Chronology of Lateglacial ice flow reorganization and deglaciation in the Gotthard Pass area, Central Swiss Alps, based on cosmogenic 10Be and in situ 14C

We reconstruct the timing of ice flow reconfiguration and deglaciation of the Central Alpine Gotthard Pass, Switzerland, using cosmogenic 10Be and in situ14C surface exposure dating. Combined with mapping of glacial erosional markers, exposure ages of bedrock surfaces reveal progressive glacier downwasting from the maximum LGM ice volume and a gradual reorganization of the paleoflow pattern with a southward migration of the ice divide. Exposure ages of ∼16–14 ka (snow corrected) give evidence for continuous early Lateglacial ice cover and indicate that the first deglaciation was contemporaneous with the decay of the large Gschnitz glacier system. In agreement with published ages from other Alpine passes, these data support the concept of large transection glaciers that persisted in the high Alps after the breakdown of the LGM ice masses in the foreland and possibly decayed as late as the onset of the Bølling warming. A younger group of ages around ∼12–13 ka records the timing of deglaciation following local glacier readvance during the Egesen stadial. Glacial erosional features and the distribution of exposure ages consistently imply that Egesen glaciers were of comparatively small volume and were following a topographically controlled paleoflow pattern. Dating of a boulder close to the pass elevation gives a minimum age of 11.1 ± 0.4 ka for final deglaciation by the end of the Younger Dryas. In situ14C data are overall in good agreement with the 10Be ages and confirm continuous exposure throughout the Holocene. However, in situ14C demonstrates that partial surface shielding, e.g. by snow, has to be incorporated in the exposure age calculations and the model of deglaciation.

Faunal turnovers in the central Pacific benthic foraminifera during the Paleocene-Eocene thermal maximum

Although it is well known that the Paleocene/Eocene thermal maximum (PETM) coincided with a major benthic foraminiferal extinction event, the detailed pattern of the faunal turnover has not yet been clarified. Our high-resolution benthic foraminiferal and carbon isotope analyses at the low latitude Pacific Ocean Shatsky Rise have revealed the following record of major faunal transitions: (1) An initial turnover which involved the benthic foraminiferal extinction event (BFE). The BFE, marked by a sharp transition from Pre-extinction fauna to Disaster fauna represented by small-sized Bolivina gracilis, expresses the onset of the PETM and the abrupt extinction of about 30% of taxa. This faunal transition lasted about 45-74 kyr after the initiation of the PETM and was followed by: (2) the appearance of Opportunistic fauna represented by Quadrimorphina profunda, which existed for about 74-91 kyr after the initiation of the PETM. These two faunas, which appeared after the extinction event, are characterized by low diversity and dwarfism, possibly due to lowered oxygen condition and decreased surface productivity. The second pronounced turnover involved the gradual recovery from Opportunistic Fauna to the establishment of Recovery fauna, which coincided with the recovery about 83-91 kyr after its initiation.

Pedogeomorphology, geochronology and paleobotany of soil profiles obtained in the Nagqu area, central Tibet

Vast areas on the Tibetan Plateau are covered by alpine sedge mats consisting of different species of the genus Kobresia. These mats have topsoil horizons rich in rhizogenic organic matter which creates turfs. As the turfs have recently been affected by a complex destruction process, knowledge concerning their soil properties, age and pedogenesis are needed. In the core area of Kobresia pygmaea mats around Nagqu (central Tibetan Plateau, ca. 4500 m a.s.l.), four profiles were subjected to pedological, paleobotanical and geochronological analyses concentrating on soil properties, phytogenic composition and dating of the turf. The turf of both dry K. pygmaea sites and wet Kobresia schoenoides sites is characterised by an enrichment of living (dominant portion) and dead root biomass. In terms of humus forms, K. pygmaea turfs can be classified as Rhizomulls mainly developed from Cambisols. Wet-site K. schoenoides turfs, however, can be classified as Rhizo-Hydromors developed from Histic Gleysols. At the dry sites studied, the turnover of soil organic matter is controlled by a non-permafrost cold thermal regime. Below-ground remains from sedges are the most frequent macroremains in the turf. Only a few pollen types of vascular plants occur, predominantly originating from sedges and grasses. Large amounts of microscopic charcoal (indeterminate) are present. Macroremains and pollen extracted from the turfs predominantly have negative AMS 14C ages, giving evidence of a modern turf genesis. Bulk-soil datings from the lowermost part of the turfs have a Late Holocene age comprising the last ca. 2000 years. The development of K. pygmaea turfs was most probably caused by an anthropo(zoo)-genetically initiated growth of sedge mats replacing former grass-dominated vegetation ('steppe'). Thus the turfs result from the transformation of pre-existing topsoils comprising a secondary penetration and accumulation of roots. K. schoenoides turfs, however, are characterised by a combined process of peat formation and penetration/accumulation of roots probably representing a (quasi) natural wetland vegetation.

Dissolved iron measurements from 32 stations in the Central Arctic Ocean and Arctic Shelf Sea during POLARSTERN expedition ARK-XXII/2

Concentrations of dissolved (<0.2 µm) Fe (DFe) in the Arctic shelf seas and in the surface waters of the central Arctic Ocean are presented. In the Barents and Kara seas, near-surface DFe minima indicate depletion of DFe by phytoplankton growth. Below the surface, lower DFe concentrations in the Kara Sea (~0.4-0.6 nM) than in the Barents Sea (~0.6-0.8 nM) likely reflect scavenging removal or biological depletion of DFe. Very high DFe concentrations (>10 nM) in the bottom waters of the Laptev Sea shelf may be attributed to either sediment resuspension, sinking of brine or regeneration of DFe in the lower layers. A significant correlation (R2 = 0.60) between salinity and DFe is observed. Using d18O, salinity, nutrients and total alkalinity data, the main source for the high (>2 nM) DFe concentrations in the Amundsen and Makarov Basins is identified as (Eurasian) river water, transported with the Transpolar Drift (TPD). On the North American side of the TPD, the DFe concentrations are low (<0.8 nM) and variations are determined by the effects of sea-ice meltwater, biological depletion and remineralization and scavenging in halocline waters from the shelf. This distribution pattern of DFe is also supported by the ratio between unfiltered and dissolved Fe (high (>4) above the shelf and low (<4) off the shelf).

Long-term persistence of Mediterranean pine forests in the Duero Basin (central Spain) during the Holocene: The case of Pinus pinaster Aiton

In the southern Duero Basin of central Spain, there are vast areas of aeolian sand sheets and dune fields. A comprehensive survey of the sand quarries in this area identified a number of palaeosols in sedimentary sequences. The identification and AMS radiocarbon dating of soil charcoal fragments collected in these palaeosols indicate the persistence of Pinus pinaster in this area throughout most of the Holocene. Although potential natural vegetation models have usually considered the Pinus pinaster forests in this inland area of artificial origin, soil charcoal analysis provides firm evidence of a natural origin. Our data fit perfectly with the pattern of Holocene vegetation development for inland areas of Iberia, which are characterised by stability of pine forests throughout the Holocene. Finally, the growing body of palaeobotanical evidence from Iberia (macrofossils and pollen) is contributing to improve our knowledge of P. pinaster ecology, showing that this species has been present in most Iberian regions during the Holocene, where it has inhabited areas characterised by a very diverse set of climatic and soil conditions.

Reconstructing the Timing and Dispersion Routes of HIV-1 Subtype B Epidemics in The Caribbean and Central America: A Phylogenetic Story.

The Caribbean and Central America are among the regions with highest HIV-1B prevalence worldwide. Despite of this high virus burden, little is known about the timing and the migration patterns of HIV-1B in these regions. Migration is one of the major processes shaping the genetic structure of virus populations. Thus, reconstruction of epidemiological network may contribute to understand HIV-1B evolution and reduce virus prevalence. We have investigated the spatio-temporal dynamics of the HIV-1B epidemic in The Caribbean and Central America using 1,610 HIV-1B partial pol sequences from 13 Caribbean and 5 Central American countries. Timing of HIV-1B introduction and virus evolutionary rates, as well as the spatial genetic structure of the HIV-1B populations and the virus migration patterns were inferred. Results revealed that in The Caribbean and Central America most of the HIV-1B variability was generated since the 80 s. At odds with previous data suggesting that Haiti was the origin of the epidemic in The Caribbean, our reconstruction indicated that the virus could have been disseminated from Puerto Rico and Antigua. These two countries connected two distinguishable migration areas corresponding to the (mainly Spanish-colonized) Easter and (mainly British-colonized) Western islands, which indicates that virus migration patterns are determined by geographical barriers and by the movement of human populations among culturally related countries. Similar factors shaped the migration of HIV-1B in Central America. The HIV-1B population was significantly structured according to the country of origin, and the genetic diversity in each country was associated with the virus prevalence in both regions, which suggests that virus populations evolve mainly through genetic drift. Thus, our work contributes to the understanding of HIV-1B evolution and dispersion pattern in the Americas, and its relationship with the geography of the area and the movements of human populations.

Climatic factors control rodent seed predation in Pinus pinea L. stands in Central Spain

- Context: Pinus pinea L. presents serious problems of natural regeneration in managed forest of Central Spain. The species exhibits specific traits linked to frugivore activity. Therefore, information on plant–animal interactions may be crucial to understand regeneration failure. - Aims: Determining the spatio-temporal pattern of P. pinea seed predation by Apodemus sylvaticus L. and the factors involved. Exploring the importance of A. sylvaticus L. as a disperser of P. pinea. Identifying other frugivores and their seasonal patterns. - Methods: An intensive 24-month seed predation trial was carried out. The probability of seeds escaping predation was modelled through a zero-inflated binomial mixed model. Experiments on seed dispersal by A. sylvaticus were conducted. Cameras were set up to identify other potential frugivores. - Results: Decreasing rodent population in summer and masting enhances seed survival. Seeds were exploited more rapidly nearby parent trees and shelters. A. sylvaticus dispersal activity was found to be scarce. Corvids marginally preyed upon P. pinea seeds. - Conclusions: Survival of P. pinea seeds is climate-controlled through the timing of the dry period together with masting occurrence. Should germination not take place during the survival period, establishment may be limited. A. sylvaticus mediated dispersal does not modify the seed shadow. Seasonality of corvid activity points to a role of corvids in dispersal.

Arquitectura industrial tabacalera en la España peninsular: secaderos y fábricas

La Arquitectura industrial del tabaco en España está representada por dos tipos de construcciones, que corresponden a las dos fases en las que se divide el proceso de producción del tabaco: los secaderos (arquitectura bioclimática donde se realiza el secado), y las fábricas (centros donde se elabora el tabaco procedente de los secaderos). Las fábricas se repartieron por todo el territorio español, ocupando preferiblemente los lugares costeros, aunque existen casos en los que su localización obedecía a razones políticas. Estos edificios, en su mayoría, incluidos en los centros históricos de las ciudades, han cambiando de uso, y las antiguas fábricas de tabaco se han transformado en su mayoría, en centros de cultura, o centros sociales y representativos. La tesis surge del análisis de las características constructivas de la arquitectura industrial del tabaco: de los secaderos y de las fábricas, por tratarse de una tipología con suficiente entidad y un ejemplo de arquitectura bioclimática de producción en el caso de los secaderos, y por conseguir haberse adaptado a otros usos en el caso de las fábricas. La arquitectura de producción emplea un lenguaje acorde con los avances de la industrialización, anticipando materiales y estructuras, y condensando en una tipología específica las complejas relaciones establecidas entre producto, hombres y espacio. Estos edificios tuvieron una extensa implantación en el territorio, y se caracterizan por una serie de valores tecnológicos, arquitectónicos, sociológicos y paisajísticos, que hacen de ellos un documento de primera magnitud para conocer: la evolución e implantación de las técnicas constructivas (materiales y estructuras), los procesos de innovación tipológica y la estructura económica y procedimientos técnicos utilizados. El territorio en el que se insertan constituye su contexto territorial, por lo que no sería adecuado considerar estos edificios como elementos aislados, sin analizar la relación con el entorno en el que se generaron. Por este motivo, se analizan las condiciones higrotérmicas ambientales de los secaderos para compararlas con las de confort humano y establecer relaciones y parámetros compatibles. Los ejemplos analizados de secaderos son todos de fábrica. El uso del ladrillo como módulo principal para la elaboración de un edificio, supone la consideración de un “grado cero” de todo el aparato constructivo y compositivo de la arquitectura. Dejar el ladrillo visto, supone hacer explícitos todos los procesos acumulativos. Este elemento mínimo, permite unas posibilidades enormemente abiertas, pero no absolutamente aleatorias, que definen su propia lógica combinatoria. La exigencia de sinceridad, característica de la arquitectura industrial, en la exposición de los materiales, exhibiéndolos en su propia naturaleza y en el modo real de ser utilizados, se hace patente en este tipo de construcción. Se realiza un estudio de permeabilidad en las fachadas de los secaderos, para determinar el grado de ventilación y su relación con la orientación, el patrón de celosía empleado y el volumen total. Este sistema de acondicionamiento climático específico, puede servir de recurso a otras construcciones, por lo que se podría trasladar el sistema constructivo y formal de los secaderos a otros usos, desde una doble vertiente: Arquitectura para la adaptación climática al entorno. Arquitectura como generadora de condiciones climáticas específicas, en el interior. La utilidad de los secaderos es fundamentalmente: proporcionar sombra, ventilación y un espacio cubierto, pero permeable en sus fachadas. La arquitectura industrial debe ser reconocida dentro del conjunto patrimonial, debido a sus características propias que permiten su diferenciación del resto de la arquitectura. Conocer la estructura productiva permite analizar correctamente estas construcciones, ya que el programa inicial es básico para entender la organización del espacio interior. Las fábricas no se situaron cerca de las zonas de producción del tabaco, excepto en dos casos: Cádiz y Palazuelo, en los que existen secaderos y campos de cultivo de hoja de tabaco en las áreas cercanas. La principal causa de esta separación es que el proceso de obtención de tabaco es un proceso dividido en dos fases principales: proceso primario y proceso secundario. En el proceso primario la hoja de tabaco se seca en los secaderos, en los que es determinante el clima, pero únicamente en el caso del secado del tabaco al aire. En el proceso secundario sin embargo, el tabaco llega previamente tratado a las fábricas, por lo que no influye el clima en esta parte del proceso. Esta razón determina que en las áreas climáticas donde se centra el estudio, haya zonas en las que existen fábrica y secaderos y otras en las que únicamente existe fábrica, o sólo secaderos. La localización de las fábricas atendía a razones de muy diferente índole, las más importantes fueron: geográficas, estratégicas, y políticas. En la mayoría de las fábricas la elección de la ciudad de emplazamiento estaba ligada a la recepción de la materia prima, que principalmente se hacía por vía marítima, o acuática (el caso de Sevilla), y por vía terrestre, utilizando como medio de transporte el ferrocarril. Sólo dos casos, de las antiguas fábricas, corresponden a razones políticas, son las dos únicas que no están en la costa: Madrid y Logroño. La de Madrid se construyó por centralidad política, y porque geográficamente ocupaba el punto central de todas las comunicaciones terrestres por carretera y ferrocarril. Muchas de las fábricas se situaron cercanas a las estaciones de ferrocarril. La de Logroño atendió, sin embargo, a razones políticas. Para finalizar, se realiza un estudio comparativo de las fábricas de Sevilla, Madrid y San Sebastián. Las razones que justifican esta elección son: - La de Sevilla fue históricamente la primera fábrica y la más importante. - La de Madrid fue la más importante a nivel administrativo, la sede de Tabacalera se instaló en la capital, y después de la de Sevilla, fue la que sirvió de modelo al resto de las fábricas. - La de San Sebastián era la más grande del Norte. Los análisis que se han realizado son de: volumen y superficies de patios, superficies de cubierta, permeabilidad o huecos en fachadas, orientación y soleamiento de patios, distribución espacial interior y organización, y evolución de usos. Podemos observar que en la mayoría de estas fábricas ha habido una transformación en el uso, pasando de ser edificios industriales a edificios culturales. Estas construcciones se pueden considerar como infraestructuras adaptables, por ser útiles, sostenibles y funcionales. ABSTRACT The Spanish industrial architecture of tobacco is represented by two construction types that correspond to the two phases of tobacco production: the drying sheds (bioclimatic constructions where the drying process takes place) and factories (centres where tobacco is processed after the drying process). The factories were distributed throughout the Spanish territory, preferably occupying coastal locations, although some of them were located elsewhere following political reasons. Most of the buildings inside city centres have suffered changes in their use, becoming cultural, social or representative centres. This thesis attempts the analysis of the constructive systems employed in tobacco industrial architecture, from drying sheds to factories. The drying sheds are an example of bioclimatic industrial architecture. The factories are a typology that have successfully adapted to new uses. Industrial architecture uses a language that follows the advances in industrialization, anticipating new materials and structures, and merging the complex relationships established among products, human beings, space and locations. These buildings were promoted extensively in the country. They are characterized by technological architectural sociological and landscaping innovations. They are considered as important examples of the evolution and the implementation of construction techniques (building materials and structures). They are also considered as examples of innovation in the building typology, in their economic structure and in the technologies that they have applied. The settings in which the drying sheds are placed have an important influence in them. They cannot be considered as isolated elements. Instead, there is a close relationship between drying sheds and the surroundings in which they are located. Drying sheds’ hygrotermal and environmental conditions are analyzed in this thesis to compare them with the values of human comfort and find suitable relationships and parameters. All the drying sheds that have been analyzed are constructed with brick. This implies a consideration of “zero degree” for both the construction and the composition of the architectural process. The detailing - entails making all the accumulative processes explicit as the brick walls are left exposed. This minimal component allows a wide range of options that are never random but based on the logic of the way in which it is combined. The “sincerity” in the exposition of material, displaying them in their very nature and showing how they are really used, is a basic characteristic of industrial architecture, and it is even more expressive in these types of buildings. The walls of the drying sheds undergo a permeability assessment in order to determine the degree of ventilation and orientation, the lattice pattern used and the overall volume. This specific conditioning system can serve as a resource for other buildings, and consequently, it could be transferred to other uses within a two-pronged approach: -Climatically adapted architecture that takes into account the surroundings. -Architecture as a generator of specific climatic conditions indoors. Drying sheds’ main purposes / aims deal with how to provide shade, ventilation and a covered space as well as permeability. The industrial architecture must be recognized as historical valuable buildings due to its intrinsic and distinctive characteristics. Knowing the productive structure, allow us to make a proper analysis of these buildings, since the basic aim, is to understand the spatial organization indoors. Factories did not come close to the tobacco production, with the exception of Cádiz and Palazuelo, where there are sheds and tobacco croplands nearby. The main reason for this separation is that the process of obtaining tobacco has two processes: the primary process and the secondary process. In the primary process tobacco leaves are left to dry. In the secondary process, previously manufactured tobacco allocated in the factories where the weather conditions are not important. This fact determines that in the climate areas where this study tales place there are some cases in which we can find both factories and drying sheds, and others where there are either factories or drying sheds only. The location of these factories met various demands, being the most outstanding the ones related to geographic, strategic and political reasons. In most factories the choice of its location was often linked to the incoming of raw goods, mainly delivered through waterways –it is the case of Seville,) and by land, using railways. The location of the factories was linked to political reasons in only two cases Madrid and Logroño, which are the only ones that are not placed near the coast. The one in Madrid was built due to its political centrality and because geographically speaking, it was the reference landmark of means of land and rail transports. Many factories, in fact, were settled nearby rail stations. For the factory in Logroño, only political reasons were taken into consideration. I should like to close by undertaking a comparative study of factories in Seville, Madrid and San Sebastian. There are a number of reasons to substantiate this choice: -The factory in Seville was historically speaking the first that was built and the most important one. -The factory in Madrid was the most important one administratively. This factory was the headquarters as well as being, after Seville, the one which provided a model for other factories. -The factory in San Sebastian is the biggest in the North of Spain. The analysis carried out are related to the volume of the buildings and the surface areas of the courtyards, the surface of the roofs, the permeability of the walls and the openings of the façade, the orientation and the sun exposure, the indoor spatial distribution and organization and evolution of the uses (formerly and currently) I observe that in most of these factories there has been a change in the use of the buildings, from industrial cultural purposes. These buildings can be considered as adaptable infrastructures based on a combination of architectural practicability, sustainability and functionality.

Structure of the imprinted mouse Snrpn gene and establishment of its parental-specific methylation pattern

The mouse Snrpn gene encodes the Smn protein, which is involved in RNA splicing. The gene maps to a region in the central part of chromosome 7 that is syntenic to the Prader–Willi/Angelman syndromes (PWS-AS) region on human chromosome 15q11-q13. The mouse gene, like its human counterpart, is imprinted and paternally expressed, primarily in brain and heart. We provide here a detailed description of the structural features and differential methylation pattern of the gene. We have identified a maternally methylated region at the 5′ end (DMR1), which correlates inversely with the Snrpn paternal expression. We also describe a region at the 3′ end of the gene (DMR2) that is preferentially methylated on the paternal allele. Analysis of Snrpn mRNA levels in a methylase-deficient mouse embryo revealed that maternal methylation of DMR1 may play a role in silencing the maternal allele. Yet both regions, DMR1 and DMR2, inherit the parental-specific methylation profile from the gametes. This methylation pattern is erased in 12.5-days postcoitum (dpc) primordial germ cells and reestablished during gametogenesis. DMR1 is remethylated during oogenesis, whereas DMR2 is remethylated during spermatogenesis. Once established, these methylation patterns are transmitted to the embryo and maintained, protected from methylation changes during embryogenesis and cell differentiation. Transfections of DMR1 and DMR2 into embryonic stem cells and injection into pronuclei of fertilized eggs reveal that embryonic cells lack the capacity to establish anew the differential methylation pattern of Snrpn. That all PWS patients lack DMR1, together with the overall high resemblance of the mouse gene to the human SNRPN, offers an excellent experimental tool to study the regional control of this imprinted chromosomal domain.

Ol-Prx 3, a member of an additional class of homeobox genes, is unimodally expressed in several domains of the developing and adult central nervous system of the medaka (Oryzias latipes)

Large-scale genetic screens for mutations affecting early neurogenesis of vertebrates have recently been performed with an aquarium fish, the zebrafish. Later stages of neural morphogenesis have attracted less attention in small fish species, partly because of the lack of molecular markers of developing structures that may facilitate the detection of discrete structural alterations. In this context, we report the characterization of Ol-Prx 3 (Oryzias latipes-Prx 3). This gene was isolated in the course of a large-scale screen for brain cDNAs containing a highly conserved DNA binding region, the homeobox helix-three. Sequence analysis revealed that this gene belongs to another class of homeobox genes, together with a previously isolated mouse ortholog, called OG-12 [Rovescalli, A. C., Asoh, S. & Nirenberg, M. (1996) Proc. Natl. Acad. Sci. USA 93, 10691–10696] and with the human SHOX gene [Rao, E., Weiss, B., Fukami, M., Rump, A., Niesler, B., et al. (1997) Nat. Genet. 16, 54–62], thought to be involved in the short-stature phenotype of Turner syndrome patients. These three genes exhibit a moderate level of identity in the homeobox with the other genes of the paired-related (PRX) gene family. Ol-Prx 3, as well as the PRX genes, are expressed in various cartilaginous structures of head and limbs. These genes might thus be involved in common regulatory pathways during the morphogenesis of these structures. Moreover, this paper reports a complex and monophasic pattern of Ol-Prx 3 expression in the central nervous system, which differs markedly from the patterns reported for the PRX genes, Prx 3 excluded: this gene begins to be expressed in a variety of central nervous system territories at late neurula stage. Strikingly, it remains turned on in some of the derivatives of each territory during the entire life of the fish. We hope this work will thus help identify common features for the PRX 3 family of homeobox genes.

Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells

In Drosophila, the chromosomal region 75C1–2 contains at least three genes, reaper (rpr), head involution defective (hid), and grim, that have important functions in the activation of programmed cell death. To better understand how cells are killed by these genes, we have utilized a well defined set of embryonic central nervous system midline cells that normally exhibit a specific pattern of glial cell death. In this study we show that both rpr and hid are expressed in dying midline cells and that the normal pattern of midline cell death requires the function of multiple genes in the 75C1–2 interval. We also utilized the P[UAS]/P[Gal4] system to target expression of rpr and hid to midline cells. Targeted expression of rpr or hid alone was not sufficient to induce ectopic midline cell death. However, expression of both rpr and hid together rapidly induced ectopic midline cell death that resulted in axon scaffold defects characteristic of mutants with abnormal midline cell development. Midline-targeted expression of the baculovirus p35 protein, a caspase inhibitor, blocked both normal and ectopic rpr- and hid-induced cell death. Taken together, our results suggest that rpr and hid are expressed together and cooperate to induce programmed cell death during development of the central nervous system midline.

UME6 is a central component of a developmental regulatory switch controlling meiosis-specific gene expression.

The UME6 gene of Saccharomyces cerevisiae was identified as a mitotic repressor of early meiosis-specific gene expression. It encodes a Zn2Cys6 DNA-binding protein which binds to URS1, a promoter element needed for both mitotic repression and meiotic induction of early meiotic genes. This paper demonstrates that a complete deletion of UME6 causes not only vegetative derepression of early meiotic genes during vegetative growth but also a significant reduction in induction of meiosis-specific genes, accompanied by a severe defect in meiotic progression. After initiating premeiotic DNA synthesis the vast majority of cells (approximately 85%) become arrested in prophase and fail to execute recombination; a minority of cells (approximately 15%) complete recombination and meiosis I, and half of these form asci. Quantitative analysis of the same early meiotic transcripts that are vegetatively derepressed in the ume6 mutant, SPO11, SPO13, IME2, and SPO1, indicates a low level of induction in meiosis above their vegetative derepressed levels. In addition, the expression of later meiotic transcripts, SPS2 and DIT1, is significantly delayed and reduced. The expression pattern of early meiotic genes in ume6-deleted cells is strikingly similar to that of early meiotic genes with promoter mutations in URS1. These results support the view that UME6 and URS1 are part of a developmental switch that controls both vegetative repression and meiotic induction of meiosis-specific genes.

Mutagenesis in the C-terminal region of human interleukin 5 reveals a central patch for receptor alpha chain recognition.

Cassette mutagenesis was used to identify side chains in human interleukin 5 (hIL-5) that mediate binding to hIL-5 receptor alpha chain (hIL-5R alpha). A series of single alanine substitutions was introduced into a stretch of residues in the C-terminal region, including helix D, which previously had been implicated in receptor alpha chain recognition and which is aligned on the IL-5 surface so as to allow the topography of receptor binding residues to be examined. hIL-5 and single site mutants were expressed in COS cells, their interactions with hIL-5R alpha were measured by a sandwich surface plasmon resonance biosensor method, and their biological activities were measured by an IL-5-dependent cell proliferation assay. A pattern of mutagenesis effects was observed, with greatest impact near the interface between the two four-helix bundles of IL-5, in particular at residues Glu-110 and Trp-111, and least at the distal ends of the D helices. This pattern suggests the possibility that residues near the interface of the two four-helix bundles in hIL-5 comprise a central patch or hot spot, which constitutes an energetically important alpha chain recognition site. This hypothesis suggests a structural explanation for the 1:1 stoichiometry observed for the complex of hIL-5 with hIL-5R alpha.

Down syndrome-critical region contains a gene homologous to Drosophila sim expressed during rat and human central nervous system development.

Many features of Down syndrome might result from the overdosage of only a few genes located in a critical region of chromosome 21. To search for these genes, cosmids mapping in this region were isolated and used for trapping exons. One of the trapped exons obtained has a sequence very similar to part of the Drosophila single-minded (sim) gene, a master regulator of the early development of the fly central nervous system midline. Mapping data indicated that this exonic sequence is only present in the Down syndrome-critical region in the human genome. Hybridization of this exonic sequence with human fetal kidney poly(A)+ RNA revealed two transcripts of 6 and 4.3 kb. In situ hybridization of a probe derived from this exon with human and rat fetuses showed that the corresponding gene is expressed during early fetal life in the central nervous system and in other tissues, including the facial, skull, palate, and vertebra primordia. The expression pattern of this gene suggests that it might be involved in the pathogenesis of some of the morphological features and brain anomalies observed in Down syndrome.

Avaliação da qualidade do Sistema de Informação de Registro de Óbitos Hospitalares (SIS-ROH), Hospital Central da Beira, Moçambique

As informações de mortalidade são úteis para avaliar a situação de saúde de uma população. Dados de mortalidade confiáveis produzidos por um sistema de informação de saúde nacional constituem uma ferramenta importante para o planejamento de saúde. Em muitos países, sobretudo em desenvolvimento, o sistema de informação de mortalidade continua precário. Apesar dos esforços feitos em Moçambique para melhoria das estatísticas de mortalidade, os desafios ainda prevalecem em termos de tecnologias de informação, capacidade técnica de recursos humanos e em termos de produção estatística. O SIS-ROH é um sistema eletrônico de registro de óbitos hospitalares de nível nacional, implementado em 2008 e tem uma cobertura de apenas 4% de todos os óbitos anuais do país. Apesar de ser um sistema de nível nacional, ele presentemente funciona em algumas Unidades Sanitárias (US), incluindo o Hospital Central da Beira (HCB). Dada a importância deste sistema para monitorar o padrão de mortalidade do HCB e, no geral, da cidade da Beira, este estudo avalia a qualidade do SIS-ROH do HCB. É um estudo descritivo sobre a completitude, cobertura, concordância e consistência dos dados do SIS-ROH. Foram analisados 3.009 óbitos de menores de 5 anos ocorridos entre 2010 e 2013 e regsitrados no SIS-ROH e uma amostra de 822 Certificados de Óbitos (COs) fetais e de menores de 5 anos do HCB. O SIS-ROH apresentou uma cobertura inferior a 50% calculados com os dados de mortalidade estimados pelo Inquérito Nacional de Causas de Morte (INCAM). Verificamos a utilização de dois modelos diferentes de CO (modelo antigo e atual) para o registro de óbitos referentes ao ano de 2013. Observou-se completitude excelente para a maioria das variáveis do SISROH. Das 25 variáveis analisadas dos COs observou-se a seguinte situação: 9 apresentaram completitude muito ruim, sendo elas relativas à identificação do falecido (tipo de óbito e idade), relativas ao bloco V em que dados da mãe devem ser obrigatoriamente preenchidos em caso de óbitos fetais e de menores de 1 ano (escolaridade, ocupação habitual, número de filhos tidos vivos e mortos, duração da gestação) e relativas às condições e às causas de óbito (autópsia e causa intermédiacódigo); 3 variáveis apresentaram completitude ruim relativas à identificação do falecido (NID) e relativas às condições e causas de morte (causa intermédia - descrição e causa básica - código); 9 apresentaram completitude regular relativas à identificação do falecido (data de nascimento e idade), relativas ao bloco V (idade da mãe, tipo de gravidez, tipo de parto, peso do feto/bebé ao nascer, morte do feto/bebé em relação ao parto) e relativas às condições e causa de óbito (causa direta- código, causa básica descrição); 2 apresentaram completitude bom relativas à identificação do falecido (sexo e raça/cor) e, por último, 2 apresentaram completitude excelente relativas ao local de ocorrência de óbito (data de internamento e data de óbito ou desaparecimento do cadáver). Algumas variáveis do SIS-ROH e dos COS apresentaram inconsistências. Observou-se falta de concordância para causa direta entre o SIS-ROH e os COs. Conclusão: Moçambique tem feito esforços para aprimorar as estatísticas de mortalidade, porém há lacunas na qualidade; a análise rotineria dos dados pode identificar essas lacunas e subsidiar seu aprimoramento.