Mining tailings alter insects: revealing fluctuating asymmetry in the caddisfly Smicridea coronata.

The Samarco/Vale/BHP mine tailing dam breach that took place in Minas Gerais, southeastern Brazil, in 2015, deposited high concentrations of metals and metalloids in the Rio Doce basin, severely impacting freshwater and riverine forest ecosystems. To assess developmental instability of caddisflies in response to the environmental impacts of the dam breach, we investigated the fluctuating asymmetry (FA) in the species Smicridea (Rhyacophylax) coronata (Trichoptera: Hydropsychidae). FA was assessed at individual and populational scales using geometric morphometric methods in the cephalic capsule and mandibles of larvae and also on the forewings of adults, both collected under the impacted condition, and under the least disturbed condition. The levels of FA increased in response to stressors on the forewings at the populational scale, and on the mandibles, at individual scale. These morphological variations in the larval and adult stages may lead to detrimental effects and result in high mortality rates as well as lower adult fitness. Trichoptera forewings are revealed as suitable traits for assessing FA, holding potential for applications in biomonitoring programs. Directional asymmetry levels were higher than FA levels for all traits, and this correlation could be explained by a transition from fluctuating to directional asymmetry in the presence of heightened disturbance. Our results validate the relationship between the impacts from the dam breach and increased developmental instability in this species with likely cascade effects on the insect community.

Balancing Act: Tubulin Glutamylation and Microtubule Dynamics in Toxoplasma gondii.

The success of the intracellular parasite Toxoplasma gondii in invading host cells relies on the apical complex, a specialized microtubule cytoskeleton structure associated with secretory organelles. The T. gondii genome encodes three isoforms of both α- and ß-tubulin, which undergo specific post-translational modifications (PTMs), altering the biochemical and biophysical proprieties of microtubules and modulating their interaction with associated proteins. Tubulin PTMs represent a powerful and evolutionarily conserved mechanism for generating tubulin diversity, forming a biochemical 'tubulin code' interpretable by microtubule-interacting factors. T. gondii exhibits various tubulin PTMs, including α-tubulin acetylation, α-tubulin detyrosination, Δ5α-tubulin, Δ2α-tubulin, α- and ß-tubulin polyglutamylation, and α- and ß-tubulin methylation. Tubulin glutamylation emerges as a key player in microtubule remodeling in Toxoplasma, regulating stability, dynamics, interaction with motor proteins, and severing enzymes. The balance of tubulin glutamylation is maintained through the coordinated action of polyglutamylases and deglutamylating enzymes. This work reviews and discusses current knowledge on T. gondii tubulin glutamylation. Through in silico identification of protein orthologs, we update the recognition of putative proteins related to glutamylation, contributing to a deeper understanding of its role in T. gondii biology.

AMOC decline and recovery in a warmer climate.

This study presents novel insight into the mechanisms of Atlantic Meridional Overturning Circulation (AMOC) reduction and its recovery under a warmer climate scenario. An one-thousand-year-long numerical simulation of a global coupled ocean-ice-atmosphere climate model, subjected to a stationary atmospheric radiative forcing, depict a coherent picture of the Arctic sea ice melting as a trigger for the initial AMOC reduction, along with decreases in the northward fluxes of salt and heat. Further atmospheric-driven ocean processes contribute to an erosion of the stable stratification of the fresher, yet colder waters in the surface layers of the North Atlantic, contributing to the recovery of a permanently altered AMOC.

A sustainable hydrometallurgical strategy for recycling efficiently platinum from spent reforming petroleum catalyst.

Platinum (Pt) is one of the most precious metals with a variety of unique industrial applications, particularly in catalytic reactions, being its recovery, after use, essential. Therefore, this work proposes a simplified hydrometallurgical strategy to recover Pt efficiently from the original (no milling) spent petrochemical Pt catalyst using an economical and environmentally sustainable process. To that end, the effectiveness of a two-step workflow constituted by one microwave-assisted leaching step using a mixture of hydrochloric acid (HCl) and hydrogen peroxide (H2O2) followed by one ion-exchange purification step was developed and optimized. It was found that complete dissolution of Pt plus aluminum (Al) and iron (Fe) from the roasted original size catalyst was achieved after microwave-assisted leaching with 25% (v/v) HCl and 2% (v/v) H2O2 during 2 cycles of 60 s. Furthermore, a strong anionic exchange (Purogold™ A194) resin used for subsequent selective purification of Pt from Al and Fe was capable of effective separation of the metals: Pt in the eluate presented a purity of 98.1%, while Al, in the raffinate, presented a purity of 99.8%. In summation, it can be concluded that the overall process is a potentially good addition to a more circular economy as it manages to recover high-quality Pt for being reused as well as other by-products, whilst minimizing the consume of reagents, leaching time (and, thus, energy), and environmental impacts.

Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection.

The intricate interplay between maternal immune response to SARS-CoV-2 and the transfer of protective factors to the fetus remains unclear. By analyzing mother-neonate dyads from second and third trimester SARS-CoV-2 infections, our study shows that neutralizing antibodies (NAbs) are infrequently detected in cord blood. We uncovered that this is due to impaired IgG-NAb placental transfer in symptomatic infection and to the predominance of maternal SARS-CoV-2 NAbs of the IgA and IgM isotypes, which are prevented from crossing the placenta. Crucially, the balance between maternal antiviral response and transplacental transfer of IgG-NAbs appears to hinge on IL-6 and IL-10 produced in response to SARS-CoV-2 infection. In addition, asymptomatic maternal infection was associated with expansion of anti-SARS-CoV-2 IgM and NK cell frequency. Our findings identify a protective role for IgA/IgM-NAbs in gestational SARS-CoV-2 infection and open the possibility that the maternal immune response to SARS-CoV-2 infection might benefit the neonate in 2 ways, first by skewing maternal immune response toward immediate viral clearance, and second by endowing the neonate with protective mechanisms to curtail horizontal viral transmission in the critical postnatal period, via the priming of IgA/IgM-NAbs to be transferred by the breast milk and via NK cell expansion in the neonate.

Tubulin Post-Translational Modifications: The Elusive Roles of Acetylation.

Microtubules (MTs), dynamic polymers of α/ß-tubulin heterodimers found in all eukaryotes, are involved in cytoplasm spatial organization, intracellular transport, cell polarity, migration and division, and in cilia biology. MTs functional diversity depends on the differential expression of distinct tubulin isotypes and is amplified by a vast number of different post-translational modifications (PTMs). The addition/removal of PTMs to α- or ß-tubulins is catalyzed by specific enzymes and allows combinatory patterns largely enriching the distinct biochemical and biophysical properties of MTs, creating a code read by distinct proteins, including microtubule-associated proteins (MAPs), which allow cellular responses. This review is focused on tubulin-acetylation, whose cellular roles continue to generate debate. We travel through the experimental data pointing to α-tubulin Lys40 acetylation role as being a MT stabilizer and a typical PTM of long lived MTs, to the most recent data, suggesting that Lys40 acetylation enhances MT flexibility and alters the mechanical properties of MTs, preventing MTs from mechanical aging characterized by structural damage. Additionally, we discuss the regulation of tubulin acetyltransferases/desacetylases and their impacts on cell physiology. Finally, we analyze how changes in MT acetylation levels have been found to be a general response to stress and how they are associated with several human pathologies.

Gut as an Alternative Entry Route for SARS-CoV-2: Current Evidence and Uncertainties of Productive Enteric Infection in COVID-19.

The gut has been proposed as a potential alternative entry route for SARS-CoV-2. This was mainly based on the high levels of SARS-CoV-2 receptor expressed in the gastrointestinal (GI) tract, the observations of GI disorders (such as diarrhea) in some COVID-19 patients and the detection of SARS-CoV-2 RNA in feces. However, the underlying mechanisms remain poorly understood. It has been proposed that SARS-CoV-2 can productively infect enterocytes, damaging the intestinal barrier and contributing to inflammatory response, which might lead to GI manifestations, including diarrhea. Here, we report a methodological approach to assess the evidence supporting the sequence of events driving SARS-CoV-2 enteric infection up to gut adverse outcomes. Exploring evidence permits to highlight knowledge gaps and current inconsistencies in the literature and to guide further research. Based on the current insights on SARS-CoV-2 intestinal infection and transmission, we then discuss the potential implication on clinical practice, including on long COVID. A better understanding of the GI implication in COVID-19 is still needed to improve disease management and could help identify innovative therapies or preventive actions targeting the GI tract.

Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework.

Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors (age, sex, genetic factors, lipid disorders, heart failure, gut dysbiosis, diet, vitamin D deficiency, air pollution and exposure to chemicals) influence COVID-19 by applying the Adverse Outcome Pathway (AOP), which is well-established in regulatory toxicology. This framework aims to model the sequence of events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how those eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.

Recovery of palladium from a low grade palladium solution by anionic-ion exchange: kinetics, equilibrium, and metal competition.

Petroleum spent catalysts may contain a significant amount of palladium (Pd) together with other major [aluminum (Al), nickel (Ni), and molybdenum (Mo)] and minor [iron (Fe), lead (Pb), and vanadium (V)] elements. Due to the high intrinsic value of Pd and its scarcity in natural ores, its recovery is highly desired. For this purpose, the ability of a strong basic anionic- resin, Purogold™ A194 resin, to remove Pd from the solution was assessed. Data from kinetic and equilibrium studies, performed under batch mode in 1 mol/L of NaCl and 1 mol/L of HNO3 at (21 ± 1) °C, revealed that the removal of Pd fits well a pseudo-second-order kinetic model [constant rate value, k2, of (0.062 ± 0.010) g/(mmol.min)] and a Langmuir isotherm [maximum sorption capacity of (0.80 ± 0.02) mmol/g with an affinity of resin binding sites towards Pd, KL, of (0.18 ± 0.02) L/mmol], respectively. The sorption of other metals (Al, Fe, Pb, Mo, Ni, and V) that may be present in spent catalyst leachates was tested under similar experimental conditions [CM = 2.5 mmol/L, 1 mol/L of NaCl and 1 mol/L of HNO3 at (21 ± 1) °C)] and the resin showed little affinity towards each one of these metals. Also, simultaneous multi-element batch experiments with Pd and the major components (M = Al, Ni, and Mo ions) ([M]/[Pd] molar ratios between 3.4 and 52 were used) pointed out that the resin is highly selective towards Pd suggesting that the resin can be used in the selective recovery of Pd from petroleum spent catalyst leachates.

Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation: Possible implications for SARS-CoV-2 impact on brain development.

The possible neurodevelopmental consequences of SARS-CoV-2 infection are presently unknown. In utero exposure to SARS-CoV-2 has been hypothesized to affect the developing brain, possibly disrupting neurodevelopment of children. Spike protein interactors, such as ACE2, have been found expressed in the fetal brain, and could play a role in potential SARS-CoV-2 fetal brain pathogenesis. Apart from the possible direct involvement of SARS-CoV-2 or its specific viral components in the occurrence of neurological and neurodevelopmental manifestations, we recently reported the presence of toxin-like peptides in plasma, urine and fecal samples specifically from COVID-19 patients. In this study, we investigated the possible neurotoxic effects elicited upon 72-hour exposure to human relevant levels of recombinant spike protein, toxin-like peptides found in COVID-19 patients, as well as a combination of both in 3D human iPSC-derived neural stem cells differentiated for either 2 weeks (short-term) or 8 weeks (long-term, 2 weeks in suspension + 6 weeks on MEA) towards neurons/glia. Whole transcriptome and qPCR analysis revealed that spike protein and toxin-like peptides at non-cytotoxic concentrations differentially perturb the expression of SPHK1, ELN, GASK1B, HEY1, UTS2, ACE2 and some neuronal-, glia- and NSC-related genes critical during brain development. Additionally, exposure to spike protein caused a decrease of spontaneous electrical activity after two days in long-term differentiated cultures. The perturbations of these neurodevelopmental endpoints are discussed in the context of recent knowledge about the key events described in Adverse Outcome Pathways relevant to COVID-19, gathered in the context of the CIAO project (https://www.ciao-covid.net/).

Antagonist G-targeted liposomes for improved delivery of anticancer drugs in small cell lung carcinoma.

Ligand-mediated targeted liposomes have the potential to increase therapeutic efficacy of anticancer drugs. This work aimed to evaluate the ability of antagonist G, a peptide targeting agent capable of blocking the action of multiple neuropeptides, to selectivity improve targeting and internalization of liposomal formulations (long circulating liposomes, LCL, and stabilized antisense lipid particles containing ionizable amino lipid, SALP) to H69 and H82 small cell lung carcinoma (SCLC) cell lines. Antagonist G-targeted LCL and SALP were prepared by two different methods (either by direct covalent linkage at activated PEG grafted onto the liposomal surface or by post-insertion of DSPE-PEG-antagonist-G-conjugates into pre-formed liposomes). Association of the liposomal formulations with target SCLC cells was studied by fluorescence microscopy using fluorescence-labelled liposomes and confirmed quantitatively with [3H]-CHE-labelled liposomes. An antisense oligodeoxynucleotide against the overexpressed oncogene c-myc(as(c-myc)) was efficiently loaded into SALP formulations, the encapsulation efficiency decreased due to the inclusion of the targeting ligand. Also, liposome size was affected by as(c-myc) physical chemical properties. The amount of antagonist G linked to the surface of the liposomal formulations was dependent on the coupling method and lipid composition used. Covalent attachment of antagonist G increased liposomes cellular association and internalization via receptor-mediated and clathrin-dependent endocytosis, as assessed in SCLC cell lines. Biodistribution studies in healthy mice revealed a preferential lung accumulation of antagonist G-targeted SALP as compared to the non-targeted counterpart. Lung levels of the former were up to 3-fold higher 24 h after administration, highlighting their potential to be used as delivery vectors for SCLC treatment.

Secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon mRNA vaccination.

In view of the scarcity of data to guide decision making, we evaluated how BNT162b2 and mRNA-1273 vaccines affect the immune response in lactating women and the protective profile of breastmilk. Compared with controls, lactating women had a higher frequency of circulating RBD memory B cells and higher anti-RBD antibody titers but similar neutralizing capacity. We show that upon vaccination, immune transfer to breastmilk occurs through a combination of anti-spike secretory IgA (SIgA) antibodies and spike-reactive T cells. Although we found that the concentration of anti-spike IgA in breastmilk might not be sufficient to directly neutralize SARS-CoV-2, our data suggest that cumulative transfer of IgA might provide the infant with effective neutralization capacity. Our findings put forward the possibility that breastmilk might convey both immediate (through anti-spike SIgA) and long-lived (via spike-reactive T cells) immune protection to the infant. Further studies are needed to address this possibility and to determine the functional profile of spike T cells.

Characterization of a MOB1 Homolog in the Apicomplexan Parasite Toxoplasma gondii.

Monopolar spindle One Binder1 (MOB1) proteins are conserved components of the tumor-suppressing Hippo pathway, regulating cellular processes such as cytokinesis. Apicomplexan parasites present a life cycle that relies on the parasites' ability to differentiate between stages and regulate their proliferation; thus, Hippo signaling pathways could play an important role in the regulation of the apicomplexan life cycle. Here, we report the identification of one MOB1 protein in the apicomplexan Toxoplasma gondii. To characterize the function of MOB1, we generated gain-of-function transgenic lines with a ligand-controlled destabilization domain, and loss-of-function clonal lines obtained through CRISPR/Cas9 technology. Contrary to what has been characterized in other eukaryotes, MOB1 is not essential for cytokinesis in T. gondii. However, this picture is complex since we found MOB1 localized between the newly individualized daughter nuclei at the end of mitosis. Moreover, we detected a significant delay in the replication of overexpressing tachyzoites, contrasting with increased replication rates in knockout tachyzoites. Finally, using the proximity-biotinylation method, BioID, we identified novel members of the MOB1 interactome, a probable consequence of the observed lack of conservation of some key amino acid residues. Altogether, the results point to a complex evolutionary history of MOB1 roles in apicomplexans, sharing properties with other eukaryotes but also with divergent features, possibly associated with their complex life cycle.

Development of Triazoles and Triazolium Salts Based on AZT and Their Anti-Viral Activity against HIV-1.

We report herein a set of 3'-azido-3'-deoxythymidine (AZT) derivatives based on triazoles and triazolium salts for HIV-1 infection. The compounds were synthesized via click chemistry with Cu(I) and Ru(II) catalysts. Triazolium salts were synthesized by reaction with methyl iodide or methyl triflate in good yields. The antiviral activity of the compounds was tested using two methodologies: In method one the activity was measured on infected cells; in method two a pre-exposure prophylaxis experimental model was employed. For method one the activity of the compounds was moderate, and in general the triazolium salts showed a decreased activity in relation to their triazole precursors. With method two the antiviral activity was higher. All compounds were able to decrease the infection, with two compounds able to clear almost all the infection, while a lower antiviral activity was noted for the triazolium salts. These results suggest that these drugs could play an important role in the development of pre-exposure prophylaxis therapies.

Amplification of Femtograms of Bacterial DNA Within 3 h Using a Digital Microfluidics Platform for MinION Sequencing.

Whole genome sequencing is emerging as a promising tool for the untargeted detection of a broad range of microbial species for diagnosis and analysis. However, it is logistically challenging to perform the multistep process from sample preparation to DNA amplification to sequencing and analysis within a short turnaround time. To address this challenge, we developed a digital microfluidic device for rapid whole genome amplification of low-abundance bacterial DNA and compared results with conventional in-tube DNA amplification. In this work, we chose Corynebacterium glutamicum DNA as a bacterial target for method development and optimization, as it is not a common contaminant. Sequencing was performed in a hand-held Oxford Nanopore Technologies MinION sequencer. Our results show that using an in-tube amplification approach, at least 1 pg starting DNA is needed to reach the amount required for successful sequencing within 2 h. While using a digital microfluidic device, it is possible to amplify as low as 10 fg of C. glutamicum DNA (equivalent to the amount of DNA within a single bacterial cell) within 2 h and to identify the target bacterium within 30 min of MinION sequencing-100× lower than the detection limit of an in-tube amplification approach. We demonstrate the detection of C. glutamicum DNA in a mock community DNA sample and characterize the limit of bacterial detection in the presence of human cells. This approach can be used to identify microbes with minute amounts of genetic material in samples depleted of human cells within 3 h.

Simple and near-zero-waste processing for recycling gold at a high purity level from waste printed circuit boards.

This work proposes an efficient and simple hydrometallurgical process based on a chlorination step followed by an ion-exchange step for recycling gold (Au) from a waste printed circuit boards (WPCBs) enriched in Au resulting from a first leaching step under mild oxidizing conditions for extracting Cu and other base metals. Under optimized [3.5 mol/L HCl and 0.46 mol/L NaClO, with a liquid/solid (L/S) ratio of 40, at 40 °C for 3 h with agitation] leaching conditions, 95% Au was extracted from the residue originating a multi-metal solution containing 1.0% Au. Subsequently, Au (initial concentration: 38 µmol/L) present in the multimetal-leached solution was purified in continuous mode using two strong anionic exchange resins: DOW™ XZ-91419.00 and Purogold™ A194. Both resins were suitable in purifying Au from the multimetal-leaching solution, with at least 70% of Au recovered relative to the initial residue. When the DOW™ XZ-91419.00 resin was used, a solution containing 1.7 mmol/L Au with a purity grade of 94% was obtained, with Pb and Sn being the major contaminants (3.3 and 2.4%, respectively). For Purogold™ A194 resin, a solution containing 0.73 mmol/L Au with a purity grade of 92% was achieved; Ag, Pb and Pd were the major contaminants (1.4, 3.6 and 1.8%, respectively). In conclusion, this work demonstrates a novel hydrometallurgical strategy for recycling Au with a high grade from WPCBs, minimizing the number of leaching and purification steps and the amount of waste created.

Direct tissue-sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients.

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. TLR4+ T cells possess a two-pronged pathogenic activity whereby direct TLR4+ engagement by endogenous ligands in the arthritic joint reprograms them from an IL-21 response, known to sponsor antibody production towards an IL-17 inflammatory program recognized to fuel tissue damage. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Mechanistically, we unveiled that T-cell HLA-DR regulates their TLR4 expression. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program.