receptors with sup 3 H-TCP in the mouse brain

    SciTech Connect

    Maurice, T.; Vignon, J. )

    1990-07-01

    The phencyclidine (PCP) derivative N-(1-(2-thienyl)cyclohexyl)-piperidine (3H-TCP) was used to label in vivo the N-methyl-D-aspartate (NMDA) receptor-associated ionic channel in the mouse brain. After the injection of a tracer dose of 3H-TCP, a spread labeling throughout the brain was observed, but was the highest in the cerebellum. Preadministration of unlabeled TCP (30 mg/kg) resulted in a 90% reduction of 3H-TCP binding. PCP, TCP, MK-801, dexoxadrol, ketamine, and SKF 10,047 isomers dose-dependently prevented the in vivo 3H-TCP binding. ID50 determined in the cerebrum and the cerebellum were respectively correlated with K0.5 for 3H TCP high (rat cortex) and low affinity (rat cerebellum) sites in vitro. The pharmacological specificity of the 3H-TCP binding site in the cerebellum was significantly different from that in the cerebrum. ID50 values were generally higher than in the cerebrum and, particularly, MK-801, the most potent drug in the cerebrum, was without significant effect in the cerebellum, at any time and at doses as high as 30 mg/kg. N-(1-(2-benzo(b) thiophenyl)cyclohexyl)piperidine (BTCP), desipramine, and atropine showed a more efficient prevention of 3H-TCP binding in the cerebellum than in the cerebrum. The prevention of the binding by TCP or PCP, at doses close to their ID50 values, was rapid and then decreased slowly. The effect of MK-801 was long-lasting. This study confirm previous in vitro studies: 3H-TCP is an efficient tool for the labeling of the NMDA receptor-associated ionic channel.

  13. Pentachlorophenol dechlorination and simultaneous Cr6+ reduction by Pseudomonas putida SKG-1 MTCC (10510): characterization of PCP dechlorination products, bacterial structure, and functional groups.

    PubMed

    Garg, Satyendra Kumar; Tripathi, Manikant; Singh, Santosh Kumar; Singh, Anamika

    2013-04-01

    It is the first report in which a novel psychrotrophic Pseudomonas putida SKG-1 strain was evaluated for simultaneous bioremediation of pentachlorophenol and Cr(6+) under various cultural and nutritional conditions. Pentachlorophenol (PCP) dechlorination products, bacterial structure, and functional groups were characterized by gas chromatography and mass spectrometry (GC-MS), scanning electron microscope and energy dispersive X-ray spectroscopy (SEM-EDS), and Fourier-transform infrared (FTIR) techniques. The strain was extremely tolerant to excessively higher individual concentration of PCP (1,400 mg l(-1)) and Cr(6+) (4,300 mg l(-1)). Increasing concentration of PCP and Cr(6+) exerted inhibitory effect on bacterial growth and toxicants' removal. The strain exhibited growth, and concomitantly remediated both the pollutants simultaneously over a broad pH (7.0-9.0) and temperature (28-32 °C) range; maximum growth, PCP dechlorination (87.5%), and Cr(6+) removal (80.0%) occurred at optimum pH 8.0 and 30 °C (from initial PCP 100 mg l(-1) and Cr(6+) 500 mg l(-1)) under shaking (150 rpm) within 72 h incubation. Optimization of agitation (125 rpm) and aeration (0.4 vvm) in bioreactor further enhanced PCP dechlorination by ~10% and Cr(6+) removal by 2%. A direct correlation existed between growth and bioremediation of both the toxicants. Among other heavy metals, mercury exerted maximum and cobalt minimum inhibitory effect on PCP dechlorination and Cr(6+) removal. Chromate reductase activity was mainly associated with the supernatant and cytosolic fraction of bacterial cells. GC-MS analysis revealed the formation of tetrachloro-p-hydroquinone, 2,4,6-trichlorophenol, and 2,6-dichlorophenol as PCP dechlorination products. FTIR spectrometry indicated likely involvement of carbonyl and amide groups in Cr(3+) adsorption, and SEM-EDS showed the presence of chromium on P. putida surface. Thus, our promising isolate can be ecofriendly employed for biotreatment of various

  14. Nemo-like kinase 1 (Nlk1) and paraxial protocadherin (PAPC) cooperatively control Xenopus gastrulation through regulation of Wnt/planar cell polarity (PCP) signaling.

    PubMed

    Kumar, Rahul; Ciprianidis, Anja; Theiß, Susanne; Steinbeißer, Herbert; Kaufmann, Lilian T

    The Wnt/planar cell polarity (PCP) pathway directs cell migration during vertebrate gastrulation and is essential for proper embryonic development. Paraxial protocadherin (PAPC, Gene Symbol pcdh8.2) is an important activator of Wnt/PCP signaling during Xenopus gastrulation, but how PAPC activity is controlled is incompletely understood. Here we show that Nemo-like kinase 1 (Nlk1), an atypical mitogen-activated protein (MAP) kinase, physically associates with the C-terminus of PAPC. This interaction mutually stabilizes both proteins by inhibiting polyubiquitination. The Nlk1 mediated stabilization of PAPC is essential for Wnt/PCP signaling, tissue separation and gastrulation movements. We identified two conserved putative phosphorylation sites in the PAPC C-terminus that are critical for Nlk1 mediated PAPC stabilization and Wnt/PCP regulation. Intriguingly, the kinase activity of Nlk1 itself was not essential for its cooperation with PAPC, suggesting an indirect regulation for example by impeding a different kinase that promotes protein degradation. Overall these results outline a novel, kinase independent role of Nlk1, wherein Nlk1 regulates PAPC stabilization and thereby controls gastrulation movements and Wnt/PCP signaling during development. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  15. In-situ generated H₂O₂ induced efficient visible light photo-electrochemical catalytic oxidation of PCP-Na with TiO₂.

    PubMed

    Liu, Wei; Liu, Huichao; Ai, Zhihui

    2015-05-15

    In this study, we developed a novel photo-electrochemical catalytic oxidation wastewater treatment system by interacting the cathodic in-situ generated H₂O₂ with TiO₂ suspension to form interfacial ≡ Ti(IV)OOH species, which endowed the PEC system with superior efficiency for degrading sodium pentachlorophenate (PCP-Na) under visible light irradiation at neutral pH. The apparent PCP-Na degradation rate constant of the PEC system was more than 10 times that of the electrochemical oxidation counterpart. In the PEC system, the interfacial ≡ Ti(IV)OOH species injected electrons to the conduction band of TiO₂ to initiate the activation of O₂ and the in-situ generated H₂O₂ adsorbed on the surface of TiO₂, lead to producing reactive oxygen species of superoxide anions and hydroxyl radicals, which were responsible for the dechlorination and mineralization of PCP-Na during the PEC process, respectively. The dosage of TiO₂ catalyst and the current intensity applied on PCP-Na degradation were optimized. This study develops a high efficient PEC oxidation system for wastewater treatment and provides new insight into the role of cathodic in-situ generated H₂O₂ on PEC oxidation of PCP-Na with TiO₂ under visible light irradiation. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. PCP-B class pollen coat proteins are key regulators of the hydration checkpoint in Arabidopsis thaliana pollen-stigma interactions.

    PubMed

    Wang, Ludi; Clarke, Lisa A; Eason, Russell J; Parker, Christopher C; Qi, Baoxiu; Scott, Rod J; Doughty, James

    2017-01-01

    The establishment of pollen-pistil compatibility is strictly regulated by factors derived from both male and female reproductive structures. Highly diverse small cysteine-rich proteins (CRPs) have been found to play multiple roles in plant reproduction, including the earliest stages of the pollen-stigma interaction. Secreted CRPs found in the pollen coat of members of the Brassicaceae, the pollen coat proteins (PCPs), are emerging as important signalling molecules that regulate the pollen-stigma interaction. Using a combination of protein characterization, expression and phylogenetic analyses we identified a novel class of Arabidopsis thaliana pollen-borne CRPs, the PCP-Bs (for pollen coat protein B-class) that are related to embryo surrounding factor (ESF1) developmental regulators. Single and multiple PCP-B mutant lines were utilized in bioassays to assess effects on pollen hydration, adhesion and pollen tube growth. Our results revealed that pollen hydration is severely impaired when multiple PCP-Bs are lost from the pollen coat. The hydration defect also resulted in reduced pollen adhesion and delayed pollen tube growth in all mutants studied. These results demonstrate that AtPCP-Bs are key regulators of the hydration 'checkpoint' in establishment of pollen-stigma compatibility. In addition, we propose that interspecies diversity of PCP-Bs may contribute to reproductive barriers in the Brassicaceae. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  17. DNQX inhibits phencyclidine (PCP) and ketamine induction of the hsp70 heat shock gene in the rat cingulate and retrosplenial cortex.

    PubMed

    Sharp, J W; Petersen, D L; Langford, M T

    1995-07-31

    Phencyclidine (PCP) and ketamine are known to block NMDA receptor mediated excitotoxicity by non-competitively blocking the NMDA receptor calcium channel. PCP and ketamine have the paradoxical effect of also inducing the heat shock gene, hsp70, in the cingulate and retrosplenial cortex of the rat. The present study shows that DNQX, a specific AMPA receptor antagonist, given as either a 5 mg/kg or 10 mg/kg intraperitoneal dose or into the lateral cerebral ventricle (5 microliters of 0.5 mg/ml) significantly diminished PCP (40 mg/kg) and ketamine (80, 100, 120 mg/kg) hsp70 induction in the posterior cingulate and retrosplenial cortex. The most dramatic decrease of hsp70 induction was seen with the intraventricular dose of DNQX. Present findings show that the AMPA receptor has a role in PCP/ketamine induction of hsp70 in the cortex. DNQX inhibition of PCP/ketamine hsp70 induction was likely related to AMPA receptor antagonism which prevented excess calcium influx via voltage-gated calcium channels.

  18. SEC14 and spectrin domains 1 (Sestd1) and Dapper antagonist of catenin 1 (Dact1) scaffold proteins cooperatively regulate the Van Gogh-like 2 (Vangl2) four-pass transmembrane protein and planar cell polarity (PCP) pathway during embryonic development in mice.

    PubMed

    Yang, XiaoYong; Cheyette, Benjamin N R

    2013-07-12

    The planar cell polarity (PCP) pathway is a conserved non-canonical (β-catenin-independent) branch of Wnt signaling crucial to embryogenesis, during which it regulates cell polarity and polarized cell movements. Disruption of PCP components in mice, including Vangl2 and Dact1, results in defective neural tube closure and other developmental defects. Here, we show that Sestd1 is a novel binding partner of Vangl2 and Dact1. The Sestd1-Dact1 interface is formed by circumscribed regions of Sestd1 (the carboxyl-terminal region) and Dact1 (the amino-terminal region). Remarkably, we show that loss of Sestd1 precisely phenocopies loss of Dact1 during embryogenesis in mice, leading to a spectrum of birth malformations, including neural tube defects, a shortened and/or curly tail, no genital tubercle, blind-ended colons, hydronephrotic kidneys, and no bladder. Moreover, as with Dact1, a knock-out mutation at the Sestd1 locus exhibits reciprocal genetic rescue interactions during development with a semidominant mutation at the Vangl2 locus. Consistent with this, examination of Wnt pathway activities in Sestd1 mutant mouse embryonic tissue reveals disrupted PCP pathway biochemistry similar to that characterized in Dact1 mutant embryos. The Sestd1 protein is a divergent member of the Trio family of GTPase regulatory proteins that lacks a guanine nucleotide exchange factor domain. Nonetheless, in cell-based assays the Sestd1-Dact1 interaction can induce Rho GTPase activation. Together, our data indicate that Sestd1 cooperates with Dact1 in Vangl2 regulation and in the PCP pathway during mammalian embryonic development.

  19. Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development.

    PubMed

    Landeira, David; Bagci, Hakan; Malinowski, Andrzej R; Brown, Karen E; Soza-Ried, Jorge; Feytout, Amelie; Webster, Zoe; Ndjetehe, Elodie; Cantone, Irene; Asenjo, Helena G; Brockdorff, Neil; Carroll, Thomas; Merkenschlager, Matthias; Fisher, Amanda G

    2015-07-28

    Jarid2 is part of the Polycomb Repressor complex 2 (PRC2) responsible for genome-wide H3K27me3 deposition. Unlike other PRC2-deficient embryonic stem cells (ESCs), however, Jarid2-deficient ESCs show a severe differentiation block, altered colony morphology, and distinctive patterns of deregulated gene expression. Here, we show that Jarid2(-/-) ESCs express constitutively high levels of Nanog but reduced PCP signaling components Wnt9a, Prickle1, and Fzd2 and lowered β-catenin activity. Depletion of Wnt9a/Prickle1/Fzd2 from wild-type ESCs or overexpression of Nanog largely phenocopies these cellular defects. Co-culture of Jarid2(-/-) with wild-type ESCs restores variable Nanog expression and β-catenin activity and can partially rescue the differentiation block of mutant cells. In addition, we show that ESCs lacking Jarid2 or Wnt9a/Prickle1/Fzd2 or overexpressing Nanog induce multiple ICM formation when injected into normal E3.5 blastocysts. These data describe a previously unrecognized role for Jarid2 in regulating a core pluripotency and Wnt/PCP signaling circuit that is important for ESC differentiation and for pre-implantation development. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development

    PubMed Central

    Landeira, David; Bagci, Hakan; Malinowski, Andrzej R.; Brown, Karen E.; Soza-Ried, Jorge; Feytout, Amelie; Webster, Zoe; Ndjetehe, Elodie; Cantone, Irene; Asenjo, Helena G.; Brockdorff, Neil; Carroll, Thomas; Merkenschlager, Matthias; Fisher, Amanda G.

    2015-01-01

    Summary Jarid2 is part of the Polycomb Repressor complex 2 (PRC2) responsible for genome-wide H3K27me3 deposition. Unlike other PRC2-deficient embryonic stem cells (ESCs), however, Jarid2-deficient ESCs show a severe differentiation block, altered colony morphology, and distinctive patterns of deregulated gene expression. Here, we show that Jarid2−/− ESCs express constitutively high levels of Nanog but reduced PCP signaling components Wnt9a, Prickle1, and Fzd2 and lowered β-catenin activity. Depletion of Wnt9a/Prickle1/Fzd2 from wild-type ESCs or overexpression of Nanog largely phenocopies these cellular defects. Co-culture of Jarid2−/− with wild-type ESCs restores variable Nanog expression and β-catenin activity and can partially rescue the differentiation block of mutant cells. In addition, we show that ESCs lacking Jarid2 or Wnt9a/Prickle1/Fzd2 or overexpressing Nanog induce multiple ICM formation when injected into normal E3.5 blastocysts. These data describe a previously unrecognized role for Jarid2 in regulating a core pluripotency and Wnt/PCP signaling circuit that is important for ESC differentiation and for pre-implantation development. PMID:26190104

  1. Increasing Endocannabinoid Levels in the Ventral Pallidum Restore Aberrant Dopamine Neuron Activity in the Subchronic PCP Rodent Model of Schizophrenia

    PubMed Central

    Chen, Li; Lodge, Daniel J

    2015-01-01

    Background: Schizophrenia is a debilitating disorder that affects 1% of the US population. While the exogenous administration of cannabinoids such as tetrahydrocannabinol is reported to exacerbate psychosis in schizophrenia patients, augmenting the levels of endogenous cannabinoids has gained attention as a possible alternative therapy to schizophrenia due to clinical and preclinical observations. Thus, patients with schizophrenia demonstrate an inverse relationship between psychotic symptoms and levels of the endocannabinoid anandamide. In addition, increasing endocannabinoid levels (by blockade of enzymatic degradation) has been reported to attenuate social withdrawal in a preclinical model of schizophrenia. Here we examine the effects of increasing endogenous cannabinoids on dopamine neuron activity in the sub-chronic phencyclidine (PCP) model. Aberrant dopamine system function is thought to underlie the positive symptoms of schizophrenia. Methods: Using in vivo extracellular recordings in chloral hydrate–anesthetized rats, we now demonstrate an increase in dopamine neuron population activity in PCP-treated rats. Results: Interestingly, endocannabinoid upregulation, induced by URB-597, was able to normalize this aberrant dopamine neuron activity. Furthermore, we provide evidence that the ventral pallidum is the site where URB-597 acts to restore ventral tegmental area activity. Conclusions: Taken together, we provide preclinical evidence that augmenting endogenous cannabinoids may be an effective therapy for schizophrenia, acting in part to restore ventral pallidal activity. PMID:25539511

  2. Analysis of HO-PCBs and PCP in blood plasma from individuals with high PCB exposure living on the Chukotka Peninsula in the Russian Arctic.

    PubMed

    Sandanger, Torkjel M; Dumas, Pierre; Berger, Urs; Burkow, Ivan C

    2004-09-01

    A trace analytical method is presented for the analysis of hydroxylated polychlorinated biphenyl metabolites (HO-PCBs) and pentachlorophenol (PCP) in human plasma. The described methodology is a modification of a previously validated method used for PCB and organochlorine pesticide analysis. The modified method enables the combined analysis of phenolic and neutral halogenated compounds. A tandem Florisil column is used for separating the HO-PCBs and PCP from the neutral fraction, instead of the more common chemical partitioning. In the same step the neutral fraction is purified for GC analysis. The extraction of the HO-PCBs and PCP was found to be highly dependent on sufficient acidification of the sample and the polarity of the extracting solvent. Analysis of plasma samples gave recovery rates for (13)C(6)-PCP and (13)C(12)-4-HO-CB 187 of 64 and 72%, respectively. The limit of detection ranged between 2-20 pg g(-1) plasma for the HO-PCBs and 5 pg g(-1) plasma for PCP. No matrix interferences were observed in the chromatograms. In plasma samples (n = 15) from the native Chukchi people in Uelen (Russian Arctic), a population with high PCB exposure, the median ratio of sum HO-PCBs to sum PCBs was as high as 0.4 and the sum HO-PCBs and PCBs were significantly correlated (r(2) > 0.7, p < 0.01). The median sum HO-PCBs (10 congeners) was 5920 pg g(-1) plasma with 4-HO-CB 107 as the dominating congener (median: 1670 pg g(-1) plasma). The median PCP level was measured at 642 pg g(-1) plasma.

  3. Identification of Developmentally Regulated PCP-Responsive Non-Coding RNA, prt6, in the Rat Thalamus

    PubMed Central

    Umino, Asami; Nishikawa, Toru

    2014-01-01

    Schizophrenia and similar psychoses induced by NMDA-type glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, usually develop after adolescence. Moreover, adult-type behavioral disturbance following NMDA receptor antagonist application in rodents is observed after a critical period at around 3 postnatal weeks. These observations suggest that the schizophrenic symptoms caused by and psychotomimetic effects of NMDA antagonists require the maturation of certain brain neuron circuits and molecular networks, which differentially respond to NMDA receptor antagonists across adolescence and the critical period. From this viewpoint, we have identified a novel developmentally regulated phencyclidine-responsive transcript from the rat thalamus, designated as prt6, as a candidate molecule involved in the above schizophrenia-related systems using a DNA microarray technique. The transcript is a non-coding RNA that includes sequences of at least two microRNAs, miR132 and miR212, and is expressed strongly in the brain and testis, with trace or non-detectable levels in the spleen, heart, liver, kidney, lung and skeletal muscle, as revealed by Northern blot analysis. The systemic administration of PCP (7.5 mg/kg, subcutaneously (s.c.)) significantly elevated the expression of prt6 mRNA in the thalamus at postnatal days (PD) 32 and 50, but not at PD 8, 13, 20, or 24 as compared to saline-treated controls. At PD 50, another NMDA receptor antagonist, dizocilpine (0.5 mg/kg, s.c.), and a schizophrenomimetic dopamine agonist, methamphetamine (4.8 mg/kg, s.c.), mimicked a significant increase in the levels of thalamic prt6 mRNAs, while a D2 dopmamine receptor antagonist, haloperidol, partly inhibited the increasing influence of PCP on thalamic prt6 expression without its own effects. These data indicate that prt6 may be involved in the pathophysiology of the onset of drug-induced schizophrenia-like symptoms and schizophrenia through the possible dysregulation of

  4. Constraints on the Small Scale Heterogeneity in D" from Precursors to Short Distance PcP Wave and Implication for Roughness of Core-Mantle Boundary

    NASA Astrophysics Data System (ADS)

    Ni, S.; Zhang, B.

    2016-12-01

    Volumetric heterogeneity in D" layer and topography variation of the Core Mantle Boundary (CMB) are well established on large scales (thousand kms) to intermediate scales with seismological approaches. However, there are controversies regarding the level of heterogeneity in D" layer at small scales ( a few km - 10 km), with lower bound estimate of 0.1% to a few percent. And there are very limited reports of small scale topography of CMB. We take advantage of the small amplitude PcP waves at near podal distances (0-10 degree), and use the ratio of short period (1 Hz) PcP and its precursors to constrain level of small scale heterogeneity in the D" layer. We computed short period synthetic seismograms with 2D finite code for a series of volumetric heterogeneity models in the crust and in D", and find that PcP is not observable if the heterogeneity in D" is above 2%. We will present evidences of clearly observed PcP at short distances and argue for weak small scale heterogeneity in D". Assuming topography of CMB is related to isostasy, the volumetric heterogeneity in D" can be used to estimate CMB roughness.

  5. A novel role of the organizer gene Goosecoid as an inhibitor of Wnt/PCP-mediated convergent extension in Xenopus and mouse.

    PubMed

    Ulmer, Bärbel; Tingler, Melanie; Kurz, Sabrina; Maerker, Markus; Andre, Philipp; Mönch, Dina; Campione, Marina; Deißler, Kirsten; Lewandoski, Mark; Thumberger, Thomas; Schweickert, Axel; Fainsod, Abraham; Steinbeißer, Herbert; Blum, Martin

    2017-02-21

    Goosecoid (Gsc) expression marks the primary embryonic organizer in vertebrates and beyond. While functions have been assigned during later embryogenesis, the role of Gsc in the organizer has remained enigmatic. Using conditional gain-of-function approaches in Xenopus and mouse to maintain Gsc expression in the organizer and along the axial midline, neural tube closure defects (NTDs) arose and dorsal extension was compromised. Both phenotypes represent convergent extension (CE) defects, arising from impaired Wnt/planar cell polarity (PCP) signaling. Dvl2 recruitment to the cell membrane was inhibited by Gsc in Xenopus animal cap assays and key Wnt/PCP factors (RhoA, Vangl2, Prickle, Wnt11) rescued Gsc-mediated NTDs. Re-evaluation of endogenous Gsc functions in MO-mediated gene knockdown frog and knockout mouse embryos unearthed PCP/CE-related phenotypes as well, including cartilage defects in Xenopus and misalignment of inner ear hair cells in mouse. Our results assign a novel function to Gsc as an inhibitor of Wnt/PCP-mediated CE. We propose that in the organizer Gsc represses CE as well: Gsc-expressing prechordal cells, which leave the organizer first, migrate and do not undergo CE like the Gsc-negative notochordal cells, which subsequently emerge from the organizer. In this model, Gsc provides a switch between cell migration and CE, i.e. cell intercalation.

  6. A novel role of the organizer gene Goosecoid as an inhibitor of Wnt/PCP-mediated convergent extension in Xenopus and mouse

    PubMed Central

    Ulmer, Bärbel; Tingler, Melanie; Kurz, Sabrina; Maerker, Markus; Andre, Philipp; Mönch, Dina; Campione, Marina; Deißler, Kirsten; Lewandoski, Mark; Thumberger, Thomas; Schweickert, Axel; Fainsod, Abraham; Steinbeißer, Herbert; Blum, Martin

    2017-01-01

    Goosecoid (Gsc) expression marks the primary embryonic organizer in vertebrates and beyond. While functions have been assigned during later embryogenesis, the role of Gsc in the organizer has remained enigmatic. Using conditional gain-of-function approaches in Xenopus and mouse to maintain Gsc expression in the organizer and along the axial midline, neural tube closure defects (NTDs) arose and dorsal extension was compromised. Both phenotypes represent convergent extension (CE) defects, arising from impaired Wnt/planar cell polarity (PCP) signaling. Dvl2 recruitment to the cell membrane was inhibited by Gsc in Xenopus animal cap assays and key Wnt/PCP factors (RhoA, Vangl2, Prickle, Wnt11) rescued Gsc-mediated NTDs. Re-evaluation of endogenous Gsc functions in MO-mediated gene knockdown frog and knockout mouse embryos unearthed PCP/CE-related phenotypes as well, including cartilage defects in Xenopus and misalignment of inner ear hair cells in mouse. Our results assign a novel function to Gsc as an inhibitor of Wnt/PCP-mediated CE. We propose that in the organizer Gsc represses CE as well: Gsc-expressing prechordal cells, which leave the organizer first, migrate and do not undergo CE like the Gsc-negative notochordal cells, which subsequently emerge from the organizer. In this model, Gsc provides a switch between cell migration and CE, i.e. cell intercalation. PMID:28220837

  7. Beliefs and social norms about cigarettes or marijuana sticks laced with embalming fluid and phencyclidine (PCP): why youth use "fry".

    PubMed

    Peters, Ronald J; Kelder, Steven H; Meshack, Angela; Yacoubian, George S; McCrimmons, Debra; Ellis, Artist

    2005-01-01

    Recent drug-use monitoring among Houston adolescents has detected a concoction of cigarettes or marijuana sticks laced with embalming fluid and PCP ("fry"). To shed light on this mixture, the current pilot study used a qualitative approach to investigate relevant beliefs and norms associated with fry initiation and perceived addiction among 38 youth who were attending outpatient and inpatient drug-user treatment programs in the spring of 2003. Respondents perceived that addiction to fry could occur as early as initial consumption, and the majority of participants indicated that their second fry event occurred either the same day as their initial use or the next day. In addition, fry use was perceived to have extremely dangerous consequences. Youth stated that users have impaired motor skills, hallucinations, long-term mental health problems, incoherent behavior, paranoia, and aggressive behaviors. Implications for these results are discussed.

  8. Effects of novel antipsychotics with mixed D(2) antagonist/5-HT(1A) agonist properties on PCP-induced social interaction deficits in the rat.

    PubMed

    Bruins Slot, Liesbeth A; Kleven, Mark S; Newman-Tancredi, Adrian

    2005-12-01

    Considerable interest has arisen in identifying antipsychotic agents with improved efficacy against negative symptoms, such as social withdrawal. In rats, a social interaction deficit can be induced by the NMDA antagonist phencyclidine (PCP). Here, we examined the effects of antipsychotics, reported to exert dual 5-HT(1A)/D(2) actions, on PCP-induced social interaction deficits. Drugs were administered daily for 3 days in combination with either vehicle or PCP (2.5mg/kg, SC) and social interaction was measured on the last day of drug treatment. Pairs of unfamiliar rats receiving the same treatment were placed in a large open field for 10 min and the number of social behaviors were scored. The results indicate that: (1) PCP significantly reduced social interaction by over 50% compared with vehicle-treated controls; (2) haloperidol (0.0025-0.16 mg/kg, SC) and clozapine (0.04-10mg/kg, IP) did not reverse PCP-induced social interaction deficits; (3) the substituted benzamide remoxipride reversed PCP-induced deficits at 0.63 and 2.5mg/kg (4) the 5-HT(1A) agonist 8-OH-DPAT was inactive (at 0.01-0.63 mg/kg, SC); (5) among compounds reported to exert dual 5-HT(1A)/D(2) actions, SSR181507 (at 0.16 mg/kg, SC) and aripiprazole (at 0.04 and 0.16 mg/kg, IP), but not ziprasidone (0.04-2.5mg/kg, IP), SLV313 (0.0025-0.16 mg/kg, SC) or bifeprunox (0.01-0.63 mg/kg, IP), significantly reversed PCP-induced social interaction deficits; and (6) the 5-HT(1A) receptor antagonist WAY100635 blocked the effects of SSR181507 and aripiprazole. These findings indicate that the balance of activity at 5-HT(1A) and D(2) receptors profoundly influences the activity of antipsychotics in this model of social withdrawal, and their potential benefit on at least some of the negative symptoms of schizophrenia.

  9. The preventive effects of taurine on neural tube defects through the Wnt/PCP-Jnk-dependent pathway.

    PubMed

    Zhang, Qinghua; Liu, Yang; Wang, Hui; Ma, Li; Xia, Hechun; Niu, Jianguo; Sun, Tao; Zhang, Li

    2017-07-17

    The aim of this study was to clarify the protective role of taurine in neuronal apoptosis and the role of the Wnt/PCP-Jnk pathway in mediating the preventive effects of taurine on neural tube defects (NTDs). HT-22 cells (a hippocampal neuron cell line) were divided into a control group, a glutamate-induced apoptosis group, and glutamate (4.0 mmol/L) plus low-dose taurine (L; 0.5 mmol/L) and high-dose taurine (H; 2.0 mmol/L) groups. The MTT assay was used to monitor cell proliferation and cell survival. Immunofluorescence and Western blot analyses were used to determine caspase 9 expression. Retinoic acid (RA) induced embryonic NTDs in Kunming mice, thus establishing an NTD model. Pregnant mice were divided into a control group, an RA (30 mg/kg body weight) group, and an RA (30 mg/kg body weight) plus taurine (free drinking of 2 g/L solution) group. Immunohistochemistry and Western blot analyses were used to detect the expression of Dvl, RhoA and phosphorylated (p)-Jnk/Jnk in the embryonic neural tubes. In HT-22 cells, the apoptosis rate was significantly higher and caspase 9 activation was also significantly increased in the glutamate-induced apoptosis group compared to the L and H taurine groups. In the NTD model, the expression levels of Dvl, RhoA, and p-Jnk were significantly higher in the RA group than in the control group, whereas they were significantly reduced in the RA + taurine group. This study suggests that taurine has positive effects on neuronal protection and NTD prevention. Moreover, the Wnt/PCP-Jnk-dependent pathway plays an important role in taurine-mediated prevention of NTDs.

  10. Extraction of weak PcP phases using the slant-stacklet transform - I: method and examples

    NASA Astrophysics Data System (ADS)

    Ventosa, Sergi; Romanowicz, Barbara

    2015-04-01

    In order to study fine scale structure of the Earth's deep interior, it is necessary to extract generally weak body wave phases from seismograms that interact with various discontinuities and heterogeneities. The recent deployment of large-scale dense arrays providing high-quality data, in combination with efficient seismic data processing techniques, may provide important and accurate observations over large portions of the globe poorly sampled until now. Major challenges are low signal-to-noise ratios (SNR) and interference with unwanted neighbouring phases. We address these problems by introducing scale-dependent slowness filters that preserve time-space resolution. We combine complex wavelet and slant-stack transforms to obtain the slant-stacklet transform. This is a redundant high-resolution directional wavelet transform with a direction (here slowness) resolution that can be adapted to the signal requirements. To illustrate this approach, we use this expansion to design coherence-driven filters that allow us to obtain clean PcP observations (a weak phase often hidden in the coda of the P wave), for events with magnitude Mw > 5.4 and distances up to 80°. In this context, we then minimize a linear misfit between P and PcP waveforms to improve the quality of PcP-P traveltime measurements as compared to a standard cross-correlation method. This significantly increases both the quantity and the quality of PcP-P differential traveltime measurements available for the modelling of structure near the core-mantle boundary. The accuracy of our measurements is limited mainly by the highest frequencies of the signals used and the level of noise. We apply this methodology to two examples of high-quality data from dense arrays located in north America. While focusing here on body-wave separation, the tools we propose are more general and may contribute to enhancing seismic signal observations in global seismology in situations of low SNR and high signal interference.

  11. A Phenotypic Screen in Zebrafish Identifies a Novel Small-Molecule Inducer of Ectopic Tail Formation Suggestive of Alterations in Non-Canonical Wnt/PCP Signaling

    PubMed Central

    Gebruers, Evelien; Cordero-Maldonado, María Lorena; Gray, Alexander I.; Clements, Carol; Harvey, Alan L.; Edrada-Ebel, Ruangelie; de Witte, Peter A. M.; Crawford, Alexander D.; Esguerra, Camila V.

    2013-01-01

    Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a zebrafish-based phenotypic screen of over 3000 plant-derived secondary metabolite extracts with the goal of identifying novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the bioactive plant extracts identified in this screen – Jasminum gilgianum, an Oleaceae species native to Papua New Guinea – induced ectopic tails during zebrafish embryonic development. As ectopic tail formation occurs when BMP or non-canonical Wnt signaling is inhibited during the tail protrusion process, we suspected a constituent of this extract to act as a modulator of these pathways. A bioassay-guided isolation was carried out on the basis of this zebrafish phenotype, identifying para-coumaric acid methyl ester (pCAME) as the active compound. We then performed an in-depth phenotypic analysis of pCAME-treated zebrafish embryos, including a tissue-specific marker analysis of the secondary tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN-193189 in inducing ectopic tails, and causing convergence-extension defects in compound-treated embryos. These results indicate that pCAME may interfere with non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP signaling (via morpholino antisense knockdown and pharmacological inhibition with the kinase inhibitor SP600125) phenocopied pCAME-treated embryos. However, immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other pathways, as possibly being involved in the ectopic tail formation activity of pCAME. Further investigation of pCAME’s mechanism of action will help determine this compound’s pharmacological utility. PMID:24349481

  12. A phenotypic screen in zebrafish identifies a novel small-molecule inducer of ectopic tail formation suggestive of alterations in non-canonical Wnt/PCP signaling.

    PubMed

    Gebruers, Evelien; Cordero-Maldonado, María Lorena; Gray, Alexander I; Clements, Carol; Harvey, Alan L; Edrada-Ebel, Ruangelie; de Witte, Peter A M; Crawford, Alexander D; Esguerra, Camila V

    2013-01-01

    Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a zebrafish-based phenotypic screen of over 3000 plant-derived secondary metabolite extracts with the goal of identifying novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the bioactive plant extracts identified in this screen - Jasminum gilgianum, an Oleaceae species native to Papua New Guinea - induced ectopic tails during zebrafish embryonic development. As ectopic tail formation occurs when BMP or non-canonical Wnt signaling is inhibited during the tail protrusion process, we suspected a constituent of this extract to act as a modulator of these pathways. A bioassay-guided isolation was carried out on the basis of this zebrafish phenotype, identifying para-coumaric acid methyl ester (pCAME) as the active compound. We then performed an in-depth phenotypic analysis of pCAME-treated zebrafish embryos, including a tissue-specific marker analysis of the secondary tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN-193189 in inducing ectopic tails, and causing convergence-extension defects in compound-treated embryos. These results indicate that pCAME may interfere with non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP signaling (via morpholino antisense knockdown and pharmacological inhibition with the kinase inhibitor SP600125) phenocopied pCAME-treated embryos. However, immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other pathways, as possibly being involved in the ectopic tail formation activity of pCAME. Further investigation of pCAME's mechanism of action will help determine this compound's pharmacological utility.

  13. Probing the electronic communication of the isocyanide bridge through the luminescence properties of the d9-d9 [ClPt(mu-dppm)2Pt(C triple bond N-PCP)]+ and A-Frame [ClPd(mu-dppm)2(mu-C=N-PCP)PdCl] complexes.

    PubMed

    Clément, Sébastien; Aly, Shawkat Mohammed; Fortin, Daniel; Guyard, Laurent; Knorr, Michael; Abd-El-Aziz, Alaa S; Harvey, Pierre D

    2008-12-01

    The homodinuclear d9-d9 ClM(mu-dppm)2MCl2 complexes, 1 (M ) Pt) and 2 (M ) Pd) react with the conjugated and luminescent PCP-NC ligand (3, PCP ) [2.2]paracyclophane) to provide the corresponding d9-d9 terminal[ClPt(mu-dppm)2Pt(CNsPCP)]Cl (4) and d8-d8 A-frame [ClPd(mu-dppm)2(mu-CdNsPCP)PdCl] (5) isocyanide complexes, respectively. These two bimetallic complexes were characterized by IR, 1H, and 31P{1H} NMR and bychemical analysis. IR data (nu(CN) bridging vs terminal) reveal a terminal isocyanide bonding mode for 4 (2147cm(-1)) and an A-frame structure for 5 (1616 cm(-1)). The optical and emission properties of the free isocyanide 3as well as those of the homodinuclear complexes 4 and 5 were studied by UV-visible and luminescence spectroscopy and by photophysical measurements. The unexpected presence of simultaneous intraligand pipi* fluorescence and phosphorescence attributable to the organic PCP-NC ligand, as well as luminescence from the inorganic M2-bonded Pt2(mu-dppm)2 center arising from a lower energy excited LMCT state (ligand-to-metal-charge-transfer) for4 at 77 K, indicates a weak conjugation between the two chromophores and an absence of efficient singlet andtriplet energy transfers. For 5, only the fluorescence and phosphorescence bands of the PCP-NC ligand are observed [since the A-frame XPd(mu-dppm)2(mu-L)PdX (L ) isocyanide, X ) halide) is not luminescent], stressing that the NtC bridge exhibits modest electronic communication properties.

  14. Effects of risperidone, clozapine and the 5-HT6 antagonist GSK-742457 on PCP-induced deficits in reversal learning in the two-lever operant task in male Sprague Dawley rats.

    PubMed

    de Bruin, N M W J; van Drimmelen, M; Kops, M; van Elk, J; Wetering, M Middelveld-van de; Schwienbacher, I

    2013-05-01

    Reasoning and problem solving deficits have been reported in schizophrenic patients. In the present study, we have tested rats in a two-lever reversal learning task in a Skinner box to model these deficits. In other studies using the Skinner box, atypical antipsychotics fully reversed phencyclidine (PCP)-induced impairments in reversal learning which is in contrast to clinical observations where antipsychotics lack the ability to fully reverse cognitive deficits in schizophrenia. Therefore, it can be argued that the outcome of these tests may lack predictive value. In the present study, after training on a spatial discrimination between two levers, rats were exposed to a reversal of the previously learned stimulus-response contingency during 5 days. We first investigated the effects of sub-chronic treatment with the non-competitive N-methyl-d-aspartate (NMDA) antagonists dizocilpine (MK-801) and PCP on reversal learning and extinction in male Sprague Dawley rats. Subsequently, we studied the effects of different PCP treatment regimes. Then, we investigated whether the atypical antipsychotics risperidone and clozapine and the 5-hydroxytryptamine6 (5-HT6) antagonist GSK-742457 could reverse the PCP-induced deficits. All drugs were administered subcutaneously (s.c.). MK-801 did not impair reversal learning, while PCP (1.0 and 2.0 mg/kg) induced a clear deficit in reversal learning. Both compounds, however, disrupted extinction at all tested doses. Risperidone and clozapine were both ineffective in significantly ameliorating the PCP-induced deficit in reversal learning which fits well with the clinical observations. The lowest dose of clozapine (1.25 mg/kg) had an intermediate effect in ameliorating the deficit in reversal learning induced by PCP (not different from control or PCP-treated rats). The lowest dose of GSK-742457 (0.63 mg/kg) fully reversed the PCP-induced deficits while the higher dose (5.0 mg/kg) had an intermediate effect.

  15. Planar Cell Polarity (PCP) Protein Vangl2 Regulates Ectoplasmic Specialization Dynamics via Its Effects on Actin Microfilaments in the Testes of Male Rats.

    PubMed

    Chen, Haiqi; Mruk, Dolores D; Lee, Will M; Cheng, C Yan

    2016-05-01

    Planar cell polarity (PCP) proteins confer polarization of a field of cells (eg, elongating/elongated spermatids) within the plane of an epithelium such as the seminiferous epithelium of the tubule during spermatogenesis. In adult rat testes, Sertoli and germ cells were found to express PCP core proteins (eg, Van Gogh-like 2 [Vangl2]), effectors, ligands, and signaling proteins. Vangl2 expressed predominantly by Sertoli cells was localized at the testis-specific, actin-rich ectoplasmic specialization (ES) at the Sertoli-spermatid interface in the adluminal compartment and also Sertoli-Sertoli interface at the blood-testis barrier (BTB) and structurally interacted with actin, N-cadherin, and another PCP/polarity protein Scribble. Vangl2 knockdown (KD) by RNA interference in Sertoli cells cultured in vitro with an established tight junction-permeability barrier led to BTB tightening, whereas its overexpression using a full-length cDNA construct perturbed the barrier function. These changes were mediated through an alteration on the organization actin microfilaments at the ES in Sertoli cells, involving actin-regulatory proteins, epidermal growth factor receptor pathway substrate 8, actin-related protein 3, and Scribble, which in turn affected the function of adhesion protein complexes at the ES during the epithelial cycle of spermatogenesis. Using Polyplus in vivo-jetPEI reagent as a transfection medium to silence Vangl2 in the testis in vivo by RNA interference with high efficacy, Vangl2 KD led to changes in F-actin organization at the ES in the epithelium, impeding spermatid and phagosome transport and spermatid polarity, meiosis, and BTB dynamics. For instance, step 19 spermatids remained embedded in the epithelium alongside with step 9 and 10 spermatids in stages IX-X tubules. In summary, the PCP protein Vangl2 is an ES regulator through its effects on actin microfilaments in the testis.

  16. Dopamine D1 receptor activation improves PCP-induced performance disruption in the 5C-CPT by reducing inappropriate responding

    PubMed Central

    Barnes, S.A.; Young, J.W.; Bate, S.T.; Neill, J.C.

    2016-01-01

    Attentional deficits contribute significantly to the functional disability of schizophrenia patients. The 5-choice continuous performance test (5C-CPT) measures attention in mice, rats, and humans, requiring the discrimination of trial types that either require a response or the inhibition of a response. The 5C-CPT, one version of human continuous performance tests (CPT), enables attentional testing in rodents in a manner consistent with humans. Augmenting the prefrontal cortical dopaminergic system has been proposed as a therapeutic target to attenuate the cognitive disturbances associated with schizophrenia. Using translational behavioural tasks in conjunction with inducing conditions relevant to schizophrenia pathophysiology enable the assessment of pro-attentive properties of compounds that augment dopaminergic activity. Here, using a repeated phencyclidine (PCP) treatment regimen and the 5C-CPT paradigm, we assess the pro-attentive properties of SKF 38393, a dopamine D1 receptor agonist, in rats. We show that repeated PCP treatment induces robust deficits in 5C-CPT performance indicative of impaired attention. Pre-treatment with SKF 38393 partially attenuates the PCP-induced deficits in 5C-CPT performance by reducing false alarm responding and increasing response accuracy. Impaired target detection was still evident in SKF 38393-treated rats however. Thus, augmentation of the dopamine D1 system improves PCP-induces deficits in 5C-CPT performance by selectively reducing aspects of inappropriate responding. These findings provide evidence to support the hypothesis that novel therapies targeting the dopamine D1 receptor system could improve aspects of attentional deficits in schizophrenia patients. PMID:26658514

  17. Dopamine D1 receptor activation improves PCP-induced performance disruption in the 5C-CPT by reducing inappropriate responding.

    PubMed

    Barnes, S A; Young, J W; Bate, S T; Neill, J C

    2016-03-01

    Attentional deficits contribute significantly to the functional disability of schizophrenia patients. The 5-choice continuous performance test (5C-CPT) measures attention in mice, rats, and humans, requiring the discrimination of trial types that either require a response or the inhibition of a response. The 5C-CPT, one version of human continuous performance tests (CPT), enables attentional testing in rodents in a manner consistent with humans. Augmenting the prefrontal cortical dopaminergic system has been proposed as a therapeutic target to attenuate the cognitive disturbances associated with schizophrenia. Using translational behavioural tasks in conjunction with inducing conditions relevant to schizophrenia pathophysiology enable the assessment of pro-attentive properties of compounds that augment dopaminergic activity. Here, using a repeated phencyclidine (PCP) treatment regimen and the 5C-CPT paradigm, we assess the pro-attentive properties of SKF 38393, a dopamine D1 receptor agonist, in rats. We show that repeated PCP treatment induces robust deficits in 5C-CPT performance indicative of impaired attention. Pre-treatment with SKF 38393 partially attenuates the PCP-induced deficits in 5C-CPT performance by reducing false alarm responding and increasing response accuracy. Impaired target detection was still evident in SKF 38393-treated rats however. Thus, augmentation of the dopamine D1 system improves PCP-induces deficits in 5C-CPT performance by selectively reducing aspects of inappropriate responding. These findings provide evidence to support the hypothesis that novel therapies targeting the dopamine D1 receptor system could improve aspects of attentional deficits in schizophrenia patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Planar Cell Polarity (PCP) Protein Vangl2 Regulates Ectoplasmic Specialization Dynamics via Its Effects on Actin Microfilaments in the Testes of Male Rats

    PubMed Central

    Chen, Haiqi; Mruk, Dolores D.; Lee, Will M.

    2016-01-01

    Planar cell polarity (PCP) proteins confer polarization of a field of cells (eg, elongating/elongated spermatids) within the plane of an epithelium such as the seminiferous epithelium of the tubule during spermatogenesis. In adult rat testes, Sertoli and germ cells were found to express PCP core proteins (eg, Van Gogh-like 2 [Vangl2]), effectors, ligands, and signaling proteins. Vangl2 expressed predominantly by Sertoli cells was localized at the testis-specific, actin-rich ectoplasmic specialization (ES) at the Sertoli-spermatid interface in the adluminal compartment and also Sertoli-Sertoli interface at the blood-testis barrier (BTB) and structurally interacted with actin, N-cadherin, and another PCP/polarity protein Scribble. Vangl2 knockdown (KD) by RNA interference in Sertoli cells cultured in vitro with an established tight junction-permeability barrier led to BTB tightening, whereas its overexpression using a full-length cDNA construct perturbed the barrier function. These changes were mediated through an alteration on the organization actin microfilaments at the ES in Sertoli cells, involving actin-regulatory proteins, epidermal growth factor receptor pathway substrate 8, actin-related protein 3, and Scribble, which in turn affected the function of adhesion protein complexes at the ES during the epithelial cycle of spermatogenesis. Using Polyplus in vivo-jetPEI reagent as a transfection medium to silence Vangl2 in the testis in vivo by RNA interference with high efficacy, Vangl2 KD led to changes in F-actin organization at the ES in the epithelium, impeding spermatid and phagosome transport and spermatid polarity, meiosis, and BTB dynamics. For instance, step 19 spermatids remained embedded in the epithelium alongside with step 9 and 10 spermatids in stages IX-X tubules. In summary, the PCP protein Vangl2 is an ES regulator through its effects on actin microfilaments in the testis. PMID:26990065

  19. THE USE OF FRY (EMBALMING FLUID AND PCP-LACED CIGARETTES OR MARIJUANA STICKS) AMONG CRACK COCAINE SMOKERS

    PubMed Central

    PETERS, RONALD J.; WILLIAMS, MARK; ROSS, MICHAEL W.; ATKINSON, JOHN; McCURDY, SHERLY A.

    2010-01-01

    Statistics show that the prevalence of crack cocaine use and embalming fluid and phencyclidine (PCP)-laced cigarettes or marijuana sticks, commonly referred to on the street as “fry” or “wet” is a problem; however, the relationship between these substances of abuse and concurrent polydrug use is unknown. In the present study, a cross-sectional survey was conducted among 426 African-American crack users in Houston, Texas, to investigate the difference between those who concurrently reported lifetime (defined as at least one usage of fry in life) fry use and those who stated they never used fry. The data were analyzed using chi-square and logistic regression analyses. Fry users were significantly more likely than non-users to not have a casual sex partner (92% users vs. 84% non-users, p ≤ 0.05) and were more likely to have been diagnosed with gonorrhea in the past 12 months (9% users vs. 2% non-users, p ≤ 0.05). In addition fry users had significantly higher odds of currently trading sex for drugs (OR = 2.30, p ≤ 0.05), marijuana use (OR = 12.11, p ≤ 0.05), and codeine (syrup) use (OR = 8.10, p ≤ 0.05). These findings are important in determining the “cultural novelties” relative to crack and fry use among younger African Americans. PMID:19157045

  20. THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the sub-chronic PCP model of schizophrenia

    PubMed Central

    Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

    2017-01-01

    Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the CSF levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared to THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. PMID:26510449

  1. Nicotine may promote tongue squamous cell carcinoma progression by activating the Wnt/β-catenin and Wnt/PCP signaling pathways.

    PubMed

    Wang, Chengze; Xu, Xin; Jin, Hairu; Liu, Gangli

    2017-05-01

    To investigate the effects and the possible underlying mechanisms of nicotine stimulation on tongue squamous cell carcinoma (TSCC) progression, a TSCC cell line Cal27 and 34 samples of paraffin-embedded TSCC were examined. Immunofluorescence, western blot analysis, and TOP/FOP flash, CCK-8, wound healing and Transwell invasion assays were used to evaluate Cal27 in response to nicotine stimulation. We also investigated expression levels of related proteins of Wnt/β-catenin and Wnt/PCP pathways in paraffin-embedded TSCC samples with or without a history of smoking by immunohistochemistry. Nicotine stimulation can promote proliferation, migration, and invasion of TSCC cells in vitro, downregulate E-cadherin, and activate the Wnt/β-catenin and Wnt/PCP pathways, which could be antagonized by the α7 nicotine acetylcholine receptor (α7 nAChR) inhibitor α-BTX. Moreover, the expression levels of β-catenin, Wnt5a and Ror2 were higher in TSCC patients with a history of smoking than those without a history of smoking. Our results suggest nicotine may promote tongue squamous carcinoma cells progression by activating the Wnt/β-catenin and Wnt/PCP signaling pathways and may play a significant role in the progression and metastasis of smoking-related TSCC.

  2. Effectiveness of an anaerobic granular activated carbon fluidized-bed bioreactor to treat soil wash fluids: a proposed strategy for remediating PCP/PAH contaminated soils.

    PubMed

    Koran, K M; Suidan, M T; Khodadoust, A P; Sorial, G A; Brenner, R C

    2001-07-01

    An integrated system has been developed to remediate soils contaminated with pentachlorophenol (PCP) and polycyclic aromatic hydrocarbons (PAHs). This system involves the coupling of two treatment technologies, soil-solvent washing and anaerobic biotreatment of the extract. Specifically, this study evaluated the effectiveness of a granular activated carbon (GAC) fluidized-bed reactor to treat a synthetic-waste stream of PCP and four PAHs (naphthalene, acenaphthene, pyrene, and benzo(b)fluoranthene) under anaerobic conditions. This waste stream was intended to simulate the wash fluids from a soil washing process treating soils from a wood-preserving site. The reactor achieved a removal efficiency of greater than 99.8% for PCP with conversion to its dechlorination intermediates averaging 46.5%. Effluent, carbon extraction, and isotherm data also indicate that naphthalene and acenaphthene were removed from the liquid phase with efficiencies of 86 and 93%, respectively. Effluent levels of pyrene and benzo(b)fluoranthene were extremely low due to the high-adsorptive capacity of GAC for these compounds. Experimental evidence does not suggest that the latter two compounds were biochemically transformed within the reactor.

  3. The effects of phencyclidine (PCP) on anxiety-like behavior in the elevated plus maze and the light-dark exploration test are age dependent, sexually dimorphic, and task dependent.

    PubMed

    Turgeon, Sarah M; Kim, Daniel; Pritchard, Melissa; Salgado, Sanjay; Thaler, Alison

    2011-11-01

    Previous research in our laboratory revealed sexually dimorphic effects of prior exposure to phencyclidine (PCP) on elevated plus maze behavior. In an attempt to examine the developmental time course of this effect and determine the extent to which it generalizes to other anxiety paradigms, young adult (61-64 days old) and adult (96-107 days old) male and female rats were treated with PCP (15 mg/kg) or saline. Following a two week withdrawal period, animals were tested in either the elevated plus maze (EPM) or a light-dark exploration (LD) test. In adults, both tests revealed a sexually dimorphic effect driven by PCP-induced decreases in anxiety in females as indicated by increased time spent in the open arms of the EPM and in the lit compartment of the LD test and increased anxiety in males as indicated by decreased time spent in the lit compartment of the LD. In young animals, PCP pretreatment decreased open arm exploration in the elevated plus maze, indicating increased anxiety. However, PCP increased time spent in the light compartment in the light-dark exploration test, indicating decreased anxiety. Corticosterone levels measured 15 min after the onset of the EPM failed to reveal an association between the behavioral effects of PCP and corticosterone levels. The results in adults substantiate the previously observed sexually dimorphic effect of PCP on elevated plus maze behavior in adults and indicate that the effect generalizes to another anxiety paradigm. The results in the younger animals suggest an age dependent effect of PCP on anxiety in general and indicate that behaviors in the elevated plus maze and the light-dark exploration test reflect dissociable psychobiological states. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Phencyclidine (PCP)-induced disruption in cognitive performance is gender-specific and associated with a reduction in brain-derived neurotrophic factor (BDNF) in specific regions of the female rat brain.

    PubMed

    Snigdha, Shikha; Neill, Joanna C; McLean, Samantha L; Shemar, Gaurav K; Cruise, Leonie; Shahid, Mohammed; Henry, Brian

    2011-03-01

    Phencyclidine (PCP), used to mimic certain aspects of schizophrenia, induces sexually dimorphic, cognitive deficits in rats. In this study, the effects of sub-chronic PCP on expression of brain-derived neurotrophic factor (BDNF), a neurotrophic factor implicated in the pathogenesis of schizophrenia, have been evaluated in male and female rats. Male and female hooded-Lister rats received vehicle or PCP (n=8 per group; 2 mg/kg i.p. twice daily for 7 days) and were tested in the attentional set shifting task prior to being sacrificed (6 weeks post-treatment). Levels of BDNF mRNA were measured in specific brain regions using in situ hybridisation. Male rats were less sensitive to PCP-induced deficits in the extra-dimensional shift stage of the attentional set shifting task compared to female rats. Quantitative analysis of brain regions demonstrated reduced BDNF levels in the medial prefrontal cortex (p<0.05), motor cortex (p<0.01), orbital cortex (p<0.01), olfactory bulb (p<0.05), retrosplenial cortex (p<0.001), frontal cortex (p<0.01), parietal cortex (p<0.01), CA1 (p<0.05) and polymorphic layer of dentate gyrus (p<0.05) of the hippocampus and the central (p<0.01), lateral (p<0.05) and basolateral (p<0.05) regions of the amygdaloid nucleus in female PCP-treated rats compared with controls. In contrast, BDNF was significantly reduced only in the orbital cortex and central amygdaloid region of male rats (p<0.05). Results suggest that blockade of NMDA receptors by sub-chronic PCP administration has a long-lasting down-regulatory effect on BDNF mRNA expression in the female rat brain which may underlie some of the behavioural deficits observed post PCP administration.

  5. Polychlorinated dibenzo-p-dioxins and dibenzofurans in blood and breast milk samples from residents of a schistosomiasis area with Na-PCP application in China.

    PubMed

    Xiao, Ke; Zhao, Xingru; Liu, Zhengtao; Zhang, Bing; Fang, Liping; Liu, Wenbin; Zheng, Minghui

    2010-04-01

    Schistosomiasis has prevailed in some areas of China for a long time. Chinese technical sodium pentachlorophenate (Na-PCP) has been used to control the spread of snail-borne schistosomiasis since the 1960s. Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), impurities contained in the Na-PCP, enter the soil and may accumulate in the food chain. In order to evaluate their potentially harmful effects on local residents, 50 breast milk samples and 20 blood samples were collected in 2004 from residents in the Dongting Lake area, one of China's known schistosomiasis areas. Levels of 17 PCDD/F congeners were measured in all samples, and DNA damage was simultaneously assessed in blood samples. The PCDD/F congener distribution patterns in human tissue samples from the Dongting Lake area were similar to those in Na-PCP, and the octachlorodibenzodioxin (OCDD) congener was predominant in all samples. We also had a primary investigation that the breast milk WHO-TEQ associated with some factors such as: age, dietary habit, body mass index (BMI) and the total menses times. In blood samples, the samples with higher OCDD level had higher DDS (DNA damage score) values than those samples with low OCDD level, which indicated that the higher DNA damage value in general population might be caused directly or indirectly by PCDD/Fs. The results also indicated that the WHO-TEQ values in blood were associated with age (r=0.6, p=0.007). 2010 Elsevier Ltd. All rights reserved.

  6. An oral oligonucleotide delivery system based on a thiolated polymer: Development and in vitro evaluation.

    PubMed

    Martien, Ronny; Hoyer, Herbert; Perera, Glen; Schnürch, Andreas Bernkop

    2011-08-01

    The purpose of this study was to develop and evaluate an oral oligonucleotide delivery system based on a thiolated polymer/reduced glutathione (GSH) system providing a protective effect toward nucleases and permeation enhancement. A polycarbophil-cysteine conjugate (PCP-Cys) was synthesized. Enzymatic degradation of a model oligonucleotide by DNase I and within freshly collected intestinal fluid was investigated in the absence and presence of PCP-Cys. Permeation studies with PCP-Cys/GSH versus control were performed in vitro on Caco-2 cell monolayers and ex vivo on rat intestinal mucosa. PCP-Cys displayed 223 ± 13.8 μmol thiol groups per gram polymer. After 4h, 61% of the free oligonucleotides were degraded by DNase I and 80% within intestinal fluid. In contrast, less than 41% (DNase I) and 60% (intestinal fluid) were degraded in the presence of 0.02% (m/v) PCP-Cys. Permeation studies revealed an 8-fold (Caco-2) and 10-fold (intestinal mucosa) increase in apparent permeability compared to buffer control. Hence, this PCP-Cys/GSH system might be a promising tool for the oral administration of oligonucleotides as it allows a significant protection toward degrading enzymes and facilitates their transport across intestinal membranes.

  7. Blonanserin reverses the phencyclidine (PCP)-induced impairment in novel object recognition (NOR) in rats: role of indirect 5-HT(1A) partial agonism.

    PubMed

    Horiguchi, M; Meltzer, H Y

    2013-06-15

    Blonanserin is an atypical antipsychotic drug (APD) which, compared to other atypical APDs, is a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist. Comparing blonanserin with more broadly acting atypical APDs could be useful to test the contributions of actions at other monoamine receptors, e.g. 5-HT1A receptors, to the reversal of PCP-induced novel object recognition (NOR) deficit. In this study, we tested the effect of blonanserin alone, and in combination with 5-HT1A agents, on NOR deficit induced by subchronic treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP; 2 mg/kg), b.i.d., for 7 days. Blonanserin, 1mg/kg, but not 0.3mg/kg, improved the PCP-induced NOR deficit. However, at 1mg/kg, object exploration was diminished. Co-administration of sub-effective doses of blonanserin (0.3 mg/kg) and the 5-HT1A partial agonist, tandospirone (0.2 mg/kg), significantly reversed the NOR deficit without diminishing activity during the acquisition or retention periods. The combination of WAY100635 (0.6 mg/kg), a 5-HT1A antagonist, and blonanserin (1 mg/kg), also diminished object exploration which prevented assessment of the effect of this combination on NOR. WAY100635 (0.6 mg/kg) blocked the ameliorating effect of risperidone (0.1 mg/kg), another atypical APD with low affinity for 5-HT1A receptors, but did not impair exploration. These results suggest that blonansein and risperidone, atypical APDs which lack a direct action on 5-HT1A receptors require 5-HT1A receptor stimulation to reverse the subchronic PCP-induced NOR deficit and provide a support for clinical trial of blonanserin in combination with tandospirone to ameliorate cognitive impairment in schizophrenia and to have fewer side effects. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats.

    PubMed

    Damgaard, Trine; Larsen, Dorrit Bjerg; Hansen, Suzanne L; Grayson, Ben; Neill, Jo C; Plath, Niels

    2010-02-11

    Cognitive deficits are a major clinical unmet need in schizophrenia. The psychotomimetic drug phencyclidine (PCP) is widely applied in rodents to mimic symptoms of schizophrenia, including cognitive deficits. Previous studies have shown that sub-chronic PCP induces an enduring episodic memory deficit in female Lister Hooded rats in the novel object recognition (NOR) task. Here we show that positive modulation of AMPA receptor (AMPAR) mediated glutamate transmission alleviates cognitive deficits induced by sub-chronic PCP treatment. Female Lister hooded rats were treated sub-chronically with either vehicle (0.9% saline) or PCP (2mg/kg two doses per day for 7 days), followed by a 7 days washout period. 30 min prior to the acquisition trial of the NOR task animals were dosed with either vehicle, CX546 (10, 40 or 80 mg/kg) or CX516 (0.5, 2.5, 10, 40 or 80 mg/kg). Our results show that sub-chronic PCP treatment induced a significant decrease in the discrimination index (DI) and both ampakines CX546 and CX516 were able to reverse this disruption of object memory in rats in the novel object recognition task. These data suggest that positive AMPAR modulation may represent a mechanism for treatment of cognitive deficits in schizophrenia.

  9. A PCP Pincer Ligand for Coordination Polymers with Versatile Chemical Reactivity: Selective Activation of CO2 Gas over CO Gas in the Solid State.

    PubMed

    He, Junpeng; Waggoner, Nolan W; Dunning, Samuel G; Steiner, Alexander; Lynch, Vincent M; Humphrey, Simon M

    2016-09-26

    A tetra(carboxylated) PCP pincer ligand has been synthesized as a building block for porous coordination polymers (PCPs). The air- and moisture-stable PCP metalloligands are rigid tetratopic linkers that are geometrically akin to ligands used in the synthesis of robust metal-organic frameworks (MOFs). Here, the design principle is demonstrated by cyclometalation with Pd(II) Cl and subsequent use of the metalloligand to prepare a crystalline 3D MOF by direct reaction with Co(II) ions and structural resolution by single crystal X-ray diffraction. The Pd-Cl groups inside the pores are accessible to post-synthetic modifications that facilitate chemical reactions previously unobserved in MOFs: a Pd-CH3 activated material undergoes rapid insertion of CO2 gas to give Pd-OC(O)CH3 at 1 atm and 298 K. However, since the material is highly selective for the adsorption of CO2 over CO, a Pd-N3 modified version resists CO insertion under the same conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death.

    PubMed

    Schuenemann, Verena J; Bos, Kirsten; DeWitte, Sharon; Schmedes, Sarah; Jamieson, Joslyn; Mittnik, Alissa; Forrest, Stephen; Coombes, Brian K; Wood, James W; Earn, David J D; White, William; Krause, Johannes; Poinar, Hendrik N

    2011-09-20

    Although investigations of medieval plague victims have identified Yersinia pestis as the putative etiologic agent of the pandemic, methodological limitations have prevented large-scale genomic investigations to evaluate changes in the pathogen's virulence over time. We screened over 100 skeletal remains from Black Death victims of the East Smithfield mass burial site (1348-1350, London, England). Recent methods of DNA enrichment coupled with high-throughput DNA sequencing subsequently permitted reconstruction of ten full human mitochondrial genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at high coverage. Comparisons of molecular damage profiles between endogenous human and Y. pestis DNA confirmed its authenticity as an ancient pathogen, thus representing the longest contiguous genomic sequence for an ancient pathogen to date. Comparison of our reconstructed plasmid against modern Y. pestis shows identity with several isolates matching the Medievalis biovar; however, our chromosomal sequences indicate the victims were infected with a Y. pestis variant that has not been previously reported. Our data reveal that the Black Death in medieval Europe was caused by a variant of Y. pestis that may no longer exist, and genetic data carried on its pPCP1 plasmid were not responsible for the purported epidemiological differences between ancient and modern forms of Y. pestis infections.

  11. Catalytic amine-borane dehydrogenation by a PCP-pincer palladium complex: a combined experimental and DFT analysis of the reaction mechanism.

    PubMed

    Rossin, Andrea; Bottari, Giovanni; Lozano-Vila, Ana M; Paneque, Margarita; Peruzzini, Maurizio; Rossi, Andrea; Zanobini, Fabrizio

    2013-03-14

    Catalytic dehydrogenation of ammonia-borane (NH(3)·BH(3), AB) and dimethylamine borane (NHMe(2)·BH(3), DMAB) by the Pd(II) complex [((tBu)PCP)Pd(H(2)O)]PF(6) [(tBu)PCP = 2,6-C(6)H(3)(CH(2)P(t)Bu(2))(2)] leads to oligomerization and formation of spent fuels of general formula cyclo-[BH(2)-NR(2)](n) (n = 2,3; R = H, Me) as reaction byproducts, while one equivalent of H(2) is released per amine-borane equivalent. The processes were followed through multinuclear ((31)P, (1)H, (11)B) variable temperature NMR spectroscopy; kinetic measurements on the hydrogen production rate and the relative rate constants were also carried out. One non-hydridic intermediate could be detected at low temperature, whose chemical nature was explored through a DFT modeling of the reaction mechanism, at the M06//6-31+G(d,p) computational level. The computational output was of help to propose a reliable mechanistic picture of the process.

  12. Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling Pathway

    PubMed Central

    Vitorino, Marta; Silva, Ana Cristina; Inácio, José Manuel; Ramalho, José Silva; Gur, Michal; Fainsod, Abraham; Steinbeisser, Herbert; Belo, José António

    2015-01-01

    Protein Kinase Domain Containing, Cytoplasmic (PKDCC) is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP) molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway. PMID:26270962

  13. The Comparative Photodegradation Activities of Pentachlorophenol (PCP) and Polychlorinated Biphenyls (PCBs) Using UV Alone and TiO2-Derived Photocatalysts in Methanol Soil Washing Solution

    PubMed Central

    Zhou, Zeyu; Zhang, Yaxin; Wang, Hongtao; Chen, Tan; Lu, Wenjing

    2014-01-01

    Photochemical treatment is increasingly being applied to remedy environmental problems. TiO2-derived catalysts are efficiently and widely used in photodegradation applications. The efficiency of various photochemical treatments, namely, the use of UV irradiation without catalyst or with TiO2/graphene-TiO2 photodegradation methods was determined by comparing the photodegadation of two main types of hydrophobic chlorinated aromatic pollutants, namely, pentachlorophenol (PCP) and polychlorinated biphenyls (PCBs). Results show that photodegradation in methanol solution under pure UV irradiation was more efficient than that with either one of the catalysts tested, contrary to previous results in which photodegradation rates were enhanced using TiO2-derived catalysts. The effects of various factors, such as UV light illumination, addition of methanol to the solution, catalyst dosage, and the pH of the reaction mixture, were examined. The degradation pathway was deduced. The photochemical treatment in methanol soil washing solution did not benefit from the use of the catalysts tested. Pure UV irradiation was sufficient for the dechlorination and degradation of the PCP and PCBs. PMID:25254664

  14. The comparative photodegradation activities of pentachlorophenol (PCP) and polychlorinated biphenyls (PCBs) using UV alone and TiO2-derived photocatalysts in methanol soil washing solution.

    PubMed

    Zhou, Zeyu; Zhang, Yaxin; Wang, Hongtao; Chen, Tan; Lu, Wenjing

    2014-01-01

    Photochemical treatment is increasingly being applied to remedy environmental problems. TiO2-derived catalysts are efficiently and widely used in photodegradation applications. The efficiency of various photochemical treatments, namely, the use of UV irradiation without catalyst or with TiO2/graphene-TiO2 photodegradation methods was determined by comparing the photodegadation of two main types of hydrophobic chlorinated aromatic pollutants, namely, pentachlorophenol (PCP) and polychlorinated biphenyls (PCBs). Results show that photodegradation in methanol solution under pure UV irradiation was more efficient than that with either one of the catalysts tested, contrary to previous results in which photodegradation rates were enhanced using TiO2-derived catalysts. The effects of various factors, such as UV light illumination, addition of methanol to the solution, catalyst dosage, and the pH of the reaction mixture, were examined. The degradation pathway was deduced. The photochemical treatment in methanol soil washing solution did not benefit from the use of the catalysts tested. Pure UV irradiation was sufficient for the dechlorination and degradation of the PCP and PCBs.

  15. Localized double-array stacking analysis of PcP: D″ and ULVZ structure beneath the Cocos plate, Mexico, central Pacific, and north Pacific

    USGS Publications Warehouse

    Hutko, Alexander R.; Lay, Thorne; Revenaugh, Justin

    2009-01-01

    A large, high quality P-wave data set comprising short-period and broadband signals sampling four separate regions in the lowermost mantle beneath the Cocos plate, Mexico, the central Pacific, and the north Pacific is analyzed using regional one-dimensional double-array stacking and modelling with reflectivity synthetics. A data-screening criterion retains only events with stable PcP energy in the final data stacks used for modelling and interpretation. This significantly improves the signal stacks relative to including unscreened observations, allows confident alignment on the PcP arrival and allows tight bounds to be placed on P-wave velocity structure above the core–mantle boundary (CMB). The PcP reflections under the Cocos plate are well modelled without any ultra-low velocity zone from 5 to 20°N. At latitudes from 15 to 20°N, we find evidence for two P-wave velocity discontinuities in the D″ region. The first is ∼182 km above the CMB with a δln Vp of +1.5%, near the same depth as a weaker discontinuity (<+0.5%) observed from 5 to 15°N in prior work. The other reflector is ∼454 km above the CMB, with a δln Vp of +0.4%; this appears to be a shallower continuation of the joint P- and S-wave discontinuity previously detected south of 15° N, which is presumed to be the perovskite to post-perovskite phase transition. The data stacks for paths bottoming below Mexico have PcP images that are well matched with the simple IASP91 structure, contradicting previous inferences of ULVZ presence in this region. These particular data are not very sensitive to any D″ discontinuities, and simply bound them to be <∼2%, if present. Data sampling the lowermost mantle beneath the central Pacific confirm the presence of a ∼15-km thick ultra-low velocity zone (ULVZ) just above the CMB, with δln Vp and δln Vs of around −3 to −4% and −4 to −8%, respectively. The ULVZ models predict previous S-wave data stacks well. The data for this region

  16. Comparison of ( sup 3 H)Phencyclidine (( sup 3 H)PCP) and ( sup 3 H) N-(1-(2-thienyl) cyclohexyl)piperidine (( sup 3 H)TCP) binding properties to rat and human brain membranes

    SciTech Connect

    Vignon, J.; Chaudieu, I.; Allaoua, H.; Journod, L.; Javoy-Agid, F.; Agid, Y.; Chicheportiche, R.

    1989-01-01

    The investigation of ({sup 3}H)PCP and ({sup 3}H)TCP binding properties to rat cerebrum and cerebellum resulted in the demonstration of multiple binding sites for the two drugs. In the two tissue preparations PCP had a lower affinity than TCP. In membranes from the cerebrum an equal number of high affinity binding sites were present for ({sup 3}H)PCP and ({sup 3}H)TCP. However, low affinity binding sites were two times more numerous for ({sup 3}H)PCP than for ({sup 3}H)TCP. In the cerebellum, the number of high and low affinity sites labeled by the two radioligands was identical, but the number of high affinity sites was about 7 fold lower than in cerebrum. In human cerebral cortex samples ({sup 3}H)TCP also bound to two different sites. The number of high and low affinity sites were 12 and 3 times, respectively, less abundant than in the rat cerebrum. Low affinity sites were of higher affinity than corresponding sites in the rat brain. In the human cerebellum ({sup 3}H)TCP binding parameters were identical to those measured in the same region in the rat.

  17. Recent advances in visible-light-responsive photocatalysts for hydrogen production and solar energy conversion--from semiconducting TiO2 to MOF/PCP photocatalysts.

    PubMed

    Horiuchi, Yu; Toyao, Takashi; Takeuchi, Masato; Matsuoka, Masaya; Anpo, Masakazu

    2013-08-28

    The present perspective describes recent advances in visible-light-responsive photocatalysts intended to develop novel and efficient solar energy conversion technologies, including water splitting and photofuel cells. Water splitting is recognized as one of the most promising techniques to convert solar energy as a clean and abundant energy resource into chemical energy in the form of hydrogen. In recent years, increasing concern is directed to not only the development of new photocatalytic materials but also the importance of technologies to produce hydrogen and oxygen separately. Photofuel cells can convert solar energy into electrical energy by decomposing bio-related compounds and livestock waste as fuels. The advances of photocatalysts enabling these solar energy conversion technologies have been going on since the discovery of semiconducting titanium dioxide materials and have extended to organic-inorganic hybrid materials, such as metal-organic frameworks and porous coordination polymers (MOF/PCP).

  18. Mechanistic insights into the role of PC- and PCP-type palladium catalysts in asymmetric hydrophosphination of activated alkenes incorporating potential coordinating heteroatoms.

    PubMed

    Yang, Xiang-Yuan; Jia, Yu-Xiang; Tay, Wee Shan; Li, Yongxin; Pullarkat, Sumod A; Leung, Pak-Hing

    2016-09-14

    The impact of the structural attributes of chiral PC- and PCP-palladium catalysts was investigated in the asymmetric hydrophosphination of various heterocycle-functionalized enone substrates. Due to the architecture of the catalysts, they are confronted with potential catalyst deactivation arising from the coordination of the electron-rich heteroatoms (P, O, N and S) to the metal center. A systematic variation of the location and identity of the heteroatoms demonstrated the impact of structural modifications on the substrates, which have a significant influence on both yields (16-99%) and enantioselectivities (0-99%). A detailed discussion on the distinct catalytic mechanisms (intra- vs. inter-molecular addition) provides important information to explain the results obtained.

  19. Genomic Insights into a New Citrobacter koseri Strain Revealed Gene Exchanges with the Virulence-Associated Yersinia pestis pPCP1 Plasmid

    PubMed Central

    Armougom, Fabrice; Bitam, Idir; Croce, Olivier; Merhej, Vicky; Barassi, Lina; Nguyen, Ti-Thien; La Scola, Bernard; Raoult, Didier

    2016-01-01

    The history of infectious diseases raised the plague as one of the most devastating for human beings. Far too often considered an ancient disease, the frequent resurgence of the plague has led to consider it as a reemerging disease in Madagascar, Algeria, Libya, and Congo. The genetic factors associated with the pathogenicity of Yersinia pestis, the causative agent of the plague, involve the acquisition of the pPCP1 plasmid that promotes host invasion through the expression of the virulence factor Pla. The surveillance of plague foci after the 2003 outbreak in Algeria resulted in a positive detection of the specific pla gene of Y. pestis in rodents. However, the phenotypic characterization of the isolate identified a Citrobacter koseri. The comparative genomics of our sequenced C. koseri URMITE genome revealed a mosaic gene structure resulting from the lifestyle of our isolate and provided evidence for gene exchanges with different enteric bacteria. The most striking was the acquisition of a continuous 2 kb genomic fragment containing the virulence factor Pla of the Y. pestis pPCP1 plasmid; however, the subcutaneous injection of the CKU strain in mice did not produce any pathogenic effect. Our findings demonstrate that fast molecular detection of plague using solely the pla gene is unsuitable and should rather require Y. pestis gene marker combinations. We also suggest that the evolutionary force that might govern the expression of pathogenicity can occur through the acquisition of virulence genes but could also require the loss or the inactivation of resident genes such as antivirulence genes. PMID:27014253

  20. Genomic Insights into a New Citrobacter koseri Strain Revealed Gene Exchanges with the Virulence-Associated Yersinia pestis pPCP1 Plasmid.

    PubMed

    Armougom, Fabrice; Bitam, Idir; Croce, Olivier; Merhej, Vicky; Barassi, Lina; Nguyen, Ti-Thien; La Scola, Bernard; Raoult, Didier

    2016-01-01

    The history of infectious diseases raised the plague as one of the most devastating for human beings. Far too often considered an ancient disease, the frequent resurgence of the plague has led to consider it as a reemerging disease in Madagascar, Algeria, Libya, and Congo. The genetic factors associated with the pathogenicity of Yersinia pestis, the causative agent of the plague, involve the acquisition of the pPCP1 plasmid that promotes host invasion through the expression of the virulence factor Pla. The surveillance of plague foci after the 2003 outbreak in Algeria resulted in a positive detection of the specific pla gene of Y. pestis in rodents. However, the phenotypic characterization of the isolate identified a Citrobacter koseri. The comparative genomics of our sequenced C. koseri URMITE genome revealed a mosaic gene structure resulting from the lifestyle of our isolate and provided evidence for gene exchanges with different enteric bacteria. The most striking was the acquisition of a continuous 2 kb genomic fragment containing the virulence factor Pla of the Y. pestis pPCP1 plasmid; however, the subcutaneous injection of the CKU strain in mice did not produce any pathogenic effect. Our findings demonstrate that fast molecular detection of plague using solely the pla gene is unsuitable and should rather require Y. pestis gene marker combinations. We also suggest that the evolutionary force that might govern the expression of pathogenicity can occur through the acquisition of virulence genes but could also require the loss or the inactivation of resident genes such as antivirulence genes.

  1. Translational Aspects of the Novel Object Recognition Task in Rats Abstinent Following Sub-Chronic Treatment with Phencyclidine (PCP): Effects of Modafinil and Relevance to Cognitive Deficits in Schizophrenia

    PubMed Central

    Redrobe, John P.; Bull, Sascha; Plath, Niels

    2010-01-01

    Phencyclidine (PCP) induces a behavioral syndrome in rodents that bears remarkable similarities to some of the core symptoms observed in schizophrenic patients, among those cognitive deficits. The successful alleviation of cognitive impairments associated with schizophrenia (CIAS) has become a major focus of research efforts as they remain largely untreated. The aim of the present study was to investigate the effects of selected antipsychotic and cognition enhancing drugs, namely haloperidol, risperidone, donepezil, and modafinil in an animal model widely used in preclinical schizophrenia research. To this end, the novel object recognition (NOR) task was applied to rats abstinent following sub-chronic treatment with PCP. Rats were administered either PCP (5 mg/kg, i.p.) or vehicle twice a day for 7 days, followed by a 7-day washout period, before testing in NOR. Upon testing, vehicle-treated rats successfully discriminated between novel and familiar objects, an effect abolished in rats that had previously been exposed to PCP treatment. Acute treatment with modafinil (64 mg/kg, p.o.) ameliorated the PCP-induced deficit in novel object exploration, whereas haloperidol (0.1 mg/kg, s.c.), risperidone (0.2 mg/kg, i.p.), and donepezil (3 mg/kg, p.o.) were without significant effect. Given the negligible efficacy of haloperidol and risperidone, and the contradictory data with donepezil to treat CIAS in the clinic, together with the promising preliminary pro-cognitive effects of modafinil in certain subsets of schizophrenic patients, the sub-chronic PCP–NOR abstinence paradigm may represent an attractive option for the identification of potential novel treatments for CIAS. PMID:21423454

  2. Population-Based Versus Practice-Based Recall for Childhood Immunizations: A Randomized Controlled Comparative Effectiveness Trial

    PubMed Central

    Saville, Alison; Dickinson, L. Miriam; Eisert, Sheri; Reynolds, Joni; Herrero, Diana; Beaty, Brenda; Albright, Karen; Dibert, Eva; Koehler, Vicky; Lockhart, Steven; Calonge, Ned

    2013-01-01

    Objectives. We compared the effectiveness and cost-effectiveness of population-based recall (Pop-recall) versus practice-based recall (PCP-recall) at increasing immunizations among preschool children. Methods. This cluster-randomized trial involved children aged 19 to 35 months needing immunizations in 8 rural and 6 urban Colorado counties. In Pop-recall counties, recall was conducted centrally using the Colorado Immunization Information System (CIIS). In PCP-recall counties, practices were invited to attend webinar training using CIIS and offered financial support for mailings. The percentage of up-to-date (UTD) and vaccine documentation were compared 6 months after recall. A mixed-effects model assessed the association between intervention and whether a child became UTD. Results. Ten of 195 practices (5%) implemented recall in PCP-recall counties. Among children needing immunizations, 18.7% became UTD in Pop-recall versus 12.8% in PCP-recall counties (P < .001); 31.8% had documented receipt of 1 or more vaccines in Pop-recall versus 22.6% in PCP-recall counties (P < .001). Relative risk estimates from multivariable modeling were 1.23 (95% confidence interval [CI] = 1.10, 1.37) for becoming UTD and 1.26 (95% CI = 1.15, 1.38) for receipt of any vaccine. Costs for Pop-recall versus PCP-recall were $215 versus $1981 per practice and $17 versus $62 per child brought UTD. Conclusions. Population-based recall conducted centrally was more effective and cost-effective at increasing immunization rates in preschool children. PMID:23237154

  3. Extraction of weak PcP phases using the slant-stacklet transform - II: constraints on lateral variations of structure near the core-mantle boundary

    NASA Astrophysics Data System (ADS)

    Ventosa, Sergi; Romanowicz, Barbara

    2015-11-01

    Resolving the topography of the core-mantle boundary (CMB) and the structure and composition of the D″ region is key to improving our understanding of the interaction between the Earth's mantle and core. Observations of traveltimes and amplitudes of short-period teleseismic body waves sensitive to lowermost mantle provide essential constraints on the properties of this region. Major challenges are low signal-to-noise ratio of the target phases and interference with other mantle phases. In a previous paper (Part I), we introduced the slant-stacklet transform to enhance the signal of the core-reflected (PcP) phase and to isolate it from stronger signals in the coda of the P wave. Then we minimized a linear misfit between P and PcP waveforms to improve the quality of PcP-P traveltime difference measurements as compared to standard cross-correlation methods. This method significantly increases the quantity and the quality of PcP-P traveltime observations available for the modelling of structure near the CMB. Here we illustrate our approach in a series of regional studies of the CMB and D″ using PcP-P observations with unprecedented resolution from high-quality dense arrays located in North America and Japan for events with magnitude Mw>5.4 and distances up to 80°. In this process, we carefully analyse various sources of errors and show that mantle heterogeneity is the most significant. We find and correct bias due to mantle heterogeneities that is as large as 1 s in traveltime, comparable to the largest lateral PcP-P traveltime variations observed. We illustrate the importance of accurate mantle corrections and the need for higher resolution mantle models for future studies. After optimal mantle corrections, the main signal left is relatively long wavelength in the regions sampled, except at the border of the Pacific large-low shear velocity province (LLSVP). We detect the northwest border of the Pacific LLSVP in the western Pacific from array observations in

  4. High-resolution mapping of D16Led-1, Gart, Gas-r, Cbr, Pcp-4, and Erg on distal mouse chromosome 16

    SciTech Connect

    Mjaatvedt, A.E.; Citron, M.P.; Reeves, R.H. )

    1993-08-01

    More than 500 backcross progeny from four inter-subspecific backcrosses were typed for six markers on distal mouse chromosome 16. Five of these represented genes that mapped within the Sod-1 to Ets-2 interval, which was shown previously to contain the weaver (wv) gene. The map order, including previously mapped reference markers, is (cen)-D16H21S16-D16Led-1-App-Sod-1-Gart-Gas-4-Cbr-wv-Pep-4-Erg-Ets-2. This gene order recapitulates the order of the genes on human chromosome 21 where known. Two of these markers further define the region containing the weaver gene to a 3.9-cM segment between Cbr and Pcp-4. In addition, Pep-4 was localized to human chromosome 21 by the presence of a human-specific restriction fragment in WAV-17, a mouse-human somatic cell hybrid with human chromosome 31 as the only human contribution. 26 refs., 3 figs., 3 tabs.

  5. Structural and Temporal Requirements of Wnt/PCP Protein Vangl2 Function for Convergence and Extension Movements and Facial Branchiomotor Neuron Migration in Zebrafish

    PubMed Central

    Pan, Xiufang; Sittaramane, Vinoth; Gurung, Suman; Chandrasekhar, Anand

    2014-01-01

    Van gogh-like 2 (Vangl2), a core component of the Wnt/Planar Cell Polarity (PCP) signaling pathway, is a four-pass transmembrane protein with N-terminal and C-terminal domains located in the cytosol, and is structurally conserved from flies to mammals. In vertebrates, Vangl2 plays an essential role in convergence and extension (CE) movements during gastrulation and in facial branchiomotor (FBM) neuron migration in the hindbrain. However, the roles of specific Vangl2 domains, of membrane association, and of specific extracellular and intracellular motifs have not been examined, especially in the context of FBM neuron migration. Through heat shock-inducible expression of various Vangl2 transgenes, we found that membrane associated functions of the N-terminal and C-terminal domains of Vangl2 are involved in regulating FBM neuron migration. Importantly, through temperature shift experiments, we found that the critical period for Vangl2 function coincides with the initial stages of FBM neuron migration out of rhombomere 4. Intriguingly, we have also uncovered a putative nuclear localization motif in the C-terminal domain that may play a role in regulating CE movements. PMID:24333599

  6. E6/E7-P53-POU2F1-CTHRC1 axis promotes cervical cancer metastasis and activates Wnt/PCP pathway

    PubMed Central

    Zhang, Rong; Lu, Huan; Lyu, Yuan-yuan; Yang, Xiao-mei; Zhu, Lin-yan; Yang, Guang-dong; Jiang, Peng-cheng; Re, Yuan; Song, Wei-wei; Wang, Jin-hao; Zhang, Can-can; Gu, Fei; Luo, Tian-jiao; Wu, Zhi-yong; Xu, Cong-jian

    2017-01-01

    Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters. CTHRC1 promotes cervical cancer cell migration and invasion in vitro and metastasis in vivo. E6/E7 regulates the expression of CTHRC1 in cervical cancer by E6/E7-p53-POU2F1 (POU class 2 homeobox 1) axis. Futhermore, CTHRC1 activates Wnt/PCP signaling pathway. Take together, E6/E7-p53-POU2F1-CTHRC1 axis promotes cervical cancer cell invasion and metastasis and may act as a potential therapeutic target for interventions against cervical cancer invasion and metastasis. PMID:28303973

  7. High average daily intake of PCDD/Fs and serum levels in residents living near a deserted factory producing pentachlorophenol (PCP) in Taiwan: influence of contaminated fish consumption.

    PubMed

    Lee, C C; Lin, W T; Liao, P C; Su, H J; Chen, H L

    2006-05-01

    An abandoned pentachlorophenol plant and nearby area in southern Taiwan was heavily contaminated by dioxins, impurities formed in the PCP production process. The investigation showed that the average serum PCDD/Fs of residents living nearby area (62.5 pg WHO-TEQ/g lipid) was higher than those living in the non-polluted area (22.5 and 18.2 pg WHO-TEQ/g lipid) (P<0.05). In biota samples, average PCDD/F of milkfish in sea reservoir (28.3 pg WHO-TEQ/g) was higher than those in the nearby fish farm (0.15 pg WHO-TEQ/g), and Tilapia and shrimp showed the similar trend. The average daily PCDD/Fs intake of 38% participants was higher than 4 pg WHO-TEQ/kg/day suggested by the world health organization. Serum PCDD/F was positively associated with average daily intake (ADI) after adjustment for age, sex, BMI, and smoking status. In addition, a prospective cohort study is suggested to determine the long-term health effects on the people living near factory.

  8. The Drosophila GIPC homologue can modulate myosin based processes and planar cell polarity but is not essential for development.

    PubMed

    Djiane, Alexandre; Mlodzik, Marek

    2010-06-21

    Epithelia often show, in addition to the ubiquitous apico-basal (A/B) axis, a polarization within the plane of the epithelium, perpendicular to the A/B axis. Such planar cell polarity (PCP) is for example evident in the regular arrangement of the stereocilia in the cochlea of the mammalian inner ear or in (almost) all Drosophila adult external structures. GIPCs (GAIP interacting protein, C terminus) were first identified in mammals and bind to the Galphai GTPase activating protein RGS-GAIP. They have been proposed to act in a G-protein coupled complex controlling vesicular trafficking. Although GIPCs have been found to bind to numerous proteins including Frizzled receptors, which participate in PCP establishment, there is little in vivo evidence for the functional role(s) of GIPCs. We show here that overexpressed Drosophila dGIPC alters PCP generation in the wing. We were however unable to find any binding between dGIPC and the Drosophila receptors Fz1 and Fz2. The effect of overexpressed dGIPC is likely due to an effect on the actin cytoskeleton via myosins, since it is almost entirely suppressed by removing a genomic copy of the Myosin VI/jaguar gene. Surprisingly, although dGIPC can interfere with PCP generation and myosin based processes, the complete loss-of-function of dGIPC gives viable adults with no PCP or other detectable defects arguing for a non-essential role of dGIPC in viability and normal Drosophila development.

  9. Pneumocystis carinii (jirovecii) pneumonia (PCP): the most common opportunistic infection observed in HIV/AIDS cases at the University Malaya Medical Centre, Kuala Lumpur, Malaysia.

    PubMed

    Jamaiah, I; Rohela, M; Tok, E L; Tan, C L; Tan, W H; Teo, W S; Leow, H F

    2012-07-01

    This retrospective study was conducted among 59 HIV/AIDS patients with opportunistic infections admitted to the University Malaya Medical Centre between 2000 and 2009. Fifty-five point nine percent of cases were Chinese, 25.4% were Malays, 11.9% were Indians and 6.8% were of unknown ethnic origin. The male:female ratio was 2.9:1 (44 males and 15 females). The highest prevalence (38.9%) occurred in the 30-39 year old age group. Men comprised 47.7% and women 53.3%; the majority of both were married. The majority of cases were Malaysians (89.8%) and the rest (10.2%) were immigrants. Most of the patients (18.6%) were non-laborers, followed by laborers (11.9%), the unemployed (5.1%) and housewives (3.4%). The most common risk factor was unprotected sexual activity (20.3%). The two most common HIV/AIDS related opportunistic infections were Pneumocystis carinii (jirovecii) pneumonia (PCP) (62.7%) and toxoplasmosis (28.8%). Seventy-two point nine percent of patients had a CD4 count <200 cells/microl and 5.1% had a CD4 count >500 cells/microl. Eleven point nine percent of cases died during study period. A low CD4 count had a greater association with opportunistic infections. Most of the patients presented with fever (44.1%), cough (42.4%) and shortness of breath (28.8%). Detection of the etiologic pathogens aids clinicians in choosing appropriate management strategies.

  10. Development of a novel, bioluminescence-based, fungal bioassay for toxicity testing.

    PubMed

    Weitz, Hedda J; Campbell, Colin D; Killham, Ken

    2002-07-01

    Naturally bioluminescent fungi, Armillaria mellea and Mycena citricolor, were used to develop a novel, bioluminescence-based bioassay for toxicity testing. Bioassays were carried out to assess the toxicity of 3,5-dichlorophenol (3,5-DCP), pentachlorophenol (PCP), copper and zinc. The results suggested that 60 min was a suitable exposure time for the bioassay. Light reduction was observed in response to 3,5-DCP, PCP and Cu for both A. mellea and M. citricolor, but to Zn only for A. mellea. Armillaria mellea was significantly less sensitive to 3,5-DCP and PCP than M. citricolor. The EC50 values for A. mellea and M. citricolor were similar to EC50 values for 3,5-DCP, PCP and Cu (but not Zn) of bioluminescence-based bacterial biosensors. They were also similar to EC50 values for Cu and Zn of a bioluminescence-based yeast biosensor. The results highlighted the importance of using both prokaryotic and eukaryotic biosensors. The novel bioassay provides a rapid and sensitive method to assess bioavailability of pollutants as well as a method to determine their toxicity to filamentous fungi. It also expands the range of organisms that can be used for bioluminescence-based toxicity testing by complementing existing biosensors.

  11. Development and evaluation of buccoadhesive tablet for selegiline hydrochloride based on thiolated polycarbophil.

    PubMed

    Wasnik, Mangesh N; Godse, Rutika D; Nair, Hema A

    2014-05-01

    Selegiline hydrochloride (SHCl), a monoamine oxidase B inhibitor, is used as an adjunct in the therapy of Parkinson's disease. This study is concerned with the preparation and evaluation of mucoadhesive buccal tablet for controlled systemic delivery of SHCl. Buccal absorption of selegiline can bypass its first-pass metabolism and improve bioavailability accompanied by greatly reduced metabolite formation, which is potentially of enhanced therapeutic value in patients with Parkinson's disease. Polycarbophil-cysteine (PCP-cys) conjugate, which is a thiolated derivative of the mucoadhesive polymer polycarbophil, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-mediated amide bond coupling. Tablets of SHCl based on native and thiolated polycarbophil were prepared. The prepared tablets were evaluated for drug content, swelling behavior, mucoadhesive strength, in vitro drug release, ex vivo permeation and in vitro cytotoxicity. PCP-cys tablets showed enhanced mucoadhesion and retarded drug release compared to polycarbophil tablets. Permeation data of SHCl from matrices prepared using the PCP-cys polymer revealed a significantly higher value of apparent permeability in comparison to polycarbophil, which supported the information in literature that thiolation imparts permeation enhancing properties to mucoadhesive polymers. In vitro cytotoxicity studies on PCP-cys using L-929 mouse fibroblast cell line indicated that conjugation with cysteine does not impart any apparent toxicity to polycarbophil. The results from the study indicate that the buccal delivery of SHCl using thiolated polycarbophil tablet could provide a way for improved therapy of Parkinson's disease.

  12. Scalable Multivariate Volume Visualization and Analysis Based on Dimension Projection and Parallel Coordinates.

    PubMed

    Guo, Hanqi; Xiao, He; Yuan, Xiaoru

    2012-09-01

    In this paper, we present an effective and scalable system for multivariate volume data visualization and analysis with a novel transfer function interface design that tightly couples parallel coordinates plots (PCP) and MDS-based dimension projection plots. In our system, the PCP visualizes the data distribution of each variate (dimension) and the MDS plots project features. They are integrated seamlessly to provide flexible feature classification without context switching between different data presentations during the user interaction. The proposed interface enables users to identify relevant correlation clusters and assign optical properties with lassos, magic wand, and other tools. Furthermore, direct sketching on the volume rendered images has been implemented to probe and edit features. With our system, users can interactively analyze multivariate volumetric data sets by navigating and exploring feature spaces in unified PCP and MDS plots. To further support large-scale multivariate volume data visualization and analysis, Scalable Pivot MDS (SPMDS), parallel adaptive continuous PCP rendering, as well as parallel rendering techniques are developed and integrated into our visualization system. Our experiments show that the system is effective in multivariate volume data visualization and its performance is highly scalable for data sets with different sizes and number of variates.

  13. School-based Screening to Identify Children At Risk for Attention-Deficit/Hyperactivity Disorder: Barriers and Implications.

    PubMed

    Barry, Tammy D; Sturner, Raymond A; Seymour, Karen; Howard, Barbara H; McGoron, Lucy; Bergmann, Paul; Kent, Ronald; Sullivan, Casey; Tomeny, Theodore S; Pierce, Jessica S; Coin, Kristen L; Goodlad, James K; Werle, Nichole

    This report describes a school-based screening project to improve early identification of children at risk for attention-deficit/hyperactivity disorder (ADHD) and communicate these concerns to parents, recommending that they contact their child's primary care provider (PCP). Of 17,440 eligible children in first through fifth grades in five school districts, 47.0% of parents provided required written consent, and teachers completed 70.4% of the online screeners (using the Vanderbilt AD/HD Diagnostic Teacher Rating Scale). Of 5,772 screeners completed, 18.1% of children (n = 1,044) were identified as at risk. Parents of at-risk children were contacted to explain risk status and recommended to visit their child's PCP for further evaluation. It was not possible to contact 39.1% of parents of at-risk children. Of the 636 parents of at-risk children who could be contacted, 53.1% (n = 338) verbally accepted the recommendation to follow-up with their PCP, which was not related to ADHD symptom severity. Parents of children with IEPs or related services were more likely to accept the recommendation to visit the PCP. Our exploration of the potential for school-based screening for ADHD identified a number of barriers to successful execution, but the data also indicated that this is an important problem to address.

  14. The European water-based environmental quality standard for pentachlorophenol is NOT protective of benthic organisms.

    PubMed

    Bettinetti, Roberta; Kopp-Schneider, Annette; Vignati, Davide A L

    2017-09-09

    Risk management of toxic substances is often based on Environmental Quality Standards (EQS) set for the water compartment, assuming they will also protect benthic organisms. In the absence of experimental data, EQS for sediments can be estimated by the equilibrium partitioning approach. The present study investigates whether this approach is protective of benthic organisms against pentachlorophenol (PCP), a legacy contaminant and EU priority substance still used in some parts of the world. Three freshwater species of invertebrates with different life cycles and feeding behaviors (the oligochaetes Lumbriculus variegatus, Tubifex tubifex and the dipteran insect Chironomus riparius) were exposed to PCP spiked sediments (2.10-46.03mgPCP/kg d.w. plus controls) in laboratory standard tests. Exposure duration was 28days for T. tubifex and L. variegatus and 10 and 28days for C. riparius; according to the corresponding OECD guidelines. For each investigated end-point, dose-response data were normalized to the mean control and fitted to a four-parameter log-logistic model for calculating the corresponding EC50 and EC10. The ranges for EC50 and EC10 estimates were 4.39 (Chironomus riparius-emergence)-27.50 (Tubifex tubifex-cocoon) and 0.30 (T. tubifex-young worms) -16.70 (T. tubifex-cocoon) mg/kg d.w., respectively. The EC50 and the EC10 values of L. variegatus were within these ranges. Following the EU Technical Guidance for deriving EQS, the lowest EC10 value of 0.30mg/kg (T. tubifex-young worms) resulted in a PCP quality standard (QS) for sediments of 30ng/g, about one fourth of the tentative QS of 119ng/g estimated by the equilibrium partitioning (EqP) approach. The response of benthic biota to PCP varied across organisms and across end-points for the same organism, so that the use of sediment PCP-QS calculated using the EqP-approach may be under-protective of the most sensitive organisms. Information on the possible effects of PCP on resident organisms must therefore be

  15. Risk of Carotid Stroke after Chiropractic Care: A Population-Based Case-Crossover Study.

    PubMed

    Cassidy, J David; Boyle, Eleanor; Côté, Pierre; Hogg-Johnson, Sheilah; Bondy, Susan J; Haldeman, Scott

    2017-04-01

    Chiropractic manipulation is a popular treatment for neck pain and headache, but may increase the risk of cervical artery dissection and stroke. Patients with carotid artery dissection can present with neck pain and/or headache before experiencing a stroke. These are common symptoms seen by both chiropractors and primary care physicians (PCPs). We aimed to assess the risk of carotid artery stroke after chiropractic care by comparing association between chiropractic and PCP visits and subsequent stroke. A population-based, case-crossover study was undertaken in Ontario, Canada. All incident cases of carotid artery stroke admitted to hospitals over a 9-year period were identified. Cases served as their own controls. Exposures to chiropractic and PCP services were determined from health billing records. We compared 15,523 cases to 62,092 control periods using exposure windows of 1, 3, 7, and 14 days prior to the stroke. Positive associations were found for both chiropractic and PCP visits and subsequent stroke in patients less than 45 years of age. These associations tended to increase when analyses were limited to visits for neck pain and headache-related diagnoses. There was no significant difference between chiropractic and PCP risk estimates. We found no association between chiropractic visits and stroke in those 45 years of age or older. We found no excess risk of carotid artery stroke after chiropractic care. Associations between chiropractic and PCP visits and stroke were similar and likely due to patients with early dissection-related symptoms seeking care prior to developing their strokes. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. A Novel Frizzled-Based Screening Tool Identifies Genetic Modifiers of Planar Cell Polarity in Drosophila Wings

    PubMed Central

    Carvajal-Gonzalez, Jose Maria; Mulero-Navarro, Sonia; Smith, Michael; Mlodzik, Marek

    2016-01-01

    Most mutant alleles in the Fz-PCP pathway genes were discovered in classic Drosophila screens looking for recessive loss-of-function (LOF) mutations. Nonetheless, although Fz-PCP signaling is sensitive to increased doses of PCP gene products, not many screens have been performed in the wing under genetically engineered Fz overexpression conditions, mostly because the Fz phenotypes were strong and/or not easy to score and quantify. Here, we present a screen based on an unexpected mild Frizzled gain-of-function (GOF) phenotype. The leakiness of a chimeric Frizzled protein designed to be accumulated in the endoplasmic reticulum (ER) generated a reproducible Frizzled GOF phenotype in Drosophila wings. Using this genotype, we first screened a genome-wide collection of large deficiencies and found 16 strongly interacting genomic regions. Next, we narrowed down seven of those regions to finally test 116 candidate genes. We were, thus, able to identify eight new loci with a potential function in the PCP context. We further analyzed and confirmed krasavietz and its interactor short-stop as new genes acting during planar cell polarity establishment with a function related to actin and microtubule dynamics. PMID:27729438

  17. Photoelectrochemical sensor for pentachlorophenol on microfluidic paper-based analytical device based on the molecular imprinting technique.

    PubMed

    Sun, Guoqiang; Wang, Panpan; Ge, Shenguang; Ge, Lei; Yu, Jinghua; Yan, Mei

    2014-06-15

    Combining microfluidic paper-based analytical device (μ-PAD) and the molecular imprinting technique, a visible light photoelectrochemical (PEC) sensing platform for the detection of pentachlorophenol (PCP) was established on gold nanoparticles (AuNPs) decorated paper working electrode using polypyrrole-functionalized ZnO nanoparticles. Ascorbic acid (AA) was exploited as an efficient and nontoxic electron donor for scavenging photogenerated holes under mild solution medium and facilitating the generation of stable photocurrent. The microfluidic molecular imprinted polymer-based PEC analytical origami device is developed for the detection of PCP in the linear range from 0.01 ng mL(-1) to 100 ng mL(-1) with a low detection limit of 4 pg mL(-1). This disposable microfluidic PEC origami device would provide a new platform for sensitive, specific, and multiplex assay in public health, environmental monitoring, and the developing world.

  18. Development of controlled drug release systems based on thiolated polymers.

    PubMed

    Bernkop-Schnürch, A; Scholler, S; Biebel, R G

    2000-05-03

    The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

  19. Primary care-based, pharmacist-physician collaborative medication-therapy management of hypertension: a randomized, pragmatic trial.

    PubMed

    Hirsch, Jan D; Steers, Neil; Adler, David S; Kuo, Grace M; Morello, Candis M; Lang, Megan; Singh, Renu F; Wood, Yelena; Kaplan, Robert M; Mangione, Carol M

    2014-09-01

    A collaborative pharmacist-primary care provider (PharmD-PCP) team approach to medication-therapy management (MTM), with pharmacists initiating and changing medications at separate office visits, holds promise for the cost-effective management of hypertension, but has not been evaluated in many systematic trials. The primary objective of this study was to examine blood pressure (BP) control in hypertensive patients managed by a newly formed PharmD-PCP MTM team versus usual care in a university-based primary care clinic. This randomized, pragmatic clinical trial was conducted in hypertensive patients randomly selected for PharmD-PCP MTM or usual care. In the PharmD-PCP MTM group, pharmacists managed drug-therapy initiation and monitoring, medication adjustments, biometric assessments, laboratory tests, and patient education. In the usual-care group, patients continued to see their PCPs. Participants were aged ≥ 18 years, were diagnosed with hypertension, had a most recent BP measurement of ≥ 140/≥ 90 mm Hg (≥ 130/≥ 80 mm Hg if codiagnosed with diabetes mellitus), were on at least 1 antihypertensive medication, and were English speaking. The primary outcome was the difference in the mean change from baseline in systolic BP at 6 months. Secondary outcomes included the percentage achieving therapeutic BP goal and the mean changes from baseline in diastolic BP and low- and high-density lipoprotein cholesterol. A total of 166 patients were enrolled (69 men; mean age, 67.7 years; PharmD-PCP MTM group, n = 75; usual-care group, n = 91). Mean reduction in SBP was significantly greater in the PharmD-PCP MTM group at 6 months (-7.1 [19.4] vs +1.6 [21.0] mm Hg; P = 0.008), but the difference was no longer statistically significant at 9 months (-5.2 [16.9] vs -1.7 [17.7] mm Hg; P = 0.22), based on an intent-to-treat analysis. In the intervention group, greater percentages of patients who continued to see the MTM pharmacist versus those who returned to their PCP were

  20. Comparison of physician referral and insurance claims data-based risk prediction as approaches to identify patients for care management in primary care: an observational study.

    PubMed

    Freund, Tobias; Gondan, Matthias; Rochon, Justine; Peters-Klimm, Frank; Campbell, Stephen; Wensing, Michel; Szecsenyi, Joachim

    2013-10-20

    Primary care-based care management (CM) could reduce hospital admissions in high-risk patients. Identification of patients most likely to benefit is needed as resources for CM are limited. This study aimed to compare hospitalization and mortality rates of patients identified for CM either by treating primary care physicians (PCPs) or predictive modelling software for hospitalization risk (PM). In 2009, a cohort of 6,026 beneficiaries of a German statutory health insurance served as a sample for patient identification for CM by PCPs or commercial PM (CSSG 0.8, Verisk Health). The resulting samples were compared regarding hospitalization and mortality rates in 2010 and in the two year period before patient selection. No CM-intervention was delivered until the end of 2010 and PCPs were blinded for the assessment of hospitalization rates. In 2010, hospitalization rates of PM-identified patients were 80% higher compared to PCP-identified patients. Mortality rates were also 8% higher in PM-identified patients if compared to PCP-identified patients (10% vs. 2%). The hospitalization rate of patients independently identified by both PM and PCPs was numerically between PM- and PCP-identified patients. Time trend between 2007 and 2010 showed decreasing hospitalization rates in PM-identified patients (-15% per year) compared to increasing rates in PCP-identified patients (+34% per year). PM identified patients with higher hospitalization and mortality rates compared to PCP-referred patients. But the latter showed increasing hospitalization rates over time thereby suggesting that PCPs may be able to predict future deterioration in patients with relatively good current health status. These patients may most likely benefit from preventive services like CM.

  1. Taking Proof based Verified Computation a Few Steps Closer to Practicality (extended version)

    DTIC Science & Technology

    2012-06-27

    Braun, Andrew J. Blumberg, and Michael Walfish The University of Texas at Austin Abstract. We describe GINGER , a built system for un- conditional...general-purpose, and nearly practical verifi- cation of outsourced computation. GINGER is based on PEPPER, which uses the PCP theorem and cryptographic...techniques to implement an efficient argument system (a kind of interactive protocol). GINGER slashes the query size and costs via theoretical

  2. A context for the 1930's Dust Bowl Drought in the Northern Great Plains, U.S. based on a rainfall reconstruction using H-isotopes of terrestrial leaf waxes

    NASA Astrophysics Data System (ADS)

    Toney, J. L.; Fritz, S. C.; Grimm, E. C.; Baker, P. A.; Nyren, P. E.; Huang, Y.

    2010-12-01

    Existing records of drought from Northern Great Plains (NGP) are based on pollen or on lake-water ion concentration (salinity) reconstructions from fossil assemblages (diatom-inferred salinity) and trace-elements (ostracode Mg/Ca) that reflect lake response to hydrological variability (precipitation (PCP) minus evaporation). In this study, we show that H-isotopes of terrestrial leaf waxes (n-acids) are a proxy for growing season PCP in the region. With this proxy we reconstruct growing season PCP at Lake George, ND at 35-yr resolution over the past 9.4 ka, at 8-yr resolution over the past 1.8 ka, and at nearly annual resolution for the past 150 years. Our PCP proxy is calibrated against the instrumental record for the past 100-yrs and validated at three regional lakes sites. We show low PCP during the early Holocene beginning at 9.1 ka, with peak drought at 8.4 ka, The H-isotopes (dD) suggest that PCP was highly variable from 8.2 ka to 3.5 ka, with alternating wet-dry periods. This variability is not evident in prior lake studies, which had lower temporal resolution in the mid-Holocene. The dD also indicates generally low rainfall but high-amplitude variation from 6.0 to 3.5 ka and low and less variable rainfall from 2.3 to 0.3 ka. The dD suggest that the 1930’s Dust Bowl Drought is one of only seven drought events throughout the past 9.4 ka to reach that severity, and only three events were more severe (8.1, 2.4, and 0.6 ka). Within the past 1.8 ka, the low rainfall events generally coincide with phases inferred to be dry in regional lakes by in-lake proxies (Rice Lake, ND, Coldwater Lake, ND, Moon Lake, ND, and Elk Lake, MN), although the decreased PCP events are abrupt and less prolonged than the inferred lake response to P-E. Spectral analysis of the H-isotope rainfall proxy does not support the 400-yr spacing of dry lake phases in the region observed in some paleosalinity records, which suggests that this spacing may be strongly affected by temperature

  3. Inner-ear sound pressures near the base of the cochlea in chinchilla: Further investigation

    PubMed Central

    Ravicz, Michael E.; Rosowski, John J.

    2013-01-01

    The middle-ear pressure gain GMEP, the ratio of sound pressure in the cochlear vestibule PV to sound pressure at the tympanic membrane PTM, is a descriptor of middle-ear sound transfer and the cochlear input for a given stimulus in the ear canal. GMEP and the cochlear partition differential pressure near the cochlear base ΔPCP, which determines the stimulus for cochlear partition motion and has been linked to hearing ability, were computed from simultaneous measurements of PV, PTM, and the sound pressure in scala tympani near the round window PST in chinchilla. GMEP magnitude was approximately 30 dB between 0.1 and 10 kHz and decreased sharply above 20 kHz, which is not consistent with an ideal transformer or a lossless transmission line. The GMEP phase was consistent with a roughly 50-μs delay between PV and PTM. GMEP was little affected by the inner-ear modifications necessary to measure PST. GMEP is a good predictor of ΔPCP at low and moderate frequencies where PV ⪢ PST but overestimates ΔPCP above a few kilohertz where PV ≈ PST. The ratio of PST to PV provides insight into the distribution of sound pressure within the cochlear scalae. PMID:23556590

  4. A residue-based toxicokinetic model for pulse-exposure toxicity in aquatic systems

    SciTech Connect

    Hickie, B.E.; McCarty, L.S.; Dixon, D.G.

    1995-12-01

    This pulse-exposure model (PULSETOX) is based on the simple one-compartment first-order kinetics (1CFOK) equation. It tracks the accumulation of waterborne organic chemicals by fish and predicts acute toxicity by means of previously established relationships between whole-body residues and lethality. The predictive capabilities of the model were tested with a data set of 27 acute pulse-exposure lethality tests with larval fathead minnows (Pimephales promelas) exposed to pentachlorophenol (PCP). Tests included eight single exposures (2 to 96 h) and 19 multiple exposures, which varied in the number (2 to 15) and duration (2 to 24 h) of pulses, and time interval between pulses (6 to 24 h). Experimental work included determination of 1CFOK kinetics parameters from [{sup 14}C]PCP uptake and clearance, and from time-toxicity curves. Lethality was expected in any exposure regime where the fish reaches or exceeds the critical body residue (CBR) of 0.30 mmol PCP/kg fish (SD, {+-} 0.02; n = 11). Using the CBR endpoint, the model accounted for between 90 and 93% of variability in the observed lethality data, depending on the toxicokinetic parameters employed. Predictive power of the model was optimized by using kinetics parameters derived from the toxicity curve for pulse-toxicity tests as shown by the regression: predicted LC50 = 1.04 {center_dot} (observed LC50) + 0.01 (p < 0.001, r{sup 2} = 0.94, n = 27).

  5. Inner-ear sound pressures near the base of the cochlea in chinchilla: further investigation.

    PubMed

    Ravicz, Michael E; Rosowski, John J

    2013-04-01

    The middle-ear pressure gain GMEP, the ratio of sound pressure in the cochlear vestibule PV to sound pressure at the tympanic membrane PTM, is a descriptor of middle-ear sound transfer and the cochlear input for a given stimulus in the ear canal. GMEP and the cochlear partition differential pressure near the cochlear base ΔPCP, which determines the stimulus for cochlear partition motion and has been linked to hearing ability, were computed from simultaneous measurements of PV, PTM, and the sound pressure in scala tympani near the round window PST in chinchilla. GMEP magnitude was approximately 30 dB between 0.1 and 10 kHz and decreased sharply above 20 kHz, which is not consistent with an ideal transformer or a lossless transmission line. The GMEP phase was consistent with a roughly 50-μs delay between PV and PTM. GMEP was little affected by the inner-ear modifications necessary to measure PST. GMEP is a good predictor of ΔPCP at low and moderate frequencies where PV > PST but overestimates ΔPCP above a few kilohertz where PV ≈ PST. The ratio of PST to PV provides insight into the distribution of sound pressure within the cochlear scalae.

  6. A sensitive electrochemical chlorophenols sensor based on nanocomposite of ZnSe quantum dots and cetyltrimethylammonium bromide.

    PubMed

    Li, Jianjun; Li, Xiao; Yang, Ran; Qu, Lingbo; Harrington, Peter de B

    2013-12-04

    In this work, a very sensitive and simple electrochemical sensor for chlorophenols (CPs) based on a nanocomposite of cetyltrimethylammonium bromide (CTAB) and ZnSe quantum dots (ZnSe-CTAB) through electrostatic self-assembly technology was built for the first time. The composite of ZnSe-CTAB introduced a favorable access for the electron transfer and gave superior electrocatalytic activity for the oxidation of CPs than ZnSe QDs and CTAB alone. Differential pulse voltammetry (DPV) was used for the quantitative determination of the CPs including 2-chlorophenol (2-CP), 2,4-dichlorophenol (2,4-DCP) and pentachlorophenol (PCP). Under the optimum conditions, the peak currents of the CPs were proportional to their concentrations in the range from 0.02 to 10.0 μM for 2-CP, 0.006 to 9.0 μM for 2,4-DCP, and 0.06 to 8.0 for PCP. The detection limits were 0.008 μM for 2-CP, 0.002 μM for 2,4-DCP, and 0.01 μM for PCP, respectively. The method was successfully applied for the determination of CPs in waste water with satisfactory recoveries. This ZnSe-CTAB electrode system provides operational access to design environment-friendly CPs sensors. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Primary Care-Based Skin Cancer Screening in a Veterans Affairs Health Care System.

    PubMed

    Swetter, Susan M; Chang, Julia; Shaub, Amanda R; Weinstock, Martin A; Lewis, Eleanor T; Asch, Steven M

    2017-08-01

    of significantly fewer postintervention dermatology referrals that lacked specific diagnoses (25 [1.0%] vs 10 [0.4%], P = .01). This pilot study suggests that PCP-based skin cancer training and screening are feasible and have the potential to improve PCP diagnostic accuracy without increasing specialty referrals or skin biopsies. Additional studies comparing screening rates, specialty referrals, and patient outcomes in trained vs untrained PCPs are needed before screening is widely implemented in large health care systems in the United States.

  8. Risk of vertebrobasilar stroke and chiropractic care: results of a population-based case-control and case-crossover study.

    PubMed

    Cassidy, J David; Boyle, Eleanor; Côté, Pierre; He, Yaohua; Hogg-Johnson, Sheilah; Silver, Frank L; Bondy, Susan J

    2009-02-01

    Population-based, case-control and case-crossover study. To investigate associations between chiropractic visits and vertebrobasilar artery (VBA) stroke and to contrast this with primary care physician (PCP) visits and VBA stroke. Chiropractic care is popular for neck pain and headache, but may increase the risk for VBA dissection and stroke. Neck pain and headache are common symptoms of VBA dissection, which commonly precedes VBA stroke. Cases included eligible incident VBA strokes admitted to Ontario hospitals from April 1, 1993 to March 31, 2002. Four controls were age and gender matched to each case. Case and control exposures to chiropractors and PCPs were determined from health billing records in the year before the stroke date. In the case-crossover analysis, cases acted as their own controls. There were 818 VBA strokes hospitalized in a population of more than 100 million person-years. In those aged <45 years, cases were about three times more likely to see a chiropractor or a PCP before their stroke than controls. Results were similar in the case control and case crossover analyses. There was no increased association between chiropractic visits and VBA stroke in those older than 45 years. Positive associations were found between PCP visits and VBA stroke in all age groups. Practitioner visits billed for headache and neck complaints were highly associated with subsequent VBA stroke. VBA stroke is a very rare event in the population. The increased risks of VBA stroke associated with chiropractic and PCP visits is likely due to patients with headache and neck pain from VBA dissection seeking care before their stroke. We found no evidence of excess risk of VBA stroke associated chiropractic care compared to primary care.

  9. Risk of vertebrobasilar stroke and chiropractic care: results of a population-based case-control and case-crossover study.

    PubMed

    Cassidy, J David; Boyle, Eleanor; Côté, Pierre; He, Yaohua; Hogg-Johnson, Sheilah; Silver, Frank L; Bondy, Susan J

    2008-02-15

    Population-based, case-control and case-crossover study. To investigate associations between chiropractic visits and vertebrobasilar artery (VBA) stroke and to contrast this with primary care physician (PCP) visits and VBA stroke. Chiropractic care is popular for neck pain and headache, but may increase the risk for VBA dissection and stroke. Neck pain and headache are common symptoms of VBA dissection, which commonly precedes VBA stroke. Cases included eligible incident VBA strokes admitted to Ontario hospitals from April 1, 1993 to March 31, 2002. Four controls were age and gender matched to each case. Case and control exposures to chiropractors and PCPs were determined from health billing records in the year before the stroke date. In the case-crossover analysis, cases acted as their own controls. There were 818 VBA strokes hospitalized in a population of more than 100 million person-years. In those aged <45 years, cases were about three times more likely to see a chiropractor or a PCP before their stroke than controls. Results were similar in the case control and case crossover analyses. There was no increased association between chiropractic visits and VBA stroke in those older than 45 years. Positive associations were found between PCP visits and VBA stroke in all age groups. Practitioner visits billed for headache and neck complaints were highly associated with subsequent VBA stroke. VBA stroke is a very rare event in the population. The increased risks of VBA stroke associated with chiropractic and PCP visits is likely due to patients with headache and neck pain from VBA dissection seeking care before their stroke. We found no evidence of excess risk of VBA stroke associated chiropractic care compared to primary care.

  10. Clinical Relevance of Multiple Single-Nucleotide Polymorphisms in Pneumocystis jirovecii Pneumonia: Development of a Multiplex PCR-Single-Base-Extension Methodology▿

    PubMed Central

    Esteves, F.; Gaspar, J.; De Sousa, B.; Antunes, F.; Mansinho, K.; Matos, O.

    2011-01-01

    Pneumocystis jirovecii pneumonia (PcP) is a major cause of respiratory illness in patients with AIDS. The identification of multiple single-nucleotide polymorphisms (SNPs) at three distinct P. jirovecii loci encoding dihydrofolate reductase (DHFR), mitochondrial large-subunit rRNA (mtLSU rRNA), and superoxide dismutase (SOD) was achieved using multiplex-PCR (MPCR) followed by direct sequencing and two single-base extension (SBE) techniques. Four SNPs (DHFR312, mt85, SOD215, and SOD110), correlated previously with parameters of disease, were amplified and genotyped simultaneously. The concordance of results between the standard sequencing technique (direct sequencing) and SBE analysis was 96.9% for the acrylamide gel electrophoresis and 98.4% for the capillary electrophoresis. The cross-genetic analysis established several statistical associations among the SNPs studied: mt85C-SOD110T, SOD110T-SOD215C, and SOD110C-SOD215T. These results were confirmed by cluster analysis. Data showed that among the isolates with low to moderate parasite burden, the highest percentages of DHFR312C, mt85C, SOD110T, and SOD215C were detected, whereas for high parasite burden cases the highest frequencies were observed among isolates with DHFR312T, mt85T, SOD110C, and SOD215T. The polymorphisms studied were shown to be suitable genetic targets potentially correlated with PcP clinical data that can be used as predictors of outcome in further studies to help clinical decision-making in the management of PcP. The MPCR/SBE protocol described for the first time in the present study was shown to be a rapid, highly accurate method for genotyping P. jirovecii SNPs encoded by different loci that could be used for epidemiological studies and as an additional procedure for the prognostic classification and diagnosis of PcP. PMID:21389160

  11. New Psychoactive Substances 3-Methoxyphencyclidine (3-MeO-PCP) and 3-Methoxyrolicyclidine (3-MeO-PCPy): Metabolic Fate Elucidated with Rat Urine and Human Liver Preparations and their Detectability in Urine by GC-MS, "LC-(High Resolution)-MSn" and "LC-(High Resolution)-MS/MS".

    PubMed

    A Michely, Julian A; Manier, Sascha K; Caspar, Achim T; Brandt, Simon D; Wallach, Jason; Maurer, Hans H

    2017-01-01

    3-Methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeOPCPy) are two new psychoactive substances (NPS). The aims of the present study were the elucidation of their metabolic fate in rat and pooled human liver microsomes (pHLM), the identification of the cytochrome P450 (CYP) isoenzymes involved, and the detectability using standard urine screening approaches (SUSA) after intake of common users' doses using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-multi-stage mass spectrometry (LC-MSn), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, rat urine samples were treated by solid phase extraction or simple precipitation with or without previous enzymatic conjugate cleavage. After analyses via LC-HR-MSn, the phase I and II metabolites were identified. Both drugs showed multiple aliphatic hydroxylations at the cyclohexyl ring and the heterocyclic ring, single aromatic hydroxylation, carboxylation after ring opening, O-demethylation, and glucuronidation. The transferability from rat to human was investigated by pHLM incubations, where Odemethylation and hydroxylation were observed. The involvement of the individual CYP enzymes in the initial metabolic steps was investigated after single CYP incubations. For 3-MeO-PCP, CYP 2B6 was responsible for aliphatic hydroxylations and CYP 2C19 and CYP 2D6 for O-demethylation. For 3-MeO-PCPy, aliphatic hydroxylation was again catalyzed by CYP 2B6 and O-demethylation by CYP 2C9 and CYP 2D6 Conclusions: As only polymorphically expressed enzymes were involved, pharmacogenomic variations might occur, but clinical data are needed to confirm the relevance. The detectability studies showed that the authors' SUSAs were suitable for monitoring the intake of both drugs using the identified metabolites. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Use of hospitalists and office-based primary care physicians' productivity.

    PubMed

    Park, Jeongyoung; Jones, Karen

    2015-05-01

    Growth in the care of hospitalized patients by hospitalists has the potential to increase the productivity of office-based primary care physicians (PCPs) by allowing them to focus on outpatient practice. Our aim was to examine the association between utilization of hospitalists and the productivity of office-based PCPs. The cross-sectional study was conducted using the 2008 Health Tracking Physician Survey Restricted Use File linked to the Area Resource File. We analyzed a total of 1,158 office-based PCPs representing a weighted total of 97,355 physicians. Utilization of hospitalists was defined as the percentage of a PCP's hospitalized patients treated by a hospitalist. The measures of PCPs' productivity were: (1) number of hospital visits per week, (2) number of office and outpatient clinic visits per week, and (3) direct patient care time per visit. We found that the use of hospitalists was significantly associated with a decreased number of hospital visits. The use of hospitalists was also associated with an increased number of office visits, but this was only significant for high users. Physicians who used hospitalists for more than three-quarters of their hospitalized patients had an extra 8.8 office visits per week on average (p = 0.05), which was equivalent to a 10 % increase in productivity over the predicted mean of 87 visits for physicians who did not use hospitalists. We did not find any significant differences in direct patient care time per visit. Our study demonstrates that the increase in productivity for the one-third of PCPs who use hospitalists extensively may not be sufficient to offset the current loss of PCP workforce. However, our findings provide cautious optimism that if more PCPs effectively and efficiently used hospitalists, this could help mitigate a PCP shortage and improve access to primary care services.

  13. Computer-Based Education in Prison Schools.

    ERIC Educational Resources Information Center

    Siegel, Martin A.

    1978-01-01

    Presents an overview of the PLATO Corrections Project (PCP) in Illinois and Minnesota, and describes recent curriculum development efforts in adult reading comprehension and vocabulary development. Data collected on student/instructor usage, attitudes, and achievement demonstrate that the PCP system is feasible, attractive, and effective in…

  14. Kernel-based variance component estimation and whole-genome prediction of pre-corrected phenotypes and progeny tests for dairy cow health traits

    PubMed Central

    Morota, Gota; Boddhireddy, Prashanth; Vukasinovic, Natascha; Gianola, Daniel; DeNise, Sue

    2014-01-01

    Prediction of complex trait phenotypes in the presence of unknown gene action is an ongoing challenge in animals, plants, and humans. Development of flexible predictive models that perform well irrespective of genetic and environmental architectures is desirable. Methods that can address non-additive variation in a non-explicit manner are gaining attention for this purpose and, in particular, semi-parametric kernel-based methods have been applied to diverse datasets, mostly providing encouraging results. On the other hand, the gains obtained from these methods have been smaller when smoothed values such as estimated breeding value (EBV) have been used as response variables. However, less emphasis has been placed on the choice of phenotypes to be used in kernel-based whole-genome prediction. This study aimed to evaluate differences between semi-parametric and parametric approaches using two types of response variables and molecular markers as inputs. Pre-corrected phenotypes (PCP) and EBV obtained for dairy cow health traits were used for this comparison. We observed that non-additive genetic variances were major contributors to total genetic variances in PCP, whereas additivity was the largest contributor to variability of EBV, as expected. Within the kernels evaluated, non-parametric methods yielded slightly better predictive performance across traits relative to their additive counterparts regardless of the type of response variable used. This reinforces the view that non-parametric kernels aiming to capture non-linear relationships between a panel of SNPs and phenotypes are appealing for complex trait prediction. However, like past studies, the gain in predictive correlation was not large for either PCP or EBV. We conclude that capturing non-additive genetic variation, especially epistatic variation, in a cross-validation framework remains a significant challenge even when it is important, as seems to be the case for health traits in dairy cows. PMID:24715901

  15. Classification epitopes in groups based on their protein family

    PubMed Central

    2015-01-01

    Background The humoral immune system response is based on the interaction between antibodies and antigens for the clearance of pathogens and foreign molecules. The interaction between these proteins occurs at specific positions known as antigenic determinants or B-cell epitopes. The experimental identification of epitopes is costly and time consuming. Therefore the use of in silico methods, to help discover new epitopes, is an appealing alternative due the importance of biomedical applications such as vaccine design, disease diagnostic, anti-venoms and immune-therapeutics. However, the performance of predictions is not optimal been around 70% of accuracy. Further research could increase our understanding of the biochemical and structural properties that characterize a B-cell epitope. Results We investigated the possibility of linear epitopes from the same protein family to share common properties. This hypothesis led us to analyze physico-chemical (PCP) and predicted secondary structure (PSS) features of a curated dataset of epitope sequences available in the literature belonging to two different groups of antigens (metalloproteinases and neurotoxins). We discovered statistically significant parameters with data mining techniques which allow us to distinguish neurotoxin from metalloproteinase and these two from random sequences. After a five cross fold validation we found that PCP based models obtained area under the curve values (AUC) and accuracy above 0.9 for regression, decision tree and support vector machine. Conclusions We demonstrated that antigen's family can be inferred from properties within a single group of linear epitopes (metalloproteinases or neurotoxins). Also we discovered the characteristics that represent these two epitope groups including their similarities and differences with random peptides and their respective amino acid sequence. These findings open new perspectives to improve epitope prediction by considering the specific antigen

  16. How University Students View Online Study: A PCP Perspective

    ERIC Educational Resources Information Center

    Wang, Wei

    2004-01-01

    With the ever-increasing impact of information technology (IT) on society, universities are pushed to deliver the courses through the Internet by the format of Web course or online study. There are relatively few studies of how students construe this new mode of delivery and study. This study aimed to better understanding of how students construe…

  17. US EPA, Pesticide Product Label, PCP 5% RTU SOLUTION ...

    EPA Pesticide Factsheets

    2011-04-21

    I'RI.t \\!lII;}~ \\RY S 1.\\11 'II \\' IS 111:"';11.1 .. to III/mill" ;In,1 11''''H',qic \\lIlIn:ll .. l;',II"IIJ~~' "I)' 1'1' 1,,11\\ If ".:111,,,,,1. 11.1"tl,,1 "I 11"'",1·.11 ,I'I.>lI!:'. Ih. "'~II1. ...

  18. US EPA, Pesticide Product Label, SURE DEATH BRAND PCP ...

    EPA Pesticide Factsheets

    2011-04-14

    ... per 1/,dl) -'

  19. Quantum mechanically based estimation of perturbed-chain polar statistical associating fluid theory parameters for analyzing their physical significance and predicting properties.

    PubMed

    Nhu, Nguyen Van; Singh, Mahendra; Leonhard, Kai

    2008-05-08

    We have computed molecular descriptors for sizes, shapes, charge distributions, and dispersion interactions for 67 compounds using quantum chemical ab initio and density functional theory methods. For the same compounds, we have fitted the three perturbed-chain polar statistical associating fluid theory (PCP-SAFT) equation of state (EOS) parameters to experimental data and have performed a statistical analysis for relations between the descriptors and the EOS parameters. On this basis, an analysis of the physical significance of the parameters, the limits of the present descriptors, and the PCP-SAFT EOS has been performed. The result is a method that can be used to estimate the vapor pressure curve including the normal boiling point, the liquid volume, the enthalpy of vaporization, the critical data, mixture properties, and so on. When only two of the three parameters are predicted and one is adjusted to experimental normal boiling point data, excellent predictions of all investigated pure compound and mixture properties are obtained. We are convinced that the methodology presented in this work will lead to new EOS applications as well as improved EOS models whose predictive performance is likely to surpass that of most present quantum chemically based, quantitative structure-property relationship, and group contribution methods for a broad range of chemical substances.

  20. Efficient Verification of Periodic Programs Using Sequential Consistency and Snapshots

    DTIC Science & Technology

    2014-10-24

    task it executes • Each PCP lock is associated with priority () • A CPU lock is a PCP lock such that = ∞ • Thread’s priority = max...its base priority, priorities of all PCP locks it holds) Lock operation encoded by “priority-test-and-set” action (, , , ,

  1. Randomized controlled trial of primary care physician motivational interviewing versus brief advice to engage adolescents with an Internet-based depression prevention intervention: 6-month outcomes and predictors of improvement.

    PubMed

    Hoek, Willemijn; Marko, Monika; Fogel, Joshua; Schuurmans, Josien; Gladstone, Tracy; Bradford, Nathan; Domanico, Rocco; Fagan, Blake; Bell, Carl; Reinecke, Mark A; Van Voorhees, Benjamin W

    2011-12-01

    We believe that primary care physicians could play a key role in engaging youth with a depression prevention intervention. We developed CATCH-IT (Competent Adulthood Transition with Cognitive Behavioral and Interpersonal Training), which is an adolescent Internet-based behavior change model. We conducted a randomized comparison of two approaches in engaging adolescents with the Internet intervention: primary care physician (PCP) motivational interview + CATCH-IT Internet program (MI) vs PCP brief advice + CATCH-IT Internet program (BA). The participants (N = 84) were recruited by screening for risk of depression in 13 primary care practices. We compared depressive disorder outcomes between groups and within groups over 6 months and examined the potential predictors and moderators of outcomes across both study arms. Depressive symptom scores declined from baseline to 6 weeks with these statistically significant reductions sustained at the 6 months follow-up in both groups. No significant interactions with treatment condition were found. However, by 6 months, the MI group demonstrated significantly fewer depressive episodes and reported less hopelessness as compared with the BA group. Hierarchical linear modeling regressions showed higher ratings of ease of use of the Internet program predicting lower depressive symptom levels over 6 months. In conclusion, a primary care/Internet-based intervention model among adolescents demonstrated reductions in depressed mood over 6 months and may result in fewer depressive episodes. Published by Mosby, Inc.

  2. A theoretical, spectroscopic, and photophysical study of 2,7-carbazolenevinylene-based conjugated derivatives.

    PubMed

    Belletête, Michel; Morin, Jean-François; Leclerc, Mario; Durocher, Gilles

    2005-08-11

    A combined theoretical and experimental study of the structure, optical, and photophysical properties of four 2,7-carbazolenevinylene-based derivatives in solution is presented. Geometry optimizations of the ground states of PCP, PCP-CN, TCT, and TCT-CN were carried out using the density functional theory (DFT/B3LYP/6-31G*). It is found that PCP and TCT are nearly planar in their ground electronic states (S0), whereas the cyano derivatives are more twisted. The nature and the energy of the first singlet-singlet electronic transitions have been obtained from time-dependent density functional theory (TDDFT) calculations performed on the optimized geometries. For all the compounds, excitation to the S1 state corresponds mainly to the promotion of one electron from the highest-occupied molecular orbital to the lowest-unoccupied molecular orbital, and the S1 <-- S0 electronic transition is strongly allowed and polarized along the long axis of the molecular frame. The optimization (relaxation) of the first singlet excited electronic state (S1) has been done using the restricted configuration interaction (singles) (RCIS/6-31G*) approach. It is observed that all four investigated compounds become more planar in their S1 relaxed excited state. Electronic transition energies from the relaxed excited states have been obtained from TDDFT calculations performed on the S1-optimized geometries. The absorption and fluorescence spectra of the carbazolenevinylenes have been recorded in chloroform. A good agreement is obtained between TDDFT vertical transitions energies and the (0,0) absorption and fluorescence bands. The change from phenylene to thiophene rings as well as the incorporation of cyano substituents induce bathochromic shifts in the absorption and fluorescence spectra. From the analysis of the energy of the frontier molecular orbitals, it is believed that thiophene rings and CN substituents induce some charge-transfer character to the first electronic transition, which

  3. Highly sensitive room temperature ammonia gas sensor based on Ir-doped Pt porous ceramic electrodes

    NASA Astrophysics Data System (ADS)

    Liu, Wenlong; Liu, Yen-Yu; Do, Jing-Shan; Li, Jing

    2016-12-01

    Room temperature NH3 gas sensors based on Pt and Pt-Ir (Ir doping Pt) porous ceramic electrodes have been fabricated by both electroplating and sputtering methods. The properties of the gaseous ammonia sensors have been examined by polarization and chronoamperometry techniques. The influence of humidity on the features of the resulting sensors in the system has also been discussed, and the working potential was optimized. Water vapors seem to hugely improve the electrochemical activity of the electrode. With increasing the relative humidity, the response of the Pt-Ir(E)/Pt(S)/PCP sensor to NH3 gas could be enhanced remarkably, and the sensitivity increases from 1.14 to 12.06 μA ppm-1 cm-2 .Then we have also discussed the sensing mechanism of the Pt-Ir sensor and the result has been confirmed by X-ray photoelectron spectroscopy of the electrode surface before and after reaction in the end.

  4. Chemical dehalogenation treatment: Base-catalyzed decomposition process (BCDP). Tech data sheet

    SciTech Connect

    Not Available

    1992-07-01

    The Base-Catalyzed Decomposition Process (BCDP) is an efficient, relatively inexpensive treatment process for polychlorinated biphenyls (PCBs). It is also effective on other halogenated contaminants such as insecticides, herbicides, pentachlorophenol (PCP), lindane, and chlorinated dibenzodioxins and furans. The heart of BCDP is the rotary reactor in which most of the decomposition takes place. The contaminated soil is first screened, processed with a crusher and pug mill, and stockpiled. Next, in the main treatment step, this stockpile is mixed with sodium bicarbonate (in the amount of 10% of the weight of the stockpile) and heated for about one hour at 630 F in the rotary reactor. Most (about 60% to 90%) of the PCBs in the soil are decomposed in this step. The remainder are volatilized, captured, and decomposed.

  5. Plant uptake of pentachlorophenol from sludge-amended soils

    SciTech Connect

    Bellin, C.A.; O'Connor, G.A.

    1990-01-01

    A greenhouse study was conducted to determine the effects of sludge on plant uptake of {sup 14}C-pentachlorophenol (PCP). Plants included tall fescue (Festuca arundinacea Schreb.), lettuce (Latuca sativa L.), carrot (Daucus carota L.), and chile pepper (Capsicum annum L.). Minimal intact PCP was detected in the fescue and lettuce by gas chromatography/mass spectrometry (GC/MS) analysis. No intact PCP was detected in the carrot tissue extracts. Chile pepper was not analyzed for intact PCP because methylene chloride extracts contained minimal {sup 14}C. The GC/MS analysis of soil extracts at harvest suggests a half-life of PCP of about 10 d independent of sludge rate or PCP loading rate. Rapid degradation of PCP in the soil apparently limited PCP availability to the plant. Bioconcentration factors (dry plant wt./initial soil PCP concentration) based on intact PCP were <0.01 for all crops, suggesting little PCP uptake. Thus, food-chain crop PCP uptake in these alkaline soils should not limit land application of sludge.

  6. Ln-Co-based rock-salt-type porous coordination polymers: vapor response controlled by changing the lanthanide ion.

    PubMed

    Kobayashi, Atsushi; Suzuki, Yui; Ohba, Tadashi; Noro, Shin-ichiro; Chang, Ho-Chol; Kato, Masako

    2011-03-21

    We synthesized new porous coordination polymers (PCPs) {Ln(III)[Co(III)(dcbpy)(3)]·nH(2)O} (Ln = La(3+), Nd(3+), Gd(3+); H(2)dcbpy = 4,4'-dicarboxy-2,2'-bipyridine) and characterized them by X-ray diffraction and vapor-adsorption measurements. These three Ln-Co-based PCPs have similar rock-salt types and highly symmetrical porous structure and show a reversible structural collapse-regeneration accompanied by water-vapor desorption-adsorption. Similar structural regeneration was also observed for the Gd-Co PCP upon exposure to MeOH and CH(3)CN vapors, whereas the remaining two PCPs barely responded to organic vapors.

  7. Genotypic variation of Pneumocystis jirovecii isolates in India based on sequence diversity at mitochondrial large subunit rRNA.

    PubMed

    Gupta, Rashmi; Mirdha, Bijay Ranjan; Guleria, Randeep; Agarwal, Sanjay Kumar; Samantaray, Jyotish Chandra; Kumar, Lalit; Kabra, Sushil Kumar; Luthra, Kalpana; Sreenivas, Vishnubhatla; Iyer, Venkateswaran K

    2011-03-01

    Pneumocystis pneumonia (PCP), a common and serious opportunistic infection in immunocompromised patients, is caused by Pneumocystis jirovecii (formerly known as Pneumocystis carinii f. sp. hominis). The aim of the present study was to describe the prevalence and distribution of genotypes of P. jirovecii based on sequence polymorphisms at mitochondrial large subunit ribosomal RNA (mt LSU rRNA) region in both HIV and non-HIV immunocompromised individuals with a positive PCR result for PCP in a tertiary health care centre in northern India. From January 2005 to October 2008, 50 patients [22 HIV-seropositive individuals, 10 post-renal transplant (PRT) recipients, 3 cancer patients, and 15 patients with various other kinds of immunosuppression] were found to be positive for P. jirovecii using PCR at the mt LSU rRNA gene. Genotyping of the positive samples was performed at the mt LSU rRNA locus. Genotype 2 was the most common accounting for 42% of total types. This was followed by the genotypes 3 (24%), 1 (20%), and 4 (8%). Mixed infection was observed in 3 cases (6%). The rates of genotype distribution were similar in HIV-seropositive individuals, cancer patients, and in patients with other kinds of immunosuppression. In the PRT recipients, genotype 1 was the most prevalent type (80%). This is the first study describing the prevalence of genotypes in HIV-infected and HIV-uninfected, immunocompromised patients based on the mt LSU rRNA gene from the Indian subcontinent. The most prevalent genotype observed was type 2 in contrast to many studies from other parts of the world where genotype 1 was the most prevalent type, suggesting geographical variation.

  8. Pneumocystis pneumonia in patients treated with long-term steroid therapy for symptom palliation: a neglected infection in palliative care.

    PubMed

    Yamaguchi, Takashi; Nagai, Yuki; Morita, Tatsuya; Kiuchi, Daisuke; Matsumoto, Mina; Hisahara, Ko; Hisanaga, Takayuki

    2014-12-01

    We report 3 cases of pneumocystis pneumonia (PCP) in patients with advanced cancer who received palliative care. All patients received long-term steroid therapy for symptom management. A diagnosis of PCP was based on clinical symptoms and a positive Pneumocystis jiroveci polymerase chain reaction test from induced sputum specimens. Despite appropriate treatment, only 1 patient recovered from PCP. Long-term steroid, often prescribed in palliative care settings, is the most common risk factor for PCP in non-HIV patients. Pneumocystis pneumonia may cause distressing symptoms such as severe dyspnea, and the mortality rate is high. Therefore, it is important to consider PCP prophylaxis for high-risk patients and to diagnose PCP early and provide appropriate treatment to alleviate PCP-related symptoms and avert unnecessary shortening of a patient's life expectancy.

  9. Clinical Pharmacist Team-Based Care in a Safety Net Medical Home: Facilitators and Barriers to Chronic Care Management.

    PubMed

    Price-Haywood, Eboni G; Amering, Sarah; Luo, Qingyang; Lefante, John J

    2017-04-01

    Collaborative care models incorporating pharmacists have been shown to improve quality of care for patients with hypertension and/or diabetes. Little is known about how to integrate such services outside of clinical trials. The authors implemented a 22-month observational study to evaluate pharmacy collaborative care for hypertension and diabetes in a safety net medical home that incorporated population risk stratification, clinical decision support, and medication dose adjustment protocols. Patients in the pharmacy group saw their primary care provider (PCP) more often and had higher baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) and A1c levels compared to patients who only received care from their PCPs. There were no significant differences in the proportion of patients achieving treatment goals (SBP <140, DBP <90; A1c < 8) or the magnitude of change in BP or A1c among patients who underwent collaborative care versus those who did not. Age, race, and number of PCP encounters were associated with BP and A1c trends. The median time to achieve disease control was longer in the pharmacy group. Although 70% of all patients with poorly controlled hypertension achieved treatment goals within 7 months, less than 50% of patients with poorly controlled diabetes achieved A1c < 8 within 15 months, suggesting that diabetes was harder to manage overall. Contextual factors that facilitated or hindered practice redesign included organizational culture, health information technology and related workflows, and pharmacy caseload optimization. Future studies should further examine implementation strategies that work best in specific settings to optimize the benefits of team-based care with clinical pharmacists.

  10. An intervention to improve mental health care for conflict-affected forced migrants in low-resource primary care settings: a WHO MhGAP-based pilot study in Sri Lanka (COM-GAP study).

    PubMed

    Siriwardhana, Chesmal; Adikari, Anushka; Van Bortel, Tine; McCrone, Paul; Sumathipala, Athula

    2013-12-09

    Inadequacy in mental health care in low and middle income countries has been an important contributor to the rising global burden of disease. The treatment gap is salient in resource-poor settings, especially when providing care for conflict-affected forced migrant populations. Primary care is often the only available service option for the majority of forced migrants, and integration of mental health into primary care is a difficult task. The proposed pilot study aims to explore the feasibility of integrating mental health care into primary care by providing training to primary care practitioners serving displaced populations, in order to improve identification, treatment, and referral of patients with common mental disorders via the World Health Organization Mental Health Gap Action Programme (mhGAP). This pilot randomized controlled trial will recruit 86 primary care practitioners (PCP) serving in the Puttalam and Mannar districts of Sri Lanka (with displaced and returning conflict-affected populations). The intervention arm will receive a structured training program based on the mhGAP intervention guide. Primary outcomes will be rates of correct identification, adequate management based on set criteria, and correct referrals of common mental disorders. A qualitative study exploring the attitudes, views, and perspectives of PCP on integrating mental health and primary care will be nested within the pilot study. An economic evaluation will be carried out by gathering service utilization information. In post-conflict Sri Lanka, an important need exists to provide adequate mental health care to conflict-affected internally displaced persons who are returning to their areas of origin after prolonged displacement. The proposed study will act as a local demonstration project, exploring the feasibility of formulating a larger-scale intervention study in the future, and is envisaged to provide information on engaging PCP, and data on training and evaluation including

  11. A Theory-Based Computer Tutorial Model.

    ERIC Educational Resources Information Center

    Dixon, Robert C.; Clapp, Elizabeth J.

    Because of the need for models to illustrate some possible answers to practical courseware development questions, a specific, three-section model incorporating the Corrective Feedback Paradigm (PCP) is advanced for applying theory to courseware. The model is reconstructed feature-by-feature against a framework of a hypothetical, one-to-one,…

  12. A touch-screen based paired-associates learning (PAL) task for the rat may provide a translatable pharmacological model of human cognitive impairment.

    PubMed

    Talpos, John C; Aerts, Nancy; Fellini, Laetitia; Steckler, Thomas

    2014-07-01

    The use of touch-screen equipped operant boxes is an increasingly popular approach for modeling human cognition in the rodent. However little data is currently available describing the effects of pharmacological manipulations on touch-screen based tasks. Owing to the relationship between performance on visual-spatial paired associates learning (PAL) with schizophrenia and Alzheimer's disease one task of specific interest is the touch-screen PAL task developed for rodents (J. Talpos et al., 2009). The goal of this study was to profile a range of the commonly used pharmacological models of schizophrenia and Alzheimer's disease to investigate the sensitivity of PAL to these models of disease. Male Lister hooded rats were trained on PAL until stable performance was obtained. The effects of PCP, ketamine, amphetamine, LSD, scopolamine, and biperiden (recently proposed as an alternative to scopolamine) were then tested on animals performing the PAL task. While all compounds influenced responding during PAL, only PCP and amphetamine impaired performance with minimal changes in secondary measures (response latencies, trials completed). Surprisingly ketamine did not cause a change in percent correct despite being an NMDA antagonist, indicating that not all NMDA antagonists are equal in the touch-screen platform. This finding is in agreement with existing literature showing differential effects of NMDA antagonists on a wide variety of behavioral assays include tasks of attention, memory, and cognitive flexibility (Gilmour et al., 2009; Dix et al., 2010; Smith et al., 2011). Moreover biperiden showed no benefit when compared to scopolamine, highlighting the current lack of an effective pharmacological model of cholinergic dysfunction in the touch-screen platform. These data demonstrate that performance on PAL can be disrupted by common pharmacological disease models, suggesting that PAL may have the sensitivity to serve as a translational test for the study of cognition in

  13. Cysteamine-modified silver nanoparticle aggregates for quantitative SERS sensing of pentachlorophenol with a portable Raman spectrometer.

    PubMed

    Jiang, Xiaohong; Yang, Min; Meng, Yanjing; Jiang, Wei; Zhan, Jinhua

    2013-08-14

    Cysteamine-modified silver nanoparticle aggregates has been fabricated for pentachlorophenol (PCP) sensing by surface-enhanced Raman spectroscopy (SERS) using a portable Raman spectrometer. The cysteamine monolayers could preconcentrate PCP close to the substrate surface through the electrostatic interaction, which makes the SERS detection of PCP possible. Moreover, the Raman bands of cysteamine could be used as the internal spectral reference in the quantitative analysis. Qualitative detection of PCP was carried out by SERS without any sample pretreatment. Quantitative analysis of PCP was further realized based on the prepared substrate, as the log-log plot of normalized SERS intensity of PCP versus its concentrations exhibits a good linear relationship. The SERS signals collected on 20 randomly selected points show that the relative standard deviation of the normalized Raman intensity is 5.8%, which indicates the substrate had good uniformity. The PCP sensor also shows good long-term stability in the analyte solution. The substrate was cyclic immersed into PCP and methanol solution; after several cycles, the sensor still had good adsorption to PCP, which revealed the sensor has good reusability. Coupling with a portable Raman spectrometer, the cysteamine-modified silver nanoparticle aggregates have the potential to be used for in situ and routine SERS analysis of PCP in environmental samples.

  14. Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage

    SciTech Connect

    Xu, Ting; Zhao, Jing; Hu, Ping; Dong, Zhangji; Li, Jingyun; Zhang, Hongchang; Yin, Daqiang; Zhao, Qingshun

    2014-06-01

    Pentachlorophenol (PCP) is a prevalent pollutant in the environment and has been demonstrated to be a serious toxicant to humans and animals. However, little is known regarding the molecular mechanism underlying its toxic effects on vertebrate early development. To explore the impacts and underlying mechanisms of PCP on early development, zebrafish (Danio rerio) embryos were exposed to PCP at concentrations of 0, 20 and 50 μg/L, and microscopic observation and cDNA microarray analysis were subsequently conducted at gastrulation stage. The morphological observations revealed that PCP caused a developmental delay of zebrafish embryos in a concentration-dependent manner. Transcriptomic data showed that 50 μg/L PCP treatment resulted in significant changes in gene expression level, and the genes involved in energy metabolism and cell behavior were identified based on gene functional enrichment analysis. The energy production of embryos was influenced by PCP via the activation of glycolysis along with the inhibition of oxidative phosphorylation (OXPHOS). The results suggested that PCP acts as an inhibitor of OXPHOS at 8 hpf (hours postfertilization). Consistent with the activated glycolysis, the cell cycle activity of PCP-treated embryos was higher than the controls. These characteristics are similar to the Warburg effect, which occurs in human tumors. The microinjection of exogenous ATP confirmed that an additional energy supply could rescue PCP-treated embryos from the developmental delay due to the energy deficit. Taken together, our results demonstrated that PCP causes a Warburg-like effect on zebrafish embryos during gastrulation, and the affected embryos had the phenotype of developmental delay. - Highlights: • We treat zebrafish embryos with PCP at gastrula stage. • PCP acts as an oxidative phosphorylation inhibitor, not an uncoupler, in gastrulation. • Exogenous ATP injection will rescue the development of effected embryos. • The transcriptome of PCP

  15. Photochemical Reduction of Low Concentrations of CO2 in a Porous Coordination Polymer with a Ruthenium(II)-CO Complex.

    PubMed

    Kajiwara, Takashi; Fujii, Machiko; Tsujimoto, Masahiko; Kobayashi, Katsuaki; Higuchi, Masakazu; Tanaka, Koji; Kitagawa, Susumu

    2016-02-18

    Direct use of low pressures of CO2 as a C1 source without concentration from gas mixtures is of great interest from an energy-saving viewpoint. Porous heterogeneous catalysts containing both adsorption and catalytically active sites are promising candidates for such applications. Here, we report a porous coordination polymer (PCP)-based catalyst, PCP-Ru(II) composite, bearing a Ru(II) -CO complex active for CO2 reduction. The PCP-Ru(II) composite showed improved CO2 adsorption behavior at ambient temperature. In the photochemical reduction of CO2 the PCP-Ru(II) composite produced CO, HCOOH, and H2 . Catalytic activity was comparable with the corresponding homogeneous Ru(II) catalyst and ranks among the highest of known PCP-based catalysts. Furthermore, catalytic activity was maintained even under a 5 % CO2 /Ar gas mixture, revealing a synergistic effect between the adsorption and catalytically active sites within the PCP-Ru(II) composite.

  16. Association of Communication Between Hospital-based Physicians and Primary Care Providers with Patient Outcomes

    PubMed Central

    Schnipper, Jeffrey L.; Auerbach, Andrew D.; Kaboli, Peter J.; Wetterneck, Tosha B.; Gonzales, David V.; Arora, Vineet M.; Zhang, James X.; Meltzer, David O.

    2008-01-01

    ABSTRACT BACKGROUND Patients admitted to general medicine inpatient services are increasingly cared for by hospital-based physicians rather than their primary care providers (PCPs). This separation of hospital and ambulatory care may result in important care discontinuities after discharge. We sought to determine whether communication between hospital-based physicians and PCPs influences patient outcomes. METHODS We approached consecutive patients admitted to general medicine services at six US academic centers from July 2001 to June 2003. A random sample of the PCPs for consented patients was contacted 2 weeks after patient discharge and surveyed about communication with the hospital medical team. Responses were linked with the 30-day composite patient outcomes of mortality, hospital readmission, and emergency department (ED) visits obtained through follow-up telephone survey and National Death Index search. We used hierarchical multi-variable logistic regression to model whether communication with the patient’s PCP was associated with the 30-day composite outcome. RESULTS A total of 1,772 PCPs for 2,336 patients were surveyed with 908 PCPs responses and complete patient follow-up available for 1,078 patients. The PCPs for 834 patients (77%) were aware that their patient had been admitted to the hospital. Of these, direct communication between PCPs and inpatient physicians took place for 194 patients (23%), and a discharge summary was available within 2 weeks of discharge for 347 patients (42%). Within 30 days of discharge, 233 (22%) patients died, were readmitted to the hospital, or visited an ED. In adjusted analyses, no relationship was seen between the composite outcome and direct physician communication (adjusted odds ratio 0.87, 95% confidence interval 0.56 – 1.34), the presence of a discharge summary (0.84, 95% CI 0.57–1.22), or PCP awareness of the index hospitalization (1.08, 95% CI 0.73–1.59). CONCLUSION Analysis of communication between PCPs

  17. Disposition of pentachlorophenol in rainbow trout (Salmo gairdneri ): Effect of inhibition of metabolism

    USGS Publications Warehouse

    Stehly, G.R.; Hayton, W.L.

    1989-01-01

    The accumulation kinetics of pentachlorophenol (PCP) were investigated in rainbow trout (Salmo gairdneri ) in the absence and presence of 25 mg/l salicylamide, an inhibitor of PCP metabolism. After exposure to 5 mu g/l PCP over 1-96 h, the amount of PCP in the whole fish, its concentration in water and the total amount of metabolites (water, whole fish and bile) were measured. Equations for these variables, based on a two compartment pharmacokinetic model, were fitted simultaneously to the data using the computer program NONLIN, which uses an iterative nonlinear least squares technique. Salicylamide decreased the metabolic clearance of PCP, which resulted in an increase in the bioconcentration factor (BCF); this increase was partially offset by a salicylamide-induced decrease in the apparent volume of distribution of PCP. A clearance-volume compartment model permitted partitioning of the BCF in terms of the underlying physiologic and biochemical processes (uptake clearance, metabolic clearance and apparent volume of distribution).

  18. Measuring patient-centered medical home access and continuity in clinics with part-time clinicians.

    PubMed

    Rosland, Ann-Marie; Krein, Sarah L; Kim, Hyunglin Myra; Greenstone, Clinton L; Tremblay, Adam; Ratz, David; Saffar, Darcy; Kerr, Eve A

    2015-05-01

    Common patient-centered medical home (PCMH) performance measures value access to a single primary care provider (PCP), which may have unintended consequences for clinics that rely on part-time PCPs and team-based care. Retrospective analysis of 110,454 primary care visits from 2 Veterans Health Administration clinics from 2010 to 2012. Multi-level models examined associations between PCP availability in clinic, and performance on access and continuity measures. Patient experiences with access and continuity were compared using 2012 patient survey data (N = 2881). Patients of PCPs with fewer half-day clinic sessions per week were significantly less likely to get a requested same-day appointment with their usual PCP (predicted probability 17% for PCPs with 2 sessions/week, 20% for 5 sessions/week, and 26% for 10 sessions/week). Among requests that did not result in a same-day appointment with the usual PCP, there were no significant differences in same-day access to a different PCP, or access within 2 to 7 days with patients' usual PCP. Overall, patients had >92% continuity with their usual PCP at the hospital-based site regardless of PCP sessions/week. Patients of full-time PCPs reported timely appointments for urgent needs more often than patients of part-time PCPs (82% vs 71%; P < .01), but reported similar experiences with routine access and continuity. Part-time PCP performance appeared worse when using measures focused on same-day access to patients' usual PCP. However, clinic-level same-day access, same-week access to the usual PCP, and overall continuity were similar for patients of part-time and full-time PCPs. Measures of in-person access to a usual PCP do not capture alternate access approaches encouraged by PCMH, and often used by part-time providers, such as team-based or non-face-to-face care.

  19. A Policy-into-Practice Intervention to Increase the Uptake of Evidence-Based Management of Low Back Pain in Primary Care: A Prospective Cohort Study

    PubMed Central

    Slater, Helen; Davies, Stephanie Joy; Parsons, Richard; Quintner, John Louis; Schug, Stephan Alexander

    2012-01-01

    Background Persistent non-specific low back pain (nsLBP) is poorly understood by the general community, by educators, researchers and health professionals, making effective care problematic. This study evaluated the effectiveness of a policy-into-practice intervention developed for primary care physicians (PCPs). Methods To encourage PCPs to adopt practical evidence-based approaches and facilitate time-efficient, integrated management of patients with nsLBP, we developed an interdisciplinary evidence-based, practical pain education program (gPEP) based on a contemporary biopsychosocial framework. One hundred and twenty six PCPs from primary care settings in Western Australia were recruited. PCPs participated in a 6.5-hour gPEP. Self-report measures recorded at baseline and at 2 months post-intervention included PCPs' attitudes, beliefs (modified Health Care Providers Pain and Impairment Relationship Scale (HC-PAIRS), evidence-based clinical practices (knowledge and skills regarding nsLBP management: 5-point Likert scale with 1 =  nil and 5 =  excellent) and practice behaviours (recommendations based on a patient vignette; 5-point Likert scale). Results Ninety one PCPs participated (attendance rate of 72%; post-intervention response rate 88%). PCP-responders adopted more positive, guideline-consistent beliefs, evidenced by clinically significant HC-PAIRS score differences (mean change  = −5.6±8.2, p<0.0001; 95% confidence interval: −7.6 to −3.6) and significant positive shifts on all measures of clinical knowledge and skills (p<0.0001 for all questions). Self management strategies were recommended more frequently post-intervention. The majority of responders who were guideline-inconsistent for work and bed rest recommendations (82% and 62% respectively) at pre-intervention, gave guideline-consistent responses at post-intervention. Conclusion An interprofessional pain education program set within a framework that aligns health policy and practice

  20. A policy-into-practice intervention to increase the uptake of evidence-based management of low back pain in primary care: a prospective cohort study.

    PubMed

    Slater, Helen; Davies, Stephanie Joy; Parsons, Richard; Quintner, John Louis; Schug, Stephan Alexander

    2012-01-01

    Persistent non-specific low back pain (nsLBP) is poorly understood by the general community, by educators, researchers and health professionals, making effective care problematic. This study evaluated the effectiveness of a policy-into-practice intervention developed for primary care physicians (PCPs). To encourage PCPs to adopt practical evidence-based approaches and facilitate time-efficient, integrated management of patients with nsLBP, we developed an interdisciplinary evidence-based, practical pain education program (gPEP) based on a contemporary biopsychosocial framework. One hundred and twenty six PCPs from primary care settings in Western Australia were recruited. PCPs participated in a 6.5-hour gPEP. Self-report measures recorded at baseline and at 2 months post-intervention included PCPs' attitudes, beliefs (modified Health Care Providers Pain and Impairment Relationship Scale (HC-PAIRS), evidence-based clinical practices (knowledge and skills regarding nsLBP management: 5-point Likert scale with 1  =  nil and 5  =  excellent) and practice behaviours (recommendations based on a patient vignette; 5-point Likert scale). Ninety one PCPs participated (attendance rate of 72%; post-intervention response rate 88%). PCP-responders adopted more positive, guideline-consistent beliefs, evidenced by clinically significant HC-PAIRS score differences (mean change  =  -5.6±8.2, p<0.0001; 95% confidence interval: -7.6 to -3.6) and significant positive shifts on all measures of clinical knowledge and skills (p<0.0001 for all questions). Self management strategies were recommended more frequently post-intervention. The majority of responders who were guideline-inconsistent for work and bed rest recommendations (82% and 62% respectively) at pre-intervention, gave guideline-consistent responses at post-intervention. An interprofessional pain education program set within a framework that aligns health policy and practice, encourages PCPs to adopt more self

  1. Temperature-based rapid toxicity test using Ceriodaphnia dubia.

    PubMed

    Jun, B H; Lee, S I; Ryu, H D; Kim, Y J

    2006-01-01

    Toxicants, which may cause the inhibition to the biological process in sewage/wastewater treatment plant, need to be monitored within short time to prevent from serious damage. A new method, Temperature-based rapid toxicity test (TempTox test) using Ceriodaphnia dubia, was developed and compared with the standard 48 hr acute bioassay (Std. 48-hr test). Inorganic toxicants of cadmium, zinc, copper, cyanide, chromium (III), chromium (VI) and organic toxicants of phenol, PCP and pesticides of BPMC, Diazinon, Fenitrothion were tested for TempTox test and Std. 48-hr test. Because the TempTox test is based on just temperature control, C. dubia neonates were exposed to toxicants under high temperature (35.5 degrees C) condition without any complicated pretreatment. After given exposure time of 1, 1.25, 1.5 hours, the number of the live (no toxic effect) or the dead (toxic effect) was counted with eye without the aid of any microscope and median effective concentrations (EC50 values) were determined. From the results for all toxicants, the TempTox test was proved to be as sensitive as the Std. 48-hr test with shorter-time of just 1.25-1.5 hours. Moreover, the TempTox test was further much more sensitive than alternative bioassays such as the 1-hour l.Q. test and 30-minute Microtox. The TempTox test showed a high applicability of toxicity bioassay for real sewage/wastewater treatment plant by its easiness, rapidity and sensitivity. Finally, the prototype for short-term TempTox test was introduced.

  2. Centriole positioning in epithelial cells and its intimate relationship with planar cell polarity

    PubMed Central

    Carvajal-Gonzalez, Jose Maria; Mulero-Navarro, Sonia; Mlodzik, Marek

    2016-01-01

    Planar cell polarity (PCP)-signaling and associated tissue polarization are evolutionarily conserved. A well documented feature of PCP-signaling in vertebrates is its link to centriole/cilia positioning, although the relationship of PCP and ciliogenesis is still debated. A recent report in Drosophila established that Frizzled (Fz)-PCP core signaling has an instructive input to polarized centriole positioning in non-ciliated Drosophila wing epithelia as a PCP read-out. Here, we review the impact of this observation in the context of recent descriptions of the relationship(s) of core Fz-PCP signaling and cilia/centriole positioning in epithelial and non-epithelial cells. All existing data are consistent with a model where Fz-PCP signaling functions upstream of centriole/cilia positioning, independent of ciliogenesis. The combined data sets indicate that the Fz-Dsh PCP complex is instructive for centriole/ciliary positioning via an actin-based mechanism. Thereby, centriole/cilia/centrosome positioning can be considered an evolutionarily conserved readout and common downstream effect of PCP-signaling from flies to mammals. PMID:27774671

  3. A Mechanism-based complementary screening approach for the amelioration and reversal of neurobehavioral teratogenicity

    PubMed Central

    Yanai, Joseph; Brick-Turin, Yael; Dotan, Sharon; Langford, Rachel; Pinkas, Adi; Slotkin, Theodore A.

    2010-01-01

    The identification of mechanisms and outcomes for neurobehavioral teratogenesis is critical to our ability to develop therapies to ameliorate or reverse the deleterious effects of exposure to developmental neurotoxicants. We established mechanistically-based complementary models for the study of cholinergic systems in the mouse and the chick, using both environmental neurotoxicants (chlorpyrifos, perfluoroalkyls) and drugs of abuse (heroin, nicotine, PCP). Behavioral evaluations were made using the Morris maze in the mouse, evaluating visuospatial memory related to hippocampal cholinergic systems, and imprinting in the chick, examining behavior dependent on cholinergic innervation of the IMHV. In both models we demonstrated the dependence of neurobehavioral deficits on impairment of cholinergic receptor-induced expression, and translocation of specific PKC isoforms. Understanding this mechanism, we were able to reverse both the synaptic and behavioral deficits with administration of neural progenitors. We discuss the prospects for clinical application of neural progenitor therapy, emphasizing protocols for reducing or eliminating immunologic rejection, as well as minimizing invasiveness of procedures through development of intravenous administration protocols. PMID:19217940

  4. The Urinary Bladder Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling.

    PubMed

    Habuka, Masato; Fagerberg, Linn; Hallström, Björn M; Pontén, Fredrik; Yamamoto, Tadashi; Uhlen, Mathias

    2015-01-01

    To understand functions and diseases of urinary bladder, it is important to define its molecular constituents and their roles in urinary bladder biology. Here, we performed genome-wide deep RNA sequencing analysis of human urinary bladder samples and identified genes up-regulated in the urinary bladder by comparing the transcriptome data to those of all other major human tissue types. 90 protein-coding genes were elevated in the urinary bladder, either with enhanced expression uniquely in the urinary bladder or elevated expression together with at least one other tissue (group enriched). We further examined the localization of these proteins by immunohistochemistry and tissue microarrays and 20 of these 90 proteins were localized to the whole urothelium with a majority not yet described in the context of the urinary bladder. Four additional proteins were found specifically in the umbrella cells (Uroplakin 1a, 2, 3a, and 3b), and three in the intermediate/basal cells (KRT17, PCP4L1 and ATP1A4). 61 of the 90 elevated genes have not been previously described in the context of urinary bladder and the corresponding proteins are interesting targets for more in-depth studies. In summary, an integrated omics approach using transcriptomics and antibody-based profiling has been used to define a comprehensive list of proteins elevated in the urinary bladder.

  5. Screening of fungi for soil remediation potential

    Treesearch

    Richard T. Lamar; Laura M. Main; Diane M. Dietrich; John A. Glaser

    1999-01-01

    The purpose of the present investigation was to determine if physiological and/or biochemical factors such as growth rate, tolerance to and ability to degrade PCP or creosote have use for predicting the potential bioremediation performance of fungi. Because we have focused the initial development of a fungal-based soil remediation technology on PCP- and/or creosote-...

  6. REMEDIATION OF SOILS CONTAMINATED WITH WOOD PRESERVING WASTES: CROSSCURRENT AND COUNTERCURRENT SOLVENT WASHING

    EPA Science Inventory

    solvent washing was evaluated as a method to remove pentachlorophenol (PCP) from aged field soils contaminated with wood treating wastes. Several soil:solvent contact ratios were considered. Solvent washing processes were evaluated based on the removal of PCP from the soil throug...

  7. Web-based classroom data collection in ADHD: a best practices case study.

    PubMed

    Bhatara, Vinod; Vogt, H Bruce; Ellis, Roland; Alshari, Ghyath; Patrick, Sarah

    2003-09-01

    Best practices research identifies and disseminates effective clinical strategies developed and refined by clinicians for their practices. As opposed to the content of health care, medical students and residents are typically not trained in the process of its provision. This paper illustrates a best practices approach to development of a Web-based classroom data collection method to improve medication management in attention deficit hyperactivity disorder (ADHD). 1) To increase Primary Care Physician (PCP) awareness of the process of best practices research, and; 2) to highlight the use of the World Wide Web as a tool for integration of care of children with ADHD. Based on the review of a large national study in ADHD, the key ingredients for the best pharmacotherapy practices were identified. The lessons from the literature were adapted for local practice using the framework and steps for best practices outlined by Mold and Gregory. A conceptual model of managing information provided by parents/caregivers and teachers to PCPs was developed. Several steps were identified, including Web-based classroom behavioral data collection by a care manager and feedback reports to PCPs from a child psychiatrist based on the data collected. This model is currently being tested. Our preliminary experience suggests that a best practices approach has potential applications to a variety of primary care settings in South Dakota. We encourage PCPs to consider best practice strategies for their own practices. The practice-based research network (Rush Net) being developed by the Center for Rural Health Improvement of the University of South Dakota School of Medicine's Department of Family Medicine can be helpful in this regard.

  8. Development of friction material by using precast prefired (pcp f) blocks

    NASA Astrophysics Data System (ADS)

    Dineshkumar, R.; Ramanamurthy, E. V. V.; Krishnapavanteja, Ch

    2017-05-01

    The braking system used to control and stop automobile system. The braking system converts the kinematic energy into heat energy by friction. The performance of the brake pad depends on composition of friction materials. The asbestos brake pads are carcinogenic nature and it makes so many health problems. The present research work is going to replacement of asbestos by new materials. The new material is made by fused ceramic materials from industrial wastage. In this study the industrial waste are recycled and conducted the suitable test to compare the performance of the new material with existing brake pad material. The wear test was conducted by pin on disc experiment. The non asbestos, nonfused, fused samples are represented by x1, x2 and x3. The new brake pad material is formed by non fused and fused ceramic materials. The brake pads are manufactured by powder compacting process.

  9. Non-canonical WNT/PCP signalling in cancer: Fzd6 takes centre stage.

    PubMed

    Corda, G; Sala, A

    2017-07-24

    Frizzled receptors are the mediators of the wnt canonical and non-canonical pathways, which play fundamental roles in cell differentiation and organism development. A large body of work indicates that dysregulation of wnt signalling is a feature of oncogenic transformation, but most of the studies published so far focus on the assessment of the consequences of aberrations of the canonical pathway in human cancer. In this review, we discuss the emerging role of the wnt non-canonical pathway regulated by frizzled receptor 6 (Fzd6) in the pathogenesis of different types of human malignancies. The function played by Fzd6 in the physiology of normal and cancer cells has been highlighted in the view that an increased knowledge of the signalling pathways upstream and downstream of this receptor could ultimately result in the identification of new targets for cancer therapy.

  10. Non-canonical WNT/PCP signalling in cancer: Fzd6 takes centre stage

    PubMed Central

    Corda, G; Sala, A

    2017-01-01

    Frizzled receptors are the mediators of the wnt canonical and non-canonical pathways, which play fundamental roles in cell differentiation and organism development. A large body of work indicates that dysregulation of wnt signalling is a feature of oncogenic transformation, but most of the studies published so far focus on the assessment of the consequences of aberrations of the canonical pathway in human cancer. In this review, we discuss the emerging role of the wnt non-canonical pathway regulated by frizzled receptor 6 (Fzd6) in the pathogenesis of different types of human malignancies. The function played by Fzd6 in the physiology of normal and cancer cells has been highlighted in the view that an increased knowledge of the signalling pathways upstream and downstream of this receptor could ultimately result in the identification of new targets for cancer therapy. PMID:28737757

  11. Possible Legal Barriers for PCP Access to Mental Health Treatment Records.

    PubMed

    Rothenberg, Leslie S; Ganz, David A; Wenger, Neil S

    2016-04-01

    Provider and payer groups have endorsed the goal of improving the integration of primary care and behavioral health across a variety of programs and settings. There is an interest in sharing patients' medical information, a goal that is permissible within HIPAA, but there are concerns about more restrictive state medical privacy laws. This article assesses whether a substantial number of state medical privacy laws are, or could be interpreted to be, more restrictive than HIPAA. Preliminary investigation found that in almost one third of the states (including large-population states such as Florida, Georgia, Massachusetts, New York, and Texas), primary care physicians (PCPs) may have difficulty accessing mental health treatment records without the patient's (or his/her guardian/conservator's) written consent. If a comprehensive legal analysis supports this conclusion, then those advocating integration of behavioral and primary care may need to consider seeking appropriate state legislative solutions.

  12. SOLIDIFICATION/STABILIZATION FOR REMEDIATON OF WOOD PRESERVING SITES: TREATMENT FOR DIOXINS, PCP, CREOSOTE, AND METALS

    EPA Science Inventory

    This article discusses the use of solidification/stabilization (S/S) to treat soils contaminated with organic and inorganic chemicals at wood preserving sites. Solidification is defined for this article as making a material into a free standing solid. Stabilization is defined as ...

  13. REDUCE-PCP study: radiographs in the emergency department utilization criteria evaluation-pediatric chest pain.

    PubMed

    Neff, Justin; Anderson, Melanie; Stephenson, Trent; Young, Joe; Hennes, Halim; Suter, Robert

    2012-05-01

    Many emergency physicians order chest x-rays (CXRs) for pediatric patients who present with a chief complaint of chest pain despite a paucity of research to support this testing, which exposes patients to radiation, cost, and delays. This study aimed to begin development of a decision making tool that will allow emergency physicians to selectively obtain CXR films in pediatric patients presenting with chest pain. We performed a retrospective cohort study of 400 consecutive pediatric patients with a chief complaint of chest pain and reviewed charts to determine how many received a CXR and which clinical characteristics were present in all patients. Chest radiograph findings were graded for significance as follows: (1) no or minor clinical significance: normal result in the CXR film without effect on the immediate evaluation of a patient; (2) moderate clinical significance: only impact on plan for follow-up; and (3) major clinical significance: result in the CXR film directly affects immediate management. We then evaluated each chart for historical or examination findings that might identify criteria associated with positive radiographic findings to propose a set of criteria that could lead to the development of a decision rule that allows a reduced utilization while having a high sensitivity for clinically significant positive findings on CXR film. Of the 400 pediatric patients reviewed, 63.5% (n = 254) received a CXR in the emergency department (ED). Of those receiving a CXR, only 8.26% (n = 21) had a finding that affected either ED management or follow-up planning. The criteria that would have identified all patients with positive results in the CXR films were abnormal vital signs, shortness of breath, palpitations, presence of comorbidities, abnormal or unilateral breath sounds, history of trauma, murmur, or cough. This pilot study demonstrates the potential for a decision rule to eliminate both cost and radiation exposure by using defined criteria to determine the need for a CXR in pediatric ED patients. We identified 8 simple criteria that would have identified all children who benefited from a CXR in this study. The next phase of this study will prospectively evaluate the utility of each of the criteria as part of a draft decision rule.

  14. SOLIDIFICATION/STABILIZATION FOR REMEDIATON OF WOOD PRESERVING SITES: TREATMENT FOR DIOXINS, PCP, CREOSOTE, AND METALS

    EPA Science Inventory

    This article discusses the use of solidification/stabilization (S/S) to treat soils contaminated with organic and inorganic chemicals at wood preserving sites. Solidification is defined for this article as making a material into a free standing solid. Stabilization is defined as ...

  15. An Ion-Selective Electrode for the Determination of Phencyclidine (PCP).

    DTIC Science & Technology

    1980-08-06

    procedure. b. Radioimmunoassay. c. Gas chromatography-flame ionization detector. d. Gas chromotography -NP detector. e. Gas chromotography - mass...methods have involved the use of gas chromatography (16-20) mass spectrometry (16, 22-24, 35) liquid chromatography (21) and very recently

  16. Dissemination of Prostate Cancer Screening to PCP’s in African American Communities

    DTIC Science & Technology

    2005-04-01

    undercurrent of " homophobia ." The PSA, as a blood test not involving rectal insertions, was not similarly "undignified." As one man expressed: "Yes, I think it’s...prostate cancer screening with the DRE] all about... maybe for some men it’s a homophobia . I think that’s the issue here. But I think with the PSA

  17. A novel physico-chemical property based model for studying the effects of mutation on the aggregation of peptides.

    PubMed

    Mathura, Venkatarajan S; Paris, Daniel; Mullan, Michael J

    2009-01-01

    Macromolecular events like protein aggregation are complex processes involving physico-chemical properties of their constituting residues. In this study, we used 5-dimensional physico-chemical property (PCP-descriptors) descriptors of amino acids, derived from 237 physico-chemical properties, to develop linear (LM) and neural network (NM) based regression models. We demonstrate their prediction performance in log values of aggregation rates (psi) for 15 human muscle acyl-phosphatase (AcP) mutants. The correlation coefficient between the predicted and the observed psi-values of the point mutations by LM and NM was 0.81 (p-value<0.001) and 0.71 (p-value<0.002) respectively. Using LM, we calculated psi-values for all possible mutations and performed an average linkage cluster analysis. We identified three groups of amino acids that differ in tolerance to mutations, resulting in increased or decreased aggregation rates. We suggest that our linear regression model can be applied to predict the aggregation propensity of point mutants where only sequence information is known. We also show that sequences containing beta-sheet classes of Structural Classification of Proteins (SCOP) have a higher propensity for aggregation.

  18. Analysis of phenolic pollutants in human samples by high performance capillary electrophoresis based on pretreatment of ultrasound-assisted emulsification microextraction and solidification of floating organic droplet.

    PubMed

    Wang, Huili; Yan, Hao; Wang, Chengjun; Chen, Fan; Ma, Meiping; Wang, Wenwei; Wang, Xuedong

    2012-08-31

    A novel, simple and rapid method, termed ultrasound-assisted emulsification microextraction and solidification of floating organic droplet (UAEM-SFO) coupled to high performance capillary electrophoresis (HPCE), was developed for preconcentration and analysis of five phenolic compounds (PCs) in human urine and blood samples. The proposed method is based on microextraction of target analytes in less-toxic organic solvent under assistance of ultrasound. A micro-droplet of less-toxic organic solvent floating on the surface of liquid samples in a sealed vial can be dispersed into sample solutions under the ultrasound frequency, solidified under ice bath, collected with a medicine spatula, molten at ambient temperature, and finally subjected to HPCE analysis. The parameters of UAEM-SFO procedure including type and volume of extraction solvent, extraction temperature, time of ultrasound-assisted extraction and centrifugation, sample pH, and ionic strength were optimized. The influence parameters on HPCE resolution such as pH, concentration of running buffer, applied voltage and injection time were also investigated. This method requires only 40 μL of 2-dodecanol extraction solvent and 8 min of pretreatment time. The enrichment factors of analytes were in the range of 114-172 and extraction recoveries (69-86%) were obtained. Good linearity was achieved for five analytes in the range of 0.05-100 μg L⁻¹ and the correlation coefficients ranged from 0.9934 to 0.9999. The limits of detection were 0.01 μg L⁻¹ for triclosan (TCS) and biophenol A (BPA), and 0.02 μg L⁻¹ for pentachlorophenol (PCP), 2,4-dichlorophenol (2,4-DCP) and 4-nonylphenol (4-NP) in urine samples, and 0.02 μg L⁻¹ for TCS and BPA, 0.04 μg L⁻¹ for PCP, 2,4-DCP and 4-NP in blood samples. The developed UAEM-SFO-HPCE method has a great potential in routine residual analysis of trace PCs in biological samples.

  19. The key microorganisms for anaerobic degradation of pentachlorophenol in paddy soil as revealed by stable isotope probing.

    PubMed

    Tong, Hui; Liu, Chengshuai; Li, Fangbai; Luo, Chunling; Chen, Manjia; Hu, Min

    2015-11-15

    Pentachlorophenol (PCP) is a common residual persistent pesticide in paddy soil and has resulted in harmful effect on soil ecosystem. The anaerobic microbial transformation of PCP, therefore, has been received much attentions, especially the functional microbial communities for the reductive transformation. However, the key functional microorganisms for PCP mineralization in the paddy soil still remain unknown. In this work, DNA-based stable isotope probing (SIP) was applied to explore the key microorganisms responsible for PCP mineralization in paddy soil. The SIP results indicated that the dominant bacteria responsible for PCP biodegradation belonged to the genus Dechloromonas of the class β-Proteobacteria. In addition, the increased production of (13)CH4 and (13)CO2 indicated that the addition of lactate enhanced the rate of biodegradation and mineralization of PCP. Two archaea classified as the genera of Methanosaeta and Methanocella of class Methanobacteria were enriched in the heavy fraction when with lactate, whereas no archaea was detected in the absence of lactate. These findings provide direct evidence for the species of bacteria and archaea responsible for anaerobic PCP or its breakdown products mineralization and reveal a new insight into the microorganisms linked with PCP degradation in paddy soil.

  20. Pentachlorophenol Degradation by Janibacter sp., a New Actinobacterium Isolated from Saline Sediment of Arid Land

    PubMed Central

    Khessairi, Amel; Jaouani, Atef; Turki, Yousra; Boudabous, Abdellatif; Hassen, Abdennaceur; Ouzari, Hadda

    2014-01-01

    Many pentachlorophenol- (PCP-) contaminated environments are characterized by low or elevated temperatures, acidic or alkaline pH, and high salt concentrations. PCP-degrading microorganisms, adapted to grow and prosper in these environments, play an important role in the biological treatment of polluted extreme habitats. A PCP-degrading bacterium was isolated and characterized from arid and saline soil in southern Tunisia and was enriched in mineral salts medium supplemented with PCP as source of carbon and energy. Based on 16S rRNA coding gene sequence analysis, the strain FAS23 was identified as Janibacter sp. As revealed by high performance liquid chromatography (HPLC) analysis, FAS23 strain was found to be efficient for PCP removal in the presence of 1% of glucose. The conditions of growth and PCP removal by FAS23 strain were found to be optimal in neutral pH and at a temperature of 30°C. Moreover, this strain was found to be halotolerant at a range of 1–10% of NaCl and able to degrade PCP at a concentration up to 300 mg/L, while the addition of nonionic surfactant (Tween 80) enhanced the PCP removal capacity. PMID:25313357

  1. Pentachlorophenol degradation by Janibacter sp., a new actinobacterium isolated from saline sediment of arid land.

    PubMed

    Khessairi, Amel; Fhoula, Imene; Jaouani, Atef; Turki, Yousra; Cherif, Ameur; Boudabous, Abdellatif; Hassen, Abdennaceur; Ouzari, Hadda

    2014-01-01

    Many pentachlorophenol- (PCP-) contaminated environments are characterized by low or elevated temperatures, acidic or alkaline pH, and high salt concentrations. PCP-degrading microorganisms, adapted to grow and prosper in these environments, play an important role in the biological treatment of polluted extreme habitats. A PCP-degrading bacterium was isolated and characterized from arid and saline soil in southern Tunisia and was enriched in mineral salts medium supplemented with PCP as source of carbon and energy. Based on 16S rRNA coding gene sequence analysis, the strain FAS23 was identified as Janibacter sp. As revealed by high performance liquid chromatography (HPLC) analysis, FAS23 strain was found to be efficient for PCP removal in the presence of 1% of glucose. The conditions of growth and PCP removal by FAS23 strain were found to be optimal in neutral pH and at a temperature of 30 °C. Moreover, this strain was found to be halotolerant at a range of 1-10% of NaCl and able to degrade PCP at a concentration up to 300 mg/L, while the addition of nonionic surfactant (Tween 80) enhanced the PCP removal capacity.

  2. Spatial and temporal variations in pentachlorophenol dissipation at the aerobic--anaerobic interfaces of flooded paddy soils.

    PubMed

    Lin, Jiajiang; Xu, Yan; Brookes, Philip C; He, Yan; Xu, Jianming

    2013-07-01

    Pentachlorophenol (PCP) dissipation occurs naturally in flooded soils and although dissipation half-lives vary between soil profiles at the millimeter-scale the reason is poorly understood. Vertical variations of PCP dissipation were investigated in three typical Chinese paddy soils; Soil 1 (Umbraqualf), Soil 2 (Plinthudult) and Soil 3 (Tropudult). The soil depth was divided into a surface and a deep layer based upon different PCP dissipations in the surface layer of 40-93, 42-88 and 16-100% for Soils 1-3 respectively. In the deep layer, PCP was greatly dissipated in Soil 2, but much less in Soil 1 and Soil 3. Correlation analysis indicated that SO4(2-) and Fe(III) were negatively related to PCP dissipation. SO4(2-) and Cl(-) were highly mobile in the flooded soil profiles. Fe(III) reduction increased with increasing soil depth, and was inhibited by high SO4(2-) concentrations.

  3. A hybrid pressure-density-based Mach uniform algorithm for 2D Euler equations on unstructured grids by using multi-moment finite volume method

    NASA Astrophysics Data System (ADS)

    Xie, Bin; Deng, Xi; Sun, Ziyao; Xiao, Feng

    2017-04-01

    We propose a novel Mach-uniform numerical model for 2D Euler equations on unstructured grids by using multi-moment finite volume method. The model integrates two key components newly developed to solve compressible flows on unstructured grids with improved accuracy and robustness. A new variant of AUSM scheme, so-called AUSM+-pcp (AUSM+ with pressure-correction projection), has been devised including a pressure-correction projection to the AUSM+ flux splitting, which maintains the exact numerical conservativeness and works well for all Mach numbers. A novel 3th-order, non-oscillatory and less-dissipative reconstruction has been proposed by introducing a multi-dimensional limiting and a BVD (boundary variation diminishing) treatment to the VPM (volume integrated average (VIA) and point value (PV) based multi-moment) reconstruction. The resulting reconstruction scheme, the limited VPM-BVD formulation, is able to resolve both smooth and non-smooth solutions with high fidelity. Benchmark tests have been used to verify the present model. The numerical results substantiate the present model as an accurate and robust unstructured-grid formulation for flows of all Mach numbers.

  4. Long-term storage and impedance-based water toxicity testing capabilities of fluidic biochips seeded with RTgill-W1 cells.

    PubMed

    Brennan, Linda M; Widder, Mark W; Lee, Lucy E J; van der Schalie, William H

    2012-08-01

    Rainbow trout gill epithelial cells (RTgill-W1) are used in a cell-based biosensor that can respond within one hour to toxic chemicals that have the potential to contaminate drinking water supplies. RTgill-W1 cells seeded on enclosed fluidic biochips and monitored using electric cell-substrate impedance sensing (ECIS) technology responded to 18 out of the 18 toxic chemicals tested within one hour of exposure. Nine of these chemical responses were within established concentration ranges specified by the U.S. Army for comparison of toxicity sensors for field application. The RTgill-W1 cells remain viable on the biochips at ambient carbon dioxide levels at 6°C for 78weeks without media changes. RTgill-W1 biochips stored in this manner were challenged with 9.4μM sodium pentachlorophenate (PCP), a benchmark toxicant, and impedance responses were significant (p<0.001) for all storage times tested. This poikilothermic cell line has toxicant sensitivity comparable to a mammalian cell line (bovine lung microvessel endothelial cells (BLMVECs)) that was tested on fluidic biochips with the same chemicals. In order to remain viable, the BLMVEC biochips required media replenishments 3 times per week while being maintained at 37°C. The ability of RTgill-W1 biochips to maintain monolayer integrity without media replenishments for 78weeks, combined with their chemical sensitivity and rapid response time, make them excellent candidates for use in low cost, maintenance-free field-portable biosensors.

  5. Development and initial validation of primary care provider mental illness management and team-based care self-efficacy scales.

    PubMed

    Loeb, Danielle F; Crane, Lori A; Leister, Erin; Bayliss, Elizabeth A; Ludman, Evette; Binswanger, Ingrid A; Kline, Danielle M; Smith, Meredith; deGruy, Frank V; Nease, Donald E; Dickinson, L Miriam

    Develop and validate self-efficacy scales for primary care provider (PCP) mental illness management and team-based care participation. We developed three self-efficacy scales: team-based care (TBC), mental illness management (MIM), and chronic medical illness (CMI). We developed the scales using Bandura's Social Cognitive Theory as a guide. The survey instrument included items from previously validated scales on team-based care and mental illness management. We administered a mail survey to 900 randomly selected Colorado physicians. We conducted exploratory principal factor analysis with oblique rotation. We constructed self-efficacy scales and calculated standardized Cronbach's alpha coefficients to test internal consistency. We calculated correlation coefficients between the MIM and TBC scales and previously validated measures related to each scale to evaluate convergent validity. We tested correlations between the TBC and the measures expected to correlate with the MIM scale and vice versa to evaluate discriminant validity. PCPs (n=402, response rate=49%) from diverse practice settings completed surveys. Items grouped into factors as expected. Cronbach's alphas were 0.94, 0.88, and 0.83 for TBC, MIM, and CMI scales respectively. In convergent validity testing, the TBC scale was correlated as predicted with scales assessing communications strategies, attitudes toward teams, and other teamwork indicators (r=0.25 to 0.40, all statistically significant). Likewise, the MIM scale was significantly correlated with several items about knowledge and experience managing mental illness (r=0.24 to 41, all statistically significant). As expected in discriminant validity testing, the TBC scale had only very weak correlations with the mental illness knowledge and experience managing mental illness items (r=0.03 to 0.12). Likewise, the MIM scale was only weakly correlated with measures of team-based care (r=0.09 to.17). This validation study of MIM and TBC self-efficacy scales

  6. Evaluating the phytoremediation potential of Phragmites australis grown in pentachlorophenol and cadmium co-contaminated soils.

    PubMed

    Hechmi, Nejla; Aissa, Nadhira Ben; Abdenaceur, Hassen; Jedidi, Naceur

    2014-01-01

    Pot-culture experiments were conducted to evaluate the phytoremediation potential of a wetland plant species, Phragmites australis in cadmium (Cd) and pentachlorophenol (PCP) co-contaminated soil under glasshouse conditions for 70 days. The treatments included Cd (0, 5 and 50 mg kg(-1)) without or with PCP (50 and 250 mg kg(-1)). The results showed that growth of P. australis was significantly influenced by interaction of Cd and PCP, decreasing with either Cd or PCP additions. Plant biomass was inhibited and reduced by the rate of 89 and 92% in the low and high Cd treatments and by 20 and 40% in the low and high PCP treatments compared to the control. The mixture of low Cd and low PCP lessened Cd toxicity to plants, resulting in improved plant growth (by 144%). Under the joint stress of the two contaminants, the ability of Cd uptake and translocation by P. australis was weak, and the BF and TF values were inferior to 1.0. A low proportion of the metal is found aboveground in comparison to roots, indicating a restriction on transport upwards and an excluding effect on Cd uptake. Thus, P. australis cannot be useful for phytoextraction. The removal rate of PCP increased significantly (70%) in planted soil. Significant positive correlations were found between the DHA and the removal of PCP in planted soils which implied that plant root exudates promote the rhizosphere microorganisms and enzyme activity, thereby improving biodegradation of PCP. Based on results, P. australis cannot be effective for phytoremediation of soil co-contaminated with Cd and PCP. Further, high levels of pollutant hamper and eventually inhibit plant growth. Therefore, developing supplementary methods (e.g. exploring the partnership of plant-microbe) for either enhancing (phytoextraction) or reducing the bioavailability of contaminants in the rhizosphere (phytostabilization) as well as plant growth promoting could significantly improve the process of phytoremediation in co-contaminated soil.

  7. Factors influencing referral of patients with voice disorders from primary care to otolaryngology.

    PubMed

    Cohen, Seth M; Kim, Jaewhan; Roy, Nelson; Courey, Mark

    2014-01-01

    To evaluate the frequency, timing, and factors that influence referral of patients with laryngeal/voice disorders to otolaryngology following initial evaluation by a primary care physician (PCP). Retrospective analysis of a large, national administrative US claims database. Patients with a laryngeal disorder based on International Classification of Diseases, Ninth Revision, Clinical Modification codes from January 1, 2004 to December 31, 2008, seen by a PCP as an outpatient (with or without otolaryngology involvement), and continuously enrolled for 12 months were included. Patient age, gender, geographic region, last PCP laryngeal diagnosis, comorbid conditions, time from first PCP visit to first otolaryngology visit, number of PCP outpatient visits, and number of PCP laryngeal diagnoses were collected. Cox and generalized linear regressions were performed. A total of 149,653 unique patients saw a PCP as an outpatient for a laryngeal/voice disorder, with 136,152 (90.9%) only seeing a PCP, 6,013 (4.0%) referred by a PCP to an otolaryngologist, and 3,820 (2.6%) self-referred to an otolaryngologist. Acute laryngitis had a lower hazard ratio (HR) for otolaryngology referral than chronic laryngitis, nonspecific dysphonia, and laryngeal cancer. Having multiple comorbid conditions was associated with a greater HR for otolaryngology referral than having no comorbidities. Patient age, gender, and geographic region also affected otolaryngology referral. The time to otolaryngology evaluation ranged from <1 month to >3 months. PCP-referred patients had less time to the otolaryngology evaluation than self-referred patients. Multiple factors affected otolaryngology referral for patients with laryngeal/voice disorders. Further education of PCPs regarding appropriate otolaryngology referral for laryngeal/voice disorders is needed. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  8. Factors Influencing Referral of Patients with Voice Disorders from Primary Care to Otolaryngology

    PubMed Central

    Cohen, SM; Kim, J; Roy, N; Courey, M

    2013-01-01

    Objective To evaluate the frequency, timing, and factors that influence referral of patients with laryngeal/voice disorders to otolaryngology following initial evaluation by a primary care physician (PCP). Study Design Retrospective analysis of a large, national administrative U.S. claims database. Methods Patients with a laryngeal disorder based on ICD-9-CM codes from January 1, 2004 to December 31, 2008, seen by a PCP as an outpatient (with or without otolaryngology involvement), and continuously enrolled for 12 months were included. Patient age, gender, geographic region, last PCP laryngeal diagnosis, comorbid conditions, time from first PCP visit to first otolaryngology visit, number of PCP outpatient visits, and number of PCP laryngeal diagnoses were collected. Cox and generalized linear regressions were performed. Results 149,653 unique patients saw a PCP as an outpatient for a laryngeal/voice disorder with 136,152 (90.9%) only seeing a PCP, 6013 (4.0%) referred by PCP to an otolaryngologist, and 3820 (2.6%) self-referred to an otolaryngologist. Acute laryngitis had a lower hazard ratio (HR) for otolaryngology referral than chronic laryngitis, non-specific dysphonia, and laryngeal cancer. Multiple comorbid conditions had a greater HR for otolaryngology referral than having no comorbidities. Patient age, gender, and geographic region also affected otolaryngology referral. The time to otolaryngology evaluation ranged from < 1 month to > 3 months. PCP referred patients had less time to the otolaryngology evaluation than self-referred patients. Conclusions Multiple factors affected otolaryngology referral for patients with laryngeal/voice disorders. Further education of PCPs regarding appropriate otolaryngology referral for laryngeal/voice disorders is needed. PMID:23794289

  9. The subchronic phencyclidine rat model: relevance for the assessment of novel therapeutics for cognitive impairment associated with schizophrenia.

    PubMed

    Janhunen, Sanna K; Svärd, Heta; Talpos, John; Kumar, Gaurav; Steckler, Thomas; Plath, Niels; Lerdrup, Linda; Ruby, Trine; Haman, Marie; Wyler, Roger; Ballard, Theresa M

    2015-11-01

    Current treatments for schizophrenia have modest, if any, efficacy on cognitive dysfunction, creating a need for novel therapies. Their development requires predictive animal models. The N-methyl-D-aspartate (NMDA) hypothesis of schizophrenia indicates the use of NMDA antagonists, like subchronic phencyclidine (scPCP) to model cognitive dysfunction in adult animals. The objective of this study was to assess the scPCP model by (1) reviewing published findings of scPCP-induced neurochemical changes and effects on cognitive tasks in adult rats and (2) comparing findings from a multi-site study to determine scPCP effects on standard and touchscreen cognitive tasks. Across four research sites, the effects of scPCP (typically 5 mg/kg twice daily for 7 days, followed by at least 7-day washout) in adult male Lister Hooded rats were studied on novel object recognition (NOR) with 1-h delay, acquisition and reversal learning in Morris water maze and touchscreen-based visual discrimination. Literature findings showed that scPCP impaired attentional set-shifting (ASST) and NOR in several labs and induced a variety of neurochemical changes across different labs. In the multi-site study, scPCP impaired NOR, but not acquisition or reversal learning in touchscreen or water maze. Yet, this treatment regimen induced locomotor hypersensitivity to acute PCP until 13-week post-cessation. The multi-site study confirmed that scPCP impaired NOR and ASST only and demonstrated the reproducibility and usefulness of the touchscreen approach. Our recommendation, prior to testing novel therapeutics in the scPCP model, is to be aware that further work is required to understand the neurochemical changes and specificity of the cognitive deficits.

  10. Towards successful coordination of electronic health record based-referrals: a qualitative analysis

    PubMed Central

    2011-01-01

    Background Successful subspecialty referrals require considerable coordination and interactive communication among the primary care provider (PCP), the subspecialist, and the patient, which may be challenging in the outpatient setting. Even when referrals are facilitated by electronic health records (EHRs) (i.e., e-referrals), lapses in patient follow-up might occur. Although compelling reasons exist why referral coordination should be improved, little is known about which elements of the complex referral coordination process should be targeted for improvement. Using Okhuysen & Bechky's coordination framework, this paper aims to understand the barriers, facilitators, and suggestions for improving communication and coordination of EHR-based referrals in an integrated healthcare system. Methods We conducted a qualitative study to understand coordination breakdowns related to e-referrals in an integrated healthcare system and examined work-system factors that affect the timely receipt of subspecialty care. We conducted interviews with seven subject matter experts and six focus groups with a total of 30 PCPs and subspecialists at two tertiary care Department of Veterans Affairs (VA) medical centers. Using techniques from grounded theory and content analysis, we identified organizational themes that affected the referral process. Results Four themes emerged: lack of an institutional referral policy, lack of standardization in certain referral procedures, ambiguity in roles and responsibilities, and inadequate resources to adapt and respond to referral requests effectively. Marked differences in PCPs' and subspecialists' communication styles and individual mental models of the referral processes likely precluded the development of a shared mental model to facilitate coordination and successful referral completion. Notably, very few barriers related to the EHR were reported. Conclusions Despite facilitating information transfer between PCPs and subspecialists, e

  11. Tinking Glutamatergically: Changing Concepts of Schizophrenia Based Upon Changing Neurochemical Models

    PubMed Central

    Kantrowitz, Joshua T.; Javitt, Daniel C.

    2016-01-01

    Clinical concepts of mental illness have always been modulated by underlying theoretical considerations. For the past fifty years, schizophrenia has been considered primarily a disease of dopaminergic neurotransmission. Although this conceptualization has helped greatly in explaining the clinical effects of psychostimulants and guiding the clinical use of both typical and atypical antipsychotics, it has nevertheless shaded how we look at the disorder from both a pathophysiological and therapeutic perspective. For example, most explanatory research in schizophrenia has focused on dopamine-rich regions of the brain, with little investigation of regions of the brain that are relatively dopamine poor. Starting approximately twenty years ago, an alternative formulation of schizophrenia was proposed based upon actions of the “dissociative anesthetic” class of psychotomimetic agents, including phencyclidine (PCP), ketamine and various designer drugs. These compounds induce psychosis by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors, suggesting an alternative model for pathogenesis in schizophrenia. As opposed to dopamine, the glutamatergic system is widely distributed throughout the brain and plays a prominent role in sensory processing as well as in subsequent stages of cortical analysis. Glutamatergic theories of schizophrenia, thus, predict that cortical dysfunction will be regionally diffuse but process specific. In addition, NMDA receptors incorporate binding sites for specific endogenous brain compounds, including the amino acids glycine and D-serine and the redox modulator glutathione, and interact closely with dopaminergic, cholinergic and γ-aminobutyric acid (GABA)-ergic systems. Glutamatergic theories, thus, open new potential approaches for treatment of schizophrenia, most of which are only now entering clinical evaluation. PMID:20880830

  12. The effect of a resident-led quality improvement project on improving communication between hospital-based and outpatient physicians.

    PubMed

    Kalanithi, Lucy; Coffey, Charles E; Mourad, Michelle; Vidyarthi, Arpana R; Hollander, Harry; Ranji, Sumant R

    2013-01-01

    This article reports on a resident-led quality improvement program to improve communication between inpatient internal medicine residents and their patients' primary care physicians (PCPs). The program included education on care transitions, standardization of documentation, audit and feedback of documented PCP communication rates with public reporting of performance, rapid-cycle data analysis and improvement projects, and a financial incentive. At baseline, PCP communication was documented in 55% of patients; after implementation of the intervention, communication was documented in 89.3% (2477 of 2772) of discharges during the program period. The program was associated with a significant increase in referring PCP satisfaction with communication at hospital admission (baseline, 27.7% "satisfied" or "very satisfied"; postintervention, 58.2%; P < .01) but not at discharge (baseline, 14.9%; postintervention, 21.8%; P = .41). Residents cited the importance of PCP communication for patient care and audit and feedback of their performance as the principal drivers of their engagement in the project.

  13. Impaired limbic cortico-striatal structure and sustained visual attention in a rodent model of schizophrenia.

    PubMed

    Barnes, Samuel A; Sawiak, Stephen J; Caprioli, Daniele; Jupp, Bianca; Buonincontri, Guido; Mar, Adam C; Harte, Michael K; Fletcher, Paul C; Robbins, Trevor W; Neill, Jo C; Dalley, Jeffrey W

    2014-10-31

    N-methyl-d-aspartate receptor (NMDAR) dysfunction is thought to contribute to the pathophysiology of schizophrenia. Accordingly, NMDAR antagonists such as phencyclidine (PCP) are used widely in experimental animals to model cognitive impairment associated with this disorder. However, it is unclear whether PCP disrupts the structural integrity of brain areas relevant to the profile of cognitive impairment in schizophrenia. Here we used high-resolution magnetic resonance imaging and voxel-based morphometry to investigate structural alterations associated with sub-chronic PCP treatment in rats. Sub-chronic exposure of rats to PCP (5mg/kg twice daily for 7 days) impaired sustained visual attention on a 5-choice serial reaction time task, notably when the attentional load was increased. In contrast, sub-chronic PCP had no significant effect on the attentional filtering of a pre-pulse auditory stimulus in an acoustic startle paradigm. Voxel-based morphometry revealed significantly reduced grey matter density bilaterally in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala. PCP-treated rats also exhibited reduced cortical thickness in the insular cortex. These findings demonstrate that sub-chronic NMDA receptor antagonism is sufficient to produce highly-localized morphological abnormalities in brain areas implicated in the pathogenesis of schizophrenia. Furthermore, PCP exposure resulted in dissociable impairments in attentional function. © The Author 2014. Published by Oxford University Press on behalf of CINP.

  14. Impaired Limbic Cortico-Striatal Structure and Sustained Visual Attention in a Rodent Model of Schizophrenia

    PubMed Central

    Barnes, Samuel A.; Sawiak, Stephen J.; Caprioli, Daniele; Jupp, Bianca; Buonincontri, Guido; Mar, Adam C.; Harte, Michael K.; Fletcher, Paul C.; Robbins, Trevor W.; Neill, Jo C.

    2015-01-01

    Background: N-methyl-d-aspartate receptor (NMDAR) dysfunction is thought to contribute to the pathophysiology of schizophrenia. Accordingly, NMDAR antagonists such as phencyclidine (PCP) are used widely in experimental animals to model cognitive impairment associated with this disorder. However, it is unclear whether PCP disrupts the structural integrity of brain areas relevant to the profile of cognitive impairment in schizophrenia. Methods: Here we used high-resolution magnetic resonance imaging and voxel-based morphometry to investigate structural alterations associated with sub-chronic PCP treatment in rats. Results: Sub-chronic exposure of rats to PCP (5mg/kg twice daily for 7 days) impaired sustained visual attention on a 5-choice serial reaction time task, notably when the attentional load was increased. In contrast, sub-chronic PCP had no significant effect on the attentional filtering of a pre-pulse auditory stimulus in an acoustic startle paradigm. Voxel-based morphometry revealed significantly reduced grey matter density bilaterally in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala. PCP-treated rats also exhibited reduced cortical thickness in the insular cortex. Conclusions: These findings demonstrate that sub-chronic NMDA receptor antagonism is sufficient to produce highly-localized morphological abnormalities in brain areas implicated in the pathogenesis of schizophrenia. Furthermore, PCP exposure resulted in dissociable impairments in attentional function. PMID:25552430

  15. Consumer satisfaction with primary care provider choice and associated trust

    PubMed Central

    Chu-Weininger, Ming Ying L; Balkrishnan, Rajesh

    2006-01-01

    Background Development of managed care, characterized by limited provider choice, is believed to undermine trust. Provider choice has been identified as strongly associated with physician trust. Stakeholders in a competitive healthcare market have competing agendas related to choice. The purpose of this study is to analyze variables associated with consumer's satisfaction that they have enough choice when selecting their primary care provider (PCP), and to analyze the importance of these variables on provider trust. Methods A 1999 randomized national cross-sectional telephone survey conducted of United States residential households, who had a telephone, had seen a medical professional at least twice in the past two years, and aged ≥ 20 years was selected for secondary data analyses. Among 1,117 households interviewed, 564 were selected as the final sample. Subjects responded to a core set of questions related to provider trust, and a subset of questions related to trust in the insurer. A previously developed conceptual framework was adopted. Linear and logistic regressions were performed based on this framework. Results Results affirmed 'satisfaction with amount of PCP choice' was significantly (p < .001) associated with provider trust. 'PCP's care being extremely effective' was strongly associated with 'satisfaction with amount of PCP choice' and 'provider trust'. Having sought a second opinion(s) was associated with lower trust. 'Spoke to the PCP outside the medical office,' 'satisfaction with the insurer' and 'insurer charges less if PCP within network' were all variables associated with 'satisfaction with amount of PCP choice' (all p < .05). Conclusion This study confirmed the association of 'satisfaction with amount of PCP choice' with provider trust. Results affirmed 'enough PCP choice' was a strong predictor of provider trust. 'Second opinion on PCP' may indicate distrust in the provider. Data such as 'trust in providers in general' and 'the role of

  16. Effects of pentachlorophenol on survival of earthworms (Lumbricus terrestris) and phagocytosis by their immunoactive coelomocytes

    SciTech Connect

    Giggleman, M.A.; Fitzpatrick, L.C.; Goven, A.J.; Venables, B.J.

    1998-12-01

    Earthworms, Lumbricus terrestris, exposed for 96 h to filter paper saturated with five nominal concentrations of pentachlorophenol, exhibited a 50% lethal concentration (LC50) of 25.0 {micro}g PCP/cm{sup 2} and corresponding whole worm body burden-based 50% lethal dose (LD50) of 877.7 {micro}g PCP/g dry mass. Linear regression modeling showed that worms increased body concentrations (BC = {micro}g PCP/g dry tissue mass) with increasing exposure concentrations (EC) according to BC = 113.5 + 29.5EC. Phagocytosis of yeast cells by immunoactive coelomocytes was suppressed only at body concentrations (863.3 {micro}g PCP/g dry mass) that approximated the calculated LD50 and overlapped those demonstrating lethality, indicating a sharp transition between sublethal and lethal toxicity. An exposure concentration of 15 {micro}g PCP/cm{sup 2} produced significant suppression of phagocytosis of yeast cells by immunoactive coelomocytes. However, the average measured body burden from this group approximated the estimated LD50, indicating a sharp toxic response slope. Exposure to 10 {micro}g PCP/cm{sup 2} with a corresponding body concentration of 501.3 {micro}g PCP/g dry mass did not affect phagocytosis. The importance of body burden data is emphasized.

  17. Outbreak of Pneumocystis jirovecii Infection among Heart Transplant Recipients: Molecular Investigation and Management of an Inter-human Transmission.

    PubMed

    Vindrios, William; Argy, Nicolas; Le Gal, Solène; Lescure, François-Xavier; Massias, Laurent; Le, Minh Patrick; Wolff, Michel; Yazdanpanah, Yazdan; Nevez, Gilles; Houze, Sandrine; Dorent, Richard; Lucet, Jean-Christophe

    2017-05-26

    An outbreak of Pneumocystis jirovecii pneumonia (PCP) occurred among heart transplant recipients (HTR) at the outpatient clinic of a university hospital, from March to September 2015. Clinical, therapeutic, biological and molecular data were analyzed to determine its origin and control the outbreak. Clinical and biological data regarding all HTR followed in the outpatient clinic were collected. PCP diagnosis was based on microscopy and real-time PCR. Investigations were performed by building a transmission map, completed by genotyping Pneumocystis isolates and by a control of chemoprophylaxis observance. Asymptomatic exposed patients were screened for colonisation using real-time PCR. Among 124 HTR, 7 PCP cases were confirmed. Screening identified three additional patients colonized by Pneumocystis jirovecii. All patients were cured and no further cases were identified after that trimethoprim-sulfamethoxazole prophylaxis was introduced in the entire cohort. Genotyping demonstrated the same strain in all PCP cases and colonized patients. All cases were linked with possible transmission chains from 2 possible index patients. Inter-human transmission was significantly associated with more frequent visits in the outpatient clinic. Six cases were receiving atovaquone as a prophylaxis. The occurrence of PCP was significantly associated with atovaquone prophylaxis. This is the first outbreak with detailed molecular analysis in HTR so far. Genotyping and transmission chain confirmed the inter-human transmission in all colonized/infected PCP cases. Outpatient clinic layout and high encounters probably caused this PCP cluster, which was controlled after systematic trimethoprim-sulfamethoxazole prophylaxis in exposed patients.

  18. Polymer-cysteamine conjugates: new mucoadhesive excipients for drug delivery?

    PubMed

    Kast, Constantia E; Bernkop-Schnürch, Andreas

    2002-03-02

    In the present study, the features of two new thiolated polymers--the so-called thiomers--were investigated. Mediated by a carbodiimide cysteamine was covalently attached to sodium carboxymethylcellulose (Na-CMC) and neutralised polycarbophil (Na-PCP). Depending on the weight-ratio polymer to cysteamine during the coupling reaction, the resulting CMC-cysteamine conjugate and PCP-cysteamine conjugate showed in maximum 43 +/- 15 and 138 +/- 22 micromole thiol groups per g polymer (mean +/- S.D.; n=3), respectively, which were used for further characterisation. Tensile studies carried out with the CMC-cysteamine conjugate on freshly excised porcine intestinal mucosa displayed no significantly (P<0.01) improved mucoadhesion, whereas, the mucoadhesive properties of the PCP-cysteamine conjugate were increased 2.5-fold compared with the unmodified polymer. The swelling behaviour of the CMC-cysteamine conjugate was uninfluenced by the covalent attachment of the sulfhydryl compound. In contrast the swelling behaviour of the PCP-cysteamine conjugate was improved significantly (P<0.01) versus unmodified PCP. Furthermore, in aqueous solutions the disintegration time of tablets based on the CMC- and PCP-cysteamine conjugates was prolonged 1.5 and 3.2-fold, respectively, in comparison to tablets containing the corresponding unmodified polymers. According to these results, especially the PCP-cysteamine conjugate represents a promising new pharmaceutical excipient for various drug delivery systems.

  19. Coupling between Pentachlorophenol Dechlorination and Soil Redox As Revealed by Stable Carbon Isotope, Microbial Community Structure, and Biogeochemical Data.

    PubMed

    Xu, Yan; He, Yan; Zhang, Qian; Xu, Jianming; Crowley, David

    2015-05-05

    Carbon isotopic analysis and molecular-based methods were used in conjunction with geochemical data sets to assess the dechlorination of pentachlorophenol (PCP) when coupled to biogeochemical processes in a mangrove soil having no prior history of anthropogenic contamination. The PCP underwent 96% dechlorination in soil amended with acetate, compared to 21% dehalogenation in control soil. Carbon isotope analysis of residual PCP demonstrated an obvious enrichment of 13C (εC, -3.01±0.1%). Molecular and statistical analyses demonstrated that PCP dechlorination and Fe(III) reduction were synergistically combined electron-accepting processes. Microbial community analysis further suggested that enhanced dechlorination of PCP during Fe(III) reduction was mediated by members of the multifunctional family of Geobacteraceae. In contrast, PCP significantly suppressed the growth of SO4(2-) reducers, which, in turn, facilitated the production of CH4 by diversion of electrons from SO4(2-) reduction to methanogenesis. The integrated data regarding stoichiometric alterations in this study gives direct evidence showing PCP, Fe(III), and SO4(2-) reduction, and CH4 production are coupled microbial processes during changes in soil redox.

  20. Standardizing primary care physician panels: is age and sex good enough?

    PubMed

    Chung, Sukyung; Eaton, Laura J; Luft, Harold S

    2012-07-01

    To determine if patient clinical conditions need to be considered when assessing primary care physician (PCP) workload in the context of standardizing panel sizes. Work resource value units (wRVUs) were used to standardize PCP panel workload. Standardized panels were created using (1) age and sex- and (2) clinical condition-based risk indicators. Billing data were used for all patients, regardless of insurance, for PCPs in a group practice (n = 190). Weighting methods were assessed for subgroups based on PCP specialty (family medicine, internal medicine, and pediatrics) and patient age (adults vs children) and for different levels of aggregation (patient vs PCP). Groupwide weights based on wRVUs of all primary care services delivered during the year were applied to individual patients and then aggregated to PCP panels. For age/sex weighting, only patient age and sex were taken into account. For condition-based weighting, 1275 disease categories, based on a combination of episode treatment groups (ETGs) and age and/or sex, were used. As expected, at the patient level, condition-based weights were far more discriminative than age/sex. At the PCP level, this discrimination was less important; panel weights varied 1.9- (age/sex-based) to 2.6-fold (condition-based) across PCPs. Correlations between the 2 weighting methods were high (r = 0.93) for child panels and moderate (r = 0.71) for adult panels (all P <.001). The heterogeneity of PCP panels should be considered when assessing PCP workload for panel management. Panel variability in workload is well captured by age/sex-based weights for children, but for adults condition-based adjustment may be necessary.

  1. Rodent Mismatch Negativity (MMN)/Theta Neuro-Oscillatory Response as a Translational Neurophysiological Biomarker for N-Methyl-D-Aspartate Receptor-Based New Treatment Development in Schizophrenia.

    PubMed

    Lee, Migyung; Balla, Andrea; Sershen, Henry; Sehatpour, Pejman; Lakatos, Peter; Javitt, Daniel C

    2017-08-17

    Deficits in the generation of auditory mismatch negativity (MMN) generation are among the most widely replicated neurophysiological abnormalities in schizophrenia and linked to underlying dysfunction of N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission. Here, we evaluate physiological properties of rodent MMN, along with sensitivity to NMDAR agonist and antagonist treatment, relative to known patterns of dysfunction in schizophrenia. Epidural neurophysiological responses to frequency- and duration-deviants, along with responses to standard stimuli, were obtained at baseline and following 2 and 4 weeks treatment from rats treated with saline, phencyclidine (PCP, 15 mg/kg/d by osmotic minipump), or PCP+glycine (16% by weight diet) interventions. Responses were analyzed using both event-related potential (ERP) and neuro-oscillatory (evoked power) approaches. At baseline, rodent duration MMN was associated with increased theta (θ)-frequency response similar to that observed in humans. PCP significantly reduced rodent duration MMN (p<0.001) and θ-band (p<0.01) response. PCP effects were prevented by concurrent glycine treatment (p<0.01 vs PCP alone). Effects related to stimulus-specific adaptation (SSA) were observed primarily in the alpha (α) and beta (β) frequency ranges. PCP-treatment also significantly reduced α-frequency response to standard stimuli while increasing θ-band response, reproducing the pattern of deficit observed in schizophrenia. Overall, we demonstrate that rodent duration MMN shows neuro-oscillatory signature similar to human MMN, along with sensitivity to the NMDAR antagonist and agonist administration. These findings reinforce recent human studies linking MMN deficits to θ-band neuro-oscillatory dysfunction and support utility of rodent duration MMN as a translational biomarker for investigation of mechanisms underlying impaired local circuit function in schizophrenia.Neuropsychopharmacology accepted article preview online

  2. Back to the roots: photodynamic inactivation of bacteria based on water-soluble curcumin bound to polyvinylpyrrolidone as a photosensitizer.

    PubMed

    Winter, Sandra; Tortik, Nicole; Kubin, Andreas; Krammer, Barbara; Plaetzer, Kristjan

    2013-10-01

    Photodynamic inactivation (PDI), the light-induced and photosensitizer-mediated overproduction of reactive oxygen species in microorganisms, represents a convincing approach to treat infections with (multi-resistant) pathogens. Due to its favourable photoactive properties combined with excellent biocompatibility, curcumin derived from the roots of turmeric (Curcuma longa) has been identified as an advantageous photosensitizer for PDI. To overcome the poor water solubility and the rapid decay of the natural substance at physiological pH, we examined the applicability of polyvinylpyrrolidone curcumin (PVP-C) in an acidified aqueous solution (solubility of PVP-C up to 2.7 mM) for photoinactivation of Gram(+) and Gram(-) bacteria. Five micromolar PVP-C incubated for 5 minutes and illuminated using a blue light LED array (435 ± 10 nm, 33.8 J cm(-2)) resulted in a >6 log10 reduction of the number of viable Staphylococcus aureus. At this concentration, longer incubation periods result in a lower phototoxicity, most likely due to degeneration of curcumin. Upon an increase of the PVP-C concentration to 50 μM (incubation for 15 or 25 min) a complete eradication of Staphylococcus aureus can be achieved. As expected for a non-cationic photosensitizer, cell wall permeabilization with CaCl2 prior to addition of 50 μM PVP-C for 15 min is necessary to induce a drop in the count of the Gram(-) Escherichia coli for more than 3 log10. As both constituents of the formulation, curcumin (E number E100) and polyvinylpyrrolidone (E1201), have been approved as food additives, a PDI based on PCP-C might allow for a very sparing clinical application (e.g. for disinfection of wounds) or even for employment in aseptic production of foodstuffs.

  3. Association of medical home team-based care functions and perceived improvements in patient-centered care at VHA primary care clinics.

    PubMed

    Helfrich, Christian D; Dolan, Emily D; Fihn, Stephan D; Rodriguez, Hector P; Meredith, Lisa S; Rosland, Ann-Marie; Lempa, Michele; Wakefield, Bonnie J; Joos, Sandra; Lawler, Lauren H; Harvey, Henry B; Stark, Richard; Schectman, Gordon; Nelson, Karin M

    2014-12-01

    Team-based care is central to the patient-centered medical home (PCMH), but most PCMH evaluations measure team structure exclusively. We assessed team-based care in terms of team structure, process and effectiveness, and the association with improvements in teams׳ abilities to deliver patient-centered care. We fielded a cross-sectional survey among 913 VA primary care clinics implementing a PCMH model in 2012. The dependent variable was clinic-level respondent-reported improvements in delivery of patient-centered care. Independent variables included three sets of measures: (1) team structure, (2) team process, and (3) team effectiveness. We adjusted for clinic workload and patient comorbidity. 4819 surveys were returned (25% estimated response rate). The highest ratings were for team structure (median of 89% of respondents being assigned to a teamlet, i.e., a PCP working with the same clinical associate, nurse care manager and clerk) and lowest for team process (median of 10% of respondents reporting the lowest level of stress/chaos). In multivariable regression, perceived improvements in patient-centered care were most strongly associated with participatory decision making (β=32, P<0.0001) and history of change in the clinic (β=18, P=0008) (both team processes). A stressful/chaotic clinic environment was associated with higher barriers to patient centered care (β=0.16-0.34, P=<0.0001), and lower improvements in patient-centered care (β=-0.19, P=0.001). Team process and effectiveness measures, often omitted from PCMH evaluations, had stronger associations with perceived improvements in patient-centered care than team structure measures. Team process and effectiveness measures may facilitate synthesis of evaluation findings and help identify positive outlier clinics. Published by Elsevier Inc.

  4. Planar graphene oxide-based magnetic ionic liquid nanomaterial for extraction of chlorophenols from environmental water samples coupled with liquid chromatography-tandem mass spectrometry.

    PubMed

    Cai, Mei-Qiang; Su, Jie; Hu, Jian-Qiang; Wang, Qian; Dong, Chun-Ying; Pan, Sheng-Dong; Jin, Mi-Cong

    2016-08-12

    A planar graphene oxide-based magnetic ionic liquid nanomaterial (PGO-MILN) was synthesized. The prepared PGO-MILN was characterized by transmission electronmicroscopy (TEM) and Fourier-transform infrared spectrometry (FTIR). The results of adsorption experiments showed that the PGO-MILN had great adsorption capacity for 2-chlorophenol (2-CP), 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), 2,3,4,6-tetrachlorophenol (2,3,4,6-TeCP) and pentachlorophenol (PCP). Based on the adsorption experimental data, a sensitive magnetic method for determination of the five CPs in environmental water samples was developed by an effective magnetic solid-phase extraction (MSPE) procedure coupled with high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The effects of main MSPE parameters including the solution pH, extraction time, desorption time, and volume of desorption solution on the extraction efficiencies had been investigated in detail. The recoveries ranged from 85.3 to 99.3% with correlation coefficients (r) higher than 0.9994 and the linear ranges were between 10 and 500ngL(-1). The limits of detection (LODs) and limits of quantification (LOQs) of the five CPs ranged from 0.2 to 2.6ngL(-1) and 0.6 to 8.7ngL(-1), respectively. The intra- and inter- day relative standard deviations (RSDs) were in the range from 0.6% to 7.4% and from 0.7% to 8.4%, respectively. It was confirmed that the PGO-MILN was a kind of highly effective MSPE materials used for enrichment of trace CPs in the environmental water. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Evaluation of Complex Toxicity of Canbon Nanotubes and Sodium Pentachlorophenol Based on Earthworm Coelomocytes Test

    PubMed Central

    Yang, Yang; Xiao, Yao; Li, Mei; Ji, Funian; Hu, Changwei; Cui, Yibin

    2017-01-01

    As a standard testing organism in soil ecosystems, the earthworm Eisenia fetida has been used widely in toxicity studies. However, tests at the individual level are time- and animal-consuming, with limited sensitivity. Earthworm coelomocytes are important for the assimilation and elimination of exogenous compounds and play a key role in the processes of phagocytosis and inflammation. In this study, we explored an optimal condition to culture coelomocytes of E. fetida in vitro and investigated the cytotoxicity of multiwalled carbon nanotubes (MWCNTs) and sodium pentachlorophenol (PCP-Na) using coelomocytes via evaluating lethal toxicity, oxidative stress, membrane damage, and DNA damage. The results showed that coelomocytes can be successfully cultured in vitro in primary under the RPMI-1640 medium with 2–4×104 cells/well (1–2×105 cells/mL) in 96-well plates at 25°C without CO2. Both MWCNTs and PCP-Na could cause oxidative damage and produce ROS, an evidence for lipid peroxidation with MDA generation and SOD and CAT activity inhibition at high stress. The two chemicals could separately damage the cell membrane structure, increasing permeability and inhibiting mitochondrial membrane potential (MMP). In addition, our results indicate that PCP-Na may be adsorbed onto MWCNTs and its toxicity on earthworm was accordingly alleviated, while a synergetic effect was revealed when PCP-Na and MWCNTs were added separately. In summary, coelomocyte toxicity in in vitro analysis is a sensitive method for detecting the adverse effects of carbon nanotubes combined with various pollutants. PMID:28125623

  6. Evaluation of Complex Toxicity of Canbon Nanotubes and Sodium Pentachlorophenol Based on Earthworm Coelomocytes Test.

    PubMed

    Yang, Yang; Xiao, Yao; Li, Mei; Ji, Funian; Hu, Changwei; Cui, Yibin

    2017-01-01

    As a standard testing organism in soil ecosystems, the earthworm Eisenia fetida has been used widely in toxicity studies. However, tests at the individual level are time- and animal-consuming, with limited sensitivity. Earthworm coelomocytes are important for the assimilation and elimination of exogenous compounds and play a key role in the processes of phagocytosis and inflammation. In this study, we explored an optimal condition to culture coelomocytes of E. fetida in vitro and investigated the cytotoxicity of multiwalled carbon nanotubes (MWCNTs) and sodium pentachlorophenol (PCP-Na) using coelomocytes via evaluating lethal toxicity, oxidative stress, membrane damage, and DNA damage. The results showed that coelomocytes can be successfully cultured in vitro in primary under the RPMI-1640 medium with 2-4×104 cells/well (1-2×105 cells/mL) in 96-well plates at 25°C without CO2. Both MWCNTs and PCP-Na could cause oxidative damage and produce ROS, an evidence for lipid peroxidation with MDA generation and SOD and CAT activity inhibition at high stress. The two chemicals could separately damage the cell membrane structure, increasing permeability and inhibiting mitochondrial membrane potential (MMP). In addition, our results indicate that PCP-Na may be adsorbed onto MWCNTs and its toxicity on earthworm was accordingly alleviated, while a synergetic effect was revealed when PCP-Na and MWCNTs were added separately. In summary, coelomocyte toxicity in in vitro analysis is a sensitive method for detecting the adverse effects of carbon nanotubes combined with various pollutants.

  7. Qualitative and Quantitative Radio-Anatomical Variation of the Posterior Clinoid Process

    PubMed Central

    Salma, Asem; Baidya, Nishanta B.; Wendt, Benjamin; Aguila, Francisco; Sammet, Steffen; Ammirati, Mario

    2011-01-01

    This study was conducted to investigate the radiological anatomy of the posterior clinoid process (PCP) to highlight preoperative awareness of its variations and its relationships to other skull base landmarks. The PCPs of 36, three-dimensional computed tomographic cadaveric heads were evaluated by studying the gross anatomy of the PCP and by measuring the distances between the PCP and other skull base anatomical landmarks relevant to transnasal or transcranial skull base approaches. PCP variations were found in five specimens (14%): in two the dorsum sellae was absent, in one the PCP and the anterior clinoid process (ACP) were connected unilaterally and in two bilaterally. The mean distance between the right/left PCP and the crista galli was 45.14 ± 4.0 standard deviation (SD_/46.24 ± 4.5 SD, respectively, while the distance to the middle point of the basion at the level of the foramen magnum was 40.41 ± 5.1 SD/41.0 ± 5.2 SD, respectively. The mean distance between the PCP and the ACP was 12.03 ± 3.18 SD on the right side and 12.11 ± 2.77 SD on the left. The data provided highlights the importance of careful preoperative evaluation of the PCP and of its relationships to other commonly encountered skull base landmarks. This information may give an idea of the exposure achievable through different transcranial and transnasal approaches. This is especially relevant when neuronavigation is not available. PMID:22547963

  8. Qualitative and quantitative radio-anatomical variation of the posterior clinoid process.

    PubMed

    Salma, Asem; Baidya, Nishanta B; Wendt, Benjamin; Aguila, Francisco; Sammet, Steffen; Ammirati, Mario

    2011-11-01

    This study was conducted to investigate the radiological anatomy of the posterior clinoid process (PCP) to highlight preoperative awareness of its variations and its relationships to other skull base landmarks. The PCPs of 36, three-dimensional computed tomographic cadaveric heads were evaluated by studying the gross anatomy of the PCP and by measuring the distances between the PCP and other skull base anatomical landmarks relevant to transnasal or transcranial skull base approaches. PCP variations were found in five specimens (14%): in two the dorsum sellae was absent, in one the PCP and the anterior clinoid process (ACP) were connected unilaterally and in two bilaterally. The mean distance between the right/left PCP and the crista galli was 45.14 ± 4.0 standard deviation (SD_/46.24 ± 4.5 SD, respectively, while the distance to the middle point of the basion at the level of the foramen magnum was 40.41 ± 5.1 SD/41.0 ± 5.2 SD, respectively. The mean distance between the PCP and the ACP was 12.03 ± 3.18 SD on the right side and 12.11 ± 2.77 SD on the left. The data provided highlights the importance of careful preoperative evaluation of the PCP and of its relationships to other commonly encountered skull base landmarks. This information may give an idea of the exposure achievable through different transcranial and transnasal approaches. This is especially relevant when neuronavigation is not available.

  9. Bifunctional sensor of pentachlorophenol and copper ions based on nanostructured hybrid films of humic acid and exfoliated layered double hydroxide via a facile layer-by-layer assembly.

    PubMed

    Yuan, Shuang; Peng, Dinghua; Hu, Xianluo; Gong, Jingming

    2013-06-27

    A new, highly sensitive bifunctional electrochemical sensor for the simultaneous determination of pentachlorophenol (PCP) and copper ions (Cu(2+)) has been developed, where organic-inorganic hybrid ultrathin films were fabricated by alternate assembly of humic acid (HA) and exfoliated Mg-Al-layered double hydroxide (LDH) nanosheets onto ITO substrates via a layer-by-layer (LBL) approach. The multilayer films were then characterized by means of UV-vis spectrometry, scanning electron microscopy (SEM), and atomic force microscope (AFM). These films were found to have a relatively smooth surface with almost equal amounts of HA incorporated in each cycle. Its electrochemical performance was systematically investigated. Our results demonstrate that such a newly designed (LDH/HA)n multilayer films, combining the individual properties of HA (dual recognition ability for organic herbicides and metal ions) together with LDH nanosheets (a rigid inorganic matrix), can be applied to the simultaneous analysis of PCP and Cu(II) without interference from each other. The LBL assembled nanoarchitectures were further investigated by X-ray photoelectron spectroscopy (XPS) and infrared spectroscopy (IR), which provides insight for bifunctional sensing behavior. Under the optimized conditions, the detection limit was found to be as low as 0.4 nM PCP, well below the guideline value of PCP in drinking water (3.7 nM) set by the United States Environmental Protection Agency (U.S. EPA), and 2.0 nM Cu(2+), much below the guideline value (2.0 mg L(-1), ~31.2 nM) from the World Health Organization (WHO), respectively. Toward the goal for practical applications, this simple and cost-effective probe was further evaluated by monitoring PCP and Cu(II) in water samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Simultaneous determination of 2,4,6-trichlorophenol and pentachlorophenol based on poly(Rhodamine B)/graphene oxide/multiwalled carbon nanotubes composite film modified electrode

    NASA Astrophysics Data System (ADS)

    Zhu, Xiaolin; Zhang, Kexin; Lu, Nan; Yuan, Xing

    2016-01-01

    In the present study, a poly(Rhodamine B)/graphene oxide/multiwalled carbon nanotubes nanocomposite modified glass carbon electrode (PRhB/GO/MWCNTs/GCE) was developed for the simultaneous determination of 2,4,6-trichlorophenol (2,4,6-TCP) and pentachlorophenol (PCP). The PRhB/GO/MWCNTs film was extensively characterized by emission scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy and electrochemical impedance spectroscopy (EIS). The electrochemical behaviors of 2,4,6-TCP and PCP were investigated by cyclic voltammetry, linear sweep voltammetry and differential pulse voltammetry. Due to the synergistic effect, the PRhB/GO/MWCNTs/GCE significantly facilitated the simultaneous electro-oxidation of 2,4,6-TCP and PCP with peak potential difference of 160 mV and enhanced oxidation currents. Under optimum conditions, the oxidation current of 2,4,6-TCP was linear to its concentration in the ranges of 4.0 × 10-9 to 1.0 × 10-7 M and 1.0 × 10-7 to 1.0 × 10-4 M with the detection limit (S/N = 3) of 8.0 × 10-10 M. And the linear concentration ranges for PCP were 2.0 × 10-9 to 1.0 × 10-7 M and 1.0 × 10-7 to 9.0 × 10-5 M with the detection limit of 5.0 × 10-10 M. Moreover, the proposed PRhB/GO/MWCNTs/GCE was successfully applied to the simultaneous determination of 2,4,6-TCP and PCP in practical water samples.

  11. Bioconcentration of 5,5',6-trichlorobiphenyl and pentachlorophenol in the midge, Chironomus riparius, as measured by a pharmacokinetic model

    USGS Publications Warehouse

    Lydy, M.J.; Hayton, W.L.; Staubus, A.E.; Fisher, S.W.

    1994-01-01

    A two compartment pharmacokinetic model was developed which describes the uptake and elimination of 5,5',6-trichlorobiphenyl (TCB) and pentachlorophenol (PCP) in the midge, Chironomus riparius. C. riparius were exposed to nominal TCB (2 ??g L-1) and PCP (9 ??g L-1) concentrations during a 16 h static uptake phase. Depuration was determined over approximately 45 h using a flowthrough system without feeding. The uptake clearance (P) was 330 ?? 61 ml g-1 midge h-1 for TCB and 55 ?? 4 ml g-1 midge h-1 for PCP, while measured bioconcentration factors (BCF) were 35,900 and 458 for TCB and PCP, respectively. Overall, the clearance-volume- based pharmacokinetic model predicted BCF values that were consistent with published values as well as with BCF values obtained from the octanol-water partition coefficient (K(ow)).

  12. Sulfa use, dihydropteroate synthase mutations, and Pneumocystis jirovecii pneumonia.

    PubMed

    Stein, Cheryl R; Poole, Charles; Kazanjian, Powel; Meshnick, Steven R

    2004-10-01

    A systematic review was conducted to examine the associations in Pneumocystis jirovecii pneumonia (PCP) patients between dihydropteroate synthase (DHPS) mutations and sulfa or sulfone (sulfa) prophylaxis and between DHPS mutations and sulfa treatment outcome. Selection criteria included study populations composed entirely of PCP patients and mutation or treatment outcome results for all patients, regardless of exposure status. Based on 13 studies, the risk of developing DHPS mutations is higher for PCP patients receiving sulfa prophylaxis than for PCP patients not receiving sulfa prophylaxis (p < 0.001). Results are too heterogeneous (p < 0.001) to warrant a single summary effect estimate. Estimated effects are weaker after 1996 and stronger in studies that included multiple isolates per patient. Five studies examined treatment outcome. The effect of DHPS mutations on treatment outcome has not been well studied, and the few studies that have been conducted are inconsistent even as to the presence or absence of an association.

  13. New Structural Data Reveal the Motion of Carrier Proteins in Nonribosomal Peptide Synthesis

    PubMed Central

    Kittilä, Tiia; Mollo, Aurelio

    2016-01-01

    Abstract The nonribosomal peptide synthetases (NRPSs) are one of the most promising resources for the production of new bioactive molecules. The mechanism of NRPS catalysis is based around sequential catalytic domains: these are organized into modules, where each module selects, modifies, and incorporates an amino acid into the growing peptide. The intermediates formed during NRPS catalysis are delivered between enzyme centers by peptidyl carrier protein (PCP) domains, which makes PCP interactions and movements crucial to NRPS mechanism. PCP movement has been linked to the domain alternation cycle of adenylation (A) domains, and recent complete NRPS module structures provide support for this hypothesis. However, it appears as though the A domain alternation alone is insufficient to account for the complete NRPS catalytic cycle and that the loaded state of the PCP must also play a role in choreographing catalysis in these complex and fascinating molecular machines. PMID:27435901

  14. The Drosophila neurogenin Tap functionally interacts with the Wnt-PCP pathway to regulate neuronal extension and guidance

    PubMed Central

    Yuan, Liqun; Hu, Shu; Okray, Zeynep; Ren, Xi; De Geest, Natalie; Claeys, Annelies; Yan, Jiekun; Bellefroid, Eric; Quan, Xiao-Jiang

    2016-01-01

    The neurogenin (Ngn) transcription factors control early neurogenesis and neurite outgrowth in mammalian cortex. In contrast to their proneural activity, their function in neurite growth is poorly understood. Drosophila has a single predicted Ngn homolog, Tap, of unknown function. Here we show that Tap is not a proneural protein in Drosophila but is required for proper axonal growth and guidance of neurons of the mushroom body, a neuropile required for associative learning and memory. Genetic and expression analyses suggest that Tap inhibits excessive axonal growth by fine regulation of the levels of the Wnt signaling adaptor protein Dishevelled. PMID:27385016

  15. TECHNOLOGY EVALUATION REPORT: SILICATE TECHNOLOGY CORPORATION - SOLIDIFICATION/STABILIZATION OF PCP AND INORGANIC CONTAMINANTS IN SOILS - SELMA, CA

    EPA Science Inventory

    This Technolgy Evaluation Report evaluates the solidification/stabilization process of Silicate Technology Corporation (STC) for the on-site treatment of contaminated soil The STC immobilization technology uses a proprietary product (FMS Silicate) to chemically stabilize and ...

  16. Hallucinogens and Dissociative Drugs, Including LSD, PCP, Ketamine, Dextromethorphan. National Institute on Drug Abuse Research Report Series.

    ERIC Educational Resources Information Center

    National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

    Research is developing a clearer picture of the dangers of mind-altering drugs. The goal of this report is to present the latest information to providers to help them strengthen their prevention and treatment efforts. A description is presented of dissociative drugs, and consideration is given as to why people take hallucinogens. The physical…

  17. Crystal structure of a PCP/Sfp complex reveals the structural basis for carrier protein posttranslational modification.

    PubMed

    Tufar, Peter; Rahighi, Simin; Kraas, Femke I; Kirchner, Donata K; Löhr, Frank; Henrich, Erik; Köpke, Jürgen; Dikic, Ivan; Güntert, Peter; Marahiel, Mohamed A; Dötsch, Volker

    2014-04-24

    Phosphopantetheine transferases represent a class of enzymes found throughout all forms of life. From a structural point of view, they are subdivided into three groups, with transferases from group II being the most widespread. They are required for the posttranslational modification of carrier proteins involved in diverse metabolic pathways. We determined the crystal structure of the group II phosphopantetheine transferase Sfp from Bacillus in complex with a substrate carrier protein in the presence of coenzyme A and magnesium, and observed two protein-protein interaction sites. Mutational analysis showed that only the hydrophobic contacts between the carrier protein's second helix and the C-terminal domain of Sfp are essential for their productive interaction. Comparison with a similar structure of a complex of human proteins suggests that the mode of interaction is highly conserved in all domains of life.

  18. TECHNOLOGY EVALUATION REPORT: SILICATE TECHNOLOGY CORPORATION - SOLIDIFICATION/STABILIZATION OF PCP AND INORGANIC CONTAMINANTS IN SOILS - SELMA, CA

    EPA Science Inventory

    This Technolgy Evaluation Report evaluates the solidification/stabilization process of Silicate Technology Corporation (STC) for the on-site treatment of contaminated soil The STC immobilization technology uses a proprietary product (FMS Silicate) to chemically stabilize and ...

  19. Effects of a Web-Based Patient Activation Intervention to Overcome Clinical Inertia on Blood Pressure Control: Cluster Randomized Controlled Trial

    PubMed Central

    Thiboutot, Jeffrey; Falkner, Bonita; Kephart, Donna K; Stuckey, Heather L; Adelman, Alan M; Curry, William J; Lehman, Erik B

    2013-01-01

    Background Only approximately half of patients with hypertension have their blood pressure controlled, due in large part to the tendency of primary care providers (PCPs) not to intensify treatment when blood pressure values are elevated. Objective This study tested the effect of an intervention designed to help patients ask questions at the point of care to encourage PCPs to appropriately intensify blood pressure treatment. Methods PCPs and their patients with hypertension (N=500) were recruited by letter and randomized into 2 study groups: (1) intervention condition in which patients used a fully automated website each month to receive tailored messages suggesting questions to ask their PCP to improve blood pressure control, and (2) control condition in which a similar tool suggested questions to ask about preventive services (eg, cancer screening). The Web-based tool was designed to be used during each of the 12 study months and before scheduled visits with PCPs. The primary outcome was the percentage of patients in both conditions with controlled blood pressure. Results Of 500 enrolled patients (intervention condition: n=282; control condition: n=218), 418 (83.6%) completed the 12-month follow-up visit. At baseline, 289 (61.5%) of participants had controlled blood pressure. Most (411/500, 82.2%) participants used the intervention during at least 6 of 12 months and 222 (62.5%) reported asking questions directly from the Web-based tool. There were no group differences in asking about medication intensification and there were no differences in blood pressure control after 12 months between the intervention condition (201/282, 71.3%) and control condition (143/218, 65.6%; P=.27) groups. More intervention condition participants discussed having a creatinine test (92, 52.6% vs 49, 35.5%; P=.02) and urine protein test (81, 44.8% vs 21, 14.6%; P<.001), but no group differences were observed in the rate of testing. The control condition participants reported more

  20. Primary care physician use across the breast cancer care continuum

    PubMed Central

    Jiang, Li; Lofters, Aisha; Moineddin, Rahim; Decker, Kathleen; Groome, Patti; Kendell, Cynthia; Krzyzanowska, Monika; Li, Dongdong; McBride, Mary L.; Mittmann, Nicole; Porter, Geoff; Turner, Donna; Urquhart, Robin; Winget, Marcy; Zhang, Yang; Grunfeld, Eva

    2016-01-01

    Abstract Objective To describe primary care physician (PCP) use and continuity of PCP care across the breast cancer care continuum. Design Population-based, retrospective cohort study using provincial cancer registries linked to health administrative databases. Setting British Columbia, Manitoba, and Ontario. Participants All women with incident invasive breast cancer from 2007 to 2012 in Manitoba and Ontario and from 2007 to 2011 in British Columbia. Main outcome measures The number and proportions of visits to PCPs were determined. Continuity of care was measured using the Usual Provider of Care index calculated as the proportion of visits to the most-often-visited PCP in the 6 to 30 months before a breast cancer diagnosis (baseline) and from 1 to 3 years following a breast cancer diagnosis (survivorship). Results More than three-quarters of patients visited their PCPs 2 or more times during the breast cancer diagnostic period, and more than 80% of patients had at least 1 PCP visit during breast cancer adjuvant treatment. Contact with the PCP decreased over time during breast cancer survivorship. Of the 3 phases, women appeared to be most likely to not have PCP contact during adjuvant treatment, with 10.7% (Ontario) to 18.7% (British Columbia) of women having no PCP visits during this phase. However, a sizable minority of women had at least monthly visits during the treatment phase, particularly in Manitoba and Ontario, where approximately a quarter of women saw a PCP at least monthly. We observed higher continuity of care with PCPs in survivorship (compared with baseline) in all provinces. Conclusion Primary care physicians were generally involved throughout the breast cancer care continuum, but the level of involvement varied across care phases and by province. Future interventions will aim to further integrate primary and oncology care. PMID:27737994

  1. Addition of C-C and C-H bonds by pincer-iridium complexes: a combined experimental and computational study.

    PubMed

    Laviska, David A; Guan, Changjian; Emge, Thomas J; Wilklow-Marnell, Miles; Brennessel, William W; Jones, William D; Krogh-Jespersen, Karsten; Goldman, Alan S

    2014-11-21

    We report that pincer-ligated iridium complexes undergo oxidative addition of the strained C-C bond of biphenylene. The sterically crowded species ((tBu)PCP)Ir ((R)PCP = κ(3)-1,3-C6H3(CH2PR2)2) initially reacts with biphenylene to selectively add the C(1)-H bond, to give a relatively stable aryl hydride complex. Upon heating at 125 °C for 24 h, full conversion to the C-C addition product, ((tBu)PCP)Ir(2,2'-biphenyl), is observed. The much less crowded ((iPr)PCP)Ir undergoes relatively rapid C-C addition at room temperature. The large difference in the apparent barriers to C-C addition is notable in view of the fact that the addition products are not particularly crowded, since the planar biphenyl unit adopts an orientation perpendicular to the plane of the (R)PCP ligands. Based on DFT calculations the large difference in the barriers to C-C addition can be explained in terms of a "tilted" transition state. In the transition state the biphenylene cyclobutadiene core is calculated to be strongly tilted (ca. 50°-60°) relative to its orientation in the product in the plane perpendicular to that of the PCP ligand; this tilt results in very short, unfavorable, non-bonding contacts with the t-butyl groups in the case of the (tBu)PCP ligand. The conclusions of the biphenylene studies are applied to interpret computational results for cleavage of the unstrained C-C bond of biphenyl by ((R)PCP)Ir.

  2. Retracing the path of planar cell polarity.

    PubMed

    Schenkelaars, Quentin; Fierro-Constain, Laura; Renard, Emmanuelle; Borchiellini, Carole

    2016-04-02

    The Planar Cell Polarity pathway (PCP) has been described as the main feature involved in patterning cell orientation in bilaterian tissues. Recently, a similar phenomenon was revealed in cnidarians, in which the inhibition of this pathway results in the absence of cilia orientation in larvae, consequently proving the functional conservation of PCP signaling between Cnidaria and Bilateria. Nevertheless, despite the growing accumulation of databases concerning basal lineages of metazoans, very few information concerning the existence of PCP components have been gathered outside of Bilateria and Cnidaria. Thus, the origin of this module or its prevalence in early emerging metazoans has yet to be elucidated. The present study addresses this question by investigating the genomes and transcriptomes from all poriferan lineages in addition to Trichoplax (Placozoa) and Mnemiopsis (Ctenophora) genomes for the presence of the core components of this pathway. Our results confirm that several PCP components are metazoan innovations. In addition, we show that all members of the PCP pathway, including a bona fide Strabismus ortholog (Van gogh), are retrieved only in one sponge lineage (Homoscleromorpha) out of four. This highly suggests that the full PCP pathway dates back at least to the emergence of homoscleromorph sponges. Consequently, several secondary gene losses would have occurred in the three other poriferan lineages including Amphimedon queenslandica (Demospongiae). Several proteins were not retrieved either in placozoans or ctenophores leading us to discuss the difficulties to predict orthologous proteins in basally branching animals. Finally, we reveal how the study of multigene families may be helpful to unravel the relationships at the base of the metazoan tree. The PCP pathway antedates the radiation of Porifera and may have arisen in the last common ancestor of animals. Oscarella species now appear as key organisms to understand the ancestral function of PCP

  3. Primary care physician use across the breast cancer care continuum: CanIMPACT study using Canadian administrative data.

    PubMed

    Jiang, Li; Lofters, Aisha; Moineddin, Rahim; Decker, Kathleen; Groome, Patti; Kendell, Cynthia; Krzyzanowska, Monika; Li, Dongdong; McBride, Mary L; Mittmann, Nicole; Porter, Geoff; Turner, Donna; Urquhart, Robin; Winget, Marcy; Zhang, Yang; Grunfeld, Eva

    2016-10-01

    To describe primary care physician (PCP) use and continuity of PCP care across the breast cancer care continuum. Population-based, retrospective cohort study using provincial cancer registries linked to health administrative databases. British Columbia, Manitoba, and Ontario. All women with incident invasive breast cancer from 2007 to 2012 in Manitoba and Ontario and from 2007 to 2011 in British Columbia. The number and proportions of visits to PCPs were determined. Continuity of care was measured using the Usual Provider of Care index calculated as the proportion of visits to the most-often-visited PCP in the 6 to 30 months before a breast cancer diagnosis (baseline) and from 1 to 3 years following a breast cancer diagnosis (survivorship). More than three-quarters of patients visited their PCPs 2 or more times during the breast cancer diagnostic period, and more than 80% of patients had at least 1 PCP visit during breast cancer adjuvant treatment. Contact with the PCP decreased over time during breast cancer survivorship. Of the 3 phases, women appeared to be most likely to not have PCP contact during adjuvant treatment, with 10.7% (Ontario) to 18.7% (British Columbia) of women having no PCP visits during this phase. However, a sizable minority of women had at least monthly visits during the treatment phase, particularly in Manitoba and Ontario, where approximately a quarter of women saw a PCP at least monthly. We observed higher continuity of care with PCPs in survivorship (compared with baseline) in all provinces. Primary care physicians were generally involved throughout the breast cancer care continuum, but the level of involvement varied across care phases and by province. Future interventions will aim to further integrate primary and oncology care. Copyright© the College of Family Physicians of Canada.

  4. Combined Quantification of Pulmonary Pneumocystis jirovecii DNA and Serum (1→3)-β-d-Glucan for Differential Diagnosis of Pneumocystis Pneumonia and Pneumocystis Colonization

    PubMed Central

    Le Gal, Solène; Da Costa, Cécilia; Virmaux, Michèle; Nevez, Gilles; Totet, Anne

    2013-01-01

    This study assessed a quantitative PCR (qPCR) assay for Pneumocystis jirovecii quantification in bronchoalveolar lavage (BAL) fluid samples combined with serum (1→3)-β-d-glucan (BG) level detection to distinguish Pneumocystis pneumonia (PCP) from pulmonary colonization with P. jirovecii. Forty-six patients for whom P. jirovecii was initially detected in BAL fluid samples were retrospectively enrolled. Based on clinical data and results of P. jirovecii detection, 17 and 29 patients were diagnosed with PCP and colonization, respectively. BAL fluid samples were reassayed using a qPCR assay targeting the mitochondrial large subunit rRNA gene. qPCR results and serum BG levels (from a Fungitell kit) were analyzed conjointly. P. jirovecii DNA copy numbers were significantly higher in the PCP group than in the colonization group (1.3 × 107 versus 3.4 × 103 copies/μl, P < 0.05). A lower cutoff value (1.6 × 103 copies/μl) achieving 100% sensitivity for PCP diagnosis and an upper cutoff value (2 × 104 copies/μl) achieving 100% specificity were determined. Applying these two values, 13/17 PCP patients and 19/29 colonized patients were correctly assigned to their patient groups. For the remaining 14 patients with P. jirovecii DNA copy numbers between the cutoff values, PCP and colonization could not be distinguished on the basis of qPCR results. Four of these patients who were initially assigned to the PCP group presented BG levels of ≥100 pg/ml. The other 10 patients, who were initially assigned to the colonization group, presented BG levels of <100 pg/ml. These results suggest that the combination of the qPCR assay, applying cutoff values of 1.6 × 103 and 2 × 104 copies/μl, and serum BG detection, applying a 100 pg/ml threshold, can differentiate PCP and colonization diagnoses. PMID:23903553

  5. Thermosetting composite matrix materials based on allyl and/or propargyl substituted cyclopentadiene, indene and fluorene

    NASA Astrophysics Data System (ADS)

    Tregre, Gregory Jude

    A series of all-hydrocarbon thermoset composite matrix resins was synthesized via electrophilic substitution of cyclopentadiene, indene, and fluorene ring systems with allyl and/or propargyl halides under phase transfer conditions. Reaction of cyclopentadiene with allyl chloride (ACP resin), propargyl bromide (PCP resin) or various feed ratios of allyl chloride and propargyl bromide (APCP resins) yielded mixtures of products with 2-6 substituents per cyclopentadiene ring. Reaction of indene with allyl chloride (Al resins) or propargyl bromide (PI resins) yielded mixtures of products with 2-4 substituents per indene. In both sets of resins the allyl functionality obtained a greater average degree of substitution than the analogous propargyl species. Differential scanning calorimetric (DSC) analysis of the multifunctional resins showed broad, high-energy thermal cures in all cases. The enthalpies of cure for ACP and PCP were 750 J/g and 805 J/g, respectively, with peak cure energies occurring at 310 and 248sp°C. The enthalpy of cure for APCP resins ranged from 750 J/g to 800 J/g with higher propargyl-functional resins yielding higher enthalpies of cure. Physically mixed ACP/PCP resin systems gave peak cure temperatures and energy values comparable to APCP resins. The enthalpies of cure for Al and PI-resins were 480 J/g and 630 J/g, respectively. Peak cure temperature for Al resin was 320sp°C, while the peak cure for PI resin occurred at 282sp°C. Infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR) were used to evaluate mechanisms of cure in the experimental resins. The allyl functional resins cured through a combination of ene reactions and polyaddition reactions. The propargyl functional resins cured through ene reactions and polyadditions but also underwent some cyclotrimerization of the propargyl functionalities. A small amount of autoxidation was seen in all of the resins. Thermal stability and carbon yields of the cured resins were

  6. Fault detection with principal component pursuit method

    NASA Astrophysics Data System (ADS)

    Pan, Yijun; Yang, Chunjie; Sun, Youxian; An, Ruqiao; Wang, Lin

    2015-11-01

    Data-driven approaches are widely applied for fault detection in industrial process. Recently, a new method for fault detection called principal component pursuit(PCP) is introduced. PCP is not only robust to outliers, but also can accomplish the objectives of model building, fault detection, fault isolation and process reconstruction simultaneously. PCP divides the data matrix into two parts: a fault-free low rank matrix and a sparse matrix with sensor noise and process fault. The statistics presented in this paper fully utilize the information in data matrix. Since the low rank matrix in PCP is similar to principal components matrix in PCA, a T2 statistic is proposed for fault detection in low rank matrix. And this statistic can illustrate that PCP is more sensitive to small variations in variables than PCA. In addition, in sparse matrix, a new monitored statistic performing the online fault detection with PCP-based method is introduced. This statistic uses the mean and the correlation coefficient of variables. Monte Carlo simulation and Tennessee Eastman (TE) benchmark process are provided to illustrate the effectiveness of monitored statistics.

  7. Design of provably physical-constraint-preserving methods for general relativistic hydrodynamics

    NASA Astrophysics Data System (ADS)

    Wu, Kailiang

    2017-05-01

    The paper develops high-order physical-constraint-preserving (PCP) methods for general relativistic hydrodynamic (GRHD) equations, equipped with a general equation of state. Here the physical constraints, describing the admissible states of GRHD, are referred to the subluminal constraint on the fluid velocity and the positivity of the density, pressure and specific internal energy. Preserving these constraints is very important for robust computations, otherwise violating one of them will lead to the ill-posed problem and numerical instability. To overcome the difficulties arising from the inherent strong nonlinearity contained in the constraints, we derive an equivalent definition of the admissible states. Using this definition, we prove the convexity, scaling invariance and Lax-Friedrichs (LxF) splitting property of the admissible state set G , and discover the dependence of G on the spacetime metric. Unfortunately, such dependence yields the nonequivalence of G at different points in curved spacetime, and invalidates the convexity of G in analyzing PCP schemes. This obstacle is effectively overcame by introducing a new formulation of the GRHD equations. Based on this formulation and the above theories, a first-order LxF scheme is designed on general unstructured mesh and rigorously proved to be PCP under a Courant-Friedrichs-Lewy (CFL) condition. With two types of PCP limiting procedures, we design high-order, provably (not probably) PCP methods under discretization on the proposed new formulation. These high-order methods include the PCP finite difference, finite volume and discontinuous Galerkin methods.

  8. Comparison of 2 real-time PCR assays for diagnosis of Pneumocystis jirovecii pneumonia in human immunodeficiency virus (HIV) and non-HIV immunocompromised patients.

    PubMed

    Montesinos, Isabel; Brancart, Françoise; Schepers, Kinda; Jacobs, Frederique; Denis, Olivier; Delforge, Marie-Luce

    2015-06-01

    A total of 120 bronchoalveolar lavage specimens from HIV and non-HIV immunocompromised patients, positive for Pneumocystis jirovecii by an "in house" real-time polymerase chain reaction (PCR), were evaluated by the Bio-Evolution Pneumocystis real-time PCR, a commercial quantitative assay. Patients were classified in 2 categories based on clinical and radiological findings: definite and unlikely Pneumocystis pneumonia (PCP). For the "in house" PCR, cycle threshold 34 was established as cut-off value to discriminate definite PCP from unlikely PCP with 65% and 85% of sensitivity and specificity, respectively. For the Bio-Evolution quantitative PCR, a cut-off value of 2.8×10(5)copies/mL was defined with 72% and 82% of sensitivity and specificity, respectively. Overlapped zones of results for definite and unlikely PCP were observed. Quantitative PCR is probably a useful tool for PCP diagnosis. However, for optimal management of PCP in non-HIV immunocompromised patients, operational thresholds should be assessed according to underlying diseases and other clinical and radiological parameters.

  9. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients.

    PubMed

    Alanio, Alexandre; Hauser, Philippe M; Lagrou, Katrien; Melchers, Willem J G; Helweg-Larsen, Jannik; Matos, Olga; Cesaro, Simone; Maschmeyer, Georg; Einsele, Hermann; Donnelly, J Peter; Cordonnier, Catherine; Maertens, Johan; Bretagne, Stéphane

    2016-09-01

    The Fifth European Conference on Infections in Leukaemia (ECIL-5) convened a meeting to establish evidence-based recommendations for using tests to diagnose Pneumocystis jirovecii pneumonia (PCP) in adult patients with haematological malignancies. Immunofluorescence assays are recommended as the most sensitive microscopic method (recommendation A-II: ). Real-time PCR is recommended for the routine diagnosis of PCP ( A-II: ). Bronchoalveolar lavage (BAL) fluid is recommended as the best specimen as it yields good negative predictive value ( A-II: ). Non-invasive specimens can be suitable alternatives ( B-II: ), acknowledging that PCP cannot be ruled out in case of a negative PCR result ( A-II: ). Detecting β-d-glucan in serum can contribute to the diagnosis but not the follow-up of PCP ( A-II: ). A negative serum β-d-glucan result can exclude PCP in a patient at risk ( A-II: ), whereas a positive test result may indicate other fungal infections. Genotyping using multilocus sequence markers can be used to investigate suspected outbreaks ( A-II: ). The routine detection of dihydropteroate synthase mutations in cases of treatment failure is not recommended ( B-II: ) since these mutations do not affect response to high-dose co-trimoxazole. The clinical utility of these diagnostic tests for the early management of PCP should be further assessed in prospective, randomized interventional studies.

  10. Degradation of pentachlorophenol by hydroxyl radicals and sulfate radicals using electrochemical activation of peroxomonosulfate, peroxodisulfate and hydrogen peroxide.

    PubMed

    Govindan, Kadarkarai; Raja, Mohan; Noel, Michael; James, E J

    2014-05-15

    The present study is to investigate the reactivity of free radicals (SO4(-) and HO) generated from common oxidants (peroxomonosulfate (PMS), peroxodisulfate (PDS) and hydrogen peroxide (HP)) activated by electrochemically generated Fe(2+)/Fe(3+) ions which furthermore are evaluated to destroy pentachlorophenol (PCP) in aqueous solution. The effect of solution pH and amount of oxidants (PMS, PDS and HP) in electrocoagulation (EC) on PCP degradation is analyzed in detail. The experimental results reveal that, optimum initial solution pH is 4.5 and PMS is more efficient oxidant addition in EC. 75% PCP degradation is achieved at 60min electrolysis time from PMS assisted EC. According to the first order rate constant, faster PCP degradation rate is obtained by PMS assisted EC. The PCP degradation rate by oxidant assisted EC is observed in the following order: EC/PMS>EC/PDS>EC/HP>EC. Further to identify the influences of experimental factors involved in PCP degradation by oxidant assisted EC, an experimental design based on an orthogonal array (OA) L9 (3(3)) is proposed using Taguchi method. The factors that most significantly affect the process robustness are identified as A (oxidant) and B (pH) which together account for nearly 86% of the variance. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Mediating Role of Psychological Capital in Relationship between Occupational Stress and Turnover Intention among Nurses at Veterans Administration Hospitals in Korea.

    PubMed

    Yim, Hee-Yun; Seo, Hyun-Ju; Cho, Yoonhyung; Kim, JinHee

    2017-03-01

    The aim of this study was to evaluate the mediating role of psychological capital (PCP) in the relationship between occupational stress and turnover intention in nurses. Data were collected from a sample of 447 nurses working at four Veterans Administration Hospitals throughout South Korea from July 1 to July 31, 2014. We collected data from the nurses using the following surveys: the Short Form Korean-Occupational Stress Scale, the Korean version of the Turnover Intention Scale, and the Korean version of the Psychological Capital Questionnaire. Multiple linear regression analysis was performed to examine the mediating role of PCP. The level of occupational stress was 1.81 ± 0.23, the level of turnover intention was 3.29 ± 0.86, and the PCP level was 3.95 ± 0.52. There were significant correlations among the three variables (occupational stress, turnover intention, and PCP). PCP played a partial mediating role (β=-0.22, p=.008) in the relationship between occupational stress and turnover intention (p<.001) among nurses working at the Veterans Administration Hospitals. Based on the findings of this study, we recommend that South Korean hospitals offer occupational stress management programs that incorporate relevant programs in efforts to strengthen the overall components of PCP among nurses to reduce turnover intentions. Further studies are required to determine the most effective intervention programs for hospital settings. Copyright © 2017. Published by Elsevier B.V.

  12. Pentachlorophenol remediation by Enterobacter sp. SG1 isolated from industrial dump site.

    PubMed

    Karn, Santosh Kumar; Geetanjali

    2014-02-01

    Chlorophenols contamination is serious concern to the environment due toxicity to all forms of life. Among all the chlorophenols, pentachlorophenol (PCP) is more detrimental to the environment. Pentachlorophenol used as pesticide, herbicide, antifungal agent and wood preservative which causes environmental pollution. In the present research a PCP degrading bacterium was isolated and characterized from industrial dump site. This isolate used PCP as its sole source of carbon and energy and was capable of degrading this compound, as indicated by stoichiometric release of chloride, ring cleavage activity and biomass formation. Based on morphological, biochemical and 16S rRNA gene sequence analysis this strain was identified as Enterobacter sp. SG1. Gas Chromatography (GC) analysis revealed that this strain was able to degrade PCP up to a concentration of 2 mM. This study showed that the removal efficiency of PCP by SG1 was found to be very effective and can be used in degradation of PCP contaminated site or waste in the environment.

  13. Using web technology and Java mobile software agents to manage outside referrals.

    PubMed

    Murphy, S N; Ng, T; Sittig, D F; Barnett, G O

    1998-01-01

    A prototype, web-based referral application was created with the objective of providing outside primary care providers (PCP's) the means to refer patients to the Massachusetts General Hospital and the Brigham and Women's Hospital. The application was designed to achieve the two primary objectives of providing the consultant with enough data to make decisions even at the initial visit, and providing the PCP with a prompt response from the consultant. The system uses a web browser/server to initiate the referral and Java mobile software agents to support the workflow of the referral. This combination provides a light client implementation that can run on a wide variety of hardware and software platforms found in the office of the PCP. The implementation can guarantee a high degree of security for the computer of the PCP. Agents can be adapted to support the wide variety of data types that may be used in referral transactions, including reports with complex presentation needs and scanned (faxed) images Agents can be delivered to the PCP as running applications that can perform ongoing queries and alerts at the office of the PCP. Finally, the agent architecture is designed to scale in a natural and seamless manner for unforeseen future needs.

  14. Localisation of phencyclidine-induced changes in brain energy metabolism.

    PubMed

    Meibach, R C; Glicks, D; Cox, R; Maayani, S

    1979-12-06

    The abuse of phencyclidine [1(1-phencylohexyl)piperidine, PCP], commonly referred to as angel dust or hog, is rapidly reaching epidemic proportions. PCP users often appear violent and increases in PCP-implicated homicides and suicides have been reported. In animal studies PCP has been demonstrated in brain up to 48 h after administration, long after blood levels become undetectable. However, there is little further information on the distribution of PCP within the central nervous system with regard to the possible sites of action. Recently, Sokoloff and associates described a new technique which can be used to visualise possible sites of drug action. The technique is based on the premise that neuronal activity is closely related to energy metabolism. Therefore, by directly monitoring 2-deoxy-D-glucose consumption before and after a pharmacological stimulus, we can obtain autoradiographic evidence of changes in neuronal activity in discrete areas brain as a response to that stimulus. Using this procedure, we now report that PCP causes dramatic changes in glucose metabolism in very specific regions of the rat brain.

  15. Using web technology and Java mobile software agents to manage outside referrals.

    PubMed Central

    Murphy, S. N.; Ng, T.; Sittig, D. F.; Barnett, G. O.

    1998-01-01

    A prototype, web-based referral application was created with the objective of providing outside primary care providers (PCP's) the means to refer patients to the Massachusetts General Hospital and the Brigham and Women's Hospital. The application was designed to achieve the two primary objectives of providing the consultant with enough data to make decisions even at the initial visit, and providing the PCP with a prompt response from the consultant. The system uses a web browser/server to initiate the referral and Java mobile software agents to support the workflow of the referral. This combination provides a light client implementation that can run on a wide variety of hardware and software platforms found in the office of the PCP. The implementation can guarantee a high degree of security for the computer of the PCP. Agents can be adapted to support the wide variety of data types that may be used in referral transactions, including reports with complex presentation needs and scanned (faxed) images Agents can be delivered to the PCP as running applications that can perform ongoing queries and alerts at the office of the PCP. Finally, the agent architecture is designed to scale in a natural and seamless manner for unforeseen future needs. PMID:9929190

  16. Solution phase and membrane immobilized iron-based free radical reactions: Fundamentals and applications for water treatment

    NASA Astrophysics Data System (ADS)

    Lewis, Scott Romak

    Membrane-based separation processes have been used extensively for drinking water purification, wastewater treatment, and numerous other applications. Reactive membranes synthesized through functionalization of the membrane pores offer enhanced reactivity due to increased surface area at the polymer-solution interface and low diffusion limitations. Oxidative techniques utilizing free radicals have proven effective for both the destruction of toxic organics and non-environmental applications. Most previous work focuses on reactions in the homogeneous phase; however, the immobilization of reactants in membrane pores offers several advantages. The use of polyanions immobilized in a membrane or chelates in solution prevents ferric hydroxide precipitation at near-neutral pH, a common limitation of iron(Fe(II/III))-catalyzed hydrogen peroxide (H 2O2) decomposition. The objectives of this research are to develop a membrane-based platform for the generation of free radicals, degrade toxic organic compounds using this and similar solution-based reactions, degrade toxic organic compounds in droplet form, quantify hydroxyl radical production in these reactions, and develop kinetic models for both processes. In this study, a functionalized membrane containing poly(acrylic acid) (PAA) was used to immobilize iron ions and conduct free radical reactions by permeating H2O2 through the membrane. The membrane's responsive behavior to pH and divalent cations was investigated and modeled. The conversion of Fe(II) to Fe(III) in the membrane and its effect on the decomposition of hydrogen peroxide were monitored and used to develop kinetic models for predicting H2O2 decomposition in these systems. The rate of hydroxyl radical production, and hence contaminant degradation can be varied by changing the residence time, H2O2 concentration, and/or iron loading. Using these membrane-immobilized systems, successful removal of toxic organic compounds, such as pentachlorophenol (PCP), from water

  17. Training community-based primary care physicians in the screeningand management of mental health disorders among Latino primary care patients

    PubMed Central

    Patel, Sapana R.; Gorritz, Magdaliz; Olfson, Mark; Bell, Michelle A.; Jackson, Elizabeth; Sánchez-Lacay, J. Arturo; Alfonso, César; Leeman, Eve; Lewis-Fernández, Roberto

    2015-01-01

    Objective Toevaluate a quality improvementintervention to improve thescreening and management (e.g., referral to psychiatric care) of common mental disorders in small independent Latino primary care practices serving patient populations of predominantly low-income Latino immigrants. Methods In 7 practices, academic detailing and consultation/liaison psychiatry were first implemented (Stage 1) and then supplemented withappointment scheduling and reminders to primary care physicians (PCP’s) by clinic staff (Stage 2).Acceptability and feasibility were assessed with independent patient samples during each stage. Results Participating PCP found the interventions acceptable and noted that referrals to language-matched specialty care and case-by-case consultation on medication management were particularly beneficial. The academic detailing and consultation/liaison intervention (Stage 1) did not significantly affect PCP screening, management or patient satisfaction with care. When support for appointment scheduling and reminders (Stage 2) was added, however, PCP referral to psychiatric services increased (p=.04) and referred patients were significantly more likely to follow through and have more visits to mental health professionals (p=.04). Conclusion Improving the quality of mental health care in low-resourced primary care settings may require academic detailing and consultation/liaison psychiatric intervention supplemented with staff outreach to achieve meaningful improvement in the processes of care. PMID:26598287

  18. Pneumocystis Infections

    MedlinePlus

    ... most common type of infection is pneumocystis pneumonia (PCP). PCP once was the major cause of death for ... or treat most cases. The key to surviving PCP is early treatment. The first signs of PCP ...

  19. Pneumocystis Pneumonia (For Parents)

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Pneumocystis Pneumonia KidsHealth > For Parents > Pneumocystis Pneumonia A A A What's in this article? About PCP Diagnosing PCP Treating PCP Pneumocystis pneumonia (PCP) is an infection caused by Pneumocystis jiroveci , ...

  20. Molecular epidemiologic analysis of a Pneumocystis pneumonia outbreak among renal transplant patients.

    PubMed

    Urabe, N; Ishii, Y; Hyodo, Y; Aoki, K; Yoshizawa, S; Saga, T; Murayama, S Y; Sakai, K; Homma, S; Tateda, K

    2016-04-01

    Between 18 November and 3 December 2011, five renal transplant patients at the Department of Nephrology, Toho University Omori Medical Centre, Tokyo, were diagnosed with Pneumocystis pneumonia (PCP). We used molecular epidemiologic methods to determine whether the patients were infected with the same strain of Pneumocystis jirovecii. DNA extracted from the residual bronchoalveolar lavage fluid from the five outbreak cases and from another 20 cases of PCP between 2007 and 2014 were used for multilocus sequence typing to compare the genetic similarity of the P. jirovecii. DNA base sequencing by the Sanger method showed some regions where two bases overlapped and could not be defined. A next-generation sequencer was used to analyse the types and ratios of these overlapping bases. DNA base sequences of P. jirovecii in the bronchoalveolar lavage fluid from four of the five PCP patients in the 2011 outbreak and from another two renal transplant patients who developed PCP in 2013 were highly homologous. The Sanger method revealed 14 genomic regions where two differing DNA bases overlapped and could not be identified. Analyses of the overlapping bases by a next-generation sequencer revealed that the differing types of base were present in almost identical ratios. There is a strong possibility that the PCP outbreak at the Toho University Omori Medical Centre was caused by the same strain of P. jirovecii. Two different types of base present in some regions may be due to P. jirovecii's being a diploid species.

  1. Pneumocystis pneumonia in HIV-positive patients in Spain: epidemiology and environmental risk factors

    PubMed Central

    Alvaro-Meca, Alejandro; Palomares-Sancho, Ines; Diaz, Asuncion; Resino, Rosa; De Miguel, Angel Gil; Resino, Salvador

    2015-01-01

    Introduction Specific environmental factors may play a role in the development of Pneumocystis pneumonia (PCP) in HIV-positive patients. The aim of this study was to estimate the PCP incidence and mortality in hospitalized HIV-positive patients in Spain during the combination antiretroviral therapy (cART) era (1997 to 2011), as well as to analyze the climatological factors and air pollution levels in relation to hospital admissions and deaths. Methods We carried out a retrospective study. Data were collected from the National Hospital Discharge Database and the State Meteorological Agency of Spain. A case-crossover analysis was applied to identify environmental risk factors related to hospitalizations and deaths. For each patient, climatic factors and pollution levels were assigned based on readings from the nearest meteorological station to his or her postal code. Results There were 13,139 new PCP diagnoses and 1754 deaths in hospitalized HIV-positive patients from 1997 to 2011. The PCP incidence (events per 1000 person-years) dropped from 11.6 in 1997 to 2000, to 5.4 in 2004 to 2011 (p<0.001). The mortality (events per 10,000 person-years) also decreased from 14.3 in 1997 to 2000, to 7.5 in 2004 to 2011 (p<0.001). Most hospital admissions and deaths occurred in the winter season and the fewest occurred in the summer, overlapping respectively with the lowest and highest temperatures of the year in Spain. Moreover, lower temperatures prior to PCP admission, as well as higher concentrations of NO2 and particulate matter up to 10 m in size (PM10) at the time of admission were associated with higher likelihoods of hospital admission due to PCP when two weeks, one month, 1.5 months or two months were used as controls (p<0.01). Furthermore, higher concentrations of ozone at one month (p=0.007), 1.5 months (p<0.001) and two months (p=0.006) prior to admission were associated with higher likelihoods of hospital admission with PCP. For PCP-related deaths, lower

  2. Effect of increasing the protein-to-fat ratio and reducing fat content on the chemical and physical properties of processed cheese product.

    PubMed

    Guinee, T P; O'Callaghan, D J

    2013-01-01

    Scientific studies indicate that the intake of dietary fat and saturated fats in the modern Western diet is excessive and contributes adversely to health, lifestyle, and longevity. In response, manufacturers of cheese and processed cheese products (PCP) are pursuing the development of products with reduced fat contents. The present study investigated the effect of altering the fat level (13.8, 18.2, 22.7, 27.9, and 32.5 g/100g) in PCP on their chemical and physical properties. The PCP were formulated in triplicate to different fat levels using Cheddar cheese, skim milk cheese, anhydrous milk fat, emulsifying salt (ES), NaCl, and water. The formulations were designed to give fixed moisture (~53 g/100g) and ES:protein ratio (0.105). The resultant PCP, and their water-soluble extracts (WSE), prepared from a macerated blend of PCP and water at a weight ratio of 1:2, were analyzed at 4d. Reducing the fat content significantly increased the firmness of the unheated PCP and reduced the flowability and maximum loss tangent (fluidity) of the melted PCP. These changes coincided with increases in the levels of total protein, water-soluble protein, water-insoluble protein, and water-soluble Ca, and a decrease in the molar ratio of water-soluble Ca to soluble P. However, both water-soluble Ca and water-soluble protein decreased when expressed as percentages of total protein and total Ca, respectively, in the PCP. The high level of protein was a major factor contributing to the deterioration in physical properties as the fat content of PCP was reduced. Diluting the protein content or reducing the potential of the protein to aggregate, and thereby form structures that contribute to rigidity, may provide a means for improving quality of reduced-fat PCP by using natural cheese with lower intact casein content and lower calcium:casein ratio, for example, or by decreasing the ratio of sodium phosphate to sodium citrate-based ES.

  3. Training community-based primary care physicians in the screening and management of mental health disorders among Latino primary care patients.

    PubMed

    Patel, Sapana R; Gorritz, Magdaliz; Olfson, Mark; Bell, Michelle A; Jackson, Elizabeth; Sánchez-Lacay, J Arturo; Alfonso, César; Leeman, Eve; Lewis-Fernández, Roberto

    2016-01-01

    To evaluate a quality improvement intervention to improve the screening and management (e.g., referral to psychiatric care) of common mental disorders in small independent Latino primary care practices serving patient populations of predominantly low-income Latino immigrants. In seven practices, academic detailing and consultation/liaison psychiatry were first implemented (Stage 1) and then supplemented with appointment scheduling and reminders to primary care physicians (PCPs) by clinic staff (Stage 2). Acceptability and feasibility were assessed with independent patient samples during each stage. Participating PCP found the interventions acceptable and noted that referrals to language-matched specialty care and case-by-case consultation on medication management were particularly beneficial. The academic detailing and consultation/liaison intervention (Stage 1) did not significantly affect PCP screening, management or patient satisfaction with care. When support for appointment scheduling and reminders (Stage 2) was added, however, PCP referral to psychiatric services increased (P=.04), and referred patients were significantly more likely to follow through and have more visits to mental health professionals (P=.04). Improving the quality of mental health care in low-resourced primary care settings may require academic detailing and consultation/liaison psychiatric intervention supplemented with staff outreach to achieve meaningful improvement in the processes of care. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Structure-activity relationships of phencyclidine derivatives in rat cerebellum.

    PubMed

    Pang, K; Johnson, S W; Maayani, S; Freedman, R

    1986-01-01

    The depressant effects of phencyclidine [1-(1-phenylcyclohexyl) piperidine, PCP] and three of its analogs (m-amino-PCP, m-nitro-PCP, and PCP-methyliodide) on the spontaneous action potential discharge of cerebellar Purkinje neurons in urethane-anesthetized rats were examined in this study. Both intraperitoneal injection and micro-pressure ejection were employed as routes of drug administration. The relative potency after parenteral administration corresponded closely with previous findings in behavioral test paradigms. PCP and m-amino-PCP were equipotent, m-nitro PCP was less potent than either PCP or m-amino-PCP, and PCP-methyliodide showed almost no activity. After local administration onto neurons, m-amino-PCP was significantly more potent than PCP, while PCP, m-nitro-PCP, and PCP-methyliodide were equipotent. Tritiated PCP, m-nitro PCP, and m-amino PCP have similar distribution and metabolism in cerebellum. PCP-methyliodide, a quaternary ion, does not cross the blood brain barrier. M-nitro PCP is appreciably less ionized at pH 7.4 than PCP or m-amino-PCP and, therefore, may be more easily sequestered into lipids. Differences between PCP and its analogs found in experiments which employ parenteral administration may reflect differences in drug distribution. These differences are minimized when these drugs are administered directly onto neurons via pressure microejection.

  5. Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers.

    PubMed

    Esteves, F; Calé, S S; Badura, R; de Boer, M G; Maltez, F; Calderón, E J; van der Reijden, T J; Márquez-Martín, E; Antunes, F; Matos, O

    2015-04-01

    The diagnosis of Pneumocystis pneumonia (PCP) relies on microscopic visualization of Pneumocystis jirovecii organisms or DNA detection in pulmonary specimens. This study aimed to assess the usefulness of (1-3)-β-d-glucan (BG), Krebs von den Lungen-6 antigen (KL-6), lactate dehydrogenase (LDH) and S-adenosyl methionine (SAM) as serologic biomarkers in the diagnosis of PCP. Serum levels of BG, KL-6, LDH and SAM were investigated in 145 Portuguese patients, 50 patients from the Netherlands, 25 Spanish patients and 40 Portuguese blood donors. Data on clinical presentation, chest imaging and gasometry tests were available. PCP cases were confirmed by microscopy and PCR techniques. A cost-effectiveness analysis was performed. BG was found to be the most reliable serologic biomarker for PCP diagnosis, followed by KL-6, LDH and SAM. The BG/KL-6 combination test was the most accurate serologic approach for PCP diagnosis, with 94.3% sensitivity and 89.6% specificity. Although less sensitive/specific than the reference standard classic methods based on bronchoalveolar lavage followed by microscopic or molecular detection of P. jirovecii organisms, the BG/KL-6 test may provide a less onerous procedure for PCP diagnosis, as it uses a minimally invasive and inexpensive specimen (blood), which may be also a major benefit for the patient's care. The BG/KL-6 combination test should be interpreted within the clinical context, and it may be used as a preliminary screening test in patients with primary suspicion of PCP, or as an alternative diagnostic procedure in patients with respiratory failure or in children, avoiding the associated risk of complications by the use of bronchoscopy.

  6. The spatio-temporal domains of Frizzled6 action in planar polarity control of hair follicle orientation.

    PubMed

    Chang, Hao; Smallwood, Philip M; Williams, John; Nathans, Jeremy

    2016-01-01

    In mammals, hair follicles cover most of the body surface and exhibit precise and stereotyped orientations relative to the body axes. Follicle orientation is controlled by the planar cell polarity (PCP; or, more generally, tissue polarity) system, as determined by the follicle mis-orientation phenotypes observed in mice with PCP gene mutations. The present study uses conditional knockout alleles of the PCP genes Frizzled6 (Fz6), Vangl1, and Vangl2, together with a series of Cre drivers to interrogate the spatio-temporal domains of PCP gene action in the developing mouse epidermis required for follicle orientation. Fz6 is required starting between embryonic day (E)11.5 and E12.5. Eliminating Fz6 in either the anterior or the posterior halves of the embryo or in either the feet or the torso leads to follicle mis-orientation phenotypes that are limited to the territories associated with Fz6 loss, implying either that PCP signaling is required for communicating polarity information on a local but not a global scale, or that there are multiple independent sources of global polarity information. Eliminating Fz6 in most hair follicle cells or in the inter-follicular epidermis at E15.5 suggests that PCP signaling in developing follicles is not required to maintain their orientation. The asymmetric arrangement of Merkel cells around the base of each guard hair follicle dependents on Fz6 expression in the epidermis but not in differentiating Merkel cells. These experiments constrain current models of PCP signaling and the flow of polarity information in mammalian skin.

  7. Primary care focus and utilization in the Medicare shared savings program accountable care organizations.

    PubMed

    Herrel, Lindsey A; Ayanian, John Z; Hawken, Scott R; Miller, David C

    2017-02-15

    Although Accountable Care Organizations (ACOs) are defined by the provision of primary care services, the relationship between the intensity of primary care and population-level utilization and costs of health care services has not been examined during early implementation of Medicare Shared Savings Program (MSSP) ACOs. Our objective was to evaluate the association between primary care focus and healthcare utilization and spending in the first performance period of the Medicare Shared Savings Program (MSSP) Accountable Care Organizations (ACOs). In this retrospective cohort study, we divided the 220 MSSP ACOs into quartiles of primary care focus based on the percentage of all ambulatory evaluation and management services delivered by a PCP (internist, family physician, or geriatrician). Using multivariable regression, we evaluated rates of utilization and spending during the initial performance period, adjusting for the percentage of non-white patients, region, number of months enrolled in the MSSP, number of beneficiary person years, percentage of dual eligible beneficiaries and percentage of beneficiaries over the age of 74. The proportion of ambulatory evaluation and management services delivered by a PCP ranged from <38% (lowest quartile, ACOs with least PCP focus) to >46% (highest quartile, ACOs with greatest PCP focus). ACOs in the highest quartile of PCP focus had higher adjusted rates of utilization of acute care hospital admissions (328 per 1000 person years vs 292 per 1000 person years, p = 0.01) and emergency department visits (756 vs 680 per 1000 person years, p = 0.02) compared with ACOs in the lowest quartile of PCP focus. ACOs in the highest quartile of PCP focus achieved no greater savings per beneficiary relative to their spending benchmarks ($142 above benchmark vs $87 below benchmark, p = 0.13). Primary care focus was not associated with increased savings or lower utilization of healthcare during the initial implementation of MSSP

  8. Predictors of primary care management of depression in the Veterans Affairs healthcare system.

    PubMed

    Chang, Evelyn T; Magnabosco, Jennifer L; Chaney, Edmund; Lanto, Andrew; Simon, Barbara; Yano, Elizabeth M; Rubenstein, Lisa V

    2014-07-01

    Primary care providers (PCPs) vary in skills to effectively treat depression. Key features of evidence-based collaborative care models (CCMs) include the availability of depression care managers (DCMs) and mental health specialists (MHSs) in primary care. Little is known, however, about the relationships between PCP characteristics, CCM features, and PCP depression care. To assess relationships between various CCM features, PCP characteristics, and PCP depression management. Cross-sectional analysis of a provider survey. 180 PCPs in eight VA sites nationwide. Independent variables included scales measuring comfort and difficulty with depression care; collaboration with a MHS; self-reported depression caseload; availability of a collocated MHS, and co-management with a DCM or MHS. Covariates included provider type and gender. For outcomes, we assessed PCP self-reported performance of key depression management behaviors in primary care in the past 6 months. Response rate was 52 % overall, with 47 % attending physicians, 34 % residents, and 19 % nurse practitioners and physician assistants. Half (52 %) reported greater than eight veterans with depression in their panels and a MHS collocated in primary care (50 %). Seven of the eight clinics had a DCM. In multivariable analysis, significant predictors for PCP depression management included comfort, difficulty, co-management with MHSs and numbers of veterans with depression in their panels. PCPs who felt greater ease and comfort in managing depression, co-managed with MHSs, and reported higher depression caseloads, were more likely to report performing depression management behaviors. Neither a collocated MHS, collaborating with a MHS, nor co-managing with a DCM independently predicted PCP depression management. Because the success of collaborative care for depression depends on the ability and willingness of PCPs to engage in managing depression themselves, along with other providers, more research is necessary to

  9. A consideration of the evidence that genetic defects in planar cell polarity contribute to the etiology of human neural tube defects.

    PubMed

    Juriloff, Diana M; Harris, Muriel J

    2012-10-01

    A variety of human birth defects originate in failure of closure of the embryonic neural tube. The genetic cause of the most common nonsyndromic defects, spina bifida (SB) or anencephaly, is considered to be combinations of variants at multiple genes. The genes contributing to the etiology of neural tube closure defects (NTDs) are unknown. Mutations in planar cell polarity (PCP) genes in mice cause a variety of defects including the NTD, craniorachischisis, and sometimes SB or exencephaly (EX); they also demonstrate the role of digenic combinations of PCP mutants in NTDs. Recent studies have sought rare predicted-to-be-deleterious alterations (putative mutations) in coding sequence of PCP genes in human cases with various anomalies of the neural tube. This review summarizes the cumulative results of these studies according to a framework based on the embryopathogenesis of NTDs, and considers some of the insights from the approaches used and the limitations. Rare putative mutations in the PCP genes VANGL2, SCRIB, DACT1, and CELSR1 cumulatively contributed to over 20% of cases with craniorachischisis, a rare defect; no contributing variants were found for PRICKLE1 or PTK7. PCP rare putative mutations had a weaker role in myelomeningocele (SB), being found in approximately 6% of cases and cumulated across CELSR1, FUZ, FZD6, PRICKLE1, VANGL1, and VANGL2. These results demonstrate that PCP gene alterations contribute to the etiology of human NTDs. We recommend that future research should explore other types of PCP gene variant such as regulatory mutations and low frequency (1 to 5%) deleterious polymorphisms.

  10. Microbially driven Fenton reaction for transformation of pentachlorophenol

    SciTech Connect

    McKinzi, A.M.; Dichristina, T.J.

    1999-06-01

    A microbially driven transformation system was developed for the oxidative degradation of pentachlorophenol (PCP). The system was based on a free radical-generating Fenton reaction between bacterially produced Fe(II) and H{sub 2}O{sub 2}. The Fe(III)-reducing, facultative anaerobe Shewanella putrefaciens strain 200 was used as a catalyst for both Fe(III) reduction and H{sub 2}O{sub 2} production by alternating between anaerobic and aerobic conditions in liquid batch cultures supplemented with Fe(III). The highest observed PCP degradation rate was approximately 0.31 {micro}M h{sup {minus}1}. Tetrachlorohydroquinone (TCHQ) and tetrachlorocatechol (TCC) were formed as the principal PCP transformation products, indicating that PCP oxidation proceeded via hydroxyl radical ({sup {sm_bullet}}OH) attack on the ortho and para positions of the aromatic ring. PCP was degraded, and TCHQ and TCC were produced in a chemically driven (biomimetic) system where H{sub 2}O{sub 2} and Fe(II) were supplied at concentrations comparable to those detected in the microbially driven system. PCP was not degraded (and PCP transformation products were not produced) in a set of control experiments that included (1) the presence of Fe(II)-chelating agents or radical scavenging compounds, (2) strict aerobic or anaerobic conditions, (3) the substitution of NO{sub 3}{sup {minus}} for Fe(III) as anaerobic electron acceptor, and (4) the omission of S. putrefaciens. The microbially driven Fenton reaction system operated at neutral pH and required neither addition of exogenous H{sub 2}O{sub 2} nor UV irradiation to regenerate Fe(II). The newly developed system may provide the basis for novel Fenton-type bioremediation strategies.

  11. Clinical Course, Radiological Manifestations, and Outcome of Pneumocystis jirovecii Pneumonia in HIV Patients and Renal Transplant Recipients

    PubMed Central

    Rauch, Andri; Furrer, Hansjakob; Cusini, Alexia; Meyer, Andreas M. J.; Weiler, Stefan; Huynh-Do, Uyen; Heverhagen, Johannes; Arampatzis, Spyridon; Christe, Andreas

    2016-01-01

    Background Pneumocystis jirovecii pneumonia (PCP) is a frequent opportunistic infection in immunocompromised patients. In literature, presentation and outcome of PCP differs between patients with human immunodeficiency virus (HIV) infection and renal transplant recipients (RTRs). Methods We conducted a cross-sectional study of patients with PCP based on the HIV and renal transplant registries at our institution. Radiological and clinical data from all confirmed PCP cases between 2005 and 2012 were compared. Results Forty patients were included: 16 with HIV and 24 RTRs. Radiologically, HIV patients had significantly more areas of diffuse lung affection (81% HIV vs. 25% RTR; p = 0.02), more ground glass nodules 5–10 mm (69% vs. 4%; p = <0.001) and enlarged hilar lymph nodes were found only in HIV patients (44%). Cough and dyspnea were the most common clinical signs (>80%) in both groups. Duration from illness onset to hospital presentation was longer in the HIV patients (median of 18 vs. 10 days (p = 0.02)), implying a less fulminant clinical course. Sixty percent of PCP cases in RTRs occurred >12 months after transplantation. Lengths of hospitalization, admission rates to the intensive care unit, and requirements for mechanical ventilation were similar. Outcome in both groups was favourable. Conclusions While important differences in radiological presentation of PCP between HIV patients and RTRs were found, clinical presentation was similar. PCP only rarely presented with fulminant respiratory symptoms requiring ICU admission, with similar results and outcomes for HIV patients and RTRs. Early diagnosis and treatment is mandatory for clinical success. PMID:27824870

  12. Current practice trends in allergy: results of a united states survey of otolaryngologists, allergist-immunologists, and primary care physicians.

    PubMed

    Ryan, Matthew W; Marple, Bradley F; Leatherman, Bryan; Mims, J Whit; Fornadley, John; Veling, Maria; Lin, Sandra Y

    2014-10-01

    Clinical practices for the diagnosis and treatment of allergic disease evolve over time in response to a variety of forces. The techniques used by various physician specialties are not clearly defined and may vary from published descriptions or recommendations in the literature. This work is a Web-based survey enrolling 250 U.S. physicians in the following specialties: otolaryngology (ENT), allergy-immunology (A/I), and primary care (PCP). Respondents reported that skin-prick testing is the most common diagnostic testing method, followed by in vitro specific immunoglobulin E (IgE) testing. ENTs were more likely to use intradermal testing compared to other specialties (p = 0.0003 vs A/I; p < 0.0001 vs PCP). Respondents reported a wide distribution in number of allergens tested, regardless of testing method (range, 11 to >60). Significant use of home immunotherapy injections (defined as >10% of immunotherapy patients) ranged from 27% to 36% of physicians, with no statistically significant difference noted based upon specialty. PCPs reported greater use of sublingual immunotherapy (PCP, 68%; A/I, 45%; otolaryngology, 35%; A/I vs PCP, p = 0.005; ENT vs PCP p < 0.001)). A variety of allergy testing and treatment methods are employed by U.S. physicians, with some differences noted based upon specialty. Home immunotherapy continues to be employed in allergy practices, and sublingual immunotherapy is a common form of delivery, especially in primary care practices. © 2014 ARS-AAOA, LLC.

  13. Unveiling the excited state energy transfer pathways in peridinin-chlorophyll a-protein by ultrafast multi-pulse transient absorption spectroscopy.

    PubMed

    Redeckas, Kipras; Voiciuk, Vladislava; Zigmantas, Donatas; Hiller, Roger G; Vengris, Mikas

    2017-04-01

    Time-resolved multi-pulse methods were applied to investigate the excited state dynamics, the interstate couplings, and the excited state energy transfer pathways between the light-harvesting pigments in peridinin-chlorophyll a-protein (PCP). The utilized pump-dump-probe techniques are based on perturbation of the regular PCP energy transfer pathway. The PCP complexes were initially excited with an ultrashort pulse, resonant to the S0→S2 transition of the carotenoid peridinin. A portion of the peridinin-based emissive intramolecular charge transfer (ICT) state was then depopulated by applying an ultrashort NIR pulse that perturbed the interaction between S1 and ICT states and the energy flow from the carotenoids to the chlorophylls. The presented data indicate that the peridinin S1 and ICT states are spectrally distinct and coexist in an excited state equilibrium in the PCP complex. Moreover, numeric analysis of the experimental data asserts ICT→Chl-a as the main energy transfer pathway in the photoexcited PCP systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. -Based Clathrate

    NASA Astrophysics Data System (ADS)

    Anno, Hiroaki; Shirataki, Ritsuko

    2014-06-01

    A polycrystalline silicon-based clathrate of nominal composition Ba8Al15Si31 was prepared by a combination of arc melting and spark plasma sintering. Its thermal stability in air and the effect on the surface of heat treatment in air, which are of practical importance for use of the material at elevated temperatures, were examined for different temperatures (873 K, 973 K, and 1073 K) and heating times (0-480 h). Thermogravimetry and differential thermal analysis in air in the range 300-1523 K indicated that Ba8Al15Si31 in the bulk form had relatively good thermal stability in air at high temperatures. X-ray diffraction measurements, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy revealed that a thin layer of oxide (probably a barium aluminate, BaAl2O4) was formed on the surface by heat treatment in air. The thickness of the oxide layer increased with increasing temperature and heating time. Growth of the oxide layer can be explained well in terms of a diffusion mechanism. The activation energy for oxidation was estimated to be approximately 201 kJ/mol, which is comparable with that for thermal oxidation of silicon. The chemical composition of the interior of the Ba8Al15Si31 was found to be stable to heat treatment in air.

  15. The developmental effects of pentachlorophenol on zebrafish embryos during segmentation: A systematic view

    NASA Astrophysics Data System (ADS)

    Xu, Ting; Zhao, Jing; Xu, Zhifa; Pan, Ruijie; Yin, Daqiang

    2016-05-01

    Pentachlorophenol (PCP) is a typical toxicant and prevailing pollutant whose toxicity has been broadly investigated. However, previous studies did not specifically investigate the underlying mechanisms of its developmental toxicity. Here, we chose zebrafish embryos as the model, exposed them to 2 different concentrations of PCP, and sequenced their entire transcriptomes at 10 and 24 hours post-fertilization (hpf). The sequencing analysis revealed that high concentrations of PCP elicited systematic responses at both time points. By combining the enrichment terms with single genes, the results were further analyzed using three categories: metabolism, transporters, and organogenesis. Hyperactive glycolysis was the most outstanding feature of the transcriptome at 10 hpf. The entire system seemed to be hypoxic, although hypoxia-inducible factor-1α (HIF1α) may have been suppressed by the upregulation of prolyl hydroxylase domain enzymes (PHDs). At 24 hpf, PCP primarily affected somitogenesis and lens formation probably resulting from the disruption of embryonic body plan at earlier stages. The proposed underlying toxicological mechanism of PCP was based on the crosstalk between each clue. Our study attempted to describe the developmental toxicity of environmental pollutants from a systematic view. Meanwhile, some features of gene expression profiling could serve as markers of human health or ecological risk.

  16. Prognosis of pneumocystis pneumonia complicated in patients with rheumatoid arthritis (RA) and non-RA rheumatic diseases.

    PubMed

    Yoshida, Yuji; Takahashi, Yuko; Minemura, Nobuyoshi; Ueda, Yo; Yamashita, Hiroyuki; Kaneko, Hiroshi; Mimori, Akio

    2012-08-01

    Clinical presentation of pneumocystis pneumonia (PCP) during immunosuppressive therapy for rheumatic diseases was compared between patients with rheumatoid arthritis (RA; n = 7) and those without RA (non-RA; n = 12) based on a chart review. Both RA and non-RA patients with PCP were treated with methotrexate (n = 7) combined with steroids (n = 6) and/or biologics (n = 4). RA-PCP patients were found to have a higher mortality rate than non-RA-PCP patients (3/7 vs. 0/12, respectively; p = 0.036) due to a later exacerbation of interstitial pneumonia and a higher presentation rate of diffuse pulmonary lesions (4/7 vs. 1/12, respectively; p = 0.036) despite lower mean levels of serum beta-D: -glucan (314 ± 214 vs. 1139 ± 1114 pg/ml, respectively; p = 0.02) that suggested a lower burden of Pneumocystis jirovecii. In conclusion, PCP in RA patients with existing pulmonary lesions may trigger subsequent progression to lethal interstitial pneumonia.

  17. Improving rates of screening and prevention by leveraging existing information systems.

    PubMed

    Neil, Nancy

    2003-11-01

    In 1997 Virginia Mason Health System (VMMC), a vertically integrated hospital and multispecialty group practice, had no process or system to deliver the right patient clinical data, in the right form, at the right place--when providers needed it for effective patient care. Without any new investment in technology, a work group of five individuals leveraged existing, primarily paper-based information systems to launch development and implementation of a provider prompting tool--a primary care and prevention (PCP) report--which prompted providers to complete screening, prevention, and disease management services at every patient appointment. The work group developed and pilot tested the report and created a mechanism by which the report could be delivered just in time before each patient's appointment. The report integrated information from independent appointment scheduling, laboratory results reporting, patient demographics, and billing data sources. MEASURING THE PCP REPORT'S IMPACT: The results of two separate analyses demonstrate improvement in rates of screening and prevention across VMMC soon after the PCP report became available. These results led senior leadership to make the PCP report's utilization a systemwide imperative. The PCP report is used by nearly all primary care providers as a prompt to complete screening, prevention, and disease management services at every patient appointment.

  18. Serological diagnosis of pneumocystosis: production of a synthetic recombinant antigen for immunodetection of Pneumocystis jirovecii.

    PubMed

    Tomás, A L; Cardoso, F; Esteves, F; Matos, O

    2016-11-08

    Diagnosis of Pneumocystis pneumonia (PcP) relies on the detection of P. jirovecii in respiratory specimens obtained by invasive techniques. Thus, the development of a serological test is urgently needed as it will allow the diagnosis of PcP using blood, an inexpensive and non-invasive specimen. This study aims to combine the production of a multi-epitope synthetic recombinant antigen (RSA) and an ELISA test for detection of anti-P. jirovecii antibodies, in order to develop a new approach for PcP diagnosis. The RSA was selected and designed based on the study of the immunogenicity of the carboxyl-terminal domain of the major surface glycoprotein. This antigen was purified and used as an antigenic tool in an ELISA technique for detection of Ig, IgG and IgM antibodies anti-P. jirovecii (patent-pending no. PT109078). Serum specimens from 88 patients previously categorized in distinct clinical subgroups and 17 blood donors, were analysed. The IgM anti-P. jirovecii levels were statistically increased in patients with PcP (p = 0.001) and the ELISA IgM anti-P. jirovecii test presented a sensitivity of 100% and a specificity of 80.8%, when associated with the clinical diagnosis criteria. This innovative approach, provides good insights about what can be done in the future serum testing for PcP diagnosis.

  19. Serological diagnosis of pneumocystosis: production of a synthetic recombinant antigen for immunodetection of Pneumocystis jirovecii

    PubMed Central

    Tomás, A. L.; Cardoso, F.; Esteves, F.; Matos, O.

    2016-01-01

    Diagnosis of Pneumocystis pneumonia (PcP) relies on the detection of P. jirovecii in respiratory specimens obtained by invasive techniques. Thus, the development of a serological test is urgently needed as it will allow the diagnosis of PcP using blood, an inexpensive and non-invasive specimen. This study aims to combine the production of a multi-epitope synthetic recombinant antigen (RSA) and an ELISA test for detection of anti-P. jirovecii antibodies, in order to develop a new approach for PcP diagnosis. The RSA was selected and designed based on the study of the immunogenicity of the carboxyl-terminal domain of the major surface glycoprotein. This antigen was purified and used as an antigenic tool in an ELISA technique for detection of Ig, IgG and IgM antibodies anti-P. jirovecii (patent-pending no. PT109078). Serum specimens from 88 patients previously categorized in distinct clinical subgroups and 17 blood donors, were analysed. The IgM anti-P. jirovecii levels were statistically increased in patients with PcP (p = 0.001) and the ELISA IgM anti-P. jirovecii test presented a sensitivity of 100% and a specificity of 80.8%, when associated with the clinical diagnosis criteria. This innovative approach, provides good insights about what can be done in the future serum testing for PcP diagnosis. PMID:27824115

  20. Immunodiagnosis of Citrus leprosis virus C using a polyclonal antibody to an expressed putative coat protein.

    PubMed

    Choudhary, Nandlal; Roy, Avijit; Guillermo, Leon M; Picton, D D; Wei, G; Nakhla, M K; Levy, L; Brlansky, R H

    2013-11-01

    Citrus leprosis virus C (CiLV-C), a causal agent for citrus leprosis disease, is present in South and Central America and is a threat for introduction into the U.S. citrus industry. A specific, inexpensive and reliable antibody based detection system is needed for the rapid identification of CiLV-C. The CiLV-C is very labile and has not been purified in sufficient amount for antibody production. The p29 gene of CiLV-C genome that codes for the putative coat protein (PCP) was codon optimized for expression in Escherichia coli and synthesized in vitro. The optimized gene was sub-cloned into the bacterial expression vector pDEST17 and transferred into E. coli BL21AI competent cells. The expression of PCP containing N-terminal His-tag was optimized by induction with l-arabinose. Induced cells were disrupted by sonication and expressed PCP was purified by affinity chromatography using Ni-NTA agarose. The purified expressed PCP was then used as an immunogen for injections into rabbits to produce polyclonal antibody (PAb). The PAb specific to the expressed PCP was identified using Western blotting. The antibody was successfully used to detect CiLV-C in the symptomatic CiLV-C infected tissues using double antibody sandwich-enzyme-linked-immunosorbent (DAS-ELISA), indirect ELISA and dot-blot immunoassay (DBIA) formats.

  1. The developmental effects of pentachlorophenol on zebrafish embryos during segmentation: A systematic view

    PubMed Central

    Xu, Ting; Zhao, Jing; Xu, Zhifa; Pan, Ruijie; Yin, Daqiang

    2016-01-01

    Pentachlorophenol (PCP) is a typical toxicant and prevailing pollutant whose toxicity has been broadly investigated. However, previous studies did not specifically investigate the underlying mechanisms of its developmental toxicity. Here, we chose zebrafish embryos as the model, exposed them to 2 different concentrations of PCP, and sequenced their entire transcriptomes at 10 and 24 hours post-fertilization (hpf). The sequencing analysis revealed that high concentrations of PCP elicited systematic responses at both time points. By combining the enrichment terms with single genes, the results were further analyzed using three categories: metabolism, transporters, and organogenesis. Hyperactive glycolysis was the most outstanding feature of the transcriptome at 10 hpf. The entire system seemed to be hypoxic, although hypoxia-inducible factor-1α (HIF1α) may have been suppressed by the upregulation of prolyl hydroxylase domain enzymes (PHDs). At 24 hpf, PCP primarily affected somitogenesis and lens formation probably resulting from the disruption of embryonic body plan at earlier stages. The proposed underlying toxicological mechanism of PCP was based on the crosstalk between each clue. Our study attempted to describe the developmental toxicity of environmental pollutants from a systematic view. Meanwhile, some features of gene expression profiling could serve as markers of human health or ecological risk. PMID:27181905

  2. Electroencephalographic, behavioral and receptor binding correlates of phencyclinoids in the rat

    SciTech Connect

    Mattia, A.; Marquis, K.L.; Leccese, A.P.; el-Fakahany, E.E.; Moreton, J.E.

    1988-08-01

    The pharmacology and structure-activity relationship of phencyclidine (PCP)-like drugs (phencyclinoids) were studied using electroencephalographic (EEG), behavioral and receptor binding techniques. The effects of PCP, 1-phenylcyclohexylamine HCl, N-methyl-1-phenycyclohexylamine HCl, N-ethyl-1-phenylcyclohexylamine HCl, N-(s-butyl)-1-phenylcyclohexylamine HCL, 1-(1-phenylcyclo-hexyl)-pyrrolidine HCl, 1-(1-(2-thienyl)cyclohexyl) piperidine HCl, 1-(1-(2-thienyl)cyclohexyl)-pyrrolidine HCl, ketamine and (+/-)-SKF 10047 were evaluated on the direct EEG and EEG spectra after acute i.v. injections (0.1-17.8 mg/kg). Similarities and differences were noted in the EEG dose-response curves. At lower doses of PCP and its analogs, low-amplitude theta waves predominated; however, at higher doses, high-amplitude, lower-frequency waves predominated. Qualitatively, the N-piperidine derivatives were similar to PCP and differed primarily in potency. The benzomorphan (+/-)-SKF 10047 produced only theta activity at doses up to 12.8 mg/kg. These EEG effects occurred in conjunction with overt behaviors including locomotion, stereotypy and ataxia, concurrently assessed via observer-based rating scales. A strong correlation (r = 0.98) was obtained between the EEG and behavioral effects and the IC50 values from (/sup 3/H)PCP displacement experiments using crude rat brain homogenates.

  3. Perceived judgment about weight can negatively influence weight loss: a cross-sectional study of overweight and obese patients.

    PubMed

    Gudzune, Kimberly A; Bennett, Wendy L; Cooper, Lisa A; Bleich, Sara N

    2014-05-01

    To examine the association between patient-perceived judgments about weight by primary care providers (PCPs) and self-reported weight loss. We conducted a national internet-based survey of 600 adults engaged in primary care with a body mass index (BMI)≥25 kg/m(2) in 2012. Our weight loss outcomes included attempted weight loss and achieved ≥10% weight loss in the last 12 months. Our independent variable was "feeling judged about my weight by my PCP." We created an interaction between perceiving judgment and PCP discussing weight loss as an independent variable. We conducted a multivariate logistic regression model adjusted for patient and PCP factors using survey weights. Overall, 21% perceived that their PCP judged them about their weight. Respondents who perceived judgment were significantly more likely to attempt weight loss [odds ratios (OR) 4.67, 95% confidence interval (CI) 1.96-11.14]. They were not more likely to achieve ≥10% weight loss [OR 0.87, 95%CI 0.42-1.76]. Among patients whose PCPs discussed weight loss, 20.1% achieved ≥10% weight loss if they did not perceive judgment by their PCP as compared to 13.5% who perceived judgment. Weight loss discussions between patients and PCPs may lead to greater weight loss in relationships where patients do not perceive judgment about their weight. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. What are patients' expectations about the organization of their primary care physicians' practices?

    PubMed

    Sebo, Paul; Herrmann, François R; Bovier, Patrick; Haller, Dagmar M

    2015-08-14

    To our knowledge no study has at the same time assessed patients' satisfaction and their expectations concerning the organizational and contextual aspects of health care provided by their primary care physician (PCP). Assessing these aspects is important to inform future primary healthcare service planning. Our objective was thus to document patients' satisfaction with and expectations from their PCP, in terms of availability and organization of their practices, and to assess whether these indicators varied across age groups and type of practice (solo, duo, group). Cross-sectional study based on the answers to questionnaires completed by patients consulting their PCP in Geneva, Switzerland. A random sample of PCPs was asked to recruit consecutively between 50 and 100 patients coming to the practice for a scheduled medical consultation. The patients were asked to complete an anonymous questionnaire centered on their satisfaction levels and expectations towards their PCP. One thousand six hundred thirty-seven patients agreed to participate (participation rate: 97%, women: 63%, mean age: 54 years). Patient satisfaction was high for all the items, except for the availability of the doctor by phone and for the waiting time in the waiting room. The satisfaction rate increased with age and was higher for small practices. In relation to patients' expectations from their doctor, older patients and patients visiting larger practices tended to be more demanding. Patients are generally highly satisfied with their PCP. They have a wide range of expectations which should be taken into account when considering potential improvements.

  5. Unraveling the Sex Chromosome Heteromorphism of the Paradoxical Frog Pseudis tocantins.

    PubMed

    Gatto, Kaleb Pretto; Busin, Carmen Silvia; Lourenço, Luciana Bolsoni

    2016-01-01

    The paradoxical frog Pseudis tocantins is the only species in the Hylidae family with known heteromorphic Z and W sex chromosomes. The Z chromosome is metacentric and presents an interstitial nucleolar organizer region (NOR) on the long arm that is adjacent to a pericentromeric heterochromatic band. In contrast, the submetacentric W chromosome carries a pericentromeric NOR on the long arm, which is adjacent to a clearly evident heterochromatic band that is larger than the band found on the Z chromosome and justify the size difference observed between these chromosomes. Here, we provide evidence that the non-centromeric heterochromatic bands in Zq and Wq differ not only in size and location but also in composition, based on comparative genomic hybridization (CGH) and an analysis of the anuran PcP190 satellite DNA. The finding of PcP190 sequences in P. tocantins extends the presence of this satellite DNA, which was previously detected among Leptodactylidae and Hylodidae, suggesting that this family of repetitive DNA is even older than it was formerly considered. Seven groups of PcP190 sequences were recognized in the genome of P. tocantins. PcP190 probes mapped to the heterochromatic band in Wq, and a Southern blot analysis indicated the accumulation of PcP190 in the female genome of P. tocantins, which suggests the involvement of this satellite DNA in the evolution of the sex chromosomes of this species.

  6. Specific disulfide cross-linking to constrict the mobile carrier domain of nonribosomal peptide synthetases

    PubMed Central

    Tarry, Michael J.; Schmeing, T. Martin

    2015-01-01

    Nonribosomal peptide synthetases are large, multi-domain enzymes that produce peptide molecules with important biological activity such as antibiotic, antiviral, anti-tumor, siderophore and immunosuppressant action. The adenylation (A) domain catalyzes two reactions in the biosynthetic pathway. In the first reaction, it activates the substrate amino acid by adenylation and in the second reaction it transfers the amino acid onto the phosphopantetheine arm of the adjacent peptide carrier protein (PCP) domain. The conformation of the A domain differs significantly depending on which of these two reactions it is catalyzing. Recently, several structures of A–PCP di-domains have been solved using mechanism-based inhibitors to trap the PCP domain in the A domain active site. Here, we present an alternative strategy to stall the A–PCP di-domain, by engineering a disulfide bond between the native amino acid substrate and the A domain. Size exclusion studies showed a significant shift in apparent size when the mutant A–PCP was provided with cross-linking reagents, and this shift was reversible in the presence of high concentrations of reducing agent. The cross-linked protein crystallized readily in several of the conditions screened and the best crystals diffracted to ≈8 Å. PMID:25713404

  7. Unraveling the Sex Chromosome Heteromorphism of the Paradoxical Frog Pseudis tocantins

    PubMed Central

    Gatto, Kaleb Pretto; Busin, Carmen Silvia; Lourenço, Luciana Bolsoni

    2016-01-01

    The paradoxical frog Pseudis tocantins is the only species in the Hylidae family with known heteromorphic Z and W sex chromosomes. The Z chromosome is metacentric and presents an interstitial nucleolar organizer region (NOR) on the long arm that is adjacent to a pericentromeric heterochromatic band. In contrast, the submetacentric W chromosome carries a pericentromeric NOR on the long arm, which is adjacent to a clearly evident heterochromatic band that is larger than the band found on the Z chromosome and justify the size difference observed between these chromosomes. Here, we provide evidence that the non-centromeric heterochromatic bands in Zq and Wq differ not only in size and location but also in composition, based on comparative genomic hybridization (CGH) and an analysis of the anuran PcP190 satellite DNA. The finding of PcP190 sequences in P. tocantins extends the presence of this satellite DNA, which was previously detected among Leptodactylidae and Hylodidae, suggesting that this family of repetitive DNA is even older than it was formerly considered. Seven groups of PcP190 sequences were recognized in the genome of P. tocantins. PcP190 probes mapped to the heterochromatic band in Wq, and a Southern blot analysis indicated the accumulation of PcP190 in the female genome of P. tocantins, which suggests the involvement of this satellite DNA in the evolution of the sex chromosomes of this species. PMID:27214234

  8. Foundation: Transforming data bases into knowledge bases

    NASA Technical Reports Server (NTRS)

    Purves, R. B.; Carnes, James R.; Cutts, Dannie E.

    1987-01-01

    One approach to transforming information stored in relational data bases into knowledge based representations and back again is described. This system, called Foundation, allows knowledge bases to take advantage of vast amounts of pre-existing data. A benefit of this approach is inspection, and even population, of data bases through an intelligent knowledge-based front-end.

  9. Gas chromatographic determination of pentachlorophenol in gelatin.

    PubMed

    Borsetti, A P; Thurston, L S

    1984-01-01

    A method is described for the determination of pentachlorophenol (PCP) in gelatin. The method employs acid and heat to hydrolyze the gelatin matrix, a base partition and wash for separation and cleanup, and a reacidification and extraction with hexane for direct determination of PCP, without preparation of a derivative, using gas chromatography (GC) with a 1% SP- 124ODA liquid phase and a 63Ni electron capture detector. Recoveries averaged 106% for fortifications between 0.02 and 1.0 ppm. The limit of quantitation is 20 ppb. The limit of detection is 4-6 ppb. The method, which has undergone a successful intralaboratory trial, is simple and rapid, and requires only general laboratory reagents and equipment. GC of the acetate derivative of PCP is used for confirmation of identity.

  10. [PRECHORDAL AND MYOEPICARDIAL PLATES: TERMINOLOGICAL ASPECTS, THE PROBLEMS OF DEFINITION].

    PubMed

    Korolyov, V A; Pototskaya, O Yu

    2015-01-01

    Most accurately, the prechordal plate (PCP) can be defined as the zone of close contact of cells of endodermal epithelium and mesenchyme in the region between the oropharyngeal membrane and the notochord. This structure is involved in the induction of the anterior parts of the brain and, in particular, the pituitary gland, as well as in the formation of some of eye muscles and bones of the skull base (chordal chondrocranium). Further studies are needed to clarify PCP involvement in the development of pharynx, esophagus, and their derivatives, as well as to determine the source and the mechanisms of development of PCP mesenchymal cells. The term "prechordal plate" should not be confused with the Spemann's organizer, head organizer, oropharyngeal membrane, mesendoderm, head process and the prechordal mesoderm, which is common in the scientific literature. The term "myoepicardial plate" falsely indicates the common origin of myocardium and epicardium, thus its usage should be avoided.

  11. Soil immobilization: New concept for biotreatment of soil contaminants

    SciTech Connect

    Karamanev, D.G.; Chavarie, C.; Samson, R.

    1998-02-20

    A new concept for the development of microbial consortia for the degradation of persistent soil pollutants and for pollutant treatment is proposed. The concept defined as soil immobilization is based on the entrapment of soil particles, showing microbial activity in degrading the target pollutant, into a solid membrane with a large pore size distribution. The particular hydrodynamic and mass transfer properties of this system result in a very efficient process. A new type of bioreactor is proposed for carrying out the immobilized soil process. The performance of the system was tested by developing a microbial system for the mineralization of pentachlorophenol (PCP). The results show that the volumetric efficiency of the process for PCP mineralization in the immobilized soil bioreactor is 1--3 orders of magnitude higher than reported literature values. Chlorine and carbon atoms of PCP are both nearly completely (99%) mineralized.

  12. Isolation, characterization, and genetics of pentachlorophenol-degrading Flavobacterium strains

    SciTech Connect

    Saber, D.L.

    1987-01-01

    Bacteria able to mineralize 100-200 ppm of pentachlorophenol (PCP) were isolated by selective enrichment from PCP-contaminated soil from 3 geographic areas in Minnesota. Sampling areas were separated from each other by up to 185 miles; history and level of contamination with a variety of compounds varied between sites. Pure cultures of bacteria were selected for further characterization based on growth properties, site of isolation, and return of radiolabeled PCP as /sup 14/CO/sub 2/ in initial serum bottle experiments. Although differing somewhat in their response to various biochemical and biophysical tests, all strains were Gram-negative, oxidase-, catalase-, and phosphatase-positive, not motile, grow as yellow colonies on solid medium, limited in their use of single carbon sources,and ranged in mol% G + C of DNA between 58.8-63,8%. All strains were assigned to the genus Flavobacterium.

  13. Providers debate pros and cons of pneumonia vaccination at discharge.

    PubMed

    2001-02-01

    When to vaccinate against pneumonia? Does it makes sense when patients are in the hospital? Or should patients wait for the first post-op visit with the PCP? Office-based and hospital-based physicians weigh the pros and cons of each.

  14. The initial effects of Physician Compensation Programs in Taiwan hospitals: implications for staff model HMOs.

    PubMed

    Chu, Hsuan-Lien; Liu, Shuen-Zen; Romeis, James C; Yaung, Chih-Liang

    2003-02-01

    This paper examines whether a Physician Compensation Program (PCP), which was based on the responsibility centers system, improved departmental efficiency in a large Taiwan teaching hospital. PCPs in Taiwan may have implications for staff-model HMOs. Monthly financial data and related information for 58 departments in the 5 months following the introduction of the program (the PCP period) and the corresponding 5 months before the introduction of the program (the pre-PCP period) were provided by the case hospital. The Data Envelopment Analysis (DEA) model is used to measure the operational efficiency of each department in the case hospital over the two periods. We first use asymptotic DEA-based tests to examine whether differences in efficiency scores between the two periods are significant. Then, a multi-factor tobit model is used to examine factors that might explain the observed differences in efficiency. The data of each month in the PCP period (November 1996-March 1997) and the pre-PCP period (November 1995-March 1996) are used to calculate efficiency scores and control for monthly effects. We find that average efficiency improves after the implementation of the PCP, with or without controlling for other related factors. Physicians' seniority and percentage of physicians' service time in the department are associated with improved efficiency. Finally, departments with higher profits and fewer numbers of employees are associated with higher efficiency. The findings suggest that to achieve an increase in hospital efficiency in Taiwan, responsibility centers should be integrated with formal physician compensation programs. Such results have implications for staff model HMOs in the US and their variants in countries with national health insurance.

  15. The PCP Protein Vangl2 Regulates Migration of Hindbrain Motor Neurons by Acting in Floor Plate Cells, and Independently of Cilia Function

    PubMed Central

    Sittaramane, Vinoth; Pan, Xiufang; Glasco, Derrick M.; Huang, Peng; Gurung, Suman; Bock, Anagha; Li, Shike; Wang, Hui; Kawakami, Koichi; Matise, Michael P.; Chandrasekhar, Anand

    2013-01-01

    Vangl2, a core component of the Planar Cell Polarity pathway, is necessary for the caudal migration of Facial Branchiomotor (FBM) neurons in the vertebrate hindbrain. Studies in zebrafish suggest that vangl2 functions largely non-cell autonomously to regulate FBM neuron migration out of rhombomere 4 (r4), but the cell-type within which it acts is not known. Here, we demonstrate that vangl2 functions largely in floor plate cells to regulate caudal neuronal migration. Furthermore, FBM neurons fail to migrate caudally in the mouse Gli2 mutant that lacks the floor plate, suggesting an evolutionarily conserved role for this cell type in neuronal migration. Although hindbrain floor plate cilia are disorganized in vangl2 mutant embryos, cilia appear to be dispensable for neuronal migration. Notably, Vangl2 is enriched in the basolateral, but not apical, membranes of floor plate cells. Taken together, our data suggest strongly that Vangl2 regulates FBM neuron migration by acting in floor plate cells, independently of cilia function. PMID:23988578

  16. Hot Topics in Primary Care: Diagnosis of Cirrhosis and Evaluation of Hepatic Encephalopathy: Common Errors and Their Significance for the PCP.

    PubMed

    Flamm, Steven L

    2017-04-01

    Cirrhosis has become the focus of greater attention in recent years largely because of the increasing prevalence of 2 of its most common causes: chronic viral hepatitis and steatohepatitis (a subset of nonalcoholic fatty liver disease [NAFLD]). Cirrhosis is the result of progressive destruction and regeneration of the liver parenchyma due to chronic liver disease (CLD).

  17. On the Reaction of Carbonyl Diphosphonic Acid with Hydroxylamine and O-alkylhydroxylamines: Unexpected Degradation of P-C-P Bridge.

    PubMed

    Khomich, Olga A; Yanvarev, Dmitry V; Novikov, Roman A; Kornev, Alexey B; Puljulla, Elina; Vepsäläinen, Jouko; Khomutov, Alex R; Kochetkov, Sergey N

    2017-06-23

    Derivatives of methylenediphosphonic acid possess wide spectra of biological activities and are used in enzymology as research tools as well as in practical medicine. Carbonyl diphosphonic acid is a promising starting building block for synthesis of functionally substituted methylenediphosphonates. Investigation of the interaction of carbonyl diphosphonic acid with hydroxylamine clearly demonstrates that it is impossible to isolate oxime within the pH range 2-12, while only cyanophosphonic and phosphoric acids are the products of the fast proceeding Beckmann-like fragmentation. In the case of O-alkylhydroxylamines, corresponding alcohols are found in the reaction mixtures in addition to cyanophosphonic and phosphoric acids. Therefore, two residues of phosphonic acid being attached to a carbonyl group provide new properties to this carbonyl group, making its oximes very unstable. This principally differs carbonyl diphosphonic acid from structurally related phosphonoglyoxalic acid and other α-ketophosphonates.

  18. New P-wave Velocity Images of the Lowermost Mantle from a Bayesian Inversion of PKP, PcP, and P4KP Differential Travel Times

    NASA Astrophysics Data System (ADS)

    Young, M.; Tkalcic, H.; Bodin, T.; Sambridge, M.; Tanaka, S.; Rawlinson, N.

    2012-12-01

    Determining the scale-length, magnitude, and distribution of chemical and thermal heterogeneities in the lowermost mantle is crucial to understanding whole mantle dynamics, and yet it remains a much debated and ongoing challenge in geophysics. Common shortcomings of current seismically-derived lowermost mantle models are often the result of a lack of access to and scrutiny in performing travel time measurements from waveform data, consequently incomplete raypath coverage, arbitrary model parameterization, inaccurate uncertainty estimates, and an inadequate definition of the misfit function in the optimization framework. In response, we present a new approach to global tomography where apart from improving the existing ray path coverage using only high quality cross-correlated waveform, the problem is addressed within a Bayesian framework and explicit regularization of model parameters is not required. Our results show that velocity heterogeneities exist on a variety of scales, with anomalies between 600 and 2900 km in lateral extent dominating the lowermost mantle heterogeneity pattern. This provides an important link between the very short-scale imaging achieved through scattering experiments and the long wave-length maps resulting from more traditional tomographic approaches. We also show that the power of heterogeneity in the lowermost mantle has an rms P-wave velocity variation of 0.88%, which is significantly larger than previous global-scale estimates, is fully justified by the data. Comparison of our P-wave velocity model with high-resolution S-wave velocity models refutes a purely thermal origin of mantle heterogeneity. The pattern of correlation between our model and S-wave models, combined with the characteristic scale-length and amplitude of heterogeneity revealed by this study, will help to significantly refine allowable models of thermo-chemical convection in the lowermost mantle. We obtain high resolution images of the lowermost mantle P-wave velocity structure using a hand-picked data set of PKPab-df, PKPbc-df, PcP-P, and P4KP-PcP differential traveltimes. By using differential travel times, the biases associated with event mislocation and lateral heterogeneity in the lithosphere are minimized. The inclusion of new PcP-P and P4KP-PcP data greatly improves the D'' coverage and further reduces unwanted mapping effects in the inversion. In addition, we focus on covering gaps in spatial sampling of the lowermost mantle from PKPab-df and PcP-P of previous studies. We use a probabilistic, Bayesian inversion scheme to invert for lowermost mantle structure and obtain an accurate representation of the complexity and amplitude of the P-wave velocity heterogeneity that is complete with uncertainty estimates. The advantage of such an inversion method is that the data variance along with the number, size, and distribution of spatial model parameters are treated as unknowns in the problem.

  19. Tribromophenol and pentachlorophenol uptake from sawdust to horticultural products.

    PubMed

    Mardones, C; Von Baer, D; Silva, J; Ruff, A; Gutierrez, L; Berg, A

    2009-10-01

    This paper presents a study of the uptake of 2,4,6-tribromophenol (TBP), pentachlorophenol (PCP), and its metabolite pentachloroanisole (PCA) from contaminated sawdust from the forest industry in horticultural products such as apples, raspberries, and fodder maize for cattle feed. The samples were obtained from Bio-Bio Province in South Chile between 2002 and 2006. The analytical parameters of the methodology applied to the different matrices are presented and discussed. The chromatographic method was applied to determine the residues in 413 horticultural product samples. Eleven per cent of fodder maize samples showed detectable or quantifiable levels of PCP, TBP or PCA, 3% of samples presented quantifiable levels, although the concentrations surpassed the maximum allowed concentrations for vegetables (>10 microg kg(-1)) in only two samples. Traces of TBP were detected in eight samples, PCA was detected in 15, and PCP in 14 samples. Based on these results, a risk analysis was performed, indicating a low probability, 0.4% for PCA, 1.6% for TBP and 1.9% for PCP, to find concentrations higher than the allowed maximum. For apples and raspberries, no residues of these compounds were detected. These results indicate that those cultivars directly exposed to sawdust, like fodder maize, could contain detectable residues in several samples. To confirm this observation, a field assay was performed on fodder maize cultivated in the presence of sawdust artificially contaminated with 30 mg of TBP and/or PCP under controlled conditions. The results showed that under the experimental conditions used in the study, TBP can be transferred from sawdust to the plant, with an uptake rate of 0.04% from the TBP applied initially with sawdust but not to the corn ear. Also, the degradation of PCP to PCA was observed in the soil.

  20. Combined serotonin (5-HT)1A agonism, 5-HT(2A) and dopamine D₂ receptor antagonism reproduces atypical antipsychotic drug effects on phencyclidine-impaired novel object recognition in rats.

    PubMed

    Oyamada, Yoshihiro; Horiguchi, Masakuni; Rajagopal, Lakshmi; Miyauchi, Masanori; Meltzer, Herbert Y

    2015-05-15

    Subchronic administration of an N-methyl-D-aspartate receptor (NMDAR) antagonist, e.g. phencyclidine (PCP), produces prolonged impairment of novel object recognition (NOR), suggesting they constitute a hypoglutamate-based model of cognitive impairment in schizophrenia (CIS). Acute administration of atypical, e.g. lurasidone, but not typical antipsychotic drugs (APDs), e.g. haloperidol, are able to restore NOR following PCP (acute reversal model). Furthermore, atypical APDs, when co-administered with PCP, have been shown to prevent development of NOR deficits (prevention model). Most atypical, but not typical APDs, are more potent 5-HT(2A) receptor inverse agonists than dopamine (DA) D2 antagonists, and have been shown to enhance cortical and hippocampal efflux and to be direct or indirect 5-HT(1A) agonists in vivo. To further clarify the importance of these actions to the restoration of NOR by atypical APDs, sub-effective or non-effective doses of combinations of the 5-HT(1A) partial agonist (tandospirone), the 5-HT(2A) inverse agonist (pimavanserin), or the D2 antagonist (haloperidol), as well as the combination of all three agents, were studied in the acute reversal and prevention PCP models of CIS. Only the combination of all three agents restored NOR and prevented the development of PCP-induced deficit. Thus, this triple combination of 5-HT(1A) agonism, 5-HT(2A) antagonism/inverse agonism, and D2 antagonism is able to mimic the ability of atypical APDs to prevent or ameliorate the PCP-induced NOR deficit, possibly by stimulating signaling cascades from D1 and 5-HT(1A) receptor stimulation, modulated by D2 and 5-HT(2A) receptor antagonism.

  1. Preventive Services by Medical and Dental Providers and Treatment Outcomes

    PubMed Central

    Kranz, A.M.; Rozier, R.G.; Preisser, J.S.; Stearns, S.C.; Weinberger, M.; Lee, J.Y.

    2014-01-01

    Objective: Nearly all state Medicaid programs reimburse nondental primary care providers (PCPs) for providing preventive oral health services to young children; yet, little is known about how treatment outcomes compare with children visiting dentists. This study compared the association between the provider of preventive services (PCP, dentist, or both) with Medicaid-enrolled children before their third birthday and subsequent dental caries-related treatment (CRT) and CRT payment. Methods: We conducted a retrospective study of young children enrolled in North Carolina Medicaid during 2000 to 2006. The annual number of CRT and CRT payments per child between the ages of 3 and 5 yr were estimated with a zero-inflated negative binomial regression and a hurdle model, respectively. Models were adjusted for relevant child- and county-level characteristics and used propensity score weighting to address observed confounding. Results: We examined 41,453 children with > 1 preventive oral health visit from a PCP, dentist, or both before their third birthday. Unadjusted annual mean CRT and payments were lowest among children who had only PCP visits (CRT = 0.87, payment = $172) and higher among children with only dentist visits (CRT = 1.48, payment = $234) and both PCP and dentist visits (CRT = 1.52, payment = $273). Adjusted results indicated that children who had dentist visits (with or without PCP visits) had significantly more CRT and higher CRT payments per year during the ages of 3 and 4 yr than children who had only PCP visits. However, these differences attenuated each year after age 3 yr. Conclusions: Because of children’s increased opportunity to receive multiple visits in medical offices during well-child visits, preventive oral health services provided by PCPs may lead to a greater reduction in CRT than dentist visits alone. This study supports guidelines and reimbursement policies that allow preventive dental visits based on individual needs. PMID:24891593

  2. In vitro profiling of endocrine disrupting effects of phenols.

    PubMed

    Li, Jian; Ma, Mei; Wang, Zijian

    2010-02-01

    Some phenols have been suspected to modulate the endocrine systems of wildlife and humans, but less is known about their interactions with different types of nuclear receptors. In this study, the ability of 2-tert-butylphenol, 2-isopropylphenol, 4-tert-octylphenol (4-t-OP), 2,4-dichlorophenol (2,4-DCP), 3,4-dichlorophenol (3,4-DCP), pentachlorophenol (PCP), bisphenols A (BPA), tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA) and 4-phenylphenol to activate estrogen receptor (ER), androgen receptor (AR), progesterone receptor (PR) and estrogen-related receptor (ERR) were determined using a set of recombined yeast strains. It was found that 4-t-OP, 3,4-DCP, PCP, BPA, TBBPA, TCBPA and 4-phenylphenol were ERalpha agonists, while 4-t-OP, PCP and 4-phenylphenol showed ERalpha antagonistic activities. 2-tert-Butylphenol, 4-t-OP, 2-isopropylphenol, 2,4-DCP, 3,4-DCP, BPA, TCBPA and 4-phenylphenol were antagonists for AR, whereas none of the compounds studied were found to be an AR agonist. TCBPA, TBBPA and PCP were PR antagonists, and 2-tert-butylphenol, 3,4-DCP, 4-t-OP, 4-phenylphenol and 2-isopropylphenol were weak inhibitors on expression under control of the PR. None of the phenols were PR agonists. 2-tert-Butylphenol, 4-t-OP and PCP were ERRgamma inverse agonists, while 2,4-DCP, 3,4-DCP, PCP, BPA, TBBPA and TCBPA exhibited the ability to reverse the ERR inhibition induced by 4-hydroxytamoxifen. Based on the functional agonistic or antagonistic receptor-mediated effects, we further discussed the possible action mechanisms of these phenols as endocrine disrupting chemicals.

  3. Effects of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine on phencyclidine-induced behavior and expression of the immediate-ear