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CD4 downregulation on infected cells is a highly conserved function of primate lentiviruses. It has been shown to positively impact viral replication by a variety of mechanisms, including enhanced viral release and infectivity, decrease of cell reinfection, and protection from antibody-dependent cellular cytotoxicity (ADCC), which is often mediated by antibodies that require CD4 to change envelope (Env) conformation. Here, we report that incorporation of CD4 into HIV-1 viral particles affects Env conformation resulting in the exposure of occluded epitopes recognized by CD4-induced antibodies. This translates into enhanced neutralization susceptibility by these otherwise nonneutralizing antibodies but is prevented by the HIV-1 Nef accessory protein. Altogether, these findings suggest that another functional consequence of Nef-mediated CD4 downregulation is the protection of viral particles from neutralization by commonly elicited CD4-induced antibodies. IMPORTANCE It has been well established that Env-CD4 complexes expose epitopes recognized by commonly elicited CD4-induced antibodies at the surface of HIV-1-infected cells, rendering them vulnerable to ADCC responses. Here, we show that CD4 incorporation has a profound impact on Env conformation at the surface of viral particles. Incorporated CD4 exposes CD4-induced epitopes on Env, rendering HIV-1 susceptible to neutralization by otherwise nonneutralizing antibodies.

The HIV-1 envelope glycoprotein (Env) trimer mediates virus entry into cells. The “closed” conformation of Env is resistant to nonneutralizing antibodies (nnAbs). These antibodies mostly recognize occluded epitopes that can be exposed upon binding of CD4 or small-molecule CD4 mimetics (CD4mc). Here, we describe a new family of small molecules that expose Env to nnAbs and sensitize infected cells to antibody-dependent cellular cytotoxicity (ADCC). These compounds have a limited capacity to inhibit virus infection directly but are able to sensitize viral particles to neutralization by otherwise nonneutralizing antibodies. Structural analysis shows that some analogs of this family of CD4mc engage the gp120 Phe43 cavity by contacting the highly conserved D368 residue, making them attractive scaffolds for drug development. IMPORTANCE HIV-1 has evolved multiple strategies to avoid humoral responses. One efficient mechanism is to keep its envelope glycoprotein (Env) in its “closed” conformation. Here, we report on a new family of small molecules that are able to “open up” Env, thus exposing vulnerable epitopes. This new family of molecules binds in the Phe43 cavity and contacts the highly conserved D368 residue. The structural and biological attributes of molecules of this family make them good candidates for drug development.

The spin switching and exchange bias effect were investigated in the rare earth orthoferrite SmFeO

Core-shell-nanostructured hematite@graphite (α-Fe2O3@C) for photoelectrochemical (PEC) water splitting was innovatively prepared from graphite-encapsulated iron (Fe@C) nanoparticles by the arc-discharge method. The graphite was successfully controlled from dozens to few layers, and Fe was transformed into α-Fe2O3 with particle size of 20–30 nm during the thermal oxidation. α-Fe2O3@C was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectroscopy techniques. The photocurrent density of α-Fe2O3@C reached a maximum of 20 μA/cm2 at 1.23 VRHE when there were 2–3 layers of graphite and the film thickness was 200 nm. Herein, graphite was proven to play the key role in coupling between light blocking and enhanced photocarrier separation rather than changing the density of the oxygen vacancies. The addition of graphite layers enhanced the photocurrent density by 20 times compared with that of the bare α-Fe2O3 particle film derived from the hydrothermal method, which was further demonstrated by electrochemical impedance spectra (EIS).

To minimize immune responses against infected cells, HIV-1 limits the surface expression of its envelope glycoprotein (Env). Here, we demonstrate that this mechanism is specific for the Env conformation and affects the efficiency of antibody-dependent cellular cytotoxicity (ADCC). Using flow cytometry and confocal microscopy, we show that broadly neutralizing antibodies (bNAbs) targeting the “closed” conformation of Env induce its internalization from the surface. In contrast, non-neutralizing antibodies (nNAbs) are displayed on the cell surface for prolonged period of times. The bNAb-induced Env internalization can be decreased by blocking dynamin function, which translates into higher susceptibilities of infected cells to ADCC. Our results suggest that antibody-mediated Env internalization is a mechanism used by HIV-1 to evade immune responses against the “closed” conformation of Env expressed on HIV-1-infected cells. IMPORTANCE HIV-1 has evolved to acquire several strategies to limit the exposure of its envelope glycoproteins (Env) on the surface of infected cells. In this study, we show that antibody-induced Env internalization is conformation specific and reduces the susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). Thus, a better understanding of this mechanism might help develop antibodies with improved capacities to mediate ADCC.

The interfacial Dzyaloshinskii-Moriya interaction (DMI) in multilayers of heavy metal and ferromagnetic metals enables the stabilization of novel chiral spin structures such as skyrmions. Magnetic insulators, on the other hand can exhibit enhanced dynamics and properties such as lower magnetic damping and therefore it is of interest to combine the properties enabled by interfacial DMI with insulating systems. Here, we demonstrate the presence of interfacial DMI in heterostructures that include insulating magnetic layers. We use a bilayer of perpendicularly magnetized insulating thulium iron garnet (TmIG) and the heavy metal platinum, and find a surprisingly strong interfacial DMI that, combined with spin-orbit torque results, in efficient switching. The interfacial origin is confirmed through thickness dependence measurements of the DMI, revealing the characteristic 1/thickness dependence with one order of magnitude longer decay length compared to metallic layers. We combine chiral spin structures and spin-orbit torques for efficient switching and identify skyrmions that allow us to establish the GGG/TmIG interface as the origin of the DMI.

Significance CD4 is known to have evolved rapidly in primates, but the reason for this diversification is unknown. Here, we show that polymorphisms in the simian immunodeficiency virus (SIV) envelope (Env) binding domain of the CD4 receptor modulate the susceptibility of chimpanzee CD4+ T cells to SIV infection by interfering with Env–CD4 interactions required for viral entry. Both amino acid substitutions and N-linked glycosylation sites in the D1 domain blocked Env-mediated entry of a number of SIVs, including viruses that infect primates on which chimpanzees prey. These data identify steric hindrance between cell entry receptor-encoded and virus surface protein-encoded glycans as a mechanism of antiviral protection and suggest that selection pressures by primate lentiviruses, both extant and extinct, have shaped the evolution of chimpanzee CD4., Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells. Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)–CD4 interactions. Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts. These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes. The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles. In silico modeling and site-directed mutagenesis identified charged residues at the CD4–Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition. CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan. CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep. One allele was associated with lower SIVcpz prevalence rates in the wild. These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry. Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.

The sphericity, κ, is introduced to describe the morphology of the magnetic grains. The effect of κ on the magnetic properties of rare earth-transition metal (RE-TM) permanent magnets was investigated using the micromagnetic simulation, where randomly aligned, irregular-shaped grains with ferromagnetic/non-ferromagnetic grain boundary (GB) phases were considered. For the simulated RE-TM systems, the coercivity increases significantly with the increase in κ. In particular, with 10 nm thick non-ferromagnetic GB phase, the coercivity, 1.74 MA/m, for к = 0.9 increases by 22% compared to 1.43 MA/m for к = 0.6 in the Nd2Fe14B system. Among the simulated materials, the SmCo5 system displays the largest increment in coercivity, increasing by 0.82 MA/m from 7.61 MA/m for к = 0.6 to 8.43 MA/m for к = 0.9. Magnetization reversal patterns under different external fields indicate that the dependence of coercivity on κ is attributed to the formation of local reversals at different regions and mechanisms of reversal propagation. Meanwhile the effect of κ cannot be neglected even at elevated temperatures. The simulated results of (Dy0.47Nd0.53)2Fe14B systems with the non-ferromagnetic GB layer of 4 nm at a temperature of 450 K show that the coercivity for к = 0.9 (1.88 MA/m) increased by 23% compared with that of к = 0.6 (1.52 MA/m). Our study demonstrates that the sphericity can be used as a key parameter to design high-coercivity RE-TM magnets.

Characterization of the humoral response to SARS-CoV-2, the etiological agent of COVID-19, is essential to help control the infection. The neutralization activity of plasma from COVID-19 patients decreases rapidly during the first weeks after recovery. However, the specific role of each immunoglobulin isotype in the overall neutralizing capacity is still not well understood. In this study, we select plasma from a cohort of COVID-19 convalescent patients and selectively deplete immunoglobulin A, M or G before testing the remaining neutralizing capacity of the depleted plasma. We find that depletion of immunoglobulin M is associated with the most substantial loss of virus neutralization, followed by immunoglobulin G. This observation may help design efficient antibody-based COVID-19 therapies and may also explain the increased susceptibility to SARS-CoV-2 of autoimmune patients receiving therapies that impair the production of IgM., Graphical Abstract, Gasser et al. highlight the importance of IgM in the capacity of plasma from convalescent donors to neutralize SARS-CoV-2.

Waste cooking oil (WCO) and stearic acid (SA) were considered to be renewable and readily available bio-oil resources to produce bio-fuel via catalytic hydrodeoxygenation. The most often used catalysts for hydrodeoxygenation were the vulcanized NiMo catalysts, however, the vulcanized catalysts tend to deactivate due to the loss and oxidation of sulfur upon treating bio-oil with high oxygen content. Therefore, it is necessary to develop sulfur-free catalysts. In present study, the reduced NiMo catalysts were prepared by loading Ni and Mo on different supports (γ-Al2O3, HZSM-5, β-zeolite, activated carbon and bentonite) using incipient-wetness impregnation method, and followed by H2 reduction. The effects of the properties of supports (acidity, porosity) and H2 reduction on the dispersity and valence state of metal components were investigated. The hydrodeoxygenation activities of the reduced catalysts were evaluated by catalytic WCO and SA. It was found that when Ni2+ was loaded on a slightly acidic supports such as γ-Al2O3 and activated carbon, Ni2+ was easier to be reduced, and aggregate to form larger particles. When Ni2+ was loaded on a strongly acid supports e.g. HZSM-5, β-zeolite or bentonite, Ni2+ was more difficult to be reduced but could uniformly disperse on the supports. The aggregated Ni atoms could promote the formation of C17, while the dispersed Ni atoms could promote the formation of C18. γ-Al2O3 supported catalyst achieved the highest SA (97.9%) and WCO (80%) conversion under the mild reaction conditions of 300 °C and 2 MPa H2 for 3 h, exhibiting the superior catalytic activity.

Binding of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological layers (layer 1, layer 2, and layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to layer 1 of HIV-1 gp120, the SIVmac239 gp120 layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could be explained by the existence of a well-conserved tryptophan at position 375 (Trp 375) in HIV-2/SIVsmm. In this study, we investigated the role of SIV layer 3 in viral entry, cell-to-cell fusion, and CD4 binding. We observed that a network of interactions involving some residues of the β8-α5 region in SIVmac239 layer 3 may contribute to CD4 binding by helping shape the nearby Phe 43 cavity, which directly contacts CD4. In summary, our results suggest that layer 3 in SIV has a greater impact on CD4 binding than in HIV-1. This work defines lineage-specific differences in layer 3 from HIV-1 and that from SIV. IMPORTANCE CD4-induced conformational changes in the gp120 inner domain involve rearrangements between three topological layers. While the role of layers 1 to 3 for HIV-1 and layers 1 and 2 for SIV on gp120 transition to the CD4-bound conformation has been reported, the role of SIV layer 3 remains unknown. Here we report that SIV layer 3 has a greater impact on CD4 binding than does layer 3 in HIV-1 gp120. This work defines lineage-specific differences in layer 3 from HIV-1 and SIV.

Human immunodeficiency virus type 1 (HIV-1) has evolved a sophisticated strategy to conceal conserved epitopes of its envelope glycoproteins (Env) recognized by antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These antibodies, which are present in the sera of most HIV-1-infected individuals, preferentially recognize Env in its CD4-bound conformation. Accordingly, recent studies showed that small CD4-mimetics (CD4mc) able to “push” Env into this conformation sensitize HIV-1-infected cells to ADCC mediated by HIV + sera. Here we test whether CD4mc also expose epitopes recognized by anti-cluster A monoclonal antibodies such as A32, thought to be responsible for the majority of ADCC activity present in HIV + sera and linked to decreased HIV-1 transmission in the RV144 trial. We made the surprising observation that CD4mc are unable to enhance recognition of HIV-1-infected cells by this family of antibodies in the absence of antibodies such as 17b, which binds a highly conserved CD4-induced epitope overlapping the co-receptor binding site (CoRBS). Our results indicate that CD4mc initially open the trimeric Env enough to allow the binding of CoRBS antibodies but not anti-cluster A antibodies. CoRBS antibody binding further opens the trimeric Env, allowing anti-cluster A antibody interaction and sensitization of infected cells to ADCC. Therefore, ADCC responses mediated by cluster A antibodies in HIV-positive sera involve a sequential opening of the Env trimer on the surface of HIV-1-infected cells. The understanding of the conformational changes required to expose these vulnerable Env epitopes might be important in the design of new strategies aimed at fighting HIV-1., Highlights • CD4-mimetics fail to enhance recognition of infected cells by anti-cluster A antibodies (Abs). • Co-receptor binding site Abs in conjunction with CD4-mimetics allow binding of Env by anti-cluster A Abs. • Co-receptor binding site Abs help CD4-mimetics sensitize HIV-1-infected cells to ADCC. HIV-1 developed sophisticated strategies to conceal vulnerable epitopes of its envelope glycoproteins (Env) recognized by antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. CD4-mimetics (CD4mc) were shown to sensitize HIV-1-infected cells to ADCC induced by HIV + sera. Here we show that this response requires a sequential opening of Env at the surface of HIV-1-infected cells. Co-receptor binding site antibodies, also present in HIV + sera, are required to expose ADCC-mediating epitopes recognized by anti-cluster A antibodies upon CD4mc addition. The understanding of the conformational changes required to expose anti-cluster A epitopes might be important in the design of new strategies aimed at fighting HIV-1., Graphical Abstract Image 2

Stearic acid (SA) was dispersed in tetralin (a hydrogen donor) and hydrotreated in a batch reactor over a fabricated sulfided NiMo/γ-Al2O3-β-zeolite catalyst to obtain a diesel-range fuel product. NiMo/γ-Al2O3-β-zeolite catalysts were prepared by loading the active components NiO and MoO3 onto a mechanically mixed γ-Al2O3 and β-zeolite support, followed by a sulfurization procedure. The effects of the catalytic properties and reaction conditions on the hydrodeoxygenation of SA were investigated. The results showed that increasing the β-zeolite in the support leads to a decrease in SA conversion and an increase in the isomerization of products; increasing the NiO and MoO3 mass fraction tends to promote the formation of alkene hydrocarbons and increase the level of isomerization; increasing the Ni molar fraction helps to promote both conversion and isomerization; and temperatures above 330 °C promoted the activities of the catalysts and tetralin. A nearly 90% SA conversion was achieved at 350 °C under H2 at a pressure of 0.8 MPa for 2 h in tetralin. The total content of C16 C18 alkanes and alkenes in the products was about 98%, and the isomerized compounds accounted for 10–40 wt%.

Impairment of Nef function, including reduced CD4 downregulation, was described in a subset of HIV-1-infected individuals that control viral replication without antiretroviral treatment (elite controllers [EC]). Elimination of HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC) requires the presence of envelope glycoproteins (Env) in the CD4-bound conformation, raising the possibility that accumulating CD4 at the surface of virus-infected cells in EC could interact with Env and thereby sensitize these cells to ADCC. We observed a significant increase in the exposure of Env epitopes targeted by ADCC-mediating antibodies at the surface of cells expressing Nef isolates from EC; this correlated with enhanced susceptibility to ADCC. Altogether, our results suggest that enhanced susceptibility of HIV-1-infected cells to ADCC may contribute to the EC phenotype. IMPORTANCE Nef clones derived from elite controllers (EC) have been shown to be attenuated for CD4 downregulation; how this contributes to the nonprogressor phenotype of these infected individuals remains uncertain. Increasing evidence supports a role for HIV-specific antibody-dependent cellular cytotoxicity (ADCC) in controlling viral infection and replication. Here, we show that residual CD4 left at the surface of cells expressing Nef proteins isolated from ECs are sufficient to allow Env-CD4 interaction, leading to increased exposure of Env CD4-induced epitopes and increased susceptibility of infected cells to ADCC. Our results suggest that ADCC might be an active immune mechanism in EC that helps to maintain durable suppression of viral replication and low plasma viremia level in this rare subset of infected individuals. Therefore, targeting Nef's ability to downregulate CD4 could render HIV-1-infected cells susceptible to ADCC and thus have therapeutic utility.

Human immunodeficiency virus type 1 (HIV-1) infection causes a progressive depletion of CD4 + T cells. Despite its importance for HIV-1 pathogenesis, the precise mechanisms underlying CD4 + T-cell depletion remain incompletely understood. Here we make the surprising observation that antibody-dependent cell-mediated cytotoxicity (ADCC) mediates the death of uninfected bystander CD4 + T cells in cultures of HIV-1-infected cells. While HIV-1-infected cells are protected from ADCC by the action of the viral Vpu and Nef proteins, uninfected bystander CD4 + T cells bind gp120 shed from productively infected cells and are efficiently recognized by ADCC-mediating antibodies. Thus, gp120 shedding represents a viral mechanism to divert ADCC responses towards uninfected bystander CD4 + T cells. Importantly, CD4-mimetic molecules redirect ADCC responses from uninfected bystander cells to HIV-1-infected cells; therefore, CD4-mimetic compounds might have therapeutic utility in new strategies aimed at specifically eliminating HIV-1-infected cells., Graphical Abstract, Highlights • Gp120 shed from productively-infected cells binds to bystander CD4 + T cells. • Gp120-coated bystander cells are highly sensitivity to ADCC responses mediated by CD4-induced antibodies. • Small-molecule CD4-mimetics redirect CD4-induced antibodies to HIV-1-infected cells. The hallmark of human immunodeficiency virus type 1 (HIV-1) infection is the progressive depletion of CD4 + T cells. Using cultures of HIV-1-infected cells, we observed that a part of the machinery that the virus uses to infect cells (gp120) binds to uninfected cells. Antibodies elicited during the course of the infection against the gp120 can recognize uninfected cells and redirect an immune response to them that results in their elimination. Importantly, this phenomenon can be blocked with a small CD4-mimetic compound that abrogates the binding of gp120 to uninfected cells and redirects the immune system to infected cells.

An open capillary evaporator is proposed to study the evaporation heat transfer performance of porous wick. Both temperature and evaporating mass are measured in this system. Besides, the temperature and relative height of the supplied fluid can be adjusted. A composite porous wick is tested through the constant and variable heat load operation, and it reaches a maximum heat load of 320 W, which corresponds to a heat flux of 25.5 W/cm2. Two types of the evaporator wall temperature curve are observed, and the effect of the initial condition is considered. Intermittent fluid supply appears and causes a temperature overshoot of the evaporator wall. But continuous intermittent fluid supply and small amount of fast-replenishing fluid does not cause the temperature overshoot. The influence of adding water on temperature overshoot is also studied. The boiling and evaporation occur at different heat loads, and the two heat transfer modes coexist at moderate heat load. The transition in heat transfer modes leads to that the evaporation heat transfer coefficient first increases and then decreases with the increase of heat load. This study is helpful to analyze the evaporation heat transfer performance of porous wick and understand the operating characteristics of loop heat pipe.

Based on our previous research on the composite porous wick with spherical-dendritic powders, this paper further adopts the orthogonal experiment to study the effect of the combination and the mixing ratio of the spherical and dendritic powders, and the particle size and volume ratio of the pore former. In order to obtain the optimal prepared parameters of the composite porous wick with spherical-dendritic powders, nine porous samples are prepared based on the orthogonal experiment, and their thermal physical properties are measured and analyzed. Five types of operating curves for temperature and evaporating mass are observed in the evaporation heat transfer experiment. The metal powder materials have significant effects on all the considered physical properties in this paper, but the mixing ratio of metal powders only has a significant effect on the critical heat load and the evaporator wall temperature. The particle size and volume ratio of the pore former also have certain influence on these indexes, except that its particle size has no influence on porosity. The highest critical heat load is 530W and occurs in the composite porous wick with the spherical nickel and the dendritic copper powders with the volume ratio of 3:7, and the particle size of 30-45 μm and the volume ratio of 40% for the pore former, which are not the conditions for the lowest effective thermal conductivity. Low evaporator wall temperature and high critical heat load are required for the excellent performance of composite porous wick. High volume ratio of dendritic copper powders is beneficial to increase the quantity of small pores with high evaporating rate, so as to increase the critical heat load and reduce the evaporator wall temperature. This study can guide the parameter design of the composite porous wick with spherical-dendritic powders to improve its performance.

In 2D magnets, interlayer exchange coupling is generally weak due to the van der Waals layered structure but it still plays a vital role in stabilizing the long-range magnetic ordering and determining the magnetic properties. Using complementary neutron diffraction, magnetic, and torque measurements, the complete magnetic phase diagram of CrPS4 crystals is determined. CrPS4 shows an antiferromagnetic ground state (A-type) formed by out-of-plane ferromagnetic monolayers with interlayer antiferromagnetic coupling along the c axis below TN = 38 K. Due to small magnetic anisotropy energy and weak interlayer coupling, the low-field metamagnetic transitions in CrPS4, that is, a spin-flop transition at ≈0.7 T and a spin-flip transition from antiferromagnetic to ferromagnetic under a relatively low field of 8 T, can be realized for H∥c. Intriguingly, with an inherent in-plane lattice anisotropy, spin-flop-induced moment realignment in CrPS4 for H∥c is parallel to the quasi-1D chains of CrS6 octahedra. The peculiar metamagnetic transitions and in-plane anisotropy make few-layer CrPS4 flakes a fascinating platform for studying 2D magnetism and for exploring prototype device applications in spintronics and optoelectronics.

The existing personalized recommendation method based on time is merely a time stamp in the traditional personalized recommendation algorithm. This paper proposes an improved personalized recommendation method based on preference-aware and time factor. The forgetting curve is used to track the changed of user’s interests with time, and then a model of personalized recommendation based on dynamic time is built. Finally, the time forgetting factor is introduced in the collaborative filtering to improve the prediction effect of the interest-aware algorithm. The experimental results show that the proposed personalized recommendation method can get more accurate recommendation performance. It also can reduce the computing time and space complexity, and improve the quality of the recommendation of personalized recommendation algorithm.

A magnetic cation-exchange resin (MCER) was prepared by copolymerization of oleic acid-grafted magnetite with styrene, divinylbenzene (DVB), and triallylisocyanurate (TAIC) for removing Cd(II) from wastewater. A non-magnetic cation-exchange polystyrene resin (CEPR) was also prepared as a reference. Structural and morphological analyses revealed that the MCER and CEPR were mesoporous microspheres; the MCER contained about 25% Fe3O4. The influence of temperature, pH, contact time, and the initial concentration of Cd(II) on the adsorption of Cd(II) was investigated. The maximum adsorption capacity of the MCER reached 88.56 mg/g, which was achieved at 343 K using a Cd(II) initial concentration of 200 mg/L. The adsorption processes attained equilibrium within 120 min for the MCER and 300 min for the CEPR, and were well described by a pseudo-second-order kinetic model. Furthermore, the equilibrium adsorption data fitted the Freundlich isotherm model better than the Langmuir model. The superior magnetic response and regeneration of the MCER make it a good candidate as an adsorbent for removing Cd(II) from wastewater.

The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a “closed” conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs). Therefore, we hypothesized that these bystander cells could impact the interpretation of ADCC measurements. To investigate this, we evaluated the ability of antibodies to CD4i epitopes and broadly neutralizing Abs (bNAbs) to mediate ADCC measured by five ADCC assays commonly used in the field. Our results indicate that the uninfected bystander cells coated with gp120 are efficiently recognized by the CD4i ligands but not the bNabs. Consequently, the uninfected bystander cells substantially affect in vitro measurements made with ADCC assays that fail to identify responses against infected versus uninfected cells. Moreover, using an mRNA flow technique that detects productively infected cells, we found that the vast majority of HIV-1-infected cells in in vitro cultures or ex vivo samples from HIV-1-infected individuals are CD4 negative and therefore do not expose significant levels of CD4i epitopes. Altogether, our results indicate that ADCC assays unable to differentiate responses against infected versus uninfected cells overestimate responses mediated by CD4i ligands., IMPORTANCE Emerging evidence supports a role for antibody-dependent cellular cytotoxicity (ADCC) in protection against HIV-1 transmission and disease progression. However, there are conflicting reports regarding the ability of nonneutralizing antibodies targeting CD4-inducible (CD4i) Env epitopes to mediate ADCC. Here, we performed a side-by-side comparison of different methods currently being used in the field to measure ADCC responses to HIV-1. We found that assays which are unable to differentiate virus-infected from uninfected cells greatly overestimate ADCC responses mediated by antibodies to CD4i epitopes and underestimate responses mediated by broadly neutralizing antibodies (bNAbs). Our results strongly argue for the use of assays that measure ADCC against HIV-1-infected cells expressing physiologically relevant conformations of Env to evaluate correlates of protection in vaccine trials.

The spin configuration in the ferromagnetic part during the magnetization reversal plays a crucial role in the exchange bias effect. Through Monte Carlo simulation, the exchange bias effect in ferromagnetic-antiferromagnetic core-shell nanoparticles is investigated. Magnetization reversals in the ferromagnetic core were controlled between the coherent rotation and the domain wall motion by modulating the ferromagnetic domain wall width with parameters of uniaxial anisotropy constant and exchange coupling strength. An anomalous monotonic dependence of exchange bias on the uniaxial anisotropy constant is found in systems with small exchange coupling, showing an obvious violation of classic Meiklejohn-Bean model, while domain walls are found to form close to the interface and propagate in the ferromagnetic core with larger uniaxial anisotropy in both branches of the hysteresis. The asymmetric magnetization reversal with the formation of a spherical domain wall dramatically reduces the coercive field in the ascending branch, leading to the enhancement of the exchange bias. The results provide another degree of freedom to optimize the magnetic properties of magnetic nanoparticles for applications.

Recent analysis of HIV-1 envelope glycoproteins (Env) dynamics showed that the unliganded Env trimer can potentially sample three conformations: a metastable "closed" conformation (State 1), an "open" CD4-bound conformation (State 3), and an intermediate "partially open" conformation (State 2). HIV-1 evolved several mechanisms to avoid "opening" its Env in order to evade immune responses such as antibody-dependent cellular cytotoxicity (ADCC), which preferentially targets Envs in the CD4-bound conformation on the surface of infected cells. Here we took advantage of a well-characterized single-residue change in the gp120 trimer association domain to modify Env conformation and evaluate its impact on ADCC responses. We found that cells infected with viruses expressing Env stabilized in States 2/3 become highly susceptible to ADCC responses by sera from HIV-1-infected individuals. Our results indicate that the conformations spontaneously sampled by the Env trimer at the surface of infected cells has a significant impact on ADCC responses.

Summary Antibodies can have an impact on HIV-1 infection in multiple ways, including antibody-dependent cellular cytotoxicity (ADCC), a correlate of protection observed in the RV144 vaccine trial. One of the most potent ADCC-inducing epitopes on HIV-1 Env is recognized by the C11 antibody. Here, we present the crystal structure, at 2.9 A resolution, of the C11-like antibody N12-i3, in a quaternary complex with the HIV-1 gp120, a CD4-mimicking peptide M48U1, and an A32-like antibody, N5-i5. Antibody N12-i3 recognizes an epitope centered on the N-terminal "eighth strand" of a critical β sandwich, which our analysis indicates to be emblematic of a late-entry state, after the gp120 detachment. In prior entry states, this sandwich comprises only seven strands, with the eighth strand instead pairing with a portion of the gp120 C terminus. The conformational gymnastics of HIV-1 gp120 thus includes altered β-strand pairing, possibly to reduce immunogenicity, although nevertheless still recognized by the human immune system.

Antibodies recognizing conserved CD4-induced (CD4i) epitopes on human immunodeficiency virus type 1 (HIV-1) Env and able to mediate antibody-dependent cellular cytotoxicity (ADCC) have been shown to be present in sera from most HIV-1-infected individuals. These antibodies preferentially recognize Env in its CD4-bound conformation. CD4 downregulation by Nef and Vpu dramatically reduces exposure of CD4i HIV-1 Env epitopes and therefore reduce the susceptibility of HIV-1-infected cells to ADCC mediated by HIV-positive (HIV+) sera. Importantly, this mechanism of immune evasion can be circumvented with small-molecule CD4 mimetics (CD4mc) that are able to transition Env into the CD4-bound conformation and sensitize HIV-1-infected cells to ADCC mediated by HIV+ sera. However, HIV-1 developed additional mechanisms to avoid ADCC, including Vpu-mediated BST-2 antagonism, which decreases the overall amount of Env present at the cell surface. Accordingly, BST-2 upregulation in response to alpha interferon (IFN-α) was shown to increase the susceptibility of HIV-1-infected cells to ADCC despite the activity of Vpu. Here we show that BST-2 upregulation by IFN-β and interleukin-27 (IL-27) also increases the surface expression of Env and thus boosts the ability of CD4mc to sensitize HIV-1-infected cells to ADCC by sera from HIV-1-infected individuals. IMPORTANCE HIV-1 evolved sophisticated strategies to conceal Env epitopes from ADCC-mediating antibodies present in HIV+ sera. Vpu-mediated BST-2 downregulation was shown to decrease ADCC responses by limiting the amount of Env present at the cell surface. This effect of Vpu was shown to be attenuated by IFN-α treatment. Here we show that in addition to IFN-α, IFN-β and IL-27 also affect Vpu-mediated BST-2 downregulation and greatly enhance ADCC responses against HIV-1-infected cells in the presence of CD4mc. These findings may inform strategies aimed at HIV prevention and eradication.

Interactions between the gp120 and gp41 subunits of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer maintain the metastable unliganded form of the viral spike. Binding of gp120 to the receptor, CD4, changes the Env conformation to promote gp120 interaction with the second receptor, CCR5 or CXCR4. CD4 binding also induces the transformation of Env into the prehairpin intermediate, in which the gp41 heptad repeat 1 (HR1) coiled coil is assembled at the trimer axis. In nature, HIV-1 Envs must balance the requirements to maintain the noncovalent association of gp120 with gp41 and to evade the host antibody response with the need to respond to CD4 binding. Here we show that the gp41 HR1 region contributes to gp120 association with the unliganded Env trimer. Changes in particular amino acid residues in the gp41 HR1 region decreased the efficiency with which Env moved from the unliganded state. Thus, these gp41 changes decreased the sensitivity of HIV-1 to cold inactivation and ligands that require Env conformational changes to bind efficiently. Conversely, these gp41 changes increased HIV-1 sensitivity to small-molecule entry inhibitors that block Env conformational changes induced by CD4. Changes in particular gp41 HR1 amino acid residues can apparently affect the relative stability of the unliganded state and CD4-induced conformations. Thus, the gp41 HR1 region contributes to the association with gp120 and regulates Env transitions from the unliganded state to downstream conformations. IMPORTANCE The development of an efficient vaccine able to prevent HIV infection is a worldwide priority. Knowledge of the envelope glycoprotein structure and the conformational changes that occur after receptor engagement will help researchers to develop an immunogen able to elicit antibodies that block HIV-1 transmission. Here we identify residues in the HIV-1 transmembrane envelope glycoprotein that stabilize the unliganded state by modulating the transitions from the unliganded state to the CD4-bound state.

SERINC5 is able to restrict HIV-1 infection by drastically impairing the infectivity of viral particles. Studies have shown that the HIV-1 Nef protein counters SERINC5 through downregulating SERINC5 from the cell surface and preventing the virion incorporation of SERINC5. In addition, the Env proteins of some HIV-1 strains can also overcome SERINC5 inhibition. However, it is unclear how HIV-1 Env does so and why HIV-1 has two mechanisms to resist SERINC5 inhibition. The results of this study show that neither Env nor Nef prevents high levels of ectopic SERINC5 from being incorporated into HIV-1 particles, except that Env, but not Nef, is able to resist inhibition by virion-associated SERINC5. Testing of a panel of HIV-1 Env proteins from different subtypes revealed a high frequency of SERINC5-resistant Envs. Interestingly, although the SERINC5-bearing viruses were not inhibited by SERINC5 itself, they became more sensitive to the CCR5 inhibitor maraviroc and some neutralizing antibodies than the SERINC5-free viruses, which suggests a possible influence of SERINC5 on Env function. We conclude that HIV-1 Env is able to overcome SERINC5 without preventing SERINC5 virion incorporation. IMPORTANCE HIV-1 Nef is known to enhance the infectivity of HIV-1 particles and to contribute to the maintenance of high viral loads in patients. However, the underlying molecular mechanism remained elusive until the recent discovery of the antiviral activity of SERINC5. SERINC5 profoundly inhibits HIV-1 but is antagonized by Nef, which prevents the incorporation of SERINC5 into viral particles. Here, we show that HIV-1 Env, but not Nef, is able to resist high levels of SERINC5 without excluding SERINC5 from incorporation into viral particles. However, the virion-associated SERINC5 renders HIV-1 more sensitive to some broadly neutralizing antibodies. It is possible that, under the pressure of some neutralizing antibodies in vivo , HIV-1 needs Nef to remove SERINC5 from viral particles, even though viral Env is able to resist virion-associated SERINC5.

Magnetic resin microspheres called MPMDG2 were prepared by suspension polymerization combined with basic and acidic hydrolysis. The adsorption property of resin microspheres to heavy metal ions was investigated. Structural and morphological analysis revealed that the resin had high specific surface area and mesoporous structure. The resin contained about 9.2 wt% Fe3O4 and exhibited a high magnetic response. Adsorption experiments showed that the resin can selectively absorb Cr(III) and Pb(II) ions. The adsorption process was well described by a pseudo-second-order kinetic model, and the equilibrium adsorption data fitted the Langmuir isotherm model better than the Freundlich model. Ion exchange along with chemistry chelating was the most probable mechanisms for the adsorption of metal ions on the resin. The superior magnetic response, regeneration and selective adsorption property of the MPMDG2 make it a good candidate as an adsorbent for removing Cr(III), Pb(II) and Cu(II) from wastewater.

The HIV-1 envelope glycoprotein (Env) (gp120-gp41)3 is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different conformational states. Before engaging CD4, Env adopts a closed conformation (State 1) that is largely antibody resistant. CD4 binding induces an intermediate state (State 2), followed by an open conformation (State 3) that is susceptible to engagement by antibodies that recognize otherwise occluded epitopes. We investigate conformational changes in Env that induce ADCC in the presence of a small-molecule CD4-mimetic compound (CD4mc). We uncover an asymmetric Env conformation (State 2A) recognized by antibodies targeting the conserved gp120 inner domain and mediating ADCC. Sera from HIV+ individuals contain these antibodies, which can stabilize Env State 2A in combination with CD4mc. Additionally, triggering State 2A on HIV-infected primary CD4+ T cells exposes epitopes that induce ADCC. Strategies that induce this Env conformation may represent approaches to fight HIV-1 infection.

Antibodies that mediate killing of HIV-infected cells through antibody-dependent cellular cytotoxicity (ADCC) have been implicated in protection from HIV infection and disease progression. Despite these observations, these types of HIV antibodies are understudied compared to neutralizing antibodies. Here we describe four monoclonal antibodies (mAbs) obtained from one individual that target the HIV transmembrane protein, gp41, and mediate ADCC activity. These four mAbs arose from independent B cell lineages suggesting that in this individual, multiple B cell responses were induced by the gp41 antigen. Competition and phage peptide display mapping experiments suggested that two of the mAbs target epitopes in the cysteine loop that are highly conserved and a common target of HIV gp41-specific antibodies. The amino acid sequences that bind these mAbs are overlapping but distinct. The two other mAbs were competed by mAbs that target the C-terminal heptad repeat (CHR) and the fusion peptide proximal region (FPPR) and appear to both target a similar unique conformational epitope. These gp41-specific mAbs mediated killing of infected cells that express high levels of Env due to either pre-treatment with interferon or deletion of vpu to increase levels of BST-2/Tetherin. They also mediate killing of target cells coated with various forms of the gp41 protein, including full-length gp41, gp41 ectodomain or a mimetic of the gp41 stump. Unlike many ADCC mAbs that target HIV gp120, these gp41-mAbs are not dependent on Env structural changes associated with membrane-bound CD4 interaction. Overall, the characterization of these four new mAbs that target gp41 and mediate ADCC provides evidence for diverse gp41 B cell lineages with overlapping but distinct epitopes within an individual. Such antibodies that can target various forms of envelope protein could represent a common response to a relatively conserved HIV epitope for a vaccine., Author summary Anti-HIV antibodies can mediate activity by neutralizing cell-free virus, or binding to infected cells and driving antibody-dependent cellular cytotoxicity (ADCC). While numerous discovery efforts have identified and characterized neutralizing antibodies, much less is known about antibodies that mediate ADCC. Here we describe four new antibodies that target the gp41 transmembrane protein of the HIV envelope. Competition experiments and peptide mapping studies together helped narrow down the binding sites for the four antibodies to two conserved regions of the protein. One pair of antibodies targets a common epitope of gp41 while the other pair binds to a more complex discontinuous epitope. In vitro activity assays indicated that this second pair of antibodies could drive killing against cells coated with various forms of gp41, and both pairs of antibodies could drive killing of HIV-infected cells. Inducing these types of antibodies following vaccination may represent a more straightforward path to generating a consistent, functional response to a more conserved portion of the HIV envelope protein.

SummaryThe interferon-inducible myxovirus resistance (Mx) proteins play important roles in combating a wide range of virus infections. MxA inhibits many RNA and DNA viruses, whereas the antiviral activity of MxB is less well established. We find that human MxB inhibits HIV-1 infection by reducing the level of integrated viral DNA. Passaging HIV-1 through MxB-expressing cells allowed the evolution of a mutant virus that escapes MxB restriction. HIV-1 escapes MxB restriction by mutating the alanine residue at position 88 in the viral capsid protein (CA), with a consequent loss of CA interaction with the host peptidylprolyl isomerase cyclophilin A (CypA), suggesting a role for CypA in MxB restriction. Consistent with this, MxB associates with CypA, and shRNA-mediated CypA depletion or cyclosporine A treatment resulted in the loss of MxB inhibition of HIV-1. Taken together, we conclude that human MxB protein inhibits HIV-1 DNA integration by a CypA-dependent mechanism.

A series of catalysts made of tungsten oxide loaded on SiO 2 , γ-Al 2 O 3 , SiO 2 –Al 2 O 3 and silica deposited γ-alumina are tested for 1-butene metathesis. Among these catalysts, the catalyst 6W/20SiO 2 /Al 2 O 3 gives the highest activity for 1-butene metathesis reaction with 1-butene conversion up to 71 mol% and the yield of propene up to 21 mol%. The excellent catalytic activity is related to the moderate dispersion of tungsten oxide and the suitable acidity of the support. The dispersion of WO x species and the acidity of supports were studied by characterization of XRD, Raman spectra, UV–vis, H 2 -TPR and NH 3 -TPD in detail. The surface properties of silica modified γ-alumina leads to the moderate aggregation of supported tungsten oxide, which appears to be more effective for 1-butene metathesis at the low temperature of 453 K. Optimized activity was realized by tuning the dispersion of tungsten species on silica deposited alumina.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by non-neutralizing antibodies (nnAbs) specific to the HIV envelope (Env) glycoproteins present at the surface of virus sensitized or infected cells plays a role in the effective adaptive immune response to HIV. Here, we explore the molecular basis for the epitope at the disulfide loop region (DLR) of the principal immunodominant domain of gp41, recognized by the well-known nnAb F240. Our structural studies reveal details of the F240-gp41 interface and describe a structure of DLR that is distinct from known conformations of this region studied in the context of either CD4-unliganded Env trimer or the gp41 peptide in the unbound state. These data coupled with binding and functional analyses indicate that F240 recognizes non-trimeric Env forms which are significantly overexpressed on intact virions but poorly represented at surfaces of cells infected with infectious molecular clones and endogenously-infected CD4 T cells from HIV-1-infected individuals. Furthermore, although we detect ADCC activities of F240 against cells spinoculated with intact virions, our data suggest that these activities result from F240 recognition of gp41 stumps or misfolded Env variants present on virions rather than its ability to recognize functional gp41 transition structures emerging on trimeric Env post CD4 receptor engagement.

Previous studies have shown that highly conserved residues in the inner domain of gp120 are required for HIV-1 envelope glycoprotein (Env) transitions to the CD4-bound conformation (A. Finzi, S. H. Xiang, B. Pacheco, L. Wang, J. Haight, et al., Mol Cell 37: 656–667, 2010, http://dx.doi.org/10.1016/j.molcel.2010.02.012 ; A. Desormeaux, M. Coutu, H. Medjahed, B. Pacheco, A. Herschhorn, et al., J Virol 87: 2549–2562, 2013, http://dx.doi.org/10.1128/JVI.03104-12 ). Moreover, W69, a highly conserved residue located at the interface between layer 1 and layer 2 of the inner domain, was recently shown to be important for efficient Env recognition by CD4-induced (CD4i) antibodies capable of potent antibody-dependent cellular cytotoxicity (W. D. Tolbert, N. Gohain, M. Veillette, J. P. Chapleau, C. Orlandi, et al., 2016, Structure 24: 697–709, http://dx.doi.org/10.1016/j.str.2016.03.005 ; S. Ding, M. Veillette, M. Coutu, J. Prevost, L. Scharf, et al., 2016, J Virol 90: 2127–2134, http://dx.doi.org/10.1128/JVI.02779-15 ). We evaluated the contribution of the hydrophobicity of W69 to conformational changes of Env by replacing it with a series of residues with aliphatic or aromatic side chains of decreasing chain length. We have found that the hydrophobicity of residue 69 is important for Env processing, CD4 binding, and its transition to the CD4-bound conformation. The most deleterious effect was observed when W69 was replaced with alanine or glycine residues. However, the functions lost due to W69 mutations could be progressively restored with amino acids of increasing aliphatic chain length and fully recovered with residues bearing an aromatic ring. Interestingly, poor CD4 binding of W69A could be fully restored by introducing a compensatory mutation within layer 2 (S115W). Structural studies of HIV-1 gp120 core e W69A/S115W mutant bound to the CD4 peptide mimetic M48U1 and Fab of anti-cluster A antibody N60-i3 revealed no perturbations to the overall structure of the double mutant compared to the wild-type protein but identified higher mobility within the interface between layer 1 and layer 2, the bridging sheet region, and the CD4 binding site. IMPORTANCE HIV-1 Env transitions to the CD4-bound conformation are required for viral entry. Previous studies identified a highly conserved residue of the inner domain, W69, as being involved in these conformational transitions (A. Finzi, S. H. Xiang, B. Pacheco, L. Wang, J. Haight, et al., Mol Cell 37:656–667, 2010, http://dx.doi.org/10.1016/j.molcel.2010.02.012 ). Here, we show that W69, located at the interface between gp120 and gp41 in the PGT151-bound trimer, plays a critical role in the interprotomer signaling induced by CD4 binding. This new information might be useful in immunogen design.

Previous studies have shown that sera from HIV-1-infected individuals contain antibodies able to mediate antibody-dependent cellular cytotoxicity (ADCC). These antibodies preferentially recognize envelope glycoprotein (Env) epitopes induced upon CD4 binding. Here, we show that a highly conserved tryptophan at position 69 of the gp120 inner domain is important for ADCC mediated by anti-cluster A antibodies and sera from HIV-1-infected individuals.

We report key mechanistic differences between the reverse transcriptases (RT) of human immunodeficiency virus type-1 (HIV-1) and of xenotropic murine leukemia virus-related virus (XMRV), a gammaretrovirus that can infect human cells. Steady and pre-steady state kinetics demonstrated that XMRV RT is significantly less efficient in DNA synthesis and in unblocking chain-terminated primers. Surface plasmon resonance experiments showed that the gammaretroviral enzyme has a remarkably higher dissociation rate (k(off)) from DNA, which also results in lower processivity than HIV-1 RT. Transient kinetics of mismatch incorporation revealed that XMRV RT has higher fidelity than HIV-1 RT. We identified RNA aptamers that potently inhibit XMRV, but not HIV-1 RT. XMRV RT is highly susceptible to some nucleoside RT inhibitors, including Translocation Deficient RT inhibitors, but not to non-nucleoside RT inhibitors. We demonstrated that XMRV RT mutants K103R and Q190M, which are equivalent to HIV-1 mutants that are resistant to tenofovir (K65R) and AZT (Q151M), are also resistant to the respective drugs, suggesting that XMRV can acquire resistance to these compounds through the decreased incorporation mechanism reported in HIV-1.

An effective method for modification of ordered mesoporous carbons is to dope boron incorporated into carbon network for improving their properties in many aspects. A one-pot synthesis is proposed with the combination of boron doping and fabrication of mesoporous carbon through sol–gel method using boric acid as the catalyst, dopant and pore-forming agent. The as-prepared materials were characterized by TEM, small-angle and wide-angle XRD, Raman, nitrogen sorption, SEM, XPS and 11 B MAS NMR measurements. And the comprehensive analysis shows the homogeneous dispersion of boron incorporated into the mesoporous carbon and indicates the presence of different boron chemical environments in the carbon. The short-cut route can simplify the synthesis process and get homogeneous dispersion of boron in carbon in both energy- and time-saving fashions, which provides a new strategy for making doped carbon materials.

SummaryThe interferon-induced transmembrane (IFITM) proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection.

Exchange bias (EB) effect has been intensively studied for more than half century due to its applications in spintronics devices, such as giant magneto resistance (GMR) read heads and magnetic random access memory (MRAM).[1] Except for conventional ferromagnetic (FM)-antiferromag-netic (AFM) system, EB has also been reported in other magnetic systems, such as ferromagnetic (FM)-ferromagnetic (FIM) system, spin glasses (SG) and nanoparticles with surface spin disorder. The most studied FM-FIM system is the Fe/Fe 3 O 4 core shell structure. It is believed that the inter-facial SG state plays a major role in the EB of this system.[2,3] However, all the studies have aimed to the stably oxidized Fe nanoparticles. The effect of the FIM thickness on the EB in this system has been neglected. In this study, a controlled oxidizing procedure was adopted to obtain Fe/Fe 3 O 4 nanoparticles with different Fe 3 O 4 thickness. The Fe 3 O 4 thickness dependence of the EB was studied.

The interferon-inducible transmembrane (IFITM) proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1) strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1NL4-3) is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1NL4-3 is profoundly inhibited by an IFITM1 mutant, known as Δ(117-125), which is deleted of 9 amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117-125) mutant diminishes HIV-1NL4-3 entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117-125) to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117-125), mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the antiviral function through controlling protein subcellular localization.

Here, we report the realization of epitaxial Y3Fe5O12 (YIG) thin films with perpendicular magnetic anisotropy (PMA). The films are grown on the substituted gadolinium gallium garnet substrate (SGGG) by pulsed laser deposition. It was found that a thin buffer layer of Sm3Ga5O12 (SmGG) grown on top of SGGG can suppress the strain relaxation, which helps induce a large enough PMA to overcome the shape anisotropy in YIG thin films. The reciprocal space mappings analysis reveals that the in-plane strain relaxation is suppressed, while the out-of-plane strain relaxation exhibits a strong dependence on the film thickness. We found that the PMA can be achieved for both bilayer (YIG/SmGG) and tri-layer (SmGG/YIG/SmGG) structural films with YIG layer thicknesses up to 20 nm and 40 nm, respectively.

Background Interferon protects cells from virus infection by inducing the expression of genes with antiviral activities. One such antiviral gene is Mx (myxovirus resistance) that was first identified in mice for its protection against influenza virus infection. Humans carry two Mx genes, MxA and MxB. Although MxA has been reported to inhibit a number of RNA and DNA viruses, the antiviral function of MxB has just begun to be revealed.