Highlights
Four-way pooling correctly identified SARS-CoV-2 in 94 % of positive samples (n = 30/32) tested.
Low viral loads, corresponding with late C
T
s, may be missed by the pooling process.
1:4 pooling is associated with expected 2 C
T
loss in analytical sensitivity.
All individually negative samples (n = 128) were also negative by 4-way pooling.
Key Points
Virus-specific IgG levels were stable for up to 1 year after CD19-CARTx in adults with durable complete remission. Preexisting humoral immunity may be preserved in adult recipients of CD19-CARTx.
Hepatitis B virus (HBV) is a pathogen of major public health importance that is largely incurable once a chronic hepatitis B (CHB) infection is established. Only humans and great apes are fully permissive to HBV replication, and this species restriction has impacted HBV research by limiting the utility of small animal models of HBV. To combat the species restriction of HBV and enable more HBV studies in vivo, liver-humanized mouse models have been developed that harbor primary human hepatocytes (PHH) and are fully permissive to HBV infection and replication. Unfortunately, these models can be difficult to establish and are expensive commercially, which has limited their academic use. As an alternative mouse model to study HBV, we evaluated liver-humanized NSG-PiZ mice and showed that they are fully permissive to HBV and can develop CHB. Mice were infected with a precore mutant clinical isolate that has now been serially passaged through 3 generations of mice without loss of fitness. HBV selectively replicates in hCK18+ human hepatocytes within chimeric livers, and HBV+ mice secrete infectious virions and HBsAg into blood, while also harboring covalently closed circular DNA (cccDNA). HBV+ mice remain viremic for at least 169 days, which should enable the study of new curative therapies targeting CHB and respond to antiviral entecavir therapy. The extended duration of viremia is sufficient to enable the study of established and new therapeutic approaches targeting CHB. Furthermore, HBV+ PHH in NSG-PiZ mice can be transduced by the hepatotropic AAV3b and AAV.LK03 vector capsids, which should enable the study of curative gene therapies that target CHB. In summary, our data demonstrates that liver humanized NSG-PiZ mice can be used as a robust and cost-effective alternative to existing CHB models and may enable more academic research labs to study HBV disease pathogenesis and antiviral therapy in a setting that is fully permissive to ongoing replication.
Printing expenses in college computing labs have been escalating along with the use of technology in instruction. Commercially available print management software requires a huge initial financial investment with uncertain cost recovery. The outcome usually involves shifting most of the print management software expense to students. Find out how the University of WisconsinWhitewater controls their printing costs using open source technology without adding a financial burden to students.
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