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Recent methodological development in phylogenetic inference has focused predominantly on molecular data. However, renewed interest in other data types, particularly morphological data, has followed from the increased recognition of the power of total evidence and tip-dating approaches, including fossil data, for inference of time-scaled trees and rates of evolution. However, attention has largely focused on the improvement of models of morphological evolution and other analytical tools with much less discussion about data acquisition itself. Here we review past and current practice for describing and collecting morphological data for phylogenetic inference. We present a systematic review of 164 phylogenetic analyses conducted over the last 35 years and focused on a diverse group of extinct arthropods: trilobites. Trends in increasing matrix size, data type, and coding strategy are evident. Where present, polymorphic characters have been predominantly derived from discretized continuous characters, although increasingly practitioners are utilizing alternative approaches for the treatment of quantitative characters. Not surprisingly, traditional indices that describe character consistency are highly correlated with matrix size but show surprising variation at different taxonomic scales. More recent attempts to describe data quality using information theory imply that characters can have high information content even if data are missing for many tips, providing support against the exclusion of characters because of missing data. In consideration of this, as well as advances in the study of developmental biology and variational complexity, we identify several avenues for increasing the quality and quantity of morphological data going forward.

Cell fate commitment is commonly thought to entail progressive restriction of developmental potential, enforced by passive, heterochromatin-based silencing of alternative lineage programs. Here we show that maintenance of neural identity during cerebellum development instead requires active repression of a starkly divergent fate by the TEAD-INSM1 transcriptional complex. Loss of TEAD1/2 or INSM1 activates the myogenic master regulator Myod1 , resulting in neural cells acquiring transcriptional, structural, and metabolic features of skeletal muscle cells. Deletion of Myod1 fully suppresses neural-to-muscle conversion while partially rescuing neural developmental defects. Our results uncover a latent alternative lineage during neurodevelopment and a surprising role for sequence-specific transcription factors in enforcing lineage boundaries, including those previously thought essentially unbreachable, with implications for understanding aberrant differentiation in disease contexts and cell-type evolution.

A catalytic machine is a model of computation where a traditional space-bounded machine is augmented with an additional, significantly larger, "catalytic" tape, which, while being available as a work tape, has the caveat of being initialized with an arbitrary string, which must be preserved at the end of the computation. Despite this restriction, catalytic machines have been shown to have surprising additional power; a logspace machine with a polynomial length catalytic tape, known as catalytic logspace ( CL ), can compute problems which are believed to be impossible for L . A fundamental question of the model is whether the catalytic condition, of leaving the catalytic tape in its exact original configuration, is robust to minor deviations. This study was initialized by Gupta et al. (2024), who defined lossy catalytic logspace ( LCL [ e ] ) as a variant of CL where we allow up to e errors when resetting the catalytic tape. They showed that LCL [ e ] = CL for any e = O ( 1 ) , which remains the frontier of our understanding. In this work we completely characterize lossy catalytic space ( LCSPACE [ s , c , e ] ) in terms of ordinary catalytic space ( CSPACE [ s , c ] ). We show that LCSPACE [ s , c , e ] = CSPACE [ Θ ( s + e log c ) , Θ ( c ) ] In other words, allowing e errors on a catalytic tape of length c is equivalent, up to a constant stretch, to an equivalent errorless catalytic machine with an additional e log c bits of ordinary working memory. As a consequence, we show that for any e, LCL [ e ] = CL implies SPACE [ e log n ] ⊆ ZPP , thus giving a barrier to any improvement beyond LCL [ O ( 1 ) ] = CL . We also extend all our results to every variant of catalytic space.

Canine leishmaniasis (CanL) is a zoonotic threat in the Mediterranean basin caused by Leishmania spp, but its epidemiology has not been characterized in Jordan. This study was conducted to determine the true seroprevalence and identify risk factors for exposure of dogs to Leishmania spp. across three major governorates of Jordan. A cross-sectional study involving 341 dogs (stray, pet, and breeding) from Amman, Irbid, and Zarqa was carried out. Serum samples were analyzed using a commercial indirect ELISA kit (Demeditec, Germany). True prevalence was estimated by Rogan-Gladen adjustment with sensitivity and specificity values of 95.6% and 98.0%, respectively. Risk factors were identified through univariate analysis with odds ratios (OR). The overall apparent seroprevalence was 7.33% (25/341), which corresponds to a true prevalence of 5.70% (95% CI: 3.6%-8.1%). The seroprevalence varied significantly by region attaining an extraordinary level of 17.7% in Irbid (OR = 5.59 against Amman, p&#x202f;<&#x202f;0.001). Breeding dogs have the highest infection rate so far recorded at 15% (OR = 2.92 compared to all other dog types combined (pet, stray, guard); p&#x202f;=&#x202f;0.015). In another surprising finding, indoor-housed dogs demonstrated significantly different seroprevalence than outdoor-housed dogs (11.6% vs. 5.0%; OR = 2.49; p&#x202f;=&#x202f;0.044). More than one-third of the seropositive were apparently healthy indicating that they constitute a silent reservoir. In Jordan, leishmaniasis is endemic in domestic dog population. Mandatory serological screening of breeding kennels combined with indoor vector-control measures should be implemented urgently as part of a One Health strategy.

Calibration of sound localization behavior in species with mobile eyes requires not only accurate visual input but also accurate oculomotor signals across the lifespan. The recent discovery of eye movement-related eardrum oscillations suggest that oculomotor signals may be incorporated into auditory processing at the level of the ear. One inference of this discovery is that individual variation in such signals might be correlated with individual variation in sound localization accuracy. Here, we tested this hypothesis in humans with normal hearing. We discovered that there is considerable variation in the accuracy of sound localization (here, saccades to sounds) even in normal individuals: median horizontal errors ranged from 2-6&#xb0;, and median vertical errors could be as large as 36&#xb0;. We separated the subject pool into groups with "good" performance (median vectorial error < 8&#xb0;) vs "poor" performance (median vectorial error > 10&#xb0;) and evaluated their respective EMREOs. The EMREOs differed across the two groups in both horizontal and vertical dimensions, in how saccade amplitude vs. initial eye position was encoded, and across time with respect to the saccade. These results are consistent with the interpretation that EMREOs are associated with underlying processes that ensure the accuracy of sound localization. The accuracy of eye movements to look at sounds varied across individuals, with median errors spanning a greater than 10-fold range. This range is surprising given that the participants passed screening for normal hearing."Good" vs "poor" sound localizers exhibited differences in their eye movement-related eardrum oscillations (EMREOs)EMREOs differed in both horizontal and vertical sensitivity, for both saccade amplitude and initial eye position, and the differences varied in timing with respect to saccade onset.We interpret the results under the theory that poor sound localization may be a consequence of poor eye movement encoding, without which linking visual and auditory space is likely inaccurate.

We study the behavior of catalytically active droplets in multicomponent conserved mixtures affected by noise. Working in the thin interface limit, we analytically determine the state diagram of the system, characterized by multiple dynamical regimes, and verify our findings using numerical simulations. In particular, we show the emergence of a nonreciprocal, chemically mediated interaction between the droplets, which leads to the formation of (meta)stable clusters of droplets of different species. We find that the clusters can display self-propulsion in a large part of the parameter space, including regions where the nonreciprocal interactions between the droplets are purely attractive. This surprising feature arises from the nonlocal nature of the chemical interactions, and points to locality violations as a general mechanism for energy dissipation and emergence of out-of-equilibrium steady states in active matter.

To investigate the associations between nutritional status and early childhood caries (ECC) in a Thai population, hypothesizing that nutritional extremes, including undernutrition and overnutrition, are associated with increased ECC risk. Data from a birth cohort study of Thai children in Khon Kaen were analyzed. Nutritional status at 2 y of age was assessed using anthropometric measurements (height-for-age, weight-for-age, weight-for-height, and body mass index-for-age [BMI-for-age]) categorized by Z-scores adjusted for age and sex. Dental caries was assessed at ages 3 to 4 y using World Health Organization criteria, with ECC defined by the presence of cavitated lesions. Modified Poisson and negative binomial regression analyses with robust variance estimated relative risks (RRs) and 95% confidence intervals (CIs) for ECC prevalence and dmft scores, adjusting for maternal education, breastfeeding duration, sweet consumption frequency, and visible plaque. Among 549 children, overweight/obese children (n = 27) exhibited a significantly lower prevalence of ECC compared with those with normal weight (n = 471) or wasting (n = 50; 59.3% versus 89% and 94%, respectively; P < 0.001). The adjusted RR for overweight/obesity was 0.66 (95% CI: 0.48-0.92) compared with normal weight and 0.64 (95% CI: 0.46 -0.90) compared with wasting. Children with normal weight and those with wasting had comparable ECC prevalence rates (P = 0.50). Similar trends were observed for dmft scores, with overweight/obese children having significantly lower scores compared with those with normal weight or wasting (4.3 versus 7.3 and 8.0, respectively; P = 0.004). Height-for-age and weight-for-age were not significantly associated with ECC, while BMI-for-age yielded results consistent with those for weight-for-height. This study reveals an unexpected inverse relationship between overweight status and ECC, suggesting a more complex interplay between nutrition and caries risk. These findings underscore the need for further research into the mechanisms underlying this relationship to inform ECC prevention strategies.Knowledge Transfer Statement:Our findings challenge the hypothesis that all nutritional extremes increase caries risk, revealing an unexpected protective effect of being overweight. This highlights the complex nutrition-caries relationship and the need for context-specific evidence. Further research into the mechanisms behind this surprising link is essential to develop effective and targeted preventive strategies, rather than assuming all nutritional improvements are beneficial for dental health.

Metabolic homeostasis has been studied primarily at the tissue and organism level, identifying molecular control mechanisms such as the energy charge-sensing kinase AMPK. Feedback loops involving AMPK and other regulators align cellular ATP generation and consumption, determining energetic balance. Recent work has demonstrated surprising oscillatory dynamics in AMPK activity, revealing unidentified kinetic modulation in single-cell homeostatic behaviour. However, probing the kinetic mechanisms of intracellular feedback requires simultaneous observation of multiple energetic parameters, and such experiments are precluded by the shared wavelength band occupied by most metabolic biosensors. We have overcome this obstacle by constructing a red-shifted FRET-based AMPK activity biosensor, RAMPKAR2, that is comparable to existing FRET-based AMPK activity biosensors. Multiplexed imaging of RAMPKAR2 with PercevalHR, which detects ATP/ADP ratio, confirmed that the kinetics of AMPK activity and ATP/ADP ratio are tightly coupled, with a lag of less than 6 minutes at the single-cell level. Pairing of RAMPKAR with HYlight, which detects the glycolytic intermediate fructose 1,6-bisphosphate (FBP), revealed that glycolytic activity co-oscillates with AMPK, shifted by ~1.5 hours, and that these oscillations are suppressed by sustained AMPK activity. Together these data advance a model in which temporally offset increases in glycolytic ATP supply and AMPK deactivation contribute to single-cell oscillations.

This retrospective study challenges the assumption that physiological variance among neonates is greater between litters than within litters of multiparous species like&#xa0;rats. Conventional wisdom holds that litters - not individual pups - should be the unit of replication due to shared perinatal environment and genetics. We provide empirical evidence contradicting this view. We measured within- versus between-litter variance in body weight of outbred Sprague-Dawley (SD) neonatal rats across three cohorts: (1) pups from 24&#xa0;mothers weighed on postnatal day 4 (P4); (2) P4 pups from 10 untreated and seven nicotine-exposed litters; and (3) breathing frequency in pups aged P3-P4 from six litters. We used Welch's ANOVA and the intraclass correlation coefficient (ICC) as primary outcome measures. Importantly, ICC quantifies raw variance distribution, unlike ANOVA's mean-square calculation. Despite significant 'litter effects' detected by conventional ANOVA for body weight, ICC analysis revealed that &#x223c;40-75% of total variance in cohort 1 originated within litters. In cohort 2, variance was distributed more equally, but between-litter variance (43%) remained less than within-litter variance (57%). Remarkably, for breathing frequency, nearly 100% of total variance originated within litters. These findings align with the genetics and developmental biology of outbred SD rats: each fetus is genetically unique and possesses its own placenta with distinct blood flow, hormone levels and nutrient delivery. We therefore argue against uniform policies mandating how many offspring per litter to use experimentally. Instead, researchers should base this decision on their specific research question, outcome variables, rat genetics, and careful consideration of the raw variance both within and between litters. KEY POINTS: Because rat littermates share a genetic background and perinatal environment, conventional wisdom assumes variance is greater between litters than within litters, which has led statisticians and reviewers to conclude that the litter, not each animal within the litter, is the true unit of replication. Our retrospective analysis of outbred Sprague-Dawley rat pups revealed the opposite: within-litter variance significantly exceeded between-litter variance for body weight (40-75% within) and breathing frequency (nearly 100% within). Even in a cohort that included pups from nicotine-exposed litters, within-litter variance (57%) exceeded between-litter variance (43%). Each outbred fetus is genetically unique with its own placenta, umbilical cord, and uterine position - making substantial within-litter variation expected, not surprising. These findings challenge conventional wisdom about littermate homogeneity and necessitate reconsideration of experimental design practices in developmental research in outbred rat strains.

Chemokine (C-X-C motif) ligand 4 (CXCL4), an antimicrobial chemokine with multiple effector functions, is a known biomarker in systemic sclerosis (SSc), but it also plays important roles in inflammatory bowel diseases, atopic dermatitis, psoriasis, systemic lupus erythematosus and other chronic inflammatory diseases. In SSc, the presence of CXCL4 correlates with severe disease progression: CXCL4 contributes to the interferon-(IFN)-I signature by forming pro-inflammatory liquid crystalline complexes with self-DNA, which have the capacity to activate TLR9 in a multivalent manner and potently induce IFN-&#x3b1; in plasmacytoid dendritic cells. Here, we show that in order to chaperone DNA to amplify TLR9 responses effectively, CXCL4 needs to retain its ability to assemble into tetramers, in addition to forming the optimal liquid crystalline structure. By comparing various mutated CXCL4 derived peptides with altered cationic charge and with ablated capacity to from stable tetramers, we find the surprising result that the physiological pre-assembly of CXCL4 into tetramers, before DNA interaction, is important for strong amplified IFN-I secretion. Most importantly, small molecules that destabilize CXCL4 tetramerization block the plasmacytoid dendritic cells IFN-&#x3b1; response, suggesting new pharmacological interventions in SSc, and possibly in other autoimmune conditions characterized by the presence of high CXCL4 and CXCL4-DNA complexes expression.

Bacterial lipopolysaccharide (LPS) is among the most potent pathogen-associated molecular patterns (PAMPs). In animals, LPS can induce endotoxic shock, a widely used model of sepsis. Studies of this system have yielded important insights into innate immunity, including key immune sensors and signaling pathways. However, how inflammatory pathways are spatially coordinated across cell types and organs in vivo during endotoxic shock remains poorly understood. Here, we systematically analyzed LPS-induced lethality in mice to define the coordinated contributions of cell death pathways, inflammatory cytokines, and lipid mediators to endotoxic shock pathology. We found that caspase-11 signaling acts primarily in nonhematopoietic cells and drives tissue injury, whereas caspase-8 and RIPK3 function predominantly in hematopoietic cells and are both controlled by TRIF. Although proinflammatory cytokines are thought to promote cell death, it is surprising that cell death and/or components of death signaling are critical for initiating the cytokine storm because disruption of these cell death pathways markedly and preferentially reduces LPS-induced cytokine production in vivo. Combined deficiency of caspase-11, RIPK3, and caspase-8 fully protected mice from LPS-induced death, and additional cyclooxygenase inhibition eliminated remaining sickness behaviors such as reduced mobility. Together, these interventions rendered LPS-treated mice nearly indistinguishable from healthy controls. Overall, we delineate the core of the integrated signaling network that governs the pathological manifestations of LPS-induced endotoxic shock in mice.

Euplectella aspergillum is a deep-sea glass sponge that has attracted the interest of the scientific community for almost 150 years, for its surprising adaptations to the asperities of the abyss. The state-of-the-art on this organism focuses on specimens in isolation, but field observations question this premise. Footage from the abyss shows instances in which E. aspergillum live in bouquets comprising several organisms. Through high performance computing of the flow physics of E. aspergillum, we discover a complex hydrodynamic entanglement that favors downstream organisms at no cost to upstream ones. Such an interaction benefits the nutrition, reproduction, and resilience of the bouquet-the first instance of a hydrodynamic advantage that emerges due to purely passive interactions in a group.

Perovskite-organic tandem solar cells (TSCs) have recently garnered significant attention due to their potential for high power conversion efficiency (PCE) and excellent stability. However, their development has been significantly hindered by the large open-circuit voltage (VOC) deficit in organic sub-cells, primarily caused by severe non-radiative recombination, which is closely related to the electroluminescence quantum efficiency (EQEEL) and the photoluminescence quantum yield (PLQY). However, mainstream non-fullerene molecules exhibit low PLQY due to the aggregation-caused quenching (ACQ) effect. In this study, an aggregation-induced emission (AIE)-active molecule (TPE-BTA3) featuring a three-dimensional rotor-stereo configuration is rationally designed with an exceptional PLQY of 68%. When TPE-BTA3 is introduced into binary Organic solar cells (OSCs), it not only dramatically enhances the PLQY of alloy-acceptor but also strengthens the utilization of near-infrared photons, leading to a significant increase in VOC and short-circuit current (JSC). By integrated above optimized ternary organic bulk-heterojunction with a wide-bandgap (1.85&#x2009;eV) perovskite, the constructed perovskite-organic TSCs achieve a surprising PCE of 26.5% (certified as 25.8%). This work establishes a conceptual bridge between high-efficiency photovoltaics and AIE molecular design paradigms.

Inducing broadly neutralizing antibodies (bnAbs) is central to HIV vaccine efforts, but bnAb precursors are rare, often inactive, and require extensive somatic hypermutation (SHM) to recognize diverse, glycan-shielded epitopes. Germline-targeting immunogens (GTs) aim to jump-start this process, but determinants of success remain unclear. Here we establish a bnAb precursor-trackable model that reveals a surprising driver: binding dynamics. Across a series of GTs, multivalent designs that engage B-cells transiently - not tightly - consistently outperformed others, boosting germinal center fitness and unlocking rare or more efficient SHM pathways for breadth. These effects were independent of affinity or precursor frequency. Single-cell transcriptomics uncovered gene programs that predict successful priming. Crucially, this scalable system provides general predictive power for immunogen performance, marking a major advance for not only HIV vaccine development, but also potentially establishing a broadly applicable framework for streamlining pre-clinical pipelines, including immunogenicity and safety evaluation.

Automated analysis of electrocardiograms relies increasingly on deep learning models. In these models, preprocessing steps may often be applied under the assumption that they inherently improve performance. This study investigates the effects of signal cleaning, trend removal, and normalization on six leading deep learning architectures for electrocardiogram classification, based on the well-established PTB-XL dataset, a widely used reference standard in electrocardiogram (ECG) data analysis. By exhaustively evaluating 24 combinations of preprocessing techniques with each model, and repeating each trial ten times for robustness, we find a surprising degree of architecture-dependent sensitivity. Notably, convolutional neural networks performed best when raw, unnormalized electrocardiograms are used, in direct contradiction to prevailing assumptions. In contrast, wavelet-based models benefited substantially from trend removal, while transformer-based models demonstrated robustness across a broad range of preprocessing options. These findings suggest that preprocessing pipelines should be designed with specific model architectures in mind, challenging the conventional wisdom of applying normalization in preprocessing for bounded signal data.

This study attempted to elucidate the alterations in ultrastructure of root cap cells and some metabolic reactions in yellow lupine (Lupinus luteus L.) root cells induced by silver nanoparticles (AgNPs) during the seed germination stage and seedling development. Also, the role of AgNPs in defense mechanisms against hemibiotrofic patogen Fusarium oxysporum f.sp. lupini was studied. Therefore, ultrastructural analysis of root cap cells of L. luteus L. cvs. Diament and Mister were performed by transmission electron microscopy (TEM). Additionally, intracellular reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2) was detected in root cells using confocal microscopy. The obtained research results showed distinct alterations in ultrastructure of root cap cells after pretreated with AgNPs or during cross-talk between AgNPs and F. oxysporum f.sp. lupini. It was surprising that the application of AgNPs caused local and clearly visible thickenings of the cell wall (CW) with a wide electron-dense apoplast space (AS) in the root cap cells. Also, an interesting observation was an increased presence of dictyosomes (D), characterized by a highly developed cisternae system in cells of the AgNPs and AgNPs&#x2009;+&#x2009;F. oxysporum variants in comparison to the control. An increase in the processes of endocytosis and exocytosis was noticed, which is associated with the transport of material enclosed or inserted into membrane vesicles. Besides, F. oxysporum infection induced strong autophagic activity and the occurrence of multivesicular bodies (MVBs) and multilamellar bodies (MLBs). Furthermore, in response to AgNPs or F. oxysporum alone, or in combination with AgNPs and F. oxysporum, increase in green fluorescence emission associated with ROS, especially H2O2 in relation to the control.

Bacterial glycoconjugates are structurally diverse, with enormous variation in sugar identity, modifications and linkages. Glycoconjugates play key roles in numerous cell functions, acting as the primary interface with the environment. Asparagine ( N )-linked glycosylation has been extensively studied in the pathogenic Campylobacter genus, due to the availability of numerous genome sequences and the highly conserved pathway logic, despite the final N -linked glycan product diversity. We recently reported on a partitioning of N -linked glycan structures between the Campylobacter species, focused on the inclusion of a C6-carboxyl-sugar in the third position of the growing glycan in Campylobacter concisus . However, at the time, the final glycan was not fully defined. Here, we identify the final glycan product in C. concisus , demonstrating surprising substrate promiscuity of the GT-A enzyme, PglI, which adds the penultimate sugar, and uncover a previously uncharacterized enzyme (GT-25) that unexpectedly adds the final sugar to complete the heptasaccharide product. Through a detailed study of these two C. concisus pathway enzymes, the intermediate and final glycans were defined, with determination of linkage positions of major and minor isomeric products following each glycan addition, through high-resolution electronic excitation dissociation tandem mass spectrometry. These findings on the Group II C. concisus N -linked glycan highlight the diversification of the glycan and the utilization, at the non-reducing end, of GlcNAc over GalNAc, which is dominant in the Group I species.

Arterial cannulation for arterial line placement is a common procedure in critically ill patients. The radial artery is usually cannulated for this purpose, but in excessive vaso-constriction or shock, this approach may be inaccessible. In such cases, the femoral artery is frequently selected for the placement of an arterial catheter. Given this, the low number of clinical trials conducted in intensive care concerning femoral artery cannulation is surprising. The femoral approach is particularly useful in patients who require hemodynamic monitoring using transpulmonary thermodilution and fluid responsiveness tests. Arterial catheters inserted through the femoral artery are considered more durable than those placed in the radial artery. In addition, arterial pressure has higher values when measured in the femoral artery than in the radial artery. This narrative review presents current evidence on percutaneous cannulation of the common femoral artery for arterial pressure measurement in critically ill patients. The cannulation techniques are described with their limitations and contraindications. In addition, practical tips that may be useful in daily practice, and some potential pitfalls, are also presented.

Uncertainty is ubiquitous. Without it, there would never be an occasion to learn or the opportunity to discover potentially beneficial new states or behaviors and there would be no surprising threats. We review recent studies examining the nature and behavioral consequences of uncertainty, placing them into the context of risk-averse and risk-seeking choices. We discuss the downsides of uncertainty, including sloth in decision-making and quantifications of risk that distort the probabilities of the worse outcomes; the upsides of uncertainty, including various notions about exploration; and finally discuss how these come together, in combinations of neophilia and neophobia, and in mixed-motive games. We conclude with some testable hypotheses.