UCLA1, a synthetic derivative of a gp120 RNA aptamer, inhibits entry of human immunodeficiency virus type 1 subtype C

Entry of human immunodeficiency virus type 1 (HIV-1) into cells is mediated by the virion surface envelope (Env) glycoproteins, making it a desirable target for antiretroviral entry inhibitors. We previously isolated a family of gp120 binding RNA aptamers and showed that they neutralized the infectivity of HIV-1. In this study, we assessed the activity of a shortened synthetic derivative of the B40 aptamer, called UCLA1, against a large panel of HIV-1 subtype C viruses. UCLA1 tightly bound to a consensus HIV-1 subtype C gp120 and neutralized isolates of the same subtype with 50% inhibitory concentrations (IC(50)s) in the nanomolar range. The aptamer had little toxicity in tests with cell lines and primary cells. Furthermore, it exhibited high therapeutic indices, suggesting that it may be effective at very low doses. Mapping of UCLA1 binding sites on gp120 revealed eight amino acid residues that modulated neutralization resistance. This included residues within the coreceptor binding site, at the base of the V3 loop, and in the bridging sheet within the conserved V1/V2 stem-loop of gp120. The aptamer was also shown to have synergistic effects with T20, a gp41 fusion inhibitor, and IgG1b12 (b12), an anti-CD4 binding site monoclonal antibody. These results suggest that UCLA1 may be suitable for development as a potent HIV-1 entry inhibitor.     

The Power of Contexts: Teaching and Learning in Recently Desegregated Schools

The following critical ethnography interrogates what it means for urban students to learn in multicultural ways, given the oppressive historical and present contexts of their newly desegregated urban district. By retelling events that occurred in the district and the classroom, I present a picture of urban students who are willing to learn and engage in classroom activities when the activities do not threaten their emotional safety. Although their actions are understandable, the students' conscious decisions to disengage from school stifles learning opportunities that would allow them to empathize and connect with other students as a move toward individual and group empowerment. Using critical race theory, I problematize the possibilities for successful multicultural classrooms in urban districts with complex legacies of injustice and racial hostility.     

The perils of integration: exploring the experiences of African American and black Caribbean students in predominately white secondary schools

Racial minority students who attend predominately white schools in the United States and England face unique challenges in their learning environments that are connected to their status as non-white students. Scholars have documented the experiences of racial and ethnic minority students in mixed-raced schools in the United States and the UK for over four decades. However, the authors explore new research territory by employing critical race analysis to further articulate the similar experiences shared by African American and black Caribbean students’ in mixed-race schools. Using data two different studies, one in the United States and one in England, the authors highlight the resemblances between the experiences of African American and black Caribbean students in predominantly white suburban and rural secondary schools. To increase racial equity in education, we must accurately understand the structural and societal barriers that racial minority students face as they continue to access education resources and quality schools.     

The Effect of a Maturing Antiretroviral Program on Early Mortality for Patients with Advanced Immune-Suppression in Soweto,South Africa

Objective

We hypothesize that time to initiate care and maturity of a treatment program impact on outcome of severely immuno-compromised patients with higher risk of mortality.

Design

We conducted a retrospective cohort analysis at the Perinatal HIV Research Unit Adult ART clinic, Soweto, South Africa.

Methods

Eligibility criteria for this analysis were: attendance for minimum one visit between August 2004 and August 2010, age >18 years, CD4 count < 50 cells/mm³ and ART-naïve at screening. We followed participants up to one year after ART initiation. We defined years 2004-2007 and 2008-2010 as the early and late eras respectively. Chi-square test and survival analysis methods were used for mortality comparisons between eras.

Results

Of 2357 patients eligible for antiretroviral treatment, 395 (17%) had CD4 counts < 50 cells/mm³ and ART-naïve at screening. Overall 261 (66%) were women. Patients had similar median age (35 vs. 33.5 years, p=0.08), time to HAART initiation (7 days, p=0.18) and baseline CD4 count (20 vs. 23 cells/mm³, p=0.5) between eras. Overall 63 (16%) patients died in their first year of treatment (2 per 100 person-months) and the main cause of death was tuberculosis (n=23, 37%). The proportion of deaths (52/262 vs. 11/133, p=0.003) and time to death from enrolment (logrank p=0.04) were significantly different between eras.

Conclusion

Mortality decreased as the ART program matured in Soweto while time to initiation of treatment remained similar in both eras. Because ART guidelines were consistent during both eras, it is possible that with time, management of patients improved as expertise was gained.     

Expression,Purification, and Biophysical Characterization of Klebsiella Pneumoniae Nicotinate Nucleotide Adenylyltransferase

The Protein Journal - Patients in health-care settings develop nosocomial infections due to prolonged hospital stay. The Gram negative Klebsiella pneumoniae (K. pneumoniae), is a bacterial pathogen...