Biogeochemical factors affecting mercury methylation rate in two contaminated floodplain soils

An automated biogeochemical microcosm system allowing controlled variation of redox potential (EH) in soil suspensions was used to assess the effect of various factors on the mobility of mercury (Hg) as well as on the methylation of Hg in two contaminated floodplain soils with different Hg concentrations (approximately 5 mg Hg kg(-1) and > 30 mg Hg kg(-1)). The experiment was conducted under stepwise variation from reducing (approximately -350 mV at pH 5) to oxidizing conditions (approximately 600 mV at pH 5). Results of phospholipid fatty acids (PLFA) analysis indicate the occurrence of sulfate reducing bacteria (SRB) such as Desulfobacter species (10Me16:0, cy17:0, 10Me18:0, cy19:0) or Desulfovibrio species (18:2 omega 6,9), which are considered to promote Hg methylation. The products of the methylation process are lipophilic, highly toxic methyl mercury species such as the monomethyl mercury ion [MeHg+], which is named as MeHg here. The ln(MeHg/Hg-t) ratio is assumed to reflect the net production of monomethyl mercury normalized to total dissolved Hg (Hg-t) concentration. This ratio increases with rising dissolved organic carbon (DOC) to Hg-t ratio (ln(DOC/Hg-t) ratio) (R-2 = 0.39, p < 0.0001, n = 63) whereas the relation between ln(MeHg/Hg-t) ratio and lnDOC is weaker (R-2 = 0.09; p < 0.05; n = 63). In conclusion, the DOC/Hg-t ratio might be a more important factor for the Hg net methylation than DOC alone in the current study. Redox variations seem to affect the biogeochemical behavior of dissolved inorganic Hg species and MeHg indirectly through related changes in DOC, sulfur cycle, and microbial community structure whereas EH and pH values, as well as concentration of dissolved Fe3+/Fe2+ and Cl-seem to play subordinate roles in Hg mobilization and methylation under our experimental condition

Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection

Dendritic cells can capture and transfer retroviruses in vitro across synaptic cell-cell contacts to uninfected cells, a process called trans-infection. Whether trans-infection contributes to retroviral spread in vivo remains unknown. Here, we visualize how retroviruses disseminate in secondary lymphoid tissues of living mice. We demonstrate that murine leukemia virus (MLV) and human immunodeficiency virus (HIV) are first captured by sinus-lining macrophages. CD169/Siglec-1, an I-type lectin that recognizes gangliosides, captures the virus. MLV-laden macrophages then form long-lived synaptic contacts to trans-infect B-1 cells. Infected B-1 cells subsequently migrate into the lymph node to spread the infection through virological synapses. Robust infection in lymph nodes and spleen requires CD169, suggesting that a combination of fluid-based movement followed by CD169-dependent trans-infection can contribute to viral spread

Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection

SummarySexual intercourse is the major route of HIV transmission. To identify endogenous factors that affect the efficiency of sexual viral transmission, we screened a complex peptide/protein library derived from human semen. We show that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus Infection (SEVI), capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen-mediated enhancement of HIV infection. Thus, they may play an important role in sexual transmission of HIV and could represent new targets for its prevention

Compression garments and fabric orthoses for rehabilitation and function: a systematic mapping review.

Background/aims: Compression garments, joint supports and dynamic movement orthoses all use elastic fibres and close-fitting designs and have been researched for their effects on movement. There is little cross-referencing between research into these interventions. This review aimed to improve inter-disciplinary understanding by analysing key characteristics of the published evidence. Methods: Systematic mapping reviews identify gaps in an evidence base and identify questions for more in-depth reviews. This review was conducted in-line with current guidance. MEDLINE, CINAHL and Sports Discuss were searched for primary research investigating compression garments and orthoses for movement and function. The following search terms were used: "elastane", "spandex", "Lycra", "elastomer*", "Theratog*", "compression", "Neoprene", "orthotic", "orthosis", "shorts", "garment*", "splint", "brace", "sock*" and "stockings". Studies were screened against predetermined criteria and key study characteristics extracted. Findings: Three hundred and fifty-one studies were selected and analysed. Compression garment research was most common (236 studies), followed by research into joint supports (64 studies) and dynamic movement orthoses (42 studies). Research largely reflects the purpose for which each intervention was originally designed. Common topics investigated include posture and movement control, proprioception and muscle activity. Pressure beneath compression garments was measured in 30% of studies. Conclusions: The review highlights a need for more robust study designs in patient populations and accurate description of interventions. There is a need for a review on the possible effects of compression and support on movement control which should be used to inform future primary research

Murine Leukemia Virus Spreading in Mice Impaired in the Biogenesis of Secretory Lysosomes and Ca2+-Regulated Exocytosis

Retroviruses have been observed to bud intracellularly into multivesicular bodies (MVB), in addition to the plasma membrane. Release from MVB is thought to occur by Ca(2+)-regulated fusion with the plasma membrane.To address the role of the MVB pathway in replication of the murine leukemia virus (MLV) we took advantage of mouse models for the Hermansky-Pudlak syndrome (HPS) and Griscelli syndrome. In humans, these disorders are characterized by hypopigmentation and immunological alterations that are caused by defects in the biogenesis and trafficking of MVBs and other lysosome related organelles. Neonatal mice for these disease models lacking functional AP-3, Rab27A and BLOC factors were infected with Moloney MLV and the spread of virus into bone marrow, spleen and thymus was monitored. We found a moderate reduction in MLV infection levels in most mutant mice, which differed by less than two-fold compared to wild-type mice. In vitro, MLV release form bone-marrow derived macrophages was slightly enhanced. Finally, we found no evidence for a Ca(2+)-regulated release pathway in vitro. Furthermore, MLV replication was only moderately affected in mice lacking Synaptotagmin VII, a Ca(2+)-sensor regulating lysosome fusion with the plasma membrane.Given that MLV spreading in mice depends on multiple rounds of replication even moderate reduction of virus release at the cellular level would accumulate and lead to a significant effect over time. Thus our in vivo and in vitro data collectively argue against an essential role for a MVB- and secretory lysosome-mediated pathway in the egress of MLV

Assembly of the Murine Leukemia Virus Is Directed towards Sites of Cell–Cell Contact

Applying 4D imaging, this study investigates the mechanism by which cell-cell contact enhances retrovirus spreading and demonstrates that viral budding is highly polarized towards sites of cell-cell contact

Live imaging of SARS-CoV-2 infection in mice reveals neutralizing antibodies require Fc function for optimal efficacy

Neutralizing antibodies (NAbs) are effective in treating COVID-19 but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment in prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. We visualized sequential spread of virus from the nasal cavity to the lungs followed by systemic spread to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days of infection. In addition to direct neutralization, in vivo efficacy required Fc effector functions of NAbs, with contributions from monocytes, neutrophils and natural killer cells, to dampen inflammatory responses and limit immunopathology. Thus, our study highlights the requirement of both Fab and Fc effector functions for an optimal in vivo efficacy afforded by NAbs against SARS-CoV-2

Organotypical tissue cultures from adult murine colon as an in vitro model of intestinal mucosa

Together with animal experiments, organotypical cell cultures are important models for analyzing cellular interactions of the mucosal epithelium and pathogenic mechanisms in the gastrointestinal tract. Here, we introduce a three-dimensional culture model from the adult mouse colon for cell biological investigations in an in vivo-like environment. These explant cultures were cultured for up to 2 weeks and maintained typical characteristics of the intestinal mucosa, including a high-prismatic epithelium with specific epithelial cell-to-cell connections, a basal lamina and various connective tissue cell types, as analyzed with immunohistological and electron microscopic methods. The function of the epithelium was tested by treating the cultures with dexamethasone, which resulted in a strong upregulation of the serum- and glucocorticoid-inducible kinase 1 similar to that found in vivo. The culture system was investigated in infection experiments with the fungal pathogen Candida albicans. Wildtype but not Δcph1/Δefg1-knockout Candida adhered to, penetrated and infiltrated the epithelial barrier. The results demonstrate the potential usefulness of this intestinal in vitro model for studying epithelial cell-cell interactions, cellular signaling and microbiological infections in a three-dimensional cell arrangement

The Scaffolding Protein Dlg1 Is a Negative Regulator of Cell-Free Virus Infectivity but Not of Cell-to-Cell HIV-1 Transmission in T Cells

Background: Cell-to-cell virus transmission of Human immunodeficiency virus type-1 (HIV-1) is predominantly mediated by cellular structures such as the virological synapse (VS). The VS formed between an HIV-1-infected T cell and a target T cell shares features with the immunological synapse (IS). We have previously identified the human homologue of the Drosophila Discs Large (Dlg1) protein as a new cellular partner for the HIV-1 Gag protein and a negative regulator of HIV-1 infectivity. Dlg1, a scaffolding protein plays a key role in clustering protein complexes in the plasma membrane at cellular contacts. It is implicated in IS formation and T cell signaling, but its role in HIV-1 cell-to-cell transmission was not studied before. Methodology/Principal Findings: Kinetics of HIV-1 infection in Dlg1-depleted Jurkat T cells show that Dlg1 modulates the replication of HIV-1. Single-cycle infectivity tests show that this modulation does not take place during early steps of the HIV-1 life cycle. Immunofluorescence studies of Dlg1-depleted Jurkat T cells show that while Dlg1 depletion affects IS formation, it does not affect HIV-1-induced VS formation. Co-culture assays and quantitative cell-to-cell HIV-1 transfer analyses show that Dlg1 depletion does not modify transfer of HIV-1 material from infected to target T cells, or HIV-1 transmission leading to productive infection via cell contact. Dlg1 depletion results in increased virus yield and infectivity of the viral particles produced. Particles with increased infectivity present an increase in their cholesterol content and during the first hours of T cell infection these particles induce higher accumulation of total HIV-1 DNA