| 1. |
|
|
| 2. |
|
|
| 3. |
- Andersson, H.O., et al.
(författare)
-
Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors
- 2003
-
Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 270:8, s. 1746-1758
-
Tidskriftsartikel (refereegranskat)abstract
- HIV-1 protease is an important target for treatment of AIDS, and efficient drugs have been developed. However, the resistance and negative side effects of the current drugs has necessitated the development of new compounds with different binding patterns. In this study, nine C-terminally duplicated HIV-1 protease inhibitors were cocrystallised with the enzyme, the crystal structures analysed at 1.8-2.3 Å resolution, and the inhibitory activity of the compounds characterized in order to evaluate the effects of the individual modifications. These compounds comprise two central hydroxy groups that mimic the geminal hydroxy groups of a cleavage-reaction intermediate. One of the hydroxy groups is located between the d-oxygen atoms of the two catalytic aspartic acid residues, and the other in the gauche position relative to the first. The asymmetric binding of the two central inhibitory hydroxyls induced a small deviation from exact C2 symmetry in the whole enzyme-inhibitor complex. The study shows that the protease molecule could accommodate its structure to different sizes of the P2/P2' groups. The structural alterations were, however, relatively conservative and limited. The binding capacity of the S3/S3' sites was exploited by elongation of the compounds with groups in the P3/P3' positions or by extension of the P1/P1' groups. Furthermore, water molecules were shown to be important binding links between the protease and the inhibitors. This study produced a number of inhibitors with Ki values in the 100 picomolar range.
|
|
| 4. |
- Andersson, Mathias H., et al.
(författare)
-
Displacement effects of ship noise on fish population : FP7 - Collaborative Project n° 314227 WP 4: Sensitivity of marine life to shipping noise Task 4.2.1
- 2015
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Ship induced noise is one of the major contributors to the elevated noise levels in the world’s oceans today. However, the knowledge about the impact on marine organisms is still scarce. Especially the effects on fish behaviour needs to be studied as fish are a fundamental part of the oceans ecosystem. Direct measurement of fish behaviour in the open sea area is technically difficult but needs to be done in order to estimate reaction thresholds and scales of any reaction. This experiment studies the long term behavioural reaction by wild cod (Gadus morhua) to ship noise and describes the character and scale of the reaction. This study took place on the Swedish west coast with a small local cod population and the area is normally without any large vessel traffic. For the ship disturbance, the Swedish Coast Guard ship KBV 032 was hired and passed thru the area nine times during three days. During the three days of ship noise exposure, the noise levels increased well above the ambient noise. The ship signature was what could be expected in terms of spectral level with most radiated noise energy between 100 - 500 Hz. The ship had a higher source level than expected (232 dB re 1μPa at 1 m, 10 - 300 Hz) but this was deliberate as the crew was asked to use the propellers in a non-optimal way to generate as much noise as possible. The result was a lot of broadband cavitation pulses generated by the ship. Then a noise footprint model was created and used in the estimates of received levels (exposure level) by the individual fish in the area based on the most probable location. It was clear in the transmission loss varied between the two sites where at the shallow site, the noise was attenuated more compared to the deep site. This is probably caused by the quite complicated propagation pattern. Also, the acoustically different bottom properties will affect the transmission loss in the area. In total, 39 cod (Gadus morhua) were caught by hand jigging and were fitted with internal acoustical tags. Bottom mounted receivers were deployed covering the area where the cod were known to inhabit. This study was designed to capture more large scale movements of hundreds of meters and not startle responses to the ship noise. Out of the 39 tagged fish, 17 and 18 fish met the set quality criterion for the short time behaviour analysis and 23 fish for long time behaviour to be included in the analysis. Some fish met the quality criteria for both the short and long term analysis. The other fish were either eaten by seals, caught by fishermen, left the area or had a malfunctioning tag. In general, the noticed reaction in terms of horizontal swimming were much smaller than expected and what the study was designed for. This results was surprising as the sound pressure levels the fish were exposed to would, based on the literature, cause a strong behaviour response in the fish. The movement was not in any large scale that would affect their energy consumption and affect their long term survival. This study was able to track fish with an accuracy of less than 10 m and estimates an interval of received noise level. This is one of the first studies of its kind that is tracking free swimming fish over a long period of time during an acoustic disturbance.
|
|
| 5. |
- Ciray, H N, et al.
(författare)
-
Presence and localization of connexins 43 and 26 in cell cultures derived from myometrial tissues from nonpregnant and pregnant women and from leiomyomas
- 2000
-
Ingår i: American Journal of Obstetrics and Gynecology. - 0002-9378 .- 1097-6868. ; 182:4, s. 926-930
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Our objective was to study the appearance and distribution of connexins 43 and 26 in various human myometrial cell cultures.STUDY DESIGN:Scrape loading, Western blotting, and immunohistochemical techniques were applied to cultured cells derived from myometrial tissues obtained from nonpregnant and pregnant women (upper and lower uterine segments) and from leiomyomas (tumor and analogous myometrial tissues).RESULTS:Scrape loading revealed the presence of metabolic coupling in all tissues. Indirect immunohistochemical studies showed membrane localization of connexin 43 in all myometrial cultures. Western blots and indirect immunohistochemical studies showed the presence and localization of the connexin 26 protein and associated gap junctions in tissues from myomas and from nonpregnant and pregnant women except for those derived from the upper segment of the pregnant uterus.CONCLUSION:These results show that human myometrial cultures express various gap junction proteins and that there are regional differences in expression of connexins in tissues from pregnant women.
|
|
| 6. |
- Rosenhall, U, et al.
(författare)
-
Autism and hearing loss
- 1999
-
Ingår i: Journal of autism and developmental disorders. - : Springer Science and Business Media LLC. - 0162-3257. ; 29:5, s. 349-357
-
Tidskriftsartikel (refereegranskat)
|
|
| 7. |
|
|
