What is paragonimus rudis (diesing, 1850)?: report on a field study in Mato Grosso, Brazil

Paragonimus rudis was found in the lungs of a giant otter Lutra (pteronura) brasiliensis by Natterer in 1828, who dissected the animal in the former capital Mato Grosso (=Vila Bela), Brazil. The flukes were described by Diesing in 1850, and redescribed by Braun in 1901. Both descriptions do not allow to identify the species. Therefore, P. rudis must be regarded a "nomen nudum". Because its rediscovery is desirable with regard to historical reasons and nomenclatoric questions, a field study was performed in Mato Grosso in 1980. Of 354 freshwater crabs from 24 localities collected and examined for parasitic infections, about 25% were found to be infected with 7kinds of trematode larvae, which differed distincly from Paragonimus-metacercariae. The question, whether P. rudis or other lung fluke species do not seem to occur or cannot be found any longer in the area investigated by us, is discussed.

El Real Conservatorio de Artes (1824-1850): Orígenes y gestación de la ingeniería industrial moderna

El "Conservatorio de Artes" tuvo un origen Ilustrado, emulando a su homónimo parisino, pero nació durante el absolutismo (1824), tras un frustrado intento afrancesado (1810). Absorbió al "Gabinete de Máquinas" y tuvo como primer director a López de Peñalver. Supuso un puente entre la Ilustración y la Ingeniería Industrial decimonónica, sobre todo, a partir de la institucionalización del envío de pensionados a la "École Centrale des Arts et Manufactures" parisina, con cuyo retorno consigue transformarse en "Real Instituto Industrial" (1850). Aparte destaca su proyección social, tanto en su papel de oficina de patentes como en la promoción de exposiciones industriales.

Redescrição de Pterobothrium crassicolle Diesing, 1850 (Cestoda: Trypanorhyncha) e revalidação da espécie

É feito um estudo dos plerocercos, larvas de Trypanorhyncha, coletados de peixes estuarinos (Bagrus marinus) e de peixes fluviais, da região de Belém, Pará; os peixes fluviais foram a dourada (Brachyplatystoma flavicans) e a piramutaba (Brachyplatystoma vaillanti). Estes plerocercos foram comparados com outros coletados de pescadas (Cynoscion) e corvinas (Micropogonias), do litoral do Rio de Janeiro. Foram identificados à espécie Pterobothrium crassicolle Diesing, 1850; é dada uma redescrição, uma vez que se considerava como espécie imperfeitamente conhecida.

Genuine savings and future well-being in Germany, 1850-2000

Genuine Savings (GS), also known as ‘net adjusted savings’, is a composite indicator of the sustainability of economic development. Genuine Savings reflects year-on-year changes in the total wealth or capital of a country, including net investment in produced capita, investment in human capital, depletion of natural resources, and damage caused by pollution. A negative Genuine Savings rate suggests that the stock of national wealth is declining and that future utility must be less than current utility, indicating that economic development is non-sustainable (Hamilton and Clemens, 1999). We make use of data over a 150 year period to examine the relationship between Genuine Savings and a number of indicators of well-being over time, and compare the relative changes in human, produced, and components of natural capital over the period. Overall, we find that the magnitude of genuine savings is positively related to changes in future consumption, with some evidence of a cointegrating relationship. However, the relationships between genuine savings and infant mortality or average heights are less clear.

The human CFTR protein expressed in CHO cells activates aquaporin-3 in a cAMP-dependent pathway: study by digital holographic microscopy.

The transmembrane water movements during cellular processes and their relationship to ionic channel activity remain largely unknown. As an example, in epithelial cells it was proposed that the movement of water could be directly linked to cystic fibrosis transmembrane conductance regulator (CFTR) protein activity through a cAMP-stimulated aqueous pore, or be dependent on aquaporin. Here, we used digital holographic microscopy (DHM) an interferometric technique to quantify in situ the transmembrane water fluxes during the activity of the epithelial chloride channel, CFTR, measured by patch-clamp and iodide efflux techniques. We showed that the water transport measured by DHM is fully inhibited by the selective CFTR blocker CFTRinh172 and is absent in cells lacking CFTR. Of note, in cells expressing the mutated version of CFTR (F508del-CFTR), which mimics the most common genetic alteration encountered in cystic fibrosis, we also show that the water movement is profoundly altered but restored by pharmacological manipulation of F508del-CFTR-defective trafficking. Importantly, whereas activation of this endogenous water channel required a cAMP-dependent stimulation of CFTR, activation of CFTR or F508del-CFTR by two cAMP-independent CFTR activators, genistein and MPB91, failed to trigger water movements. Finally, using a specific small-interfering RNA against the endogenous aquaporin AQP3, the water transport accompanying CFTR activity decreased. We conclude that water fluxes accompanying CFTR activity are linked to AQP3 but not to a cAMP-stimulated aqueous pore in the CFTR protein.

Viajar a través del Cosmos: la medida de la creación de riqueza y la serie histórica del producto interior bruto en España (1850-2008)

Este trabajo responde a la réplica de Leandro Prados de la Escosura acerca de mi estimación de la serie histórica del Producto Interior Bruto de España (R.E.A., 49 (XVII), 2009, págs. 5 a 45). Demuestra que el IPC es el mejor deflactor disponible para reconstruir el PIB antes de la CNE porque mide correctamente las variaciones interanuales del nivel general de precios. Emplea un procedimiento de enlace de la serie histórica de la contabilidad nacional que es consistente con los nuevos sistemas de cuentas nacionales SCN-93 y SEC-95 y coincide con los empleados por todos los organismos económicos internacionales. La actualización del sistema contable, con la inclusión de la economía sumergida y de la producción para uso final propio, ha dejado obsoletas las estimaciones anteriores y exige estimaciones de segunda generación, con la inevitable readaptación de los niveles relativos de las distintas economías.

CHO expression of a novel human recombinant IgG1 anti-RhD antibody isolated by phage display.

Replacement of the hyperimmune anti-Rhesus (Rh) D immunoglobulin, currently used to prevent haemolytic disease of the newborn, by fully recombinant human anti-RhD antibodies would solve the current logistic problems associated with supply and demand. The combination of phage display repertoire cloning with precise selection procedures enables isolation of specific genes that can then be inserted into mammalian expression systems allowing production of large quantities of recombinant human proteins. With the aim of selecting high-affinity anti-RhD antibodies, two human Fab libraries were constructed from a hyperimmune donor. Use of a new phage panning procedure involving bromelin-treated red blood cells enabled the isolation of two high-affinity Fab-expressing phage clones. LD-6-3 and LD-6-33, specific for RhD. These showed a novel reaction pattern by recognizing the D variants D(III), D(IVa), D(IVb), D(Va), D(VI) types I and II. D(VII), Rh33 and DFR. Full-length immunoglobulin molecules were constructed by cloning the variable regions into expression vectors containing genomic DNA encoding the immunoglobulin constant regions. We describe the first, stable, suspension growth-adapted Chinese hamster ovary (CHO) cell line producing a high affinity recombinant human IgG1 anti-RhD antibody adapted to pilot-scale production. Evaluation of the Fc region of this recombinant antibody by either chemiluminescence or antibody-dependent cell cytotoxicity (ADCC) assays demonstrated macrophage activation and lysis of red blood cells by human lymphocytes. A consistent source of recombinant human anti-RhD immunoglobulin produced by CHO cells is expected to meet the stringent safety and regulatory requirements for prophylactic application.

Redescription of Prosthenhystera obesa (Diesing, 1850) (Callodistomidae, Digenea) with New Host Records and Data on Morphological Variability

Prosthenhystera obesa (Diesing,1850) Travassos, 1922 from the gall bladder of Astyanax bimaculatus, Caranx gibbosus, Galeocharax humeralis, Leporinus copelandii, Pimelodus fur, Pseudopimelodus roosevelti, Salminus brevidens, Salminus maxillosus and from the new hosts, Cynopotamus amazonum and Triurobrycon lundii is redescribed, demonstrating a large morphological variation, mainly in body and testes size and shape. New hosts harbouring immature specimens of P. obesa are presented: Brycon sp., Leporellus vittatus, Pachyurus squamipinnis, Pimelodus clarias, Pseudoplatystoma corruscans and Salminus hilarii. Scanning electron microscopy micrographies, original figures and measurements of adult and immature specimens from different Brazilian hosts and localities are presented

Characterization of the effects of IL-17F on CHO cell line generation

CHO is the most commonly used mammalian host for the generation of cell lines allowing for the production of high quality therapeutic proteins. The generation of such cell lines is a lengthy and resource-intensive process requiring extensive screening in order to isolate candidates with optimal characteristics, such as growth, stability and productivity. For this reason, the biotechnology industry invests much effort in attempts to optimize CHO expression systems in order to streamline and shorten the cell line selection process. Based on preliminary observations of a facilitated selection of CHO-GS cell lines expressing members of the IL-17 cytokine family, this study investigates the use of IL-17F as a novel enhancing factor for CHO cell line generation. Using two different CHO expression systems (exploiting GS and DHFR-based selection), we demonstrated that IL-17F expression caused a significant increase in the occurrence of colonies during the selection process. All colonies selected produced substantial amounts of IL-17F, suggesting that benefits were conferred, during selection, to those cells expressing the cytokine. Furthermore, transgene expression levels were significantly increased when the selection pressure was raised to a level that would not normally be permissive for colony selection (i.e. 100 |o.M MSX for the CHO-GS expression system or 1000 nM MTX for the CHO-DHFR system). Finally, IL-17F expression was also found to enhance the rate of appearance of clones during single cell subcloning in the absence of selection pressure. Overall, these benefits have the potential to allow a substantial reduction in the length of cell line generation while significantly increasing cell line productivity. Nevertheless, we found that the high IL-17F expression levels required to convey enhancing effects was a limitation when attempting to co-express IL-17F and a recombinant soluble protein of therapeutic interest from independent CMV promoters within the same expression vector. In order to understand and overcome this limitation, studies were designed to characterize the IL-17F enhancing effect at the molecular and cellular level. Regular supplementation of recombinant biologically-active IL-17F into the culture medium during cell line selection was not able to reproduce the enhancing effects of endogenous IL-17F expression. In addition, increased IL-17F expression correlated with increased CHO-GS selection transgene expression at the single cell level. This data suggested a possible effect of IL-17F on viral promoter activity or transgene mRNA stability. It also provided direct evidence that the cells expressing the highest amounts of IL-17F obtained the most benefit. Overall data obtained from these study implied that IL-17F may act through an intracellular mechanism, possibly exerted during secretion. We therefore initiated experiments designed to determine the specific compartment(s) within which IL-17F triggers its effect. This work has identified IL-17F as a potentially powerful tool to optimize the CHO cell line generation process. The characterization of this enhancing effect at the molecular level has given us several insights into overcoming the current limitations, thus paving the way for the development of a viable technology that can be exploited within the biotechnology industry. - La CHO est la cellule hôte de mammifere la plus couramment utilisée dans la création de lignée cellulaire produisant des protéines thérapeutiques de haute qualité. La génération de ces lignées cellulaires est un processus long et exigeant l'utilisation de techniques de sélection robustes afin d'isoler des candidats possédants les caractéristiques optimales de croissance, de productivité et de stabilité d'expression. Les industries biopharmaceutiques ont investi beaucoup d'efforts afin d'optimiser les systèmes d'expression CHO dans le but raccourcir la longueur du procédé de sélection de lignées cellulaires et aussi d'en augmenter l'efficacité. A partir d'observations préliminaires obtenues lors de la génération de lignées cellulaires CHO- GS exprimant une cytokine appartenant à la famille des IL-17, nous avons réalisé une étude portant sur l'utilisation de l'IL-17F humaine (IL-17F) comme nouveau facteur d'optimisation pour la génération de lignées cellulaires CHO. Nous avons démontré, en utilisant les deux systèmes de sélection et d'expression CHO couramment utilisés (le premier exploitant la GS et l'autre basée sur la DHFR), que l'expression de l'IL-17F permet une augmentation significative de la fréquence d'apparition de colonies durant le processus de sélection de lignées cellulaires. Les différentes colonies sélectionnées expriment des quantités substantielles d'IL-17F, suggérant un effet bénéfique lors de la sélection qui serait exclusivement conféré aux cellules exprimant la cytokine. En outre, le niveau d'expression du transgene se trouve significativement augmenté lorsque la pression de sélection est portée à un niveau habituellement trop élevé pour permettre la sélection de colonies (soit 100 |JM MSX pour le système d'expression CHO-GS ou 1000 nM MTX pour le système CHO- DHFR). Enfin, l'expression d'IL-17F permet également d'améliorer la vitesse d'apparition de clones pendant une étape de sous-clonage en l'absence de pression de sélection. L'ensemble de ces effets bénéfiques permettent une réduction substantielle de la durée de génération de lignées cellulaires tout en augmentant considérablement la productivité des lignées obtenues. Néanmoins, nous avons constaté que la nécessité d'exprimer des niveaux élevés d'IL-17F afin obtenir l'ensemble de ses effets bénéfiques devient une contrainte lors de l'utilisation d'un vecteur d'expression composé de deux promoteurs CMV indépendants pour la co-expression de la cytokine et d'une protéine soluble présentant un intérêt thérapeutique. Afin de mieux comprendre et de surmonter cette limitation, plusieurs études ont été effectuées dans le but de mieux caractériser l'effet de IL-17F au niveau subcellulaire. L'apport régulier en IL-17F recombinante et biologiquement active dans le milieu de culture lors de la sélection de lignées cellulaires ne permet pas de reproduire les effets bénéfiques observés par l'expression endogène d'IL-17F. En outre, nous avons constaté que, lors de l'utilisation du système CHO- GS, l'augmentation d'expression de 1TL-17F est corrélée à un accroissement de l'expression du marqueur de sélection au niveau cellulaire. Ces résultats suggèrent un possible effet d'IL- 17F sur l'activité des promoteurs viraux et ainsi fournissent une preuve directe que les cellules exprimant de haut niveau d'IL-17F sont celles qui en profitent le plus. L'ensemble de ces observations mettrait en avant que l'effet d'IL-17F se ferait selon un mécanisme intracellulaire. Nous avons donc étudié le(s) compartiment(s) spécifique(s) dans lequel IL-17F pourrait exercer son effet. Ce travail a permis de définir IL-17F comme un puissant outil pour l'optimisation des procédés de génération de lignées cellulaires CHO. La caractérisation de cette amélioration de l'effet au niveau moléculaire nous a donné plusieurs indications sur la manière de dépasser les limitations actuelles, ouvrant ainsi la voie au développement d'une technologie viable qui peut être exploitée pars l'industrie biotechnologique.

Neocucullanus neocucullanus Travassos, Artigas et Pereira, 1928 (Nematoda: Cucullanidae) from the Characidae fish, Brycon hilarii Valenciennes, 1850, from Brazil

During investigation on the helminth parasites from Brycon hilarii Valenciennes, 1850 (Characiformes, Characidae), from River Juba, Tangará da Serra, state of Mato Grosso, Brazil, several specimens of the nematode Neocucullanus Travassos, Artigas et Pereira, 1928 were detected. A detailed study of this material, including scanning electron microscopy, allowed to identify these nematodes as N. neocucullanus Travassos, Artigas et Pereira, 1928 and to confirm N. multipapillatus Petter, 1989 as a junior synonym of N. neocucullanus.

Infectious disease among enslaved African Americans at Eaton's Estate, Warren County, North Carolina, ca. 1830-1850

The skeletal remains of 17 people buried in the Eaton Ferry Cemetery in northern North Carolina provide a means of examining health and infectious disease experience in the XIX century South. The cemetery appears to contain the remains of African Americans enslaved on the Eaton family estate from approximately 1830-1850, and thus offers a window into the biological impacts of North American slavery in the years preceding the Civil War. The sample includes the remains of six infants, one child, and one young and nine mature adults (five men, four women, and one unknown). Skeletal indices used to characterize health and disease in the Eaton Ferry sample include dental caries, antemortem tooth loss, enamel hypoplasia, porotic hyperostosis, periosteal lesions, lytic lesions, and stature. These indicators reveal a cumulative picture of compromised health, including high rates of dental disease, childhood growth disruption, and infectious disease. Specific diseases identified in the sample include tuberculosis and congenital syphilis. Findings support previous research on the health impacts of slavery, which has shown that infants and children were the most negatively impacted segment of the enslaved African American population.

Use of the chicken lysozyme 5' matrix attachment region to generate high producer CHO cell lines.

Scaffold or matrix attachment region (S/MAR) genetic elements have previously been proposed to insulate transgenes from repressive effects linked to their site of integration within the host cell genome. We have evaluated their use in various stable transfection settings to increase the production of recombinant proteins such as monoclonal antibodies from Chinese hamster ovary (CHO) cell lines. Using the green fluorescent protein coding sequence, we show that S/MAR elements mediate a dual effect on the population of transfected cells. First, S/MAR elements almost fully abolish the occurrence of cell clones that express little transgene that may result from transgene integration in an unfavorable chromosomal environment. Second, they increase the overall expression of the transgene over the whole range of expression levels, allowing the detection of cells with significantly higher levels of transgene expression. An optimal setting was identified as the addition of a S/MAR element both in cis (on the transgene expression vector) and in trans (co-transfected on a separate plasmid). When used to express immunoglobulins, the S/MAR element enabled cell clones with high and stable levels of expression to be isolated following the analysis of a few cell lines generated without transgene amplification procedures.