Single amino acid substitutions in either YhjD or MsbA confer viability to 3-deoxy-d- manno -oct-2-ulosonic acid-depleted Escherichia coli

The Escherichia coli K-12 strain KPM22, defective in synthesis of 3-deoxy-d- manno -oct-2-ulosonic acid (Kdo), is viable with an outer membrane (OM) composed predominantly of lipid IV A , a precursor of lipopolysaccharide (LPS) biosynthesis that lacks any glycosylation. To sustain viability, the presence of a second-site suppressor was proposed for transport of lipid IV A from the inner membrane (IM), thus relieving toxic side-effects of lipid IV A accumulation and providing sufficient amounts of LPS precursors to support OM biogenesis. We now report the identification of an arginine to cysteine substitution at position 134 of the conserved IM protein YhjD in KPM22 that acts as a compensatory suppressor mutation of the lethal δKdo phenotype. Further, the yhjD400 suppressor allele renders the LPS transporter MsbA dispensable for lipid IV A transmembrane trafficking. The independent derivation of a series of non-conditional KPM22-like mutants from the Kdo-dependent parent strain TCM15 revealed a second class of suppressor mutations localized to MsbA. Proline to serine substitutions at either residue 18 or 50 of MsbA relieved the Kdo growth dependence observed in the isogenic wild-type strain. The possible impact of these suppressor mutations on structure and function are discussed by means of a computationally derived threading model of MsbA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75126/1/MMI_6074_sm_Figure_S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75126/2/j.1365-2958.2007.06074.x.pd

Case report: mechanisms of HIV elite control in two African women

Background The majority of people living with HIV require antiretroviral therapy (ART) for controlling viral replication, however there are rare HIV controllers who spontaneously and durably control HIV in the absence of treatment. Understanding what mediates viral control in these individuals has provided us with insights into the immune mechanisms that may be important to induce for a vaccine or functional cure for HIV. To date, few African elite controllers from high incidence settings have been described. We identified virological controllers from the CAPRISA 002 cohort of HIV-1 subtype C infected women in KwaZulu Natal, South Africa, two (1%) of whom were elite controllers. We examined the genetic, clinical, immunological and virological characteristics of these two elite HIV controllers in detail, to determine whether they exhibit features of putative viral control similar to those described for elite controllers reported in the literature. Case presentation In this case report, we present clinical features, CD4+ T cell and viral load trajectories for two African women over 7 years of HIV infection. Viral load became undetectable 10 months after HIV infection in Elite Controller 1 (EC1), and after 6 weeks in Elite Controller 2 (EC2), and remained undetectable for the duration of follow-up, in the absence of ART. Both elite controllers expressed multiple HLA Class I and II haplotypes previously associated with slower disease progression (HLA-A*74:01, HLA-B*44:03, HLA-B*81:01, HLA-B*57:03, HLA-DRB1*13). Fitness assays revealed that both women were infected with replication competent viruses, and both expressed higher mRNA levels of p21, a host restriction factor associated with viral control. HIV-specific T cell responses were examined using flow cytometry. EC1 mounted high frequency HIV-specific CD8+ T cell responses, including a B*81:01-restricted Gag TL9 response. Unusually, EC2 had evidence of pre-infection HIV-specific CD4+ T cell responses. Conclusion We identified some features typical of elite controllers, including high magnitude HIV-specific responses and beneficial HLA. In addition, we made the atypical finding of pre-infection HIV-specific immunity in one elite controller, that may have contributed to very early viral control. This report highlights the importance of studying HIV controllers in high incidence settings

Neighborhood and Nation in Neoliberal Times: Urban Upheaval, Resistance, and National Identity in Buenos Aires, Argentina

Winner, 2010 Library Research Award for Undergraduates, Senior/Honors Thesis DivisionIn the wake of the devastating Argentine economic crisis of 2001, Buenos Aires has undergone one of the largest real estate booms in the city’s history – a boom that is fundamentally reconfiguring the urban landscape. In the midst of a whirlwind of urban development, several self-identified middle-class neighborhood activist groups have emerged to contest the effects of the boom on the identity of their neighborhoods and city. One of these activist groups, Palermo Despierta, began a campaign in the Palermo district to prevent the construction of residential mega-towers – an icon of urban development since the crisis. This middle-class activism largely contradicts scholarship that categorizes middle-class urban dwellers as agents of “globalization-oriented urban development.” I argue that underlying this resistance is a desire to defend a historically imagined, national narrative of middle-class European identity inscribed in the urban space of Buenos Aires. In a city recovering from economic crisis, porteños (Buenos Aires residents) are contesting the globalizing of their city in order to re-emplace national narratives that remain at the heart of their urban identity. This nascent activism is deeply contradictory and problematic, however, as the narratives animating Palermo Despierta operate on the basis of historic racial and class hierarchies that exclude the racialized urban poor from the right to the city

AT&T's Digital Divide in California

This report looks at the deployment of fiber-to-the-home (FTTH) service in California by AT&T, the largest telecom company in the state. The findings show that the early deployment of the company’s “gigapower” all-fiber service is concentrated in wealthier communities, relegating lower-income neighborhoods to less advanced technologies that offer markedly slower speeds

AT&T's Digital Divide in California

This report looks at the deployment of fiber-to-the-home (FTTH) service in California by AT&T, the largest telecom company in the state. The findings show that the early deployment of the company’s “gigapower” all-fiber service is concentrated in wealthier communities, relegating lower-income neighborhoods to less advanced technologies that offer markedly slower speeds

Estimated Impact of a Proposed Minimum Wage Law for the North Bay

This paper analyzes the prospective impact of that proposal in the four North Bay counties—Marin, Sonoma, Napa and Solano

XANTHOPHYLLS AND CAROTENES OF DIATOMS, BROWN ALGAE, DINOFLAGELLATES, AND SEA-ANEMONES

Volume: 86Start Page: 169End Page: 19

Report of the Commission on United States Relations with Russia

Created as part of the 2009 Jackson School for International Studies SIS 495: Task Force. Robert T. Huber, Task Force Advisor; David Kramer, Evaluator; Michael Jussaume, Coordinator