Human Immunology Core

Small cell lung cancer (SCLC) has a 6% 5-year overall survival rate. C-X-C chemokine receptor 4 (CXCR4) is an attractive target for theranostic agents, is highly expressed in SCLCs, and can be targeted with pentixather using the theranostic pair 212Pb/203Pb. The hypothesis that 212Pb/203Pb-pentixather can be used safely and effectively for imaging and therapy in SCLC in xenograft models was tested. SPECT-CT imaging and biodistribution studies of tumor-bearing mice injected with 203Pb-pentixather...

The lifestyle of Vibrio cholerae is primarily environmental, yet a chance encounter with a human host can lead to cholera, a potentially lethal form of diarrhea. Strains belonging to O1 and O139 serogroups have pandemic potential, but the contribution of non-O1/non-O139 serovars towards the genesis of cholera remains unclear. Endemic V. cholerae lineages were investigated given several historical accounts describing cholera epidemics and sporadic, contemporary cholera-like outbreaks along the...

Therapeutic gene editing strategies utilize endogenous DNA repair pathways-nonhomologous end joining (NHEJ) or homology-directed repair (HDR)-to introduce targeted genomic modifications. Because HDR is restricted to dividing cells, whereas NHEJ functions in both dividing and non-dividing cells, NHEJ-based approaches are better suited for in vivo gene editing in the largely post-mitotic airway epithelium. Homology-independent targeted insertion (HITI), an NHEJ-based method, offers a promising...

CONCLUSIONS: Among individuals who underwent VZV testing in CSF, VZV reactivation was present in 1 of 5 patients with AIS/transient ischemic attack. Patients with HIV were at particularly high risk of VZV reactivation and recurrent ischemic stroke.

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Pyrethroid insecticides represent a broad class of chemicals used widely in agriculture and household applications. Human studies show mixed effects of maternal pyrethroid exposure on fetal growth and neurodevelopment. Assessment of shared pyrethroid metabolites as a biomarker for exposure obscures effects of specific chemicals within this broader class. To better characterize pyrethroid effects on fetal development, we investigated maternal exposure to permethrin, a type I pyrethroid, and...

Human anatomy is a foundational course in graduate health professional programs. Given the increased enrollment in anatomy courses, along with the development of new technologies, institutions are increasingly compelled to provide alternative course formats, including online learning. Similarly, higher education is increasingly transitioning from traditional lecture-based learning to methods that allow students to actively participate in their own learning process (i.e., active learning). Active...

Stem cells are known to provide signals that contribute to the maintenance and function of neighboring cells. We demonstrate that Notch signaling arising from airway basal stem cells is necessary for the function of a unique population of intraepithelial airway macrophages (IAMs) in the murine trachea. Without this stem cell signaling, IAMs lose MHC II expression, which in turn prevents antigen-induced allergic inflammation. Distal murine airways do not harbor basal stem cells, and, in this...

Recent studies have highlighted the presence of memory T cells in human brains, some of which are specific for peripheral infections. To address their potential origins, we used two models of polymicrobial exposure to 'normalize' the immune systems of specific pathogen-free mice and queried the impact on brain T cell biology. Here, we show that cohousing and sequential infection induce marked enhancement of memory T cells in the brain tissue of mice. These resident and circulating memory T cells...

Hemagglutinin (HA) plays a critical role in the entry of influenza and thus HA is a target for the development of entry inhibitors as antivirals. One of the first small molecule inhibitors of influenza entry to be described was tert-butylhydroquinone (TBHQ), a commonly used antioxidant. This compound was shown to inhibit influenza containing Group 2 HA, such as H3 and H7 HA circulating in humans and avians. One limitation of TBHQ is the propensity to oxidize in solution, resulting in a less...