Synergistic recruitment of UbcH7~Ub and phosphorylated Ubl domain triggers parkin activation

The E3 ligase parkin ubiquitinates outer mitochondrial membrane proteins during oxidative stress and is linked to early-onset Parkinson’s disease. Parkin is autoinhibited but is activated by the kinase PINK1 that phosphorylates ubiquitin leading to parkin recruitment, and stimulates phosphorylation of parkin’s N-terminal ubiquitin-like (pUbl) domain. How these events alter the structure of parkin to allow recruitment of an E2~Ub conjugate and enhanced ubiquitination is an unresolved question. We present a model of an E2~Ub conjugate bound to the phosphoubiquitin-loaded C-terminus of parkin, derived from NMR chemical shift perturbation experiments. We show the UbcH7~Ub conjugate binds in the open state whereby conjugated ubiquitin binds to the RING1/IBR interface. Further, NMR and mass spectrometry experiments indicate the RING0/RING2 interface is re-modelled, remote from the E2 binding site, and this alters the reactivity of the RING2(Rcat) catalytic cysteine, needed for ubiquitin transfer. Our experiments provide evidence that parkin phosphorylation and E2~Ub recruitment act synergistically to enhance a weak interaction of the pUbl domain with the RING0 domain and rearrange the location of the RING2(Rcat) domain to drive parkin activity

Development of light weight magnesium alloys for low temperature applications Annual progress report, Jun. 19, 1965 - Mar. 20, 1966

Lightweight magnesium alloys for cryogenic application

Development of Light Weight Magnesium Alloys for Low Temperature Applications Annual Progress Report, 19 Jun. 1964 - 18 Jun. 1965

Lightweight, wrought magnesium alloys for high strength and ductility and low notch sensitivity applications at cryogenic temperature

Including the public in pandemic planning: a deliberative approach

Background: Against a background of pandemic threat posed by SARS and avian H5N1 influenza, this study used deliberative forums to elucidate informed community perspectives on aspects of pandemic planning. Methods: Two deliberative forums were carried out with members of the South Australian community. The forums were supported by a qualitative study with adults and youths, systematic reviews of the literature and the involvement of an extended group of academic experts and policy makers. The forum discussions were recorded with simultaneous transcription and analysed thematically. Results: Participants allocated scarce resources of antiviral drugs and pandemic vaccine based on a desire to preserve society function in a time of crisis. Participants were divided on the acceptability of social distancing and quarantine measures. However, should such measures be adopted, they thought that reasonable financial, household and psychological support was essential. In addition, provided such support was present, the participants, in general, were willing to impose strict sanctions on those who violated quarantine and social distancing measures. Conclusions: The recommendations from the forums suggest that the implementation of pandemic plans in a severe pandemic will be challenging, but not impossible. Implementation may be more successful if the public is engaged in pandemic planning before a pandemic, effective communication of key points is practiced before and during a pandemic and if judicious use is made of supportive measures to assist those in quarantine or affected by social isolation measures.Annette J Braunack-Mayer, Jackie M Street, Wendy A Rogers, Rodney Givney, John R Moss, Janet E Hiller, Flu Views tea

Mode of socio-economic development and occupational structure: the case of contemporary Russia

The given paper assumes the existence of a correlation between the occupational structure and the mode of social and economic development of a country. It is shown that the modern stage of development in advanced economies could be described by the post-industrial phase with (a) the specific proportions in the occupational structure (predominance of professional managers and technical experts); (b) particular nature of work and the corresponding extent of labor division according to specialization and qualification (highly skilled labor with broad specialization and a new criterion of creativity included within qualifications). Within the certain historical framework these indicators, combined onto the entire scheme, produce the criteria to distinct different types of socio-economic development and arrange them in consistent order. The analysis of occupational structure of Russian population shows that the reforms of 1990s have facilitated the process of deindustrialization alongside with the growth of semi- and low-skilled jobs. According to the scheme, Russia seems to have reached the stage of the development that is similar to one of the 1950–1960s in the USA and the Europe