Publications by authors named "Pratima Pandey"

14 Publications

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Dauer formation in is modulated through AWC and ASI dependent chemosensation.

eNeuro 2021 Mar 11. Epub 2021 Mar 11.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, SAS Nagar, Manauli PO 140306, Punjab, India

The perception of our surrounding environment is an amalgamation of stimuli detected by sensory neurons. In olfaction is an essential behavior that determines various behavioral functions such as locomotion, feeding and development. Sensory olfactory cues also initiate downstream neuroendocrine signaling that controls ageing, learning, development and reproduction. Innate sensory preferences towards odors (food, pathogens) and reproductive pheromones are modulated by 11 pairs of amphid chemosensory neurons in the head region of Amongst these sensory neurons, the ASI neuron has neuroendocrine functions and secretes neuropeptides, insulin-like peptide (DAF-28) and the TGF-β protein, DAF-7. Its expression levels are modulated by the presence of food (increased levels) and population density (decreased levels). A recent study has shown that EXP-1, an excitatory GABA receptor regulates DAF-7/TGF-β levels and participates in DAF-7/TGF- β mediated behaviors such as aggregation and bordering. Here, we show that mutants show defective responses towards AWC sensed attractive odors in a non-autonomous manner through ASI neurons. Our dauer experiments reveal that in 7 mutants, ASI expressed EXP-1 and STR-2 (a G-protein coupled receptor) that partially maintained reproductive growth of animals. Further, studies suggest that neuronal connections between ASI and AWC neurons are allowed at least partially through ASI secreted DAF-7 or through alternate TGF- β pathway/s regulated by EXP-1 and STR-2. Together our behavioral, genetic and imaging experiments propose that EXP-1 and STR-2 integrate food cues and allow the animals to display DAF-7/TGF-β neuroendocrine dependent or independent behavioral responses contributing to chemosensensory and developmental plasticity.This work sheds light on a possible developmental and post-developmental function for the excitatory GABA receptor, EXP-1. We show that mutants of exp-1 are defective in their response towards AWC-sensed odors. Our genetic, behavioral and expression studies reveal that EXP-1 functions in the ASI neuron to modulate chemosensation and to regulate the behavioral switch between dauer and the reproductive state. EXP-1 has been shown to function in a DAF-7/TGF-β dependent manner. However, in the absence of DAF-7/TGF-β, EXP-1 and a G-protein coupled receptor, STR-2 integrate sensory information to maintain the reproductive state of the animal through an ASI dependent alternate pathway.
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http://dx.doi.org/10.1523/ENEURO.0473-20.2021DOI Listing
March 2021

Increased dopaminergic neurotransmission results in ethanol dependent sedative behaviors in Caenorhabditis elegans.

PLoS Genet 2021 Feb 1;17(2):e1009346. Epub 2021 Feb 1.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Mohali, India.

Ethanol is a widely used drug, excessive consumption of which could lead to medical conditions with diverse symptoms. Ethanol abuse causes dysfunction of memory, attention, speech and locomotion across species. Dopamine signaling plays an essential role in ethanol dependent behaviors in animals ranging from C. elegans to humans. We devised an ethanol dependent assay in which mutants in the dopamine autoreceptor, dop-2, displayed a unique sedative locomotory behavior causing the animals to move in circles while dragging the posterior half of their body. Here, we identify the posterior dopaminergic sensory neuron as being essential to modulate this behavior. We further demonstrate that in dop-2 mutants, ethanol exposure increases dopamine secretion and functions in a DVA interneuron dependent manner. DVA releases the neuropeptide NLP-12 that is known to function through cholinergic motor neurons and affect movement. Thus, DOP-2 modulates dopamine levels at the synapse and regulates alcohol induced movement through NLP-12.
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http://dx.doi.org/10.1371/journal.pgen.1009346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877767PMC
February 2021

Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein.

Nat Cell Biol 2020 06 25;22(6):674-688. Epub 2020 May 25.

Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.

The dynamin GTPase is known to bundle actin filaments, but the underlying molecular mechanism and physiological relevance remain unclear. Our genetic analyses revealed a function of dynamin in propelling invasive membrane protrusions during myoblast fusion in vivo. Using biochemistry, total internal reflection fluorescence microscopy, electron microscopy and cryo-electron tomography, we show that dynamin bundles actin while forming a helical structure. At its full capacity, each dynamin helix captures 12-16 actin filaments on the outer rim of the helix. GTP hydrolysis by dynamin triggers disassembly of fully assembled dynamin helices, releasing free dynamin dimers/tetramers and facilitating Arp2/3-mediated branched actin polymerization. The assembly/disassembly cycles of dynamin promote continuous actin bundling to generate mechanically stiff actin super-bundles. Super-resolution and immunogold platinum replica electron microscopy revealed dynamin along actin bundles at the fusogenic synapse. These findings implicate dynamin as a unique multifilament actin-bundling protein that regulates the dynamics and mechanical strength of the actin cytoskeletal network.
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http://dx.doi.org/10.1038/s41556-020-0519-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953826PMC
June 2020

Control of Locomotory Behavior of by the Immunoglobulin Superfamily Protein RIG-3.

Genetics 2020 01 18;214(1):135-145. Epub 2019 Nov 18.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Manauli 140306, India

Cell surface immunoglobulin superfamily (IgSF) proteins play important roles in the development and function of the nervous system . Here we define the role of a IgSF protein, RIG-3, in the function of the AVA command interneuron. This study reveals that RIG-3 regulates the abundance of the glutamate receptor subunit, GLR-1, in the AVA command interneuron and also regulates reversal behavior in The mutant strain lacking ( ()) shows increased reversal frequency during local search behaviors. Genetic and behavioral experiments suggest that RIG-3 functions through GLR-1 to regulate reversal behavior. We also show that the increased reversal frequency seen in mutants is dependent on the increase in GLR-1 abundance at synaptic inputs to AVA, suggesting that RIG-3 alters the synaptic strength of incoming synapses through GLR-1 Consistent with the imaging experiments, altered synaptic strength was also reflected in increased calcium transients in mutants when compared to wild-type control animals. Our results further suggest that animals lacking show increased AVA activity, allowing the release of FLP-18 neuropeptide from AVA, which is an activity-dependent signaling molecule. Finally, we show that FLP-18 functions through the neuropeptide receptor, NPR-5, to modulate reversal behavior in .
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http://dx.doi.org/10.1534/genetics.119.302872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944407PMC
January 2020

Cellular Targets and Receptor of Sexual Transmission of Zika Virus.

Appl Immunohistochem Mol Morphol 2017 Nov/Dec;25(10):679-686

Department of Biology and South Carolina Center for Biotechnology, Claflin University, Orangeburg, SC.

Study Question: What is the mechanism of sexual transmission of Zika virus (ZIKV)?

Summary Answer: By utilizing exquisite reverse transcriptase-initiated in situ polymerase chain reaction (RT-in situ PCR), which enables an improved visualization of spermatozoa's subcellular compartment, we precisely localized the mid-piece of sperm that carry receptors for ZIKV.

What Is Already Known: ZIKV is transmitted sexually and recent studies have verified ZIKV presence in semen of previously Zika-infected patients for >6-month postinfection when ZIKV had disappeared from blood, saliva, and urine. Strong serial analyses of various body fluids suggest that ZIKV can be transmitted between sexual partners. Currently, there is limited information on the association of the virus with human semen cell types that may carry the virus.

Study Design, Size, Duration: Analyses were carried out to localize ZIKV for subcellular localization of ZIKV on cell types. The Tyro3 receptor for ZIKV was colocalized by dual immunocytochemistry with specific monoclonal antibodies.

Participants/materials, Setting, Methods: Three semen specimens were purchased from a commercial sperm bank. Motile sperm was separated from nonmotile cells by the "swim-up" technique. Each of the semen fractions was infected with ZIKV at the multiplicity of infection of 0.1.0 and 1.0 and evaluated for the primary targets of ZIKV in the semen cells by RT-in situ PCR and confirmed by real-time RT-PCR.

Main Results And The Role Of Chance: ZIKV was present primarily at the mid-piece of mature spermatozoa in about 30% of the sperm. In addition, we determined that Tyro3 receptors, primarily expressed on mid-piece of human spermatozoa, play a role in ZIKV-binding and entry into spermatozoa. Our data strongly suggest a potential sexual/horizontal route of transmission for ZIKV primarily via infected sperms; most likely ZIKV enters the sperm via the Tyro3 receptor found at the mid-piece of the mature spermatozoa.

Limitations, Reasons For Caution: We are uncertain as to what phase of spermatogenesis, that in human takes about 120 days, sperms are permissive to ZIKV. If permissiveness was very early during spermatogenesis males could be infectious for ∼120 days after the disappearance of viremia in an infected man.

Wider Implications Of The Findings: Our findings bring a new focus on the current affords to develop ZIKV vaccine. Why in the presence of anti-ZIKV antibodies infected men are still able to transmit the virus sexually? We suggest that only certain subclass of immunoglobulin (Ig)G (ie, IgG4) can cross the blood-Sertoli barrier therefore, a successful vaccine must provoke a subclass of IgG can quell ZIKV inside the seminiferous tubules.
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http://dx.doi.org/10.1097/PAI.0000000000000580DOI Listing
November 2018

Regulation of WNT Signaling at the Neuromuscular Junction by the Immunoglobulin Superfamily Protein RIG-3 in .

Genetics 2017 07 17;206(3):1521-1534. Epub 2017 May 17.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Mohali, Punjab 140306, India

Perturbations in synaptic function could affect the normal behavior of an animal, making it important to understand the regulatory mechanisms of synaptic signaling. Previous work has shown that in Caenorhabditis elegans an immunoglobulin superfamily protein, RIG-3, functions in presynaptic neurons to maintain normal acetylcholine receptor levels at the neuromuscular junction (NMJ). In this study, we elucidate the molecular and functional mechanism of RIG-3. We demonstrate by genetic and BiFC (Bi-molecular Fluorescence Complementation) assays that presynaptic RIG-3 functions by directly interacting with the immunoglobulin domain of the nonconventional Wnt receptor, ROR receptor tyrosine kinase (RTK), CAM-1, which functions in postsynaptic body-wall muscles. This interaction in turn inhibits Wnt/LIN-44 signaling through the ROR/CAM-1 receptor, and allows for maintenance of normal acetylcholine receptor, AChR/ACR-16, levels at the neuromuscular synapse. Further, this work reveals that RIG-3 and ROR/CAM-1 function through the β-catenin/HMP-2 at the NMJ. Taken together, our results demonstrate that RIG-3 functions as an inhibitory molecule of the Wnt/LIN-44 signaling pathway through the RTK, CAM-1.
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http://dx.doi.org/10.1534/genetics.116.195297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500148PMC
July 2017

The tumor promoter-activated protein kinase Cs are a system for regulating filopodia.

Cytoskeleton (Hoboken) 2017 Aug 24;74(8):297-314. Epub 2017 May 24.

Department of Applied Statistics and Operations Research, Bowling Green State University, 344 Business Administration Building, Bowling Green, Ohio, 43403.

Different protein kinase C (PKC) isoforms have distinct roles in regulating cell functions. The conventional (α, β, γ) and novel (δ, ɛ, η, θ) classes are targets of phorbol ester tumor promoters, which are surrogates of endogenous second messenger, diacylglycerol. The promoter-stimulated disappearance of filopodia was investigated by use of blocking peptides (BPs) that inhibit PKC maturation and/or docking. Filopodia were partially rescued by a peptide representing PKC ɛ hydrophobic sequence, but also by a myristoylated PKC α/β pseudosubstrate sequence, and an inhibitor of T-cell protein tyrosine phosphatase (TC-PTP). The ability to turn over filopodia was widely distributed among PKC isoforms. PKC α and η hydrophobic sequences enhanced filopodia in cells in the absence of tumor promoter treatment. With transcriptional knockdown of PKC α, the content of PKC ɛ predominated over other isoforms. PKC ɛ could decrease filopodia significantly in promoter-treated cells, and this was attributed to ruffling. The presence of PKC α counteracted the PKC ɛ-mediated enhancement of ruffling. The results showed that there were two mechanisms of filopodia downregulation. One operated in the steady-state and relied on PKC α and η. The other was stimulated by tumor promoters and relied on PKC ɛ. Cycles of protrusion and retraction are characteristic of filopodia and are essential for the cell to orient itself during chemotaxis and haptotaxis. By suppressing filopodia, PKC ɛ can create a long-term "memory" of an environmental signal that may act in nature as a mnemonic device to mark the direction of a repulsive signal.
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http://dx.doi.org/10.1002/cm.21373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575509PMC
August 2017

Changes in DNA methylation levels during seed development in Jatropha curcas.

J Genet 2016 Oct 7;95(4):e13-e18. Epub 2016 Oct 7.

TERI University, 10 Institutional Area, Vasant Kunj, New Delhi 110 070, India.

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http://dx.doi.org/10.1007/s12041-016-0703-5DOI Listing
October 2016

A synergistic approach towards understanding the functional significance of dopamine receptor interactions.

J Mol Signal 2013 Dec 5;8(1):13. Epub 2013 Dec 5.

Department of Biological Sciences, Center for Neuroscience Research, Delaware State University, Dover, DE 19901, USA.

The importance of the neurotransmitter dopamine (DA) in the nervous system is underscored by its role in a wide variety of physiological and neural functions in both vertebrates and invertebrates. Binding of dopamine to its membrane receptors initiates precise signaling cascades that result in specific cellular responses. Dopamine receptors belong to a super-family of G-protein coupled receptors (GPCRs) that are characterized by seven trans-membrane domains. In mammals, five dopamine receptors have been identified which are grouped into two different categories D1- and D2-like receptors. The interactions of DA receptors with other proteins including specific Gα subunits are critical in deciding the fate of downstream molecular events carried out by effector proteins. In this mini-review we provide a synopsis of known protein-protein interactions of DA receptors and a perspective on the potential synergistic utility of Caenorhabditis elegans as a model eukaryote with a comparatively simpler nervous system to gain insight on the neuronal and behavioral consequences of the receptor interactions.
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http://dx.doi.org/10.1186/1750-2187-8-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3878971PMC
December 2013

GPA-14, a Gα(i) subunit mediates dopaminergic behavioral plasticity in C. elegans.

Behav Brain Funct 2013 Apr 22;9:16. Epub 2013 Apr 22.

Department of Biological Sciences, Delaware State University, Dover, DE 19901, USA.

Background: Precise levels of specific neurotransmitters are required for appropriate neuronal functioning. The neurotransmitter dopamine is implicated in modulating behaviors, such as cognition, reward and memory. In the nematode Caenorhabditis elegans, the release of dopamine during behavioral plasticity is in part modulated through an acid-sensing ion channel expressed in its eight dopaminergic neurons. A D2-like C. elegans dopamine receptor DOP-2 co-expresses along with a Gα(i) subunit (GPA-14) in the anterior deirid (ADE) pair of dopaminergic neurons.

Findings: In follow-up experiments to our recently reported in vitro physical interaction between DOP-2 and GPA-14, we have behaviorally characterized worms carrying deletion mutations in gpa-14 and/or dop-2. We found both mutants to display behavioral abnormalities in habituation as well as associative learning, and exogenous supply of dopamine was able to revert the observed behavioral deficits. The behavioral phenotypes of dop-2 and gpa-14 loss-of-function mutants were found to be remarkably similar, and we did not observe any cumulative defects in their double mutants.

Conclusion: Our results provide genetic and phenotypic support to our earlier in vitro results where we had shown that the DOP-2 dopamine receptor and the GPA-14 Gα(i) subunit physically interact with each other. Results from behavioral experiments presented here together with our previous in-vitro work suggests that the DOP-2 functions as a dopamine auto-receptor to modulate two types of learning, anterior touch habituation and chemosensory associative conditioning, through a G-protein complex that comprises GPA-14 as its Gα subunit.
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http://dx.doi.org/10.1186/1744-9081-9-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679979PMC
April 2013

The Caenorhabditis elegans D2-like dopamine receptor DOP-2 physically interacts with GPA-14, a Gαi subunit.

J Mol Signal 2012 Jan 26;7(1). Epub 2012 Jan 26.

Department of Biological Sciences, Delaware State University, Dover, DE 19901, USA.

Dopaminergic inputs are sensed on the cell surface by the seven-transmembrane dopamine receptors that belong to a superfamily of G-protein-coupled receptors (GPCRs). Dopamine receptors are classified as D1-like or D2-like receptors based on their homology and pharmacological profiles. In addition to well established G-protein coupled mechanism of dopamine receptors in mammalian system they can also interact with other signaling pathways. In C. elegans four dopamine receptors (dop-1, dop-2, dop-3 and dop-4) have been reported and they have been implicated in a wide array of behavioral and physiological processes. We performed this study to assign the signaling pathway for DOP-2, a D2-like dopamine receptor using a split-ubiquitin based yeast two-hybrid screening of a C. elegans cDNA library with a novel dop-2 variant (DOP-2XL) as bait. Our yeast two-hybrid screening resulted in identification of gpa-14, as one of the positively interacting partners. gpa-14 is a Gα coding sequence and shows expression overlap with dop-2 in C. elegans ADE deirid neurons. In-vitro pull down assays demonstrated physical coupling between dopamine receptor DOP-2XL and GPA-14. Further, we sought to determine the DOP-2 region necessary for GPA-14 coupling. We generated truncated DOP-2XL constructs and performed pair-wise yeast two-hybrid assay with GPA-14 followed by in-vitro interaction studies and here we report that the third intracellular loop is the key domain responsible for DOP-2 and GPA-14 coupling. Our results show that the extra-long C. elegans D2-like receptor is coupled to gpa-14 that has no mammalian homolog but shows close similarity to inhibitory G-proteins. Supplementing earlier investigations, our results demonstrate the importance of an invertebrate D2-like receptor's third intracellular loop in its G-protein interaction.
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http://dx.doi.org/10.1186/1750-2187-7-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3297496PMC
January 2012

MTHFR and ACE gene polymorphisms and risk of vascular and degenerative dementias in the elderly.

Brain Cogn 2009 Dec 27;71(3):295-9. Epub 2009 Aug 27.

Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.

Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as degenerative dementia. Among genetic factors, role of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes as putative risk factors has been examined but the outcome of these studies remain inconclusive. Present study attempted to see the importance of ACE alu insertion/deletion and MTHFR C677T polymorphisms as genetic predisposers to dementia. The study comprised of 80 vascular dementia patients, 90 degenerative dementia patients and 170 age matched controls. All were genotyped for ACE, MTHFR and APOE polymorphisms using PCR-RFLP method. Frequency of ACE D allele was seemingly high in dementia cases (26.7%) when compared to controls (11.2%). However, after adjusting for age and APOE E4*, none of the ACE alleles showed good correlation. MTHFR genotypes or alleles also did not show any correlation. Our study suggests no true correlation of ACE or MTHR genes with dementia in elderly.
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http://dx.doi.org/10.1016/j.bandc.2009.07.007DOI Listing
December 2009

Presenilin gene predisposes to late-onset degenerative but not vascular dementia: a comparative study of PS1 and ApoE genes in a North Indian Cohort.

Dement Geriatr Cogn Disord 2007 10;24(3):151-61. Epub 2007 Jul 10.

Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Background: Variation in the presenilin gene shifts the cleavage site of amyloid precursor protein producing an insoluble peptide Abeta(42) (instead of Abeta(40), which is soluble when produced in restricted amount), which is prone to aggregation in the brain in the form of amyloid plaques not only in Alzheimer's disease (AD) but also in other degenerative dementias. The role of presenilin 1 (PS1) and apolipoprotein E (ApoE) genes has not been explored in degenerative dementias other than AD.

Objective: To study the association of PS1 intron 8 and ApoE epsilon4 gene polymorphism in degenerative and vascular dementia patients in the North Indian population.

Design: A hospital-based association study on degenerative and vascular dementia patients proven on the basis of clinical profile and MRI.

Participants: A group of 107 dementia patients and 162 age- and sex-matched controls from a North Indian cohort participated in the study. All patients had Mini Mental State Examination scores less than 24 and met the DSM-IV criteria for dementia.

Results: The frequency of genotype 1/1 and allele 1 in degenerative dementias (73.12 and 83.70%, respectively) was higher than what had been reported so far in AD. A significant association of PS1 intron 8 polymorphism was found with degenerative dementias but not with vascular dementias (OR 2.50, 95% CI 1.27-5.00). On the other hand, ApoE epsilon4 allele was found to significantly increase the risk for both vascular and degenerative dementias (p = 0.0001, OR 3.45, 95% CI 1.74-6.86).

Conclusion: While ApoE epsilon4 allele increases the susceptibility to both degenerative and vascular dementia, PS1 allele 1 increases the susceptibility to degenerative dementias only.
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http://dx.doi.org/10.1159/000105483DOI Listing
October 2007

Spontaneous long-term remission of intractable partial epilepsy in childhood.

J Child Neurol 2002 Jun;17(6):466-70

Department of Transitional Medicine, Children's Hospital of Michigan/Detroit Medical Center, Wayne State University School of Medicine, 48201, USA.

Drug-resistant partial epilepsy in children often has a major impact on cognitive development, and early surgical intervention has been advocated to prevent adverse neurobehavioral effects of seizures in such patients. We report a 5-year-old boy who had cryptogenic partial epilepsy of right parietal origin as documented by ictal electroencephalogram (EEG) and glucose metabolism positron emission tomographic (PET) scan. His atonic seizures could not be controlled by multiple antiepilepsy drugs; therefore, cortical resection was scheduled. However, his seizures remitted spontaneously after 1 year of failed medical treatment. The epileptiform abnormality disappeared on the follow-up EEGs, and a glucose PET scan also normalized. This boy has fully retained his cognitive and motor functions and has remained seizure free in the past 4z\x years off medications.
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http://dx.doi.org/10.1177/088307380201700616DOI Listing
June 2002