Browse Articles

Hidden Markov models reveal behavioral state dynamics in depth-related locomotion in mice

Understanding how mice process and respond to visual depth cues is crucial for studying visual perception, yet traditional behavioral analyses often miss key aspects of this process, such as the dynamic transitions between behavioral states and the integration of multiple spatial cues that shape depth-related behaviors. Here we demonstrate that mouse responses to visual depth cues are more sophisticated than previously recognized, involving both direct avoidance behaviors and complex modulations of exploratory patterns. By combining a modified circular apparatus with Hidden Markov Model analysis, we reveal that mice transition between three distinct behavioral states—resting, exploring, and navigating—in response to visual depth cues. Using this framework, we uncover several fundamental aspects of mouse visual processing: depth perception has an optimal range of spatial frequencies, with strongest responses to patterns between 6–8 cm; visual processing integrates multiple spatial cues rather than triggering simple avoidance; and initial strong cliff-avoidance responses evolve into more nuanced behavioral adaptations over time. Comparisons between wild-type C57BL/6J mice ( Mus musculus ), retinal degeneration models (rd1-2J, C57BL/6J background, Mus musculus ), and control conditions confirm that these behavioral patterns specifically reflect visual processing rather than general exploratory behavior. These findings reveal that mouse depth perception involves sophisticated neural processing that modulates overall exploratory behavior rather than simply triggering avoidance responses. Our approach establishes a new framework for analyzing complex behavioral sequences in neuroscience research, demonstrating how refined behavioral analysis can reveal previously undetectable aspects of sensory processing.

Diverse thioether macrocyclized peptides through a radical SAM maturase

Disulfide bonds stabilize many bioactive peptides, but their susceptibility to reduction under physiological conditions limits broad applicability in biotechnology. PapB is a promiscuous radical S -adenosyl-L-methionine enzyme that is involved in the maturation of PapA, which is a ribosomally produced and posttranslationally modified polypeptide. PapB introduces six thioether linkages between internal Cys residues and carbon atom that is α to the side-chain carboxylate of Asp/Glu residues C-terminal to the Cys residues. Herein, we show that PapB also efficiently couples an internal Cys thiol to the C-terminal carboxylate of peptides terminating in D- or β-amino acids, forming α- or β-thioether macrocycles. Moreover, PapB tolerates β- and N-methyl amino acids within the peptide, resulting in the formation of macrocycles that are comprised entirely of unnatural amino acids, such as peptides containing all β-residues. These findings establish PapB as a sequence-agnostic thioether ligase for efficient C-terminal macrocyclization. Our work expands the enzymatic toolbox for constructing conformationally constrained peptides for therapeutics and chemical biology.

The influence of citrus rootstocks on lime genotype tolerance to witches’ broom disease

Optimizing reliability of RBC signal oscillation measures from hyperpolarized 129Xe MRI

Recent advances to gas exchange hyperpolarized 129Xe MRI (Xe-MRI) have demonstrated that cardiogenic oscillations within the xenon red blood cell (RBC) signal are sensitive to pulmonary disease. Moreover, by implementing keyhole image reconstruction with gas exchange images collected using standard methodology, maps of regional oscillation amplitude can be generated. While such mapping has been demonstrated on a limited basis, validating these maps remains challenging due to the absence of easily measured biomarkers of pulmonary microvascular health. Moreover, as this is a very new technique, each of the previous implementations has used different methodology; it is unclear which of these methods provides optimal measures of regional oscillation amplitude. In this study, we evaluated oscillation mapping using the different published methods to determine which has the best same-day reliability. Because there are no easily obtainable measures of pulmonary vascular health, reliability serves as a valuable endpoint for validating that these maps are sensitive to real pulmonary physiology. We evaluated the same-day reliability of RBC oscillation measures in patients with systemic sclerosis (N = 6) and pulmonary arterial hypertension (PAH; N = 10), using single-time-point data from healthy volunteers (N = 9) to demonstrate “healthy” oscillation amplitude maps. Global measures of RBC oscillation amplitude (intraclass correlation coefficient; ICC = 0.88) had comparable reliability to standard xenon MRI measures (ICC ≥ 0.82). When examining oscillation mapping, some regional features showed disagreement across scans, but reliability of overall means was strong (ICC ≥ 0.86). Moreover, we show that recent advances in oscillation amplitude mapping for generating both amplitude and phase can provide equivalent maps to those methods that only provide amplitude. Overall, our findings demonstrate that Xe-MRI oscillation mapping has strong reliability when using optimized methods, even in participants with pulmonary disease.

Negative interplay between HIV-1 Gag and amyloid precursor protein centers around competition for VPS4A and TSG101

Intracellular multivesicular bodies (MVBs) act as sites of assembly and release of HIV type 1 (HIV-1) in macrophages and microglia. Recent work has shown that processing of amyloid precursor protein (APP) into a C-terminal fragment (CTF), termed C99, inhibits HIV-1 access to CD63+ MVBs and to counteract this, HIV-1 Group-specific antigen (Gag) increases C99 processing into toxic amyloids. However, the underlying reasons for this negative interplay between Gag and C99 remain unclear. Here, we show that HIV-1 Gag polyprotein and APP processing pathways intersect and compete, relying in different ways on two vesicular trafficking components: the endosomal sorting complexes required for transport protein, TSG101, and vacuolar protein sorting (VPS) subunit, VPS4A. VPS4A plays a complex role in infection by both directly regulating virion production and the abundance of distinct CTFs with differing subcellular localizations and effects on infection. Meanwhile, APP and C99’s use of TSG101 for insertion into vesicles limits Gag access to MVBs. Depletion of TSG101 resulted in impaired Gag localization to MVBs and processing into mature virions, and this could be partially reversed by codepletion of APP. By contrast, modulation of TSG101 or APP levels had no effect on the localization patterns of a Gag-P6 mutant that is unable to bind TSG101, while this mutant also failed to promote C99 degradation. Our findings reveal how CTF processing and HIV-1 maturation at MVBs converge in complex ways around VPS4A and TSG101, which in turn underlies how these processes negatively influence one another during virus replication in microglia.

Correction: Characterization and health risk assessment of airborne microplastics in Delhi NCR

Double hit of foetal growth restriction and postnatal hyperoxia alters lung structure and function in a preterm rabbit model of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a disease with a multi-factorial pathophysiology; however, current animal models lack complexity. We employed a double-hit model with an antenatal insult of foetal growth restriction paired with milder postnatal hyperoxia exposure. We induced foetal growth restriction (FGR) by injecting N(G)-nitro-L-arginine methyl ester (L-NAME) in the pregnant rabbit, and exposed preterm-born kittens to 70% hyperoxia for 7 days. L-NAME effectively induced FGR, and mortality rates were acceptable. The double-hit group exhibited adverse outcomes, including decreased lung compliance, increased airway resistance, and structural changes such as alveolar simplification and thickened septa. Gene expression analysis in the L-NAME group revealed downregulation of vascular growth factors, suggesting impaired vascular development. In contrast to traditional hyperoxia models, our double-hit approach enables lower hyperoxia exposure, aligning more closely with clinical practice guidelines in neonatology. The findings underscore the importance of antenatal factors in BPD pathophysiology and reinforce the need for refined animal models that accurately reflect the complexities of preterm lung development.

^FADD DED filaments coordinate complex IIa assembly during TNF-induced apoptosis

Extrinsic apoptosis is initiated by signaling from death receptors, leading to the assembly of RIPK1, FADD, and caspase-8 complex. Subsequently, caspase-8 forms a filamentous structure through the oligomerization of its tandem death effector domain (tDED), resulting in caspase activation and cell death. Although the DED of FADD ( FADD DED) is homologous to the tDEDs of caspase-8 ( casp8 tDED) and both oligomerize to function, the functional form of FADD DED oligomer in extrinsic apoptosis remains unclear. Here, using cryogenic-electron microscopy, we elucidate the structure of FADD DED filaments comprising three helical chains assembled through three types of iterative interactions. Mutations disrupting FADD DED filament formation impair the recruitment of RIPK1 and caspase-8, and abrogate the cell death response, suggesting that FADD DED filamentation represents an important mechanistic step in the initiation of TNF-induced extrinsic apoptosis. Contrary to the belief that the homotypic death domains of RIPK1 and FADD are solely responsible for their interaction, we here show this interaction requires FADD DED filamentation. Furthermore, cFLIP can disrupt FADD DED filaments, uncovering an additional antiapoptotic mechanism of cFLIP beyond its disruption of caspase-8 filament. Molecular dynamics simulations reveal that FADD DED filament thermodynamically favors casp8 tDED monomer over FADD DED monomer, thus explaining the hierarchy and stoichiometry of FADD/caspase-8 complex assembly. These findings highlight the hitherto unappreciated roles of FADD DED filament formation in extrinsic apoptosis.

Phenotypic characterisation and prevalence of carbapenem-resistant Enterobacterales in a tertiary care centre in Bihar India

High-temperature thin-film thermocouple for aero-engines

A thin-film thermocouple sensor directly deposited on nickel-based superalloys was investigated for aero-engine applications. To address the high-temperature and harsh environment challenges, the sensor’s film structure was meticulously designed. A NiCrAlY thin-film transition layer was deposited via magnetron sputtering, while an Al₂O₃ thin-film insulation layer and protective layer were prepared using electron beam evaporation and RF magnetron sputtering. Additionally, a Pt10Rh/Pt thin-film sensitive layer was fabricated via DC magnetron sputtering. Results indicate that the thin-film thermocouple sensor can operate at temperatures up to 1100 °C, with a Seebeck coefficient of 8.16 μV/°C, a maximum temperature error below ±1%, and a service life exceeding 20 hours. This sensor withstands the harsh conditions of aero engines, significantly improves local temperature measurement accuracy, and offers valuable insights for turbine blade lifespan and cooling design.

Synaptic transmission is dispensable for selecting the winner input but is crucial for the subsequent events of synapse elimination

Synaptic transmission has long been thought to regulate neuronal wiring during postnatal development, but this assumption remains largely untested. Selective strengthening of a single “winner” climbing fiber (CF) afferent to each Purkinje cell (PC) and elimination of the other “loser” CF axons in the cerebellum has been a representative model of neural circuit refinement. Here, we examined the role of neurotransmission at CF-PC synapses in their postnatal development. We labeled a subset of CFs in neonatal mice with fluorescent markers and the tetanus toxin light chain to ablate neurotransmitter release from these CFs. Surprisingly, we found that such neurotransmitter release–deficient CFs were able to become the winners. However, synaptic transmission was crucial for the winning CF to extend its synaptic territory along the PC dendritic arbor and eliminate the loser CFs. These findings reveal how synaptic transmission governs multiple steps of synapse elimination but not the selection of the winner input that persists throughout life.

Holographic hyperbranched polymer nanocomposite grating with exceptionally large neutron scattering length density modulation amplitudes

Abstract Nanoparticle–polymer composite gratings incorporating ultrahigh-refractive-index hyperbranched polymers as organic nanoparticles have demonstrated exceptional light optical properties, yet their potential for neutron diffraction applications remains unexplored. We report on the neutron optical properties of a holographically structured hyperbranched-polymer–dispersed nanocomposite grating at a quasi-monochromatic neutron wavelength of 2 nm. We show that neutron diffraction measurements performed at the SANS-I instrument of the Paul Scherrer Institute (Switzerland) reveal exceptionally high neutron scattering length density modulation amplitudes. These scattering length density modulation amplitudes are the highest reported to date. Very high neutron diffraction efficiency is expected with the use of thicker uniform gratings and longer neutron wavelengths, with low angular and wavelength selectivity constraints.

A fog-assisted group-based truth discovery framework over mobile crowdsensing data streams

With the proliferation of mobile crowdsensing (MCS) and crowdsourcing, new challenges are emerging every day. Although crowdsensing has become a popular sensing paradigm to aggregate sensor readings from a variety of sources, data inconsistency has arisen as a serious challenge. Truth discovery (TD) has been developed as an effective method for reducing data inconsistency and as a validity assessment for conflicting data from various sources. In addition, MCS applications and services are moving beyond a single individual participant to community groups and are influenced by group behavior. To address these challenges in this paper, we propose a novel Fog-assisted Group-based Truth Discovery Framework over MCS Data Streams, an efficient TD system for real-time applications. Specifically, we first initialized the weights for the weight update process in TD with the participants’ credibility level. Then, we developed a novel Two-layer Group-based Truth Discovery (TGTD) mechanism in which the first layer estimates the truth of the group’s members and the second layer estimates the aggregated truth for the groups. We have conducted extensive experiments over synthetic and real-world datasets to prove the effectiveness and efficiency of our framework. The results indicate that TGTD achieves superior truth discovery accuracy compared to current streaming truth discovery approaches, while maintaining a reasonable running time. The organization of the streaming process within the fog architecture simulation is identified as an area for further investigation and future work.

Self-generated chemotaxis of mixed cell populations

Cell and tissue movement in development, cancer invasion, and immune response relies on chemical or mechanical guidance cues. In many systems, this behavior is locally directed by self-generated signaling gradients rather than long-range, prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally and navigate through self-generated gradients remains largely unexplored. Here, we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous cell populations. We find that the relative chemotactic sensitivities of different cell populations control their long-time coupling and comigration dynamics, with boundary conditions such as external cell and attractant reservoirs substantially influencing the migration patterns. Our model predicts an optimal parameter regime that enables robust and colocalized migration. We test our theoretical predictions with in vitro experiments demonstrating the comigration of distinct immune cell populations, and quantitatively reproduce observed migration patterns under wild-type and perturbed conditions. Interestingly, immune cell comigration occurs close to the predicted optimal regime. Finally, we incorporate mechanical interactions into our framework, revealing a nontrivial interplay between chemotactic and mechanical nonreciprocity in driving collective migration. Together, our findings suggest that self-generated chemotaxis is a robust strategy for the navigation of mixed cell populations.

Proximity to forests, fire and plantation characteristics influence understory plant species richness more than phylogenetic diversity in African mahogany plantations

Behavioral and genetic analysis of the effects of the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) in C. elegans

Psychedelics show promise in treating depression, PTSD, and substance use disorder, prompting research into their mechanisms of action. Most studies use rodent models, but genetic tools can be challenging to apply in this approach. Invertebrate models, like C. elegans , offer a cost-effective alternative with short generation times and genetic tractability. This study examined the worm’s response to the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) by assessing four serotonergic behaviors. Effects of DOI exposure on locomotion speed, swimming frequency, and egg-laying were undetectable, but DOI strongly inhibited feeding. Interestingly, this effect was independent of serotonin receptors, suggesting DOI may act through alternative pathways. These findings indicate that C. elegans can serve as a useful model for studying psychedelic drug effects, potentially revealing novel mechanisms beyond the serotonergic system. Further research could help clarify these pathways, improving our understanding of the therapeutic potential of psychedelics and refining their efficacy in treating neuropsychiatric disorders.

Nano-biochar regulates phage–host interactions, reducing antibiotic resistance genes in vermicomposting systems

Biochar amendment reshapes microbial community dynamics in vermicomposting, but the mechanism of how phages respond to this anthropogenic intervention and regulate the dissemination of antibiotic resistance genes (ARGs) remains unclear. In this study, we used metagenomics, viromics, and laboratory validation to explore how nano-biochar affects phage–host interactions and ARGs dissemination in vermicomposting. Our results revealed distinct niche-specific phage life strategies. In vermicompost, lytic phages dominated and used a “kill-the-winner” strategy to suppress antibiotic-resistant bacteria (ARB). In contrast, lysogenic phages prevailed in the earthworm gut, adopting a “piggyback-the-winner” strategy that promoted ARGs transduction through mutualistic host interactions. Nano-biochar induced the conversion of lysogenic to lytic phages in the earthworm gut, while concurrently reducing the abundance of lysogenic phages and their encoded auxiliary metabolic genes carried by ARB. This shift disrupted phage–host mutualism and inhibited ARGs transmission via a “phage shunting” mechanism. In vitro validation with batch culture experiments further confirmed that lysogenic phages increased transduction of ARGs in the earthworm gut, while nano-biochar reduced the spread of ARGs by enhancing lysis infectivity. Our study constructs a mechanistic framework linking nano-biochar induced shifts in phage lifestyles that suppress ARG spread, offering insights into phage–host coadaptation and resistance mitigation strategies in organic waste treatment ecosystems.

Shared SNP effects across breeds increase the genomic prediction accuracy for numerically small breeds

Political affiliation or need for cognition? It depends on the post: Comparing key factors related to detecting health disinformation in the U.S.

We investigate why people believe disinformation about health-related issues. Acting on disinformation could lead to severe injuries and even death. Five hundred eight American respondents each reviewed 10 different social media posts about health-related topics, and 60% of the posts contained disinformation. They were asked to evaluate the posts for their honesty and explain their decisions. Respondents successfully detected disinformation about 2/3 of the time. Across all participant responses, need for cognition was the only factor important to successful detection of disinformation. When investigating each social media post individually, need for cognition was key for 35% of the posts, while political affiliation was key for 15%. Neither factor was important for the remaining 50% of posts. People with a high need for cognition were adept at detecting online disinformation, but those with conservative political affiliations were not. Those best suited to detecting health-related disinformation either had a high need for cognition or a liberal political affiliation.

Aphid herbivory on macrophytes drives adaptive evolution in an aquatic community via indirect effects

Indirect ecological effects occur when the impact of one species on another is mediated by a third species or the shared environment. Although indirect effects are ubiquitous in nature, we know remarkably little about how they may drive ecoevolutionary processes across community boundaries. Here, we show that insect (aphid) herbivory on macrophytes (duckweed) drove the adaptive evolution of a planktonic crustacean ( Daphnia magna ) in large outdoor aquatic mesocosms via indirect ecological effects. Aphid herbivory reduced duckweed growth and increased the nutrient and light availability in the water column, which promoted phytoplankton growth and boosted the abundance of D. magna that feed on phytoplankton. Whole-genome pool-sequencing and phenotypic assays revealed aphid-herbivory-mediated evolutionary changes to Daphnia population. Transplant experiments indicated that these evolutionary changes were adaptive. Furthermore, aphid-herbivory-mediated biotic and abiotic changes in the aquatic community increased the performance of the macrophytes and aphids. These results demonstrate that indirect ecological effects can shape ecoevolutionary interactions between seemingly independent species in natural communities.