Aproximación a la arquitectura popular en la Mancha Baja. El caso de Manzanares

La tesis se compone de una primera parte introductoria, en la que se recogen las distintas opiniones y definiciones de la arquitectura “popular”, el estado de la cuestión, comentando los artículos y publicaciones realizados sobre la Mancha. La segunda parte profundiza en aspectos generales previos al análisis edificatorio central de la tesis, con los siguientes capítulos: -Estudio de los condicionantes físicos, históricos, socio-económicos y culturales de la comarca de la Mancha Baja. Acotando el territorio. -Una visión general sobre la arquitectura tradicional de la provincia de Ciudad Real, por comarcas. -Un estudio de las distintas tipologías edificatorias tradicionales, con ejemplos en la comarca manchega. -El análisis de materiales constructivos, elementos y sistemas utilizados en las construcciones tradicionales en la Mancha Baja. La tercera parte, desde la premisa de la representación gráfica, apoyado en un anexo con dibujos de ciento treinta y siete edificios populares de Manzanares y comarca, estudia: El trazado urbano y las casas de Manzanares; desde los levantamientos de plantas, alzados y secciones, emplazamiento en la manzana y fotografías, se realiza una descripción completa, con noventa y seis ejemplos. Además de llegar a las conclusiones derivadas del análisis de estas edificaciones, los objetivos pretendidos con este estudio serían también: Realizar un primer trabajo aproximativo, desde la visión arquitectónica, de la arquitectura tradicional manchega. Recopilar toda la información existente que pueda relacionarse con la arquitectura popular en la comarca, y citar los escritos y publicaciones de referencia para posteriores estudios. Se estudia la geomorfología, el clima, el territorio, la economía, la sociología, etc…, para obtener una información clave, además de los materiales, técnicas constructivas y morfología de las edificaciones. Se destaca el apartado de los edificios preindustriales tradicionales, como molinos de viento, de agua, palomares, pósitos y bodegas con el análisis de varios ejemplos, por su importante presencia en las poblaciones. Por último se desarrolla un amplio bloque sobre bibliografía de arquitectura popular, la consultada y la general. La arquitectura popular de la mancha baja es tapial cubierto de teja árabe, cerrada al exterior, pero abierta a grandes patios, de planta baja y cámaras altas, con elementos auxiliares de protección y acceso, que revisten la aparente simplicidad volumétrica de estos complejos, viviendas-almacén. Con un complejo programa tanto agrícola como doméstico. De gran protección frente al clima, con escasa decoración, esquemas espaciales primitivos y con mayor envergadura estructural en las dependencias agropecuarias. Una arquitectura que mezcla el uso doméstico y el productivo, pero que al evolucionar aumenta su diferenciación. Edificios que mantienen las mismas cualidades estéticas, repitiendo formas y volúmenes, pero de peculiares configuraciones espaciales, se repiten los materiales y técnicas constructivas, así como elementos arquitectónicos con pocas variaciones, pero no existen dos conjuntos similares. No podemos utilizar un ejemplo como modelo de casa manchega. Evoluciona de la casa bloque, básica y primitiva, con ejemplos escasos en las poblaciones más deprimidas, a la casa compleja, donde se separan con claridad las dependencias agropecuarias de las vivideras. Evoluciona de una casa rural, con los mismos esquemas, ya se ubique en el campo o en núcleos de población, a la casa urbana, entre medianerías, en la que se puede encontrar una transformación paralela, desarrollándose programas domésticos, más especializados, mezclados con arquitecturas cultas, con programas que reflejan las nuevas necesidades de la sociedad urbana del siglo XX. ABSTRACT The thesis is composed of a first part that is collected as introducing different views and definitions of popular architecture, the state of affairs, commenting on articles and publications carried out at the Mancha. The second part explores general issues before the main urban analysis of the thesis, with the following chapters: -A study of the geographic, historical, socio-economic and cultural conditions of the region of the Mancha Baja. Delimiting the territory -A tour with an overview of the province of Ciudad Real by regions. -A study of the different traditional building types, with examples in the region from the Mancha. -The Analysis of building materials, components and systems used in traditional buildings in the Mancha Lower The third part studies from the premise of the drawing: The urban planning of the towns to study and houses of Manzanares, from the execution of plans, elevations and sections, sites in the blocks, old photographs, a full description is made, covering a wide range of examples, highlighting the “evolution during the twentieth century, in its last quarter, buildings of popular character “, which is the ultimate aim of the thesis. In addition to reaching the conclusions drawn from the analysis cards of these buildings, the objectives pursued with this study would be also: This paper is the realization of a first rough work from the architectural vision of traditional architecture from the Mancha. To Search a work method for approaching the popular architecture, other than those made so far by other studies of historians, engineers and sociologists, with the graphical representation and the buildings would be studied like living organisms that evolve over time. To collect all the current information that It can be able to connect itself with the popular architecture in the region, and cite the writings and publications of reference for future studies. Geomorphology, climate, topography of the place is studied to obtain a key information about materials, construction techniques and morphology of the buildings. A section is opened to study the case of traditional industrial buildings like windmills, flour mill, pigeon lofts, public granary, threshing floor and cellars with the analysis of several examples; its importance is highlighted in the urban plan of the town. Finally a large block of popular literature on architecture is developed, consulted for work is distinct from the general existing on the subject. The popular architecture from the Mancha is built of rammed earth and roofs inclined of Arabic tiles, the buildings are closed to the outside, but they are open around large courtyards, and ground floor and camera high, with additional elements of protection, they are opened to patios. The manor has a complex program on agricultural and domestic activity. Large climate protection, poor decoration, quite primitive in shaping living spaces, and more structural scale in storage and processing units of agriculture-related products, mainly wine, cereal and to a lesser extent oil. These architecture combines the domestic and productive use, but which will evolve and they are distinguishing, both enclosed spaces such as courtyards. The buildings keep the same aesthetic qualities because they repeat shapes and volumes, but they maintain their spatial configuration individually; the materials, building techniques and architectural elements are repeated with slight variations, but there aren´t two identical houses. This architecture evolved from the block, basic and primitive house, with few examples in the most deprived towns, to the complex house, where agricultural units are clearly separated of domestic rooms. It developed from a country house (with the same patterns) whether it is located in the countryside or in the towns, to an urban house, in which we can find a parallel transformation, developing domestic programs, more specialized, mixed with cultivated architectures, with programs that reflect the changing needs of urban society of the twentieth century.

Ludomática, herramienta de aprendizaje

Desde los comienzos de la enseñanza, siempre se han buscado formas innovadoras para transmitir el conocimiento de profesor a alumno. Desde recursos materiales hasta sistemas de enseñanza complejos, todos juegan un papel esencial en el aprendizaje del alumno. Durante el siglo XVII comienzan a desarrollarse nuevas corrientes de enseñanza cuyo objetivo era el aprendizaje ameno del individuo. Hoy en día pueden utilizarse multitud de medios para desarrollar estos métodos pedagógicos, entre ellos, los juegos interactivos. Con el boom de la tecnología y el desarrollo de las tecnologías de la información, los tutores encuentran en los dispositivos electrónicos todo un apoyo para realizar esta tarea, lo cual viene acompañado de una revolución inminente en la enseñanza. El objetivo de este proyecto es la creación de un videojuego educativo que permita tanto aprender más fácilmente a los alumnos como evaluar los conocimientos adquiridos por éstos a los profesores. Se ha creado Ludomática, un videojuego de tipo juego de mesa donde los jugadores tendrán que utilizar sus conocimientos en determinados temas para ganar la partida. El videojuego puede ser configurado con distintas preguntas del tema que se desee y en tres niveles de dificultad. Además, cuenta con la posibilidad de configurar el número de jugadores, de preguntas y de puntuación máxima, con objeto de crear partidas más o menos largas. Ludomática se constituye como una herramienta educativa completa y personalizable, además de atractiva, mediante la cual los profesores pueden innovar su forma de enseñanza y los alumnos pueden aprender divirtiéndose---ABSTRACT---Since the beginning of teaching, professors have always looked for innovative ways to transmit knowledge from teacher to student. From material resources to teaching complex systems, they all play a vital role in student learning. The development of new forms of education aimed to create enjoyable ways to teach started during the XVII century. Nowadays, It’s easy to find multiple elements to develop this pedagogical methods, including interactive games. Because of the “tech boom” and the rise of the Information and Communication Technologies, teachers can have a lot of support in electronic devices to carry out this task, which comes with an inminent revolution of teaching. The objective of this project is to create an educational video game that allows not only learn much more easily for students, but also evaluate the knowledge acquired by these for teachers. Ludomática has been created as a board videogame where players have to use their knowledge in specific topics to win the game. The game can be configured with different questions of the topic desired and three difficulty levels. It also has the ability to set the number of players, questions and maximum score, in order to control the duration of the game. Ludomática constitutes a complete and customizable educational tool, also attractive, whereby teachers can innovate their teaching forms and students can learn while having fun.

Protocolos de diseño y cálculo de luz natural en arquitectura

Esta tesis doctoral aborda el problema de la falta de un protocolo que conecte las elevadas y variadas expectativas formales que plantea la arquitectura singular respecto de la luz natural con las distintas herramientas de cálculo y sus métricas asociadas disponibles. La pregunta que la tesis responde es la siguiente “¿Es posible definir un protocolo que ordene las decisiones de diseño y cálculo en la resolución de los problemas de luz natural en la arquitectura singular en forma de procesos, de modo suficientemente genérico y operativo, creando conocimiento útil sobre el problema de que se trate en cada etapa del mismo?” Metodológicamente se desarrolla en dos ciclos de investigación enlazados: primero se DEFINE de modo científico el protocolo y luego se EVALÚA SU APLICABILIDAD. La construcción del protocolo se resuelve utilizando el método inductivo a partir de un corpus previo de problemas de luz natural ya resueltos por el autor. Son analizados de modo sistemático y aplicando diversas estrategias de reducción y síntesis. conducen a un enunciado inicial del protocolo. Una vez enunciado el protocolo, que se denomina DAYLIGHTING CANVAS, se valora su la aplicabilidad mediante experimentación directa, que se realiza a través de tres experiencias diferentes. En la primera evaluamos su aplicabilidad en un problema representativo, en la segunda su aplicabilidad para resolución de problemas planteados de modo aleatorio, y por último su aplicabilidad en el caso de ser empleado por diferentes autores. ABSTRACT The Ph.D. thesis address the lack of a protocol capable to link the higher expectations regarding daylighting of the singular architecture practice with the available daylighting calculation tools and metrics. The thesis question is as follows: “Is it possible to define a protocol capable to arrange the design and calculation decisions needed to be made to solve a daylighting problem for a singular architecture project, as a process, in a way as generic as operational, by building daylighting related knowledge in each step of it?” Methodologically the research is developed in two linked stages: first the protocol is scientifically DEFINED and then its APPLICABILITY is tested. The protocol is built up by using the inductive method over a group of previously solved daylighting projects provided by the thesis author. Those projects has been systematically analyzed by applying some reduction and synthesis strategies, which leads to a preliminary protocol formulation. Once the protocol is fully formulated under the name of “DAYLIGHTING CANVAS”, its applicability is assessed by direct experimentation, done through three different experiments. In the first one the applicability to a complex problem is assessed; in the second one its applicability to non predicted daylighting problems; and finally its applicability for different users.

A conceptual insight on digital paralell workshops for urban planning

The educational realm in Urban Plan ning needs a review because of the global challenges that human settlements will face in the near futu re. In this scenario, international boards of research call for the development of common frameworks of research, accredita tion, and planning best-pra ctices, that need to transcend the limits of local competences, which at the same time affect educational structures. A central issue on achieving this pursued consensus is in ternational cooperation among academic institutions, seeking global awareness on urban challenges, built equally upon a variety of context-based experiences. The rise of ICT's and digital tools are widely perceived as a great field of opportunity to establish complex and de-centralized networks of knowledge-bu ilding that can be critical to address these needs.

Structural kinetics of transcription activation at the malT promoter of Escherichia coli by UV laser footprinting

We have studied the kinetics of transcriptional initiation and activation at the malT and malTp1 promoters of Escherichia coli using UV laser footprinting. Contrary to previous studies and because of the very rapid signal acquisition by this technique, we can obtain structural information about true reaction intermediates of transcription initiation. The consequences of adding a transcriptional activator, the cAMP receptor protein/cAMP complex (CRP), are monitored in real time, permitting us to assign specific interactions to the activation of discrete steps in transcription initiation. Direct protein–protein contacts between CRP and the RNA polymerase appeared very rapidly, followed by DNA melting around the −10 hexamer. CRP slightly increased the rate of this isomerization reaction but, more importantly, favored the establishment of additional contacts between the DNA upstream of the CRP binding site and RNA polymerase subsequent to open complex formation. These contacts make a major contribution to transcriptional activation by stabilizing open forms of the promoter complex, thereby indirectly accelerating promoter escape. The ensemble of the kinetic, structural signals demonstrated directly that CRP exerts most of its activating effects on the late stages of transcriptional initiation at the malT promoter.

The 2.0-Å resolution crystal structure of a trimeric antibody fragment with noncognate VH–VL domain pairs shows a rearrangement of VH CDR3

The 2.0-Å resolution x-ray crystal structure of a novel trimeric antibody fragment, a “triabody,” has been determined. The trimer is made up of polypeptides constructed in a manner identical to that previously described for some “diabodies”: a VL domain directly fused to the C terminus of a VH domain—i.e., without any linker sequence. The trimer has three Fv heads with the polypeptides arranged in a cyclic, head-to-tail fashion. For the particular structure reported here, the polypeptide was constructed with a VH domain from one antibody fused to the VL domain from an unrelated antibody giving rise to “combinatorial” Fvs upon formation of the trimer. The structure shows that the exchange of the VL domain from antibody B1-8, a Vλ domain, with the VL domain from antibody NQ11, a Vκ domain, leads to a dramatic conformational change in the VH CDR3 loop of antibody B1-8. The magnitude of this change is similar to the largest of the conformational changes observed in antibody fragments in response to antigen binding. Combinatorial pairing of VH and VL domains constitutes a major component of antibody diversity. Conformationally flexible antigen-binding sites capable of adapting to the specific CDR3 loop context created upon VH–VL pairing may be employed by the immune system to maximize the structural diversity of the immune response.

Genetic control of social organization in an ant

A central issue in evolutionary biology is the extent to which complex social organization is under genetic control. We have found that a single genomic element marked by the protein-encoding gene Gp-9 is responsible for the existence of two distinct forms of social organization in the fire ant Solenopsis invicta. This genetic factor influences the reproductive phenotypes and behavioral strategies of queens and determines whether workers tolerate a single fertile queen or multiple queens per colony. Furthermore, this factor affects worker tolerance of queens with alternate genotypes, thus explaining the dramatic differences in Gp-9 allele frequencies observed between the two social forms in the wild. These findings reveal how a single genetic factor can have major effects on complex social behavior and influence the nature of social organization.

Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse

The microrchidia, or morc, autosomal recessive mutation results in the arrest of spermatogenesis early in prophase I of meiosis. The morc mutation arose spontaneously during the development of a mouse strain transgenic for a tyrosinase cDNA construct. Morc −/− males are infertile and have grossly reduced testicular mass, whereas −/− females are normal, indicating that the Morc gene acts specifically during male gametogenesis. Immunofluorescence to synaptonemal complex antigens demonstrated that −/− male germ cells enter meiosis but fail to progress beyond zygotene or leptotene stage. An apoptosis assay revealed massive numbers of cells undergoing apoptosis in testes of −/− mice. No other abnormal phenotype was observed in mutant animals, with the exception of eye pigmentation caused by transgene expression in the retina. Spermatogenesis is normal in +/− males, despite significant transgene expression in germ cells. Genomic analysis of −/− animals indicates the presence of a deletion adjacent to the transgene. Identification of the gene inactivated by the transgene insertion may define a novel biochemical pathway involved in mammalian germ cell development and meiosis.

Jasmonate is essential for insect defense in Arabidopsis

The signaling pathways that allow plants to mount defenses against chewing insects are known to be complex. To investigate the role of jasmonate in wound signaling in Arabidopsis and to test whether parallel or redundant pathways exist for insect defense, we have studied a mutant (fad3–2 fad7–2 fad8) that is deficient in the jasmonate precursor linolenic acid. Mutant plants contained negligible levels of jasmonate and showed extremely high mortality (≈80%) from attack by larvae of a common saprophagous fungal gnat, Bradysia impatiens (Diptera: Sciaridae), even though neighboring wild-type plants were largely unaffected. Application of exogenous methyl jasmonate substantially protected the mutant plants and reduced mortality to ≈12%. These experiments precisely define the role of jasmonate as being essential for the induction of biologically effective defense in this plant–insect interaction. The transcripts of three wound-responsive genes were shown not to be induced by wounding of mutant plants but the same transcripts could be induced by application of methyl jasmonate. By contrast, measurements of transcript levels for a gene encoding glutathione S-transferase demonstrated that wound induction of this gene is independent of jasmonate synthesis. These results indicate that the mutant will be a good genetic model for testing the practical effectiveness of candidate defense genes.

Working memory constrains human cooperation in the Prisoner’s Dilemma

Many problems in human society reflect the inability of selfish parties to cooperate. The “Iterated Prisoner’s Dilemma” has been used widely as a model for the evolution of cooperation in societies. Axelrod’s computer tournaments and the extensive simulations of evolution by Nowak and Sigmund and others have shown that natural selection can favor cooperative strategies in the Prisoner’s Dilemma. Rigorous empirical tests, however, lag behind the progress made by theorists. Clear predictions differ depending on the players’ capacity to remember previous rounds of the game. To test whether humans use the kind of cooperative strategies predicted, we asked students to play the iterated Prisoner’s Dilemma game either continuously or interrupted after each round by a secondary memory task (i.e., playing the game “Memory”) that constrained the students’ working-memory capacity. When playing without interruption, most students used “Pavlovian” strategies, as predicted, for greater memory capacity, and the rest used “generous tit-for-tat” strategies. The proportion of generous tit-for-tat strategies increased when games of Memory interfered with the subjects’ working memory, as predicted. Students who continued to use complex Pavlovian strategies were less successful in the Memory game, but more successful in the Prisoner’s Dilemma, which indicates a trade-off in memory capacity for the two tasks. Our results suggest that the set of strategies predicted by game theorists approximates human reality.

Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes

We have asked whether comparative genome analysis and rat transgenesis can be used to identify functional regulatory domains in the gene locus encoding the hypothalamic neuropeptides oxytocin (OT) and vasopressin. Isotocin (IT) and vasotocin (VT) are the teleost homologues of these genes. A contiguous stretch of 46 kb spanning the Fugu IT-VT locus has been sequenced, and nine putative genes were found. Unlike the OT and vasopressin genes, which are closely linked in the mammalian genome in a tail-to-tail orientation, Fugu IT and VT genes are linked head to tail and are separated by five genes. When a cosmid containing the Fugu IT-VT locus was introduced into the rat genome, we found that the Fugu IT gene was specifically expressed in rat hypothalamic oxytocinergic neurons and mimicked the response of the endogenous OT gene to an osmotic stimulus. These data show that cis-acting elements and trans-acting factors mediating the cell-specific and physiological regulation of the OT and IT genes are conserved between mammals and fish. The combination of Fugu genome analysis and transgenesis in a mammal is a powerful tool for identifying and analyzing conserved vertebrate regulatory elements.

TGF-β–induced Phosphorylation of Smad3 Regulates Its Interaction with Coactivator p300/CREB-binding Protein

Smads are intermediate effector proteins that transduce the TGF-β signal from the plasma membrane to the nucleus, where they participate in transactivation of downstream target genes. We have shown previously that coactivators p300/CREB-binding protein are involved in TGF-β–mediated transactivation of two Cdk inhibitor genes, p21 and p15. Here we examined the possibility that Smads function to regulate transcription by directly interacting with p300/CREB-binding protein. We show that Smad3 can interact with a C-terminal fragment of p300 in a temporal and phosphorylation-dependent manner. TGF-β–mediated phosphorylation of Smad3 potentiates the association between Smad3 and p300, likely because of an induced conformational change that removes the autoinhibitory interaction between the N- and C-terminal domains of Smad3. Consistent with a role for p300 in the transcription regulation of multiple genes, overexpression of a Smad3 C-terminal fragment causes a general squelching effect on multiple TGF-β–responsive reporter constructs. The adenoviral oncoprotein E1A can partially block Smad-dependent transcriptional activation by directly competing for binding to p300. Taken together, these findings define a new role for phosphorylation of Smad3: in addition to facilitating complex formation with Smad4 and promoting nuclear translocation, the phosphorylation-induced conformational change of Smad3 modulates its interaction with coactivators, leading to transcriptional regulation.

Nck-2, a Novel Src Homology2/3-containing Adaptor Protein That Interacts with the LIM-only Protein PINCH and Components of Growth Factor Receptor Kinase-signaling Pathways

Many of the protein–protein interactions that are essential for eukaryotic intracellular signal transduction are mediated by protein binding modules including SH2, SH3, and LIM domains. Nck is a SH3- and SH2-containing adaptor protein implicated in coordinating various signaling pathways, including those of growth factor receptors and cell adhesion receptors. We report here the identification, cloning, and characterization of a widely expressed, Nck-related adaptor protein termed Nck-2. Nck-2 comprises primarily three N-terminal SH3 domains and one C-terminal SH2 domain. We show that Nck-2 interacts with PINCH, a LIM-only protein implicated in integrin-linked kinase signaling. The PINCH-Nck-2 interaction is mediated by the fourth LIM domain of PINCH and the third SH3 domain of Nck-2. Furthermore, we show that Nck-2 is capable of recognizing several key components of growth factor receptor kinase-signaling pathways including EGF receptors, PDGF receptor-β, and IRS-1. The association of Nck-2 with EGF receptors was regulated by EGF stimulation and involved largely the SH2 domain of Nck-2, although the SH3 domains of Nck-2 also contributed to the complex formation. The association of Nck-2 with PDGF receptor-β was dependent on PDGF activation and was mediated solely by the SH2 domain of Nck-2. Additionally, we have detected a stable association between Nck-2 and IRS-1 that was mediated primarily via the second and third SH3 domain of Nck-2. Thus, Nck-2 associates with PINCH and components of different growth factor receptor-signaling pathways via distinct mechanisms. Finally, we provide evidence indicating that a fraction of the Nck-2 and/or Nck-1 proteins are associated with the cytoskeleton. These results identify a novel Nck-related SH2- and SH3-domain–containing protein and suggest that it may function as an adaptor protein connecting the growth factor receptor-signaling pathways with the integrin-signaling pathways.

Initiation of Assembly of the Cell Envelope Barrier Structure of Stratified Squamous Epithelia

The cell envelope (CE) is a specialized structure that is important for barrier function in terminally differentiated stratified squamous epithelia. The CE is formed inside the plasma membrane and becomes insoluble as a result of cross-linking of constituent proteins by isopeptide bonds formed by transglutaminases. To investigate the earliest stages of assembly of the CE, we have studied human epidermal keratinocytes induced to terminally differentiate in submerged liquid culture as a model system for epithelia in general. CEs were harvested from 2-, 3-, 5-, or 7-d cultured cells and examined by 1) immunogold electron microscopy using antibodies to known CE or other junctional proteins and 2) amino acid sequencing of cross-linked peptides derived by proteolysis of CEs. Our data document that CE assembly is initiated along the plasma membrane between desmosomes by head-to-tail and head-to-head cross-linking of involucrin to itself and to envoplakin and perhaps periplakin. Essentially only one lysine and two glutamine residues of involucrin and two glutamines of envoplakin were used initially. In CEs of 3-d cultured cells, involucrin, envoplakin, and small proline-rich proteins were physically located at desmosomes and had become cross-linked to desmoplakin, and in 5-d CEs, these three proteins had formed a continuous layer extending uniformly along the cell periphery. By this time >15 residues of involucrin were used for cross-linking. The CEs of 7-d cells contain significant amounts of the protein loricrin, typically expressed at a later stage of CE assembly. Together, these data stress the importance of juxtaposition of membranes, transglutaminases, and involucrin and envoplakin in the initiation of CE assembly of stratified squamous epithelia.

Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression

The nervous system maintains a delicate balance between excitation and inhibition, partly through the complex interplay between voltage-gated sodium and potassium ion channels. Because K+ channel blockade or gene deletion causes hyperexcitability, it is generally assumed that increases in K+ channel gene expression should reduce neuronal network excitability. We have tested this hypothesis by creating a transgenic mouse that expresses a Shaker-type K+ channel gene. Paradoxically, we find that addition of the extra K+ channel gene results in a hyperexcitable rather than a hypoexcitable phenotype. The presence of the transgene leads to a complex deregulation of endogenous Shaker genes in the adult central nervous system as well as an increase in network excitability that includes spontaneous cortical spike and wave discharges and a lower threshold for epileptiform bursting in isolated hippocampal slices. These data suggest that an increase in K+ channel gene dosage leads to dysregulation of normal K+ channel gene expression, and it may underlie a mechanism contributing to the pathogenesis of human aneuploidies such as Down syndrome.