Genetic variation in selenoprotein S influences inflammatory response

Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1beta and TNF-alpha. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatory cytokines. One promoter variant, -105G --> A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-alpha. To investigate further the significance of the observed associations, we genotyped -105G --> A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significant association with both TNF-alpha (P = 0.0049) and IL-1beta (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation.     

Endocrine control of sexual behavior in mammals

Résumé L'auteur présente une revue critique des bases expérimentales de l'hypothèse neuro-endocrine du comportement sexuel des mammifères.

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Presented before the symposium on sexual behavior sponsored by the section of Animal Behavior and Sociobiology of the Ecological Society at the 1957 Meeting of the AAAS. Paper No. 2254 in the journal series of the Pennsylvania Experiment Station.     

Ozone production by a corona-type loudspeaker and its toxic effects in mice

Résumé L'ionophone est un émetteur sonique et ultra-sonique qui utilise la particularité qu'ont les gaz d'être ionisés sous l'effet d'une tension électrique très élevée et de haute fréquence. Ce générateur est aussi un ozoniseur efficient et il est nécessaire de ne l'employer qu'avec une ventilation appropriée.

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Paper No. 2397 in the Journal Series of the Agricultural Experiment Station.     

Asian tapeworm ( Bothriocephalus acheilognathi ) in native fishes from the Little Colorado River, Grand Canyon, Arizona

Examination of gastrointestinal tracts of native cyprinids from the Little Colorado River (LCR) in Grand Canyon, Arizona, 1990-1994, revealed varying rates of prevalence and infrapopulation levels of Asian tapeworm ( Bothriocephalus acheilognathi ). Mean prevalence was 28% (range 0-78%) in humpback chub ( Gila cypha ) and 8% (range 0-46%) in speckled dace ( Rhinichthys osculus ), with infrapopulations as high as 46 and 28, respectively. We also note Asian tapeworm infection of nonnatives common carp ( Cyprinus carpio ), fathead minnow ( Pimephales promelas ), and plains killifish ( Fundulus zebrinus ) from the LCR. Reported pathogenic and chronic effects of this cestode to its definitive hosts add concern for the status of the Grand Canyon population of the federally endangered humpback chub. The rapidity which Asian tapeworm has spread to different drainages of the Colorado River Basin likely portends an eventual cosmopolitan basin distribution in lower elevations suitable to the parasite's thermophilic life history. Such biotic changes must be considered among the most serious threats to conservation and recovery of native fish populations.     

Collective synthesis of natural products by means of organocascade catalysis

Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine.     

A conditional knockout resource for the genome-wide study of mouse gene function

Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.     

Has the Earth's sixth mass extinction already arrived?

Palaeontologists characterize mass extinctions as times when the Earth loses more than three-quarters of its species in a geologically short interval, as has happened only five times in the past 540?million years or so. Biologists now suggest that a sixth mass extinction may be under way, given the known species losses over the past few centuries and millennia. Here we review how differences between fossil and modern data and the addition of recently available palaeontological information influence our understanding of the current extinction crisis. Our results confirm that current extinction rates are higher than would be expected from the fossil record, highlighting the need for effective conservation measures.     

Transfer of the immunization to a bacterial antigen by RNA

Riassunto L'iniezione ad animali normali di ARN estratto dalla milza di animali immunizzati con antigene H diS. typhi, provoca la comparsa, nel siero degli animali riceventi, di anticorpi diretti contro tale antigene.