Activation and degradation of open reading frame 45 by the replication and transcription activator of Kaposi's sarcoma-associated herpesvirus.

The open reading frame 45 (ORF45) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is an immediate-early phosphorylated tegument protein critical for viral escape from host immune surveillance. Its expression is upregulated by the viral replication and transcription activator (RTA), a key protein that controls the switch from latency to lytic replication. We report here that ORF45 expression was not only upregulated by RTA, but ORF45 could also be degraded by RTA in a proteasome-dependent manner. The ORF45 was activated by RTA via activation of the ORF45 promoter, and the promoter region from nt 69 271 to nt 69 026 was involved. In chronic KSHV infected TRE-BCBL-1 RTA cells, the endogenous ORF45 protein increased dramatically after the induction of RTA expression, but then decreased rapidly after 8 h post-induction. Our study suggests that RTA might control the kinetics of viral replication through fine-tuning of the level of ORF45 and other viral/host proteins.

Lysine residues of interferon regulatory factor 7 affect the replication and transcription activator-mediated lytic replication of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8.

Kaposi's sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory factor 7 (IRF-7), a key regulator of host innate immune response. Lysine residues are potential sites for post-translational modification of IRF-7, and were suggested to be critical for its activity. In this study, we analysed the 15 lysine residues for their effects on IRF-7 function by site-directed mutagenesis. We found that some mutations affect the ability of IRF-7 to activate interferon (IFN)-α1 and IFN-ß promoters, to suppress RTA-mediated lytic gene expression and to repress KSHV reactivation and lytic replication. However, other mutations affect only a subset of these four functions. These findings demonstrate that the lysine residues of IRF-7 play important roles in mediating IFN synthesis and modulating viral lytic replication.

How Does Urban Green Space Impact Residents' Mental Health: A Literature Review of Mediators.

In recent years, the interest in the relationship between urban green space and residents' mental health has gradually risen. A number of researchers have investigated the causal relationship and possible mediators between the two, although few have summarized these mediators. For this reason, we searched for relevant studies and filtered them by criteria and quality score, and analyzed the mediators and paths of the impact of urban green space on residents' mental health. The mediators can be divided into environmental factors, outdoor activity, and social cohesion. From the perspective of heterogeneity, both individual characteristics (e.g., age and gender) and group characteristics (e.g., level of urban development and urban density) of residents are considered to be the cause of various mediating effects. Types of urban green space tend to affect residents' mental health through different paths. Furthermore, this review discusses the details of each part under the influence paths. Finally, the policy implications for urban green space planning from three mediator levels are put forward based on an analysis of the situation in different countries.

Predictors of residual dizziness in patients with benign paroxysmal positional vertigo after successful repositioning: A multi-center prospective cohort study.

BACKGROUND: While patients with benign paroxysmal positional vertigo (BPPV) commonly develop residual dizziness (RD) after successful repositioning, the factors predictive of RD remain controversial. OBJECTIVE: To identify factors predictive of RD onset in patients with BPPV following successful repositioning. METHODS: This multi-center prospective cohort study enrolled 243 patients with idiopathic BPPV. Vestibular functional and psychological wellbeing assessments administered before repositioning provided the data used to identify factors predictive of RD with a log-binomial model. The endpoint was RD at 1 week after successful repositioning. RESULTS: Of the enrolled patients, 118 reported RD. After adjusting for cofounders, mild [risk ratio (RR), 2.06; 95% confidence interval (CI), 1.39-3.04] or severe (RR, 3.08; 95% CI, 2.17-4.38) anxiety and abnormal vestibular ratio of sensory organization test (RR, 2.68; 95% CI, 1.82-3.95) were identified as risk predictors. Presence of ocular vestibular evoked myogenic potentials responses, either unilateral (RR, 0.55; 95% CI, 0.44-0.69) or bilateral (RR, 0.49; 95% CI, 0.36-0.68), were protective factors. CONCLUSIONS: Anxiety and abnormal balance are significant predictors of RD, while the presence of ocular vestibular evoked myogenic potentials responses predicts against it. These findings may help to improve BPPV outcomes by informing prognoses and guiding treatment strategies. TRIAL REGISTRATION: ChiCTR1800018004 (date of registration: 26 August 2018).

Assessment of liver volume variation to evaluate liver function.

In order to assess the value of liver volumetry in cirrhosis and acute liver failure (ALF) patients, we explored the correlation between hepatic volume and severity of the hepatic diseases. The clinical data of 48 cirrhosis patients with 60 normal controls and 39 ALF patients were collected. Computed tomography-derived liver volume (CTLV) and body surface area (BSA) of normal controls were calculated to get a regression formula for standard liver volume (SLV) and BSA. Then CTLV and SLV of all patients were calculated and grouped by Child-Turcotte-Pugh classification for cirrhosis patients and assigned according to prognosis of ALF patients for further comparison. It turned out that the mean liver volume of the control group was 1,058 ± 337 cm(3). SLV was correlated with BSA according to the regression formula. The hepatic volume of cirrhosis patients in Child A, B level was not reduced, but in Child C level it was significantly reduced with the lowest liver volume index (CTLV/SLV). Likewise, in the death group of ALF patients, the volume index was significantly lower than that of the survival group. Based on volumetric study, we proposed an ROC (receiver operating characteristic) analysis to predict the prognosis of ALF patients that CTLV/SLV < 83.9% indicates a poor prognosis. In conclusion, the CTLV/SLV ratio, which reflects liver volume variations, correlates well with the liver function and progression of cirrhosis and ALF. It is also a very useful marker for predicting the prognosis of ALF.

Generation and application of polyclonal antibody against replication and transcription activator of Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma, the most common neoplasm in untreated HIV-1-infected individuals, and several B cell disorders. KSHV infection goes through lytic and latent phases, and the switch from latency to lytic replication is governed by viral replication and transcription activator (RTA). RTA consists of 691 amino acids, containing an N-terminal DNA-binding and a C-terminal activation domain. In the present study, polyclonal antibody against RTA was generated and evaluated. The C-terminal region of RTA (E482 approximately D691) was expressed in Escherichia coli, purified by affinity chromatography, and utilized to raise polyclonal antibody in BALB/c mice. High-affinity antisera were obtained, which successfully detected the antigen at a dilution of 1:13,500 for ELISA and 1:20,000 for Western blot analysis. The antibody can specifically recognize full-length RTA expressed in both E. coli and mammalian cells. Furthermore, endogenous RTA can be detected with the antibody in TPA-induced BCBL-1 cells under various conditions. These results suggested that the antibody is valuable for the investigation of biochemical properties and biological functions of RTA.