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Cis-regulatory evolution of Wnt family genes contributes to a morphological difference between silkworm species.

Tomihara K, Pinharanda A, Kwon YM … +7 more , Taverner AM, Kors LS, Aardema ML, Holder JC, Poyraz L, Kiuchi T, Andolfatto P

PLoS Biol · 2026 Mar · PMID 41805792 · Full text

Closely related species often exhibit distinct morphologies that can contribute to species-specific adaptations and reproductive isolation. One example is Lepidopteran caterpillar appendages, such as the "caudal horn" of... Closely related species often exhibit distinct morphologies that can contribute to species-specific adaptations and reproductive isolation. One example is Lepidopteran caterpillar appendages, such as the "caudal horn" of Bombycoidea moths, which have evolved substantial morphological diversity among species in this group. Using interspecific crosses, we identify the genetic basis of the caudal horn size difference between Bombyx mori and its closest relative Bombyx mandarina. The three largest of eight QTL account for one third the mean horn length difference between the species. The largest of these, on chromosome 4, encompasses a conserved Wnt family gene cluster, key upstream regulators that are well-known for their roles in morphological diversification in animals. Using allele-specific expression analysis and CRISPR/Cas9 knockouts, we show that tissue-specific cis-regulatory changes to Wnt1 and Wnt6 contribute to the species difference in caudal horn size. This kind of modularity enables highly pleiotropic genes, including key upstream growth regulators, to contribute to the evolution of morphological traits without causing widespread deleterious effects.

Expanding invasive species impact assessments to the ecosystem level with EEICAT.

Carneiro L, Pincheira-Donoso D, Leroy B … +9 more , Bertolino S, Camacho-Cervantes M, Cuthbert RN, Bang A, Catford JA, South J, Cooke SJ, Angulo E, Courchamp F

PLoS Biol · 2026 Mar · PMID 41805746 · Full text

The ecological impacts of biological invasions vary widely in type, scale, and severity, highlighting the need for consistent assessment tools. The Environmental Impact Classification for Alien Taxa (EICAT) provides a st... The ecological impacts of biological invasions vary widely in type, scale, and severity, highlighting the need for consistent assessment tools. The Environmental Impact Classification for Alien Taxa (EICAT) provides a standardized framework for assessing their effects, but focuses mainly on population-level impacts. We introduce the Extended EICAT (EEICAT), which incorporates impacts across three ecological dimensions, from individuals to ecosystems, with an impact-based approach. EEICAT enables classification of 19 impact types at the invasion-event level, making it suitable for primary research, synthesis, and management. This framework aims to improve the detection, comparison, and communication of complex ecological impacts caused by biological invasions.

A GABAergic network from AVP- to VIP-neurons in the suprachiasmatic nucleus sets the timing of circadian behavior rhythms.

Peng Y, Tsuno Y, Maejima T … +4 more , Wang M, Jung J, Matsui A, Mieda M

PLoS Biol · 2026 Mar · PMID 41802008 · Full text

The central circadian clock of the suprachiasmatic nucleus (SCN) consists of a network of multiple types of γ-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the precise role of GABAergic transmission in... The central circadian clock of the suprachiasmatic nucleus (SCN) consists of a network of multiple types of γ-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the precise role of GABAergic transmission in the SCN remains unclear. In this study, we investigated the GABAergic regulation from arginine vasopressin (AVP)-producing neurons in the SCN shell to vasoactive intestinal polypeptide (VIP)-producing neurons in the SCN core. Blocking GABA release from AVP neurons via deletion of the vesicular GABA transporter (Vgat) gene lengthened the activity time (the interval between the onset and offset of locomotor activity) and shortened the duration of high Ca2+ activity in VIP neurons to correspond to the behavioral rest time. Conversely, eliminating functional GABAA receptors (GABAAR) in VIP neurons by in vivo genome editing reduced morning locomotor activity level and shortened the activity time, while lengthening the high Ca2+ duration in VIP neurons. Optogenetic activation of AVP neurons in vivo increased Ca2+ levels in VIP neurons during the night; this effect was significantly reduced in AVP neuron-specific Vgat-deficient mice. A similar Ca2+ response in VIP neurons following AVP neuronal activation was observed in SCN slices and was inhibited by the GABAAR antagonist gabazine. Importantly, gabazine application alone elevated baseline Ca2+ levels in VIP neurons, suggesting tonic GABA-mediated inhibition of these neurons. Moreover, AVP neuronal activation decreased Ca2+ levels in non-AVP neurons located between AVP- and VIP-rich regions of the SCN. These results suggest that GABA released from AVP neurons indirectly disinhibits VIP neurons by suppressing intermediate non-AVP neurons, thereby precisely setting behavioral activity/rest time.

Sub-daily virus sampling at the Bermuda Atlantic Time Series reveals diel and depth-structured population dynamics without community-level shifts.

Carrillo A, Hageman E, Chittick L … +13 more , Mackey AI, Ndlovu KS, Tian F, Gilbert NE, Muratore D, Vik D, LeCleir GR, Sun C, Jang HB, Pavan RR, Weitz JS, Wilhelm SW, Sullivan MB

PLoS Biol · 2026 Mar · PMID 41790828 · Full text

Ocean microbes contribute to biogeochemical cycles and ecosystem function, but they do so under top-down pressure imposed by viruses. While viruses are increasingly understood spatially and beginning to be incorporated i... Ocean microbes contribute to biogeochemical cycles and ecosystem function, but they do so under top-down pressure imposed by viruses. While viruses are increasingly understood spatially and beginning to be incorporated into predictive modeling, high-frequency ocean virus dynamics remain understudied due to methodological challenges. Here we sampled stratified Bermuda Atlantic Time Series (BATS) waters for 112 hours at sub-daily 4- (surface) or 12- (deep chlorophyll maximum) hour intervals, purified viral particles from these samples, sequenced their metagenomes, and used the resulting data to characterize high-frequency virus community dynamics. Aggregated community diversity metrics changed with depth, but were not statistically significant temporally at a fixed location. However, finer-scale population-level analyses revealed both depth and temporal change, including physicochemical depth-driven differences and, in surface waters, thousands of viral populations that exhibited statistically significant diel rhythms. Statistical analyses revealed three main archetypes of temporal dynamics that themselves differed in abundance patterns, host predictions, viral taxonomy, and gene functions. Among these, highlights include viruses resembling an archetype with a night peaking pattern in activity that include an over-representation of viruses that putatively infect Prochlorococcus, a phototrophic cyanobacteria. Together, these efforts provide baseline community- and population-scale short-time-frame observations relevant to future climate state modeling.

The adaptor protein TASL is required for age-related B cell emergence and lupus-like disease development in mice.

Johnstone JC, Mitchell R, Vyse TJ … +1 more , Clarke AJ

PLoS Biol · 2026 Mar · PMID 41785302 · Full text

The autoimmune disease systemic lupus erythematosus (SLE) is associated with genetic variants in the X-linked gene CXORF21, which encodes the protein TASL. TASL acts as an adaptor in the IRF5 pathway and is necessary for... The autoimmune disease systemic lupus erythematosus (SLE) is associated with genetic variants in the X-linked gene CXORF21, which encodes the protein TASL. TASL acts as an adaptor in the IRF5 pathway and is necessary for the phosphorylation of IRF5 in response to TLR7 or TLR9 stimulation. Here, we investigate the role of TASL in the humoral immune response, and in the development of lupus in the B6.MRLlpr murine model of SLE. We find that while TASL is dispensable for their development, it is required for the full activation of B cells via TLR9 stimulation, and consequent interferon signaling and inflammatory cytokine expression. Additionally, TASL is crucial for the emergence of age-associated B cells (ABCs), a B cell population derived from the extrafollicular response that increases with age and is expanded in autoimmune disease, and the production of IgG2c antibodies. We also find that deletion of TASL prevents the onset of autoimmunity in the genetically-determined B6.MRLlpr model of lupus.

Gpc3 selectively suppresses subcutaneous adipogenesis in diet-induced obesity.

Li Y, Tao M, Ibáñez CF … +1 more , Xie M

PLoS Biol · 2026 Mar · PMID 41779769 · Full text

Subcutaneous and visceral adipose depots employ distinct expansion strategies in response to dietary cues, yet the molecular regulators underlying these depot-specific adaptations remain poorly understood. Through integr... Subcutaneous and visceral adipose depots employ distinct expansion strategies in response to dietary cues, yet the molecular regulators underlying these depot-specific adaptations remain poorly understood. Through integrated proteomic profiling of human subcutaneous and visceral adipose tissues from paired obese/non-obese donors and temporal transcriptomic analysis of mouse adipose stem and progenitor cells (ASPCs) during dietary transitions, we identified Glypican 3 (Gpc3) as an obesity-responsive gene exhibiting reciprocal expression patterns between depots. ASPC-specific Gpc3 deletion in mice amplified high-fat diet-induced weight and fat mass gain, with a selective enhancement of expansion in inguinal white adipose tissue (WAT) without affecting epididymal WAT. Mechanistically, Gpc3 loss biased ASPC fate toward adipogenesis over proliferation through depot-specific modulation of canonical Wnt signaling. These findings establish Gpc3 as a regulator for regional adipose plasticity, offering a molecular target for reprogramming pathological fat distribution in obesity and related metabolic disorders.

Developing monoclonal antibody therapies for measles could lead to adverse pathogen evolution.

Kennedy DA

PLoS Biol · 2026 Mar · PMID 41774743 · Full text

Monoclonal antibody therapies are being developed to treat measles in response to its recent resurgence. These therapies risk driving measles virus evolution in ways that might undermine the protection offered by vaccina... Monoclonal antibody therapies are being developed to treat measles in response to its recent resurgence. These therapies risk driving measles virus evolution in ways that might undermine the protection offered by vaccination, outweighing potential benefits.

Magnesium depletion by Candida albicans unleashes two unusual modes of colistin resistance in Pseudomonas aeruginosa with different fitness costs.

Hsieh YP, O'Keefe IP, Wang Z … +7 more , Sun W, Yang H, Vu LM, Smalley NE, Ernst RK, Dandekar AA, Malik HS

PLoS Biol · 2026 Mar · PMID 41774708 · Full text

Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. Previous studies have shown that Mg2+ depletion enables Pseudomonas aeruginosa to become resistant to colistin. Here, w... Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. Previous studies have shown that Mg2+ depletion enables Pseudomonas aeruginosa to become resistant to colistin. Here, we show that magnesium sequestration by Candida albicans also enables P. aeruginosa to evolve a nearly hundredfold higher level of colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg2+-sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway involves early mutations in htrB2, a non-essential gene involved in lipid A biosynthesis, which enhances resistance but compromises outer membrane integrity, resulting in fitness costs and increased susceptibility to other antibiotics. A second pathway achieves increased colistin resistance independently of htrB2 mutations without compromising membrane integrity. In both cases, reduced colistin binding to the bacterial membrane underlies resistance. Our findings reveal that Mg2+ scarcity triggers novel evolutionary trajectories, leading to extremely high colistin resistance in P. aeruginosa.

Glutamatergic projections from the substantia nigra pars reticulata to the dorsal raphe nucleus regulate male social hierarchies.

Fan Y, Ge S, Lu L … +4 more , Niu W, Wang Z, Jiao X, Fang G

PLoS Biol · 2026 Mar · PMID 41774700 · Full text

Social hierarchy constitutes a fundamental organizational characteristic among various social species, significantly influencing individual survival, health, and reproductive success within these societies. Neurons in th... Social hierarchy constitutes a fundamental organizational characteristic among various social species, significantly influencing individual survival, health, and reproductive success within these societies. Neurons in the substantia nigra pars reticulata (SNr) exhibit extensive connectivity with the dorsal raphe nucleus (DRN), a critical structure implicated in social interaction, reward processing, and the establishment of social rank. However, the specific neuronal types within the SNr, as well as the associated neural circuits that regulate social dominance, remain inadequately characterized. This study aims to elucidate the crucial role of SNr glutamatergic (SNrGlu) neurons in the establishment and maintenance of social hierarchy in male mice. Employing fiber photometry, we observed that the activation of SNrGlu neurons increased during the initiation of effortful behaviors in the tube test. Further investigations revealed that optogenetic activation or chemogenetic inhibition of the SNrGlu neurons induced upward or downward shifts in social ranks, respectively. Additionally, our findings indicate that the activation of SNr glutamatergic terminals in DRN elevates social status and reduces anxiety levels in mice. Collectively, these results broaden our understanding of the functions associated with SNrGlu neurons and underscore their critical role in regulating social hierarchy among male mice. This work enhances our understanding of the functions of SNrGlu neurons in both physiological contexts and neurological disorders.

Deep learning in biology faces a transferability crisis.

O'Shea-Wheller TA, Murray KI

PLoS Biol · 2026 Mar · PMID 41774686 · Full text

Creating generalizable models is a conserved aim in deep learning-however, misleading claims of transferability threaten to obfuscate reliable performance evaluation. We outline the severity of this issue in the bioscien... Creating generalizable models is a conserved aim in deep learning-however, misleading claims of transferability threaten to obfuscate reliable performance evaluation. We outline the severity of this issue in the biosciences, and suggest potential solutions.

Dynamic expectation strength and precision shape human pain perception through shared and dissociable α-oscillatory mechanisms.

Li J, Chen S, Zhang L … +4 more , Weng L, Lin X, Tu Y, Peng W

PLoS Biol · 2026 Mar · PMID 41770797 · Full text

Human pain perception is not solely driven by sensory input but is dynamically modulated by what we expect to feel and how confident we are in those expectations. Yet, the temporal mechanisms through which evolving expec... Human pain perception is not solely driven by sensory input but is dynamically modulated by what we expect to feel and how confident we are in those expectations. Yet, the temporal mechanisms through which evolving expectations shape pain remain poorly understood. Here, we combined a probabilistic cueing paradigm with computational modeling and EEG to dissociate two core components of expectation: strength (a recency-weighted estimate of predicted pain) and precision (the inverse variability of recent predictions). Trial-wise strength estimates closely tracked subjective expectations and outperformed static cue labels, validating the model's psychological relevance. Expectation strength and precision exerted dissociable effects on pain processing: strength enhanced, whereas precision suppressed, pain-evoked responses. Critically, anticipatory α-band activity mediated these effects via distinct topographical patterns-expectation strength reduced fronto-central α power (reflecting heightened vigilance), while precision increased contralateral sensorimotor α-synchronization (supporting sensory gating). Source-level mediation analyses identified a right-lateralized dorsolateral prefrontal-sensorimotor cortices (DLPFC-SM1) integrating both components, with strength-specific engagement of the medial prefrontal cortex (mPFC). These effects were supported by Bayesian inference and pooled mega-analyses, underscoring their robustness. Together, these findings highlight cortical α-oscillations as dual-control mechanisms for predictive integration, with DLPFC-SM1 as a shared expectation hub and mPFC as a strength-specific node. By moving beyond static cue-based models, this framework captures the adaptive dynamics of expectation and provides a neurocomputational foundation for targeted interventions in chronic pain.

Ischemic stroke triggers brain-wide synaptic remodeling within four hours.

Chen H, Wei Y, Ruje L … +5 more , Du F, Feng Z, Wan Q, Spivakov M, Glebov OO

PLoS Biol · 2026 Mar · PMID 41770794 · Full text

Physiological mechanisms of the key hyperacute (0-24 hours) stage of stroke are poorly understood, hampering the development of new therapies. Synaptic plasticity has been strongly implicated in early stages of neurodege... Physiological mechanisms of the key hyperacute (0-24 hours) stage of stroke are poorly understood, hampering the development of new therapies. Synaptic plasticity has been strongly implicated in early stages of neurodegenerative and neurodevelopmental disorders, yet its relevance in early stroke remains unclear. Here, we describe the emergence of distinct region-specific forms of synaptic remodeling following middle cerebral artery occlusion in rats, arising within the critical 4-hour period. Synapses within the severely ischemic core region were rapidly lost, while those in the mildly ischemic penumbra, albeit largely structurally intact, were functionally diminished. In contrast, the contralateral cortex exhibited increased synaptic staining and synaptic vesicle cycling. Systemic pharmacological blockade of NMDA-type glutamate receptors abolished contralateral synaptic increase and exacerbated synaptic decline in the penumbra. Proteomic and transcriptomic analyses showed that cross-brain synaptic plasticity is independent of local gene expression and revealed metabolic rearrangement and synaptic downregulation in the penumbra. These findings identify brain-wide synaptic rebalancing as a potential mechanism for rapid functional compensation in hyperacute stroke, highlighting the extent of brain response to acute perturbation.

Behavioral convergence under urbanization: An overlooked dimension of biotic homogenization.

Mikula P, Blumstein DT, Tryjanowski P

PLoS Biol · 2026 Mar · PMID 41770723 · Full text

A variety of human activities, especially urbanization, are not only homogenizing species composition but also eroding behavioral diversity. This Essay introduces the concept of behavioral homogenization: the human-drive... A variety of human activities, especially urbanization, are not only homogenizing species composition but also eroding behavioral diversity. This Essay introduces the concept of behavioral homogenization: the human-driven convergence of behavioral traits across individuals, populations, and species across space and time. Global examples of fear responses, foraging, communication, activity patterns, social behavior, cognition and exploration, habitat use, breeding-site choice, migration, and heterospecific interaction networks are used to argue that spatial and temporal beta-diversity in behavior is shrinking in human-dominated landscapes. Ecological and evolutionary consequences, including for animal cultures and human-wildlife conflict, are outlined and opportunities to quantify and integrate behavioral homogenization into biodiversity conservation and management are highlighted.

Formalizing our commitment to code sharing.

Pariente N, Cadwallader L, PLOS Biology Staff Editors

PLoS Biol · 2026 Feb · PMID 41746948 · Full text

In support of open science, PLOS Biology routinely asks authors to openly share their research code before publication. We are now formalizing this practice with a mandatory code-sharing policy and clarifying what we tal... In support of open science, PLOS Biology routinely asks authors to openly share their research code before publication. We are now formalizing this practice with a mandatory code-sharing policy and clarifying what we talk about when we talk about code.

Microbial tryptophan metabolism activates host lysosomal activity to facilitate lipid breakdown.

Zhang K, Luo Z, Chen Y … +8 more , Li Y, Wang L, Liu Y, Yang R, Li Q, Zhao J, Qi B, Shan Z

PLoS Biol · 2026 Feb · PMID 41746947 · Full text

Lysosomes are central to lipid metabolism, yet how gut microbiota-derived metabolites regulate lysosomal function to influence host lipid homeostasis remains unknown. Here, we identify a mechanism in which bacterial tryp... Lysosomes are central to lipid metabolism, yet how gut microbiota-derived metabolites regulate lysosomal function to influence host lipid homeostasis remains unknown. Here, we identify a mechanism in which bacterial tryptophan metabolism activates lysosomal activity to promote lipid breakdown in Caenorhabditis elegans, and show that the bacterial tryptophan metabolite indole recapitulates these effects in mammalian hepatocytes. By developing a lysosomal-responsive lipid reporter in C. elegans to screen for bacterial metabolic states that modulate host lipid storage, we discover that Escherichia coli tryptophan catabolism via tryptophanase TnaA induces lysosomal lipid chaperone LBP-8, driving lipid mobilization. Moreover, tryptophan metabolite indole enhanced lysosomal acidification and degradation capacity, while genetic disruption of lysosomal regulators reversed these effects. Strikingly, bacterial tryptophan metabolism further promoted mitochondrial β-oxidation through lysosomal lipase activity. This pathway was conserved in mammalian hepatocytes, where E. coli-derived tryptophan metabolite indole enhances lysosomal function and reduce lipid accumulation. Our work uncovers microbiota-regulated lysosomal activation as a critical axis in lipid homeostasis, highlighting its potential as a therapeutic target for metabolic disorders linked to lysosomal dysfunction.

Host plant phylogeny predicts arbuscular mycorrhizal fungal communities, but plant life history and fungal genetic change predict feedback.

Ramos RJ, Richards BL, Schultz PA … +1 more , Bever JD

PLoS Biol · 2026 Feb · PMID 41739865 · Full text

Symbioses exert strong influence on host phenotypes; however, benefits from symbionts can increase or degrade over time. Understanding the context-dependence of reinforcing or degrading dynamics is pivotal to predicting... Symbioses exert strong influence on host phenotypes; however, benefits from symbionts can increase or degrade over time. Understanding the context-dependence of reinforcing or degrading dynamics is pivotal to predicting stability of symbiotic benefits. Host phylogenetic relationships and host life history traits are two candidate axes that have been proposed to structure symbioses. However, the relative influence of host evolutionary history and life history on symbiont composition, and whether changes in symbiont composition translate into stronger mutualistic benefits is unknown. We tested the influence of plant phylogenetic relationships and plant life history on the composition of arbuscular mycorrhizal (AM) fungi, perhaps the most ancestral and influential of plant symbionts, and then tested whether AM fungal differentiation resulted in improved mutualism as expected from coadaptation. We constructed mycobiomes composed of seven AM fungal isolates derived from tallgrass prairie and grew them for two growing seasons with 38 grassland plant species. We found that host phylogenetic structure was a significant predictor of the composition of AM fungal communities and the genetic composition of AM fungal species, patterns consistent with phylosymbiosis. However, the phylogenetic structure of AM fungi failed to translate to improved benefits to their host. While AM fungi generally improved plant growth and mycorrhizal feedback was generally positive, the strength of feedback was not predicted by plant phylogenetic distance. The composition of the AM fungal community and genetic composition within AM fungal species were also significantly influenced by plant life history and feedbacks between early and late successional species were generally positive. Interestingly, positive mycorrhizal feedback was predicted by changes in genetic composition of the two most abundant AM fungal species, not by changes in species composition. Positive mycorrhizal feedbacks across life history can mediate plant species turnover during succession and suggests that consideration of mycorrhizal dynamics could improve ecosystem restoration.

Fetal inflammatory signals regulate maternal investment during marsupial pregnancy.

Stadtmauer DJ, Maziarz JD, Griffith OW … +1 more , Wagner GP

PLoS Biol · 2026 Feb · PMID 41734225 · Full text

Marsupial pregnancy is strikingly short: placental attachment in the gray short-tailed opossum Monodelphis domestica lasts only two days. The attachment period is characterized by a spike in inflammatory signaling, devel... Marsupial pregnancy is strikingly short: placental attachment in the gray short-tailed opossum Monodelphis domestica lasts only two days. The attachment period is characterized by a spike in inflammatory signaling, development of an expanded uterine capillary network, and exponential fetal growth. This brevity has historically been attributed to a maternal immune response to fetal contact that only eutherian mammals have evolved mechanisms to tolerate. However, several inflammatory cytokines, including interleukin-1A (IL-1A) and interleukin-6 (IL-6), are produced primarily by fetal cells. We hypothesized that placental cytokines function as solicitation signals that increase maternal investment. To test this, we treated pregnant opossums with inhibitors of IL-1 and IL-6 during the rapid growth phase. Inhibition of IL-1 and IL-6 signaling significantly increased average biomass per fetus (+14% and +12%), and as such these signals impose costs, rather than direct benefits, to intrauterine growth. However, controls showed greater surviving litter sizes than IL-1-inhibited animals, suggesting that IL-1A promotes offspring survival. Single-cell transcriptomes reveal that maternal vascular endothelial cells, perivascular cells, and fibroblasts are the primary targets of fetal IL-1A, and that maternal cells simultaneously up-regulate IL-1 antagonists IL1R2 and IL1RN late in gestation, suggesting maternal resistance to fetal signaling. Placental transcriptomics reveals that the cytokine surge is restricted to the final day of pregnancy when placental cells fuse to form syncytial knots, and that these cells produce additional vasomodulatory signals including a truncated isoform of VEGFA. We propose that marsupial fetuses co-opted inflammatory signaling to perform a novel solicitation function promoting their and their littermates' survival, possibly by altering maternal vascular development.

Vasopressin and angiotensin II pathways differentially modulate human fear response dynamics to looming threats.

Han M, Dong W, Fu K … +8 more , Wang J, Xu Y, Zheng Y, Kendrick K, Ferraro S, Xu T, Yao D, Becker B

PLoS Biol · 2026 Feb · PMID 41734211 · Full text

While basal threat processing dynamics (e.g., visual looming) are well characterized in animals, the underlying mechanisms and their modulation by neuropeptide systems with different modulatory roles in threat processing... While basal threat processing dynamics (e.g., visual looming) are well characterized in animals, the underlying mechanisms and their modulation by neuropeptide systems with different modulatory roles in threat processing (vasopressin, angiotensin II) remain poorly understood in humans. In a randomized, placebo-controlled eye-tracking study (N = 111), we administered vasopressin (AVP) or an angiotensin II receptor blocker (via Losartan, LT) during a time-to-collision threat paradigm. This study was prospectively registered at ClinicalTrials.gov (NCT06329076, NCT06329063) on April 11, 2024, prior to participant enrollment. Behaviorally, AVP induced a systematic time overestimation while LT induced temporal compression and reduced state anxiety. Pupillometry revealed distinguishable profiles: AVP induced sustained constriction during stimulus approach followed by post-stimulus threat-specific dilation, LT maintained sustained pupillary constriction throughout both approach and occlusion phases yet preserving threat-specificity, while placebo (PLC) showed no threat-specific modulation. A computational framework (combining Functional Principal Component Analysis, clustering, and Markov chain analysis) underscored the distinct modulations: AVP stabilized a high-arousal state characterized by the co-activation of vigilance, threat-proactive preparation and a shift from perception to internal simulation. LT suppressed transitions to high-arousal states and exhibited maximal sequence entropy, reflecting flexible response patterns-contrasting with placebo's lowest entropy dynamics. These results demonstrate that AVP and LT differentially regulate basal threat processing via separable neuropeptide pathways: AVP sustains hypervigilance while LT promotes anxiolysis and adaptive flexibility. Our findings suggest neuropeptide pathway-specific targets maladaptive threat processing in trauma- or anxiety-related disorders.

Screening, sorting, and the feedback cycles that imperil peer review.

Bergstrom CT, Gross K

PLoS Biol · 2026 Feb · PMID 41734152 · Full text

Scholarly journals rely on peer review to identify the science most worthy of publication. Yet finding willing and qualified reviewers to evaluate manuscripts has become an increasingly challenging task, possibly even th... Scholarly journals rely on peer review to identify the science most worthy of publication. Yet finding willing and qualified reviewers to evaluate manuscripts has become an increasingly challenging task, possibly even threatening the long-term viability of peer review as an institution. What can or should be done to salvage it? Here, we develop mathematical models to reveal the intricate interactions among incentives faced by authors, reviewers, and readers in their endeavors to identify the best science. Two facets are particularly salient. First, peer review partially reveals authors' private sense of their work's quality through their decisions of where to send their manuscripts. Second, journals' reliance on traditionally unpaid and largely unrewarded review labor deprives them of a standard market mechanism-wages-to recruit additional reviewers when review labor is in short supply. We highlight a resulting feedback loop that threatens to overwhelm the peer review system: (1) an increase in submissions overtaxes the pool of suitable peer reviewers; (2) the accuracy of review drops because journals must either solicit assistance from less qualified reviewers or ask current reviewers to do more; (3) as review accuracy drops, submissions further increase as more authors try their luck at venues that might otherwise be a stretch. We illustrate how this cycle is propelled by the increasing emphasis on high-impact publications, the proliferation of journals, and competition among these journals for peer reviews. Finally, we suggest interventions that could slow or even reverse this cycle of peer-review meltdown.

Frequency-specific attentional mechanisms phasically modulate the influence of distractors on task performance.

Redding ZV, Ding Y, Fiebelkorn IC

PLoS Biol · 2026 Feb · PMID 41730000 · Full text

The Rhythmic Theory of Attention proposes that visual spatial attention is characterized by alternating states that promote either sampling at the present focus of attention or a higher likelihood of shifting attentional... The Rhythmic Theory of Attention proposes that visual spatial attention is characterized by alternating states that promote either sampling at the present focus of attention or a higher likelihood of shifting attentional resources to another location. While theta-rhythmically (4-8 Hz) occurring windows of opportunity for shifting attentional resources might provide cognitive flexibility, these windows might also make us more susceptible to distractors. Here, we used EEG in humans to test how frequency-specific neural activity phasically influences behavioral performance and visual processing when high-contrast distractors co-occur with low-contrast targets. For trials with and without distractors, perceptual sensitivity at the cued target location depended on pre-stimulus theta phase (~7 Hz) recorded at central electrodes. For trials with distractors, there was a greater increase in false alarm rates at the same theta phase associated with lower hit rates (i.e., during the proposed "shifting state"), confirming theta-rhythmically occurring windows of increased susceptibility to distractors. In addition to these phase-behavior effects at central electrodes, we observed phase-behavior effects at frontocentral and occipital electrodes that (i) only occurred on trials with distractors, (ii) peaked in the alpha-frequency range (~9-10 Hz), and (iii) were strongest at occipital electrodes that were contralateral to distractors. Alpha phase at these electrodes was also associated with fluctuations in the amplitude of distractor-evoked visual responses, consistent with an alpha-mediated gating of distractors. The present findings thus provide evidence for distinct theta- and alpha-mediated mechanisms of spatial attention that phasically modulate the influence of distractors on task performance.
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