Protein aggregates and abnormal proteins are toxic and associated with neurodegenerative diseases. There are several mechanisms to help cells get rid of aggregates but little is known on how cells ...prevent aggregate-prone proteins from being synthesised. The EBNA1 of the Epstein-Barr virus (EBV) evades the immune system by suppressing its own mRNA translation initiation in order to minimize the production of antigenic peptides for the major histocompatibility (MHC) class I pathway. Here we show that the emerging peptide of the disordered glycine-alanine repeat (GAr) within EBNA1 dislodges the nascent polypeptide-associated complex (NAC) from the ribosome. This results in the recruitment of nucleolin to the GAr-encoding mRNA and suppression of mRNA translation initiation in cis. Suppressing NAC alpha (NACA) expression prevents nucleolin from binding to the GAr mRNA and overcomes GAr-mediated translation inhibition. Taken together, these observations suggest that EBNA1 exploits a nascent protein quality control pathway to regulate its own rate of synthesis that is based on sensing the nascent GAr peptide by NAC followed by the recruitment of nucleolin to the GAr-encoding RNA sequence.
Colloid-sized microplastics (MPs) are ubiquitous in aquatic environments and can share the same transport route together with various crystalline, poorly crystalline and freshly formed iron oxides. ...However, the colloidal interactions between these colloid constituents are not fully understood. This study was designed to investigate the colloidal properties of polystyrene microplastics (PSMPs) under the influence of haematite, goethite, ferrihydrite and freshly formed Fe oxide (FFFO). Dynamic light scattering was coupled with a test tube method to observe changes in the surface charge and colloidal dynamics of suspensions of PSMPs and Fe oxides. The overall effects on the aggregation of PSMPs are found to decrease in the following order: FFFO > ferrihydrite > goethite > haematite. The effects of these Fe oxides are found to strongly depend on pH. While the crystalline oxides play a dominant role in the acidic environment, poorly crystalline oxides show greater effects on PSMP aggregation in an alkaline environment. Heteroaggregation due to decreasing electrostatic interactions is the major mechanism that governs the colloidal dynamics of PSMPs and Fe oxides. It can be inferred that the copresence of Fe oxides and MPs can delay the transport of MPs or even change the destination for MPs.
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•PSMPs carry negative charges and exhibit high mobility in aqueous solution.•Fe oxides show their ability to stimulate aggregation of PSMPs.•Heteroaggregation due to electrostatic interactions is the major mechanism.•Fe oxides and PSMPs can delay the transport of PSMPs.
The Epstein-Barr virus (EBV) is the first oncogenic virus described in human. EBV infects more than 90% of the human population worldwide, but most EBV infections are asymptomatic. After the primary ...infection, the virus persists lifelong in the memory B cells of the infected individuals. Under certain conditions the virus can cause several human cancers, that include lymphoproliferative disorders such as Burkitt and Hodgkin lymphomas and non-lymphoid malignancies such as 100% of nasopharyngeal carcinoma and 10% of gastric cancers. Each year, about 200,000 EBV-related cancers emerge, hence accounting for at least 1% of worldwide cancers. Like all gammaherpesviruses, EBV has evolved a strategy to escape the host immune system. This strategy is mainly based on the tight control of the expression of its Epstein-Barr nuclear antigen-1 (EBNA1) protein, the EBV-encoded genome maintenance protein. Indeed, EBNA1 is essential for viral genome replication and maintenance but, at the same time, is also highly antigenic and T cells raised against EBNA1 exist in infected individuals. For this reason, EBNA1 is considered as the Achilles heel of EBV and the virus has seemingly evolved a strategy that employs the binding of nucleolin, a host cell factor, to RNA G-quadruplex (rG4) within EBNA1 mRNA to limit its expression to the minimal level required for function while minimizing immune recognition. This review recapitulates in a historical way the knowledge accumulated on EBNA1 immune evasion and discusses how this rG4-dependent mechanism can be exploited as an intervention point to unveil EBV-related cancers to the immune system.
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Coronavirus disease 2019 (COVID-19) and associated social responses may uniquely affect people living with HIV (PLHIV). SARS-CoV-2 antibody testing and a cross-sectional survey on COVID-19’s ...socio-behavioral impacts were conducted among a large PLHIV cohort in Hanoi, Vietnam. We examined anonymous antibody test results for 1243 PLHIV (99.8%) from whom plasma was obtained and completed surveys were collected in June/July 2020, just after the end of the first COVID-19 outbreak and nationwide lockdown. Three participants (0.2%) tested positive for anti-SARS-CoV-2 IgG antibodies. HIV treatment was generally maintained without antiretroviral therapy interruption, but COVID-19 had substantial impacts on economic security and risky health behaviors among PLHIV, which may have amplified psychological stress. These findings highlight the need for continuous monitoring of COVID-19’s impacts on PLHIV and for efforts to mitigate these impacts.
The mobilization of arsenic (As) in paddy soil has received much attention because it might accelerate the transfer of As from soil to rice. This study aims to elucidate whether earthworms can ...mobilize As through their casts. Cast samples were collected from 23 different paddy fields in the Red River delta. We first analysed different forms of As through fractionation and then performed batch experiments under reducing conditions to identify factors that govern the mobility of As in casts. Because the dissociation of casts may induce colloids that carry As, the colloidal properties of cast suspensions were also examined. The median value of As in casts (obtained from aqua regia digestion) was 5.11 mg kg−1, which was lower than that in the surrounding soil (6.7 mg kg−1). Compared with the surrounding soil, casts contain less As, possibly because cast As is more labile and more easily lost due to leaching. Various processes, including the reductive dissolution of Fe oxides, decomposition of organic matter, and sorption competition of soluble anionic substances, such as P, Si and DOC, were found to strongly correlate with the release of As from casts. We propose that earthworms, via their casts, may accelerate the As cycle in paddy soils, potentially intensifying As exposure to human health. The dissociation of cast could release colloids containing As; therefore, the cotransport of As with cast-induced colloids should also be considered in future works.
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•In the Red River delta, earthworm casts contain approximately 5 mg As kg−1.•Cast As occurs in labile forms that can be easily released under reducing conditions.•Through their casts, earthworms may accelerate the As cycle in paddy soil.•Cast dissociation could release colloids that contain As.•Cotransport of As with cast-induced colloids should also be considered.
Abstract Background Integrated care models for HIV and substance use disorders (SUD) care are proposed as a strategy for closing gaps in the HIV care continuum and reaching decreasing HIV ...transmission. We examined attitudes regarding integration of HIV and SUD treatment among HIV-infected patients with illicit drug and unhealthy alcohol use. Method We conducted a cross-sectional survey of HIV-infected patients receiving care at 5 HIV clinics in Hanoi, Vietnam, regarding substance use and attitudes toward HIV and SUD treatment integration. We used multivariate logistic regression to identify correlates of integrated care preference. Result Among 312 participants with current or past illicit drug use or unhealthy alcohol use, 81.4% preferred integrated treatment for HIV and SUD. In multivariate analysis, completing a college education (aOR 0.22, 95% CI 0.08, 0.65), risk of depression (aOR 3.51, 95% CI 1.57, 7.87), ever having received medication-assisted treatment for opioid use disorder (aOR 4.20, 95% CI 1.65, 10.69), being comfortable discussing substance use with counselors/nurses (aOR 3.86, 95% CI 1.38, 10.81) and having discussed alcohol use with their health providers (aOR 2.34, 95% CI 1.09, 4.99) were associated with patients' preference for integrated care, after adjusting for age and gender. Conclusion Most, but not all, HIV-infected patients with substance use preferred integrated HIV and SUD treatment. Our findings suggest that policies to expand integration of HIV and SUD treatment will be well received by most patients, and that stand-alone treatment options should be preserved for a significant minority.
The incorporation of straw into soil has been encouraged as an alternative straw‐disposal strategy to the on‐site burning that occurs in many paddy regions. However, this practice may lead to changes ...in the colloidal properties of soil clays that potentially intensify clay and nutrient losses. This study aimed to demonstrate the effect of engineered microsized straw powder on the colloidal properties of two soil clays, that is, illitic and kaolinitic soil clays. Dynamic light scattering was coupled with the test tube method to evaluate time‐resolved changes in the particle size, zeta potential and dispersibility for the suspensions of straw powder and its mixtures with illitic and kaolinitic soil clays. Data from kinetic experiments over a time span of 20 days revealed that straw powder remarkably increased the dispersibility of soil clays. It was found that straw particles carried negative charges; thus, the introduction of straw powder into the clay suspensions increased the number of negative charges in the system, thereby increasing internal repulsive forces and eventually favouring clay dispersion. Moreover, certain mutual processes, that is, the biodegradation and dissolution of phytoliths (silica in straw), resulted in the release of dissolved organic matter and silicon, which aggravated clay dispersibility. In addition to the “traditional” awareness of the impacts of straw incorporation, for example, creating toxic, reduced environments or increasing CH4 emissions, the changes in the colloidal properties of soil clays should also be highlighted. We propose that the incorporation of straw requires additional solutions for the prevention of clay loss.
Highlights
Straw powder was examined for possible effect on colloidal properties of soil clays
It was found that straw particles carried negative charges
Introduction of straw powder increase repulsive forces and favor clay dispersion
Microorganism, B. amyloliquefaciens, enhances the effect of straw powder
This paper provides a novel application of the multi-criteria decision-making (MCDM) method to the multi-objective optimization problem (MOOP) of creating a two-stage helical gearbox (TSHG) with ...second-stage double gear sets (SDGSs). The aim of the study is to determine the optimum major design components for enhancing the gearbox efficiency while reducing the gearbox volume. In this work, three primary design parameters are chosen to accomplish this: the gear ratio of the first stage and the coefficients of the wheel face width (CWFW) of the first and second stages. Additionally, the study is conducted with two distinct objectives in mind: the lowest gearbox volume and the maximum gearbox efficiency. Moreover, phase 1 and phase 2, respectively, are the two stages of the MOOP. Phase 2 handles the MOOP to identify the ideal primary design factors as well as the single-objective optimization problem to minimize the difference between the variable levels. Additionally, the Multi-Attributive Ideal–Real Comparative Analysis (MAIRCA) approach is selected to deal with the MOOP. The results of the study are utilized to determine the ideal values for three crucial design parameters in order to create a TSHG with SDGSs.
The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome maintenance but is also ...highly antigenic. Hence, EBV seemingly evolved a system in which the glycine-alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA to the minimal level to ensure its essential function, thereby, at the same time, minimizing immune recognition. Therefore, defining intervention points at which to interfere with GAr-based inhibition of translation is an important step to trigger an immune response against EBV-carrying cancers. The host protein nucleolin (NCL) plays a critical role in this process via a direct interaction with G-quadruplexes (G4) formed in the GAr-encoding sequence of the viral EBNA1 mRNA. Here we show that the C-terminal arginine-glycine-rich (RGG) motif of NCL is crucial for its role in GAr-based inhibition of translation by mediating interaction of NCL with G4 of EBNA1 mRNA. We also show that this interaction depends on the type I arginine methyltransferase family, notably PRMT1 and PRMT3: drugs or small interfering RNA that target these enzymes prevent efficient binding of NCL on G4 of EBNA1 mRNA and relieve GAr-based inhibition of translation and of antigen presentation. Hence, this work defines type I arginine methyltransferases as therapeutic targets to interfere with EBNA1 and EBV immune evasion.
Abstract
BCL-x is a master regulator of apoptosis whose pre-mRNA is alternatively spliced into either a long (canonical) anti-apoptotic Bcl-xL isoform, or a short (alternative) pro-apoptotic Bcl-xS ...isoform. The balance between these two antagonistic isoforms is tightly regulated and overexpression of Bcl-xL has been linked to resistance to chemotherapy in several cancers, whereas overexpression of Bcl-xS is associated to some forms of diabetes and cardiac disorders. The splicing factor RBM25 controls alternative splicing of BCL-x: its overexpression favours the production of Bcl-xS, whereas its downregulation has the opposite effect. Here we show that RBM25 directly and specifically binds to GQ-2, an RNA G-quadruplex (rG4) of BCL-x pre-mRNA that forms at the vicinity of the alternative 5′ splice site leading to the alternative Bcl-xS isoform. This RBM25/rG4 interaction is crucial for the production of Bcl-xS and depends on the RE (arginine-glutamate-rich) motif of RBM25, thus defining a new type of rG4-interacting domain. PhenDC3, a benchmark G4 ligand, enhances the binding of RBM25 to the GQ-2 rG4 of BCL-x pre-mRNA, thereby promoting the alternative pro-apoptotic Bcl-xS isoform and triggering apoptosis. Furthermore, the screening of a combinatorial library of 90 putative G4 ligands led to the identification of two original compounds, PhenDH8 and PhenDH9, superior to PhenDC3 in promoting the Bcl-xS isoform and apoptosis. Thus, favouring the interaction between RBM25 and the GQ-2 rG4 of BCL-x pre-mRNA represents a relevant intervention point to re-sensitize cancer cells to chemotherapy.
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