Children with congenital colorectal malformations during the UK Sars-CoV-2 pandemic lockdown: an assessment of telemedicine and impact on health.

PURPOSE: This pilot study was designed to assess bowel function and quality of life (QoL) in children and adolescents with congenital colorectal malformations (CCM) during the first UK COVID lockdown period. METHODS: Changes in health were assessed through semi-structured interviews, gastrointestinal functional outcomes using Krickenbeck scoring and QoL by the modified disease-specific HAQL (Hirschsprung's disease anorectal malformation quality of life questionnaire). The State-Trait Anxiety Inventory (STAI)™ for adults was used to assess parental anxiety. RESULTS: Thirty-two families were interviewed; 19 (59%) reported no change in their child's health during the lockdown, 5 (16%) a deterioration and 8 (25%) an improvement. Neither the severity of the CCM, nor the degree of bowel dysfunction, correlated with any deterioration. The HAQL score was not correlated to a change in health. Anxiety scores ranged from no anxiety to clinical concerns. Telemedicine was well accepted by 28/32 parents (88%); however, in-person appointments were preferred if there were clinical concerns. CONCLUSION: In the follow-up of children and adolescents with CCM during the first UK lockdown using telemedicine we found that over half had stable health conditions. Patients needing additional care could not be predicted by the severity of their disease or their bowel function alone.

Low-fidelity Paediatric Surgical Simulation: Description of Models in Low-Resource Settings.

BACKGROUND: Surgical simulation is an important aspect of competency-based training. Recent trends in paediatric surgical simulations have migrated towards high-fidelity simulation with advanced technology resulting in models which are expensive and largely inaccessible in low- and middle-income countries. METHODS: This article describes four wet simulation models of common surgical procedures in paediatric population created with animal tissue from local abattoir. The models are designed to provide a framework for others to make the models and benefit from the training opportunity they provide especially in low-middle-income countries. RESULTS: The models created in the wet laboratory are neonatal bowel anastomosis, duodenoduodenostomy for discrepancy anastomosis, gastrostomy and pyeloplasty. These models are easily reproducible in resource-challenged healthcare setting as they are low cost, utilise locally available resources and require only a basic set of surgical instruments with which to perform the procedures. CONCLUSION: These models provide locally accessible material for sustainable training programmes which are fundamental in developing safe and affordable surgical care worldwide.

Assessing the validity of the clinician-rated distress thermometer in palliative care.

BACKGROUND: The distress of patients suffering from a terminal illness can lead to a state of despair and requests for euthanasia and assisted suicide. It is a major challenge for palliative care workers. The Distress Thermometer (DT) is recommended by the National Comprehensive Cancer Network as a means of more easily assessing distress. It is available as a Self-assessment reported Distress Thermometer, but for a wider use in palliative care it should also be implemented in the form of a clinician-reported outcome (clinRO). Clinicians need to rate patient's distress when the patient is not able to do so (subject that cannot be addressed, defensive patient…). The primary aim of the quantitative study was to assess the validity of the Clinician-Rated Distress Thermometer in palliative care. METHOD: The assessments were performed by teams working in three palliative care centres. The primary endpoint was concordance between the patient and clinicians' responses via Lin's concordance coefficient. Eligible patients were aged 18 years or older, suffering from a severe disease in the palliative phase, and with a sufficient level of awareness to consent to participate in the study. A total of 51 patients were recruited, 55% were male, with a mean age of 65.8 years [39-90 years]. RESULTS: Three hundred sixty-four clinician-Rated Distress Thermometer and 467 Self-Reported Distress Thermometer were performed. Only 364 of the 467 Self-Reported Distress Thermometer were used for the study, as investigators did not systematically ask the patient to give an account of his distress. Concordance between patient and clinician responses: The Lin's concordance coefficient with a threshold (alpha) of 5% was 0.46 [0.38; 0.54]. At the first assessment, it was 0.61 [0.44; 0.79]. The Cohen's kappa coefficient was 0.52, with a concordance rate of 79.6%. The sensitivity was 82.9% [66.4-93.4] and the specificity 71.4% [41.9-91.6]. CONCLUSION: The first assessment gave the best results in terms of concordance between Clinician-Rated DT and Self-Reported DT. In the next assessments, the Clinician-Rated DT were less consistent with the patients' Self-Reported DT.

[IPADAM quali study. Intervention of the Pharmacist in the Issue of Self-medication: Experience of pharmacy team focus groups and patients' perceptions]. / IPADAM quali « Interventions Pharmaceutiques À propos du Dossier pharmaceutique et de l'AutoMédication ¼ : expérience des équipes officinales et ressenti des patients.

OBJECTIVES: This study had two main aims: (i) document the experience of community pharmacists receiving a spontaneous request for ibuprofen and oral pseudoephedrine, and their use of pharmaceutical records, and (ii) explore patients' perceptions of pharmaceutical records and pharmaceutical interventions. METHODS: The study was conducted over two weeks between February and April 2014 in 482 community pharmacies and 8 French faculties of pharmacy. It was based on data collected by pharmacy team focus groups during patient telephone interviews using standardized question grids. Textual and thematic analyses were made of the patient responses. RESULTS: Four pharmacy team focus groups carried out 49 telephone interviews. Examination of the practice of the groups showed that pharmaceutical interventions, although incompletely registered, are performed on a daily basis and enhance the value of the pharmacist's function. Analysis of the telephone interviews also showed the importance of the advisory role of the pharmacist in dispensing an optional medical prescription. The thematic analysis of the results identified a positive response of patients to pharmaceutical interventions if made by their regular pharmacist and accompanied by explanatory information. The focus groups and patients agreed that pharmaceutical records were not consulted often enough. CONCLUSION: This study underlines the need for greater safety in the use of optional medical prescription drugs. Promoting responsible self-medication in compliance with proper use should include systematic reference to a PR and informed dialogue with the patient.

[Pharmacist's interview with type 2 diabetes: Development of a follow-up form]. / L'entretien pharmaceutique pour le patient diabétique de type 2 : élaboration d'une fiche de suivi.

OBJECTIVES: Type 2 diabetes is a major public health concern because of its prevalence, the severity of complications and the financial implications. Compliance and patient's autonomy in medications intake play key roles in the success of treatment. Pharmacists' interviews ensure an optimized and individual follow-up. Type 2 diabetes is not one of the targeted diseases to perform pharmacists' interviews on under Health Insurance. We thus judged useful to contribute to their development. METHODS: We applied a cross-disciplinary methodological process in order to define the specifications of the follow-up form useful to conduct the pharmacist's interview 1 by focusing on the identification of a non-compliance and its origins. A feasibility study was carried out in order to check its workability to the pharmacy practice. RESULTS: The follow-up form, associated with a pharmacist practical guide, includes 3 parts: (1) General informations, (2) Survey establishing patient's knowledge, (3) Summary including a level of knowledge assessment grid. Outcomes provide a long but appropriate-felt duration, few difficulties to conduct the interview and a proven usefulness in 90% of all cases that make the follow-up form suitable to the pharmacy practice. CONCLUSIONS: This tool could serve as a model for the pharmacist to conduct his future interviews for the type 2 diabetes patients, thus improving patient care, together with other health professionals.

Localisation of the SMC loading complex Nipbl/Mau2 during mammalian meiotic prophase I.

Evidence from lower eukaryotes suggests that the chromosomal associations of all the structural maintenance of chromosome (SMC) complexes, cohesin, condensin and Smc5/6, are influenced by the Nipbl/Mau2 heterodimer. Whether this function is conserved in mammals is currently not known. During mammalian meiosis, very different localisation patterns have been reported for the SMC complexes, and the localisation of Nipbl/Mau2 has just recently started to be investigated. Here, we show that Nipbl/Mau2 binds on chromosomal axes from zygotene to mid-pachytene in germ cells of both sexes. In spermatocytes, Nipbl/Mau2 then relocalises to chromocenters, whereas in oocytes it remains bound to chromosomal axes throughout prophase to dictyate arrest. The localisation pattern of Nipbl/Mau2, together with those seen for cohesin, condensin and Smc5/6 subunits, is consistent with a role as a loading factor for cohesin and condensin I, but not for Smc5/6. We also demonstrate that Nipbl/Mau2 localises next to Rad51 and γH2AX foci. NIPBL gene deficiencies are associated with the Cornelia de Lange syndrome in humans, and we find that haploinsufficiency of the orthologous mouse gene results in an altered distribution of double-strand breaks marked by γH2AX during prophase I. However, this is insufficient to result in major meiotic malfunctions, and the chromosomal associations of the synaptonemal complex proteins and the three SMC complexes appear cytologically indistinguishable in wild-type and Nipbl (+/-) spermatocytes.

Selective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats.

The natural reservoir of Ebola virus (EBOV), agent of a zoonosis burdening several African countries, remains unidentified, albeit evidence points towards bats. In contrast, the ecology of the related Marburg virus is much better understood; with experimental infections of bats being instrumental for understanding reservoir-pathogen interactions. Experiments have focused on elucidating reservoir competence, infection kinetics and specifically horizontal transmission, although, vertical transmission plays a key role in many viral enzootic cycles. Herein, we investigate the permissiveness of Angolan free-tailed bats (AFBs), known to harbour Bombali virus, to other filoviruses: Ebola, Marburg, Taï Forest and Reston viruses. We demonstrate that only the bats inoculated with EBOV show high and disseminated viral replication and infectious virus shedding, without clinical disease, while the other filoviruses fail to establish productive infections. Notably, we evidence placental-specific tissue tropism and a unique ability of EBOV to traverse the placenta, infect and persist in foetal tissues of AFBs, which results in distinct genetic signatures of adaptive evolution. These findings not only demonstrate plausible routes of horizontal and vertical transmission in these bats, which are expectant of reservoir hosts, but may also reveal an ancillary transmission mechanism, potentially required for the maintenance of EBOV in small reservoir populations.

[Effect of inorganic salts on free radicals production by near UV irradiation of frozen aqueous solutions of adenine and its derivatives].

The addition of Na and Ca chlorides to adenine (A), adenosine (Ado) and adenosine diphosphate solutions at pH 5.3 has been shown to result in intensification of EPR signals in samples irradiated by near UV at 77 K and appearance of signals of Cl2-* and peroxyl radicals. The peroxyl radicals contribution can exceed 30% of total amount of paramagnetic products. The addition of inorganic phosphate reduces the contribution of peroxyl radicals. Possible mechanisms of the processes involved are discussed.

Multispecies model of cell lineages and feedback control in solid tumors.

We develop a multispecies continuum model to simulate the spatiotemporal dynamics of cell lineages in solid tumors. The model accounts for protein signaling factors produced by cells in lineages, and nutrients supplied by the microenvironment. Together, these regulate the rates of proliferation, self-renewal and differentiation of cells within the lineages, and control cell population sizes and distributions. Terminally differentiated cells release proteins (e.g., from the TGFß superfamily) that feedback upon less differentiated cells in the lineage both to promote differentiation and decrease rates of proliferation (and self-renewal). Stem cells release a short-range factor that promotes self-renewal (e.g., representative of Wnt signaling factors), as well as a long-range inhibitor of this factor (e.g., representative of Wnt inhibitors such as Dkk and SFRPs). We find that the progression of the tumors and their response to treatment is controlled by the spatiotemporal dynamics of the signaling processes. The model predicts the development of spatiotemporal heterogeneous distributions of the feedback factors (Wnt, Dkk and TGFß) and tumor cell populations with clusters of stem cells appearing at the tumor boundary, consistent with recent experiments. The nonlinear coupling between the heterogeneous expressions of growth factors and the heterogeneous distributions of cell populations at different lineage stages tends to create asymmetry in tumor shape that may sufficiently alter otherwise homeostatic feedback so as to favor escape from growth control. This occurs in a setting of invasive fingering, and enhanced aggressiveness after standard therapeutic interventions. We find, however, that combination therapy involving differentiation promoters and radiotherapy is very effective in eradicating such a tumor.

[Influence of inorganic phosphate on the production of free radicals in UV-irradiated frozen tyrosine solutions].

The role of inorganic phosphate as a catalyzer of the production of tyrosyl radical in frozen tyrosine solutions irradiated with near UV light at 77K has been demonstrated by the EPR method. It was shown that the increase in the yield of tyrosyl radicals at pH < 7 correlates with the production of H* atoms and can be explained by the fact that phosphate acts as an acceptor of photoejected electrons. At pH > 7, the increase in the yield of tyrosyl radicals is accompanied by the production of phosphate radicals and OH* and is caused, presumably, by the catalysis of the formation of triplet states of tyrosine molecules by the HPO4(2-) form of phosphate, the fact shown by a number of authors. A quantitative estimation of relative concentrations of photosensitized paramagnetic products was carried out on the basis of computer analysis of resultant EPR signals.

Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir - Mastomys natalensis.

Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir. The natural route of infection and transmission of LASV within M. natalensis remains unknown, and the clinical impact of LASV in M. natalensis is mostly undescribed. Herein, using an outbred colony of M. natalensis, we investigate the replication and dissemination dynamics of LASV in this reservoir following various inoculation routes. Inoculation with LASV, regardless of route, resulted in a systemic infection and accumulation of abundant LASV-RNA in many tissues. LASV infection in the Natal multimammate mice was subclinical, however, clinical chemistry values were transiently altered and immune infiltrates were observed histologically in lungs, spleens and livers, indicating a minor disease with coordinated immune responses are elicited, controlling infection. Intranasal infection resulted in unique virus tissue dissemination dynamics and heightened LASV shedding, compared to subcutaneous inoculation. Our study provides important insights into LASV infection in its natural reservoir using a contemporary infection system, demonstrating that specific inoculation routes result in disparate dissemination outcomes, suggesting intranasal inoculation is important in the maintenance of LASV in the natural reservoir, and emphasizes that selection of the appropriate inoculation route is necessary to examine aspects of viral replication, transmission and responses to zoonotic viruses in their natural reservoirs.

Relationship between neuronal migration and cell-substratum adhesion: laminin and merosin promote olfactory neuronal migration but are anti-adhesive.

Regulation by the extracellular matrix (ECM) of migration, motility, and adhesion of olfactory neurons and their precursors was studied in vitro. Neuronal cells of the embryonic olfactory epithelium (OE), which undergo extensive migration in the central nervous system during normal development, were shown to be highly migratory in culture as well. Migration of OE neuronal cells was strongly dependent on substratum-bound ECM molecules, being specifically stimulated and guided by laminin (or the laminin-related molecule merosin) in preference to fibronectin, type I collagen, or type IV collagen. Motility of OE neuronal cells, examined by time-lapse video microscopy, was high on laminin-containing substrata, but negligible on fibronectin substrata. Quantitative assays of adhesion of OE neuronal cells to substrata treated with different ECM molecules demonstrated no correlation, either positive or negative, between the migratory preferences of cells and the strength of cell-substratum adhesion. Moreover, measurements of cell adhesion to substrata containing combinations of ECM proteins revealed that laminin and merosin are anti-adhesive for OE neuronal cells, i.e., cause these cells to adhere poorly to substrata that would otherwise be strongly adhesive. The evidence suggests that the anti-adhesive effect of laminin is not the result of interactions between laminin and other ECM molecules, but rather an effect of laminin on cells, which alters the way in which cells adhere. Consistent with this view, laminin was found to interfere strongly with the formation of focal contacts by OE neuronal cells.

Cerebroglycan: an integral membrane heparan sulfate proteoglycan that is unique to the developing nervous system and expressed specifically during neuronal differentiation.

Heparan sulfate proteoglycans (HSPGs) are found on the surface of all adherent cells and participate in the binding of growth factors, extracellular matrix glycoproteins, cell adhesion molecules, and proteases and antiproteases. We report here the cloning and pattern of expression of cerebroglycan, a glycosylphosphatidylinositol (GPI)-anchored HSPG that is found in the developing rat brain (previously referred to as HSPG M13; Herndon, M. E., and A. D. Lander. 1990. Neuron. 4:949-961). The cerebroglycan core protein has a predicted molecular mass of 58.6 kD and five potential heparan sulfate attachment sites. Together with glypican (David, G., V. Lories, B. Decock, P. Marynen, J.-J. Cassiman, and H. Van den Berghe. 1990. J. Cell Biol. 111:3165-3176), it defines a family of integral membrane HSPGs characterized by GPI linkage and conserved structural motifs, including a pattern of 14 cysteine residues that is absolutely conserved. Unlike other known integral membrane HSPGs, including glypican and members of the syndecan family of transmembrane proteoglycans, cerebroglycan is expressed in only one tissue: the nervous system. In situ hybridization experiments at several developmental stages strongly suggest that cerebroglycan message is widely and transiently expressed by immature neurons, appearing around the time of final mitosis and disappearing after cell migration and axon outgrowth have been completed. These results suggest that cerebroglycan may fulfill a function related to the motile behaviors of developing neurons.

Purification of a factor that promotes neurite outgrowth: isolation of laminin and associated molecules.

When culture medium, conditioned by any of several cell types, is applied to a polycationic substratum, a substance is adsorbed that causes neurons cultured on that substratum to extend processes (neurites) rapidly and profusely. We have purified the factor responsible for this effect from medium conditioned by bovine corneal endothelial cells, and have shown that it is composed of the glycoprotein laminin and two associated laminin-binding molecules: a sulfated protein known as entactin, and a large heparan sulfate proteoglycan. Of these molecules, only laminin was found to be present throughout the purification in all fractions possessing neurite outgrowth-promoting activity and absent from all fractions lacking activity. Laminin, purified from other sources, has been shown previously to promote extensive outgrowth by cultured neurons. These and other data presented here support the conclusion that laminin is responsible for the neurite outgrowth-promoting activity of the conditioned medium factor. Evidence is also presented that the association of a proteoglycan with laminin promotes efficient attachment of laminin to polycationic substrata, particularly in the presence of competing molecules.

Mapping the heparin-binding sites on type I collagen monomers and fibrils.

The glycosaminoglycan chains of cell surface heparan sulfate proteoglycans are believed to regulate cell adhesion, proliferation, and extracellular matrix assembly, through their interactions with heparin-binding proteins (for review see Ruoslahti, E. 1988. Annu. Rev. Cell Biol. 4:229-255; and Bernfield, M., R. Kokenyesi, M. Kato, M. T. Hinkes, J. Spring, R. L. Gallo, and E. J. Lose. 1992. Annu. Rev. Cell Biol. 8:365-393). Heparin-binding sites on many extracellular matrix proteins have been described; however, the heparin-binding site on type I collagen, a ubiquitous heparin-binding protein of the extracellular matrix, remains undescribed. Here we used heparin, a structural and functional analogue of heparan sulfate, as a probe to study the nature of the heparan sulfate proteoglycan-binding site on type I collagen. We used affinity coelectrophoresis to study the binding of heparin to various forms of type I collagen, and electron microscopy to visualize the site(s) of interaction of heparin with type I collagen monomers and fibrils. Using affinity coelectrophoresis it was found that heparin has similar affinities for both procollagen and collagen fibrils (Kd's approximately 60-80 nM), suggesting that functionally similar heparin-binding sites exist in type I collagen independent of its aggregation state. Complexes of heparin-albumin-gold particles and procollagen were visualized by rotary shadowing and electron microscopy, and a preferred site of heparin binding was observed near the NH2 terminus of procollagen. Native or reconstituted type I collagen fibrils showed one region of significant heparin-gold binding within each 67-nm period, present near the division between the overlap and gap zones, within the "a" bands region. According to an accepted model of collagen fibril structure, our data are consistent with the presence of a single preferred heparin-binding site near the NH2 terminus of the collagen monomer. Correlating these data with known type I collagen sequences, we suggest that the heparin-binding site in type I collagen may consist of a highly basic triple helical domain, including several amino acids known sometimes to function as disaccharide acceptor sites. We propose that the heparin-binding site of type I collagen may play a key role in cell adhesion and migration within connective tissues, or in the cell-directed assembly or restructuring of the collagenous extracellular matrix.

Characterization of a factor that promotes neurite outgrowth: evidence linking activity to a heparan sulfate proteoglycan.

Rat sympathetic neurons, plated onto extracellular matrix produced by cultured bovine corneal endothelial cells, rapidly extended neurites in the absence of nerve growth factor (NGF). The response was unaffected by antiserum to NGF. Rapid outgrowth also occurred when sympathetic neurons were plated onto polylysine-coated surfaces that had been exposed to serum-free medium conditioned by corneal endothelial cells (CMSF). A response was seen even when the neurons were cultured without serum. When plated onto a polylysine-coated dish treated with CMSF over half its surface, only the neurons on the treated half extended neurites. The active factor in CMSF was destroyed by trypsin, acid (pH 1.6), base (pH 12.7), or heating to 80 degrees C; it was stable to heating to 60 degrees C, collagenase, deoxyribonuclease, and neuraminidase. The factor elutes just after the void volume of a Sepharose 6B column. In associative cesium chloride gradients, it sediments as a peak centered at a density of 1.36-1.37, corresponding to a peak of material that can be biosynthetically labeled with [35S]sulfate or [3H]leucine. Material from this fraction was inactivated by heparinase, but not chondroitinase ABC, implying that a heparin sulfate proteoglycan is essential for the factor's activity. Inactivation by contaminants in the heparinase preparation was ruled out. Further purification indicated that the active factor may exist as an aggregate containing a heparin sulfate proteoglycan and other molecules. CMSF also promoted neurite outgrowth by other types of neurons. Furthermore, a variety of cell types were shown to produce factors similar to that in CMSF.

[Effect of irradiation intensity on the production of free radicals by near-UV photosensitization of frozen adenine solutions with an inorganic phosphate].

The effect of light intensity on the production of free radicals by near-UV photosensitization at 77 K of frozen aqueous solutions of adenine in the presence of inorganic phosphate has been studied. A quantitative estimation of relative concentrations of the products: hydrogen atoms (H*), adenine, phosphate and OH* radicals was carried out using the computer analysis of EPR spectra of irradiated samples. It was found that the formation of phosphate and OH* radicals in a photosystem results predominantly from the absorption of two photons in the band of illumination. The production of H* occurs in two ways, which involve the absorption of one photon or two photons.

Pertussis toxin specifically inhibits growth cone guidance by a mechanism independent of direct G protein inactivation.

An assay employing patterned laminin substrata was used to screen for compounds that disrupt neurite guidance. One molecule, pertussis toxin, caused neurites to wander from patterns that normally guided them, yet had no significant effect on rates of neurite outgrowth. Wandering was greatest on patterns requiring frequent guidance (e.g., laminin stripes with periodic gaps). Surprisingly, the B oligomer of pertussis toxin, which lacks the subunit that inactivates G proteins, was equipotent at disrupting neurite guidance. Pertussis toxin probably acts by binding cell surface carbohydrates, since neurites lacking complex-type N-linked oligosaccharides were insensitive to the effects of the toxin. The B oligomer also blocked growth cone collapse induced by a brain membrane-derived factor; such factors are thought to act as repulsive guidance cues in vivo. That a single reagent can inhibit neuronal responses to both attractive and repulsive guidance cues suggests that such cues may share signaling pathways.

A diverse set of developmentally regulated proteoglycans is expressed in the rat central nervous system.

Cellular interactions in neural development are influenced by various extracellular proteins, many of which bind glycosaminoglycans or proteoglycans. Precise functions of nervous system proteoglycans remain unknown, in part because neural proteoglycan composition is poorly understood. In this study, 25 putative proteoglycan core proteins were identified in subcellular fractions of rat brain. Levels of many of these varied considerably during development. Membrane-associated proteoglycans included two heparan sulfate proteoglycans (cores of 50 and 59 kd) that are covalently linked to glycosyl-phosphatidylinositol lipid, as well as several that appear to aggregate either with themselves or with copurifying proteins. These data indicate that brain proteoglycans exhibit the abundance, structural diversity, and developmental regulation that would be anticipated for molecules with diverse developmental functions.

Inhibitors and promoters of thalamic neuron adhesion and outgrowth in embryonic neocortex: functional association with chondroitin sulfate.

When embryonic thalamic neurons are plated onto living slices of mouse forebrain, cell attachment and neurite outgrowth on different layers of the developing cerebral cortex vary dramatically, in ways that correlate with the timing and pattern of thalamocortical innervation. These layer-specific differences can be eliminated from embryonic day 16 slices by enzymatic removal of chondroitin sulfate (CS). The cortical plate (a zone avoided by thalamic axons in vivo) possesses inhibitory activity (anti-adhesive, neurite repelling) and the intermediate zone and subplate (in which thalamic axons normally grow) possess stimulatory activity (adhesive, neurite promoting), both of which are chondroitinase sensitive. These opposing activities appear not to reflect the presence of different CS proteoglycans (CSPGs) in different zones, but rather the presence of differentially localized CS-binding molecules, which can be competed away by soluble CS. This model reconciles conflicting reports on the actions of CSPGs in neural development, and suggests a role for CSPGs in the organization of matrix-bound cues in the brain.