61 research outputs found
Städer i öst och väst : sammanfattande rapport etapp I
No full textThis contribution compares the medieval towns in central and western Sweden, putting forward the point of view that urbanism differed in the two regions. The chronology of urban development in the two areas is studied; as is also the stability of the urbanization, that is, was the urban structure relatively firmly established or was it unstable, with discontinuity, changes of site etc? The strength and stability of the towns can also reflect the extent to which they had secular and ecclesiastical institutions and administrative functions. It is more difficult to postulate the size of the towns but, even so, an attempt is made here to specify their surface area. The author believes that there is a significant difference between the two regions. In central Sweden a stable and buoyant urban organization was established during a relatively short period in the 13th century, while in western Sweden, which was split up among three countries in the Middle Ages, it was a long time before anything similar was established. There were many changesof site; there were few institutionsin the towns which appear mainly tohave been economically weak. There are many explanations for this. In central Sweden there was a healthy economic hinterland (with agriculture and mining). Power was centralized nearby and it could both promote and direct the foundation of towns. Western Sweden was peripheral to all the three bordering countries among which it was split in the middle ages. Central power had more difficulty in making itself felt. Urbanization has been associated with other political, economic and administrative changes which occurred within the realm. This study suggests that it might also be fruitful to look at urbanism in the light of variable regional development
Accumulation of long-chain bases in yeast promotes their conversion to a long-chain base vinyl ether
Get PDFLong-chain bases (LCBs) are the precursors to ceramide and sphingolipids in eukaryotic cells. They are formed by the action of serine palmitoyl-CoA transferase (SPT), a complex of integral membrane proteins located in the endoplasmic reticulum. SPT activity is negatively regulated by Orm proteins to prevent the toxic overaccumulation of LCBs. Here we show that overaccumulation of LCBs in yeast results in their conversion to a hitherto undescribed LCB derivative, an LCB vinyl ether. The LCB vinyl ether is predominantly formed from phytosphingosine (PHS) as revealed by conversion of odd chain length tracers C17-dihydrosphingosine and C17- PHS into the corresponding LCB vinyl ether derivative. PHS vinyl ether formation depends on ongoing acetyl-CoA synthesis, and its levels are elevated when the LCB degradative pathway is blocked by deletion of the major LCB kinase, LCB4, or the LCB phosphate lyase, DPL1. PHS vinyl ether formation thus appears to constitute a shunt for the LCB phosphate- and lyase-dependent degradation of LCBs. Consistent with a role of PHS vinyl ether formation in LCB detoxification, the lipid is efficiently exported from the cells
Urbaniseringsprocessen i det medeltida Sverige : en forskningsöversikt
No full textThe report was written for the XVII Conference of Scandinavian Historians in Trondheim, 1977. It was published together with summaries of the research carried out in the other Scandinavian countries in Urbaniseringsprosessen i Norden. 1. Middelaldersteder, edited by Grete Authén Blom, Oslo 1977. The report summarizes the present state of research on Swedish medieval towns. Towns which belonged to Denmark or Norway before the mid-17th century are not included. The report is divided into two main parts: urban society up to c 1350 (p 5-32) and the late medieval development (p 32-35). The headings in the table of contents give the subject of each chapter. Some general ideas relating to the process of urbanisation are presented in a couple of summaries. The author looks upon the development in the earlier period as follows (p 31-32): In prehistoric times places appear where the existence of trade and specialized crafts can be observed (Helgö, Birka, Paviken, Köpingsvik, Eketorp), sometimes together with a densely built-up settlement (Birka, Eketorp). Helgö, Birka and Paviken cease to exist before the Middle Ages but other places continue during the early Middle Ages. As regards these places there is no evidence that they had other central functions than the economic, with the possible exception of Birka. A partly parallel development to these places, which in one instance began already in prehistoric times, was the emergence of densely populated areas which simultaneously or somewhat later can be shown to have had functions other than purely economic. To begin with they were very few: Sigtuna, Lödöse, Kalmar, Visby, and perhaps Skara, but in the late 12th century their number increases considerably with a concentration to the eastern part of central Sweden. All these places were in one way or another closely tied to administrative structures, either secular or ecclesiastical. Some of them were episcopal seats and/or deaneries, in others there were royal citadels or mints. Several of these places can also be connected with an even older structure of provincial centres, which were the sites of markets, things, and perhaps cult ceremonies and the later ecclesiastical division was probably based on this structure. It can thus be shown that in these early towns there was a close connection between economic, ecclesiastical and secular administrative functions. In many instances the structure of provincial centres can be traced far back. The development during the late part of the 13th century is in some respects different. The new towns do not seem to have been tied to existing administrative structures in the same way as the old ones. The division into bailiwichs does, it is true, follow the existing forts-towns, but already in the beginning of the 14th century the ties between fort-town-bailiwick began to be loosened up. Skara was replaced by Axvall and Lödöse by Älvsborg. Most of the new towns never became centres of bailiwichs. The towns developed mainly into instruments for regulating and controlling the economic activity of a region. Privileges were granted and laws made. The civic administration was reorganised but the strong influence of the Crown was maintained. Prohibitions against trade outside the towns were issued. This process was subjected, at times, very strongly, to external influences, not least due to the position of the Hanseatic trade. It is more difficult to decide if, apart from the administrative reorganisation, any decisive changes took place, for instance with regard to topography. As for the commercial centres, or to express it more cautiously -the nonagrarian communities, it is possible that the disappearance of some of these around 1300 should be interpreted as a result of a failure to incorporate them into the regulated urban communites. On the other hand it needs pointing out that the existence of regulated towns did not exclude small trading places, particularly in areas which completely lacked towns as was the case in Norrland. The economic activities which gave rise to the development of the towns were the mining and agriculture in the central parts of Sweden. Mining on an industrial scale can be followed back to the late 13th century and can be connected with the process of urbanisation in the region around Lake Mälaren: the establishment of new towns, most notably Stockholm, and the development of the existing towns. The role of agriculture in relation to urbanisation is much more difficult to establish. But an examination of the early towns shows that they were all to a marked extent situated in, or close to, good farming districts. The question arises whether it was of importance for the development of urbanisation in these parts that they were the relatively speaking most densely populated districts. On the basis of this evidence it would seem that the development in Sweden after the emergence of the prehistoric trading centres shows two well-defined transitional periods, namely the decades before and after 1200 and the latter half of the 13th century. The last-mentioned period was mainly characterized by administrative reorganisation whereas topographical and functional conditions were established during the earlier period. As for the functions of the town it is possible that to a certain extent they became more limited to the purely economic aspects during the latter part of the period under discussion. The late Middle Ages, which in Sweden has been studied much less than the early period is characterized as follows (p 35): Only a few points are referred to with regard to the towns of the late Middle Ages. Generally speaking there were no decisive changes in the structure of the towns. New towns arose but only a few of these were of importance. There was, however, a shift in status among the towns. This is particularly true of Stockholm which was markedly different from other Swedish towns also with regard to its physical form. New Lödöse was the only new town which could assert itself, due to the fact that it succeeded to the role of the most important port on the west coast, but also perhaps due to the changes in the economy and the agricultural geography which can be followed in the late Middle Ages, an increase in animal production and a change in outlook as regards the border trade. One scholar has called the late Middle Ages the period of urban decline. As a matter of fact this is the period when the towns established their positions and gained increased economic importance. During this period urbanisation began to expand outside the central settled regions. A foundation was laid for the spread of urbanisation to Norrland. But the lasting impression is the picture of continuity from the early Middle Ages. Translation: Birgitta Frykma
Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control
No full textYeast members of the ORMDL family of endoplasmic reticulum (ER) membrane proteins play a central role in lipid homeostasis and protein quality control. In the absence of yeast Orm1 and Orm2, accumulation of long chain base, a sphingolipid precursor, suggests dysregulation of sphingolipid synthesis. Physical interaction between Orm1 and Orm2 and serine palmitoyltransferase, responsible for the first committed step in sphingolipid synthesis, further supports a role for the Orm proteins in regulating sphingolipid synthesis. Phospholipid homeostasis is also affected in orm1∆ orm2∆ cells: the cells are inositol auxotrophs with impaired transcriptional regulation of genes encoding phospholipid biosynthesis enzymes. Strikingly, impaired growth of orm1∆ orm2∆ cells is associated with constitutive unfolded protein response, sensitivity to stress, and slow ER-to-Golgi transport. Inhibition of sphingolipid synthesis suppresses orm1∆ orm2∆ phenotypes, including ER stress, suggesting that disrupted sphingolipid homeostasis accounts for pleiotropic phenotypes. Thus, the yeast Orm proteins control membrane biogenesis by coordinating lipid homeostasis with protein quality control
Clinical and metabolic consequences of L-serine supplementation in hereditary sensory and autonomic neuropathy type 1C
Get PDFHereditary sensory neuropathy type 1 (HSAN1) may be the first genetic neuropathy amenable to a specific mechanism-based treatment, as L-serine supplementation can be used to lower the neurotoxic levels of 1-deoxysphingolipids (1-deoxySL) that cause the neurodegeneration. The treatment is so far untested in HSAN1C caused by variants in the serine palmitoyl transferase subunit 2 (SPTLC2) gene. The aim of this study was to establish whether oral L-serine lowers 1-deoxySL in a patient with HSAN1C, to perform a dose escalation to find the minimal effective dose, and to assess the safety profile and global metabolic effects of the treatment. Our patient underwent a 52-wk treatment in which the L-serine dose was titrated up to 400 mg/kg/day. She was followed up by repeated clinical examination, nerve conduction testing, and skin biopsies to document effects on small nerve fibers. Serum was assayed for 1-deoxySL and metabolomics analysis of 111 metabolites. We found a robust lowering of 1-deoxySL, which correlated in a near-linear fashion with increased serum L-serine levels. Metabolomics analysis showed a modest elevation in glycine and a marked reduction in the level of cytosine, whereas most of the other assayed metabolites did not change. There were no direct side effects from the treatment, but the patient developed a transitory toe ulceration during the course of the study. The Charcot–Marie–Tooth neuropathy score increased by 1 point. We conclude that oral supplementation of L-serine decreases 1-deoxySL in HSAN1C without major global effects on metabolism. L-serine is therefore a potential treatment for HSAN1C.Peer reviewe
Krukor i Museer : Hur, Varför och Vad ställer vi ut?
No full textThis thesis is a study of pottery in the museum world. Throughout the study, questions along the lines of how, why and what we exhibit are brought up and answered. The study is done through observations and interviews with seven different museums, four of which are located in Sweden and three in Italy. The author has also used museological literature and theories in order to strengthen the essay and show that the issues brought up in the observations are known since before in the field, but still exist in the museums today.The exhibiting of pottery comes with several issues, such as overcrowding of displays, requirements of pre-knowledge from the visitors, aesthetical problems with broken, coarse or fine pottery and epistemological prob-lems. Epistemology is a subject that seems to be partly ignored in the observed museums, despite it being general knowledge that fewer visitors will read the text the longer it is. Other epistemological problems that are brought up are the issues of text placement, vocabulary and actual mediated information. These problems are brought up throughout the essay and explained, with a smaller section that discusses possible improvements to them, which have been brought up by researchers in the field.In interviews with curators of the museums, thoughts about what the visitors see and understand compared to what the museums want them the see are presented. Also their views on the possibilities of interaction with pottery as a mediator and whether they focus primarily on aesthetics or learning in the exhibitions are shown. This essay is not meant to be a decider between what is right or wrong concerning the exhibiting of pottery, but could be used as a stepping-stone towards such studies. This is a two years master’s thesis in Archive, Library and Museum studies.Den här uppsatsen är en studie av krukor i museivärlden. Genomgående i studien kommer frågor som hur, varför och vad vi ställer ut tas upp och besvaras. Studien har gjorts genom observationer och intervjuer med sju olika museer, fyra belägna i Sverige och tre i Italien. Författaren har också använt sig av museologisk litteratur och museologiska teorier för att stärka uppsatsen och visa att de problem som tagits upp i observationerna är kända sedan tidigare inom fältet, men trots det existerar i museer idag.Utställande av krukor medför flera problem, såsom överfulla montrar, krav på förkunskaper hos besökarna, estetiska problem med trasig, bruks- eller finkeramik samt epistemologiska problem. Epistemologi verkar vara ett ämne som delvis ignoreras i de observerade museerna, trots att det är allmänt känt att färre besökare kommer att läsa texten ju längre den är. Andra epistemologiska problem som behandlas är sådana som textplacering, vokabu-lär och faktiskt förmedlad kunskap. Dessa problem tas upp och förklaras i uppsatsen med en mindre sektion som diskuterar möjliga förbättringar av dem, baserat på idéer från forskare inom fältet.I intervjuerna med curatorer från museerna presenteras deras tankar om vad besökarna ser och förstår jäm-fört med vad museerna vill att de ska förstå. Också deras syn på möjligheterna av interaktion genom krukor och huruvida de fokuserar främst på det estetiska eller pedagogiska i utställningarna visas. Den här uppsatsen är inte menad att skilja mellan rätt och fel vid utställandet av krukor, men kan användas som ett avstamp mot sådana studier. Det här är en två-årig masteruppsats i Arkiv-, Biblioteks- och Museivetenskap
A novel sit4 phosphatase complex is involved in the response to ceramide stress in yeast
Get PDFCeramide is a building block for complex sphingolipids in the plasma membrane, but it also plays a significant role in secondary signalling pathways regulating cell proliferation and apoptosis in response to stress. Ceramide activated protein phosphatase activity has been previously observed in association with the Sit4 protein phosphatase. Here we find that sit4Δ mutants have decreased ceramide levels and display resistance to exogenous ceramides and phytosphingosine. Mutants lacking SIT4 or KTI12 display a shift towards nonhydroxylated forms of long chain bases and sphingolipids, suggesting regulation of hydroxylase (SUR2) or ceramide synthase by Sit4p. We have identified novel subunits of the Sit4 complex and have also shown that known Sit4 regulatory subunits—SAP proteins—are not involved in the ceramide response. This is the first observation of separation of function between Sit4 and SAP proteins. We also find that the Sit4p target Elongator is not involved in the ceramide response but that cells deficient in Kti12p—an accessory protein with an undefined regulatory role—have similar ceramide phenotypes to sit4Δ mutants. Therefore, Kti12p may play a similar secondary role in the ceramide response. This evidence points to a novel Sit4-dependent regulatory mechanism in response to ceramide stress
SPTLC1 p.Leu38Arg, a novel mutation associated with childhood ALS
No full textAmyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease. Recently, several gain-of-function mutations in SPTLC1 were associated with juvenile ALS. SPTLC1 encodes for a subunit of the serine-palmitoyltransferase (SPT) - the rate-limiting enzyme in the de novo synthesis of sphingolipids (SL). SPT activity, and thus SL de novo synthesis, is tightly controlled by a homeostatic feedback mechanism mediated by ORMDL proteins. Here we report a novel SPTLC1p.L38R mutation in a young Chinese girl with a signature of juvenile ALS. The patient presented with muscular weakness and atrophy, tongue tremor and fasciculation, breathing problems and positive pyramidal signs. All SPTLC1-ALS mutations including the SPTLC1 p.L38R are located within a single membrane-spanning domain of the protein and impede the interaction with the regulatory ORMDL subunit of SPT. Pertinent to the altered homeostatic control, lipid analysis showed overall increased SL levels in the patient plasma. An increased SPT activity and SL de novo synthesis was confirmed in p.L38R expressing HEK293 cells. Particularily dihydro-sphingolipids (dhSL) were signficantly increased in patient plasma and p.L38R mutant expressing cells. Increased dhSL formation has been previously linked to neurotoxicity and may be involved in the pathomechanism of SPTLC1-ALS mutations
CaMtw1, a member of the evolutionarily conserved Mis12 kinetochore protein family, is required for efficient inner kinetochore assembly in the pathogenic yeast Candida albicans
No full textSerine Palmitoyltransferase Subunit 3 and Metabolic Diseases
No full textSphingolipids (SL) are a class of chemically diverse lipids that have important structural and physiological functions in eukaryotic cells. SL entail a long chain base (LCB) as the common structural element, which is typically formed by the condensation of L-serine and long chain acyl-CoA. This condensation is the first and the rate-limiting step in the de novo SL synthesis and catalyzed by the enzyme serine palmitoyltransferase (SPT). Although palmitoyl-CoA is the preferred substrate, SPT can also metabolize other acyl-CoAs, thereby forming a variety of LCBs, which differ in structures and functions. The mammalian SPT enzyme is composed of three core subunits: SPTLC1, SPTLC2, and SPTLC3. Whereas SPTLC1 and SPTLC2 are ubiquitously expressed, SPTLC3 expression is restricted to a few specific tissues. The SPTLC1 subunit is essential and can associate with either SPTLC2 or SPTLC3 to form an active enzyme. Depending on the stoichiometry of the SPTLC2 and SPTLC3 subunits, the spectrum of SPT products varies. While SPTLC1 and SPTLC2 primarily form C18 and C20 LCBs, the combination of SPTLC1 and SPTLC3 produces a broader spectrum of LCBs. Genetic and population based studies have shown that SPTLC3 expression and function are associated with an altered plasma SL profile and an increased risk for cardio-metabolic diseases. Animal and in vitro studies showed that SPTLC3 might be involved in hepatic and cardiac pathology and could be a therapeutic target for these conditions.Here we present an overview of the current data on the role of SPTLC3 in normal and pathological conditions
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