Hippocampal long-term depression and depotentiation are defective in mice carrying a targeted disruption of the gene encoding the RI beta subunit of cAMP-dependent protein kinase.

The cAMP-dependent protein kinase (PKA) has been shown to play an important role in long-term potentiation (LTP) in the hippocampus, but little is known about the function of PKA in long-term depression (LTD). We have combined pharmacologic and genetic approaches to demonstrate that PKA activity is required for both homosynaptic LTD and depotentiation and that a specific neuronal isoform of type I regulatory subunit (RI beta) is essential. Mice carrying a null mutation in the gene encoding RI beta were established by use of gene targeting in embryonic stem cells. Hippocampal slices from mutant mice show a severe deficit in LTD and depotentiation at the Schaffer collateral-CA1 synapse. This defect is also evident at the lateral perforant path-dentate granule cell synapse in RI beta mutant mice. Despite a compensatory increase in the related RI alpha protein and a lack of detectable changes in total PKA activity, the hippocampal function in these mice is not rescued, suggesting a unique role for RI beta. Since the late phase of CA1 LTP also requires PKA but is normal in RI beta mutant mice, our data further suggest that different forms of synaptic plasticity are likely to employ different combinations of regulatory and catalytic subunits.

Directed selection of recombinant human monoclonal antibodies to herpes simplex virus glycoproteins from phage display libraries.

Human monoclonal antibodies have considerable potential in the prophylaxis and treatment of viral disease. However, only a few such antibodies suitable for clinical use have been produced to date. We have previously shown that large panels of human recombinant monoclonal antibodies against a plethora of infectious agents, including herpes simplex virus types 1 and 2, can be established from phage display libraries. Here we demonstrate that facile cloning of recombinant Fab fragments against specific viral proteins in their native conformation can be accomplished by panning phage display libraries against viral glycoproteins "captured" from infected cell extracts by specific monoclonal antibodies immobilized on ELISA plates. We have tested this strategy by isolating six neutralizing recombinant antibodies specific for herpes simplex glycoprotein gD or gB, some of which are against conformationally sensitive epitopes. By using defined monoclonal antibodies for the antigen-capture step, this method can be used for the isolation of antibodies to specific regions and epitopes within the target viral protein. For instance, monoclonal antibodies to a nonneutralizing epitope can be used in the capture step to clone antibodies to neutralizing epitopes, or antibodies to a neutralizing epitope can be used to clone antibodies to a different neutralizing epitope. Furthermore, by using capturing antibodies to more immunodominant epitopes, one can direct the cloning to less immunogenic ones. This method should be of value in generating antibodies to be used both in the prophylaxis and treatment of viral infections and in the characterization of the mechanisms of antibody protective actions at the molecular level.

Transplantation of a 17-amino acid alpha-helical DNA-binding domain into an antibody molecule confers sequence-dependent DNA recognition.

Recombinant antibodies capable of sequence-specific interactions with nucleic acids represent a class of DNA- and RNA-binding proteins with potential for broad application in basic research and medicine. We describe the rational design of a DNA-binding antibody, Fab-Ebox, by replacing a variable segment of the immunoglobulin heavy chain with a 17-amino acid domain derived from TFEB, a class B basic helix-loop-helix protein. DNA-binding activity was studied by electrophoretic mobility-shift assays in which Fab-Ebox was shown to form a specific complex with DNA containing the TFEB recognition motif (CACGTG). Similarities were found in the abilities of TFEB and Fab-Ebox to discriminate between oligodeoxyribonucleotides containing altered recognition sequences. Comparable interference of binding by methylation of cytosine residues indicated that Fab-Ebox and TFEB both contact DNA through interactions along the major groove of double-stranded DNA. The results of this study indicate that DNA-binding antibodies of high specificity can be developed by using the modular nature of both immunoglobulins and transcription factors.

Human autoantibody recognition of DNA.

Combinatorial IgG Fab phage display libraries prepared from a systemic lupus erythematosus (SLE) donor and a healthy donor were affinity selected against human placental DNA. Human monoclonal antibody Fab fragments specific for DNA were isolated from both libraries, although Fabs of the highest affinity were isolated only from the lupus library. Generally, apparent affinities of the Fabs for human placental DNA, purified double-stranded DNA, and denatured DNA were approximately equivalent. Surface plasmon resonance indicated Fab binding constants for a double-stranded oligodeoxynucleotide of 0.2-1.3 x 10(8) M-1. The higher-affinity Fabs, as ranked by binding to human placental DNA or to the oligonucleotide probe, tested positive in the Crithidia luciliae assay commonly used in the diagnosis of SLE, and interestingly the genes encoding the heavy-chain variable regions of these antibodies displayed evidence of only minimal somatic hypermutation. The heavy chains of the SLE Fabs were characterized by a predominance of basic residues toward the N terminus of complementarity-determining region 3 (CDR3). The crucial role of heavy-chain CDR3 (HCDR3) in high-affinity DNA recognition was suggested by the creation of DNA binding in an unrelated antibody by HCDR3 transplantation from SLE antibodies. We propose that high-affinity DNA-binding antibodies can arise in SLE without extensive somatic hypermutation in the variable-region genes because of the expression of inappropriate HCDR3s.

Estudio bibliométrico de programas e intervenciones sobre educación alimentaria y nutricional en el medio escolar en España

Introducción: La obesidad en la población infantil y juvenil en España se sitúa actualmente en el 13,9%, y el sobrepeso se encuentra en el 26,3%. Esto hace que sea fundamental la adopción en los primeros años de vida de unos hábitos alimentarios correctos, donde la educación alimentaria y nutricional, desarrollada dentro de los programas de educación para la salud en el medio escolar, juega un papel fundamental. El objetivo del presente trabajo fue analizar, mediante revisión bibliométrica, la producción científica existente sobre programas o intervenciones de educación alimentaria y nutricional desarrollados en el medio escolar en España que muestran influencia en la salud y/o en los hábitos alimentarios de los escolares. Material y Métodos: Estudio descriptivo transversal de los resultados obtenidos en la búsqueda bibliográfica de las bases de datos Medline, Cochrane Library Plus en Español, Cuiden, Excelencia clínica, IBECS, Scielo, CSIC (ICYT, ISOC e IME), Lilacs, Cuidatge y Teseo. Se estudiaron indicadores bibliométricos: bases de datos, revistas, documentos publicados, idiomas, autoría, Índice de colaboración y grado de obsolescencia (Semiperíodo de Burton y Kebler e Índice de Price), entre otros. Resultados: La búsqueda proporcionó un total de 148 registros. La tasa final de artículos pertinentes fue de 49 (33,11%). La base de datos que más registros pertinentes proporcionó fue Medline con 24 (48,98%). 42 de los registros seleccionados (85,71%) pertenecían a artículos originales. La revista Nutrición Hospitalaria fue la que presentó mayor número de publicaciones, con 11 (22,45%). El Semiperíodo de Burton y Kebler fue de 6 años y el Índice de Price fue de 42,86%. Conclusiones: Existe una gran producción de artículos científicos relacionados con programas de educación alimentaria y nutricional en el medio escolar en España, lo cual es un indicador de la importancia de la adquisición de hábitos alimentarios saludables en la población infantil y juvenil y del interés que despiertan.

La aplicación de stop-motion en arquitectura: materia y luz

Se inicia un análisis de los procesos de trabajo de stop-motion porque ayudan a comprender las diferentes escalas en arquitectura donde las maquetas se convierten en futuros prototipos de infraestructuras de edificios o de paisaje. Stop motion es una técnica de animación fotograma a fotograma de objetos estáticos mediante la manipulación de figuras de plastilina en entornos fijos con cambios de luz, color y sonido. Igual que dicha técnica reúne lo mejor del rodaje tradicional -story board, escenografía, fotografía, personajes, iluminación- la animación de maquetas de interiores sintetiza micro-procesos de mayor repercusión -habitaciones con cambios de humedad, de temperatura, de ventilación y de iluminación- incorporando efectos especiales que son procesados digitalmente en post-producción. Se construyen varios prototipos de habitación con parámetros fijos como el tamaño y la posición de la cámara y otros variables como los materiales, los personajes y la iluminación. Representan un mundo en miniatura que intenta aportar un acercamiento sensorial y atmosférico analizando la magia y la fantasía que Junichirô Tanizaki describe en la penumbra de las construcciones tradicionales japonesas y estudiando las imperfecciones de los escenarios que Tim Burton manipula en su películas de animación con una textura que las tecnologías digitales no pueden igualar. El objetivo es utilizar una escala micro para realizar unos modelos interiores donde las condiciones atmosféricas están controladas y reducidas, y tomar datos que se podrían aplicar a un proceso de modelado a escala intermedia para testar prototipos de edificios como el túnel de viento; o, finalmente, a una escala macro con maquetas de un sector de la costa o de un río donde los fenómenos meteorológicos son los protagonistas para simular inundaciones y diseñar futuras medidas de prevención y seguridad.

The social evil in Chicago: a study of existing conditions with recommendations by the Vice Commission of Chicago, a municipal body appointed by the Mayor and the City Council of the City of Chicago, and submitted as its report to the Mayor and City Council of Chicago

Preface -- Outline of study -- Resolution of appreciation -- Introduction and summary -- Proposed ordinance -- Recommendations -- Existing conditions in Chicago -- The social evil and the saloon -- The social evil and the police -- Sources of supply -- Child protection and education -- Rescue and reform -- The social evil and its medical aspects -- Appendices: Text of revised statutes of Illinois and ordinances of the City of Chicago ; Tables ; Exhibits.

Catharine Waugh McCullouch papers in the Mary Earhart Dillon collection, 1869-1945

Collection primarily documents McCulloch's research on women's legal status, and her work with the Illinois Equal Suffrage Association, the National American Woman Suffrage Association, and the League of Women Voters. There is also documentation of women in the legal profession, of McCulloch's friendships with the other women suffragists and lawyers, and some biographical material. The papers contain little information about her family or social life.

Palladin's Plant physiology.

3rd ed.

Sm-Nd isotope and Mn/Ca ratios for cleaned Neogloboquadrina pachyderma from ODP Hole 105-647A (Table 1)

The neodymium (Nd) isotope composition of ancient seawater is a potentially useful tracer of changes in continental inputs and ocean circulation on timescales of a few ka. Here we present the first Nd isotope record for seawater using sedimentary foraminifera cleaned using standard oxidative-reductive techniques. The data, along with Mn/Ca ratios, suggest that cleaned foraminifera provide a reliable record of Nd in seawater and hold out the prospect of using Nd in foraminifera to examine changes in seawater that accompany glacial-interglacial climatic cycles. The principal potential problem to be overcome with the use of forams as records of trace elements in ancient seawater is their diagenetic Fe-Mn coatings. These contain large amounts of Nd and other trace elements but can be cleaned off using highly reducing reagents. Mn(Ca ratios for the majority of the cleaned sedimentary foraminifera analysed here lie within the range (10-100 µmol/mol) that has yielded success in studies of transition elements in forams. Mass-balance modelling suggests that for residual Mn/Ca ratios <100 µmol/mol, Nd added to the foram in the coating will never shift the measured Nd isotope composition significantly away from the seawater value acquired by the foram test in the water column. Additionally, Nd concentrations measured in cleaned sedimentary foraminifera are comparable with those for a modern sample that has never encountered diagenetic fluids. Finally, core-top planktonic foraminifera for two sites have Nd isotope compositions that are identical to local surface seawater. The data we present here for Labrador Sea forams over the past 2.5 m.y. are interpreted in terms of changes in the seawater isotopic composition. The data show a pronounced shift from epsilon-Nd values of ~-12 to ~-19 in the period 2.5-1.5 Ma. This change is interpreted to result from the initiation of Northern Hemisphere glaciation and the increased derivation of Labrador Sea Nd via ice-rafting from Archaean terranes in central Canada. In combination with stable isotope and foraminiferal relative species abundance data, the new Nd data are consistent with the surface hydrography of the Labrador Sea being dominated by a fluctuating balance between cold, polar waters containing unradiogenic Nd and warm, subtropical waters containing more radiogenic Nd. The major change in Labrador Sea Nd that is observed in the past 2.5 Ma can, on its own, account for the change in the Nd isotope composition of North Atlantic Deep Water over the same time period.