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- Golding, H, et al.
(författare)
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CCR5 N-terminal region plays a critical role in HIV-1 inhibition by Toxoplasma gondii-derived cyclophilin-18
- 2005
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 280:33, s. 29570-29577
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mimicry of chemokine ligands has been described for several pathogens. Toxoplasma gondii produces a protein, cyclophilin-18 (C-18), which binds to the human immunodeficiency virus (HIV) co-receptor CCR5 and inhibits fusion and infection of T cells and macrophages by R5 viruses but not by X4 viruses. We recently identified structural determinants of C-18 required for anti-HIV activity (Yarovinsky, F., Andersen, J. F., King, L. R., Caspar, P., Aliberti, J., Golding, H., and Sher, A. ( 2004) J. Biol. Chem. 279, 53635 - 53642). Here we have elucidated the fine specificity of CCR5 residues involved in binding and HIV inhibitory potential of C-18. To delineate the regions of CCR5 involved in C-18 binding, we analyzed C-18 inhibition of cells expressing CXCR4/CCR5 chimeric receptors and CCR5 with a truncated N terminus (Delta 2-19). These experiments identified a critical role for the N terminus of CCR5 in C-18 binding and anti-HIV activity. Studies with a large panel of CCR5 N-terminal peptides, including Tyr-sulfated analogues, truncated peptides, and alanine-scanning mutants, suggested that each of the 12 - 17 amino acids in the N terminus of CCR5 are essential for C-18 binding and inhibitory activity. Tyr sulfation did not improve C-18 reactivity. This finding is of interest because the same CCR5 N-terminal region was shown previously to play a key role in binding of HIV-1 envelope glycoproteins. The elucidation of the functional C-18-binding mechanism may help in the rational design of novel antiviral agents against HIV.
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- Kabat, G. C., et al.
(författare)
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Metabolic phenotypes of obesity : frequency, correlates and change over time in a cohort of postmenopausal women
- 2017
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 41:1, s. 170-177
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The possibility that a subset of persons who are obese may be metabolically healthy—referred to as the ‘metabolically healthy obese’ (MHO) phenotype—has attracted attention recently. However, few studies have followed individuals with MHO or other obesity phenotypes over time to assess change in their metabolic profiles. The aim of the present study was to examine transitions over a 6-year period among different states defined simultaneously by body mass index (BMI) and the presence/absence of the metabolic syndrome (MetS).Methods: We used repeated measurements available for a subcohort of participants enrolled in the Women’s Health Initiative (N=3512) and followed for an average of 6 years to examine the frequency of different metabolic obesity phenotypes at baseline, the 6-year transition probabilities to other states and predictors of the risk of different transitions. Six phenotypes were defined by cross-tabulating BMI (18.5–<25.0, 25.0–<30.0, 30.0 kg m−2) by MetS (yes, no). A continuous-time Markov model was used to estimate 6-year transition probabilities from one state to another.Results: Over the 6 years of follow-up, one-third of women with the healthy obese phenotype transitioned to the metabolically unhealthy obese (MUO) phenotype. Overall, there was a marked tendency toward increased metabolic deterioration with increasing BMI and toward metabolic improvement with lower BMI. Among MHO women, the 6-year probability of becoming MUO was 34%, whereas among unhealthy normal-weight women, the probability of ‘regressing’ to the metabolically healthy normal-weight phenotype was 52%.Conclusions: The present study demonstrated substantial change in metabolic obesity phenotypes over a 6-year period. There was a marked tendency toward metabolic deterioration with greater BMI and toward metabolic improvement with lower BMI.
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- Suni, T., et al.
(författare)
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The significance of land-atmosphere interactions in the Earth system-iLEAPS achievements and perspectives
- 2015
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Ingår i: Anthropocene. - : Elsevier BV. - 2213-3054. ; 12, s. 69-84
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Tidskriftsartikel (refereegranskat)abstract
- The integrated land ecosystem-atmosphere processes study (iLEAPS) is an international research project focussing on the fundamental processes that link land-atmosphere exchange, climate, the water cycle, and tropospheric chemistry. The project, iLEAPS, was established 2004 within the International Geosphere-Biosphere Programme (IGBP). During its first decade, iLEAPS has proven to be a vital project, well equipped to build a community to address the challenges involved in understanding the complex Earth system: multidisciplinary, integrative approaches for both observations and modeling. The iLEAPS community has made major advances in process understanding, land-surface modeling, and observation techniques and networks. The modes of iLEAPS operation include elucidating specific iLEAPS scientific questions through networks of process studies, field campaigns, modeling, long-term integrated field studies, international interdisciplinary mega-campaigns, synthesis studies, databases, as well as conferences on specific scientific questions and synthesis meetings. Another essential component of iLEAPS is knowledge transfer and it also encourages community-and policy-related outreach activities associated with the regional integrative projects. As a result of its first decade of work, iLEAPS is now setting the agenda for its next phase (2014-2024) under the new international initiative, future Earth. Human influence has always been an important part of land-atmosphere science but in order to respond to the new challenges of global sustainability, closer ties with social science and economics groups will be necessary to produce realistic estimates of land use and anthropogenic emissions by analysing future population increase, migration patterns, food production allocation, land management practices, energy production, industrial development, and urbanization.
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