Estudio acústico de la iglesia de San Sebastián de Alcorisa (Teruel). Comparación de resultados obtenidos a partir de planos anteriores y posteriores a la reforma y propuesta de soluciones

En el presente trabajo se ha realizado un estudio acústico de la Iglesia de San Sebastián de Alcorisa (Teruel). La finalidad del trabajo es averiguar cómo afectó a la acústica del recinto la reforma que se llevó a cabo en el año 2001, la cual adecuó la nave principal como sala de conciertos y conferencias. Además de esto se propondrán posibles mejoras acústicas para el recinto. Para llevar a cabo dicho estudio se ha utilizado el proyecto de restauración de dicha iglesia, firmado por la empresa mmt,S.L en enero de 2001. A partir de los planos de este proyecto se han construido dos modelos en tres dimensiones de la sala (uno anterior a la reforma y otro posterior) con los que se ha hecho una simulación acústica. La simulación del recinto actual ha sido ajustada a partir de las medidas acústicas llevadas a cabo in-situ, de tal forma que las soluciones acústicas que se integren al modelo se comporten de una forma lo más realista posible. Además de las soluciones acústicas a nivel arquitectónico, se propondrá un sistema de sonorización que permita un adecuado uso del recinto como sala de conciertos y conferencias. ABSTRACT. In the following thesis, an acoustic study of the church San Sebastian in Alcorisa (Teruel) has been made. The aim is to find how the reformation in 2001 affected or changed the acoustic characteristics of the concert and conference hall area. Moreover, suggestion for improvements will also be presented later in the work. To start the study, the restoration project of the church, which was signed by the company mmt, SL in January 2001 is used. Based on the maps found in this project, two and three dimensions models of the room have been built before and after the restoration, to use them in the acoustic simulation. The simulation of the area studied has been adjusted according to the measurement in site, which will help giving the most realistic result possible. In addition to the architectural acoustic solutions, a sound system is collocated so that the hall can be used for concerts and conferences.

[Colección de fotografías del Monasterio de San Miguel de los Reyes] [Material gráfico]

[1]. Monasterio de San Miguel de los Reyes (Valencia); [2]. Puerta de entrada al recinto de San Miguel de los Reyes; [3]. Vista de la fachada de la iglesia del monasterio; [4]. Ángel tenente con los escudos de los Duque de Calabria, fundadores del monasterio. Detalle de la fachada de la iglesia; [5]. San Miguel. Detalle de la fachada de la iglesia; [6]. San Jerónimo. Detalle de la fachada de la iglesia; [7]. Santa Paula. Detalle de la fachada de la iglesia; [8]. Cúpula de la iglesia; [9]. El presbiterio con el altar mayor de San Miguel de los Reyes; [10]. Aspecto de la nave central de la iglesia y del coro; [11]. Arco lateral de entrada al coro; [12]. Vista parcial de la fachada de la iglesia y del ala sur del monasterio, muy alterada por su uso carcelario desde el siglo XIX. Adosados, barracones de una antigua escuela que se instaló provisionalmente en el jardín delantero del monasterio; [13]. Aspecto del ala norte del monasterio e instalaciones escolares provisionales en el jardín delantero; [14]. Escalera claustra del monasterio que arranca en un corredor situado justo detrás del presbiterio de la iglesia -- [15]. Detalle de la puerta de acceso a la Biblioteca Nueva; [16]. Sala capitular; [17]. Vista parcial del claustro sur; [18]. Arcos cegados del claustro sur; [19]. Detalle del estado actual del claustro sur; [20]. Galería del claustro inferior; [21]. Galería sur del piso inferior del claustro, con la puerta de entrada del Salón de Actos; [22]. Galería del piso superior del claustro sur; [23]. Interior de la galería penitenciaria en el lado oeste del claustro sur; [24]. Estado en que se encontraba la escalera claustral; [25]. Aspecto parcial del patio norte; [26]. Detalle de la fachada este del patio norte; [27]. Puerta de acceso al patio norte, fachada sur; [28]. Torreta de vigilancia del muro de la prisión construido a finales del siglo XIX; [29]. Detalle de ornamento sobre el dintel de la puerta de entrada del Salón de actos

Espacios máximos con recursos mínimos : edificio Central Lechera CLESA, Alejandro de la Sota

La tesis aborda el estudio de la Central lechera CLESA, uno de los edificios industriales de Alejandro de la Sota más significativos de la década de los años cincuenta en España. Las centrales lecheras fueron abordadas por Sota en distintas ocasiones entre 1955 y 1969, siendo CLESA la única de todas ellas que llega a construirse. Se trata de uno de los exponentes más brillantes de la arquitectura moderna industrial española de la posguerra, incluido en "La arquitectura de la industria, REGISTRO DOCOMOMO IBÉRICO”1 entre la veintena de edificios seleccionados de la arquitectura madrileña de este periodo. Plantea una solución singular para alcanzar la diafanidad exigida en la implantación del proceso de producción. La estructura de las naves se realiza con hormigón pretensado, siendo uno de los pioneros en la utilización de esta técnica. La hipótesis de partida considera la realidad del proyecto construido como respuesta desde la arquitectura a un programa industrial resuelto con sencillez, que partiendo de una economía de recursos que le es inherente, consigue desde la coherencia del planteamiento, soluciones donde la complejidad espacial constituye una respuesta eficaz y del máximo interés. Los objetivos de esta tesis son contribuir a un conocimiento riguroso del edificio, que permita descubrir la particularidad de su entramado espacial y el interés de las soluciones adoptadas en su configuración final, en aras de contrastar su calidad arquitectónica. El edificio de la Central Lechera CLESA, si bien es un edificio muy conocido, lo es de una manera superficial. Aparece en numerosas publicaciones, en muchas ocasiones formando parte de un relato extenso de la obra de su autor. El libro monográfico publicado en 2007 por la Fundación Alejandro de la Sota, cuya edición está a cargo de Teresa Couceiro, es la única publicación específica sobre él. Tras una breve introducción, en la que se destaca la intensa dedicación de Sota a esta obra, reúne una colección de planos, fotografías y croquis, junto a la memoria del proyecto. Ofrece una visión fragmentada, que permite vislumbrar el interés de esta obra, pero no facilita comprenderla en su integridad. Es importante destacar la publicación de CLESA en el libro editado por Pronaos (1989), que incluye una selección, realizada por el autor, de plantas, alzados y secciones que corresponden al proyecto construido junto a fotografías de la obra terminada, además de un breve texto tan conciso como esclarecedor. Sobre Alejandro de la Sota se han escrito, tesis doctorales, numerosos artículos, varios libros así como realizado exposiciones que recogen su obra global, reflejados en este documento en las consiguientes bibliografías específicas. Cabe destacar la exposición realizada en la sede del COAM en 2014, con ocasión de su centenario, que el edificio CLESA protagoniza en cierto modo, por su riesgo de desaparición.2 La tesis se estructura en cuatro capítulos: descripción, análisis, síntesis y conclusiones. El primer capítulo contempla la descripción del edificio objeto de la tesis, con una introducción que nos sitúa en el contexto histórico, económico, cultural y social en el que se desarrolla el encargo, proyecto y obra de la central lechera. La descripción propiamente dicha del conjunto industrial, partiendo del encargo de la central lechera al autor del proyecto, pasando por el anteproyecto, el proyecto visado y llegando a la obra realizada. Se compara el proyecto visado, la obra terminada y la CLESA publicada, así como el devenir del edificio. La segunda parte corresponde al análisis, en primer lugar desde el programa como planteamiento general, estudiando las circulaciones, relaciones espaciales, geométricas, esqueléticas, geográficas -parte a parte- que integran el conjunto de la central. La estructura, introducción explicativa de las soluciones adoptadas por Alejandro de la Sota; análisis del sistema esquelético del edificio por partes, operaciones geométricas y espaciales. Construcción, análisis de la materialización de la obra, sistemas constructivos empleados en cerramientos, cubiertas, lucernarios; de lo general a lo particular, estudiando los sistemas. Finalmente a través de la pequeña escala se compendian elementos singulares que forman parte de sistemas complejos, como las múltiples escaleras, barandillas, carpinterías, miradores. Se recapitula en una síntesis que configura un todo con la suma de las partes, mediante la utilización de recursos de enlace de esa arquitectura aditiva, como es el módulo, los recorridos y los enlaces visuales. El capítulo final de Conclusiones contrasta la hipótesis de partida de la tesis en cuanto a una arquitectura de espacios máximos con recursos mínimos. Recoge también diversas reflexiones como la dialéctica entre el espacio fragmentado y el espacio único; crecimiento expansivo o inclusivo; imagen singular y representación; escala doméstica y escala industrial; renuncias estructurales o limitaciones de medios. Quizás, el mayor interés de esta tesis reside los dibujos realizados en axonométrica del complejo CLESA, que han permitido restituir y reconstruir idealmente la fábrica al inicio de su actividad. Teniendo en cuenta su posible desaparición total o parcial, esta restitución cobra relevancia como testimonio de lo que fue. ABSTRACT The thesis deals with the study of CLESA's Dairy Plant, one of the most significant industrial buildings of the Decade of the fifties in Spain, by Alejandro de la Sota. The Dairies were addressed by Sota at various occasions between 1955 and 1969, being the CLESA plant the only one that is has been built. This is one of the most brilliant exponents of Spanish industrial post-war modern architecture, included in "The architecture industry, IBERIAN DOCOMOMO RECORD"3 between the score of selected buildings of Madrid architecture of this period. It poses a singular solution to achieve the openness of the space required in the implementation of the manufacturing process. The structure of the nave is done with prestressed concrete, being one of the pioneers in the use of this technique. The initial hypothesis considers the reality of the project built from the architecture in response to an industrial program solved with simplicity, that from a resource economy that is inherent, gets from the consistency of the approach, solutions where the space complexity is an effective response of great interest. The objectives of this thesis are to contribute to a rigorous knowledge of the building, which allows to discover the particularity of its space lattice and the interest of the solutions adopted in its final configuration, in order to contrast its architectural quality. The building of the Central Lechera CLESA, despite it is a well known building, is in a superficial way. It appears in several publications, often as part of an extensive account of the work of its author. The monograph published in 2007 by the Foundation Alejandro de la Sota, whose edition is run by Teresa Couceiro, is the only specific publication about it. After a brief introduction, in which Sota's intense dedication to this work stands out, it brings together a collection of drawings, photographs and sketches, along with the project report. It offers a fragmented view, which enable to glimpse the interest of this work, but not helps to understand it in full. It is important to highlight the publication of CLESA in the book edited by Pronaos (1989), which includes a selection made by the author of plants, elevations and sections corresponding to the project built, next to photographs of the finished construction, in addition to a brief text as concise as enlightening. About Alejandro de la Sota have been written doctoral thesis, numerous articles, several books as well as held exhibitions collecting his global work, which have been reflected in this document in the resulting specific bibliographies. It should be noted the exhibition in COAM headquarters in 2014, on the occasion of its Centennial, where the building CLESA has a leading role, in a certain way, because of its risk of disappearance.4 The thesis is structured in four chapters: description, analysis, synthesis, and conclusions. The first chapter provides the description of the building object of this thesis. Includes an introduction that puts us in the historic, economic, cultural and social context in which it is developed the commission, the project and construction of the dairy building. The description itself of the industrial complex, starts with the order of the dairy to the author of the project, moves through the draft, the visa project and reaches the completion of the work. The visa project, CLESA's finished and published work, as well as the future of the building is compared. The second part corresponds to the analysis, first from the program as a general approach, studying the circulations, geometric, spatial, skeletal, geographical relations - bit by bit - comprising the manufacturing plant ("la central"). The structure, explanatory introduction of the solutions adopted by Alejandro de la Sota; analysis of the skeletal system of the building by parts, geometric and spatial operations. Construction, analysis of the realization of the work, constructive systems used in the building enclosures, roofs, skylights; from the general to the particular and studying the systems. Finally through small scale unique elements that are part of complex systems, such as multiple stairs, railings, carpentry, viewpoints are summarized. It is recapitulated in a synthesis which forms a whole with the sum of the parts, using linking resources that belongs to the additive architecture, such as the module, tours and visual links The final chapter of Conclusions contrast the hypothesis of the thesis regarding the maximum space architecture with minimal resources. It also includes various reflections as the dialectic between the fragmented space and the single space; expansive or inclusive growth; unique image and representation; domestic and industrial scale; structural abandonment or limitation of means. Perhaps the greatest interest of this thesis lies in the axonometric drawings made of the CLESA complex, which ideally have allowed to restore and rebuild the factory back to the beginning of its activity. Considering its potential full or partial disappearance, such recovery becomes relevant as a testimonial evidence of what it was.

PARTICIPAÇÃO ESCOLAR: UMA ANÁLISE A PARTIR DA HISTÓRIA DE VIDA DOS PARTICIPANTES

Esta dissertação consiste essencialmente numa reflexão sobre a participação numa escola pública da rede estadual de ensino de São Paulo, a partir da história de vida dos sujeitos que nela atuam, visando a compreender o que mantém motivadas as pessoas que se destacam por sua participação. É um estudo de natureza qualitativa, em que se relatam as experiências da própria autora e de mais duas pessoas da comunidade escolar, utilizando-se o método da história de vida. Esta pesquisa se estrutura em três etapas. Na primeira, através da metodologia adotada, buscou-se conhecer os sujeitos envolvidos no processo de participação. Na segunda, estudouse a literatura corrente sobre os conceitos de participação e voluntariado. A terceira etapa constitui-se em uma reflexão sobre a leitura das histórias de vida dos sujeitos sob a perspectiva da interculturalidade, da participação e do voluntariado. Na narrativa das histórias de vida, é visível a mudança que viveram as pessoas envolvidas, que, de uma participação ingênua, passaram a ter uma participação crítica.(AU)

PARTICIPAÇÃO ESCOLAR: UMA ANÁLISE A PARTIR DA HISTÓRIA DE VIDA DOS PARTICIPANTES

Esta dissertação consiste essencialmente numa reflexão sobre a participação numa escola pública da rede estadual de ensino de São Paulo, a partir da história de vida dos sujeitos que nela atuam, visando a compreender o que mantém motivadas as pessoas que se destacam por sua participação. É um estudo de natureza qualitativa, em que se relatam as experiências da própria autora e de mais duas pessoas da comunidade escolar, utilizando-se o método da história de vida. Esta pesquisa se estrutura em três etapas. Na primeira, através da metodologia adotada, buscou-se conhecer os sujeitos envolvidos no processo de participação. Na segunda, estudouse a literatura corrente sobre os conceitos de participação e voluntariado. A terceira etapa constitui-se em uma reflexão sobre a leitura das histórias de vida dos sujeitos sob a perspectiva da interculturalidade, da participação e do voluntariado. Na narrativa das histórias de vida, é visível a mudança que viveram as pessoas envolvidas, que, de uma participação ingênua, passaram a ter uma participação crítica.(AU)

Developmental exposure to vasopressin increases aggression in adult prairie voles

Although the biological roots of aggression have been the source of intense debate, the precise physiological mechanisms responsible for aggression remain poorly understood. In most species, aggression is more common in males than females; thus, gonadal hormones have been a focal point for research in this field. Although gonadal hormones have been shown to influence the expression of aggression, in many cases aggression can continue after castration, indicating that testicular steroids are not completely essential for the expression of aggression. Recently, the mammalian neuropeptide arginine vasopressin (AVP) has been implicated in aggression. AVP plays a particularly important role in social behavior in monogamous mammals, such as prairie voles (Microtus ochrogaster). In turn, the effects of social experiences may be mediated by neuropeptides, including AVP. For example, sexually naïve prairie voles are rarely aggressive. However, 24 h after the onset of mating, males of this species become significantly aggressive toward strangers. Likewise, in adult male prairie voles, central (intracerebroventricular) injections of AVP can significantly increase intermale aggression, suggesting a role for AVP in the expression of postcopulatory aggression in adult male prairie voles. In this paper, we demonstrate that early postnatal exposure to AVP can have long-lasting effects on the tendency to show aggression, producing levels of aggression in sexually naïve, adult male prairie voles that are comparable to those levels observed after mating. Females showed less aggression and were less responsive to exogenous AVP, but the capacity of an AVP V1a receptor antagonist to block female aggression also implicates AVP in the development of female aggression.

CD8 T cell ignorance or tolerance to islet antigens depends on antigen dose

There are two major mechanisms reported to prevent the autoreactivity of islet-specific CD8+ T cells: ignorance and tolerance. When ignorance is operative, naïve autoreactive CD8+ T cells ignore islet antigens and recirculate without causing damage, unless activated by an external stimulus. In the case of tolerance, CD8+ T cells are deleted. Which factor(s) contributes to each particular outcome was previously unknown. Here, we demonstrate that the concentration of self antigen determines which mechanism operates. When ovalbumin (OVA) was expressed at a relatively low concentration in the pancreatic islets of transgenic mice, there was no detectable cross-presentation, and the CD8+ T cell compartment remained ignorant of OVA. In mice expressing higher doses of OVA, cross-presentation was detectable and led to peripheral deletion of OVA-specific CD8+ T cells. When cross-presentation was prevented by reconstituting the bone marrow compartment with cells incapable of presenting OVA, deletional tolerance was converted to ignorance. Thus, the immune system uses two strategies to avoid CD8+ T cell-mediated autoimmunity: for high dose antigens, it deletes autoreactive T cells, whereas for lower dose antigens, it relies on ignorance.

A transgenic mouse model to analyze CD8+ effector T cell differentiation in vivo

Antigen-specific effector T cells are prerequisite to immune protection, but because of the lack of effector cell-specific markers, their generation and differentiation has been difficult to study. We report that effector cells are highly enriched in a T cell subset that can be specifically identified in transgenic (T-GFP) mice expressing green fluorescent protein (GFP) under control of the murine CD4 promoter and proximal enhancer. Consistent with previous studies of these transcriptional control elements, GFP was strongly and specifically expressed in nearly all resting and short-term activated CD4+ and CD8+ T cells. However, when T-GFP mice were challenged with vaccinia virus, allogeneic tumor cells, or staphylococcal enterotoxin A, the cytotoxic and IFN-γ-producing T cells lost GFP expression. Upon T cell receptor (TCR) ligation by αCD3, sorted GFP+ cells fluxed calcium and proliferated vigorously. In contrast, GFP− effector cells showed a diminished calcium flux and did not proliferate. Instead, they underwent apoptosis unless supplied with exogenous IL-2. By reverse transcription–PCR analysis, the GFP− cells up-regulated the pro-apoptotic molecule, Fas-L, and down-regulated gene expression of the proximal TCR signaling molecule, CD3ζ, and c-jun, a component of the AP-1 transcription factor. Thus, differential regulation of TCR signaling may explain the divergent responses of naïve and effector T cells to antigen stimulation.

Dependence of lymphopenia-induced T cell proliferation on the abundance of peptide/ MHC epitopes and strength of their interaction with T cell receptors

Factors that affect naïve T cell proliferation in syngeneic lymphopenic hosts were investigated. 2C T cell receptor (TCR) transgenic T cells lacking both CD8 and CD4 survived but hardly proliferated. Proliferation of CD8+ 2C cells was proportional to the abundance of cognate peptide/MHC complexes and was severely inhibited by injection of anti-CD8 antibody. Weakly reactive self-peptides slightly enhanced CD8+ 2C cell proliferation whereas a potent agonist peptide promoted much more rapid proliferation, but inflammation-stimulating adjuvant had only a small effect on the rate of cell proliferation. The findings suggest that under uniform lymphopenic conditions, the widely different rates of proliferation of T cells expressing various TCR, or the same TCR in the presence or absence of CD8, reflect the strength of interaction between TCR and MHC associated with particular self-peptides.

Catalytic efficiency and vitality of HIV-1 proteases from African viral subtypes

The vast majority of HIV-1 infections in Africa are caused by the A and C viral subtypes rather than the B subtype prevalent in the United States and Western Europe. Genomic differences between subtypes give rise to sequence variations in the encoded proteins, including the HIV-1 protease. Because some amino acid polymorphisms occur at sites that have been associated with drug resistance in the B subtype, it is important to assess the effectiveness of protease inhibitors that have been developed against different subtypes. Here we report the enzymatic characterization of HIV-1 proteases with sequences found in drug-naïve Ugandan adults. The A protease used in these studies differs in seven positions (I13V/E35D/M36I/R41K/R57K/H69K/L89M) in relation to the consensus B subtype protease. Another protease containing a subset of these amino acid polymorphisms (M36I/R41K/H69K/L89M), which are found in subtype C and other HIV subtypes, also was studied. Both proteases were found to have similar catalytic constants, kcat, as the B subtype. The C subtype protease displayed lower Km values against two different substrates resulting in a higher (2.4-fold) catalytic efficiency than the B subtype protease. Indinavir, ritonavir, saquinavir, and nelfinavir inhibit the A and C subtype proteases with 2.5–7-fold and 2–4.5-fold weaker Kis than the B subtype. When all factors are taken into consideration it is found that the C subtype protease has the highest vitality (4–11 higher than the B subtype) whereas the A subtype protease exhibits values ranging between 1.5 and 5. These results point to a higher biochemical fitness of the A and C proteases in the presence of existing inhibitors.

CD8+ T cells control the TH phenotype of MBP-reactive CD4+ T cells in EAE mice

Trimolecular interactions between the T cell antigen receptor and MHC/peptide complexes, together with costimulatory molecules and cytokines, control the initial activation of naïve T cells and determine whether the helper precursor cell differentiates into either T helper (TH)1 or TH2 effector cells. We now present evidence that regulatory CD8+ T cells provide another level of control of TH phenotype during further evolution of immune responses. These regulatory CD8+ T cells are induced by antigen-triggered CD4+ TH1 cells during T cell vaccination and, in vitro, distinguish mature TH1 from TH2 cells in a T cell antigen receptor Vβ-specific and Qa-1-restricted manner. In vivo, protection from experimental autoimmune encephalomyelitis (EAE) induced by T cell vaccination depends on CD8+ T cells, and myelin basic protein-reactive TH1 Vβ8+ clones, but not TH2 Vβ8+ clones, used as vaccine T cells, protect animals from subsequent induction of EAE. Moreover, in vivo depletion of CD8+ T cells during the first episode of EAE results in skewing of the TH phenotype toward TH1 upon secondary myelin basic protein stimulation. These data provide evidence that CD8+ T cells control autoimmune responses, in part, by regulating the TH phenotype of self-reactive CD4+ T cells.

How the protease thrombin talks to cells

How does a protease act like a hormone to regulate cellular functions? The coagulation protease thrombin (EC 3.4.21.5) activates platelets and regulates the behavior of other cells by means of G protein-coupled protease-activated receptors (PARs). PAR1 is activated when thrombin binds to and cleaves its amino-terminal exodomain to unmask a new receptor amino terminus. This new amino terminus then serves as a tethered peptide ligand, binding intramolecularly to the body of the receptor to effect transmembrane signaling. The irreversibility of PAR1’s proteolytic activation mechanism stands in contrast to the reversible ligand binding that activates classical G protein-coupled receptors and compels special mechanisms for desensitization and resensitization. In endothelial cells and fibroblasts, activated PAR1 rapidly internalizes and then sorts to lysosomes rather than recycling to the plasma membrane as do classical G protein-coupled receptors. This trafficking behavior is critical for termination of thrombin signaling. An intracellular pool of thrombin receptors refreshes the cell surface with naïve receptors, thereby maintaining thrombin responsiveness. Thus cells have evolved a trafficking solution to the signaling problem presented by PARs. Four PARs have now been identified. PAR1, PAR3, and PAR4 can all be activated by thrombin. PAR2 is activated by trypsin and by trypsin-like proteases but not by thrombin. Recent studies with knockout mice, receptor-activating peptides, and blocking antibodies are beginning to define the role of these receptors in vivo.

Regulatory function of in vivo anergized CD4+ T cells

It has been suggested that anergic T cells may not be only inert cells but may rather play an active role, for example by regulating immune responses. We have previously reported the existence of “anergic” IL-10-producing CD4+ T cells generated in vivo by continuous antigenic stimulation. Using a gene transfer system where the antigen recognized by such T cells is expressed in skeletal muscle by two different DNA viral vectors, we show that these cells not only remain tolerant toward their cognate antigen but also can suppress the immune response of naïve T cells against the immunogenic adenoviral proteins. Furthermore, they can completely inhibit tissue destruction that takes place as a result of an immune response. The system presented here is unique in that the T cells have been anergized in vivo, their antigen specificity and functional status are known, and the amount, form, and timing of antigen expression can be manipulated. This model will therefore permit us to carefully dissect the mechanisms by which these anergic T cells regulate the priming and/or effector function of naïve T cells.

How αβ T cells deal with induced TCRα ablation

On deletion of the gene encoding the constant region of the T cell antigen receptor (TCR)α chain in mature T cells by induced Cre-mediated recombination, the cells lose most of their TCR from the cell surface within 7–10 days, but minute amounts of surface-bound TCRβ chains are retained for long periods of time. In a situation in which cellular influx from the thymus is blocked, TCR-deficient naïve T cells decay over time, the decay rates being faster for CD8+ cells (t1/2 ≈ 16 days) than for CD4+ cells (t1/2 ≈ 46 days). TCR+ naïve cells are either maintained (CD8+) or decay more slowly (CD4+; t1/2 ≈ 78 days.) Numbers of TCR-deficient memory T cells decline very slowly (CD8+ cells; t1/2 ≈ 52 days) or not at all (CD4+ cells), but at the population level, these cells fail to expand as their TCR+ counterparts do. Together with earlier data on T cell maintenance in environments lacking appropriate major histocompatibility complex antigens, these data argue against the possibility that spontaneous ligand-independent signaling by the αβTCR contributes significantly to T-cell homeostasis.

Dominant-negative action of the jimpy mutation in mice complemented with an autosomal transgene for myelin proteolipid protein.

Mutations in genes encoding membrane proteins have been associated with cell death of unknown cause from invertebrate development to human degenerative diseases. A point mutation in the gene for myelin proteolipid protein (PLP) underlies oligodendrocyte death and dysmyelination in jimpy mice, an accurate model for Pelizaeus-Merzbacher disease. To distinguish the loss of PLP function from other effects of the misfolded protein, we took advantage of the X chromosomal linkage of the gene and have complemented jimpy with a wild-type PLP transgene. In this artificial heterozygous situation, the jimpy mutation emerged as genetically dominant. At the cellular level oligodendrocytes showed little increase in survival although endogenous PLP gene and autosomal transgene were truly coexpressed. In surviving oligodendrocytes, wild-type PLP was functional and immunodetectable in myelin. Moreover, compacted myelin sheaths regained their normal periodicity. This strongly suggests that, despite the presence of functional wild-type PLP, misfolded jimpy PLP is by itself the primary cause of abnormal oligodendrocyte death.