BACKGROUND: The genomes of Aedes spp. mosquitoes host hundreds of non-retroviral endogenous viral elements (nrEVEs). The majority of nrEVEs are confined in piRNA clusters and produce P-element-induced wimpy testis-intera...BACKGROUND: The genomes of Aedes spp. mosquitoes host hundreds of non-retroviral endogenous viral elements (nrEVEs). The majority of nrEVEs are confined in piRNA clusters and produce P-element-induced wimpy testis-interacting RNAs (piRNAs), which were shown to be antiviral. Whether this is a universal mechanism or some nrEVEs have been exapted for antiviral functions as transcribed RNA or translated proteins remains unknown. RESULTS: We identified 20 nrEVEs located outside piRNA clusters and encompassing complete viral open reading frame in the genome of the Asian tiger mosquito Aedes albopictus. By integrating in vivo and in vitro experimental approaches using Aag2 cells, we provide evidence suggesting that one nrEVE, designated Flavi24, is translated in adult mosquitoes and contributes to controlling cognate viral infection. CONCLUSION: Our results expand the functions of Ae. albopictus nrEVEs suggesting they can regulate host-virus interactions through various mechanisms.
BACKGROUND: Environmental sex determination (ESD) enables organisms to adjust their sexual fate in response to external cues. Fluctuating sex ratios have long suggested the presence of ESD in populations of plant-parasit...BACKGROUND: Environmental sex determination (ESD) enables organisms to adjust their sexual fate in response to external cues. Fluctuating sex ratios have long suggested the presence of ESD in populations of plant-parasitic nematodes. RESULTS: We show that in the potato cyst nematode Globodera pallida sex is regulated by nutritional cues. By manipulating sucrose availability to the host plant, we could steer the sex determination of G. pallida. Whereas high-sucrose medium promotes female development, low-sucrose medium promotes male development. Transcriptome analyses on the early stages of parasitism reveal that female development requires extensive transcriptional activation and post-transcriptional regulation. We identify Gp-lin-29, a transcription factor homologous to lin-29 in Caenorhabditis elegans, as a potential regulator of ESD. Small RNA sequencing uncovered the male-biased expression of Gp-let-7, a putative repressor of Gp-lin-29, and the female-biased expression of four miRNAs, including Gp-miR-100, located at the same genomic locus as Gp-let-7. Target prediction and enrichment analyses suggest that these female-biased miRNAs may actively suppress male developmental programs. CONCLUSIONS: Together, our findings support a model in which G. pallida juveniles follow a default male developmental trajectory unless redirected by favourable environmental cues to become female. This study provides mechanistic insight into ESD in cyst nematodes and positions G. pallida as a tractable system for exploring epigenetic regulation of developmental plasticity.
In this Perspective, we suggest combining physiological, neurobiological, behavioural, and social data from multiple marine mammal species to create evolutionary models of the emergence of social vocal coordination. Mari...In this Perspective, we suggest combining physiological, neurobiological, behavioural, and social data from multiple marine mammal species to create evolutionary models of the emergence of social vocal coordination. Marine mammal sound production mechanisms have evolved to manage vocalizing and breathing in an aquatic environment, potentially releasing functional constraints on the control of vocal timing. Intervals in rhythmic cetacean vocalizations cover a remarkable temporal range, from less than a millisecond in porpoise burst pulses to 10 s in sperm whale slow clicks. Many cetaceans demonstrate temporally coordinated social behaviour, while pinnipeds express high variability in vocal plasticity and social behaviour. The systematic variability of vocal production mechanisms, vocal rhythms, and sociality can be compared phylogenetically to generate models for the evolution of social rhythm in the vocal domain.
BACKGROUND: Alzheimer's disease and related dementias (ADRD) pose a critical challenge for the aging U.S. population, yet many biological pathways remain unclear. Recent work has focused on whether peripheral immunosenes...BACKGROUND: Alzheimer's disease and related dementias (ADRD) pose a critical challenge for the aging U.S. population, yet many biological pathways remain unclear. Recent work has focused on whether peripheral immunosenescence contributes to cognitive aging. Using the Health and Retirement Study (HRS), we examined associations between peripheral immunosenescence and domain-specific cognitive function. RESULTS: Immune function was associated with general and domain-specific cognition, with variation by sex and immune marker. The CD4 + EMRA:Naïve T Cell Ratio, CD4 + Naïve:CD8 + EMRA Ratio, and CMV IgG showed the most consistent associations, particularly with general and executive function. A one-SD increase in CMV IgG was associated with 0.06 SD lower executive function (95% CI: -0.07, -0.05), persisting after adjustment for confounders. CONCLUSIONS: Associations with peripheral immune markers suggest a potential role for peripheral immunosenescence in cognitive aging. The immune system may be an early contributor to cognitive vulnerability, underscoring the need to integrate immune aging into ADRD research.
BACKGROUND: Behavioural plasticity may contribute to the ability of wild animals to survive disease outbreaks. In absence of endogen heat control, ectothermic animals adjust their body temperature behaviourally. While ma...BACKGROUND: Behavioural plasticity may contribute to the ability of wild animals to survive disease outbreaks. In absence of endogen heat control, ectothermic animals adjust their body temperature behaviourally. While many studies reported behavioural fever, its opposite, behavioural cooling-when infected animals lower their body temperature by using cool microenvironments-remains poorly documented. RESULTS: Here, we report the first experimental evidence of behavioural cooling in an ectothermic vertebrate as a response to pathogenic infection. We investigated thermoregulatory responses in tadpoles of the agile frog Rana dalmatina, a cool-adapted amphibian, following experimental infection with a ranavirus that can replicate well at high temperatures. Tadpoles were placed either in thermal gradients or homogeneously cool environments for 5 days post-exposure. In thermal gradients, all tadpoles reduced their preferred temperatures over time, but this decrease was steeper in infected tadpoles, and individuals with higher infection intensities preferred cooler temperatures. Infected tadpoles decreased the range of their preferred body temperatures over time, while a similar trend was not detectable in non-infected tadpoles. Infection prevalence was similar between the two thermal environments, yet infection intensities were significantly higher in the thermal gradient. CONCLUSIONS: These results suggest fine-tuned thermoregulation by infected tadpoles to balance out the benefits of behavioural cooling for fighting a pathogen versus the immune-suppressive and developmental costs of low temperatures.
Montassar K, Raphaelle Y, Margaux B
… +7 more, Alexis H, Salvatore S, Paul-Alain J, Tristan M, Mathieu B, Aurore F, Tony LG
J Photochem Photobiol B
· 2026 Jun · PMID 42392010
·
Publisher ↗
Click chemistry is a powerful and versatile method for grafting various moieties onto a chemical backbone, enabling the integration of multiple functionalities into a single molecular scaffold. Here, a previously reporte...Click chemistry is a powerful and versatile method for grafting various moieties onto a chemical backbone, enabling the integration of multiple functionalities into a single molecular scaffold. Here, a previously reported cationic lipophosphoramidate, BSV36, was employed in a series of liposomes functionalized with either a naphthalimide or a nitroaniline moiety. These modifications were introduced via aminolysis of phosphonodithioester click reaction, performed either before or after liposome formation. The various liposomes obtained could display - separately or in combination - multiple properties, i.e., fluorescence, nitric oxide (NO) photorelease, and reactive oxygen species (ROS) photogeneration. They were used to conduct a series of assays providing proof-of-principle that a single click-modified liposomal preparation can fluorescently label and photo-inactivate clinical bacterial strains, particularly Staphylococcus aureus, as well as to deliver plasmid DNA into human-derived cell lines. Importantly, comparison of liposome performance enabled the evaluation of the compatibility of the aforementioned features within a single entity. This work therefore offers new insights into the broadened applications of multimodular nanovesicles across diverse biomedical fields. In particular, it highlights their relevance for the treatment of recalcitrant infections in the context of genetic diseases, where the combined implementation of gene therapy and antimicrobial control could provide substantial therapeutic benefit.
High-throughput single-cell assays reveal data that defies discrete categorization. The 'cell cloud' model, grounded in established systems biology principles, offers a framework to navigate biological plasticity alongsi...High-throughput single-cell assays reveal data that defies discrete categorization. The 'cell cloud' model, grounded in established systems biology principles, offers a framework to navigate biological plasticity alongside technical variability.
Flexible behavior requires the ability to modulate sensory processing based on task context, yet the circuit-level mechanisms supporting this capacity remain poorly understood. Here, we combine recurrent neural network m...Flexible behavior requires the ability to modulate sensory processing based on task context, yet the circuit-level mechanisms supporting this capacity remain poorly understood. Here, we combine recurrent neural network modeling and neural recordings from mouse visual cortex to investigate how task context shapes sensory coding. Networks trained on an instruction-based discrimination task develop a disinhibitory interneuron-to-interneuron motif that dynamically gates task-relevant sensory information. Perturbation and lesion analyses show that this motif is necessary for task performance and for maintaining distinct sensory representations across contexts. We validate key predictions in mouse visual cortex, where interneuron activity patterns exhibit comparable task-dependent modulation. These results identify a biologically plausible circuit motif that supports flexible sensory processing and link recurrent connectivity structure to adaptive context integration in both artificial and biological systems.
BACKGROUND: Exposure to DNA damaging agents during fish embryogenesis can induce malformations and developmental disorders. However, there is scarcity of knowledge on dynamics of embryonic DNA repair and its effect on or...BACKGROUND: Exposure to DNA damaging agents during fish embryogenesis can induce malformations and developmental disorders. However, there is scarcity of knowledge on dynamics of embryonic DNA repair and its effect on organogenesis. To address this knowledge gap, we exposed sterlet (Acipenser ruthenus) embryos to DNA-alkylating agent, methyl methanesulfonate (MMS), during blastulation (from 2 to 24 h post-fertilization (hpf)) and observed the effects at hatching (8 days post-fertilization (dpf)) and post-hatching stage (10 dpf). RESULTS: In contrast to control, DNA alkylation damage in treated embryos significantly persisted up to 3 dpf but was resolved by 8 dpf. These observations coincided with a significant increase in expression of key base excision repair (BER) genes (apex1, ogg1, polβ, xrcc1, lig3) and 1.5-fold increase in APE1 protein levels by hatching. These findings suggest that sterlet embryos activate functional BER pathway in response to DNA alkylation. Despite successful DNA repair, embryos exhibited disrupted retinal layers differentiation and reduced expression of tyrosine hydroxylase (TH) at 10 dpf. CONCLUSIONS: Collectively, our results suggest that DNA alkylation can interfere with organogenesis, potentially through misregulation of DNA repair proteins during critical developmental windows. We speculate that DNA alkylation can affect expression of genes critical for early brain and eye development indicating an organ-specific DNA damage response. Notably, this study emphasizes that future studies should address the link between activation of BER pathway and developmental abnormalities when sterlet embryos are genotoxically challenged.
Advances in artificial intelligence (AI)-driven bioinformatics promise democratized discovery, yet major inequities persist. Equitable adoption of bioinformatics tools will require sustained investment in infrastructure,...Advances in artificial intelligence (AI)-driven bioinformatics promise democratized discovery, yet major inequities persist. Equitable adoption of bioinformatics tools will require sustained investment in infrastructure, training, institutions, and global communities, not just access.
Begum MY, Rajkumar M, Govindaraj P
… +3 more, Meenambigai K, Alhamod M, Alotaibi H
J Photochem Photobiol B
· 2026 Jun · PMID 42378734
·
Publisher ↗
Phytofabrication of polymer-based nanocomposites has emerged as a promising approach for developing multifunctional biomaterials with enhanced therapeutic efficacy. In the present study, chitosan-coated magnesium oxide n...Phytofabrication of polymer-based nanocomposites has emerged as a promising approach for developing multifunctional biomaterials with enhanced therapeutic efficacy. In the present study, chitosan-coated magnesium oxide nanocomposites (CS-MgONCs) were successfully synthesized via a green biogenic route using Abutilon indicum leaf extract, integrating the advantages of biopolymers and metal oxides. The formation of CS-MgONCs was preliminarily confirmed by UV-Vis spectroscopy with a characteristic absorption peak at 280 nm. FTIR analysis revealed the involvement of key functional groups responsible for reduction and stabilization, while XRD patterns confirmed the crystalline nature of the nanocomposites. HR-TEM demonstrated a predominantly semi-spherical morphology with an average particle size of 58.93 nm. DLS and zeta potential analyses indicated good colloidal stability, with a surface charge of +8.76 mV, attributed to the chitosan coating. Functionally, CS-MgONCs exhibited significant dose-dependent antioxidant activity, achieving a maximum DPPH radical scavenging efficiency of 78.37 ± 1.34% at 200 μg/mL. The nanocomposites also demonstrated potent antibacterial activity against both Gram-positive and Gram-negative pathogens, with notable zones of inhibition against Staphylococcus aureus (20.71 ± 0.74 mm) and Escherichia coli (19.71 ± 0.74 mm). Furthermore, marked anti-inflammatory activity was observed through inhibition of cyclooxygenase (COX), with 77.58 ± 1.37% suppression of COX-2 activity, suggesting effective modulation of inflammatory pathways. Biocompatibility assessment in zebrafish embryo models indicated acceptable safety profiles, with a 70% survival rate at 200 μg/mL. Importantly, the nanocomposites exhibited pronounced anticancer activity against HT-29 colon cancer cells, reducing cell viability to 21.48 ± 0.98% in a concentration-dependent manner. In conclusion, the findings highlight that biogenically synthesized CS-MgONCs integrate structural stability with multifunctional biological performance, positioning them as promising candidates for future biomedical and therapeutic applications.
BACKGROUND: Circular RNAs (circRNAs) are an emerging class of non-coding RNAs with covalently closed loop structures and have been increasingly recognized for their regulatory roles in disease progression and drug respon...BACKGROUND: Circular RNAs (circRNAs) are an emerging class of non-coding RNAs with covalently closed loop structures and have been increasingly recognized for their regulatory roles in disease progression and drug response. Accurately identifying circRNA-drug sensitivity associations is therefore essential for understanding therapeutic mechanisms and advancing precision medicine. However, most existing computational methods fail to effectively integrate semantic and structural information and overlook cross-modal feature co-optimization, thereby limiting their predictive performance. RESULTS: To address these limitations, we develop an end-to-end graph representation learning framework for circRNA-drug sensitivity prediction by jointly modeling homogeneous similarity structures and heterogeneous interaction relationships. The framework integrates fused similarity graphs, semantic feature encoding with pre-norm residual attention, and structural representation learning via graph convolutional networks with Top-K sparse adjacency. In addition, a large-scale heterogeneous graph and a cross-modal collaborative feature mining module are employed to jointly optimize multi-source representations. Experimental results from 5-fold and 10-fold cross-validation, independent test evaluations, ablation study, and case study demonstrate that the proposed framework consistently achieves superior performance compared with state-of-the-art methods. CONCLUSIONS: The proposed framework provides a robust and effective computational strategy for circRNA-drug sensitivity prediction and offers a valuable tool for uncovering potential therapeutic associations, thereby facilitating future research in drug response analysis and precision medicine.
BACKGROUND: Negative regulation of interferon (IFN) responses is crucial for preventing IFN-induced cellular damage and restoring immune homeostasis after viral clearance. However, whether such regulation occurs at the r...BACKGROUND: Negative regulation of interferon (IFN) responses is crucial for preventing IFN-induced cellular damage and restoring immune homeostasis after viral clearance. However, whether such regulation occurs at the receptor level has not been explored in lower vertebrates. RESULTS: Here we characterized a decoy receptor (CRFB15) in zebrafish, belonging to the cytokine receptor family B, that functions as a decoy receptor to antagonize IFN-mediated signaling. CRFB15 was shown to be upregulated upon viral infection. It bound to IFN ligands and suppressed STAT1 phosphorylation and downstream antiviral effector gene expression, ultimately promoting viral replication. It also interacted with IFN receptors, including CRFB1, CRFB2, and CRFB5, selectively promoting degradation of CRFB2 and CRFB5 and attenuating IFN-induced antiviral response. Furthermore, crfb15 zebrafish exhibited enhanced resistance to viral infection, confirming its role as a negative regulator of IFN signaling. CONCLUSIONS: This study establishes CRFB15 as a key negative regulator of teleost type I IFN signaling. Upon viral infection, CRFB15 is upregulated and suppresses IFN signaling through two distinct pathways: by functioning as a decoy receptor that competitively binds type I IFNs and their functional receptors, and/or by promoting the degradation of the key receptor subunits CRFB2 and CRFB5.
Zhang D, Shen Z, Hu D
… +5 more, Sun J, Li F, Gao L, Fu F, Jiang T
J Photochem Photobiol B
· 2026 Jun · PMID 42364301
·
Publisher ↗
Ocean acidification (OA) exerts diverse effects on marine macroalgae, with calcified species being particularly vulnerable. Due to calcified skeletons can contribute to physical screening against solar ultraviolet radiat...Ocean acidification (OA) exerts diverse effects on marine macroalgae, with calcified species being particularly vulnerable. Due to calcified skeletons can contribute to physical screening against solar ultraviolet radiation (UVR), OA-driven calcification loss may increase exposure of the photosynthetic apparatus to UVR. Here, we cultured Corallina officinalis under ambient CO₂ (∼420 μatm) or elevated CO₂ (∼1000 μatm), with or without UVR, under natural solar radiation. Our results confirmed that OA reduced calcification and, under UVR, enhanced donor-side impairment of photosystem II (PSII), as evidenced by an increase in the relative K-step (W, an indicator of OEC damage) and a decrease in the maximum quantum yield of PSII (Fᵥ/Fₘ). This donor-side injury was accompanied by a reconfiguration of energy fluxes per PSII reaction center, particularly under combined OA and UVR. These impairments further extended to intersystem electron transport and limited the linear electron flow from PSII to the intersystem chain. Photosystem I (PSI) related electron transport was also functionally constrained, as evidenced by the reduced electron transfer probability and terminal reduction yield. This, together with the reduction of cyclic electron transport around PSI, resulted in over-reduction of the intersystem chain and making PSI the limiting photosystem. Together, these results indicate that OA amplified UVR-induced net photodamage and weakened PSII repair capacity in C. officinalis, while also constraining PSI-related electron transport. These findings highlight the potential vulnerability of calcified red algae under future high-CO₂, high-UVR coastal oceans.
BACKGROUND: Cervical cancer remains a leading cause of cancer-related mortality in women, with high-risk HPV types (16, 18, 31, 33, 45, 52, and 58) playing a key role in its development. Platinum-based chemotherapy is st...BACKGROUND: Cervical cancer remains a leading cause of cancer-related mortality in women, with high-risk HPV types (16, 18, 31, 33, 45, 52, and 58) playing a key role in its development. Platinum-based chemotherapy is standard for recurrent or metastatic cervical cancer, but platinum resistance remains a major challenge. The link between HPV infection and platinum resistance is not well understood. Tumor organoids offer a physiologically relevant model for investigating drug resistance mechanisms in cervical cancer. RESULTS: We successfully established 37 cervical cancer organoids (CCOs), with 27 expanded for characterization and drug sensitivity testing. CCOs recapitulated the biomarker expression patterns and genomic features of their corresponding tissues. Drug sensitivity assays revealed increased cisplatin/carboplatin resistance in the non-HPV16 high-risk HPV CCOs subgroup, compared to HPV-negative CCOs. Single-cell RNA sequencing identified diverse cellular populations within CCOs, with platinum-resistant CCOs showing enhanced DNA repair, activation of the PI3K/AKT pathway, and suppressed apoptotic signaling. We also found that the PI3K/AKT inhibitor BYL719 enhanced the response to cisplatin and carboplatin in non-HPV16 high-risk HPV CCOs but not in HPV-negative CCOs. CONCLUSIONS: Cervical cancer organoids faithfully replicate the histopathological and genomic characteristics of their parental tumors, demonstrating their potential as preclinical models for studying cancer progression and drug resistance. Our findings suggest that the non-HPV16 high-risk HPV infections may contribute to increased platinum resistance through enhanced DNA repair mechanisms, increased PI3K/AKT activation and suppressed apoptosis, providing new insights for personalized cervical cancer treatment. The PI3K/AKT inhibitor BYL719 may serve as a potential therapeutic adjunct to enhance platinum efficacy in those patients with platinum-resistant cervical cancer.
Cognitive control is believed to arise from task-dependent interactions among networks of brain regions. Although several debilitating neuropsychiatric disorders are characterized by cognitive network dysfunction, the ne...Cognitive control is believed to arise from task-dependent interactions among networks of brain regions. Although several debilitating neuropsychiatric disorders are characterized by cognitive network dysfunction, the neural circuit mechanisms supporting task-dependent network activity are largely unknown. External and internal task demands elicit opposing responses from key cognitive networks, and claustrum projections target regions associated with both network states. We tested if claustrum supports task-dependent network activity in humans using fMRI during tasks with externally and internally driven demands: working memory (n = 420) and autobiographical memory (n = 35). Claustrum activity increased in both tasks. Claustrum exhibited anatomical connectivity with regions representing all implicated networks, and claustrum effective connectivity suggested an excitatory influence on regions in multiple task-associated networks. Task response and connectivity measures differed between the claustrum and regions prominently implicated in directing network states-the anterior insula and pulvinar. These findings establish a role for the claustrum in supporting task-dependent network states subserving cognitive control.
Recombination suppression leads to genomic erosion through an accumulation of deleterious mutations. A new study in PLOS Biology reveals an outstanding increase in aberrant splicing in non-recombining genomic regions in...Recombination suppression leads to genomic erosion through an accumulation of deleterious mutations. A new study in PLOS Biology reveals an outstanding increase in aberrant splicing in non-recombining genomic regions in green algae.
Gao F, Wang K, Song JL
… +5 more, Wang DN, Wen DK, Liang FM, Feng YZ, Cheng ZY
J Photochem Photobiol B
· 2026 Jun · PMID 42349088
·
Publisher ↗
Acute lung injury (ALI) induced by pneumonia is a life-threatening disease with high mortality, and neutrophil elastase (NE) overexpression is closely associated with its progression. Herein, a NE-activatable molecular p...Acute lung injury (ALI) induced by pneumonia is a life-threatening disease with high mortality, and neutrophil elastase (NE) overexpression is closely associated with its progression. Herein, a NE-activatable molecular probe SO3-NE was synthesized using hemicyanine dye as the scaffold, modified with sulfonic acid groups to improve water solubility. The probe's performance was systematically evaluated: it exhibited negligible cytotoxicity, high sensitivity (LOD = 0.05 U/L), excellent selectivity for NE, and optimal response at physiological pH 7.4 and 37 °C. In vivo experiments on C57 mice (Healthy, ALI, and SIV-treated groups) showed that SO3-NE specifically imaged NE levels, with ALI group exhibiting significantly higher fluorescence signals than the other two groups. Ex vivo assays and organ HE staining confirmed the probe's reliability and low biotoxicity. This probe provides a promising tool for real-time NE detection during pneumonia progression.