| 1. |
- Ericsson, Rolf
(författare)
-
A Comparative Study of Head Development in Mexican Axolotl and Australian Lungfish: Cell Migration, Cell Fate and Morphogenesis
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of the vertebrate head is a complex process involving interactions between a multitude of cell types and tissues. This thesis describes the development of the cranial neural crest and of the visceral arch muscles in the head of two species. One, the Mexican axolotl (Ambystoma mexicanum), is a basal tetrapod, whereas the other, the Australian lungfish (Neoceratodus forsteri), belongs to the Dipnoi, the extant sister group of the Tetrapoda. The migration of neural crest cells, which form most of the bones and connective tissues in the head, and the morphogenesis of the jaw, was determined in the Mexican axolotl. It was shown that both the upper and lower jaws form from ventral condensations of neural crest cells in the mandibular arch. The dorsal condensation, earlier considered to give rise to the upper jaw, was shown to form the trabecula cranii.The normal spatio-temporal development of visceral arch muscles was investigated in both the Mexican axolotl and the Australian lungfish. In axolotl, the muscles tended to start forming almost simultaneously in all visceral arches at their future origins and extend towards their future insertions at the onset of muscle fibre formation. In lungfish, fibres formed simultaneously throughout most of each muscle anlage in the first and second visceral arch, but were delayed in the branchial arches. The anlagen were first observed at their future insertion, from which they developed towards future origins. To test the ability of neural crest cells to pattern the visceral arch muscles, migrating crest cells were extirpated from axolotl embryos, which resulted in a wide range of muscle malformations. In most cases, the muscles appeared in the right position but were small and extended in abnormal directions. This shows that neural crest cells are responsible not for the position of the muscles but for their correct anatomical pattern. Fate mapping showed that connective tissue surrounding myofibers is, at least partly, neural crest derived.In conclusion, the work presented in this thesis shows that although early development may map out the patterns of later development, the differences between axolotl and lungfish head development are not seen until during morphogenesis. Further investigation of morphogenesis is needed to explain the great variation of head morphology seen in vertebrates today.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Pendleton, Hillevi, et al.
(författare)
-
Motilin concentrations in relation to gastro intestinal dysmotility in diabetes mellitus.
- 2009
-
Ingår i: European journal of internal medicine. - : Elsevier BV. - 1879-0828 .- 0953-6205. ; 20:6, s. 654-9
-
Tidskriftsartikel (refereegranskat)abstract
- AIM: Dysmotility in the upper gastro intestinal (GI) tract are common problems in diabetics. Many peptides are involved in the regulation of the motility. The aim of this study was to examine whether plasma levels of motilin were related to dysfunction in the oesophagus and stomach in a well-defined diabetic patient group. METHODS: Nineteen patients with symptoms from the GI tract who had been examined with oesophageal manometry, gastric emptying scintigraphy and deep-breathing test were included. They received a fat-rich meal, after which blood samples were collected and analysed for motilin concentrations. RESULTS: Symptoms of abdominal fullness and gastro oesophageal reflux significantly associated with delayed gastric emptying, whereas no symptom correlated to oesophageal dysmotility. Plasma levels of motilin were increased after the fat-rich meal (p=0.000), with no difference between the groups. Abnormal manometry was characterized by aperistalsis and/or simultaneous contractions. The percentage of simultaneous contractions correlated to basic and peak motilin values (r(s)=0.898, p=0.006 and r(s)=0.842, p=0.017, respectively). Gastric emptying did not influence motilin concentrations. CONCLUSION: Plasma motilin concentrations vary with abnormalities of oesophageal motility in diabetics, but not with abnormalities of gastric emptying.
|
|
| 5. |
- Yu, Wenqiang, et al.
(författare)
-
Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation
- 2004
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 36:10, s. 1105-1110
-
Tidskriftsartikel (refereegranskat)abstract
- Chromatin insulators demarcate expression domains by blocking the cis effects of enhancers or silencers in a position-dependent manner1, 2. We show that the chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation. Chromatin immunoprecipitation analysis showed that a poly(ADP-ribosyl)ation mark, which exclusively segregates with the maternal allele of the insulator domain in the H19 imprinting control region, requires the bases that are essential for interaction with CTCF3. Chromatin immunoprecipitation−on−chip analysis documented that the link between CTCF and poly(ADP-ribosyl)ation extended to more than 140 mouse CTCF target sites. An insulator trap assay showed that the insulator function of most of these CTCF target sites is sensitive to 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase activity. We suggest that poly(ADP-ribosyl)ation imparts chromatin insulator properties to CTCF at both imprinted and nonimprinted loci, which has implications for the regulation of expression domains and their demise in pathological lesions.
|
|
| 6. |
- Andersson, Niklas, 1970, et al.
(författare)
-
A gene expression fingerprint of mouse stomach ECL cells.
- 2005
-
Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 332:2, s. 404-10
-
Tidskriftsartikel (refereegranskat)abstract
- Many of the endocrine cells in the stomach are poorly characterized with respect to physiological significance. In some cases, the anticipated hormone has not yet been identified. Global gene expression analysis of mouse stomach was performed in an attempt to identify the ECL-cell peptide/protein. Specific functional activation (omeprazole-induced hypergastrinaemia) was used as a tool to generate a gene expression fingerprint of the ECL cells. The proposed fingerprint includes 14 genes, among them six are known to be expressed by ECL cells (=positive controls), and some novel ones, which are likely to be ECL-cell-related. The known ECL-cell-related genes are those encoding histidine decarboxylase, chromogranin A and B, vesicular monoamine transporter 2, synaptophysin, and the cholecystokinin-B receptor. In addition, the fingerprint included five genes, which might be involved in the process of secretion and three ESTs with unknown function. Interestingly, parathyroid hormone-like hormone (Pthlh) was identified as a candidate ECL-cell peptide hormone.
|
|
| 7. |
- Andersson, Niklas, 1970, et al.
(författare)
-
Drug-induced prevention of gastrectomy- and ovariectomy-induced osteopaenia in the young female rat.
- 2002
-
Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 175:3, s. 695-703
-
Tidskriftsartikel (refereegranskat)abstract
- Both ovariectomy (Ovx) and gastrectomy (Gx) induce osteopaenia in rats and humans. While the effect of Ovx has been ascribed to oestrogen deficiency, the underlying mechanism behind Gx is poorly understood. Alendronate, oestrogen and parathyroid hormone (PTH) are known to prevent the osteopaenia induced by Ovx in rats. The purpose of the present study was to determine whether alendronate, oestrogen or PTH could also prevent Gx-evoked osteopaenia. Rats were Ovx-, Gx-, or were sham-operated (Sham) and were then treated with alendronate (50 micro g/kg/day), oestrogen (10 micro g/kg/day) or PTH(1-84) (75 micro g/kg/day) for eight weeks. At sacrifice, serum PTH was unaffected by surgery (Ovx, 64+/-8 pg/ml; Gx, 75+/-13 pg/ml; Sham, 58+/-11 pg/ml). The bone mineral density (BMD) of the fifth lumbar vertebra (L5) was analysed. Ovx and Gx reduced the BMD (ash weight/Volume) of the L5 by 15+/-4% and 22+/-3% respectively. Trabecular BMD and the cortical bone mineral content (BMC) of the femur were assessed using peripheral computed tomography. Both Ovx and Gx markedly reduced trabecular BMD in the metaphyseal area of the distal femur (Ovx, -37+/-7%; Gx, -49+/-7%). The cortical BMC of the femur was only slightly reduced. Alendronate prevented trabecular bone loss after both Ovx and Gx, while oestrogen and PTH prevented trabecular bone loss after Ovx but not after Gx. In conclusion, the bisphosphonate alendronate prevented both Ovx- and Gx-induced trabecular bone loss. In contrast, PTH and oestrogen prevented Ovx-induced but not Gx-induced trabecular bone loss, suggesting that the mechanism behind the trabecular bone loss in Ovx rats differs from that in Gx rats. The results support the notion that the mechanism of action for the bone-sparing effect of these drugs differs. The ability of alendronate, and probably also other bisphosphonates, to prevent Gx-evoked osteopaenia in the rat might be of potential clinical interest when dealing with post-Gx osteopaenia in humans.
|
|
| 8. |
- Andersson, Niklas, 1970, et al.
(författare)
-
Pharmacological treatment of osteopenia induced by gastrectomy or ovariectomy in young female rats.
- 2004
-
Ingår i: Acta orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470 .- 1651-1964. ; 75:2, s. 201-9
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both gastrectomy (GX) and ovariectomy (OVX) induce osteopenia in man and experimental animals. The present study addresses the question--can alendronate, estrogen or parathyroid hormone (PTH) be used to treat established GX- or OVX -evoked osteopenia? METHODS: Rats were GX-, OVX- or SHAM-operated 8 weeks before starting the treatment with drugs. Each group was then treated for 8 weeks with 50 microg/kg/day alendronate, 10 microg/kg/day estrogen or 75 microg/kg/day PTH(1-84); n = 8 rats/group. Peripheral Quantitative Computed Tomography (pQCT) was used to measure trabecular bone mineral density (BMD) and various cortical bone parameters. RESULTS: At killing, 16 weeks after surgery, GX and OVX rats had a greatly reduced trabecular BMD in the metaphysis of the distal femur (GX -44% and OVX -55%). Alendronate increased the trabecular BMD by 44% in GX rats and by 64% in OVX rats, while PTH increased it by 51% and 115%, respectively. However, estrogen increased the trabecular BMD in GX rats (35%), but not in OVX rats (15%, not significant). Cortical bone parameters were adversely (but moderately) affected by GX, but not by OVX or by treatment with the three drugs. INTERPRETATION: Alendronate, estrogen and PTH restored the trabecular bone loss in rats with an established GX-evoked osteopenia. In contrast, alendronate and PTH, but not estrogen, restored the trabecular bone loss after OVX. Hence, the mechanism underlying GX-evoked bone loss differs from that underlying OVX-evoked bone loss. The ability of alendronate, estrogen and PTH to reverse the GX-evoked osteopenia in the rat may be of clinical interest when dealing with bone loss in humans after GX.
|
|
| 9. |
|
|
| 10. |
- Bengtsson, Tommy, et al.
(författare)
-
Age-specific mortality and short-term changes in the standard of living : Sweden, 1751-1859
- 1985
-
Ingår i: European Journal of Population. - 0168-6577. ; 1:4, s. 309-326
-
Tidskriftsartikel (refereegranskat)abstract
- The response of mortality to short-term changes in real wages is analyzed here not just in its own right but more particularly as an indicator of long-term shifts in the general standard of living. It is hypothesized that the response would have been stronger the lower the standard of living. The relationship between age-specific mortality levels and real-wage series for Sweden 1751–1860 is analyzed using a distributed-lag model and spectral analysis. The results suggest a real shift in the material standard of living during the period.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Bengtsson, Tommy, et al.
(författare)
-
Population and Economic Fluctuations in Sweden 1949-1914
- 1984
-
Ingår i: Pre-Industrial Population Change : The Mortality Decline and Short-Term Population Movements - The Mortality Decline and Short-Term Population Movements. - 9122007415 ; , s. 277-298
-
Bokkapitel (refereegranskat)
|
|
| 15. |
|
|
| 16. |
- Bengtsson, Tommy, et al.
(författare)
-
Sveriges befolkning - myter och verklighet
- 1993
-
Ingår i: Äventyret Sverige : En ekonomisk och social historia - En ekonomisk och social historia. - 9126933004 ; , s. 113-132
-
Bokkapitel (populärvet., debatt m.m.)
|
|
| 17. |
- Bengtsson, Tommy, et al.
(författare)
-
The Demographic Transition Revised
- 1994
-
Ingår i: Population, Economy, and Welfare in Sweden. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 3540584234 ; , s. 13-36
-
Bokkapitel (refereegranskat)
|
|
| 18. |
|
|
| 19. |
- Bergström, Rosita, et al.
(författare)
-
CTCF Regulates Asynchronous Replication of the Imprinted H19/Igf2 Domain
- 2007
-
Ingår i: Cell Cycle. - : Informa UK Limited. - 1538-4101 .- 1551-4005. ; 6:4, s. 450-454
-
Tidskriftsartikel (refereegranskat)abstract
- Asynchronous replication during S phase is a universal characteristic of genomically imprinted genes. Replication timing in imprinted domains is determined epigenetically, as it is parent of origin specific, and is seen in the absence of sequence divergence between the two alleles. At the imprinted H19/lgf2 domain, the methylated paternal allele replicates early while the CTCF-bound maternal allele replicates late during S phase. CTCF regulates the allele-specific epigenetic characteristics of this domain, including methylation, transcription and chromosome conformation. Here we show that maternal, but not paternal inheritance of a mutated H19 imprinting control region, lacking functional CTCF binding sites, underlies a late to early switch in replication timing of the maternal H19/ lgf2 domain.
|
|
| 20. |
- Bergström, Rosita, 1978-
(författare)
-
Epigenetic Regulation of Replication Timing and Signal Transduction
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Upon fertilization the paternal and maternal genomes unite, giving rise to the embryo, with its unique genetic code. All cells in the human body are derived from the fertilized ovum: hence they all contain (with a few exceptions) the same genetic composition. However, by selective processes, genes are turned on and off in an adaptable, and cell type-specific, manner. The aim of this thesis is to investigate how signals coming from outside the cell and epigenetic factors residing in the cell nucleus, cooperate to control gene expression. The transforming growth factor-β (TGF-β) superfamily consists of around 30 cytokines, which are essential for accurate gene regulation during embryonic development and adult life. Among these are the ligands TGF-β1 and bone morphogenetic (BMP) -7, which interact with diverse plasma membrane receptors, but signal via partly the same Smad proteins. Smad4 is essential to achieve TGF-β-dependent responses. We observed that by regulating transcription factors such as Id2 and Id3 in a specific manner, TGF-β1 and BMP-7 achieve distinct physiological responses. Moreover, we demonstrate that CTCF, an insulator protein regulating higher order chromatin conformation, is able to direct transcription by recruiting RNA polymerase II to its target sites. This is the first mechanistic explanation of how an insulator protein can direct transcription, and reveals a link between epigenetic modifications and classical regulators of transcription. We also detected that DNA loci occupied by CTCF replicate late. The timing of replication is a crucial determinant of gene activity. Genes replicating early tend to be active, whereas genes replicating late often are silenced. Thus, CTCF can regulate transcription at several levels. Finally, we detected a substantial cross-talk between CTCF and TGF-β signaling. This is the first time that a direct interplay between a signal transduction pathway and the chromatin insulator CTCF is demonstrated.
|
|
| 21. |
|
|
| 22. |
- Bergström, Rosita, et al.
(författare)
-
Transforming growth factor β promotes complexes between Smad proteins and the CCCTC-binding factor on the H19 imprinting control region chromatin
- 2010
-
Ingår i: Journal of Biological Chemistry. - USA : The American Society for Biochemistry and Molecular Biology, Inc.. - 0021-9258 .- 1083-351X. ; 285:26, s. 19727-19737
-
Tidskriftsartikel (refereegranskat)abstract
- Whether signal transduction pathways regulate epigenetic states in response to environmental cues remains poorly understood. We demonstrate here that Smad3, signaling downstream of transforming growth factor beta, interacts with the zinc finger domain of CCCTC-binding factor (CTCF), a nuclear protein known to act as "the master weaver of the genome." This interaction occurs via the Mad homology 1 domain of Smad3. Although Smad2 and Smad4 fail to interact, an alternatively spliced form of Smad2 lacking exon 3 interacts with CTCF. CTCF does not perturb well established transforming growth factor beta gene responses. However, Smads and CTCF co-localize to the H19 imprinting control region (ICR), which emerges as an insulator in cis and regulator of transcription and replication in trans via direct CTCF binding to the ICR. Smad recruitment to the ICR requires intact CTCF binding to this locus. Smad2/3 binding to the ICR requires Smad4, which potentially provides stability to the complex. Because the CTCF-Smad complex is not essential for the chromatin insulator function of the H19 ICR, we propose that it can play a role in chromatin cross-talk organized by the H19 ICR.
|
|
| 23. |
|
|
| 24. |
- Boisvert, Catherine Anne, 1978-
(författare)
-
The Origin of Tetrapod Limbs and Girdles: Fossil and Developmental Evidence
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Around 375 million years ago, the first tetrapods appeared, marking one of the most important events in vertebrate evolutionary history. The fin to limb transition saw the appearance of fingers and a weight bearing pelvic girdle. While very little research has been done on the evolution of the tetrapod pelvic girdle, a fair amount has been done on the origins of fingers but some aspects remained controversial. A combination of palaeontology, developmental biology and comparative morphology was therefore used in this thesis to better understand the fin to limb transition. The pectoral fin of Panderichthys, a sarcopterygian fish closely related to tetrapods was CT-scanned and modeled in three dimensions and its pelvic girdle and fin were examined with traditional techniques. This information from the fossil record was integrated with comparisons of the development of the Australian lungfish, Neoceratodus forsteri, our closest living fish relative and the axolotl (Ambystoma mexicanum), a salamander representing well the condition of early tetrapods. Development of bone and cartilage was studied through clearing and staining and development of skeletal muscles through immunostaining. In situ hybridizations were performed on the lungfish to study the expression of Hoxd13, associated with the formation of digits in tetrapods. This work shows that the late expression phase of Hoxd13 is present in Neoceratodus and is associated with the formation of radials. Redescription of the pectoral fin of Panderichthys reveals that distal radials are present, which, in addition to other information, lead us to conclude that digits are not novelties in tetrapods but rather have evolved from the distal radials present in the fins of all sarcopterygian fish. The earliest tetrapods lack a full set of wrist + carpals/ankle + tarsal bones. Here, we propose that this region of the limbs evolved after fingers and toes through an expansion of the region between the proximal limb bones and the digits. As for the pelvic girdle, it is very primitive in Panderichthys but comparison of its development in Neoceratodus and Ambystoma suggest that the ischium evolved through the posterior expansion of the pubis and the ilium, through an elongation of the iliac process already present in sarcopterygian fishes. The results of this thesis help to better understand the fin to limb transition and show that it is more gradual than previously believed.
|
|
| 25. |
- Borg, Julia, et al.
(författare)
-
Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus.
- 2007
-
Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 24:11, s. 1235-1239
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Gastroparesis is a common gastrointestinal complication in diabetes mellitus, whereas dysfunction in the other gastrointestinal organs has been less thoroughly investigated. Furthermore, it is not known whether there is any relationship between motility and dysmotility between these organs. The aim of this study was to examine whether diabetic patients with gastrointestinal symptoms also have motility disturbances in the oesophagus and stomach and, if so, whether there are any associations between these disturbances. Methods Thirty-one patients with diabetes mellitus who complained of gastrointestinal symptoms were asked to complete a questionnaire about their symptoms. They were further investigated with oesophageal manometry and gastric emptying scintigraphy. Results Fifty-eight per cent of the patients had abnormal oesophageal function, and 68% had delayed gastric emptying. Abdominal fullness was the only symptom that related to any dysfunction, and it was associated with delayed gastric emptying (P = 0.02). We did not find any relationship in motility or dysmotility between the oesophagus and the stomach. Conclusion Oesophageal dysmotility, as well as gastroparesis, are common in patients with diabetes who have gastrointestinal symptoms. It is important to investigate these patients further, to be able to reach an accurate diagnosis and instigate appropriate treatment. Our findings indicate that the oesophagus and the stomach function as separate organs and that pathology in one does not necessarily mean pathology in the other.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Chen, Xingqi, et al.
(författare)
-
Chromatin in situ proximity (ChrISP) : Single-cell analysis of chromatin proximities at a high resolution
- 2014
-
Ingår i: BioTechniques. - : Future Science Ltd. - 0736-6205 .- 1940-9818. ; 56:3, s. 117-124
-
Tidskriftsartikel (refereegranskat)abstract
- Current techniques for analyzing chromatin structures are hampered by either poor resolution at the individual cell level or the need for a large number of cells to obtain higher resolution. This is a major problem as it hampers our understanding of chromatin conformation in single cells and how these respond to environmental cues. Here we describe a new method, chromatin in situ proximity (ChrISP), which reproducibly scores for proximities between two different chromatin fibers in 3-D with a resolution of similar to 170 angstrom in single cells. The technique is based on the in situ proximity ligation assay (ISPLA), but ChrISP omits the rolling circle amplification step (RCA). Instead, the proximities between chromatin fibers are visualized by a fluorescent connector oligonucleotide DNA, here termed splinter, forming a circular DNA.with another circle-forming oligonucleotide, here termed backbone, upon ligation. In contrast to the regular ISPLA technique, our modification enables detection of chromatin fiber proximities independent of steric hindrances from nuclear structures. We use this method to identify higher order structures of individual chromosomes in relation to structural hallmarks of interphase nuclei and beyond the resolution of the light microscope.
|
|
| 30. |
- Chernukhin, Igor, et al.
(författare)
-
CTCF Interacts with and Recruits the Largest Subunit of RNA Polymerase II to CTCF Target Sites Genome-Wide
- 2007
-
Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 27:5, s. 1631-1648
-
Tidskriftsartikel (refereegranskat)abstract
- CTCF is a transcription factor with highly versatile functions ranging from gene activation and repression to the regulation of insulator function and imprinting. Although many of these functions rely on CTCF-DNA interactions, it is an emerging realization that CTCF-dependent molecular processes involve CTCF interactions with other proteins. In this study, we report the association of a subpopulation of CTCF with the RNA polymerase II (Pol II) protein complex. We identified the largest subunit of Pol II (LS Pol II) as a protein significantly colocalizing with CTCF in the nucleus and specifically interacting with CTCF in vivo and in vitro. The role of CTCF as a link between DNA and LS Pol II has been reinforced by the observation that the association of LS Pol II with CTCF target sites in vivo depends on intact CTCF binding sequences. "Serial" chromatin immunoprecipitation (ChIP) analysis revealed that both CTCF and LS Pol II were present at the β-globin insulator in proliferating HD3 cells but not in differentiated globin synthesizing HD3 cells. Further, a single wild-type CTCF target site (N-Myc-CTCF), but not the mutant site deficient for CTCF binding, was sufficient to activate the transcription from the promoterless reporter gene in stably transfected cells. Finally, a ChIP-on-ChIP hybridization assay using microarrays of a library of CTCF target sites revealed that many intergenic CTCF target sequences interacted with both CTCF and LS Pol II. We discuss the possible implications of our observations with respect to plausible mechanisms of transcriptional regulation via a CTCF-mediated direct link of LS Pol II to the DNA.
|
|
| 31. |
- de la Cour, Charlotta, et al.
(författare)
-
Ghrelin treatment reverses the reduction in weight gain and body fat in gastrectomised mice.
- 2005
-
Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 54:7, s. 907-13
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The gastric hormone ghrelin has been reported to stimulate food intake, increase weight gain, and cause obesity but its precise physiological role remains unclear. We investigated the long term effects of gastrectomy evoked ghrelin deficiency and of daily ghrelin injections on daily food intake, body weight, fat mass, lean body mass, and bone mass in mice. METHODS: Ghrelin was given by subcutaneous injections (12 nmol/mouse once daily) for eight weeks to young female mice subjected to gastrectomy or sham operation one week previously. RESULTS: Gastrectomy reduced plasma concentrations of total ghrelin (octanoylated and des-octanoylated) and active (octanoylated) ghrelin by approximately 80%. Immediately after injection of ghrelin, the plasma concentration was supraphysiological and was still elevated 16 hours later. Daily food intake was not affected by either gastrectomy or ghrelin treatment. The effect of ghrelin on meal initiation was not studied. At the end point of the study, mean body weight was 15% lower in gastrectomised mice than in sham operated mice (p<0.001); daily ghrelin injections for eight weeks partially prevented this weight loss. In sham operated mice, ghrelin had no effect on body weight. The weight of fat was reduced in gastrectomised mice (-30%; p<0.01). This effect was reversed by ghrelin, enhancing the weight of fat in sham operated mice also (+20%; p<0.05). Gastrectomy reduced lean body mass (-10%; p<0.01) and bone mass (-20%; p<0.001) compared with sham operated mice. Ghrelin replacement prevented the gastrectomy induced decrease in lean body mass but did not affect bone. In sham operated mice, ghrelin affected neither of these two parameters. CONCLUSIONS: Ghrelin replacement partially reversed the gastrectomy induced reduction in body weight, lean body mass, and body fat but not in bone mass. In sham operated mice, ghrelin only increased fat mass. Our results suggest that ghrelin is mainly concerned with the control of fat metabolism and that ghrelin replacement therapy may alleviate the weight loss associated with gastrectomy.
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
- Franklin, Gary C., et al.
(författare)
-
An Inr-containing sequence flanking the TATA box of the human c-sis (PDGF-B) proto-oncogene promoter functions in cis as a co-activator for its intronic enhancer
- 1995
-
Ingår i: Oncogene. - 0950-9232 .- 1476-5594. ; 11:9, s. 1873-1884
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- High-level activity of the human PDGF-B promoter in choriocarcinoma cell lines depends upon an atypical, intronic enhancer-like element which does not function with heterologous promoters tested. An extensive series of mutant PDGF-B promoter-driven constructs identified a sequence flanking the TATA box which is required specifically for enhancer-mediated transcription in human choriocarcinoma cell lines. This element, which we here term an enhancer-dependent cis co-activator (EDC) contains an Inr (initiator) consensus sequence upstream of the TATA box which is required, but not sufficient for its function. Requirement for the EDC is cell type-specific, since it was dispensable for enhancer-mediated transcription in a human breast cancer cell line. Although it lies within the region defined, the TATA box itself is not required for EDC function, or for basal promoter function which may derive from a second Inr-like sequence situated at the transcriptional start site. These observations indicate that interactions between some promoter and enhancer elements may be more complex than that generally described for 'classical' enhancer systems and may suggest an additional function for the initiator motif.
|
|
| 35. |
|
|
| 36. |
- Gréen, Anna, 1973-
(författare)
-
Histone H1 : Subtypes and phosphorylation in cell life and death
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The genetic information of a human diploid cell is contained within approximately 2 metres of linear DNA. The DNA molecules are compacted and organized in various ways to fit inside the cell nucleus. Various kinds of histones are involved in this compaction. One of these histones, histone H1 is the topic of the present thesis. In addition to its structural role, H1 histones have been implicated in various processes, for example gene regulation and inhibition of chromatin replication.H1 histones, also termed linker histones, are relatively conserved proteins, and the various subtypes seem to have different and important functions even though redundancy between the subtypes has been demonstrated. Despite the sequence conservation of H1 subtypes, two sequence variations were detected within the H1.2 and H1.4 subtypes using hydrophilic interaction liquid chromatographic separation of H1 proteins from K562 and Raji cell lines in Paper I in the present thesis. The variations were confirmed by genetic analysis, and the H1.2 sequence variation was also found in genomic DNA of normal blood donors, in an allele frequency of 6.8%. The H1.4 sequence variation was concluded to be Raji specific. The significance of H1 microsequence variants is unclear, since the physiological function of H1 histones remains to be established.H1 histones can be phosphorylated at multiple sites. Changes in H1 phosphorylation has been detected in apoptosis, the cell cycle, gene regulation, mitotic chromatin condensation and malignant transformation. Contradictory data have been obtained on H1 phosphorylation in apoptosis, and many results indicate that H1 dephosphorylation occurs during apoptosis. We and others hypothesized that cell cycle effects by the apoptosis inducers may have affected previous studies. In Paper II, the H1 phosphorylation pattern was investigated in early apoptosis in Jurkat cells, taking cell cycle effects into account. In receptor-mediated apoptosis, apoptosis occurs with a mainly preserved phosphorylation pattern, while Camptothecin induced apoptosis results in rapid dephosphorylation of H1 subtypes, demonstrating that H1 dephosphorylation is not a general event in apoptosis, but may occur upon apoptosis induction via the mitochondrial pathway. The dephosphorylation may also be a result of early cell cycle effects or signalling.Therefore, the H1 phosphorylation pattern in the cell cycle of normal activated T cells was investigated in Paper IV in this thesis. Some studies, which have been made using cancer cell lines from various species and cell synchronization, have indicated a sequential addition of phosphate groupsacross the cell cycle. Normal T cells and cell sorting by flow cytometry were used to circumvent side-effects from cell synchronization. The data demonstrate that a pattern with phosphorylated serines is established in late G1/early S phase, with some additional phosphorylation occurring during S, and further up-phosphorylation seems to occur during mitosis. Malignant transformation may lead to an altered G1 H1 phosphorylation pattern, as was demonstrated using sorted Jurkat T lymphoblastoid cells.During mitosis, certain H1 subtypes may be relocated to the cytoplasm. In Paper III, the location of histones H1.2, H1.3 and H1.5 during mitosis was investigated. Histone H1.3 was detected in cell nuclei in all mitotic stages, while H1.2 was detected in the nucleus during prophase and telophase, and primarily in the cytoplasm during metaphase and early anaphase. H1.5 was located mostly to chromatin during prophase and telophase, and to both chromatin and cytoplasm during metaphase and anaphase. Phosphorylated H1 was located in chromatin in prophase, and in both chromatin and cytoplasm during metaphase, anaphase and telophase, indicating that the mechanism for a possible H1 subtype relocation to the cytoplasm is phosphorylation.In conclusion, data obtained during this thesis work suggest that H1 histones and their phosphorylation may participate in the regulation of events in the cell cycle, such as S-phase progression and mitosis, possibly through altered interactions with chromatin, and/or by partial or complete removal of subtypes or phosphorylated variants from chromatin.
|
|
| 37. |
- Guibert, Sylvain, et al.
(författare)
-
CTCF-binding sites within the H19 ICR differentially regulate local chromatin structures and cis-acting functions
- 2012
-
Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 7:4, s. 361-369
-
Tidskriftsartikel (refereegranskat)abstract
- It is generally assumed that CTCF-binding sites are synonymous with the demarcation of expression domains by promoting the formation of chromatin loops. We have proposed earlier, however, that such features may be context-dependent. In support of this notion, we show here that chromatin loop structures, impinging on CTCF-binding sites 1/2 and 3/4 at the 5' and 3'-ends, respectively, within the maternal allele of the H19 imprinting control region (ICR), differ significantly. Although abrogation of CTCF binding to the maternal H19 ICR allele results in loss of chromatin loops in the 3'-region, there is a dramatic gain of long-range chromatin loops impinging on the 5'-region. As the degree of occupancy of its four CTCF-binding sites discriminates between the chromatin insulator and replication timing functions, we submit that the CTCF-binding sites within the H19 ICR are functionally diverse and organize context-dependent higher order chromatin conformations.
|
|
| 38. |
- Gustafsson, Rita, et al.
(författare)
-
Esophageal Dysmotility is More Common Than Gastroparesis in Diabetes Mellitus and is Associated With Retinopathy.
- 2011
-
Ingår i: Review of Diabetic Studies. - 1614-0575. ; 8:2, s. 268-275
-
Tidskriftsartikel (refereegranskat)abstract
- Gastroparesis is a well-known complication of diabetes mellitus, both in symptomatic and asymptomatic patients. Esophageal dysmotility has also been described, but is not as well-characterized. The etiology and effect of these complications need to be clarified. The aim of the present study was to evaluate esophageal and gastric motility, complications, gastrointestinal symptoms, and plasma biomarkers in a cross-sectional study comprising patients with diabetes mellitus.
|
|
| 39. |
|
|
| 40. |
- Göndör, Anita, et al.
(författare)
-
Chromatin insulators and cohesins
- 2008
-
Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 9:4, s. 327-329
-
Tidskriftsartikel (refereegranskat)
|
|
| 41. |
|
|
| 42. |
- Göndör, Anita, et al.
(författare)
-
High-resolution circular chromosome conformation capture assay
- 2008
-
Ingår i: Nature protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 3:2, s. 303-313
-
Tidskriftsartikel (refereegranskat)abstract
- The pioneering chromosome conformation capture (3C) method provides the opportunity to study chromosomal folding in the nucleus. It is based on formaldehyde cross-linking of living cells followed by enzyme digestion, intramolecular ligation and quantitative (Q)-PCR analysis. However, 3C requires prior knowledge of the bait and interacting sequence (termed interactor) rendering it less useful for genome-wide studies. As several recent reports document, this limitation has been overcome by exploiting a circular intermediate in a variant of the 3C method, termed 4C (for circular 3C). The strategic positioning of primers within the bait enables the identification of unknown interacting sequences, which form part of the circular DNA. Here, we describe a protocol for our 4C method, which produces a high-resolution interaction map potentially suitable for the analysis of cis-regulatory elements and for comparison with chromatin marks obtained by chromatin immunoprecipitation (ChIP) on chip at the sites of interaction. Following optimization of enzyme digestions and amplification conditions, the protocol can be completed in 2-3 weeks.
|
|
| 43. |
- Göndör, Anita, et al.
(författare)
-
Transcription in the loop.
- 2006
-
Ingår i: Nat Genet. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 38:11, s. 1229-30
-
Tidskriftsartikel (refereegranskat)
|
|
| 44. |
- Göndör, Anita, et al.
(författare)
-
Window into the Complexities of Chromosome Interactomes
- 2010
-
Ingår i: Cold Spring Harbor Symposia on Quantitative Biology. - : Cold Spring Harbor Laboratory. - 0091-7451 .- 1943-4456. ; 75, s. 493-500
-
Tidskriftsartikel (refereegranskat)abstract
- DNA is folded into increasingly complex yet highly mobile structures to organize the chromosomes. In the interphase nucleus, chromosomes or part of the chromosomes encounter one another preferentially at the boundaries between chromosomal territories. Although this situation implies that the preferred chromosomal neighborhood is a key determinant of interactions between chromosomes, what this means in functional terms is currently not well understood. Using the H19 imprinting control region as a window, it has been demonstrated that epigenetic information of the primary chromatin fiber has dual functions. Thus, epigenetic marks not only influence the proximity between chromatin fibers but also transfer epigenetic states between chromatin fibers both in cis and in trans. High-throughput sequence and DNA fluorescence it situ hybridization (FISH) analyses reveal that these features require chromatin movements that are restricted in space and time. The mechanisms involved in the establishment of chromosome interactomes may provide insight of fundamental importance into pivotal regulatory processes in the nucleus, such as the coordination of transcriptional programs and replication timing.
|
|
| 45. |
- Hancock, Anne L, et al.
(författare)
-
A CTCF-binding silencer regulates the imprinted genes AWT1 and WT1-AS and exhibits sequential epigenetic defects during Wilms' tumourigenesis
- 2007
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 16:3, s. 343-354
-
Tidskriftsartikel (refereegranskat)abstract
- We have shown previously that AWT1 and WT1-AS are functionally imprinted in human kidney. In the adult kidney, expression of both transcripts is restricted to the paternal allele, with the silent maternal allele retaining methylation at the WT1 antisense regulatory region (WT1 ARR). Here, we report characterization of the WT1 ARR differentially methylated region and show that it contains a transcriptional silencer element acting on both the AWT1 and WT1-AS promoters. DNA methylation of the silencer results in increased transcriptional repression, and the silencer is also shown to be an in vitro and in vivo target site for the imprinting regulator protein CTCF. Binding of CTCF is methylation-sensitive and limited to the unmethylated silencer. Potentiation of the silencer activity is demonstrated after CTCF protein is knocked down, suggesting a novel silencer-blocking activity for CTCF. We also report assessment of WT1 ARR methylation in developmental and tumour tissues, including the first analysis of Wilms' tumour precursor lesions, nephrogenic rests. Nephrogenic rests show increases in methylation levels relative to foetal kidney and reductions relative to the adult kidney, together with biallelic expression of AWT1 and WT1-AS. Notably, the methylation status of CpG residues within the CTCF target site appears to distinguish monoallelic and biallelic expression states. Our data suggest that failure of methylation spreading at the WT1 ARR early in renal development, followed by imprint erasure, occurs during Wilms' tumourigenesis. We propose a model wherein imprinting defects at chromosome 11p13 may contribute to Wilms' tumourigenesis.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
