Exploring Race: The Collaborative Inquiry Experience of a Group of Black Social Work Faculty

Through a partnership presentation, presenters discussed the co-inquiry group process through which they explored their experiences as Black faculty who teach race based content in social work programs. They shared insights into what it means, what it takes, and what it costs to teach such content, and the benefits of the group process

Mycobacterium tuberculosis reactivates latent HIV-1 in T cells in vitro

Following proviral integration into the host cell genome and establishment of a latent state, the human immunodeficiency virus type 1 (HIV-1) can reenter a productive life cycle in response to various stimuli. HIV-1 reactivation occurs when transcription factors, such as nuclear factor-κB (NF-κB), nuclear factor of activated T cells (NFAT), and activator protein -1 (AP-1), bind cognate sites within the long terminal repeat (LTR) region of the HIV-1 provirus to promote transcription. Interestingly, pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) can reactivate latent HIV-1 through activation of the transcription factor NF-κB. Some PRRs are expressed on central memory CD4+ T cells (TCM), which in HIV-1 patients constitute the main reservoir of latent HIV-1. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), interacts with PRRs through membrane components. However, the ability of Mtb to reactivate latent HIV-1 has not been extensively studied. Here we show that phosphatidylinositol mannoside 6 (PIM6), a component of the Mtb membrane, in addition to whole bacteria in co-culture, can reactivate HIV-1 in a primary TCM cell model of latency. Using a JLAT model of HIV-1 latency, we found this interaction to be mediated through Toll-like receptor-2 (TLR-2). Thus, we describe a mechanism by which Mtb can exacerbate HIV-1 infection. We hypothesize that chronic Mtb infection can drive HIV-1 reactivation. The phenomenon described here could explain, in part, the poor prognosis that characterizes HIV-1/Mtb co-infection

“Nothing is impossible”: characteristics of Hispanic females participating in an informal STEM setting

Factors that influence the underrepresentation of females in STEM careers begin early in childhood when gender biases and stereotypes emerge. Stereotypes have a psychosocial effect on females that can lead to low self-efficacy and less interest in learning and pursuing STEM careers. This study investigated the effect of a STEM summer camp on K-12 students learning in which upper elementary students explored STEM concepts through magnetic levitation (MagLev) train activities, middle school students built and programmed robots, and high school students explored STEM through both MagLev train and robotics activities. A mixed methods design was used to analyze pre/posttest scores of all students and interviews of randomly selected Hispanic female students. Data indicated that Hispanic, high school females were less likely to participate in the STEM summer camp as compared to their elementary or middle school counterparts. In addition, there were no gender differences in academic achievement at the elementary level, but Hispanic females reported significantly higher learning gains than Hispanic males. In high school, Hispanic females reported significantly lower pretest scores than males. We conclude that there is a change in the characteristics, attitudes, and academic achievement of Hispanic females from elementary to high school, but informal STEM opportunities can mitigate this change

Reactivation of HIV by H37Ra, PIM6, and H37Rv lysate in a primary T_CM model of latency.

<p>Cultured T_CM cells following 72-hour incubation with test conditions or co-stimulation with αCD3/αCD28. (A) Levels of intracellular p24 Gag were measured by flow cytometry. The horizontal line within the box represents the median, the boundaries of the box represent the 25^th- and 75^th-percentile, and the whiskers represent the maximum and minimum values. Significance for intracellular p24 Gag was determined using a 2-tailed, paired Student’s t-test versus PBS (*p<0.05). (B) Relative luminescence was measured from supernatant of cultured T_CM cells following 72-hour incubation with conditions or co-stimulation with αCD3/αCD28. The horizontal line within the box represents the median, the boundaries of the box represent the 25^th- and 75^th-percentile, and the whiskers represent the maximum and minimum values. Significance was determined using a 2-tailed, paired Student’s t-test versus PBS (*p<0.05). Significance of individual test conditions are as follows: αCD3/αCD28 (p≤0.01), PIM6 (p<0.05), H37Ra (p≤0.01), and <i>M</i>. <i>smegmatis</i> (p≤0.01).</p

PIM6 and H37Rv lysate induce GFP expression through TLR-2.

<p>A) JLAT cells were incubated for 16 hours and GFP expression was measured by flow cytometry. Data represent mean ± SD of four independent experiments run in triplicate. *p<0.05 compared to PBS control. B) JLAT-TLR2 cells were incubated for 16 hours and GFP expression was measured by flow cytometry. Data represent mean ± SD of ten independent experiments run in triplicate. *p<0.05 compared to PBS control. <b>C</b>) JLAT-TLR2 cells were pre-incubated with the TLR-2 neutralizing antibody, PAb-hTLR2, for 30 minutes prior to addition of test conditions. Cells were subsequently incubated for 16 hours and GFP expression was measured by flow cytometry. Data represent mean ± SD. *p<0.05 test condition in the absence of TLR-2 neutralizing antibody compared to test condition in the presence of TLR-2 neutralizing antibody. D) JLAT-TLR2 cells pre-incubated with BAY 11–7082 for 30 minutes prior to addition of conditions. Cells were subsequently incubated for 16 hours and GFP expression was measured by flow cytometry. Data represent mean ± SD. *p<0.05 test condition in the absence of BAY 11–7082 compared to test condition in the presence of BAY 11–7082.</p

The latency reversing agent HODHBt synergizes with IL-15 to enhance cytotoxic function of HIV-specific CD8+ T-cells

IL-15 is under clinical investigation towards the goal of curing HIV infection, due to its abilities to reverse HIV latency and enhance immune effector function. However, increased potency through combination with other agents may be needed. 3-hydroxy-1,2,3-benzotriazin-4(3H)-one (HODHBt) enhances IL-15-mediated latency reversal and NK function, by increasing STAT5 activation. We hypothesized that HODHBt would also synergize with IL-15, via STAT5, to directly enhance HIV-specific cytotoxic T-cell responses. We show that ex vivo IL-15+HODHBt treatment markedly enhances HIV-specific granzyme B-releasing T-cell responses in PBMCs from ARV-suppressed donors. We also observed upregulation of antigen processing and presentation in CD4+ T-cells, and increased surface MHC-I. In ex vivo PBMCs, IL-15+HODHBt was sufficient to reduce intact proviruses in 1 of 3 ARV-suppressed donors. Our findings reveal the potential for 2nd-generation IL-15 studies incorporating HODHBt-like therapeutics. Iterative studies layering on additional latency reversal or other agents are needed to achieve consistent ex vivo reservoir reductions

Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges