Nuclear Quantum Effects in Liquid Water Are Marginal for Its Average Structure but Significant for Dynamics.

Isotopic substitution, which can be realized in both experiment and computer simulations, is a direct approach to assess the role of nuclear quantum effects on the structure and dynamics of matter. However, the impact of nuclear quantum effects on the structure of liquid water as probed in experiment by comparing normal to heavy water has remained controversial. To settle this issue, we employ a highly accurate machine-learned high-dimensional neural network potential to perform converged coupled cluster-quality path integral simulations of liquid HO versus DO at ambient conditions.

Synthesis and Stability of Biomolecules in C-H-O-N Fluids under Earth's Upper Mantle Conditions.

How life started on Earth is an unsolved mystery. There are various hypotheses for the location ranging from outer space to the seafloor, subseafloor, or potentially deeper. Here, we applied extensive ab initio molecular dynamics simulations to study chemical reactions between NH, HO, H, and CO at pressures () and temperatures () approximating the conditions of Earth's upper mantle (i.

Nanoconfinement facilitates reactions of carbon dioxide in supercritical water.

The reactions of CO in water under extreme pressure-temperature conditions are of great importance to the carbon storage and transport below Earth's surface, which substantially affect the carbon budget in the atmosphere. Previous studies focus on the CO(aq) solutions in the bulk phase, but underground aqueous solutions are often confined to the nanoscale, and nanoconfinement and solid-liquid interfaces may substantially affect chemical speciation and reaction mechanisms, which are poorly known on the molecular scale. Here, we apply extensive ab initio molecular dynamics simulations to study aqueous carbon solutions nanoconfined by graphene and stishovite (SiO) at 10 GPa and 1000 ~ 1400 K.

The Lightest 2D Nanomaterial: Freestanding Ultrathin Li Nanosheets by In Situ Nanoscale Electrochemistry.

As the lightest solid element and also the simplest metal, lithium (Li) is one of the best representations of quasi-free electron model in both bulk form and the reduced dimensions. Herein, the controlled growth of 2D ultrathin Li nanosheets is demonstrated by utilizing an in situ electrochemical platform built inside transmission electron microscope (TEM). The as-grown freestanding 2D Li nanosheets have strong structure-anisotropy with large lateral dimensions up to several hundreds of nanometers and thickness limited to just a few nanometers.

Water-Gas Shift Reaction Produces Formate at Extreme Pressures and Temperatures in Deep Earth Fluids.

The water-gas shift reaction is one of the most important reactions in industrial hydrogen production and plays a key role in Fischer-Tropsch-type synthesis, which is widely believed to generate hydrocarbons in the deep carbon cycle but is little known at extreme pressure-temperature conditions found in the Earth's upper mantle. Here, we performed extensive ab initio molecular dynamics simulations and free energy calculations to study the water-gas shift reaction. We found the direct formation of formic acid from CO and supercritical water at 10-13 GPa and 1400 K without any catalyst.

Large Presence of Carbonic Acid in CO-Rich Aqueous Fluids under Earth's Mantle Conditions.

The chemistry of carbon in aqueous fluids at extreme pressure and temperature conditions is of great importance to Earth's deep carbon cycle, which substantially affects the carbon budget at Earth's surface and global climate change. At ambient conditions, the concentration of carbonic acid in water is negligible; therefore, aqueous carbonic acid was simply ignored in previous geochemical models. However, by applying extensive ab initio molecular dynamics simulations at pressure and temperature conditions similar to those in Earth's upper mantle, we found that carbonic acid can be the most abundant carbon species in aqueous CO solutions at ∼10 GPa and 1000 K.

Interface charge-transfer induced intralayer excited-state biexcitons in graphene/WS van der Waals heterostructures.

Monolayer transition metal dichalcogenides (TMDCs) are an ideal platform for multi-carrier bound states, the excitons and trions of which have been well identified and investigated. However, the formation and identification of biexcitons with certain configurations are more complicated. Here, we report a strategy to generate the hole-trion bound state, i.

A simian immunodeficiency virus V3 loop mutant that does not efficiently use CCR5 or common alternative coreceptors is moderately attenuated in vivo.

Sexually transmitted HIV-1 strains utilize the chemokine receptor CCR5 for viral entry and inhibitors targeting this coreceptor offer great promise for antiretroviral therapy. They also raise the question, however, whether viral variants exhibiting altered coreceptor interactions and resistance against these antiviral agents might still be pathogenic. In the present study, we analyzed a SIVmac239 envelope (Env) mutant (239DL) containing two mutations in the V3 loop which reduced viral entry via CCR5 by 10- to 20-fold, disrupted utilization of common alternative SIV coreceptors and changed the way Env engaged CCR5.

Importance of the N-distal AP-2 binding element in Nef for simian immunodeficiency virus replication and pathogenicity in rhesus macaques.

Point mutations in SIVmac239 Nef disrupting CD4 downmodulation and enhancement of virion infectivity attenuate viral replication in acutely infected rhesus macaques, but changes selected later in infection fully restore Nef function (A. J. Iafrate et al.

Induction of neutralising antibodies restricts the use of human granulocyte/macrophage colony stimulating factor for vaccine studies in rhesus macaques.

Granulocyte/macrophage-colony stimulating factor (GM-CSF) is a valuable adjuvant to enhance induction of cellular immune responses in rodents. Less information is available regarding its use as an adjuvant in primates or humans. We explored recombinant human GM-CSF for potential vaccine studies in rhesus macaques and focused on its effect on peripheral monocytes as progenitors of dendritic cells and its potential immunogenicity.

Reactivation of a Trypanosoma cruzi infection in a rhesus monkey (Macaca mulatta) experimentally infected with SIV.

Trypanosoma cruzi-like flagellates were incidentally noted in blood smears of a routinely monitored rhesus monkey experimentally infected with the simian immunodeficiency virus (SIV). Immunodeficiency in the course of the SIV infection reactivated a chronic infection of Chagas' disease that had been unnoticed when the macaque was imported to Europe. The animal developed no specific clinical symptoms of American trypanosomiasis, but histologically a chagasic myocarditis was detected.

T-cell receptor:CD3 down-regulation is a selected in vivo function of simian immunodeficiency virus Nef but is not sufficient for effective viral replication in rhesus macaques.

We investigated the function of severely truncated simian immunodeficiency virus (SIV) Nef proteins (tNef) in vitro and in vivo. These variants emerged in rhesus monkeys infected with SIVmac239 containing a 152-bp deletion in the nef-unique region and have been suggested to enhance SIV virulence (E. T.

Lack of simian immunodeficiency virus (SIV) specific IgA response in the intestine of SIV infected rhesus macaques.

Background: Little is known about secretory immunity-the major defence mechanism at mucosal surfaces-in human immunodeficiency virus (HIV) infected patients, especially in the early stages of the disease.

Aims: The aim of the study was to analyse mucosal immunoglobulin production and simian immunodeficiency virus (SIV) specific antibody response in the intestinal mucosa during the course of SIV infection in comparison with serum and saliva.

Animals And Methods: IgG, IgA, and IgM concentrations were determined in supernatants of short term cultured duodenal biopsies, serum, and saliva from SIV infected rhesus macaques (n=8) and controls (n=2) by ELISA at defined times before and after infection.

The simian immunodeficiency virus deltaNef vaccine, after application to the tonsils of Rhesus macaques, replicates primarily within CD4(+) T cells and elicits a local perforin-positive CD8(+) T-cell response.

Deletion of the nef gene from simian immunodeficiency virus (SIV) strain SIVmac239 yields a virus that undergoes attenuated growth in rhesus macaques and offers substantial protection against a subsequent challenge with some SIV wild-type viruses. We used a recently described model to identify sites in which the SIVDeltanef vaccine strain replicates and elicits immunity in vivo. A high dose of SIVDeltanef was applied to the palatine and lingual tonsils, where it replicated vigorously in this portal of entry at 7 days.

Efficient class I major histocompatibility complex down-regulation by simian immunodeficiency virus Nef is associated with a strong selective advantage in infected rhesus macaques.

Substitution of Y223F disrupts the ability of simian immunodeficiency virus (SIV) Nef to down-modulate major histocompatibility complex (MHC) class I from the cell surface but has no effect on other Nef functions, such as down-regulation of CD4, CD28, and CD3 cell surface expression or stimulation of viral replication and enhancement of virion infectivity. Inoculation of three rhesus macaques with the SIVmac239 Y223F-Nef variant revealed that this point mutation consistently reverts and that Nef activity in MHC class I down-modulation is fully restored within 4 weeks after infection. Our results demonstrate a strong selective pressure for a tyrosine at amino acid position 223 in SIV Nef, and they constitute evidence that Nef-mediated MHC class I down-regulation provides a selective advantage for viral replication in vivo.

Simian immunodeficiency virus in which nef and U3 sequences do not overlap replicates efficiently in vitro and in vivo in rhesus macaques.

The nef genes of human immunodeficiency virus and simian immunodeficiency virus (SIV) overlap about 80% of the U3 region of the 3' long terminal repeat (LTR) and contain several essential cis-acting elements (here referred to as the TPI region): a T-rich region, the polypurine tract, and attachment (att) sequences required for integration. We inactivated the TPI region in the nef reading frame of the pathogenic SIVmac239 clone (239wt) by 13 silent point mutations. To restore viral infectivity, intact cis-regulatory elements were inserted just downstream of the mutated nef gene.

Simian immunodeficiency virus containing mutations in N-terminal tyrosine residues and in the PxxP motif in Nef replicates efficiently in rhesus macaques.

SIVmac Nef contains two N-terminal tyrosines that were proposed to be part of an SH2-ligand domain and/or a tyrosine-based endocytosis signal and a putative SH3-ligand domain (P(104)xxP(107)). In the present study, we investigated the effects of combined mutations in these tyrosine and proline residues on simian immunodeficiency virus (SIV) Nef interactions with the cellular signal transduction and endocytic machinery. We found that mutation of Y(28)F, Y(39)F, P(104)A, and P(107)A (FFAA-Nef) had little effect on Nef functions such as the association with the cellular tyrosine kinase Src, downregulation of cell surface expression of CD4 and class I major histocompatibility complex, and enhancement of virion infectivity.

Enhanced cellular immune response and reduced CD8(+) lymphocyte apoptosis in acutely SIV-infected Rhesus macaques after short-term antiretroviral treatment.

Losing the decisive virus-specific functions of both CD4(+) and CD8(+) T lymphocytes in the first weeks after immunodeficiency virus infection ultimately leads to AIDS. The SIV/rhesus monkey model for AIDS was used to demonstrate that a 4-week chemotherapeutic reduction of viral load during acute SIV infection of macaques allowed the development of a competent immune response able to control virus replication after discontinuation of treatment in two of five monkeys. Increasing SIV-specific CD4(+) T-helper-cell proliferation was found in all macaques several weeks after treatment, independent of their viral load.

Total numbers of lymphocyte subsets in different lymph node regions of uninfected and SIV-infected macaques.

Human immunodeficiency virus (HIV) infection leads to a decline of CD4+ T-cells in blood. Because blood represents only a small proportion of the total lymphocyte pool, it is important to investigate other lymphoid organs. So far, only relative proportions of lymphocyte subsets in single peripheral lymph node (LN) regions of HIV-infected patients and simian immunodeficiency virus (SIV)-infected macaques have been documented.

Packaging of small molecules into VP1-virus-like particles of the human polyomavirus JC virus.

Recombinantly expressed VP1-virus-like particles (VP1-VLP) of human polyomavirus JC virus (JCV) were described recently as a new DNA transporter system. It was shown that DNA molecules could be packaged into VP1-VLP during a controlled chemical reassociation/dissociation process. In the present study VP1-VLP were studied as carriers for pharmaceutical substances.

Homozygosity for a conserved Mhc class II DQ-DRB haplotype is associated with rapid disease progression in simian immunodeficiency virus-infected macaques: results from a prospective study.

In human immunodeficiency virus type 1 (HIV-1)-infected individuals, disease progression varies considerably. This is also observed after experimental infection of macaques with simian immunodeficiency virus (SIV). Major histocompatibility complex (MHC) genes may influence disease progression in both species.

Co-receptor usage of BOB/GPR15 in addition to CCR5 has no significant effect on replication of simian immunodeficiency virus in vivo.

Human immunodeficiency virus type 2 (HIV-2) and the closely related simian immunodeficiency viruses (SIVs) frequently use the orphan receptor BOB/GPR15 in addition to the chemokine receptor CCR5 for efficient entry and replication. However, the role of BOB/GPR15 in replication and pathogenesis of HIV-2 and SIV in vivo is unclear. This study shows that a single amino acid substitution in the V3 loop of the pathogenic SIVmac239 clone, 321P-->S, impaired the ability to use BOB/GPR15 for entry and replication but had little effect on the ability to use CCR5.

The human immunodeficiency virus type 1 nef gene can to a large extent replace simian immunodeficiency virus nef in vivo.

The nef gene of the pathogenic simian immunodeficiency virus (SIV) 239 clone was replaced with primary human immunodeficiency virus type 1 (HIV-1) nef alleles to investigate whether HIV-1 Nef can substitute for SIV Nef in vivo. Initially, two rhesus macaques were infected with the chimeric viruses (Nef-SHIVs). Most of the nef alleles obtained from both animals predicted intact open reading frames.

Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus.

The early events during infection with an immunodeficiency virus were followed by application of pathogenic simian immunodeficiency virus atraumatically to the tonsils of macaques. Analyses by virologic assays and in situ hybridization revealed that the infection started locally in the tonsils, a mucosal-associated lymphoid organ, and quickly spread to other lymphoid tissues. At day 3, there were few infected cells, but then the number increased rapidly, reaching a high plateau between days 4 and 7.