Appendicular myology of Skorpiovenator bustingorryi: A first attempt to reconstruct pelvic and hindlimb musculature in an abelisaurid theropod.

We present the pelvic and hindlimb musculature of the abelisaurid Skorpiovenator bustingorryi, constituting the most comprehensive muscle reconstruction to date in ceratosaur theropods. Using extant phylogenetic bracket method, we reconstructed 39 muscles that can commonly found in extant archosaurs. Through the identification of bone correlates, we recognized thigh and hindlimb muscles including knee extensors, m. iliofibularis, m. flexor tibialis externus, mm. caudofemorales, mm. puboischiofemorales, and crus muscles important in foot extension and flexion (e.g., m. tibialis anterior, mm. gastrocnemii). Also, autopodial intrinsic muscles were reconstructed whose function involve extension (m. extensor digiti 2-4), flexion (mm. flexor digitorum brevis superficialis), interdigital adduction (m. interosseus dorsalis) and abduction (m. interosseous plantaris, m. abductor 4). Abelisaurids like Skorpiovenator show a deep pre- and postacetabular blade of the ilia and enlarged cnemial crests, which would have helped increasing the moment arm of muscles related to hip flexion and hindlimb extension. Also, pedal muscles related to pronation were probably present but reduced (e.g., m. pronator profundus). Despite some gross differences in the autopodial morphology in extant outgroups (e.g., crocodilian metatarsus and avian tarsometatarsus), the present study allows us to hypothesize several pedal muscles in Skorpiovenator. These muscles would not be arranged in tendinous bundles as in Neornithes, but rather the condition would be similar to that of crocodilians with several layers formed by fleshy bellies on the plantar and dorsal aspects of the metatarsus. The musculature of Skorpiovenator is key for future studies concerning abelisaurid biomechanics, including the integration of functional morphology and ichnological data.

Synergistic information supports modality integration and flexible learning in neural networks solving multiple tasks.

Striking progress has been made in understanding cognition by analyzing how the brain is engaged in different modes of information processing. For instance, so-called synergistic information (information encoded by a set of neurons but not by any subset) plays a key role in areas of the human brain linked with complex cognition. However, two questions remain unanswered: (a) how and why a cognitive system can become highly synergistic; and (b) how informational states map onto artificial neural networks in various learning modes. Here we employ an information-decomposition framework to investigate neural networks performing cognitive tasks. Our results show that synergy increases as networks learn multiple diverse tasks, and that in tasks requiring integration of multiple sources, performance critically relies on synergistic neurons. Overall, our results suggest that synergy is used to combine information from multiple modalities-and more generally for flexible and efficient learning. These findings reveal new ways of investigating how and why learning systems employ specific information-processing strategies, and support the principle that the capacity for general-purpose learning critically relies on the system's information dynamics.

Unravelling consciousness and brain function through the lens of time, space, and information.

Disentangling how cognitive functions emerge from the interplay of brain dynamics and network architecture is among the major challenges that neuroscientists face. Pharmacological and pathological perturbations of consciousness provide a lens to investigate these complex challenges. Here, we review how recent advances about consciousness and the brain's functional organisation have been driven by a common denominator: decomposing brain function into fundamental constituents of time, space, and information. Whereas unconsciousness increases structure-function coupling across scales, psychedelics may decouple brain function from structure. Convergent effects also emerge: anaesthetics, psychedelics, and disorders of consciousness can exhibit similar reconfigurations of the brain's unimodal-transmodal functional axis. Decomposition approaches reveal the potential to translate discoveries across species, with computational modelling providing a path towards mechanistic integration.

Survey of Leafminers on American Chestnut and other Castanea spp. (Fagales: Fagaceae) on Long Island, NY.

The effect of the 20th-century functional extinction of the American Chestnut (Fagaceae: Castanea dentata (Marshall) Borkh) on associated herbivorous insects is unknown. These insects include leafminers that spend at least part of their larval phase feeding between the epidermises of leaves. We surveyed leafminers on C. dentata, nonnative Castanea spp., and hybrids on Long Island, NY. We found 10 leafminer species feeding on Castanea spp. A first New York State record was documented for Stigmella castaneaefoliella (Chambers) (Lepidoptera: Nepticulidae). New host records are established for 6 lepidopterans, including a new host genus for Phyllonorycter basistrigella (Clemens) (Lepidoptera: Gracillariidae). We found no significant differences in the mean intensity of S. castaneaefoliella leaf mines on native and nonnative Castanea spp.; however, our sample size was small. Thus, we guardedly conclude that nonnative Castanea spp. can serve as refugia for C. dentata leafminers native to North America while acknowledging that the extent to which nonnative species are utilized requires further investigation.

Quantifying synergy and redundancy between networks.

Understanding how different networks relate to each other is key for understanding complex systems. We introduce an intuitive yet powerful framework to disentangle different ways in which networks can be (dis)similar and complementary to each other. We decompose the shortest paths between nodes as uniquely contributed by one source network, or redundantly by either, or synergistically by both together. Our approach considers the networks' full topology, providing insights at multiple levels of resolution: from global statistics to individual paths. Our framework is widely applicable across scientific domains, from public transport to brain networks. In humans and 124 other species, we demonstrate the prevalence of unique contributions by long-range white-matter fibers in structural brain networks. Across species, efficient communication also relies on significantly greater synergy between long-range and short-range fibers than expected by chance. Our framework could find applications for designing network systems or evaluating existing ones.

Molecular Evolution of RAMOSA1 (RA1) in Land Plants.

RAMOSA1 (RA1) is a Cys2-His2-type (C2H2) zinc finger transcription factor that controls plant meristem fate and identity and has played an important role in maize domestication. Despite its importance, the origin of RA1 is unknown, and the evolution in plants is only partially understood. In this paper, we present a well-resolved phylogeny based on 73 amino acid sequences from 48 embryophyte species. The recovered tree topology indicates that, during grass evolution, RA1 arose from two consecutive SUPERMAN duplications, resulting in three distinct grass sequence lineages: RA1-like A, RA1-like B, and RA1; however, most of these copies have unknown functions. Our findings indicate that RA1 and RA1-like play roles in the nucleus despite lacking a traditional nuclear localization signal. Here, we report that copies diversified their coding region and, with it, their protein structure, suggesting different patterns of DNA binding and protein-protein interaction. In addition, each of the retained copies diversified regulatory elements along their promoter regions, indicating differences in their upstream regulation. Taken together, the evidence indicates that the RA1 and RA1-like gene families in grasses underwent subfunctionalization and neofunctionalization enabled by gene duplication.

A new abelisaurid dinosaur from the end Cretaceous of Patagonia and evolutionary rates among the Ceratosauria.

Gondwanan dinosaur faunae during the 20 Myr preceding the Cretaceous-Palaeogene (K/Pg) extinction included several lineages that were absent or poorly represented in Laurasian landmasses. Among these, the South American fossil record contains diverse abelisaurids, arguably the most successful groups of carnivorous dinosaurs from Gondwana in the Cretaceous, reaching their highest diversity towards the end of this period. Here we describe Koleken inakayali gen. et sp. n., a new abelisaurid from the La Colonia Formation (Maastrichtian, Upper Cretaceous) of Patagonia. Koleken inakayali is known from several skull bones, an almost complete dorsal series, complete sacrum, several caudal vertebrae, pelvic girdle and almost complete hind limbs. The new abelisaurid shows a unique set of features in the skull and several anatomical differences from Carnotaurus sastrei (the only other abelisaurid known from the La Colonia Formation). Koleken inakayali is retrieved as a brachyrostran abelisaurid, clustered with other South American abelisaurids from the latest Cretaceous (Campanian-Maastrichtian), such as Aucasaurus, Niebla and Carnotaurus. Leveraging our phylogeny estimates, we explore rates of morphological evolution across ceratosaurian lineages, finding them to be particularly high for elaphrosaurine noasaurids and around the base of Abelisauridae, before the Early Cretaceous radiation of the latter clade. The Noasauridae and their sister clade show contrasting patterns of morphological evolution, with noasaurids undergoing an early phase of accelerated evolution of the axial and hind limb skeleton in the Jurassic, and the abelisaurids exhibiting sustained high rates of cranial evolution during the Early Cretaceous. These results provide much needed context for the evolutionary dynamics of ceratosaurian theropods, contributing to broader understanding of macroevolutionary patterns across dinosaurs.

Key HPI axis receptors facilitate light adaptive behavior in larval zebrafish.

The vertebrate stress response (SR) is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and contributes to generating context appropriate physiological and behavioral changes. Although the HPA axis plays vital roles both in stressful and basal conditions, research has focused on the response under stress. To understand broader roles of the HPA axis in a changing environment, we characterized an adaptive behavior of larval zebrafish during ambient illumination changes. Genetic abrogation of glucocorticoid receptor (nr3c1) decreased basal locomotor activity in light and darkness. Some key HPI axis receptors (mc2r [ACTH receptor], nr3c1), but not nr3c2 (mineralocorticoid receptor), were required to adapt to light more efficiently but became dispensable when longer illumination was provided. Such light adaptation was more efficient in dimmer light. Our findings show that the HPI axis contributes to the SR, facilitating the phasic response and maintaining an adapted basal state, and that certain adaptations occur without HPI axis activity.

Inactivation of cytidine triphosphate synthase 1 prevents fatal auto-immunity in mice.

De novo synthesis of the pyrimidine, cytidine triphosphate (CTP), is crucial for DNA/RNA metabolism and depends on the CTP synthetases, CTPS1 and -2. Partial CTPS1 deficiency in humans has previously been shown to lead to immunodeficiency, with impaired expansion of T and B cells. Here, we examine the effects of conditional and inducible inactivation of Ctps1 and/or Ctps2 on mouse embryonic development and immunity. We report that deletion of Ctps1, but not Ctps2, is embryonic-lethal. Tissue and cells with high proliferation and renewal rates, such as intestinal epithelium, erythroid and thymic lineages, activated B and T lymphocytes, and memory T cells strongly rely on CTPS1 for their maintenance and growth. However, both CTPS1 and CTPS2 are required for T cell proliferation following TCR stimulation. Deletion of Ctps1 in T cells or treatment with a CTPS1 inhibitor rescued Foxp3-deficient mice from fatal systemic autoimmunity and reduced the severity of experimental autoimmune encephalomyelitis. These findings support that CTPS1 may represent a target for immune suppression.

Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression.

BACKGROUND: There is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling. AIMS: Using data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes. METHODS: Exploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored. RESULTS/OUTCOMES: In the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found. CONCLUSION: Discontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required.

A large therian mammal from the Late Cretaceous of South America.

Theria represent an extant clade that comprises placental and marsupial mammals. Here we report on the discovery of a new Late Cretaceous mammal from southern Patagonia, Patagomaia chainko gen. et sp. nov., represented by hindlimb and pelvic elements with unambiguous therian features. We estimate Patagomaia chainko attained a body mass of 14 kg, which is considerably greater than the 5 kg maximum body mass of coeval Laurasian therians. This new discovery demonstrates that Gondwanan therian mammals acquired large body size by the Late Cretaceous, preceding their Laurasian relatives, which remained small-bodied until the beginning of the Cenozoic. Patagomaia supports the view that the Southern Hemisphere was a cradle for the evolution of modern mammalian clades, alongside non-therian extinct groups such as meridiolestidans, gondwanatherians and monotremes.

Sodium nitroprusside enhances stepping test performance and increases medium spiny neurons responsiveness to cortical inputs in a rat model of Levodopa-induced dyskinesias.

Levodopa (L-DOPA) is the classical gold standard treatment for Parkinson's disease. However, its chronic administration can lead to the development of L-DOPA-induced dyskinesias (LIDs). Dysregulation of the nitric oxide-cyclic guanosine monophosphate pathway in striatal networks has been linked to deficits in corticostriatal transmission in LIDs. This study investigated the effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on behavioural and electrophysiological outcomes in sham-operated and 6-hydroxydopamine-lesioned rats chronically treated with vehicle or L-DOPA, respectively. In sham-operated animals, systemic administration of SNP increased the spike probability of putative striatal medium spiny neurons (MSNs) in response to electrical stimulation of the primary motor cortex. In 6-hydroxydopamine-lesioned animals, SNP improved the stepping test performance without exacerbating abnormal involuntary movements. Additionally, SNP significantly increased the responsiveness of putative striatal MSNs in the dyskinetic striatum. These findings highlight the critical role of the NO signalling pathway in facilitating the responsiveness of striatal MSNs in both the intact and dyskinetic striata. The study suggests that SNP has the potential to enhance L-DOPA's effects in the stepping test without exacerbating abnormal involuntary movements, thereby offering new possibilities for optimizing Parkinson's disease therapy. In conclusion, this study highlights the involvement of the NO signalling pathway in the pathophysiology of LIDs.

Deciphering Density Fluctuations in the Hydration Water of Brownian Nanoparticles via Upconversion Thermometry.

We investigate the intricate relationship among temperature, pH, and Brownian velocity in a range of differently sized upconversion nanoparticles (UCNPs) dispersed in water. These UCNPs, acting as nanorulers, offer insights into assessing the relative proportion of high-density and low-density liquid in the surrounding hydration water. The study reveals a size-dependent reduction in the onset temperature of liquid-water fluctuations, indicating an augmented presence of high-density liquid domains at the nanoparticle surfaces. The observed upper-temperature threshold is consistent with a hypothetical phase diagram of water, validating the two-state model. Moreover, an increase in pH disrupts the organization of water molecules, similar to external pressure effects, allowing simulation of the effects of temperature and pressure on hydrogen bonding networks. The findings underscore the significance of the surface of suspended nanoparticles for understanding high- to low-density liquid fluctuations and water behavior at charged interfaces.

Bayesian at heart: Towards autonomic outflow estimation via generative state-space modelling of heart rate dynamics.

Recent research is revealing how cognitive processes are supported by a complex interplay between the brain and the rest of the body, which can be investigated by the analysis of physiological features such as breathing rhythms, heart rate, and skin conductance. Heart rate dynamics are of particular interest as they provide a way to track the sympathetic and parasympathetic outflow from the autonomic nervous system, which is known to play a key role in modulating attention, memory, decision-making, and emotional processing. However, extracting useful information from heartbeats about the autonomic outflow is still challenging due to the noisy estimates that result from standard signal-processing methods. To advance this state of affairs, we propose a novel approach in how to conceptualise and model heart rate: instead of being a mere summary of the observed inter-beat intervals, we introduce a modelling framework that views heart rate as a hidden stochastic process that drives the observed heartbeats. Moreover, by leveraging the rich literature of state-space modelling and Bayesian inference, our proposed framework delivers a description of heart rate dynamics that is not a point estimate but a posterior distribution of a generative model. We illustrate the capabilities of our method by showing that it recapitulates linear properties of conventional heart rate estimators, while exhibiting a better discriminative power for metrics of dynamical complexity compared across different physiological states.

Effects of External Stimulation on Psychedelic State Neurodynamics.

Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes, such as personality changes. These findings are particularly intriguing, given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g., from wakefulness to sleep). However, little is known about how context impacts the entropy-enhancing effect of psychedelics, which carries important implications for how it can be exploited in, for example, psychedelic psychotherapy. This article investigates how brain entropy is modulated by stimulus manipulation during a psychedelic experience by studying participants under the effects of lysergic acid diethylamide (LSD) or placebo, either with gross state changes (eyes closed vs open) or different stimuli (no stimulus vs music vs video). Results show that while brain entropy increases with LSD under all of the experimental conditions, it exhibits the largest changes when subjects have their eyes closed. Furthermore, brain entropy changes are consistently associated with subjective ratings of the psychedelic experience, but this relationship is disrupted when participants are viewing a video─potentially due to a "competition" between external stimuli and endogenous LSD-induced imagery. Taken together, our findings provide strong quantitative evidence of the role of context in modulating neural dynamics during a psychedelic experience, underlining the importance of performing psychedelic psychotherapy in a suitable environment.

Information decomposition and the informational architecture of the brain.

To explain how the brain orchestrates information-processing for cognition, we must understand information itself. Importantly, information is not a monolithic entity. Information decomposition techniques provide a way to split information into its constituent elements: unique, redundant, and synergistic information. We review how disentangling synergistic and redundant interactions is redefining our understanding of integrative brain function and its neural organisation. To explain how the brain navigates the trade-offs between redundancy and synergy, we review converging evidence integrating the structural, molecular, and functional underpinnings of synergy and redundancy; their roles in cognition and computation; and how they might arise over evolution and development. Overall, disentangling synergistic and redundant information provides a guiding principle for understanding the informational architecture of the brain and cognition.

Comments on the pelvic girdle anatomy of Lagerpeton chanarensis Romer, 1971 (Archosauria) and its implications on the posture and gait of early pterosauromorphs.

Lagerpeton chanarensis is an early avemetatarsalian from the lower Carnian (lowermost Upper Triassic) levels of the Chañares Formation, La Rioja Province, Argentina. Lagerpeton and its kin were traditionally interpreted as dinosaur precursors of cursorial habits, with a bipedal posture and parasagittal gait. Some authors also speculated saltatorial capabilities for this genus. Recent analyses indicate that lagerpetids are early-diverging pterosauromorphs, a hypothesis that invites a review of most aspects of their anatomy and function. A revision of available specimens and additional preparation of previously known individuals indicate that Lagerpeton lacked a parasagittal gait and was probably a sprawling archosaur. This latter inference is based on the femoral head articulation with the acetabulum. The acetabular rim has a strongly laterally projected posteroventral antitrochanteric corner, which results in a position of the legs that recalls that of sprawling living reptiles, such as lizards, and departs from the parasagittally positioned limbs of dinosaurs. This may indicate that early pterosauromorphs had a sprawling posture of their hindlegs, casting doubts on the significance of bipedal posture and parasagittal gait for the radiation of early ornithodirans, given that both traits have been regarded as key features that triggered the ecological and evolutionary success of the clade. Our results bolster recent claims of a high ecomorphological diversity among early avemetatarsalians.

Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression.

BACKGROUND: To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075). METHODS: We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin. RESULTS: Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm. CONCLUSIONS: Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.

The Emerging Role of Tertiary Lymphoid Structures in Breast Cancer: A Narrative Review.

This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, and current ways of recognizing them. A comprehensive literature review was performed using the PubMed/Medline, Scopus, and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response. In this context, tertiary lymphoid structures (TLSs) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLSs are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or TILs (tumor-infiltrating lymphocytes).