Basic Principles of SSM Modeling: An Examination of CATWOE from a Soft Perspective

This paper examines the SSM technique CATWOE, which focuses on defining necessary elements that together constitute a human activity system from a certain perspective. Despite its recognition within the literature and its numerous uses, there are few studies on how the technique can be improved. This research reflects on each of the elements both from a theoretical and a practical perspective. Findings point to the fact that some of the terms have a meaning in everyday language that differs from its definition within CATWOE. Other concepts are not well-defined. This is unfortunate and may both lead to misunderstandings and limit analysis. The paper points to a number of ways in which the use of CATWOE can be developed in order to further support the process of eliciting novel ideas for future actions. Hence, the overall conclusion is that the elements need to be rethought and some of them renamed.     

Light dependent mating inhibition in the white-eye mutant ofDrosophila pseudoobscura

Summary White-eyeDrosophila pseudoobscura males display a deficiency in their mating ability in the light, although they are able to mate readily in the dark. The present data suggest that the mating deficit is due to a neurobehavioral disruption produced by faulty visual input.     

The effect of kidney-bean leucoagglutinin on homograft rejection in mice

Zusammenfassung Nach der Wirkung auf die Überlebenszeit von Transplantaten bei Mäusen zu schliessen, besitzt Leucoagglutinin ausPhaseolus vulgaris extrahiert, eine nur schwache immunosuppressive Aktivität. Sie ist nicht deutlich mit der lymphozytenstimulierenden oder agglutinierenden Aktivität verknüpft. Eine starke akute Toxizität von Leukoagglutinin wurde festgestellt.

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Supported by grants from the Sigrid Jusélius Foundation, the Finnish Medical Research Council, the Åhlén Foundation and the Swedish Cancer Society.     

Retardation of protein synthesis in rat tumours on inhibiting histamine formation

Zusammenfassung Untersuchung der Proteinsynthese bei Virustumoren. Anhand der Inkorporierungsgeschwindigkeit von¹⁴C-Leucin wurde festgestellt, dass die Hemmung der Proteinsynthese im Rous-Sarkom höher ist als im Walker-Karzinom.     

Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease

Integration of genome-wide expression profiling with linkage analysis is a new approach to identifying genes underlying complex traits. We applied this approach to the regulation of gene expression in the BXH/HXB panel of rat recombinant inbred strains, one of the largest available rodent recombinant inbred panels and a leading resource for genetic analysis of the highly prevalent metabolic syndrome. In two tissues important to the pathogenesis of the metabolic syndrome, we mapped cis- and trans-regulatory control elements for expression of thousands of genes across the genome. Many of the most highly linked expression quantitative trait loci are regulated in cis, are inherited essentially as monogenic traits and are good candidate genes for previously mapped physiological quantitative trait loci in the rat. By comparative mapping we generated a data set of 73 candidate genes for hypertension that merit testing in human populations. Mining of this publicly available data set is expected to lead to new insights into the genes and regulatory pathways underlying the extensive range of metabolic and cardiovascular disease phenotypes that segregate in these recombinant inbred strains.     

Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins

Haems are metalloporphyrins that serve as prosthetic groups for various biological processes including respiration, gas sensing, xenobiotic detoxification, cell differentiation, circadian clock control, metabolic reprogramming and microRNA processing. With a few exceptions, haem is synthesized by a multistep biosynthetic pathway comprising defined intermediates that are highly conserved throughout evolution. Despite our extensive knowledge of haem biosynthesis and degradation, the cellular pathways and molecules that mediate intracellular haem trafficking are unknown. The experimental setback in identifying haem trafficking pathways has been the inability to dissociate the highly regulated cellular synthesis and degradation of haem from intracellular trafficking events. Caenorhabditis elegans and related helminths are natural haem auxotrophs that acquire environmental haem for incorporation into haemoproteins, which have vertebrate orthologues. Here we show, by exploiting this auxotrophy to identify HRG-1 proteins in C. elegans, that these proteins are essential for haem homeostasis and normal development in worms and vertebrates. Depletion of hrg-1, or its paralogue hrg-4, in worms results in the disruption of organismal haem sensing and an abnormal response to haem analogues. HRG-1 and HRG-4 are previously unknown transmembrane proteins, which reside in distinct intracellular compartments. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations and, most strikingly, profound defects in erythropoiesis-phenotypes that are fully rescued by worm HRG-1. Human and worm proteins localize together, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1. These findings reveal conserved pathways for cellular haem trafficking in animals that define the model for eukaryotic haem transport. Thus, uncovering the mechanisms of haem transport in C. elegans may provide insights into human disorders of haem metabolism and reveal new drug targets for developing anthelminthics to combat worm infestations.     

Common variants at 6q22 and 17q21 are associated with intracranial volume

During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 × 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 × 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 × 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 × 10(-3) for 6q22 and 1.2 × 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.     

Nuclear isomers in superheavy elements as stepping stones towards the island of stability

A long-standing prediction of nuclear models is the emergence of a region of long-lived, or even stable, superheavy elements beyond the actinides. These nuclei owe their enhanced stability to closed shells in the structure of both protons and neutrons. However, theoretical approaches to date do not yield consistent predictions of the precise limits of the 'island of stability'; experimental studies are therefore crucial. The bulk of experimental effort so far has been focused on the direct creation of superheavy elements in heavy ion fusion reactions, leading to the production of elements up to proton number Z = 118 (refs 4, 5). Recently, it has become possible to make detailed spectroscopic studies of nuclei beyond fermium (Z = 100), with the aim of understanding the underlying single-particle structure of superheavy elements. Here we report such a study of the nobelium isotope 254No, with 102 protons and 152 neutrons--the heaviest nucleus studied in this manner to date. We find three excited structures, two of which are isomeric (metastable). One of these structures is firmly assigned to a two-proton excitation. These states are highly significant as their location is sensitive to single-particle levels above the gap in shell energies predicted at Z = 114, and thus provide a microscopic benchmark for nuclear models of the superheavy elements.     

CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.