FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2023956478> ?p ?o ?g. }

• W2023956478 endingPage "324" @default.
• W2023956478 startingPage "321" @default.
• W2023956478 abstract "One hundred years ago Charles Sherrington's studies on neural control of muscle movements led him to propose that the integrative activity of ensembles of neurons in a network is the fundamental unit of behavior. Since these initial studies, considerable strides have been made in unraveling the physiological and anatomical properties of motor circuits. However, many important details are still missing. To a large extent understanding spinal motor circuit function in the adult has been, until recently, the domain of physiologists and systems neurobiologists. Molecular neurobiologists have, for the most part, restricted their interests to questions related to the embryonic development of the spinal cord. The advent of molecular genetic tools has sparked a veritable explosion of work defining genes and proteins that regulate multiple aspects of spinal cord development. Much of this work has focused on the development of spinal motor neurons and their projections to muscle targets, with attention only recently being paid to more elusive and diverse interneuron populations. The main goal of this minireview is to illustrate that the significance of recent work on the neuronal specification is far broader than its embryonic roots and that ultimately insights generated in development may have profound implications for understanding the neuronal circuits in the adult spinal cord and the behaviors that the motor networks control. The spinal cord has many attributes that make it a potentially ideal system for studying how neurons assemble into functional circuits. First, its anatomical organization is relatively simple. The neuronal populations that make up the spinal cord locomotor circuits are relatively few. Second, the spinal cord contains an intrinsic circuitry, a central pattern generator (CPG), which can function independently of outside influence and allows for the alternating and rhythmic movement characteristics of locomotion. The spinal cord CPG shares many characteristics with the locomotor circuit of lower vertebrates. The CPG of lamprey is the best studied of vertebrate CPGs. Although the locomotory behavior of the lamprey and tetrapods differs, their functioning components are remarkably similar (Grillner et al. 1995Grillner S Deliagina T Ekeberg O el Manira A Hill R.H Lansner A Orlovsky G.N Wallen P Trends Neurosci. 1995; 18: 270-279Abstract Full Text PDF PubMed Scopus (365) Google Scholar). Like the tetrapod limb CPG that produces alternating flexor and extensor bursts, the lamprey CPG produces alternating motor rhythms on the left and right sides of the body. The neuronal populations that make up the lamprey CPG, like the locomotor circuits in higher vertebrates, are composed of three main classes of neurons: excitatory interneurons that receive reticulospinal inputs for generating the rhythmic output and that then distribute activity to all neurons on the same side of the body; two inhibitory interneurons, one contralateral and one ipsilateral, which control alternation of the left and right motor rhythms; and output motor neurons (Grillner et al. 1995Grillner S Deliagina T Ekeberg O el Manira A Hill R.H Lansner A Orlovsky G.N Wallen P Trends Neurosci. 1995; 18: 270-279Abstract Full Text PDF PubMed Scopus (365) Google Scholar). This simple circuit is perhaps the basic unit upon which new motor neuron and interneuron classes have been added, as animals needed more muscles for novel functions and as new classes of neurons were needed to coordinate the activity. How does one dissect a neural circuit? A critical first step toward dissecting a neural circuit is to identify the neurons that contribute to its function. This entails two steps. First, different classes of neurons need to be identified. It has generally been assumed that neurons with similar morphological, physiological, and pharmacological properties perform the same function and, therefore, define the same class. Once identified, the second step, testing their role in the neural circuit, can be undertaken. In the case of the spinal motor circuits, classical approaches have relied on physiological and pharmacological characteristics to define specific neuronal classes in the mammalian spinal cord (Jankowska 1999Jankowska E Brain Res.Bull. 1999; 50: 327Google Scholar). More recently, restricted expression of genes and gene products have provided a rich arsenal of tools to mark, identify, and subject individual classes of neurons to tests of their function. The past few years have seen an explosion of research aimed at identifying inductive and transcriptional mechanisms that determine neuronal identity in the spinal cord. In the ventral spinal cord, graded concentrations of Sonic Hedgehog (Shh), a secreted morphogen, set up domains of gene expression along the dorsal–ventral axis. Five classes of neurons develop from these domains, namely V0, V1, V2, and V3 interneurons, and motor neurons (Figure 1; for review see Jessell 2000Jessell T.M Nat. Rev. Genet. 2000; 1: 20-29Crossref PubMed Scopus (1555) Google Scholar). The post mitotic V0, V1, V2, and V3 interneurons express transcription factors Evx1/2, En1, Chx10/Lhx3, and Sim1, respectively (Burrill et al. 1997Burrill J.D Moran L Goulding M.D Saueressig H Development. 1997; 124: 4493-4503PubMed Google Scholar, Ericson et al. 1997Ericson J Briscoe J Rashbass P van Heyningen V Jessell T.M Cold Spring Harb.Symp. Quant. Biol. 1997; 62: 451-466Crossref PubMed Google Scholar, Matise and Joyner 1997Matise M.P Joyner A.L J. Neurosci. 1997; 17: 7805-7816Crossref PubMed Google Scholar, Pierani et al. 1999Pierani A Brenner-Morton S Chiang C Jessell T.M Cell. 1999; 97: 903-915Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar, Briscoe et al. 2000Briscoe J Pierani A Jessell T.M Ericson J Cell. 2000; 101: 435-445Abstract Full Text Full Text PDF PubMed Scopus (892) Google Scholar), whereas motor neurons are marked by the expression of Isl1/2 and HB9 (Tsuchida et al. 1994Tsuchida T Ensini M Morton S.B Baldassare M Edlund T Jessell T.M Pfaff S.L Cell. 1994; 79: 957-970Abstract Full Text PDF PubMed Scopus (853) Google Scholar, Arber et al. 1999Arber S Han B Mendelsohn M Smith M Jessell T.M Sockanathan S Neuron. 1999; 23: 659-674Abstract Full Text Full Text PDF PubMed Scopus (455) Google Scholar, Thaler et al. 1999Thaler J Harrison K Sharma K Lettieri K Kehrl J Pfaff S.L Neuron. 1999; 23: 675-687Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar). With this information in hand, developmental biologists have focused on three important questions: (1) How do these inductive processes set up domains of gene activation in the ventral neural precursors? (2) Which of these genes control neuronal subtype identity? (3) How do combinations of genetic factors control multiple neuronal characteristics? More recently, a fourth issue has emerged: (4) Do genetically determined neuronal subtypes represent physiologically identified neuronal classes? In this issue of Neuron, two studies from the labs of Tom Jessell and Martyn Goulding address the above questions with respect to the issue of mechanisms that determine interneuron cell fate (Pierani et al. 2001Pierani A Moran-Rivard L Sunshine M.J Littman D.R Goulding M Jessell T.M Neuron. 2001; 29 (this issue,): 367-384Abstract Full Text Full Text PDF PubMed Scopus (264) Google Scholar, Moran-Rivard et al. 2001Moran-Rivard L Kagawa T Saueressig H Gross M.K Burrill J Goulding M Neuron. 2001; 29 (this issue,): 385-399Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar). Using similar genetic and molecular approaches, the two papers dissect the respective roles of the homeobox transcription factors Dbx1 and Evx1 in the specification of V0 interneuron fate. First, these studies use genetic and retrograde dye labeling techniques to demonstrate that the neurons marked by the expression of homeodomain factor Evx1 are commissural interneurons that project locally, extending 1–4 spinal segments after crossing the floor plate (Moran-Rivard et al. 2001Moran-Rivard L Kagawa T Saueressig H Gross M.K Burrill J Goulding M Neuron. 2001; 29 (this issue,): 385-399Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar). In contrast to Dbx1, which marks neuronal progenitors (Pierani et al. 2001Pierani A Moran-Rivard L Sunshine M.J Littman D.R Goulding M Jessell T.M Neuron. 2001; 29 (this issue,): 367-384Abstract Full Text Full Text PDF PubMed Scopus (264) Google Scholar), Evx1 expression is activated in postmitotic neurons (Moran-Rivard et al. 2001Moran-Rivard L Kagawa T Saueressig H Gross M.K Burrill J Goulding M Neuron. 2001; 29 (this issue,): 385-399Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar). Elimination of the genes encoding Dbx1 or Evx1 showed that these genes are necessary for the development of locally projecting commissural V0 interneurons. Interestingly, in the absence of Dbx1 or Evx1, V0 interneurons adopt phenotypes characteristic of the V1 interneurons. V0 commissural interneurons are located in a domain that abuts the domain of V1 interneurons. Although they are generated in close proximity, the phenotypes of V1 and V0 populations are quite distinct. Migration of V0 neuronal cell bodies follows a medial migratory path, while V1 neurons migrate along a more lateral route. In contrast to the commissural projections of the V0 neurons, V1 axons remain ipsilateral, suggesting that Dbx1 and Evx1 may play a role in the distinction between V0 and V1 interneuron fate. Elimination of either Dbx1 or Evx1 is able to convert the fate of a V0 interneuron to a cell with V1-like characteristics, including a change in expression patterns, migratory route, and axonal trajectories. Conversely, ectopic expression of either Evx1 or Dbx1 suppresses En1 expression, a marker for V1s. Together, these results demonstrate that a single transcription factor can specify many basic characteristics of neurons, including axon projections and neurotransmitter identity. A particularly interesting aspect of these results is reflected in the temporal differences in expression of Dbx1 and Evx1. Dbx1 is expressed primarily in early neuronal progenitors, suggesting that it functions in early aspects of a specification program. Evx1 is only expressed after cells have left the cell cycle and taken on the life of a neuron. Together, these two studies suggest a pathway for V0 fate determination where Dbx expression in progenitor populations leads to a restriction of V0 fate via activation of Evx1 in postmitotic, V0-fated interneurons. Thus, specification is not a one-step trigger. Rather, there is a critical postmitotic window during which the differentiation program of postmitotic neurons can still be altered. However, since misfated V0s seem to specifically take on the V1 fate rather than just a random neuronal fate, to some extent, a cell's differentiation potential must be restricted. Finally, it is also worth noting that although, in the case of Dbx1 and Evx1, gene expression correlates with functions in cell fate specification, such correlation does not always hold true. Cell-type-specific expression need not necessarily reflect a role in specification. For example, although En1 is a marker for V1 interneurons, it is not required for the formation of the characteristic V1 ipsilateral projections. It is, however, required for later aspects of V1 function, such as axon fasciculation and target recognition (Burrill et al. 1997Burrill J.D Moran L Goulding M.D Saueressig H Development. 1997; 124: 4493-4503PubMed Google Scholar). The work on Dbx1 and Evx1 in interneuron development highlights a number of unifying principles that have emerged from studies of both interneuron and motor neuron cell fate specification. First, neuronal specification depends on multiple factors acting at different stages of neuronal differentiation. Both Dbx1 and Evx1 are required for V0 fate specification. However, while Dbx1 affects V0 fate specification by acting in neuronal progenitors before they have left the cell cycle, Evx1 functions in postmitotic neurons. Second, just as specification of some neuronal classes seems to require the combinatorial expression of multiple factors, some transcription factors appear to be required for the specification of multiple neuronal subtypes. One example of this is the LIM homeodomain factor Lhx3 that is expressed in both interneurons and motor neurons (Tsuchida et al. 1994Tsuchida T Ensini M Morton S.B Baldassare M Edlund T Jessell T.M Pfaff S.L Cell. 1994; 79: 957-970Abstract Full Text PDF PubMed Scopus (853) Google Scholar). The net effect of Lhx3 expression appears to be dependent on the context of other factors expressed in the cell. In the case of motor neurons, both Lhx3 and the related factor Lhx4 are required to specify all somatic motor neurons in the spinal cord, whereas in interneurons Lhx3 activates Chx10 expression (Tanabe et al., 1998; Sharma et al. 1998Sharma K Sheng H.Z Lettieri K Li H Karavanov A Potter S Westphal H Pfaff S.L Cell. 1998; 95: 817-828Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar). Third, neuronal cell fate specification may also involve repression of alternative differentiation programs. For instance, motor neuron specification requires the expression of the homeobox factor HB9, which appears to function by actively suppressing an interneuron determination program (Arber et al. 1999Arber S Han B Mendelsohn M Smith M Jessell T.M Sockanathan S Neuron. 1999; 23: 659-674Abstract Full Text Full Text PDF PubMed Scopus (455) Google Scholar, Thaler et al. 1999Thaler J Harrison K Sharma K Lettieri K Kehrl J Pfaff S.L Neuron. 1999; 23: 675-687Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar). Further indication that repression plays an important role in the generation of motor and interneurons comes from studies on the transcription factors Nkx6.1, Nkx2.2, and Irx3 (Briscoe et al. 2000Briscoe J Pierani A Jessell T.M Ericson J Cell. 2000; 101: 435-445Abstract Full Text Full Text PDF PubMed Scopus (892) Google Scholar). One potential limitation to generalizing conclusions from the aforementioned studies is that the interneuron subtypes identified thus far are distributed rather evenly throughout the spinal cord. This is in sharp contrast to the distribution of motor neurons and locomotor CPGs (Figure 2). Motor neurons that innervate epaxial (dorsal ramus) and the hypaxial (ventral ramus) muscles are present at most spinal cord levels. In contrast, limb motor neurons are generated only at the cervical and lumbar levels. Are limb-specific interneurons generated in the cervical and lumbar spinal cord? If so, what kind of molecular mechanisms would be needed to generate such neurons? We are beginning to understand patterning along the D/V axis, but the forces that regulate patterning along the A/P axis are relatively unexplored. It seems likely that interneuron development at limb levels shares some of the mechanisms that control the A/P patterning of motor neuron pools. In the case of motor neurons, neurons that innervate the same muscle are arranged in pools along the A/P axis within the same motor column (Matise and Lance-Jones 1996Matise M.P Lance-Jones C Development. 1996; 122: 659-669PubMed Google Scholar, Lin et al. 1998Lin J.H Saito T Anderson D.J Lance-Jones C Jessell T.M Arber S Cell. 1998; 95: 393-407Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar). Secondary inductive interactions are required to generate limb-type motor neurons. For instance, while motor neurons in all four columns need Lhx3 and Lhx4 function for proper development, only the MMCm motor neurons express these factors at the time of muscle innervation (Sharma et al. 1998Sharma K Sheng H.Z Lettieri K Li H Karavanov A Potter S Westphal H Pfaff S.L Cell. 1998; 95: 817-828Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar, Sharma et al. 2000Sharma K Leonard A.E Lettieri K Pfaff S.L Nature. 2000; 406: 515-519Crossref PubMed Scopus (105) Google Scholar). Retinoid signaling, which is restricted to the cervical and lumbar spinal cord, results in the localized expression of another LIM-homeodomain factors, Lim1, in motor neurons only at these levels (Sockanathan and Jessell 1998Sockanathan S Jessell T.M Cell. 1998; 94: 503-514Abstract Full Text Full Text PDF PubMed Scopus (323) Google Scholar). Thus, generation of limb-specific motor neuron classes appears to be dependent on multiple factors and inductive interactions. Although it remains unclear whether patterning of interneuron populations is responsive to precisely the same inputs, given the parallels between other aspects of motor neuron and interneuron development, it seems likely that at least some of the mechanisms will be held in common. An important but still unresolved issue is the correlation between gene expression and neuronal function. To what extent does expression of a transcription factor reflect the functional identity of the neuron? For the most part, genetic studies have relied on cell body location, axon projections, and neurotransmitter phenotypes to define subtype identities. For example, the position and projection patterns of Evx1 neurons suggest that they may be a part of a crossed reflex pathway similar to those reported in cat. These neurons are also in a location that is similar to that of interneurons in the neonatal spinal cord, which have been shown by physiological studies to be required for alternate activation of the left and the right limb (Kjaerulff and Kiehn 1996Kjaerulff O Kiehn O J. Neurosci. 1996; 16: 5777-5794PubMed Google Scholar, Moran-Rivard et al. 2001Moran-Rivard L Kagawa T Saueressig H Gross M.K Burrill J Goulding M Neuron. 2001; 29 (this issue,): 385-399Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar). However, until recently, few studies have attempted to correlate molecular phenotypes of these cells with phsyiological analyses. In cases where such studies have been carried out (for instance, in the case of physiological analyses of the En1+ V1 interneurons), the results suggest that a note of caution is appropriate when using gene expression alone to define functional subtypes of neurons. To address similar issues, Wenner and colleagues (Wenner et al. 2000Wenner P.W O'Donovan M Matise M.P J. Neurophysiol. 2000; 84: 2651Crossref PubMed Scopus (56) Google Scholar) recently made use of whole-cell recording in isolated spinal cord preparations to assess the synaptic connections of En1+ interneurons in the chicken spinal cord. While most of the En1+ neurons made monosynaptic connections with motor neurons, they were as likely as the non-En1+ interneurons to receive direct connections from the sensory afferents, suggesting that En1 expression may not alone be sufficient to define a restricted functional subclass of interneurons. The Pierani paper appears to also shed some light on this dilemma. Examination of the Dbx1 knockout revealed that while the majority of En1+ neurons are generated from Dbx1− precursors, a minority fraction of En1+ neurons are generated from precursors that transiently express Dbx1 (Pierani et al. 2001Pierani A Moran-Rivard L Sunshine M.J Littman D.R Goulding M Jessell T.M Neuron. 2001; 29 (this issue,): 367-384Abstract Full Text Full Text PDF PubMed Scopus (264) Google Scholar). Despite these genetic and physiological differences among the En1+ interneurons, it is worth noting that at present there is no experimental evidence that neurons with subtle physiological differences have different roles in the control of motor circuits and it remains possible that these neurons share common functions in sensory-motor coordination. A complete understanding of the role that distinct neuronal subclasses with defined transcription factor expression patterns play in circuit behavior will require physiological and behavioral analyses in the adult. An important characteristic of the motor circuits is the ability of animals to simultaneously control and coordinate movement of the four limbs (Figure 2). Motor rhythms generated by a CPG are communicated to similar circuits that control movements in the other limbs by two sets of interneurons. The commissural interneurons coordinate movement of limbs on the opposite sides of the body, whereas propriospinal neurons coordinate activity of the ipsilateral motor neurons. At present, neurons within the CPGs and those that connect them have not been identified by physiological or genetic methodologies. Nevertheless, it seems clear that understanding neural control of locomotion will require identification of such neural classes. Genetic markers will be useful tools for labeling and testing the function of physiologically characterized interneurons. How might we move from identification of genetic markers for embryonic neurons toward understanding the adult circuits? What approaches seem feasible and what are the caveats and problems that still remain? Two examples of genetic techniques that have been used to analyze neural circuits are discussed below. One approach is to use a combination of cell-specific gene targeting strategies to ablate selected neurons. As such, it should be possible to generate cell-type-specific or potentially even circuit-specific knockouts. Similar approaches have already been used to dissect circuits in other systems. For instance, an immunotoxin-mediated cell-targeting technique has been used to dissect the role of the cerebellar golgi cells in motor coordination, and it seems that, in principle, this technique should be applicable to the spinal cord circuits (Watanabe et al. 1998Watanabe D Inokawa H Hashimoto K Suzuki N Kano M Shigemoto R Hirano T Toyama K Kaneko S Yokoi M et al.Cell. 1998; 95: 17-27Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar). The main advantage of the immunotoxin-mediated approach is that circuits can be specifically ablated in the adult, thereby circumventing potential developmental effects of cell ablation. An alternative, less drastic approach than killing cells in a circuit, might involve the misexpression of specific ion channels to change the excitability of the test neurons. A variant of this strategy has been used effectively in invertebrate systems. For instance, in C. elegans it is known that five pairs of command interneurons control coordinated movement of the worm. By targeting a mutated and constitutively active version of the non-NMDA glutamate receptor glr-1 to these neurons, Zheng and colleagues were able to demonstrate a role for this circuit in particular locomotor behavior (Zheng et al. 1999Zheng Y Brockie P.J Mellem J.E Madsen D.M Maricq A.V Neuron. 1999; 24: 347-361Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar). The main advantage of this technique over the ablation paradigms is that the test neurons remain part of an intact neural circuit. The recent studies provide us with insights into the genetic mechanisms that control development of the spinal cord. By identifying genetic markers that label specific cell types in the spinal cord, these studies provide a potential interface between developmental studies in the embryo and physiological studies of the motor function in the adult. A unifying goal for all neuroscientists, be they focused on the molecular, cellular, or systems levels approaches or working in vertebrates or invertebrates, is to understand how neurons control behaviors. Ultimately, from a developmental standpoint, this comes down to understanding how neurons are generated, how groups of neurons are assembled into networks, and how then the activity of these circuits is coordinated to generate complex behavior. The recent work defining genes that control spinal interneuron cell fate is a critical step in this direction.Tanabe William Jessell 1988Tanabe Y William C Jessell T.M Cell. 1988; 95: 67-80Abstract Full Text Full Text PDF Scopus (295) Google Scholar" @default.
• W2023956478 created "2016-06-24" @default.
• W2023956478 creator A5030490799 @default.
• W2023956478 creator A5077513831 @default.
• W2023956478 date "2001-02-01" @default.
• W2023956478 modified "2023-10-16" @default.
• W2023956478 title "Spinal Motor Circuits" @default.
• W2023956478 cites W1491433834 @default.
• W2023956478 cites W1982630660 @default.
• W2023956478 cites W1983983875 @default.
• W2023956478 cites W1993982470 @default.
• W2023956478 cites W2000101032 @default.
• W2023956478 cites W2006169062 @default.
• W2023956478 cites W2009266803 @default.
• W2023956478 cites W2010364898 @default.
• W2023956478 cites W2028183921 @default.
• W2023956478 cites W2058615553 @default.
• W2023956478 cites W2060601033 @default.
• W2023956478 cites W2070533417 @default.
• W2023956478 cites W2081235375 @default.
• W2023956478 cites W2103635980 @default.
• W2023956478 cites W2110068087 @default.
• W2023956478 cites W2151892983 @default.
• W2023956478 cites W2155291163 @default.
• W2023956478 cites W2161691215 @default.
• W2023956478 cites W2260413756 @default.
• W2023956478 cites W4246912672 @default.
• W2023956478 cites W4248042899 @default.
• W2023956478 cites W4298312742 @default.
• W2023956478 doi "https://doi.org/10.1016/s0896-6273(01)00208-2" @default.
• W2023956478 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11239425" @default.
• W2023956478 hasPublicationYear "2001" @default.
• W2023956478 type Work @default.
• W2023956478 sameAs 2023956478 @default.
• W2023956478 citedByCount "25" @default.
• W2023956478 countsByYear W20239564782012 @default.
• W2023956478 countsByYear W20239564782014 @default.
• W2023956478 countsByYear W20239564782017 @default.
• W2023956478 countsByYear W20239564782021 @default.
• W2023956478 countsByYear W20239564782022 @default.
• W2023956478 countsByYear W20239564782023 @default.
• W2023956478 crossrefType "journal-article" @default.
• W2023956478 hasAuthorship W2023956478A5030490799 @default.
• W2023956478 hasAuthorship W2023956478A5077513831 @default.
• W2023956478 hasBestOaLocation W20239564781 @default.
• W2023956478 hasConcept C15744967 @default.
• W2023956478 hasConcept C169760540 @default.
• W2023956478 hasConcept C71924100 @default.
• W2023956478 hasConcept C99508421 @default.
• W2023956478 hasConceptScore W2023956478C15744967 @default.
• W2023956478 hasConceptScore W2023956478C169760540 @default.
• W2023956478 hasConceptScore W2023956478C71924100 @default.
• W2023956478 hasConceptScore W2023956478C99508421 @default.
• W2023956478 hasIssue "2" @default.
• W2023956478 hasLocation W20239564781 @default.
• W2023956478 hasLocation W20239564782 @default.
• W2023956478 hasOpenAccess W2023956478 @default.
• W2023956478 hasPrimaryLocation W20239564781 @default.
• W2023956478 hasRelatedWork W2053487507 @default.
• W2023956478 hasRelatedWork W2067108088 @default.
• W2023956478 hasRelatedWork W2077865380 @default.
• W2023956478 hasRelatedWork W2083375246 @default.
• W2023956478 hasRelatedWork W2085372204 @default.
• W2023956478 hasRelatedWork W2134894512 @default.
• W2023956478 hasRelatedWork W2748952813 @default.
• W2023956478 hasRelatedWork W2765597752 @default.
• W2023956478 hasRelatedWork W2899084033 @default.
• W2023956478 hasRelatedWork W2931662336 @default.
• W2023956478 hasVolume "29" @default.
• W2023956478 isParatext "false" @default.
• W2023956478 isRetracted "false" @default.
• W2023956478 magId "2023956478" @default.
• W2023956478 workType "article" @default.