Human APOBEC3F is an anti-retroviral single strand DNA cytosine deaminase, susceptible to degradation by the HIV-1 protein Vif. In this study the crystal structure of the HIV Vif binding, catalytically active, C-terminal domain of APOBEC3F (A3F-CTD) was determined. The A3F-CTD shares structural motifs with portions of APOBEC3G-CTD, APOBEC3C and APOBEC2. Residues identified to be critical for Vif-dependent degradation of APOBEC3F all fit within a predominantly negatively charged contiguous region on the surface of A3F-CTD. Specific sequence motifs, previously shown to play a role in Vif susceptibility and virion encapsidation, are conserved across APOBEC3’s and between APOBEC3’s and HIV-1 Vif. In this structure these motifs pack against each other at intermolecular interfaces, providing potential insights both into APOBEC3 oligomerization and Vif interactions.
BackgroundMobile health technologies have been found to improve the self-management of chronic diseases. However, there is limited research regarding their feasibility in supporting recovery from substance use disorders (SUDs) in China.ObjectiveThe objective of this study was to examine the feasibility of a mobile phone-based ecological momentary assessment (EMA) app by testing the concordance of drug use assessed by the EMA, urine testing, and a life experience timeline (LET) assessment.MethodsA total of 75 participants dependent on heroin or amphetamine-type stimulant (ATS) in Shanghai were recruited to participate in a 4-week pilot study. Of the participants, 50 (67% [50/75]) were randomly assigned to the experimental group and 25 (33% [25/75]) were assigned to the control group. The experimental group used mobile health (mHealth) based EMA technology to assess their daily drug use in natural environments and received 2 short health messages each day, whereas the control group only received 2 short health messages each day from the app. Urine tests and LET assessments were conducted each week and a post-intervention survey was administered to both groups. The correlations among the EMA, the LET assessment, and the urine test were investigated.ResultsThe mean age of the participants was 41.6 (SD 8.0) years, and 71% (53/75) were male. During the 4 weeks of observation, 690 daily EMA survey data were recorded, with a response rate of 49.29% (690/1400). With respect to drug use, the percent of agreement between the EMA and the LET was 66.7%, 79.2%, 72.4%, and 85.8%, respectively, for each of the 4 weeks, whereas the percent of agreement between the EMA and the urine test was 51.2%, 65.1%, 61.9%, and 71.5%, respectively. The post-intervention survey indicated that 46% (32/70) of the participants preferred face-to-face interviews rather than the mHealth app.ConclusionsThis study demonstrated poor agreement between the EMA data and the LET and found that the acceptance of mHealth among individuals with SUDs in China was not positive. Hence, greater efforts are needed to improve the feasibility of mHealth in China.
Background: Inactivating genes in vivo is an important technique for establishing their function in the adult nervous system. Unfortunately, conventional knockout mice may suffer from several limitations including embryonic or perinatal lethality and the compensatory regulation of other genes. One approach to producing conditional activation or inactivation of genes involves the use of Cre recombinase to remove loxP-flanked segments of DNA. We have studied the effects of delivering Cre to the hippocampus and neocortex of adult mice by injecting replication-deficient adeno-associated virus (AAV) and lentiviral (LV) vectors into discrete regions of the forebrain.
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