Prototipos experimentales modernos: la colonia de Schorlemerallee y las villas Am Rupenhorn de los Luckhardt y Anker. Berlín 1924-1930

La colonia experimental de Schorlemerallee y las villas Am Rupenhorn son dos proyectos concluidos en 1930 por los hermanos Wassili y Hans Luckhardt con Alfons Anker en Berlín. Ambos proyectos forman parte del mismo proceso, que comienza en la Colonia -una exploración sobre el lenguaje moderno en una serie de fases sucesivas- y culmina con las Villas. Éstas últimas, realizadas inmediatamente después de la Colonia, son la síntesis de esa experiencia, aunque finalmente acabaron trascendiéndola, ya que se convirtieron en un modelo sobre la casa en la naturaleza, sobre la idea de la villa clásica y sobre los nuevos modos de habitar, alcanzando con el tiempo la condición de canon moderno. A pesar de ello, no es esta condición lo más importante. Lo singular en este caso, es el propio proceso de proyecto –Colonia versus Villas- un verdadero experimento en su concepción, método y resultados, a través del cual sus autores investigan nuevas tecnologías aplicadas a nuevas formas de habitar y desarrollan un nuevo lenguaje, cuyo resultado son unos prototipos tecnológicos, con los que pretenden, como diría Mies van der Rohe: “Me he esforzado por construir una arquitectura para una sociedad tecnológica. He intentado que todo resultara razonable y claro.....para que cualquiera pueda hacer arquitectura.” El momento y lugar no pueden ser más propicios: Berlín entre 1924 y 1930, en el mismo origen del Movimiento Moderno. El experimento se plantea con auténtico rigor científico. Los arquitectos diseñan, construyen y financian su proyecto, controlando todas sus variables. Especialmente, por lo insólito, es el control de la variable económica. Porque este factor, la economía, es para ellos una clave fundamental del proceso. Se trataba de demostrar que la Nueva Arquitectura (o Neues Bauen, como les gustaba denominarla) era capaz de construir mejor y más rápido la vivienda para una nueva sociedad. La revolución y la vanguardia van de la mano: son el Zeitgeist o espíritu de la época, un contexto que es parte sustancial del proceso, y como lo calificarían los Smithson, un contexto heroico. El concepto se centra en la tríada Bauhaus: diseño + tecnología x economía. En cuanto al método, se fijan una serie de parámetros –las variables del experimento- que se agrupan en tres categorías distintas: topología, tipología y tecnología. La combinación de las variables de cada categoría dará lugar a un sistema con unas características determinadas: una definición del espacio, una forma, un lenguaje y una tecnología, características que permiten establecer las reglas para su desarrollo. Los sistemas resultantes son tres, denominados según su doble condición tipológica/ tecnológica: 1. Sistema de muro de carga: Viviendas adosadas en zig-zag o Mauerwerksbauten. 2. Sistema de esqueleto de acero: Viviendas aisladas o Stahlskelettbauten 3. Sistema de hormigón armado: Viviendas en hilera recta o Betonbauten Las villas Am Rupenhorn se plantean a continuación como verificación de este proceso: la síntesis de las categorías desarrolladas en la Colonia. Pero llegan en un momento de gracia, justo cuando los Luckhardt y Anker se encuentran profundamente implicados en el proceso de desarrollo de un nuevo lenguaje y con la reciente experiencia de la Colonia, que ha sido un éxito en casi todos los aspectos posibles. “En 1930, están en la cumbre”, como diría su mejor crítico y antiguo colaborador: Achim Wendschuh. En las Villas, los arquitectos integran su lenguaje, ya plenamente moderno, con sus experiencias previas: las que los relacionan con su reciente expresionismo (que se podría calificar como Kunstwollen) y con la tradición clásica de la cultura arquitectónica alemana: el sentido del material que deben a Semper y la sensibilidad hacia el paisaje, que toman de Schinkel. El extraordinario interés de las Villas se debe a factores como el tratamiento de la relación dual, poco habitual en la arquitectura moderna, la síntesis de lenguajes y las circunstancias de su momento histórico, factores que las han convertido en una propuesta única e irrepetible de una de las vías experimentales más interesantes y desconocidas de la Modernidad. ABSTRACT The experimental Housing Estate of Schorlemerallee and the Am Rupenhorn Villas are two projects completed by the brothers Wassili and Hans Luckhardt with Alfons Anker in Berlin in 1930. Both projects are part of the same process, starting with the Housing Estate --an exploration of the modern language in a series of phases- which culminates with the Villas project. The Villas Am Ruperhorn, designed immediately after the Housing development, are the synthesis and crowning point of this experience, even finally over passing it, since they have become a model of the house in nature, related with both the ideal of the classical villa and the new ways of life, reaching the condition of a modern canon. However, this is not its most important issue. The most remarkable condition is the project process itself -Housing versus Villas- a true experiment in concept, method and results, in which the authors research new technologies for new ways of living, developing an innovative language, with results in new prototypes, in the way Mies van der Rohe was looking for: “I have tried to make an architecture for a technological society. I have wanted to keep everything reasonable and clear… to have an architecture that anybody can do." The time and place could not be more favourable: Berlin from 1924 to 1930, in the very origin of Modern Movement. The experiment takes place with genuine scientific accuracy. Architects design, build and finance their own project, controlling all variables. Especially, and quite unusual, the control of the economic variable. Precisely the economic factor is for them a fundamental key to the process. It was shown to prove that the new architecture (or Neues Bauen, as they liked to call it) was able to build not only faster, better and more efficient dwellings for a new society, but also at lower cost. Revolution and Avant-garde use to move forward together, because they share the Zeitgeist --or time's spirit--, a context which is a substantial part of the process, and as the Alison & Peter Smithsons would describe, an heroic context. The concept focuses on the Bauhaus triad: Design + Technology x Economy. For the method, a number of variables are fixed --the experimental parameters-- that are later grouped into three distinct categories: Topology, Typology and Technology. The combination of these variables within each category gives way to several systems, with specific characteristics: a definition of space, a form, a language and a technology, thus allowing to establish the rules for its development: The resulting systems are three, called by double typological / technological issue: 1. Terraced Housing in zig-zag or Mauerwerksbauten (bearing wall system) 2. Detached Housing or Stahlskelettbauten (steel skeleton system) 3. Terraced Housing in one row or Betonbauten (reinforced concrete system) The Am Rupenhorn Villas are planned as the check of this process: the synthesis of the categories developed all through the Housing Estate research. The Am Ruperhorn project is developed in a crucial moment, just as the Luckhardts and Anker are deeply involved in the definition process of a new language after the recent experience of Schorlemerallee, which has been a success in almost all possible aspects. "In 1930, they are on the top” has said his best critic and long-time collaborator, Achim Wendschuh. In the Villas, the authors make up their fully modern language with their own background, related with their recent Expressionist trend (Kunstwollen) and with the classical tradition of the German architectural culture: the notion of material related with Semper and the sensible approach to the landscape, linked with Schinkel. Its extraordinary interest lay on diverse factors, such as dual relationships, unusual in modern architecture, synthesis of languages and circumstances of their historical moment, all factors that have become a unique and unrepeatable proposal in one of the most extraordinary experimental ways of Modernity.

A neuromodulatory role of interleukin-1β in the hippocampus

It is widely accepted that interleukin-1β (IL-1β), a cytokine produced not only by immune cells but also by glial cells and certain neurons influences brain functions during infectious and inflammatory processes. It is still unclear, however, whether IL-1 production is triggered under nonpathological conditions during activation of a discrete neuronal population and whether this production has functional implications. Here, we show in vivo and in vitro that IL-1β gene expression is substantially increased during long-term potentiation of synaptic transmission, a process considered to underlie certain forms of learning and memory. The increase in gene expression was long lasting, specific to potentiation, and could be prevented by blockade of potentiation with the N-methyl-d-aspartate (NMDA) receptor antagonist, (±)-2-amino-5-phosphonopentanoic acid (AP-5). Furthermore, blockade of IL-1 receptors by the specific interleukin-1 receptor antagonist (IL-1ra) resulted in a reversible impairment of long-term potentiation maintenance without affecting its induction. These results show for the first time that the production of biologically significant amounts of IL-1β in the brain can be induced by a sustained increase in the activity of a discrete population of neurons and suggest a physiological involvement of this cytokine in synaptic plasticity.

Control of time-dependent biological processes by temporally patterned input

Temporal patterning of biological variables, in the form of oscillations and rhythms on many time scales, is ubiquitous. Altering the temporal pattern of an input variable greatly affects the output of many biological processes. We develop here a conceptual framework for a quantitative understanding of such pattern dependence, focusing particularly on nonlinear, saturable, time-dependent processes that abound in biophysics, biochemistry, and physiology. We show theoretically that pattern dependence is governed by the nonlinearity of the input–output transformation as well as its time constant. As a result, only patterns on certain time scales permit the expression of pattern dependence, and processes with different time constants can respond preferentially to different patterns. This has implications for temporal coding and decoding, and allows differential control of processes through pattern. We show how pattern dependence can be quantitatively predicted using only information from steady, unpatterned input. To apply our ideas, we analyze, in an experimental example, how muscle contraction depends on the pattern of motorneuron firing.

Use of intrinsic modes in biology: Examples of indicial response of pulmonary blood pressure to ± step hypoxia

Recently, a new method to analyze biological nonstationary stochastic variables has been presented. The method is especially suitable to analyze the variation of one biological variable with respect to changes of another variable. Here, it is illustrated by the change of the pulmonary blood pressure in response to a step change of oxygen concentration in the gas that an animal breathes. The pressure signal is resolved into the sum of a set of oscillatory intrinsic mode functions, which have zero “local mean,” and a final nonoscillatory mode. With this device, we obtain a set of “mean trends,” each of which represents a “mean” in a definitive sense, and together they represent the mean trend systematically with different degrees of oscillatory content. Correspondingly, the oscillatory content of the signal about any mean trend can be represented by a set of partial sums of intrinsic mode functions. When the concept of “indicial response function” is used to describe the change of one variable in response to a step change of another variable, we now have a set of indicial response functions of the mean trends and another set of indicial response functions to describe the energy or intensity of oscillations about each mean trend. Each of these can be represented by an analytic function whose coefficients can be determined by a least-squares curve-fitting procedure. In this way, experimental results are stated sharply by analytic functions.

Carbohydrate-deficient glycoprotein syndrome type V: Deficiency of dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase

Deficiency of dolichyl-P-Glc:Man9GlcNAc2-PP-dolichyl glucosyltransferase is the cause of an additional type of carbohydrate-deficient glycoprotein syndrome (CDGS type V). Clinically this type resembles the classical type Ia of CDGS caused by the deficiency of phosphomannomutase. As a result of the glucosyltransferase deficiency in CDGS type V nonglucosylated lipid-linked oligosaccharides accumulate. The defect is leaky and glucosylated oligosaccharides are found on nascent glycoproteins. The limited availability of glucosylated lipid-linked oligosaccharides explains the incomplete usage of N-glycosylation sites in glycoproteins. This finding is reflected in the presence of transferrin forms in serum that lack one or both of the two N-linked oligosaccharides and the reduction of mannose incorporation to about one-third of control in glycoproteins of fibroblasts.

A new mechanism of sound generation in songbirds

Our current understanding of the sound-generating mechanism in the songbird vocal organ, the syrinx, is based on indirect evidence and theoretical treatments. The classical avian model of sound production postulates that the medial tympaniform membranes (MTM) are the principal sound generators. We tested the role of the MTM in sound generation and studied the songbird syrinx more directly by filming it endoscopically. After we surgically incapacitated the MTM as a vibratory source, zebra finches and cardinals were not only able to vocalize, but sang nearly normal song. This result shows clearly that the MTM are not the principal sound source. The endoscopic images of the intact songbird syrinx during spontaneous and brain stimulation-induced vocalizations illustrate the dynamics of syringeal reconfiguration before phonation and suggest a different model for sound production. Phonation is initiated by rostrad movement and stretching of the syrinx. At the same time, the syrinx is closed through movement of two soft tissue masses, the medial and lateral labia, into the bronchial lumen. Sound production always is accompanied by vibratory motions of both labia, indicating that these vibrations may be the sound source. However, because of the low temporal resolution of the imaging system, the frequency and phase of labial vibrations could not be assessed in relation to that of the generated sound. Nevertheless, in contrast to the previous model, these observations show that both labia contribute to aperture control and strongly suggest that they play an important role as principal sound generators.

Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein

The identification of the neutralization domains of hepatitis C virus (HCV) is essential for the development of an effective vaccine. Here, we show that the hypervariable region 1 (HVR1) of the envelope 2 (E2) protein is a critical neutralization domain of HCV. Neutralization of HCV in vitro was attempted with a rabbit hyperimmune serum raised against a homologous synthetic peptide derived from the HVR1 of the E2 protein, and the residual infectivity was evaluated by inoculation of HCV-seronegative chimpanzees. The source of HCV was plasma obtained from a patient (H) during the acute phase of posttransfusion non-A, non-B hepatitis, which had been titered for infectivity in chimpanzees. The anti-HVR1 antiserum induced protection against homologous HCV infection in chimpanzees, but not against the emergence of neutralization escape mutants that were found to be already present in the complex viral quasispecies of the inoculum. The finding that HVR1 can elicit protective immunity opens new perspectives for the development of effective preventive strategies. However, the identification of the most variable region of HCV as a critical neutralization domain poses a major challenge for the development of a broadly reactive vaccine against HCV.

Stimulation of bacteriophage T4 middle transcription by the T4 proteins MotA and AsiA occurs at two distinct steps in the transcription cycle

The bacteriophage T4 encodes proteins that are responsible for tightly regulating mRNA synthesis throughout phage development in Escherichia coli. The three classes of T4 promoters (early, middle, and late) are utilized sequentially by the host RNA polymerase as a result of phage-induced modifications. One such modification is the tight binding of the T4 AsiA protein to the σ70 subunit of the RNA polymerase. This interaction is pivotal for the transition between T4 early and middle transcription, since it both inhibits recognition of host and T4 early promoters and stimulates T4 middle mode synthesis. The activation of T4 middle transcription also requires the T4 MotA protein, bound specifically to its recognition sequence, the “Mot box,” which is centered at position −30 of these promoters. Accordingly, the two T4 proteins working in concert are sufficient to effectively switch the transcription specificity of the RNA polymerase holoenzyme. Herein, we investigate the mechanism of transcription activation and report that, while the presence of MotA and AsiA increases the initial recruitment of RNA polymerase to a T4 middle promoter, it does not alter the intrinsic stability of the discrete complexes formed. In addition, we have characterized the RNA polymerase-promoter species by UV laser footprinting and followed their evolution from open into initiating complexes. These data, combined with in vitro transcription assays, indicate that AsiA and MotA facilitate promoter escape, thereby stimulating the production of full-length transcripts.

Naturally variant autosomal and sex-linked loci determine the severity of iron overload in β2-microglobulin-deficient mice

Hereditary hemochromatosis (HH) is a common chronic human genetic disorder whose hallmark is systemic iron overload. Homozygosity for a mutation in the MHC class I heavy chain paralogue gene HFE has been found to be a primary cause of HH. However, many individuals homozygous for the defective allele of HFE do not develop iron overload, raising the possibility that genetic variation in modifier loci contributes to the HH phenotype. Mice deficient in the product of the β2-microglobulin (β2M) class I light chain fail to express HFE and other MHC class I family proteins, and they have been found to manifest many characteristics of the HH phenotype. To determine whether natural genetic variation plays a role in controlling iron overload, we performed classical genetic analysis of the iron-loading phenotype in β2M-deficient mice in the context of different genetic backgrounds. Strain background was found to be a major determinant in iron loading. Sex played a role that was less than that of strain background but still significant. Resistance and susceptibility to iron overload segregated as complex genetic traits in F1 and back-cross progeny. These results suggest the existence of naturally variant autosomal and Y chromosome-linked modifier loci that, in the context of mice genetically predisposed by virtue of a β2M deficiency, can profoundly influence the severity of iron loading. These results thus provide a genetic explanation for some of the variability of the HH phenotype.

Cerebral organization for language in deaf and hearing subjects: Biological constraints and effects of experience

Cerebral organization during sentence processing in English and in American Sign Language (ASL) was characterized by employing functional magnetic resonance imaging (fMRI) at 4 T. Effects of deafness, age of language acquisition, and bilingualism were assessed by comparing results from (i) normally hearing, monolingual, native speakers of English, (ii) congenitally, genetically deaf, native signers of ASL who learned English late and through the visual modality, and (iii) normally hearing bilinguals who were native signers of ASL and speakers of English. All groups, hearing and deaf, processing their native language, English or ASL, displayed strong and repeated activation within classical language areas of the left hemisphere. Deaf subjects reading English did not display activation in these regions. These results suggest that the early acquisition of a natural language is important in the expression of the strong bias for these areas to mediate language, independently of the form of the language. In addition, native signers, hearing and deaf, displayed extensive activation of homologous areas within the right hemisphere, indicating that the specific processing requirements of the language also in part determine the organization of the language systems of the brain.

Structural Analysis and Molecular Model of a Self-Incompatibility RNase from Wild Tomato1

Self-incompatibility RNases (S-RNases) are an allelic series of style glycoproteins associated with rejection of self-pollen in solanaceous plants. The nucleotide sequences of S-RNase alleles from several genera have been determined, but the structure of the gene products has only been described for those from Nicotiana alata. We report on the N-glycan structures and the disulfide bonding of the S3-RNase from wild tomato (Lycopersicon peruvianum) and use this and other information to construct a model of this molecule. The S3-RNase has a single N-glycosylation site (Asn-28) to which one of three N-glycans is attached. S3-RNase has seven Cys residues; six are involved in disulfide linkages (Cys-16-Cys-21, Cys-46-Cys-91, and Cys-166-Cys-177), and one has a free thiol group (Cys-150). The disulfide-bonding pattern is consistent with that observed in RNase Rh, a related RNase for which radiographic-crystallographic information is available. A molecular model of the S3-RNase shows that four of the most variable regions of the S-RNases are clustered on one surface of the molecule. This is discussed in the context of recent experiments that set out to determine the regions of the S-RNase important for recognition during the self-incompatibility response.

Antisense ribosomes: rRNA as a vehicle for antisense RNAs.

Although rRNA has a conserved core structure, its size varies by more than 2000 bases between eubacteria and vertebrates, mostly due to the size variation of discrete variable regions. Previous studies have shown that insertion of foreign sequences into some of these variable regions has little effect on rRNA function. These properties make rRNA a potentially very advantageous vehicle to carry other RNA moieties with biological activity, such as "antisense RNAs." We have explored this possibility by inserting antisense RNAs targeted against one essential and two nonessential genes into a site within a variable region in the Tetrahymena thermophila large subunit rRNA gene. Expression of each of the three genes tested can be drastically reduced or eliminated in transformed T. thermophila lines containing these altered rRNAs. In addition, we found that only antisense rRNAs containing RNA sequences complementary to the 5' untranslated region of the targeted mRNA were effective. Lines containing antisense rRNAs targeted against either of the nonessential genes grow well, indicating that the altered rRNAs fulfill their functions within the ribosome. Since functional rRNA is extremely abundant and stable and comes into direct contact with translated mRNAs, it may prove to be an unparalleled vehicle for enhancing the activity of functional RNAs that act on mRNAs.

Activation of muscarinic acetylcholine receptors via their allosteric binding sites.

Ligands that bind to the allosteric-binding sites on muscarinic acetylcholine receptors alter the conformation of the classical-binding sites of these receptors and either diminish or increase their affinity for muscarinic agonists and classical antagonists. It is not known whether the resulting conformational change also affects the interaction between the receptors and the G proteins. We have now found that the muscarinic receptor allosteric modulators alcuronium, gallamine, and strychnine (acting in the absence of an agonist) alter the synthesis of cAMP in Chinese hamster ovary (CHO) cells expressing the M2 or the M4 subtype of muscarinic receptors in the same direction as the agonist carbachol. In addition, most of their effects on the production of inositol phosphates in CHO cells expressing the M1 or the M3 muscarinic receptor subtypes are also similar to (although much weaker than) those of carbachol. The agonist-like effects of the allosteric modulators are not observed in CHO cells that have not been transfected with the gene for any of the subtypes of muscarinic receptors. The effects of alcuronium on the formation of cAMP and inositol phosphates are not prevented by the classical muscarinic antagonist quinuclidinyl benzilate. These observations demonstrate for the first time that the G protein-mediated functional responses of muscarinic receptors can be evoked not only from their classical, but also from their allosteric, binding sites. This represents a new mechanism of receptor activation.

Mitochondrial diversity and the origins of African and European cattle.

The nature of domestic cattle origins in Africa are unclear as archaeological data are relatively sparse. The earliest domesticates were humpless, or Bos taurus, in morphology and may have shared a common origin with the ancestors of European cattle in the Near East. Alternatively, local strains of the wild ox, the aurochs, may have been adopted by peoples in either continent either before or after cultural influence from the Levant. This study examines mitochondrial DNA displacement loop sequence variation in 90 extant bovines drawn from Africa, Europe, and India. Phylogeny estimation and analysis of molecular variance verify that sequences cluster significantly into continental groups. The Indian Bos indicus samples are most markedly distinct from the others, which is indicative of a B. taurus nature for both European and African ancestors. When a calibration of sequence divergence is performed using comparisons with bison sequences and an estimate of 1 Myr since the Bison/Bos Leptobos common ancestor, estimates of 117-275,000 B.P. and 22-26,000 B.P. are obtained for the separation between Indians and others and between African and European ancestors, respectively. As cattle domestication is thought to have occurred approximately 10,000 B.P., these estimates suggest the domestication of genetically discrete aurochsen strains as the origins of each continental population. Additionally, patterns of variation that are indicative of population expansions (probably associated with the domestication process) are discernible in Africa and Europe. Notably, the genetic signatures of these expansions are clearly younger than the corresponding signature of African/European divergence.

Acridones: a chemically new group of protonophores.

Although the interaction of proton-conducting ionophores (protonophores) with photosynthetic electron transport has been extensively studied during the past decade, the mode of action of protonophores remained uncertain. For a better understanding of the molecular mechanism of the action of protonophores, the introduction of chemically new types of molecules will be required. In this work, we demonstrate that acridones (9-azaanthracene-10-ones) completely fulfill this requirement. At low concentrations of acridones, the thermoluminescence bands at +20 degrees C and +10 degrees C were strongly inhibited, while normal electron transport activity was retained. This indicates that the concentrations of S2 and S3 states involved in the generation of these bands are reduced. At higher concentrations, an increased activity of electron transport was observed, which is attributed to the typical uncoupler effect of protonophores. Indeed, acridones accelerate the decay of the electrochromic absorbance change at 515 nm and also inhibit the generation of the transmembrane proton gradient, measured as an absorbance transient of neutral red. Variable fluorescence induction was quenched even at low concentrations of acridones but was restored by either a long-term illumination or high light intensity. Acridones, similarly to other protonophores, promoted the autooxidation of the high-potential form of cytochrome b559 and partially converted it to lower potential forms. These results suggest that acridones, acting as typical protonophores, uncouple electron transport, accelerate the deactivation of the S2 and S3 states on the donor side, and facilitate the oxidation of cytochrome b559 on the acceptor side of photosystem II.