| 1551. |
- Wu, S.R., et al.
(författare)
-
Turning of the receptor binding domains opens up the murine leukaemia virus Env for membrane fusion
- 2008
-
Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 27:20, s. 2799-2808
-
Tidskriftsartikel (refereegranskat)abstract
- The activity of the membrane fusion protein Env of Moloney mouse leukaemia virus is controlled by isomerization of the disulphide that couples its transmembrane (TM) and surface (SU) subunits. We have arrested Env activation at a stage prior to isomerization by alkylating the active thiol in SU and compared the structure of isomerization-arrested Env with that of native Env. Env trimers of respective form were isolated from solubilized particles by sedimentation and their structures were reconstructed from electron microscopic images of both vitrified and negatively stained samples. We found that the protomeric unit of both trimers formed three protrusions, a top, middle and a lower one. The atomic structure of the receptor-binding domain of SU fitted into the upper protrusion. This was formed similar to a bent finger. Significantly, in native Env the tips of the fingers were directed against each other enclosing a cavity below, whereas they had turned outward in isomerization-arrested Env transforming the cavity into an open well. This might subsequently guide the fusion peptides in extended TM subunits into the target membrane.
|
|
| 1552. |
- Wu, X. P., et al.
(författare)
-
Alternative Cytotoxic Effects of the Postulated IGF-IR Inhibitor Picropodophyllin In Vitro
- 2013
-
Ingår i: Molecular Cancer Therapeutics. - : American Association for Cancer Research (AACR). - 1535-7163 .- 1538-8514. ; 12:8, s. 1526-1536
-
Tidskriftsartikel (refereegranskat)abstract
- The insulin-like growth factor-1 (IGF-I) and its receptors play an important role in transformation and progression of several malignancies. Inhibitors of this pathway have been developed and evaluated but generally performed poorly in clinical trials, and several drug candidates have been abandoned. The cyclolignan picropodophyllin (PPP) has been described as a potent and selective IGF-IR inhibitor and is currently undergoing clinical trials. We investigated PPP's activity in panels of human cancer cell lines (e. g., esophageal squamous carcinoma cell lines) but found no effects on the phosphorylation or expression of IGF-IR. Nor was the cytotoxic activity of PPP related to the presence or spontaneous phosphorylation of IGF-IR. However, its activity correlated with that of known tubulin inhibitors, and it destabilized microtubule assembly at cytotoxic concentrations also achievable in patients. PPP is a stereoisomer of podophyllotoxin (PPT), a potent tubulin inhibitor, and an equilibrium between the two has previously been described. PPPcould thus potentially act as a reservoir for the continuous generation of low doses of PPT. Interestingly, PPP also inhibited downstream signaling from tyrosine kinase receptors, including the serine/threonine kinase Akt. This effect is associated with microtubule-related downregulation of the EGF receptor, rather than the IGF-IR. These results suggest that the cytotoxicity and pAkt inhibition observed following treatment with the cyclolignan PPP in vitro result from microtubule inhibition (directly or indirectly by spontaneous PPT formation), rather than any effect on IGF-IR. It is also suggested that PPT should be used as a reference compound in all future studies on PPP. (C)2013 AACR.
|
|
| 1553. |
|
|
| 1554. |
- Wurst, FM, et al.
(författare)
-
World Health Organization/International Society for Biomedical Research on Alcoholism study on state and trait markers of alcohol use and dependence: Back to the future
- 2005
-
Ingår i: Alcoholism: Clinical and Experimental Research. - 0145-6008. ; 29:7, s. 1268-1275
-
Tidskriftsartikel (refereegranskat)abstract
- This article summarizes content proceedings of a symposium held at the 2004 International Society for Biomedical Research on Alcoholism Congress in Mannheim, Germany. The chairs were Boris Tabakoff and Friedrich M. Wurst. The presentations were (1) Genetic associations with alcoholism and affective disorders, by Paula Hoffman; (2) Proteomic analysis of blood constituents in alcoholism, by Boris Tabakoff; (3) Contrasts between the responses of GGT and CDT to high alcohol intake, and a test of their combined use, by John Whitfield; (4) Direct ethanol metabolites such as ethyl glucuronide, fatty acid ethyl esters, phosphatidylethanol and ethyl sulfate: a new line of sensitive and specific biomarkers, by Friedrich Martin Wurst; and (5) Genetic studies of alcoholism subtypes in a Han Taiwanese population, by Ru-Band Lu.
|
|
| 1555. |
- Yang, Jun, 1979, et al.
(författare)
-
A compact core-jet structure in the changing-look Seyfert NGC 2617
- 2021
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 503:3, s. 3886-3895
-
Tidskriftsartikel (refereegranskat)abstract
- The nearby face-on spiral galaxy NGC 2617 underwent an unambiguous 'inside-out' multiwavelength outburst in Spring 2013, and a dramatic Seyfert-type change probably between 2010 and 2012, with the emergence of broad optical emission lines. To search for the jet activity associated with this variable accretion activity, we carried out multiresolution and multiwavelength radio observations. Using the very long baseline interferometric (VLBI) observations with the European VLBI Network at 1.7 and 5.0 GHz, we find that NGC 2617 shows a partially synchrotron self-absorbed compact radio core with a significant core shift, and an optically thin steep-spectrum jet extending towards the north up to about 2 pc in projection. We also observed NGC 2617 with the electronic Multi-Element Remotely Linked Interferometer Network at 1.5 and 5.5 GHz, and revisited the archival data of the Very Large Array (VLA) and the Very Long Baseline Array (VLBA). The radio core had a stable flux density of similar to 1.4 mJy at 5.0 GHz between 2013 June and 2014 January, in agreement with the expectation of a supermassive black hole in the low accretion rate state. The northern jet component is unlikely to be associated with the 'inside-out' outburst of 2013. Moreover, we report that most optically selected changing-look active galactic nuclei (AGN) at z < 0.83 are sub-mJy radio sources in the existing VLA surveys at 1.4 GHz, and it is unlikely that they are more active than normal AGN at radio frequencies.
|
|
| 1556. |
|
|
| 1557. |
- Yeap, Bu B, et al.
(författare)
-
Serum testosterone is inversely, and sex hormone-binding globulin directly, associated with all-cause mortality in men.
- 2021
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 106:2
-
Tidskriftsartikel (refereegranskat)abstract
- Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase.To analyse associations of baseline serum testosterone and SHBG concentrations, and calculated free testosterone (cFT) values, with all-cause and cause-specific mortality in men.The UK Biobank prospective cohort study of community-dwelling men 40-69 years-old, followed for 11 years.All-cause, atherosclerotic cardiovascular disease (CVD) and cancer-related mortality. Cox proportional hazards regression was performed, adjusting for age, waist circumference, medical conditions and other covariates. Models for testosterone included SHBG, and vice versa.In complete case analysis of 149,436 men with 10,053 deaths (1,925 CVD and 4,927 cancer-related), men with lower testosterone had higher mortality from any cause (lowest vs highest quintile, Q1 vs Q5, fully-adjusted hazard ratio [HR]=1.14, 95% confidence interval [CI]=1.06-1.22, overall trend P<0.001), and cancer (HR=1.20, CI=1.09-1.33, P<0.001), with no association for CVD deaths. Similar results were seen for cFT. Men with lower SHBG had lower mortality from any cause (Q1 vs Q5, HR=0.68, CI=0.63-0.73, P<0.001), CVD (HR=0.70, CI=0.59-0.83, P<0.001), and cancer (HR=0.80, CI=0.72-0.89, P<0.001). A multiply-imputed dataset (N=208,425, 15,914 deaths, 3,128 CVD and 7,468 cancer-related) and analysis excluding deaths within first two years (9,261, 1,734 and 4,534 events) yielded similar results.Lower serum testosterone is independently associated with higher all-cause and cancer-related, but not CVD-related, mortality in middle-aged to older men. Lower SHBG is independently associated with lower all-cause, CVD-related and cancer-related mortality. Confirmation and determination of causality requires mechanistic studies and prospective trials.
|
|
| 1558. |
- Yeung, L W Y, 1981-, et al.
(författare)
-
Perfluorooctanesulfonate and related fluorochemicals in human blood samples from China
- 2006
-
Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 40:3, s. 715-720
-
Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctanesulfonylfluoride (POSF)-based compounds have been manufactured and used in a variety of industrial applications. These compounds degrade to perfluorooctanesulfonate (PFOS) which is regarded as a persistent end-stage metabolite and is found to accumulate in tissues of humans and wildlife. PFOS, perfluorohexanesulfonate (PFHxS), perfluorooctanoate (PFOA), and perfluorooctanesulfonamide (PFOSA) have been found in human sera from the United States. In this study, concentrations of PFHxS, perfluorobutanesulfonate (PFBS), PFOS, perfluorohexanoic acid (PFHxA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and PFOSA were measured in 85 samples of whole human blood collected from nine cities (eight provinces) in China, including Shenyang (Liaoning), Beijing (Hebei), Zhengzhou (Henan), Jintan (Jiangsu), Wuhan (Hubei), Zhoushan (Zhejiang), Guiyang (Guizhou), Xiamen (Fujian), and Fuzhou (Fujian). Among the 10 perfluorinated compounds (PFCs) measured, PFOS was the predominant compound. The mean concentration of PFOS was greatest in samples collected from Shenyang (79.2 ng/mL) and least in samples from Jintan (3.72 ng/mL). PFHxS was the next most abundant perfluorochemical in the samples. No age-related differences in the concentrations of PFOA, PFOS, PFOSA, and PFHxS were observed. Gender-related differences were found, with males higher for PFOS and PFHxS, and females higher in PFUnOA. Concentrations of PFHxS were positively correlated with those of PFOS, while concentrations of PFNA, PFOA, and PFUnOA were positively correlated with those of PFOA. There were differences in the concentration profiles (percentage composition) of various PFCs in the samples among the nine cities.
|
|
| 1559. |
|
|
| 1560. |
|
|
