The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains

We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2 contribute to selectivity, and most mutations, including mutation of residues in the triplets GYG and GFG in P1 and P2, made channels nonselective. We interpret the effects of these—and of other mutations—in terms of the way the pore is likely to be stabilised structurally. We show also that residues in the outer pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of selectivity (e.g. I94S, G95A) were associated with slowing of the response of channels to depolarisation. More important physiologically, pH sensitivity is also lost or altered by such mutations. Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter

The impact of cluster connectedness on firm innovation: R&D effort and outcomes in the textile industry

This is an Author's Accepted Manuscript of an article published in "The impact of cluster connectedness on firm innovation: R&D effort and outcomes in the textile industry" version of the article as published in the Entrepreneurship and Regional Development, 2012 september,[copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/08985626.2012.710260"[EN] Recent research into the clustering effect on firms has moved away from a simplistic view to a more complex approach. More realistic and complex causal relationships are now considered when analysing these territorial networks. Specifically, this paper attempts to analyse how cluster connect- edness moderates the relationship of a firm's innovation effort and the results obtained from this effort. We want to question the commonly accepted direct and positive impact of R&D effort, and moreover, we suggest the existence of a saturation effect and that the level of cluster's inter-connectedness in the cluster moderates this effect. We have developed our empirical study focusing on the Spanish textile industrial cluster. This is a complex manufacturing industry that uses relatively low-technology manufacturing and R&D. Our findings suggest that the degree to which a firm is involved with, or connected to, other firms in the cluster can moderate the effect of the R&D effort on its innovation results. More generally, we aim to contribute to the discussion on the degree to which firms should be involved in the cluster network in order to operate efficiently and gain the maximum competitive advantages. Our findings have implications both in recent cluster and network literature as well for institutional policy.Molina Morales, FX.; Expósito Langa, M. (2012). The impact of cluster connectedness on firm innovation: R&D effort and outcomes in the textile industry. Entrepreneurship and Regional Development. 24(7-8):685-704. doi:10.1080/08985626.2012.710260S685704247-8Agarwal, R., Audretsch, D., & Sarkar, M. B. (2007). The process of creative construction: knowledge spillovers, entrepreneurship, and economic growth. Strategic Entrepreneurship Journal, 1(3-4), 263-286. doi:10.1002/sej.36Aharonson, B. S., Baum, J. A. C., & Feldman, M. P. (2007). Desperately seeking spillovers? Increasing returns, industrial organization and the location of new entrants in geographic and technological space. Industrial and Corporate Change, 16(1), 89-130. doi:10.1093/icc/dtl034Albino, V., Carbonara, N., & Giannoccaro, I. (2006). Innovation in industrial districts: An agent-based simulation model. International Journal of Production Economics, 104(1), 30-45. doi:10.1016/j.ijpe.2004.12.023Audretsch, D. B., & Lehmann, E. E. (2005). Does the Knowledge Spillover Theory of Entrepreneurship hold for regions? Research Policy, 34(8), 1191-1202. doi:10.1016/j.respol.2005.03.012Bell, G. G. (2005). Clusters, networks, and firm innovativeness. Strategic Management Journal, 26(3), 287-295. doi:10.1002/smj.448Bell, M., & Albu, M. (1999). Knowledge Systems and Technological Dynamism in Industrial Clusters in Developing Countries. World Development, 27(9), 1715-1734. doi:10.1016/s0305-750x(99)00073-xBelussi, F., & Arcangeli, F. (1998). A typology of networks: flexible and evolutionary firms. Research Policy, 27(4), 415-428. doi:10.1016/s0048-7333(98)00074-2Cantwell, J., & Piscitello, L. (2005). Recent Location of Foreign-owned Research and Development Activities by Large Multinational Corporations in the European Regions: The Role of Spillovers and Externalities. Regional Studies, 39(1), 1-16. doi:10.1080/0034340052000320824Boschma, R. A., & ter Wal, A. L. J. (2007). Knowledge Networks and Innovative Performance in an Industrial District: The Case of a Footwear District in the South of Italy. Industry & Innovation, 14(2), 177-199. doi:10.1080/13662710701253441Brass, D. J. (1984). Being in the Right Place: A Structural Analysis of Individual Influence in an Organization. Administrative Science Quarterly, 29(4), 518. doi:10.2307/2392937Breschi, S. (2001). Knowledge Spillovers and Local Innovation Systems: A Critical Survey. Industrial and Corporate Change, 10(4), 975-1005. doi:10.1093/icc/10.4.975CALANTONE, R. (1997). New product activities and performance: The moderating role of environmental hostility. Journal of Product Innovation Management, 14(3), 179-189. doi:10.1016/s0737-6782(97)00004-0Chell, E., & Baines, S. (2000). Networking, entrepreneurship and microbusiness behaviour. Entrepreneurship & Regional Development, 12(3), 195-215. doi:10.1080/089856200413464Chung, S. (Andy), Singh, H., & Lee, K. (2000). Complementarity, status similarity and social capital as drivers of alliance formation. Strategic Management Journal, 21(1), 1-22. doi:10.1002/(sici)1097-0266(200001)21:13.0.co;2-pCockburn, I. M., & Henderson, R. M. (2003). Absorptive Capacity, Coauthoring Behavior, and the Organization of Research in Drug Discovery. The Journal of Industrial Economics, 46(2), 157-182. doi:10.1111/1467-6451.00067Cohen, W. M., & Levinthal, D. A. (1989). Innovation and Learning: The Two Faces of R & D. The Economic Journal, 99(397), 569. doi:10.2307/2233763Cohen, W. M., & Levinthal, D. A. (1990). Absorptive Capacity: A New Perspective on Learning and Innovation. Administrative Science Quarterly, 35(1), 128. doi:10.2307/2393553Coleman, J. S. (1988). Social Capital in the Creation of Human Capital. American Journal of Sociology, 94, S95-S120. doi:10.1086/228943Coombs, J. E., Deeds, D. L., & Duane Ireland, R. (2009). Placing the choice between exploration and exploitation in context: a study of geography and new product development. Strategic Entrepreneurship Journal, 3(3), 261-279. doi:10.1002/sej.74Crestanello, P., & Tattara, G. (2011). Industrial Clusters and the Governance of the Global Value Chain: The Romania–Veneto Network in Footwear and Clothing. Regional Studies, 45(2), 187-203. doi:10.1080/00343401003596299Dierickx, I., & Cool, K. (1989). Asset Stock Accumulation and Sustainability of Competitive Advantage. Management Science, 35(12), 1504-1511. doi:10.1287/mnsc.35.12.1504Dyer, J. H., & Singh, H. (1998). The Relational View: Cooperative Strategy and Sources of Interorganizational Competitive Advantage. The Academy of Management Review, 23(4), 660. doi:10.2307/259056Eraydin, A., & Armatli-Köroğlu, B. (2005). Innovation, networking and the new industrial clusters: the characteristics of networks and local innovation capabilities in the Turkish industrial clusters. Entrepreneurship & Regional Development, 17(4), 237-266. doi:10.1080/08985620500202632Evenson, R. E., & Kislev, Y. (1973). Research and Productivity in Wheat and Maize. Journal of Political Economy, 81(6), 1309-1329. doi:10.1086/260129Expósito-Langa, M., Molina-Morales, F. X., & Capó-Vicedo, J. (2011). New Product Development and Absorptive Capacity in Industrial Districts: A Multidimensional Approach. Regional Studies, 45(3), 319-331. doi:10.1080/00343400903241535Foss, N. J. (1996). Higher-order industrial Capabilities and competitive advantage. Journal of Industry Studies, 3(1), 1-20. doi:10.1080/13662719600000001George, G., Robley Wood, D., & Khan, R. (2001). Networking strategy of boards: implications for small and medium-sized enterprises. Entrepreneurship & Regional Development, 13(3), 269-285. doi:10.1080/08985620110058115Giuliani, E. 2005. The structure of cluster knowledge networks: Uneven and selective, not pervasive and collective. DRUID Working Paper no. 05-11Giuliani, E., & Bell, M. (2005). The micro-determinants of meso-level learning and innovation: evidence from a Chilean wine cluster. Research Policy, 34(1), 47-68. doi:10.1016/j.respol.2004.10.008Glasmeier, A. (1991). Technological discontinuities and flexible production networks: The case of Switzerland and the world watch industry. Research Policy, 20(5), 469-485. doi:10.1016/0048-7333(91)90070-7Grant, R. M. (1996). Prospering in Dynamically-Competitive Environments: Organizational Capability as Knowledge Integration. Organization Science, 7(4), 375-387. doi:10.1287/orsc.7.4.375Guerrieri, P., & Pietrobelli, C. (2004). Industrial districts’ evolution and technological regimes: Italy and Taiwan. Technovation, 24(11), 899-914. doi:10.1016/s0166-4972(03)00048-8Huggins, R., & Johnston, A. (2010). Knowledge flow and inter-firm networks: The influence of network resources, spatial proximity and firm size. Entrepreneurship & Regional Development, 22(5), 457-484. doi:10.1080/08985620903171350Ibarra, H. (1992). Homophily and Differential Returns: Sex Differences in Network Structure and Access in an Advertising Firm. Administrative Science Quarterly, 37(3), 422. doi:10.2307/2393451Lane, P. J., & Lubatkin, M. (1998). Relative absorptive capacity and interorganizational learning. Strategic Management Journal, 19(5), 461-477. doi:10.1002/(sici)1097-0266(199805)19:53.0.co;2-lLechner, C., Frankenberger, K., & Floyd, S. W. (2010). Task Contingencies in the Curvilinear Relationships Between Intergroup Networks and Initiative Performance. Academy of Management Journal, 53(4), 865-889. doi:10.5465/amj.2010.52814620Levin, D. Z., & Cross, R. (2004). The Strength of Weak Ties You Can Trust: The Mediating Role of Trust in Effective Knowledge Transfer. Management Science, 50(11), 1477-1490. doi:10.1287/mnsc.1030.0136Madill, J. J., Haines, G. H., & Riding, A. L. (2004). Networks and linkages among firms and organizations in the Ottawa-region technology cluster. Entrepreneurship & Regional Development, 16(5), 351-368. doi:10.1080/0898562042000188414Maskell, P. (1998). Low-Tech Competitive Advantages and the Role Of Proximity. European Urban and Regional Studies, 5(2), 99-118. doi:10.1177/096977649800500201Maskell, P. (2001). Towards a Knowledge-based Theory of the Geographical Cluster. Industrial and Corporate Change, 10(4), 921-943. doi:10.1093/icc/10.4.921McEvily, B., & Marcus, A. (2005). Embedded ties and the acquisition of competitive capabilities. Strategic Management Journal, 26(11), 1033-1055. doi:10.1002/smj.484McEvily, B., & Zaheer, A. (1999). Bridging ties: a source of firm heterogeneity in competitive capabilities. Strategic Management Journal, 20(12), 1133-1156. doi:10.1002/(sici)1097-0266(199912)20:123.0.co;2-7Xavier Molina-Morales, F., & Teresa Martínez-Fernández, M. (2006). Industrial districts: something more than a neighbourhood. Entrepreneurship & Regional Development, 18(6), 503-524. doi:10.1080/08985620600884750Molina-Morales, F. X., & Martínez-Fernández, M. T. (2009). Too much love in the neighborhood can hurt: how an excess of intensity and trust in relationships may produce negative effects on firms. Strategic Management Journal, 30(9), 1013-1023. doi:10.1002/smj.766Morrison, A. (2008). Gatekeepers of Knowledgewithin Industrial Districts: Who They Are, How They Interact. Regional Studies, 42(6), 817-835. doi:10.1080/00343400701654178Morrison, A., & Rabellotti, R. (2009). Knowledge and Information Networks in an Italian Wine Cluster. European Planning Studies, 17(7), 983-1006. doi:10.1080/09654310902949265Mowery, D. C., Oxley, J. E., & Silverman, B. S. (1996). Strategic alliances and interfirm knowledge transfer. Strategic Management Journal, 17(S2), 77-91. doi:10.1002/smj.4250171108Nahapiet, J., & Ghoshal, S. (1998). Social Capital, Intellectual Capital, and the Organizational Advantage. The Academy of Management Review, 23(2), 242. doi:10.2307/259373O’Connor, G. C. (1998). Market Learning and Radical Innovation: A Cross Case Comparison of Eight Radical Innovation Projects. Journal of Product Innovation Management, 15(2), 151-166. doi:10.1111/1540-5885.1520151Oba, B., & Semerciöz, F. (2005). Antecedents of trust in industrial districts: an empirical analysis of inter-firm relations in a Turkish industrial district. Entrepreneurship & Regional Development, 17(3), 163-182. doi:10.1080/08985620500102964Parrilli, M. D. (2009). Collective efficiency, policy inducement and social embeddedness: Drivers for the development of industrial districts. Entrepreneurship & Regional Development, 21(1), 1-24. doi:10.1080/08985620801886513Podolny, J. M., & Baron, J. N. (1997). Resources and Relationships: Social Networks and Mobility in the Workplace. American Sociological Review, 62(5), 673. doi:10.2307/2657354Porter, M. E. (1990). The Competitive Advantage of Nations. doi:10.1007/978-1-349-11336-1Pouder, R., & St. John, C. H. (1996). Hot Spots and Blind Spots: Geographical Clusters of Firms and Innovation. Academy of Management Review, 21(4), 1192-1225. doi:10.5465/amr.1996.9704071867Torre, A., & Rallet, A. (2005). Proximity and Localization. Regional Studies, 39(1), 47-59. doi:10.1080/0034340052000320842Rosenkopf, L., & Almeida, P. (2003). Overcoming Local Search Through Alliances and Mobility. Management Science, 49(6), 751-766. doi:10.1287/mnsc.49.6.751.16026Rosenthal, S. S., & Strange, W. C. (2003). Geography, Industrial Organization, and Agglomeration. Review of Economics and Statistics, 85(2), 377-393. doi:10.1162/003465303765299882Rowley, T., Behrens, D., & Krackhardt, D. (2000). Redundant governance structures: an analysis of structural and relational embeddedness in the steel and semiconductor industries. Strategic Management Journal, 21(3), 369-386. doi:10.1002/(sici)1097-0266(200003)21:33.0.co;2-mRusso, M. (1985). Technical change and the industrial district: The role of interfirm relations in the growth and transformation of ceramic tile production in Italy. Research Policy, 14(6), 329-343. doi:10.1016/0048-7333(85)90003-4Sammarra, A., & Belussi, F. (2006). Evolution and relocation in fashion-led Italian districts: evidence from two case-studies. Entrepreneurship & Regional Development, 18(6), 543-562. doi:10.1080/08985620600884685Simmie, J. (2004). Innovation and Clustering in the Globalised International Economy. Urban Studies, 41(5-6), 1095-1112. doi:10.1080/00420980410001675823Sparrowe, R. T., Liden, R. C., Wayne, S. J., & Kraimer, M. L. (2001). SOCIAL NETWORKS AND THE PERFORMANCE OF INDIVIDUALS AND GROUPS. Academy of Management Journal, 44(2), 316-325. doi:10.2307/3069458STABER, U. (2007). Contextualizing Research on Social Capital in Regional Clusters. International Journal of Urban and Regional Research, 31(3), 505-521. doi:10.1111/j.1468-2427.2007.00742.xStock, G. N., Greis, N. P., & Fischer, W. A. (2001). Absorptive capacity and new product development. The Journal of High Technology Management Research, 12(1), 77-91. doi:10.1016/s1047-8310(00)00040-7Tallman, S., Jenkins, M., Henry, N., & Pinch, S. (2004). Knowledge, Clusters, and Competitive Advantage. The Academy of Management Review, 29(2), 258. doi:10.2307/20159032Thompson, P., & Fox-Kean, M. (2005). Patent Citations and the Geography of Knowledge Spillovers: A Reassessment. American Economic Review, 95(1), 450-460. doi:10.1257/0002828053828509Tsai, W. (2001). KNOWLEDGE TRANSFER IN INTRAORGANIZATIONAL NETWORKS: EFFECTS OF NETWORK POSITION AND ABSORPTIVE CAPACITY ON BUSINESS UNIT INNOVATION AND PERFORMANCE. Academy of Management Journal, 44(5), 996-1004. doi:10.2307/3069443Tsai, W., & Ghoshal, S. (1998). SOCIAL CAPITAL AND VALUE CREATION: THE ROLE OF INTRAFIRM NETWORKS. Academy of Management Journal, 41(4), 464-476. doi:10.2307/257085Tushman, M., & Nadler, D. (1986). Organizing for Innovation. California Management Review, 28(3), 74-92. doi:10.2307/41165203Uzzi, B. (1997). Social Structure and Competition in Interfirm Networks: The Paradox of Embeddedness. Administrative Science Quarterly, 42(1), 35. doi:10.2307/2393808Varaldo, R., & Ferrucci, L. (1996). The evolutionary nature of the firm within industrial districts. European Planning Studies, 4(1), 27-34. doi:10.1080/09654319608720327Waxell, A., & Malmberg, A. (2007). What is global and what is local in knowledge-generating interaction? The case of the biotech cluster in Uppsala, Sweden. Entrepreneurship & Regional Development, 19(2), 137-159. doi:10.1080/08985620601061184Yli-Renko, H., Autio, E., & Sapienza, H. J. (2001). Social capital, knowledge acquisition, and knowledge exploitation in young technology-based firms. Strategic Management Journal, 22(6-7), 587-613. doi:10.1002/smj.183ZUCKER, L. G., DARBY, M. R., & ARMSTRONG, J. (1998). GEOGRAPHICALLY LOCALIZED KNOWLEDGE: SPILLOVERS OR MARKETS? Economic Inquiry, 36(1), 65-86. doi:10.1111/j.1465-7295.1998.tb01696.

Morphological characterization of sweet and sour cherry cultivars in a germplasm bank at Portugal

Nine sweet cherry and eight sour cherry varieties located in a germplasm bank at Fundauo, Portugal, were studied from the viewpoint of characterization. Most of them were autochthonous cultivars that have a high risk of extinction since at the present they are markedly minor varieties. Morphological characteristics were evaluated in different organs: crown and trunk of the trees, leaves, flowers and fruits, over a three consecutive years period. Statistical analyses were carried out in order to detect similarities between cultivars as well as the existence of synonymies. Qualitative characteristics of the fruits were scored in order to carry out the multivariate analysis. A dendrogram of the evaluated characters shows the marked differentiation between sour and sweet cherries and suggests the existing synonymies. Conservation of the autochthonous cultivars in the future is highly recommended

Gain in cellular organization of inflammatory breast cancer: A 3D in vitro model that mimics the in vivo metastasis

<p>Abstract</p> <p>Background</p> <p>The initial step of metastasis in carcinomas, often referred to as the epithelial-mesenchymal transition (EMT), occurs via the loss of adherens junctions (e.g. cadherins) by the tumor embolus. This leads to a subsequent loss of cell polarity and cellular differentiation and organization, enabling cells of the embolus to become motile and invasive. However highly malignant inflammatory breast cancer (IBC) over-expresses E-cadherin. The human xenograft model of IBC (MARY-X), like IBC, displays the signature phenotype of an exaggerated degree of lymphovascular invasion (LVI) <it>in situ </it>by tumor emboli. An intact E-cadherin/α, β-catenin axis mediates the tight, compact clump of cells found both <it>in vitro </it>and <it>in vivo </it>as spheroids and tumor emboli, respectively.</p> <p>Methods</p> <p>Using electron microscopy and focused ion beam milling to acquire <it>in situ </it>sections, we performed ultrastructural analysis of both an IBC and non-IBC, E-cadherin positive cell line to determine if retention of this adhesion molecule contributed to cellular organization.</p> <p>Results</p> <p>Here we report through ultrastructural analysis that IBC exhibits a high degree of cellular organization with polar elements such as apical/lateral positioning of E-cadherin, apical surface microvilli, and tortuous lumen-like (canalis) structures. In contrast, agarose-induced spheroids of MCF-7, a weakly invasive E-cadherin positive breast carcinoma cell line, do not exhibit ultrastructural polar features.</p> <p>Conclusions</p> <p>This study has determined that the highly metastatic IBC with an exaggerated malignant phenotype challenges conventional wisdom in that instead of displaying a loss of cellular organization, IBC acquires a highly structured architecture.</p> <p>These findings suggest that the metastatic efficiency might be linked to the formation and maintenance of these architectural features. The comparative architectural features of both the spheroid and embolus of MARY-X provide an <it>in vitro </it>model with tractable <it>in vivo </it>applications.</p

PhosTryp: a phosphorylation site predictor specific for parasitic protozoa of the family trypanosomatidae

<p>Abstract</p> <p>Background</p> <p>Protein phosphorylation modulates protein function in organisms at all levels of complexity. Parasites of the <it>Leishmania </it>genus undergo various developmental transitions in their life cycle triggered by changes in the environment. The molecular mechanisms that these organisms use to process and integrate these external cues are largely unknown. However <it>Leishmania </it>lacks transcription factors, therefore most regulatory processes may occur at a post-translational level and phosphorylation has recently been demonstrated to be an important player in this process. Experimental identification of phosphorylation sites is a time-consuming task. Moreover some sites could be missed due to the highly dynamic nature of this process or to difficulties in phospho-peptide enrichment.</p> <p>Results</p> <p>Here we present PhosTryp, a phosphorylation site predictor specific for trypansomatids. This method uses an SVM-based approach and has been trained with recent <it>Leishmania </it>phosphosproteomics data. PhosTryp achieved a 17% improvement in prediction performance compared with Netphos, a non organism-specific predictor. The analysis of the peptides correctly predicted by our method but missed by Netphos demonstrates that PhosTryp captures <it>Leishmania</it>-specific phosphorylation features. More specifically our results show that <it>Leishmania </it>kinases have sequence specificities which are different from their counterparts in higher eukaryotes. Consequently we were able to propose two possible <it>Leishmania</it>-specific phosphorylation motifs.</p> <p>We further demonstrate that this improvement in performance extends to the related trypanosomatids <it>Trypanosoma brucei </it>and <it>Trypanosoma cruzi</it>. Finally, in order to maximize the usefulness of PhosTryp, we trained a predictor combining all the peptides from <it>L. infantum, T. brucei and T. cruzi</it>.</p> <p>Conclusions</p> <p>Our work demonstrates that training on organism-specific data results in an improvement that extends to related species. PhosTryp is freely available at <url>http://phostryp.bio.uniroma2.it</url></p

Spain: Underwater Exploration on a Narrow Continental Shelf

In spite of Spain’s long coastline (nearly 8000 km) and its well-established tradition in underwater archaeology, the prehistoric settlement of the continental shelf is practically unknown with very few finds. Underwater research has focused on naval archaeology and, until very recently, no attempt had been made to look for prehistoric underwater sites. In the past decade,new research projects have been launched to explore selected areas on the Cantabrian shelf and offshore of Gibraltar. This chapter summarises the currently available evidence of submerged prehistoric archaeology and the preliminary results of these new project

Clinical features and health-related quality of life in adult patients with mucopolysaccharidosis IVA: the Spanish experience

Background: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults. The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL). Results: Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5–40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106–136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03–2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68–3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25–2.34) versus 2.25 (1.62–3.00) in patients not treated with ERT. Conclusions: The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams