Migration and Settlement: 3. Sweden

The purpose of this report is to give a detailed overview of the internal migration patterns and regional policies in Sweden. This report is organized as follows. Sections 1.2 and 1.3 discuss the administrative subdivisions of Sweden and the organization of the population statistics, respectively. Section 1.4 describes the settlement pattern of Sweden in a historical perspective. Chapter 2 deals with current patterns of spatial population growth and of its components (fertility, mortality and migration). The problem of regional aggregation is also discussed, to some extent, and various regional systems are proposed. In Chapter 3 the results of the multiregional population analysis are presented: life tables, population projections, and fertility and migration analysis. Chapter 4 presents an outline of population policies in Sweden, with special emphasis on the regional labor market and internal migration policies

Tissue-Specific Impact of Autophagy Genes on the Ubiquitin–Proteasome System in C. elegans

The ubiquitin–proteasome system (UPS) and the autophagy–lysosomal pathway (ALP) are the two main eukaryotic intracellular proteolytic systems involved in maintaining proteostasis. Several studies have reported on the interplay between the UPS and ALP, however it remains largely unknown how compromised autophagy affects UPS function in vivo. Here, we have studied the crosstalk between the UPS and ALP by investigating the tissue-specific effect of autophagy genes on the UPS at an organismal level. Using transgenic Caenorhabditis elegans expressing fluorescent UPS reporters, we show that the downregulation of the autophagy genes lgg-1 and lgg-2 (ATG8/LC3/GABARAP), bec-1 (BECLIN1), atg-7 (ATG7) and epg-5 (mEPG5) by RNAi decreases proteasomal degradation, concomitant with the accumulation of polyubiquitinated proteasomal substrates in a tissue-specific manner. For some of these genes, the changes in proteasomal degradation occur without a detectable alteration in proteasome tissue expression levels. In addition, the lgg-1 RNAi-induced reduction in proteasome activity in intestinal cells is not dependent on sqst-1/p62 accumulation. Our results illustrate that compromised autophagy can affect UPS in a tissue-specific manner, and demonstrate that UPS does not function as a direct compensatory mechanism in an animal. Further, a more profound understanding of the multilayered crosstalk between UPS and ALP can facilitate the development of therapeutic options for various disorders linked to dysfunction in proteostasis

Tissue-Specific Impact of Autophagy Genes on the Ubiquitin–Proteasome System in C. elegans

The ubiquitin–proteasome system (UPS) and the autophagy–lysosomal pathway (ALP) are the two main eukaryotic intracellular proteolytic systems involved in maintaining proteostasis. Several studies have reported on the interplay between the UPS and ALP, however it remains largely unknown how compromised autophagy affects UPS function in vivo. Here, we have studied the crosstalk between the UPS and ALP by investigating the tissue-specific effect of autophagy genes on the UPS at an organismal level. Using transgenic Caenorhabditis elegans expressing fluorescent UPS reporters, we show that the downregulation of the autophagy genes lgg-1 and lgg-2 (ATG8/LC3/GABARAP), bec-1 (BECLIN1), atg-7 (ATG7) and epg-5 (mEPG5) by RNAi decreases proteasomal degradation, concomitant with the accumulation of polyubiquitinated proteasomal substrates in a tissue-specific manner. For some of these genes, the changes in proteasomal degradation occur without a detectable alteration in proteasome tissue expression levels. In addition, the lgg-1 RNAi-induced reduction in proteasome activity in intestinal cells is not dependent on sqst-1/p62 accumulation. Our results illustrate that compromised autophagy can affect UPS in a tissue-specific manner, and demonstrate that UPS does not function as a direct compensatory mechanism in an animal. Further, a more profound understanding of the multilayered crosstalk between UPS and ALP can facilitate the development of therapeutic options for various disorders linked to dysfunction in proteostasis

Tissue-Specific Impact of Autophagy Genes on the Ubiquitin–Proteasome System in C. elegans

The ubiquitin–proteasome system (UPS) and the autophagy–lysosomal pathway (ALP) are the two main eukaryotic intracellular proteolytic systems involved in maintaining proteostasis. Several studies have reported on the interplay between the UPS and ALP, however it remains largely unknown how compromised autophagy affects UPS function in vivo. Here, we have studied the crosstalk between the UPS and ALP by investigating the tissue-specific effect of autophagy genes on the UPS at an organismal level. Using transgenic Caenorhabditis elegans expressing fluorescent UPS reporters, we show that the downregulation of the autophagy genes lgg-1 and lgg-2 (ATG8/LC3/GABARAP), bec-1 (BECLIN1), atg-7 (ATG7) and epg-5 (mEPG5) by RNAi decreases proteasomal degradation, concomitant with the accumulation of polyubiquitinated proteasomal substrates in a tissue-specific manner. For some of these genes, the changes in proteasomal degradation occur without a detectable alteration in proteasome tissue expression levels. In addition, the lgg-1 RNAi-induced reduction in proteasome activity in intestinal cells is not dependent on sqst-1/p62 accumulation. Our results illustrate that compromised autophagy can affect UPS in a tissue-specific manner, and demonstrate that UPS does not function as a direct compensatory mechanism in an animal. Further, a more profound understanding of the multilayered crosstalk between UPS and ALP can facilitate the development of therapeutic options for various disorders linked to dysfunction in proteostasis.The ubiquitin–proteasome system (UPS) and the autophagy–lysosomal pathway (ALP) are the two main eukaryotic intracellular proteolytic systems involved in maintaining proteostasis. Several studies have reported on the interplay between the UPS and ALP, however it remains largely unknown how compromised autophagy affects UPS function in vivo. Here, we have studied the crosstalk between the UPS and ALP by investigating the tissue-specific effect of autophagy genes on the UPS at an organismal level. Using transgenic Caenorhabditis elegans expressing fluorescent UPS reporters, we show that the downregulation of the autophagy genes lgg-1 and lgg-2 (ATG8/LC3/GABARAP), bec-1 (BECLIN1), atg-7 (ATG7) and epg-5 (mEPG5) by RNAi decreases proteasomal degradation, concomitant with the accumulation of polyubiquitinated proteasomal substrates in a tissue-specific manner. For some of these genes, the changes in proteasomal degradation occur without a detectable alteration in proteasome tissue expression levels. In addition, the lgg-1 RNAi-induced reduction in proteasome activity in intestinal cells is not dependent on sqst-1/p62 accumulation. Our results illustrate that compromised autophagy can affect UPS in a tissue-specific manner, and demonstrate that UPS does not function as a direct compensatory mechanism in an animal. Further, a more profound understanding of the multilayered crosstalk between UPS and ALP can facilitate the development of therapeutic options for various disorders linked to dysfunction in proteostasis.Peer reviewe

Immunohistochemical analysis reveals variations in proteasome tissue expression in C. elegans

The ubiquitin-proteasome system (UPS) plays a crucial part in normal cell function by mediating intracellular protein clearance. We have previously shown that UPS-mediated protein degradation varies in a cell type-specific manner in C. elegans. Here, we use formalin-fixed, paraffin-embedded C. elegans sections to enable studies on endogenous proteasome tissue expression. We show that the proteasome immunoreactivity pattern differs between cell types and within subcellular compartments in adult wild-type (N2) C. elegans. Interestingly, widespread knockdown of proteasome subunits by RNAi results in tissue-specific changes in proteasome expression instead of a uniform response. In addition, long-lived daf-2 (e1370) mutants with impaired insulin/IGF-1 signaling (IIS) display similar proteasome tissue expression as aged-matched wild-type animals. Our study emphasizes the importance of alternate approaches to the commonly used whole animal lysate-based methods to detect changes in proteasome expression occurring at the sub-cellular, cell or tissue resolution level in a multicellular organism.Peer reviewe

Tissue-specific effects of temperature on proteasome function

Variation in ambient growth temperature can cause changes in normal animal physiology and cellular functions such as control of protein homeostasis. A key mechanism for maintaining proteostasis is the selective degradation of polyubiquitinated proteins, mediated by the ubiquitin-proteasome system (UPS). It is still largely unsolved how temperature changes affect the UPS at the organismal level. Caenorhabditis elegans nematodes are normally bred at 20 °C, but for some experimental conditions, 25 °C is often used. We studied the effect of 25 °C on C. elegans UPS by measuring proteasome activity and polyubiquitinated proteins both in vitro in whole animal lysates and in vivo in tissue-specific transgenic reporter strains. Our results show that an ambient temperature shift from 20 to 25 °C increases the UPS activity in the intestine, but not in the body wall muscle tissue, where a concomitant accumulation of polyubiquitinated proteins occurs. These changes in the UPS activity and levels of polyubiquitinated proteins were not detectable in whole animal lysates. The exposure of transgenic animals to 25 °C also induced ER stress reporter fluorescence, but not the fluorescence of a heat shock responsive reporter, albeit detection of a mild induction in hsp-16.2 mRNA levels. In conclusion, C. elegans exhibits tissue-specific responses of the UPS as an organismal strategy to cope with a rise in ambient temperature.Peer reviewe

Regional Demographic Development in Southwest Skane

This Collaborative Paper deals with the population development of Southwest Skane and the rest of Sweden from the 1960s up until the turn of the century. A new type of projection model, developed at IIASA, is hereby used. This population model is one in the set mentioned above and has previously been tested on limited data from Sweden and other countries (see Andersson and Holmberg: Migration and Settlement. 3: Sweden, RR-80-5, IIASA) . The current application is more extensive. Ingvar Holmberg of the Demographic Research Group at the University of Gothenburg, Sweden, is responsible for the adaptation of the model to Swedish conditions and for the numerical computations. The results have been evaluated by Ake Andersson, Ingvar Holmberg, Joergen Schultz, and Folke Snickars, all of whom have contributed to this policy-oriented report. Hopefully this work will further stimulate the continued discussion about regional population development in Sweden and elsewhere

The Structure of the Outer Halo of the Galaxy and its Relationship to Nearby Large-Scale Structure

We present evidence to support an earlier indication that the Galaxy is embedded in an extended, highly inclined, triaxial halo outlined by the spatial distribution of companion galaxies to the Milky Way. Signatures of this spatial distribution are seen in 1) the angular variation of the radial-velocity dispersion of the companion galaxies, 2) the spatial distribution of the M~31 sub-group of galaxies, 3) the spatial distribution of the isolated, mainly dwarf irregular, galaxies of the Local Group, 4) the velocity anisotropy quadrupole of a sub-group of high-velocity clouds, and 5) the spatial distribution of galaxies in the Coma-Sculptor cloud. Tidal effects of M~31 and surrounding galaxies on the Galaxy are not strong enough to have affected the observed structure. We conclude that this distribution is a reflection of initial conditions. A simple galaxy formation scenario is proposed which ties together the results found here with those of Holmberg (1969) and Zaritsky et al. (1997) on the peculiar distribution of satellites around a large sample of spiral galaxies.Comment: Accepted for publication in the Astron J., March 2000, 12 pages with 1 figur

C. elegans dss-1 is functionally conserved and required for oogenesis and larval growth

<p>Abstract</p> <p>Background</p> <p>Dss1 (or Rpn15) is a recently identified subunit of the 26S proteasome regulatory particle. In addition to its function in the protein degradation machinery, it has been linked to BRCA2 (breast cancer susceptibility gene 2 product) and homologous DNA recombination, mRNA export, and exocytosis. While the fungal orthologues of Dss1 are not essential for viability, the significance of Dss1 in metazoans has remained unknown due to a lack of knockout animal models.</p> <p>Results</p> <p>In the current study deletion of <it>dss-1 </it>was studied in <it>Caenorhabditis elegans </it>with a <it>dss-1 </it>loss-of-function mutant and <it>dss-1 </it>directed RNAi. The analysis revealed an essential role for <it>dss-1 </it>in oogenesis. In addition, <it>dss-1 </it>RNAi caused embryonic lethality and larval arrest, presumably due to loss of the <it>dss-1 </it>mRNA maternal contribution. DSS-1::GFP fusion protein localised primarily in the nucleus. No apparent effect on proteasome function was found in <it>dss-1 </it>RNAi treated worms. However, expression of the <it>C. elegans dss-1 </it>in yeast cells deleted for its orthologue <it>SEM1 </it>rescued their temperature-sensitive growth phenotype, and partially rescued the accumulation of polyubiquitinated proteins in these cells.</p> <p>Conclusion</p> <p>The first knockout animal model for the gene encoding the proteasome subunit DSS-1/Rpn15/Sem1 is characterised in this study. In contrast to unicellular eukaryotes, the <it>C. elegans dss-1 </it>encodes an essential protein, which is required for embryogenesis, larval growth, and oogenesis, and which is functionally conserved with its yeast and human homologues.</p

The Relationship Between Baryons and Dark Matter in Extended Galaxy Halos

The relationship between gas-rich galaxies and Ly-alpha absorbers is addressed in this paper in the context of the baryonic content of galaxy halos. Deep Arecibo HI observations are presented of two gas-rich spiral galaxies within 125 kpc projected distance of a Ly-alpha absorber at a similar velocity. The galaxies investigated are close to edge-on and the absorbers lie almost along their major axes, allowing for a comparison of the Ly-alpha absorber velocities with galactic rotation. This comparison is used to examine whether the absorbers are diffuse gas rotating with the galaxies' halos, outflow material from the galaxies, or intergalactic gas in the low redshift cosmic web. The results indicate that if the gas resides in the galaxies' halos it is not rotating with the system and possibly counter-rotating. In addition, simple geometry indicates the gas was not ejected from the galaxies and there are no gas-rich satellites detected down to 3.6 - 7.5 x 10^6 Msun, or remnants of satellites to 5-6 x 10^{18} cm^{-2}. The gas could potentially be infalling from large radii, but the velocities and distances are rather high compared to the high velocity clouds around the Milky Way. The most likely explanation is the galaxies and absorbers are not directly associated, despite the vicinity of the spiral galaxies to the absorbers (58-77 kpc from the HI edge). The spiral galaxies reside in a filament of intergalactic gas, and the gas detected by the absorber has not yet come into equilibrium with the galaxy. These results also indicate that the massive, extended dark matter halos of spiral galaxies do not commonly have an associated diffuse baryonic component at large radii.Comment: Accepted by AJ, 33 pages preprint format, see http://www.astro.lsa.umich.edu/~mputman/putman1.pdf for a higher resolution versio