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Article: Human substance P receptor undergoes agonist-dependent phosphorylation by G protein-coupled receptor kinase 5 in vitro.

Warabi, Kengo / Richardson, Mark D / Barry, William T / Yamaguchi, Keisuke / Roush, Eric D / Nishimura, Kinya / Kwatra, Madan M

FEBS letters

2001 Volume 521, Issue 1-3, Page(s) 140–144

Abstract: G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied G protein-coupled ... characterized. GRK5 is negatively regulated by protein kinase C. We investigated whether human substance P ... of substance P. The phosphorylation has a high stoichiometry (20+/-4 mol phosphate/mol hSPR) and a low K(m) (1 ...

Abstract	G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied G protein-coupled receptors, leading to receptor desensitization. Seven GRKs, designated GRK1 through 7, have been characterized. GRK5 is negatively regulated by protein kinase C. We investigated whether human substance P receptor (hSPR) is a substrate of GRK5. We report that membrane-bound hSPR is phosphorylated by purified GRK5, and that both the rate and extent of phosphorylation increase dramatically in the presence of substance P. The phosphorylation has a high stoichiometry (20+/-4 mol phosphate/mol hSPR) and a low K(m) (1.7+/-0.1 nM). These data provide the first evidence that hSPR is a substrate of GRK5.
MeSH term(s)	Amino Acid Sequence ; Animals ; Catalysis ; Cell Line ; Cell Membrane/metabolism ; G-Protein-Coupled Receptor Kinase 5 ; GTP-Binding Proteins/metabolism ; Humans ; Kinetics ; Molecular Sequence Data ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/isolation & purification ; Protein-Serine-Threonine Kinases/metabolism ; Receptors, Neurokinin-1/agonists ; Receptors, Neurokinin-1/metabolism ; Spodoptera ; Substance P/metabolism ; Substrate Specificity
Chemical Substances	Receptors, Neurokinin-1 ; Substance P (33507-63-0) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; G-Protein-Coupled Receptor Kinase 5 (EC 2.7.11.16) ; GRK5 protein, human (EC 2.7.11.16) ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2001-12-19
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1016/s0014-5793(02)02858-2
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Article: Dual signalling by the adenosine A2a receptor involves activation of both N- and P-type calcium channels by different G proteins and protein kinases in the same striatal nerve terminals.

Gubitz, A K / Widdowson, L / Kurokawa, M / Kirkpatrick, K A / Richardson, P J

Journal of neurochemistry

1996 Volume 67, Issue 1, Page(s) 374–381

Abstract: ... acylase, protein kinase A, and P-type calcium channels; the other is mediated by a cholera toxin ... insensitive G protein, protein kinase C, and N-type calcium channels. The effects of these two pathways are ...

Abstract	Many Gs-linked receptors have been reported to use multiple signalling pathways in transfected cels but few in their normal cell environment. We show that the adenosine A2a receptor uses two signalling pathways to increase the release of acetylcholine from striatal nerve terminals. One pathway involves activation of Gs, adenylyl acylase, protein kinase A, and P-type calcium channels; the other is mediated by a cholera toxin-insensitive G protein, protein kinase C, and N-type calcium channels. The effects of these two pathways are not additive, the second pathway being inhibited by the first; but they are equally sensitive to the A2a receptor antagonist KF17837. This demonstrates that the A2a receptor activates two signalling systems in striatal cholinergic neurons.
MeSH term(s)	1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; 8-Bromo Cyclic Adenosine Monophosphate/pharmacology ; Acetylcholine/metabolism ; Adenosine/analogs & derivatives ; Adenosine/pharmacology ; Agatoxins ; Alkaloids ; Animals ; Antihypertensive Agents/pharmacology ; Benzophenanthridines ; Calcium Channel Blockers/pharmacology ; Calcium Channels/physiology ; Cholera Toxin/pharmacology ; Cholinergic Fibers/enzymology ; Cholinergic Fibers/ultrastructure ; Colforsin/pharmacology ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Enzyme Inhibitors/pharmacology ; GTP-Binding Proteins/physiology ; Isoquinolines/pharmacology ; Neostriatum/cytology ; Neurons/enzymology ; Neurons/ultrastructure ; Phenanthridines/pharmacology ; Phenethylamines/pharmacology ; Piperazines/pharmacology ; Potassium/pharmacology ; Presynaptic Terminals/physiology ; Protein Kinase C/metabolism ; Protein Kinases/physiology ; Rats ; Rats, Wistar ; Receptors, Purinergic P1/physiology ; Signal Transduction/physiology ; Spider Venoms/pharmacology ; Stereoisomerism ; Sulfonamides ; Tritium/metabolism ; Xanthines/pharmacology
Chemical Substances	Agatoxins ; Alkaloids ; Antihypertensive Agents ; Benzophenanthridines ; Calcium Channel Blockers ; Calcium Channels ; Enzyme Inhibitors ; Isoquinolines ; Phenanthridines ; Phenethylamines ; Piperazines ; Receptors, Purinergic P1 ; Spider Venoms ; Sulfonamides ; Xanthines ; omega-agatoxin-Aa4b ; Tritium (10028-17-8) ; 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine (120225-54-9) ; KF 17837 (152881-18-0) ; Colforsin (1F7A44V6OU) ; 8-Bromo Cyclic Adenosine Monophosphate (23583-48-4) ; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (84477-87-2) ; Cholera Toxin (9012-63-9) ; N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (91742-10-8) ; chelerythrine (E3B045W6X0) ; Protein Kinases (EC 2.7.-) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Protein Kinase C (EC 2.7.11.13) ; GTP-Binding Proteins (EC 3.6.1.-) ; Adenosine (K72T3FS567) ; Acetylcholine (N9YNS0M02X) ; Potassium (RWP5GA015D)
Language	English
Publishing date	1996-07
Publishing country	England
Document type	Journal Article
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1046/j.1471-4159.1996.67010374.x
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Article: Reduced Proactive and Reactive Cognitive Flexibility in Older Adults Underlies Performance Costs During Dual-Task Walking: A Mobile Brain/Body Imaging (MoBI) Study.

Richardson, David P / Foxe, John J / Freedman, Edward G

bioRxiv : the preprint server for biology

2024

Abstract: Age-related reductions in cognitive flexibility may limit modulation of control processes during systematic increases to cognitive-motor demands, exacerbating dual-task costs. In this study, behavioral and neurophysiologic changes to proactive and ... ...

Abstract	Age-related reductions in cognitive flexibility may limit modulation of control processes during systematic increases to cognitive-motor demands, exacerbating dual-task costs. In this study, behavioral and neurophysiologic changes to proactive and reactive control during progressive cognitive-motor demands were compared across older and younger adults to explore the basis for age-differences in cognitive-motor interference (CMI). 19 younger (19 - 29 years old, mean age = 22.84 +/- 2.75 years, 6 male, 13 female) and 18 older (60 - 77 years old, mean age = 67.89 +/- 4.60 years, 9 male, 9 female) healthy adults completed cued task-switching while alternating between sitting and walking on a treadmill. Gait kinematics, task performance measures, and brain activity were recorded using electroencephalography (EEG) based Mobile Brain/Body Imaging (MoBI). Response accuracy on easier trial types improved in younger, but not older adults when they walked while performing the cognitive task. As difficulty increased, walking provoked accuracy costs in older, but not younger adults. Both groups registered faster responses and reduced gait variability during dual-task walking. Older adults exhibited lower amplitude modulations of proactive and reactive neural activity as cognitive-motor demands systematically increased, which may reflect reduced flexibility for progressive preparatory and reactive adjustments over behavioral control.
Language	English
Publishing date	2024-01-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.27.577090
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Article ; Online: Defibrotide improves COVID-19-related acute respiratory distress syndrome in myeloma patients after chimeric antigen receptor T-cell treatment without compromising virus-specific and anti-myeloma T-cell responses.

Kocoglu, Mehmet H / Richardson, Paul G / Mo, Clifton C / Rapoport, Aaron P / Atanackovic, Djordje

Haematologica

2024

Abstract: Not available. ...

Abstract	Not available.
Language	English
Publishing date	2024-02-22
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.284793
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Article ; Online: Quantifying the HIV reservoir with dilution assays and deep viral sequencing.

Lotspeich, Sarah C / Richardson, Brian D / Baldoni, Pedro L / Enders, Kimberly P / Hudgens, Michael G

Biometrics

2024 Volume 80, Issue 1

Abstract: People living with HIV on antiretroviral therapy often have undetectable virus levels by standard assays, but "latent" HIV still persists in viral reservoirs. Eliminating these reservoirs is the goal of HIV cure research. The quantitative viral outgrowth ...

Abstract	People living with HIV on antiretroviral therapy often have undetectable virus levels by standard assays, but "latent" HIV still persists in viral reservoirs. Eliminating these reservoirs is the goal of HIV cure research. The quantitative viral outgrowth assay (QVOA) is commonly used to estimate the reservoir size, that is, the infectious units per million (IUPM) of HIV-persistent resting CD4+ T cells. A new variation of the QVOA, the ultra deep sequencing assay of the outgrowth virus (UDSA), was recently developed that further quantifies the number of viral lineages within a subset of infected wells. Performing the UDSA on a subset of wells provides additional information that can improve IUPM estimation. This paper considers statistical inference about the IUPM from combined dilution assay (QVOA) and deep viral sequencing (UDSA) data, even when some deep sequencing data are missing. Methods are proposed to accommodate assays with wells sequenced at multiple dilution levels and with imperfect sensitivity and specificity, and a novel bias-corrected estimator is included for small samples. The proposed methods are evaluated in a simulation study, applied to data from the University of North Carolina HIV Cure Center, and implemented in the open-source R package SLDeepAssay.
MeSH term(s)	Humans ; Virus Latency ; HIV-1/genetics ; HIV Infections ; CD4-Positive T-Lymphocytes ; Computer Simulation ; Viral Load
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	213543-7
ISSN	1541-0420 ; 0099-4987 ; 0006-341X
ISSN (online)	1541-0420
ISSN	0099-4987 ; 0006-341X
DOI	10.1093/biomtc/ujad018
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Article ; Online: Demographic Differences in Gender Dysphoria Diagnosis and Access to Gender-Affirming Care Among Adolescents.

Kahn, Nicole F / Asante, Peter G / Coker, Tumaini R / Kidd, Kacie M / Christakis, Dimitri A / Richardson, Laura P / Sequeira, Gina M

LGBT health

2024

Abstract: Purpose: ...

Abstract	Purpose:
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2727303-9
ISSN	2325-8306 ; 2325-8292
ISSN (online)	2325-8306
ISSN	2325-8292
DOI	10.1089/lgbt.2023.0273
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Article ; Online: Correspondence on "Crystalline Porous Organic Salt for Ultrarapid Adsorption/Desorption-Based Atmospheric Water Harvesting by Dual Hydrogen Bond System".

Muang-Non, Phonlakrit / Richardson, Christopher / White, Nicholas G

Angewandte Chemie (International ed. in English)

2023 Volume 62, Issue 8, Page(s) e202212962

Abstract: In a recent Research Article, Ben and co-workers reported a hydrogen-bonded framework prepared from a ... ...

Abstract	In a recent Research Article, Ben and co-workers reported a hydrogen-bonded framework prepared from a 4
Language	English
Publishing date	2023-01-19
Publishing country	Germany
Document type	Letter
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.202212962
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Article ; Online: Appropriate Categorization of Inequality to Inform Policy Decisions: Estimating Distribution of Lifetime Health Using Alternative Approaches to Socioeconomic Stratification.

Murphy, Peter / Hinde, Sebastian / Richardson, Gerry

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research

2023 Volume 27, Issue 1, Page(s) 26–34

Abstract: Objectives: Estimation of gradients in lifetime health, notably quality-adjusted life expectancy (QALE), has largely focused on index of multiple deprivation to categorize the population by socioeconomic position. In this article, we estimate QALE using ...

Abstract	Objectives: Estimation of gradients in lifetime health, notably quality-adjusted life expectancy (QALE), has largely focused on index of multiple deprivation to categorize the population by socioeconomic position. In this article, we estimate QALE using alternate, individual- rather than area-level, indicators of socioeconomic position. Methods: Building on previous research methods, the distribution of QALE is estimated across education and income groups based on data from the Health Survey for England and the Office for National Statistics. QALE is estimated for each group by combining multivariate mortality rates and health-related quality of life (HRQL) weights using life tables. HRQL weights were estimated using ordinary least squares and missing data were handled using multiple imputation. Results: The estimated lifetime HRQL weights decreased with increased age, lower educational attainment, and lower income. For example, the QALE at birth for males in the lowest educational attainment group was 61.69 quality-adjusted life-years (QALYs), 1.54 QALYs lower than females in the same group. This is in contrast to 76.58 and 75.89 QALYs for males and females in the highest educational attainment group, respectively. A similar trend was observed across income quintiles albeit the gap was less pronounced. Conclusions: The use of index of multiple deprivation to assess health inequalities may be masking important information about individual-level variation. Decisions makers should consider this alongside the merits of using area-level approaches to categorizing the population if individual-level approaches are preferable.
MeSH term(s)	Male ; Infant, Newborn ; Female ; Humans ; Quality of Life ; Life Expectancy ; Quality-Adjusted Life Years ; Educational Status ; Policy ; Socioeconomic Factors
Language	English
Publishing date	2023-10-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1471745-1
ISSN	1524-4733 ; 1098-3015
ISSN (online)	1524-4733
ISSN	1098-3015
DOI	10.1016/j.jval.2023.10.001
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Article ; Online: Reply to G. R. Mohyuddin et al and A. Garfall et al.

Richardson, Paul G / Moreau, Philippe

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2021 Volume 40, Issue 1, Page(s) 107–108

Language	English
Publishing date	2021-10-15
Publishing country	United States
Document type	Research Support, Non-U.S. Gov't ; Letter ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.21.02081
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Article: Identification and Assessment of Outcome Measurement Instruments in Cauda Equina Syndrome: A Systematic Review.

Richardson, George E / Millward, Christopher P / Mitchell, James W / Clark, Simon / Wilby, Martin / Marson, Anthony G / Williamson, Paula R / Srikandarajah, Nisaharan

Global spine journal

2024 , Page(s) 21925682241227916

Abstract: Study design: This was a systematic review of surgically managed Cauda Equina Syndrome (CES) Outcome Measurement Instruments (OMI).: Objective: A core outcome set (COS) defines agreed outcomes which should be reported as a minimum in any research ... ...

Abstract	Study design: This was a systematic review of surgically managed Cauda Equina Syndrome (CES) Outcome Measurement Instruments (OMI). Objective: A core outcome set (COS) defines agreed outcomes which should be reported as a minimum in any research study for a specific condition. This study identified OMIs used in the wider CES literature and compare these to the established CESCOS. Methods: To identify measurement methods and instruments in the CES surgical outcome evidence base, a systematic review was performed. Medline, Embase and CINAHL plus databases were queried. In addition, a secondary search for validation studies of measurement instruments in CES was undertaken. Identified studies from this search were subject to the COSMIN risk of bias assessment. Results: In total, 112 studies were identified investigating surgical outcomes for CES. The majority (80%, n = 90) of these OMI studies were retrospective in nature and only 55% (n = 62) utilised a measurement method or instrument. The remaining 50 studies used study specific definitions for surgical outcomes defined within their methods. Of the 59 measurement instruments identified, 60% (n = 38 instruments) were patient reported outcome measures. Only one validated instrument was identified, which was a patient reported outcome measure. The validated instrument was not used in any study identified in the initial search (to identify measurement instruments). Conclusions: This review highlights the wide heterogeneity of measurement instruments used in surgically managed CES research. Subsequently, there is need for consensus agreement on which instrument or instruments should be used to measure each core outcome for CES surgical outcomes.
Language	English
Publishing date	2024-01-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2648287-3
ISSN	2192-5690 ; 2192-5682
ISSN (online)	2192-5690
ISSN	2192-5682
DOI	10.1177/21925682241227916
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