Search Results (545)

Human immunodeficiency virus type 1 exhibits extensive genetic diversity, which has important implications for molecular epidemiology, recombinant-pattern assessment, and antiretroviral resistance surveillance. In Mexico, HIV-1 molecular surveillance has historically relied mainly on partial pol gene sequencing, limiting the ability to compare lineage assignments across gag, pol, and env regions. We analyzed plasma samples from 40 treatment-naïve adults receiving care at a tertiary-care hospital in Mexico using a commercial amplicon-based multiregion HIV-1 genomic sequencing workflow. DeepChek^® was used as the primary workflow for read processing, mutation calling, region-level subtype assignment, and antiretroviral resistance interpretation. Resistance interpretation was restricted to antiretroviral target regions with sufficient coverage, mainly reverse transcriptase, protease, integrase, and capsid, when available. Drug resistance mutations were identified in 6/40 participants (15.0%) when mutation-level resistance findings in RT, PR, and IN were considered; one additional sample showed a capsid inhibitor-nonsusceptible NGS call. NNRTI-associated findings were identified in 2/40 patients (5.0%), whereas NRTI- and PI-associated findings were identified in 1/40 patients (2.5%). Accessory or secondary INSTI-associated substitutions were detected in 2/40 patients (5.0%). Region-level subtype analysis revealed frequent discordant assignments across amplified segments, which is consistent with complex mosaic profiles; however, these findings are interpreted as region-level subtypes and recombinant-pattern assignments rather than continuous whole-genome recombination maps. One sample had insufficient RT/PROT/INT coverage for drug resistance interpretation in the complete DeepChek report and was retained only for regions meeting quality thresholds. These findings support the value of multiregion HIV-1 sequencing for local molecular surveillance while emphasizing the need for transparent region-level coverage reporting, cautious interpretation of recombinant-pattern calls, and transparent repository reporting. Full article

Essential host functions are often maintained by conserved molecular systems, but in biological contexts shaped by evolutionary conflict, the genes that execute such functions may be unstable, replaceable, or repeatedly recruited from different evolutionary sources. Mammalian placentation provides a striking example of this principle. Trophoblast cell fusion is essential for placental development, yet this function is mediated in different mammalian lineages by distinct endogenous retrovirus-derived envelope proteins, including syncytin-1, syncytin-2, and other lineage-specific Env-derived fusogens. Here, I propose the Baton Pass model as a conceptual framework for explaining how host-level biological functions can be maintained despite turnover of the molecular agents that execute them. This model differs from conventional examples of antagonistic coevolution, which often emphasize recurrent mutations within the same interacting genes, and from non-orthologous gene displacement, which generally concerns replacement among cellular genes. In the syncytin paradigm, the molecular executors are repeatedly supplied by exogenous retroviral env genes that become endogenized, domesticated, and incorporated into host developmental programs. I further discuss how receptor compatibility, placental expression control, and host–virus evolutionary conflict may together destabilize individual Env–receptor systems while allowing the host-level function of trophoblast fusion to persist. Analogous functional reassignment is also observed in primate lentiviruses, where antagonism of BST-2 shifts among distinct viral genes. The Baton Pass model therefore describes a testable evolutionary principle: essential host functions can be preserved not only through conservation of specific genes, but also through dynamic succession of genes of distinct evolutionary origins. Full article

This study evaluates the vulnerability of Siberian larch (Larix sibirica L.) populations to future climate change using a genomic offset (GO) framework that integrates genome-wide SNP data with environmental variables. We analyzed 488 individuals from 37 populations across climatically diverse regions of Russia, genotyped by sequencing at over 20,000 SNP loci using the ddRADseq method. Gene–environment association (GEA) analyses (BayeScEnv, LFMM2, and RDA) identified candidate adaptive loci linked to six key bioclimatic variables. Based on these loci, GO was estimated using three approaches implemented in RONA–RDA, RDA, and Gradient Forest frameworks under multiple climate models (MIROC6, BCC-CSM2-MR, MRI-ESM2-0), scenarios (SSP2-4.5, SSP3-7.0, SSP5-8.5), and time periods (2041–2060, 2061–2080, and 2081–2100). Results revealed consistent spatial patterns of vulnerability, with northern and high-altitude populations, as well as populations from more continental and moisture-limited regions, exhibiting the highest GO and thus the greatest risk of maladaptation. In contrast, several central and southern populations showed relatively low vulnerability. The importance of temperature stability (isothermality) and precipitation of the driest month as key drivers of adaptive variation was highlighted. Despite differences in SNP datasets, population rankings remained highly consistent, supporting the robustness of predictions. Overall, our findings demonstrate substantial heterogeneity in climate vulnerability across the species range and provide a genomic basis for conservation strategies, including assisted gene exchange and climate-adaptive forest management. Full article

Background/Objectives: As important post-transcriptional and epigenetic regulators of gene expression, miRNAs play a pivotal role in modulating host–virus interactions. While prior reviews have addressed either direct miRNA–HIV genome interactions or miRNA-mediated immune modulation in isolation, the integrated dual functionality of these molecules has not been systematically characterized. This review aimed to comprehensively explore how miRNAs that target the HIV-1 genome simultaneously modulate key innate and adaptive host immune signaling pathways. The conceptual novelty of this study is determined not by the identification of previously unknown miRNA-target gene pairs, but by the systemic integration of two regulatory levels (direct inhibition of the viral genome and modulation of the host cell immune signaling pathways) within a unified analytical framework. Such an integrated approach reveals a proviral regulatory network that remains non-obvious when each of these levels is examined separately. Methods: A narrative review was conducted using PubMed, Scopus, Web of Science, and Google Scholar (all years through 2025). In Stage 1, publications reporting experimentally confirmed interactions between host miRNAs and the HIV-1 genome were identified, yielding a curated set of 15 miRNAs. In Stage 2, target genes for each miRNA were retrieved from miRTarBase, TarBase (experimentally validated) and TargetScan 8.0 (in silico predicted). In Stage 3, target genes were manually mapped to key immune signaling pathways (TLR, NF-κB, JAK-STAT). In Stage 4, targeted literature searches were performed for each miRNA–target gene pair to identify direct experimental evidence of interaction. All stages were performed by two independent researchers, with discrepancies resolved by a third. Results: Fifteen host miRNAs with experimentally confirmed binding to the HIV-1 genome were identified, targeting viral genes including nef, pol, vpr, gag, env, vif, and the 3′-UTR. Thirteen of these miRNAs were found to regulate components of major immune pathways. miR-92a-3p, miR-29a/b-3p, miR-150-5p, and miR-125b-5p emerged as the most pleiotropic regulators, simultaneously suppressing TLR signaling (TLR3, TLR7, TLR8, MyD88, TRAF3/6, IRAK1/4), NF-κB components (REL, RELA, NFKB1), JAK-STAT effectors (STAT1–3, STAT5A/B, JAK2), and negative regulators of cytokine signaling (SOCS and PIAS family proteins). miR-133b and miR-196b-5p were found to selectively regulate SOCS/PIAS proteins without involvement in other analyzed pathways, suggesting potential for selective therapeutic targeting. Conclusions: The analyzed miRNAs exhibit functional dualism, acting as direct post-transcriptional suppressors of the HIV-1 genome while simultaneously functioning as epigenetic modulators of host immune signaling. These two modes of action are not independent but together form a conceptual framework of a self-reinforcing proviral regulatory network that, based on the synthesis of published evidence, is proposed to promote viral latency and immune evasion. The identified miRNAs represent promising, albeit complex, targets for novel therapeutic strategies aimed at eliminating latent HIV reservoirs. Full article

The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1), driven by high mutation and recombination rates, poses significant challenges for diagnostics, therapy, and vaccine development. While variable regions enable immune escape, hyperconserved regions are critical for viral function and represent promising targets for novel therapeutic interventions. This study aimed to develop and validate a bioinformatic algorithm for quantitative assessment of sequence conservation and automated identification of functionally significant conserved regions across all major HIV-1 proteins. A total of 1119 full-length HIV-1 genome sequences representing major subtypes (A1, A2, A6, B, C, D, F1, F2, G, H, J, K) were analyzed. Normalized Shannon entropy (S-index) was calculated for each alignment column. Statistical thresholds for conserved regions were established using 95% confidence intervals derived from bootstrap resampling. Two complementary algorithms, clustering and local maxima detection, were applied to identify conserved regions, which were subsequently mapped to known functional domains based on literature data. Protein conservation varied markedly, with S_m values ranging from 0.784 (Vpu) to 0.920 (Pol). Gag, Pol, and Vpr demonstrated the highest overall conservation, while Env, Rev, Tat, and Vpu exhibited pronounced variability interspersed with conserved domains. In total, 25 conserved regions in Gag, 49 in Pol, 28 in Env, and 6–4 regions in accessory proteins (Vif, Vpr, Rev, Tat, Nef, Vpu) were identified. These regions corresponded to critical functional elements including enzyme catalytic centers, zinc fingers, receptor-binding sites, protein interaction interfaces, and membrane-anchoring domains. The developed computational framework enables statistically grounded identification of evolutionarily constrained regions across analyzed HIV-1 subtypes. The identified conserved regions represent candidate sites for further investigation and may inform downstream studies focused on antiviral target prioritization, immunogen design, and diagnostic assay development. However, their translational applicability requires additional analytical, structural, and experimental validation. Full article

Salmonella enterica serovar Infantis, an important zoonotic pathogen with increasing prevalence in the poultry industry, often persists despite rigorous disinfection. This study characterized the transcriptomic response of the multidrug-resistant Salmonella Infantis strain SE016, isolated from a poultry plant, to osmotic stress, a condition frequently induced by the use of industrial disinfectants. Phenotypic assays demonstrated that stress induced by 15% sucrose simulated osmotic stress, producing a drastic reduction in flagellar motility and a significant increase in biofilm formation in SE016, compared with a susceptible control strain. RNA-seq analysis indicated that SE016 undergoes coordinated transcriptional changes consistent with altered metabolic activity under osmotic stress. Key mechanisms include metabolic braking through repression of tricarboxylic acid (TCA) cycle genes (icd, mdh) and induction of anaerobic nitrate respiration (narGHI, narZWV) as an energy contingency. Furthermore, SE016 showed increased expression of genes involved in osmoprotectant uptake, including the proU transport system and endogenous trehalose synthesis (ostAB) while repressing proline degradation (putA). Furthermore, robust biofilm formation was observed despite repression of the master regulator csgD. This was mediated by the CsgD-independent induction of the diguanylate cyclase adrA, activating cellulose synthesis (bcs). These results suggest that pathways associated with the OmpR/EnvZ two-component system may contribute to energy balance and persistence-related phenotypes under industrial-like stress conditions. Full article

To assess the potential risk of expansion of the sweet potato weevil (Cylas formicarius) in China under climate change, we combined principal component analysis in environmental space (PCA-env) with a Biomod2 ensemble model, using 173 occurrence records from its native range in India and its invaded range in China. We quantified the dynamics of the climatic niche between the native and invaded ranges and projected both current and future climatically suitable areas in China. Precipitation during the wettest month (Bio13), mean temperature during the driest quarter (Bio9), and isothermality (Bio3) were the key climatic predictors. Niche overlap between India and China was low (Schoener’s D = 0.107). The invaded niche was characterized by high stability (0.991) with very limited expansion (0.009), indicating strong niche conservatism. However, a relatively high unfilling value (0.633) suggests that the species has not yet occupied all potentially suitable climatic space in China. The current suitable area was estimated at 37.55 × 10⁴ km², primarily concentrated in South China and the southeastern coastal region. Under future climate scenarios, suitable habitat is projected to expand overall, extending into Central, Eastern, and Southwestern China. This study provides a climate-informed forecasting framework for assessing the potential spread of C. formicarius in China and offers practical support for quarantine surveillance and region-specific management. Full article

Smart retail adoption (SRA) is widely seen as a way to improve operations. But how it affects business performance (BP) is still unclear. This study builds a framework using information theory and the Technology–Organization–Environment (TOE) framework. We use data from 220 Chinese retail firms (2012–2023). Our analysis shows that SRA significantly improves BP. It does so by first reducing incomplete information (measured by analyst forecast dispersion, AFD) and then lowering uncertainty (UNC). These two factors work in sequence. Technological conditions (TECH), organizational conditions (ORG), and environmental conditions (ENV) all strengthen this effect. SRA also has strong long-term benefits. The effect is greater in non-state-owned firms, large firms, firms in central China, and those that rely mainly on offline channels. This study explains how SRA boosts BP and offers practical insights for retail transformation. Full article

Human endogenous retroviruses (HERVs) represent 8% of our genome. They are remnants of ancient infections of germinal cells. HERVs are no longer infectious, but their enhanced expression is implicated in several diseases, including neuropsychiatric disorders. Their transcription is regulated by TRIM28 and SETDB1, which are involved in the regulation of epigenetic processes, in neural cell differentiation, and brain inflammation. We explored the expressions of HERVs and TRIM28/SETDB1 in adolescents affected by anorexia nervosa (AN). Through real-time PCR, we assessed the transcription levels of pol genes of HERV-H, -K, and -W, of env genes of Syncytin 1 (SYN1), Syncytin 2 (SYN2), and of HERV-W, and of TRIM28 and SETDB1 in whole blood of 37 adolescents with AN and in healthy controls (HCs) of comparable age. HERV-H-pol, HERV-K-pol and SETDB1 transcriptional levels were significantly higher in adolescents with AN as compared with HCs, while HERV-W-pol and -env were downregulated in the former. No differences were observed for SYN1, SYN2, and TRIM28 between the two groups. The observed expression pattern of HERVs is specific for AN as compared to other neuropsychiatric disorders. These aberrant expressions suggest a potential role of retroviral elements in the pathophysiology of AN, opening the way for innovative diagnostic and therapeutic strategies. Full article

Bovine leukemia virus (BLV) is an oncogenic retrovirus and the etiological agent of enzootic bovine leukosis (EBL), which is spread worldwide. This study presents data on the genetic diversity of BLV in the Novosibirsk region of Russia. ELISA-positive samples were selected from six districts of the Novosibirsk region (Dovolnoye, Barabinsk, Tatarsk, Toguchin, Bolotnoye, and Kochenyovo districts). To assess the diversity of circulating BLV genotypes, samples were collected from settlements and districts that were geographically distant from each other and had no shared pasture lands. In total, 1410 bp fragments encoding the env gene region were obtained from 417 BLV-positive samples. Phylogenetic analysis classified 325 BLV strains (77.9%) as genotype 4 (G4) and 92 strains (22.1%) as genotype 7 (G7). A pairwise identity matrix was constructed for 268 amino acid residues. Pairwise identity of BLV amino acid sequences in the gp51 region ranged from 96.6% to 100% for G4 and from 97.4% to 100% for G7. Multiple alignment of the amino acid sequences identified 74 mutations found in the Russian BLV variants. Through the addition of 417 novel env BLV sequences to GenBank, this study significantly expands the foundational data and knowledge of BLV molecular epidemiology in Russia. Full article

The DIGIT experiment was launched at the Tournemire Underground Research Laboratory (URL) with the aim of determining the effects of temperature on the transfer of tracers mimicking the most mobile radionuclides in the Toarcian clay rock. The properties of this rock are similar to those of the host rocks being considered for a future deep geological repository for high-level radioactive waste (HLW). The experiment involves the monitoring of the interaction between a test water doped with stable halides and deuterium at constant concentration, and the porewater of the Toarcian clay rock under constant ambient conditions, as well as at higher temperature induced by artificial heating. This experiment seeks to partially address questions regarding the potential spread of contaminants during the thermal phase of HL waste packages. Specifically, the in situ experiment aims to evaluate the role of scale effects, thermodiffusion, a process that combines Fick’s law, the Soret effect, and convection in the transfer of radionuclides. This paper is the second part of a companion paper dedicated to predictive calculations and the installation of the experimental device. It presents the main experimental and modeling results obtained since the beginning of the installation and after 20 months of heat at 70 °C. The test was carried out in five phases, finishing with a sampling campaign: a phase 0 called “initial conditions”, followed by a pure diffusion phase (5 months), then three phases in a heated period lasting 1 year and 8 months. In total, 47 rock cores were analyzed, with approximately 170 samples tested by four diffusion methods (radial, outgoing, through and in vapor-phase) to determine the tracer concentrations in the porewater, their water content and their diffusive transport parameters. The results show a decrease in tracer concentrations with distance from the test zone, in the directions parallel and perpendicular to the stratification. The anisotropy of the medium results in greater migration in the direction parallel to the stratification. Thermal properties also confirm anisotropy with a higher thermal conductivity in the direction parallel to the stratification. Finally, an activation energy of 22.9 ± 1.7 kJ·mol⁻¹ could be proposed by NMR for deuterium, indicating diffusion behavior following an Arrhenius law between 30 and 70 °C. The experimental data allowed for the calibration of a 2D axisymmetric numerical model using the commercial finite element software COMSOL Multiphysics^®. The Fick’s law corrected by an Arrhenius law best reproduces the penetration of deuterium and anions. The Soret effect, integrated into certain scenarios, is only significant for anions’ migration, using a fitted Soret coefficient of 0.1 K⁻¹, as proposed in the literature for the Callovo-Oxfordian, the host rock of the Cigéo project in the east of France. The calibration of the simulated data with the experimental data allowed for the characterization of damaged and/or disturbed zones evolving over time. Simulations over 150 years, the duration of the thermal maximum for HLW packages, show that advection—modeled by Darcy’s law—would have a negligible role in this context due to the low permeability of the upper Toarcian. In conclusion, the DIGIT test showed that, for the Upper Toarcian clay rocks at the Tournemire URL in France, diffusion, corrected for the effect of temperature, is the mechanism that characterizes the transport of radionuclide analogues. The study showed that thermodiffusion has a limited influence on deuterium migration but remains significant for anions in the case of a coupling between temperature correction and thermodiffusion. The test also highlighted the impact of temperature on the spatiotemporal development of a damaged and/or disturbed zone. These new and relevant results in the field will need to be confirmed later through additional experiments. Full article

The beneficial use of mining waste aligns with circular economy thinking: saving primary resources can extend their lifetime and maintain availability, reduce the volume of legacy mining waste and its environmental impacts, and develop a resource beneficiation industry that is less energy and water intensive; mining lower grades at larger scale inevitably requires more beneficial reuse. Existing classifications applicable to different types of mine waste were reviewed. These include factors such as the mode of origin during the mining operation, grain size, chemical composition and stability. The result shows that these factors also largely control their civil engineering applications, suitability for end use sectors and potential hazards. Long-term liabilities related to chemical stability were identified as the most difficult challenge. When developing a reuse project, either by the end users or by the mine operator, it is likely that resource screening covering a comprehensive range of factors will be required, as none of the existing schemes individually cover all of the aspects needed to fully assess suitability for beneficial use. In conclusion, there is a need for a systematic and structured approach to classification of mining waste to facilitate reuse as raw materials, such as that presented in our review. Full article

Antimicrobial resistance has renewed interest in bacteriophage therapy, yet bacterial evolution frequently undermines treatment efficacy. Combination phage therapy is commonly implemented as simultaneous phage cocktails, but whether this is optimal remains in question. Here, we experimentally compared simultaneous versus sequential administration of two phages, an evolved λ called ‘λtrn’ and T2, on Escherichia coli K-12 under controlled laboratory conditions. Across replicated experiments, treatment outcome depended strongly on delivery strategy, dosing order, and timing. Contrary to expectations, sequential delivery consistently achieved greater and more sustained bacterial suppression than simultaneous cocktails, although only when T2 initiated the sequence. Phenotypic assays revealed that treatment differences were driven by the accessibility and timing of cross-resistance evolution. λ-first treatments rapidly selected for cross-resistant bacteria prior to exposure to the second phage, rendering subsequent treatment ineffective. In contrast, T2-first sequential treatments delayed or limited cross-resistance and frequently produced single-phage resistance or collateral sensitivity. Cocktail treatments showed intermediate dynamics, with cross-resistance evolving more slowly but consistently. Whole genome sequencing identified distinct genetic routes to cross-resistance, including regulatory mutations in envZ affecting expression of the phage receptor OmpF, as well as envelope-modifying, mucoidy-associated mutations. Engineering envZ mutations into unevolved backgrounds confirmed the mutation’s sufficiency to confer low-cost cross-resistance. Together, these results demonstrated that phage therapy efficacy depended not only on phage composition but on how selection pressures were ordered in time, highlighting evolutionary steering as a powerful principle for multi-phage therapy design. Full article

Human T-cell leukemia virus type-1 (HTLV-1) is endemic to numerous regions worldwide, including Central Australia. The Australo-Melanesian subtype-C is endemic within Australia and Oceania, whereas subtype-A is the most widely distributed subtype globally. The lack of an approved vaccine highlights HTLV-1 as a neglected public health issue. To inform the development of HTLV-1 Envelope (Env)-based vaccines, we assessed anti-Env antibodies in an HTLV-1c+ cohort of First Nations individuals in Central Australia. Of the 62 plasma samples from patients with confirmed HTLV-1 serological diagnosis, 76% were positive for Env binding in ELISA, but 90% neutralized HTLV-1c pseudovirus (PSV) infection. Neutralization breadth with the capability of blocking both subtype-A and subtype-C PSV infection was identified in 100% of samples tested. Proviral load was positively associated with anti-Env response, with binding epitopes mapping to the proline-rich region of gp46-SU. Env-directed IgG showed the capacity to engage Fcγ receptors key to inducing antibody-dependent cellular cytotoxicity/phagocytosis responses. Serological response was not associated with comorbidities linked to HTLV-1c in this population (bronchiectasis, chronic kidney disease, diabetes). These findings demonstrate that potent humoral immunity arises and is sustained during HTLV-1 infection, suggesting that an Env-based vaccine displaying authentically native epitopes will be capable of recapitulating these neutralizing responses. Full article

With the increasing deployment of autonomous driving systems, the opaque nature of deep reinforcement learning (DRL) decision models hinders understanding and validation of driving decisions. To address this challenge, we propose a Hybrid Attribution-based Interpretable Deep Reinforcement Learning framework (HA-IDRL) for autonomous driving behavior decision-making. The framework introduces a Hybrid Gradient–LRP (HGL) attribution mechanism that integrates gradient-based attribution and Layer-wise Relevance Propagation (LRP) to capture complementary sensitivity and contribution information, producing more consistent and comprehensive post hoc explanations. In addition to post hoc interpretability, we enhance structural interpretability by replacing the conventional multilayer perceptron (MLP) in the Dueling Deep Q-Network (Dueling DQN) architecture with Kolmogorov–Arnold Networks (KAN). By representing nonlinear interactions through learnable univariate functions and explicit summation structures, KAN provides inherently interpretable functional decompositions. The proposed framework is evaluated on a highway lane-changing task using the highway-env simulator. Experimental results show that HA-IDRL achieves decision-making performance comparable to representative DRL baselines, including Dueling DQN and Soft Actor-Critic (SAC), while providing explanations that are more stable and better aligned with human driving semantics. Moreover, the proposed method produces explanations with low computational overhead, enabling efficient and real-time interpretability in practical autonomous driving applications. Overall, HA-IDRL advances trustworthy autonomous driving by enabling high-performance decision-making and rigorous, multi-level interpretability, thereby improving the transparency and operational reliability of DRL-based driving policies. Full article