Inhibition of HIV derived lentiviral production by TAR RNA binding domain of TAT protein

BACKGROUND: A critical step in the production of new HIV virions involves the TAT protein binding to the TAR element. The TAT protein contains in close proximity its TAR RNA binding domain and protein transduction domain (PTD). The PTD domain of TAT has been identified as being instrumental in the protein's ability to cross mammalian cell and nuclear membranes. All together, this information led us to form the hypothesis that a protein containing the TAR RNA binding domain could compete with the native full length TAT protein and effectively block the TAR RNA binding site in transduced HIV infected cells. RESULTS: We synthesized a short peptide named Tat-P, which contained the TAR RNA binding and PTD domains to examine whether the peptide has the potential of inhibiting TAT dependent HIV replication. We investigated the inhibiting effects of Tat-P in vitro using a HIV derived lentiviral vector model. We found that the TAT PTD domain not only efficiently transduced test cells, but also effectively inhibited the production of lentiviral particles in a TAT dependent manner. These results were also supported by data derived from the TAT activated LTR-luciferase expression model and RNA binding assays. CONCLUSION: Tat-P may become part of a category of anti-HIV drugs that competes with full length TAT proteins to inhibit HIV replication. In addition, this study indicates that the HIV derived lentiviral vector system is a safe and reliable screening method for anti-HIV drugs, especially for those targeting the interaction of TAT and TAR RNAs

Kinetics and Mechanism of Oxidation of Diethanolamine and Triethanolamine by Potassium Ferrate

Abstract: The kinetics of oxidation of diethanolamine and triethanolamine by potassium ferrate(VI) in alkaline liquids at a constant ionic strength has been studied spectrophotometrically in the temperature range of 278.2 K-293.2 K. The reaction shows first order dependence on potassium ferrate(VI), first order dependence on each reductant, The observed rate constant (k obs ) decreases with the increase in [OH -], the reaction is negative fraction order with respect to [OH -]. A plausible mechanism is proposed and the rate equations derived from the mechanism can explain all the experimental results. The rate constants of the ratedetermining step and the thermodynamic activation parameters are calculated

Preventing Over-Smoothing for Hypergraph Neural Networks

In recent years, hypergraph learning has attracted great attention due to its capacity in representing complex and high-order relationships. However, current neural network approaches designed for hypergraphs are mostly shallow, thus limiting their ability to extract information from high-order neighbors. In this paper, we show both theoretically and empirically, that the performance of hypergraph neural networks does not improve as the number of layers increases, which is known as the over-smoothing problem. To tackle this issue, we develop a new deep hypergraph convolutional network called Deep-HGCN, which can maintain the heterogeneity of node representation in deep layers. Specifically, we prove that a $k$-layer Deep-HGCN simulates a polynomial filter of order $k$ with arbitrary coefficients, which can relieve the problem of over-smoothing. Experimental results on various datasets demonstrate the superior performance of the proposed model comparing to the state-of-the-art hypergraph learning approaches

Prediction of Electricity Consumption of a HVAC System in a Multi-Complex Building Using Back Propagation and Radial Basis Function Neural Networks

This study examined approaches to predict electricity consumption of a Heating, Ventilation and Air- Conditioning (HVAC) system in a multi-complex building using two neural network models: Back Propagation (BP) and Radial Basis Function (RBF) with input nodes, e.g., temperature, humidity ratio, and wind speed. Predicting HVAC energy consumption of buildings is a crucial part of energy management systems. We used two main neural network models, BP and RBF, to evaluate the prediction performance of electricity consumption of HVAC systems. The BP neural network method exhibited good performance, but it exhibited relatively large fluctuations and slow convergence in the training process. In contrast, RBF exhibited relatively fast learning and reduced computing costs. The HVAC energy consumption rate of working days was higher than that of non-working days. The results indicate that the prediction of HVAC energy consumption using neural networks can effectively control the relationship between the HVAC system and environment conditions.publishedVersio

Origin and tuning of the magnetocaloric effect for the magnetic refrigerant MnFe(P1-xGex)

Neutron diffraction and magnetization measurements of the magneto refrigerant Mn1+yFe1-yP1-xGex reveal that the ferromagnetic and paramagnetic phases correspond to two very distinct crystal structures, with the magnetic entropy change as a function of magnetic field or temperature being directly controlled by the phase fraction of this first-order transition. By tuning the physical properties of this system we have achieved a maximum magnetic entropy change exceeding 74 J/Kg K for both increasing and decreasing field, more than twice the value of the previous record.Comment: 6 Figures. One tabl

Protease Cleavage Leads to Formation of Mature Trimer Interface in HIV-1 Capsid

During retrovirus particle maturation, the assembled Gag polyprotein is cleaved by the viral protease into matrix (MA), capsid (CA), and nucleocapsid (NC) proteins. To form the mature viral capsid, CA rearranges, resulting in a lattice composed of hexameric and pentameric CA units. Recent structural studies of assembled HIV-1 CA revealed several inter-subunit interfaces in the capsid lattice, including a three-fold interhexamer interface that is critical for proper capsid stability. Although a general architecture of immature particles has been provided by cryo-electron tomographic studies, the structural details of the immature particle and the maturation pathway remain unknown. Here, we used cryo-electron microscopy (cryoEM) to determine the structure of tubular assemblies of the HIV-1 CA-SP1-NC protein. Relative to the mature assembled CA structure, we observed a marked conformational difference in the position of the CA-CTD relative to the NTD in the CA-SP1-NC assembly, involving the flexible hinge connecting the two domains. This difference was verified via engineered disulfide crosslinking, revealing that inter-hexamer contacts, in particular those at the pseudo three-fold axis, are altered in the CA-SP1-NC assemblies compared to the CA assemblies. Results from crosslinking analyses of mature and immature HIV-1 particles containing the same Cys substitutions in the Gag protein are consistent with these findings. We further show that cleavage of preassembled CA-SP1-NC by HIV-1 protease in vitro leads to release of SP1 and NC without disassembly of the lattice. Collectively, our results indicate that the proteolytic cleavage of Gag leads to a structural reorganization of the polypeptide and creates the three-fold interhexamer interface, important for the formation of infectious HIV-1 particles. © 2012 Meng et al

Vitamin D, vitamin D supplementation and atrial fibrillation risk in the general population: updated systematic review and meta-analysis of prospective studies

BackgroundSince the association of vitamin D with atrial fibrillation (AF) risk is still unclear, we conducted this updated meta-analysis of prospective studies to identify the relationship between vitamin D or vitamin D supplementation and AF in the general population.MethodsWe conducted a comprehensive search of multiple databases up to May 2023 for studies reporting vitamin D and AF. The hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled by a random-effects model.ResultsA total of seven studies were included in this meta-analysis. Vitamin D deficiency (<20 ng/ml) was associated with increased AF incidence (HR: 1.12, 95% CI: 1.005–1.25). The HR was not significant with vitamin D insufficiency (20–30 ng/ml; HR: 1.09, 95% CI: 0.98–1.21). Each 10 ng/ml increase in serum vitamin D was associated with a significantly decreased AF incidence (HR: 0.95, 95% CI: 0.93–0.97). Two studies reported the effect of vitamin D supplements on AF incidence but reached inconsistent results.ConclusionsVitamin D deficiency or insufficiency was associated with an increased risk of AF in the general population. The role of vitamin D supplementation in AF prevention needs further investigation