Spatial estimation of groundwater quality, hydrogeochemical investigation, and health impacts of shallow groundwater in Kabul city, Afghanistan

The management of groundwater in densely populated areas with no centralized water treatment is critical for the prevention of diseases and maintaining sanitation. Here, we determine the bacteriological and chemical characteristics of groundwater in Kabul city, a resource that 4.1 million individuals rely on. Groundwater samples were analyzed from 41 newly established piezometric wells across Kabul, and data were compared with the last detailed study, undertaken in 2007, to understand contamination trends in an area that has undergone significant development and social changes. Piper diagrams, Gibbs diagrams, correlation analysis, and bivariate plots examine the hydrogeochemical and natural occurring processes of groundwater. The average concentration of cations followed the order Na+  > Mg2+  > Ca2+  > K+, and anions HCO3− > NO3− > Cl− > SO42− > F with Gibbs diagrams indicating mainly rock-weathering influence groundwater chemistry. An increase in nitrate (NO3−) and E. coli indicates anthropogenic activities impacting the shallow groundwater quality, with significantly elevated nitrate (over 50 mg/L) and E. coli (up to 250 CFU/100 mL). The increasing presence of E. coli and NO3− in the shallow groundwater of Kabul city in turn suggests problematic links to the prevalence of waterborne diseases. Additionally, the water quality index (WQI) was used to assess groundwater quality, and rank its suitability for drinking purposes. The WQI analysis showed that less than 35% of shallow groundwater samples had good water quality. The findings of this study are crucial for the development and sustainable management of groundwater in the city. In short term, we propose interventions such as point-of-use (POU) water purification which may offer temporary respite for waterborne disease prevention. Kabul city requires immediate attention to developing sustainable groundwater management policies, expansion of the water supply network, groundwater quality monitoring, and wastewater management

The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition

Assisted evolution enables HIV-1 to overcome a high trim5α-imposed genetic barrier to rhesus macaque tropism

Diversification of antiretroviral factors during host evolution has erected formidable barriers to cross-species retrovirus transmission. This phenomenon likely protects humans from infection by many modern retroviruses, but it has also impaired the development of primate models of HIV-1 infection. Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α). Initially, we attempted to derive rhTRIM5α-resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in engineered human cells expressing rhTRIM5α. Second, a library of randomly mutagenized capsid protein (CA) sequences was screened for mutations that reduced rhTRIM5α sensitivity. Both approaches identified several individual mutations in CA that reduced rhTRIM5α sensitivity. However, neither approach yielded mutants that were fully resistant, perhaps because the locations of the mutations suggested that TRIM5α recognizes multiple determinants on the capsid surface. Moreover, even though additive effects of various CA mutations on HIV-1 resistance to rhTRIM5α were observed, combinations that gave full resistance were highly detrimental to fitness. Therefore, we employed an 'assisted evolution' approach in which individual CA mutations that reduced rhTRIM5α sensitivity without fitness penalties were randomly assorted in a library of viral clones containing synthetic CA sequences. Subsequent passage of the viral library in rhTRIM5α-expressing cells resulted in the selection of individual viral species that were fully fit and resistant to rhTRIM5α. These viruses encoded combinations of five mutations in CA that conferred complete or near complete resistance to the disruptive effects of rhTRIM5α on incoming viral cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants encoding these CA substitutions and SIVmac239 Vif replicated efficiently in primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5α is difficult to but not impossible to evade, and doing so should facilitate the development of primate models of HIV-1 infection

Independent evolution of an antiviral TRIMCyp in rhesus macaques

The antiretroviral restriction factor TRIM5 has recently emerged as an important mediator of innate immunity and species-specific inhibition of retroviral replication in mammals. Selection pressure from pathogenic infection has driven rapid evolution of TRIM5 genes, leading to the antiviral specificities we see today. Remarkably, the New World owl monkey (Aotus trivirgatus) encodes a TRIM5 protein in which the antiviral determinants in the B30.2 domain have been replaced by cyclophilin A (CypA) encoded by a retrotransposed cDNA. The owl monkey TRIMCyp protein restricts infection by a subset of lentiviruses that recruit CypA to their capsids, including HIV-1 and feline immunodeficiency virus. Here, we show that the Old World monkey, rhesus macaque (Macaca mulatta), also encodes a TRIMCyp protein that has arisen independently from that in owl monkeys. The rhesus TRIMCyp is encoded by a single, but common, allele (Mamu7) of the rhesus TRIM5 gene, among at least six further alleles that encode full-length TRIM5 proteins with no homology to CypA. The antiviral specificity of the rhesus TRIMCyp is distinct, restricting infection of HIV-2 and feline immunodeficiency virus but not HIV-1. Restriction by rhesus TRIMCyp is before reverse transcription and inhibited by blocking CypA binding, with cyclosporine A, or by mutation of the capsid CypA binding site. These observations suggest a mechanism of restriction that is conserved between TRIMCyp proteins. The lack of activity against HIV-1 suggests that Mamu7 homozygous animals will be null for TRIM5-mediated restriction of HIV-1 and could contribute to improved animal models for HIV/AIDS

Development and validation of a GC Orbitrap-MS method for the analysis of phthalate esters (PAE) and bis(2-ethylhexyl)adipate (DEHA) in atmospheric particles and its application for screening PM _2.5 from Curitiba, Brazil

Phthalates or phthalic acid esters (PAE) and bis(2-ethylhexyl) adipate (DEHA) are ubiquitous chemicals often used as plasticisers and additives in many industrial products and are classified as both persistent organic pollutants (POPs) and new emerging pollutants (NEPs). Exposure to these chemicals, especially through inhalation, is linked to a wide range of negative health effects, including endocrine disruption. Air particulate matter (PM) with an aerodynamic diameter < 2.5 µm can be enriched with PAEs and DEHA and if inhaled can cause multi-system human toxicity. Therefore, proper monitoring of PAEs and DEHA in PM is required to assess human exposure to these pollutants. In this work, we developed and validated a new and sensitive gas-chromatography high-resolution mass (GC-HRMS) method for the targeted analysis of PAEs including dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), bis-2-ethylhexyl adipate (DEHA), bis-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DOP), in PM. Analytical aspects including sample preparation steps and GC-HRMS parameters, e.g., quadrupole isolation window, to enhance method sensitivity have been assessed. The estimated limit of detection (LODs) of target PAEs and DEHA ranged from 5.5 to 17 pg µL-1, allowing their trace-level detection in PM. Extraction efficiencies of 78% - 101% were obtained for the target compounds. Low DMP and DEP extraction efficiencies from the spiked filter substrates indicated that significant losses of higher volatility PAEs can occur during the sample collection when filter-based techniques are used. This work is the first targeted method based on GC-Orbitrap MS for PAEs and DEHA in environmental samples The validated method was successfully applied for the targeted analysis of PAEs and DEHA in PM2.5 samples from the eighth most populous city in Brazil, Curitiba. This work is the first to report DBP, DEHA, DEHP, and DOP in urban PM from Brazil. The observed concentrations of PAEs (up to 29 ng m-3) in PM2.5 from Curitiba may not represent the extent of pollution by these toxic compounds since the analysed samples were collected during a COVID-19 restriction when anthropogenic activities were reduced

Plastic pyrolysis over HZSM-5 zeolite and fluid catalytic cracking catalyst under ultra-fast heating

Plastic pollution compromises the environment and human well-being, and a global transition to a circular economy of plastics is vital to address this challenge. Pyrolysis is a key technology for the end-of-life recycling of plastics, although high energy consumption limits the economic feasibility of the process. Various research has shown that the application of induction heating in biomass pyrolysis reduces energy consumption when compared to conventional heating. Nevertheless, the potential of induction heating in plastic pyrolysis is rarely explored. This paper presents an exploratory study on the thermal and catalytic pyrolysis of high-density polyethylene, low-density polyethylene, and polypropylene in a fixed bed reactor through induction heating. An MFI-type HZSM-5 zeolite (SiO2/Al2O3 = 23) and an FAU-type spent fluid catalytic cracking (FCC) catalyst with distinctive Brønsted acidity and textural properties were used. A complete conversion of the plastic feedstocks was achieved within 10 minutes, even without a catalyst. Thermal pyrolysis produced wax (72.4-73.9 wt.%) and gas products, indicating a limited degree of polymer cracking. Catalytic pyrolysis over HZSM-5 and FCC catalyst significantly improved polymer cracking, leading to higher gas (up to 75.2 wt.%) and liquid product (up to 35.9 wt.%) yields at the expense of wax yield (up to 25.4 wt.%). In general, the gas products were rich in C3 and C4 compounds. The liquid product composition was highly dependent on the catalyst properties, for example, the HZSM-5 produced high aromatics, while the FCC catalyst produced high alkenes in the liquid products. The catalyst acidity and textural properties played an essential role in plastic pyrolysis within the short reaction time. This study demonstrated the feasibility of a fast, energy-efficient, and versatile plastic valorisation technology based on the application of induction heating, where the plastic feed can be converted into wax, gas, and liquid products depending on the end-use applications