Nephronophthisis

Nephronophthisis (NPH) is an autosomal recessive disease characterized by a chronic tubulointerstitial nephritis that progress to terminal renal failure during the second decade (juvenile form) or before the age of 5 years (infantile form). In the juvenile form, a urine concentration defect starts during the first decade, and a progressive deterioration of renal function is observed in the following years. Kidney size may be normal, but loss of corticomedullary differentiation is often observed, and cysts occur usually after patients have progressed to end-stage renal failure. Histologic lesions are characterized by tubular basement membrane anomalies, tubular atrophy, and interstitial fibrosis. The infantile form is characterized by cortical microcysts and progression to end-stage renal failure before 5 years of age. Some children present with extrarenal symptoms: retinitis pigmentosa (Senior-Løken syndrome), mental retardation, cerebellar ataxia, bone anomalies, or liver fibrosis. Positional cloning and candidate gene approaches led to the identification of eight causative genes (NPHP1, 3, 4, 5, 6, 7, 8, and 9) responsible for the juvenile NPH and one gene NPHP2 for the infantile form. NPH and associated disorders are considered as ciliopathies, as all NPHP gene products are expressed in the primary cilia, similarly to the polycystic kidney disease (PKD) proteins

From Physical to Virtual: Widening the Perspective on Multi-Agent Environments

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-23850-0_9Since more than a decade, the environment is seen as a key element when analyzing, developing or deploying Multi-Agent Systems (MAS) applications. Especially, for the development of multi-agent platforms it has become a key concept, similarly to many application in the area of location-based, distributed systems. An emerging, prominent application area for MAS is related to Virtual Environments. The underlying technology has evolved in a way, that these applications have grown out of science fiction novels till research papers and even real applications. Even more, current technologies enable MAS to be key components of such virtual environments. In this paper, we widen the concept of the environment of a MAS to encompass new and mixed physical, virtual, simulated, etc. forms of environments. We analyze currently most interesting application domains based on three dimensions: the way different "realities" are mixed via the environment, the underlying natures of agents, the possible forms and sophistication of interactions. In addition to this characterization, we discuss how this widened concept of possible environments influences the support it can give for developing applications in the respective domains.Carrascosa Casamayor, C.; Klugl, F.; Ricci, A.; Boissier, O. (2015). From Physical to Virtual: Widening the Perspective on Multi-Agent Environments. En Agent Environments for Multi-Agent Systems IV. 4th International Workshop, E4MAS 2014 - 10 Years Later, Paris, France, May 6, 2014. 133-146. https://doi.org/10.1007/978-3-319-23850-0_9S133146Aggarwal, J.K., Ryoo, M.S.: Human activity analysis: a review. ACM Comput. Surv. 43(3), 16:1–16:43 (2011)Argente, E., Boissier, O., Carrascosa, C., Fornara, N., McBurney, P., Noriega, P., Ricci, A., Sabater-Mir, J., et al.: The role of the environment in agreement technologies. AI Rev. 39(1), 21–38 (2013)Barreteau, O., et al.: Our companion modelling approach. J. Artif. Soc. Soc. Simul. 6(1), 1–6 (2003)Boissier, O., Bordini, R.H., Hübner, J.F., Ricci, A., Santi, A.: Multi-agent oriented programming with jacamo. Sci. Comput. Program. 78(6), 747–761 (2013)Burdea, G., Coiffet, P.: Virtual Reality Technology. Wiley, New York (2003)Castelfranchi, C., Pezzullo, G., Tummolini, L.: Behavioral implicit communication (BIC): communicating with smart environments via our practical behavior and its traces. Int. J. Ambient Comput. Intell. 2(1), 1–12 (2010)Castelfranchi, C., Piunti, M., Ricci, A., Tummolini, L.: AMI systems as agent-based mirror worlds: bridging humans and agents through stigmergy. In: Bosse, T. (ed.) Agents and Ambient Intelligence, Ambient Intelligence and Smart Environments, pp. 17–31. IOS Press, Amsterdam (2012)Ferber, J.: Multi-Agent Systems: An Introduction to Distributed Artificial Intelligence. Addison Wesley Longman, Harlow (1999)Gelernter, D.: Mirror Worlds - or the Day Software Puts the Universe in a Shoebox: How it Will Happen and What it Will Mean. Oxford University Press, New York (1992)Gibson, W.: Neuromancer. Ace, New York (1984)Klügl, F., Fehler, M., Herrler, R.: About the role of the environment in multi-agent simulations. In: Weyns, D., Van Parunak, H.D., Michel, F. (eds.) E4MAS 2004. LNCS (LNAI), vol. 3374, pp. 127–149. Springer, Heidelberg (2005)Krueger, M.: Artificial Reality II. Addison-Wesley, New York (1991)Luck, M., Aylett, R.: Applying artificial intelligence to virtual reality: intelligent virtual environments. Appl. Artif. Intell. 14(1), 3–32 (2000)Dorigo, M., Floreano, D., Gambardella, L.M., et al.: Swarmanoid: a novel concept for the study of heterogeneous robotic swarms. IEEE Robot. Autom. Mag. 20(4), 60–71 (2013)Milgram, P., Kishino, A.F.: Taxonomy of mixed reality visual displays. IEICE Trans. Inf. Syst. E77–D(12), 1321–1329 (1994)Olsson, T., Salo, M.: Online user survey on current mobile augmented reality applications. In: Proceedings of the 2011 10th IEEE International Symposium on Mixed and Augmented Reality, ISMAR 2011, pp. 75–84. IEEE Computer Society, Washington, DC, USA (2011)Saunier, J., Balbo, F., Pinson, S.: A formal model of communication and context awareness in multiagent systems. J. Logic Lang. Inform. 23(2), 219–247 (2014)Stephenson, N.: Snow Crash. Bantam Books, New York (1992)Tummolini, L., Castelfranchi, C.: Trace signals: the meanings of stigmergy. In: Weyns, D., Van Parunak, H.D., Michel, F. (eds.) E4MAS 2006. LNCS (LNAI), vol. 4389, pp. 141–156. Springer, Heidelberg (2007)Weyns, D., Omicini, A., Odell, J.: Environment as a first class abstraction in multiagent systems. Auton. Agent. Multi-Agent Syst. 14(1), 5–30 (2007)Weyns, D., Schelfthout, K., Holvoet, T., Lefever, T.: Decentralized control of e’gv transportation systems. In: Proceedings of the Fourth International Joint Conference on Autonomous Agents and Multiagent Systems, pp. 67–74. ACM (2005)Weyns, D., Schumacher, M., Ricci, A., Viroli, M., Holvoet, T.: Environments in multiagent systems. Knowl. Eng. Rev. 20(2), 127–141 (2005

The opposite of Dante's hell? The transfer of ideas for social housing at international congresses in the 1850s–1860s

With the advent of industrialization, the question of developing adequate housing for the emergent working classes became more pressing than before. Moreover, the problem of unhygienic houses in industrial cities did not stop at the borders of a particular nation-state; sometimes literally as pandemic diseases spread out 'transnationally'. It is not a coincidence that in the nineteenth century the number of international congresses on hygiene and social topics expanded substantially. However, the historiography about social policy in general and social housing in particular, has often focused on individual cases because of the different pace of industrial and urban development and is thus dominated by national perspectives. In this paper, I elaborate on transnational exchange processes and local adaptations and transformations. I focus on the transfer of the housing model of SOMCO in Mulhouse, (a French house building association) during social international congresses. I examine whether cross-national networking enabled and facilitated the implementation of ideas on the local scale. I will elaborate on the transmission and the local adaptation of the Mulhouse-model in Belgium. Convergences, divergences, and different factors that influenced the local transformations (personal choice, political situation, socioeconomic circumstances) will be taken into accoun

Policultivo: prática agrícola de conservação on farm de fruteiras nativas da Amazônia.

Policultivo é uma pratica importante para manter a biodiversidade do sistema agrícola. Na Amazônia é grande a diversidade de frutas nativas, com aptidão para mesa e/ou indústria. Contudo, a maioria dessas frutíferas é desconhecida, perdendo a importância de conservação. Disponibilizar frutíferas nativas a sistemas de policultivo de espécies nativas cultivadas e culturas alimentares, contribui ao acesso da população, tornando-as conhecidas e ampliando a diversidade alimentar. Com a prática, realiza-se o resgate dessas espécies, conservando- as, evitando a erosão genética, perda das propriedades e valores nutricionais, medicinais e os sabores. No contexto, objetivou-se avaliar os resultados preliminares da prática de policultivo de espécies frutíferas nativas da Amazônia, estimulando o uso e a conservação on farm das espécies. Para tanto, instalou-se em áreas de produtores, estando o cupuaçuzeiro (Theobroma grandiflorum) e o açaizeiro (Euterpe oleracea), frutíferas nativas, ocupando 80% da área e, 20% da área com espécies frutíferas nativas não tradicionalmente cultivadas ou conhecidas de agricultores e/ou consumidores

Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies

PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Biallelic KIF24 Variants Are Responsible for a Spectrum of Skeletal Disorders Ranging From Lethal Skeletal Ciliopathy to Severe Acromesomelic Dysplasia

Skeletal dysplasias comprise a large spectrum of mostly monogenic disorders affecting bone growth, patterning, and homeostasis, and ranging in severity from lethal to mild phenotypes. This study aimed to underpin the genetic cause of skeletal dysplasia in three unrelated families with variable skeletal manifestations. The six affected individuals from three families had severe short stature with extreme shortening of forelimbs, short long-bones, and metatarsals, and brachydactyly (family 1); mild short stature, platyspondyly, and metaphyseal irregularities (family 2); or a prenatally lethal skeletal dysplasia with kidney features suggestive of a ciliopathy (family 3). Genetic studies by whole genome, whole exome, and ciliome panel sequencing identified in all affected individuals biallelic missense variants in KIF24, which encodes a kinesin family member controlling ciliogenesis. In families 1 and 3, with the more severe phenotype, the affected subjects harbored homozygous variants (c.1457A>G; p.(Ile486Val) and c.1565A>G; p.(Asn522Ser), respectively) in the motor domain which plays a crucial role in KIF24 function. In family 2, compound heterozygous variants (c.1697C>T; p.(Ser566Phe)/c.1811C>T; p.(Thr604Met)) were found C-terminal to the motor domain, in agreement with a genotype-phenotype correlation. In vitro experiments performed on amnioblasts of one affected fetus from family 3 showed that primary cilia assembly was severely impaired, and that cytokinesis was also affected. In conclusion, our study describes novel forms of skeletal dysplasia associated with biallelic variants in KIF24. To our knowledge this is the first report implicating KIF24 variants as the cause of a skeletal dysplasia, thereby extending the genetic heterogeneity and the phenotypic spectrum of rare bone disorders and underscoring the wide range of monogenetic skeletal ciliopathies. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Peer reviewe

Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization

Ciliopathies are a large group of clinically and genetically heterogeneous disorders caused by defects in primary cilia. Here we identified mutations in TRAF3IP1 (TNF Receptor-Associated Factor Interacting Protein 1) in eight patients from five families with nephronophthisis (NPH) and retinal degeneration, two of the most common manifestations of ciliopathies. TRAF3IP1 encodes IFT54, a subunit of the IFT-B complex required for ciliogenesis. The identified mutations result in mild ciliary defects in patients but also reveal an unexpected role of IFT54 as a negative regulator of microtubule stability via MAP4 (microtubule-associated protein 4). Microtubule defects are associated with altered epithelialization/polarity in renal cells and with pronephric cysts and microphthalmia in zebrafish embryos. Our findings highlight the regulation of cytoplasmic microtubule dynamics as a role of the IFT54 protein beyond the cilium, contributing to the development of NPH-related ciliopathies

Estrogenic Plant Extracts Reverse Weight Gain and Fat Accumulation without Causing Mammary Gland or Uterine Proliferation

Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the risk of breast cancer, as wells as endometrial cancer if used without progestins. Animal studies indicate that beneficial effects of estrogens in adipose tissue and adverse effects on mammary gland and uterus are mediated by estrogen receptor alpha (ERα). One strategy to improve the safety of estrogens to prevent/treat obesity, diabetes and metabolic syndrome is to develop estrogens that act as agonists in adipose tissue, but not in mammary gland and uterus. We considered plant extracts, which have been the source of many pharmaceuticals, as a source of tissue selective estrogens. Extracts from two plants, Glycyrrhiza uralensis (RG) and Pueraria montana var. lobata (RP) bound to ERα, activated ERα responsive reporters, and reversed weight gain and fat accumulation comparable to estradiol in ovariectomized obese mice maintained on a high fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on mammary gland and uterus. Gene expression profiling demonstrated that RG and RP induced estradiol-like regulation of genes in abdominal fat, but not in mammary gland and uterus. The compounds in extracts from RG and RP might constitute a new class of tissue selective estrogens to reverse weight gain, fat accumulation and metabolic syndrome in postmenopausal women