| 1. |
- Abramsson, Alexandra, 1973, et al.
(författare)
-
Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development
- 2007
-
Ingår i: GENES & DEVELOPMENT. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 21:3, s. 316-331
-
Tidskriftsartikel (refereegranskat)abstract
- During vascular development, endothelial platelet-derived growth factor B (PDGF-B) is critical for pericyte recruitment. Deletion of the conserved C-terminal heparin-binding motif impairs PDGF-BB retention and pericyte recruitment in vivo, suggesting a potential role for heparan sulfate (HS) in PDGF-BB function during vascular development. We studied the participation of HS chains in pericyte recruitment using two mouse models with altered HS biosynthesis. Reduction of N-sulfation due to deficiency in N-deacetylase/N-sulfotransferase-1 attenuated PDGF-BB binding in vitro, and led to pericyte detachment and delayed pericyte migration in vivo. Reduced N-sulfation also impaired PDGF-BB signaling and directed cell migration, but not proliferation. In contrast, HS from glucuronyl C5-epimerase mutants, which is extensively N- and 6-O-sulfated, but lacks 2-O-sulfated L-iduronic acid residues, retained PDGF-BB in vitro, and pericyte recruitment in vivo was only transiently delayed. These observations were supported by in vitro characterization of the structural features in HS important for PDGF-BB binding. We conclude that pericyte recruitment requires HS with sufficiently extended and appropriately spaced N-sulfated domains to retain PDGF-BB and activate PDGF receptor β (PDGFRβ) signaling, whereas the detailed sequence of monosaccharide and sulfate residues does not appear to be important for this interaction.
|
|
| 2. |
- 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.
|
|
| 3. |
- Dahlman, Joakim, 1974-, et al.
(författare)
-
Performance and Autonomic Responses during Motion Sickness
- 2009
-
Ingår i: Human Factors. - : SAGE Publications. - 0018-7208 .- 1547-8181. ; 51:1, s. 56-66
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to investigate how motion sickness, triggered by an optokinetic drum, affects short term memory performance and to explore autonomic responses to perceived motion sickness. Background: Previous research has found motion sickness to decrease performance, but it is not known how short term memory in particular is affected. Method: Thirty-eight healthy participants performed a listening span test while seated in a rotating optokinetic drum. Measurements of motion sickness, performance, heart rate, skin conductance, blood volume pulse, and pupil size were performed simultaneously throughout the experiment. Results: A total of 16 participants terminated the trial due to severe nausea, while the other 22 endured the full 25 minutes. Perceived motion sickness increased over time in both groups, but less among those who endured the trial. Short term memory performance decreased towards the end for those who terminated, while it increased for the other group. Results from the measured autonomic responses were ambiguous. Conclusion: The present study concludes that performance, measured as short term memory, declines as perceived motion sickness progresses. Application: This research has potential implications for command and control personnel in risk of developing motion sickness.
|
|
| 4. |
|
|
| 5. |
- Ledin, Johan, et al.
(författare)
-
Enzymatically active N-deacetylase/N-sulfotransferase-2 is present in liver but does not contribute to heparan sulfate N-sulfation
- 2006
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 281:47, s. 35727-35734
-
Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) proteoglycans influence embryonic development through interactions with growth factors and morphogens. The interactions depend on HS structure, which is largely determined during biosynthesis by Golgi enzymes. NDST ( glucosaminyl N-deacetylase/N-sulfotransferase), responsible for HSN-sulfation, is a key enzyme directing further modifications including O-sulfation. To elucidate the roles of the different NDST isoforms in HS biosynthesis, we took advantage of mice with targeted mutations in NDST1 and NDST2 and used liver as our model organ. Of the four NDST isoforms, only NDST1 and NDST2 transcripts were shown to be expressed in control liver. The absence of NDST1 or NDST2 in the knock-out mice did not affect transcript levels of other NDST isoforms or other HS modification enzymes. Although the sulfation level of HS synthesized in NDST1(-/-) mice was drastically lowered, liver HS from wild-type mice, from NDST1(-/-), NDST2(-/-), and NDST1(-/-), NDST2(-/-) mice all had the same structure despite greatly reduced NDST enzyme activity (30% of control levels in NDST1(-/-) NDST2(-/-) embryonic day 18.5 embryos). Enzymatically active NDST2 was shown to be present in similar amounts in wild-type, NDST1(-/-), and NDST1(-/-) embryonic day 18.5 liver. Despite the substantial contribution of NDST2 to total NDST enzyme activity in embryonic day 18.5 liver (approximate to 40%), its presence did not appear to affect HS structure as long as NDST1 was also present. In NDST1(-/-) embryonic day 18.5 liver, in contrast, NDST2 was responsible for N-sulfation of the low sulfated HS. A tentative model to explain these results is presented.
|
|
