HIV-1 and other retroviruses occasionally undergo hypermutation, characterized by a high rate of G-to-A substitution. Recently, the human apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (APOBEC3G), first identified as CEM15, was shown to be packaged into retroviral virions and to deaminate deoxycytidine to deoxyuridine in newly synthesized viral minusstrand DNA, thereby inducing G-to-A hypermutation. This innate mechanism of resistance to retroviral infection is counteracted by the HIV-1 viral infectivity factor (Vif), which protects the virus by preventing the incorporation of APOBEC3G into virions by rapidly inducing its ubiquitination and proteasomal degradation. To gain insights into the mechanism by which Vif protects HIV-1 from APOBEC3G, we substituted several amino acids in human APOBEC3G with equivalent residues in simian APOBEC3Gs that are resistant to HIV-1 Vif and determined the effects of the mutations on HIV-1 replication in the presence and absence of Vif. We found that a single amino acid substitution mutant of human APOBEC3G (D128K) can interact with HIV-1 Vif but is not depleted from cells; thus, it inhibits HIV-1 replication in an HIV-1 Vif-resistant manner. Interestingly, rhesus macaque simian immunodeficiency virus 239 or HIV-2 Vif coexpression depleted the intracellular steady state levels of the D128K mutant and abrogated its antiviral activity, indicating that it can be a substrate for the proteasomal pathway. The HIV-1 Vif-resistant mutant APOBEC3G could provide a gene therapy approach to combat HIV-1 infection.

Hierarchical NiCo2O4@NiCo2O4 core/shell nanoflake arrays on nickel foam for high-performance supercapacitors are fabricated by a two-step solution-based method which involves in hydrothermal process and chemical bath deposition. Compared with the bare NiCo2O4 nanoflake arrays, the core/shell electrode displays better pseudocapacitive behaviors in 2 M KOH, which exhibits high areal specific capacitances of 1.55 F cm(-2) at 2 mA cm(-2) and 1.16 F cm(-2) at 40 mA cm(-2) before activation as well as excellent cycling stability. The specific capacitance can achieve a maximum of 2.20 F cm(-2) at a current density of 5 mA cm(-2), which can still retain 2.17 F cm(-2) (98.6% retention) after 4000 cycles. The enhanced pseudocapacitive performances are mainly attributed to its unique core/shell structure, which provides fast ion and electron transfer, a large number of active sites, and good strain accommodation.

This article provides an overview of solution-based methods for the controllable synthesis of metal oxides and their applications for electrochemical energy storage. Typical solution synthesis strategies are summarized and the detailed chemical reactions are elaborated for several common nanostructured transition metal oxides and their composites. The merits and demerits of these synthesis methods and some important considerations are discussed in association with their electrochemical performance. We also propose the basic guideline for designing advanced nanostructure electrode materials, and the future research trend in the development of high power and energy density electrochemical energy storage devices.

We have used coreceptor-targeted inhibitors to investigate which coreceptors are used by human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency viruses (SIV), and human immunodeficiency virus type 2 (HIV-2) to enter peripheral blood mononuclear cells (PBMC). The inhibitors are TAK-779, which is specific for CCR5 and CCR2, aminooxypentane-RANTES, which blocks entry via CCR5 and CCR3, and AMD3100, which targets CXCR4. We found that for all the HIV-1 isolates and all but one of the HIV-2 isolates tested, the only relevant coreceptors were CCR5 and CXCR4. However, one HIV-2 isolate replicated in human PBMC even in the presence of TAK-779 and AMD3100, suggesting that it might use an undefined, alternative coreceptor that is expressed in the cells of some individuals. SIV mac 239 and SIV mac 251 (from macaques) were also able to use an alternative coreceptor to enter PBMC from some, but not all, human and macaque donors. The replication in human PBMC of SIV rcm (from a red-capped mangabey), a virus which uses CCR2 but not CCR5 for entry, was blocked by TAK-779, suggesting that CCR2 is indeed the paramount coreceptor for this virus in primary cells.

Long noncoding RNAs (lncRNAs) play multiple key regulatory roles in various cellular pathways. However, their functions in HIV-1 latent infection remain largely unknown. Here we show that a lncRNA named NRON, which is highly expressed in resting CD4+ T lymphocytes, could be involved in HIV-1 latency by specifically inducing Tat protein degradation. Our results suggest that NRON lncRNA potently suppresses the viral transcription by decreasing the cellular abundance of viral transactivator protein Tat. NRON directly links Tat to the ubiquitin/proteasome components including CUL4B and PSMD11, thus facilitating Tat degradation. Depletion of NRON, especially in combination with a histone deacetylase (HDAC) inhibitor, significantly reactivates the viral production from the HIV-1-latently infected primary CD4+ T lymphocytes. Our data indicate that lncRNAs play a role in HIV-1 latency and their manipulation could be a novel approach for developing latency-reversing agents.

SUMMARYThe delay-dependent stability problem of linear continuous/discrete systems with time-varying delay is investigated based on a piecewise analysis method (PAM). In the method, the variation interval of the time delay is firstly divided into several subintervals. By checking the variation of the Lyapunov functional in every subinterval, some new delay-dependent stability criteria are derived. Several numerical examples show that our method can lead to much less conservative results than those in the existing references. Moreover, when the number of the divided subintervals increases, the corresponding criteria can provide an improvement on the results.

During the presummer rainy season (April–June), southern China often experiences frequent occurrences of extreme rainfall, leading to severe flooding and inundations. To expedite the efforts in improving the quantitative precipitation forecast (QPF) of the presummer rainy season rainfall, the China Meteorological Administration (CMA) initiated a nationally coordinated research project, namely, the Southern China Monsoon Rainfall Experiment (SCMREX) that was endorsed by the World Meteorological Organization (WMO) as a research and development project (RDP) of the World Weather Research Programme (WWRP). The SCMREX RDP (2013–18) consists of four major components: field campaign, database management, studies on physical mechanisms of heavy rainfall events, and convection-permitting numerical experiments including impact of data assimilation, evaluation/improvement of model physics, and ensemble prediction. The pilot field campaigns were carried out from early May to mid-June of 2013–15. This paper: i) describes the scientific objectives, pilot field campaigns, and data sharing of SCMREX; ii) provides an overview of heavy rainfall events during the SCMREX-2014 intensive observing period; and iii) presents examples of preliminary research results and explains future research opportunities.

Cell surface glycosaminoglycans (GAGs), in particular heparan sulfate (HS), have been proposed to mediate the attachment of human immunodeficiency virus type 1 (HIV-1) to target cells prior to virus entry, and both the viral gp120 envelope protein and virion-associated cyclophilin A (CypA) have been shown to directly interact with HS and its analogues. To determine the role of GAGs in HIV attachment and infection, we generated HIV-susceptible derivatives of CHO cell lines that either express high levels of GAGs (CHO-K1) or lack GAGs (pgsA745). Using a panel of HIV-1 envelopes, we found that cell surface GAG-mediated effects on virion attachment and infection vary in an envelope strain-dependent but coreceptor-independent manner. In fact, cell surface GAG-mediated enhancement of infection is confined to isolates that contain a highly positively charged V3-loop sequence, while infection by most strains is apparently inhibited by the presence of GAGs. Moreover, the enhancing and inhibitory effects of polycations and polyanions on HIV-1 infection are largely dependent on the presence of cell surface GAGs. These observations are consistent with a model in which GAGs influence in vitro HIV-1 infection primarily by modifying the charge characteristics of the target cell surface. Finally, the effects of GAGs on HIV-1 infection are observed to an equivalent extent whether CypA is present in or absent from virions. Overall, these data exclude a major role for GAGs in mediating the attachment of many HIV-1 strains to target cells via interactions with virion-associated gp120 or CypA.