Person: Alonso, Jose
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Publication Crystal Structure of the Complete Integrin αVβ3 Ectodomain Plus an α/β Transmembrane Fragment
(The Rockefeller University Press, 2009) Mahalingham, Bhuvaneshwari; Borrelli, Laura Ann; Rysiok, Thomas; Müller-Pompalla, Dirk; Goodman, Simon L.; Xiong, Jian-Ping; Alonso, Jose; Rui, Xianliang; Anand, Saurabh; Hyman, Bradley; Arnaout, M.We determined the crystal structure of 1TM-αVβ3, which represents the complete unconstrained ectodomain plus short C-terminal transmembrane stretches of the αV and β3 subunits. 1TM-αVβ3 is more compact and less active in solution when compared with ΔTM-αVβ3, which lacks the short C-terminal stretches. The structure reveals a bent conformation and defines the α–β interface between IE2 (EGF-like 2) and the thigh domains. Modifying this interface by site-directed mutagenesis leads to robust integrin activation. Fluorescent lifetime imaging microscopy of inactive full-length αVβ3 on live cells yields a donor–membrane acceptor distance, which is consistent with the bent conformation and does not change in the activated integrin. These data are the first direct demonstration of conformational coupling of the integrin leg and head domains, identify the IE2–thigh interface as a critical steric barrier in integrin activation, and suggest that inside-out activation in intact cells may involve conformational changes other than the postulated switch to a genu-linear state.
Publication Cross-national prevalence and risk factors for suicidal ideation, plans and attempts
(Royal College of Psychiatrists, 2008) Nock, Matthew; Borges, G.; Bromet, E. J.; Alonso, Jose; Angermeyer, M.; Beautrais, A.; Bruffaerts, R.; Chiu, Wai; de Girolamo, G.; Gluzman, S.; de Graaf, R.; Gureje, O.; Haro, J. M.; Huang, Y.; Karam, E.; Kessler, Ronald; Lepine, J. P.; Levinson, D.; Medina-Mora, M. E.; Ono, Y.; Posada-Villa, J.; Williams, DavidBackground
Suicide is a leading cause of death world-wide; however, the prevalence and risk factors for the immediate precursors to suicide: suicidal ideation, plans and attempts, are not well-known, especially in developing countries.
Aims
To report on the prevalence and risk factors for suicidal behaviors across 17 countries.
Method
84,850 adults were interviewed regarding suicidal behaviors and socio-demographic and psychiatric risk factors.
Results
The cross-national lifetime prevalence (standard error) of suicidal ideation, plans, and attempts is 9.2% (0.1), 3.1% (0.1), and 2.7% (0.1). Across all countries, 60% of transitions from ideation to plan and attempt occur within the first year after ideation onset. Consistent cross-national risk factors included being: female, younger, less educated, unmarried, and having a mental disorder. Interestingly, the strongest diagnostic risk factors were mood disorders in developed countries but impulse-control disorders in developing countries.
Conclusion
Despite cross-national variability in prevalence, there is strong consistency in the characteristics of and risk factors for suicidal behaviors. These findings have significant implications for the prediction and prevention of suicidal behaviors.