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The Anatomical Record

Wiley

Preprints posted in the last 30 days, ranked by how well they match The Anatomical Record's content profile, based on 11 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

1
Scaling and ecomorphology of lagomorph body shape and appendicular skeleton

Huizenga, C.; Brice, N.; Law, C. J.

2026-05-12 evolutionary biology 10.64898/2026.05.07.723560 medRxiv
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The diversity of body shapes is one of the most prominent features of phenotypic variation in mammals. Yet, mammalian body shapes are poorly quantified and the underlying components contributing to its diversity as well as its relationship to other components of the skeleton are rarely tested. Here, we use lagomorphs (hares, rabbits and pikas) as a model system to (1) investigate which components of the skeleton contributed the most to body shape diversity, (2) examine the relationships between body shape and relative limb lengths, and (3) test how body size, ecotype, burrowing behavior, and locomotor mode influenced variation in lagomorph body shape and appendicular morphology. We quantified the body shape and functional proxies of the appendicular skeleton in 40 lagomorph species from osteological specimens held at museum collections. Using phylogenetic comparative methods, we found the relative length of the ribs and elongation or shortening of the thoracic and lumbar regions contributed the most to body shape evolution across lagomorphs. Second, we found that only leporids (hares and rabbits) exhibited a significant relationship between limb length and body shape, where more elongate species exhibit relatively shorter forelimbs and hindlimbs. Lastly, we found that models incorporating body size were the best predictors of lagomorph body shape and the majority of the appendicular traits, whereas models incorporating burrowing behavior and locomotor mode were largely poor fits. Broadly, these results indicate that larger lagomorphs tend to exhibit more robust body shapes with longer, more gracile forelimbs, whereas smaller lagomorphs tend to exhibit more elongate body shapes with shorter, more robust forelimbs. Overall, this work contributes to the growing understanding of mammalian body shape evolution and demonstrates the importance of not omitting body size in ecomorphological analyses.

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Differential maturation in vestibular neuronal groups related to developmental motor reorganization in amphibians

Barrios, G.; Olechowski-Bessaguet, A.; Cardoit, L.; Fevrier, T.; Wattignier, A.; Tostivint, H.; Cattaert, D.; Thoby-Brisson, M.; Lambert, F. M.

2026-05-13 neuroscience 10.64898/2026.05.12.724497 medRxiv
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Vestibular neurons are core elements of the pathways involved in vestibulo-motor functions, such as vestibulo-spinal and vestibulo-ocular reflexes. To meet behavioral needs, electrophysiological neuronal properties are adequately adapted to the sensory-motor computation sustaining these distinct vestibular reflexes. During frog metamorphosis, there is a complete reorganization of the posturo-locomotor system while the oculomotor system remains minimally changed, probably associated to so far unknown changes in vestibular neuronal properties. We used this unique model to investigate the central developmental mechanisms underlying such a reconfiguration of vestibular-associated behaviors. Central vestibular neurons exhibit two types of electrophysiological phenotypes: tonic neurons with a continuous discharge and phasic neurons with a transitory discharge mainly due to the activation of Kv1.1 channel. Electrophysiological recordings and Kv1.1 immunolabeling of vestibulospinal (VS) and vestibulo-ocular (VO) neurons at both larval and juvenile stages revealed that the majority of VS neurons exhibited a tonic discharge in larvae but a phasic discharge in juvenile, while VO neurons remained mainly tonic throughout development. Changes in phasic and tonic neurons proportions in VS population are partly explained by neurogenesis. But we provide evidences that an electrophysiological phenotype switch is a concomitant developmental mechanism participating in the maturation of these central vestibular neurons. All together our results showed that the maturation process in central vestibular neuronal groups is highly related to the metamorphosis-induced remodeling of vestibulo-motor functions they are involved in, with the ultimate purpose of ensuring an adequate adaptation of neuronal elements properties to the developmental changes of behavioral constrains.

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Greater gray matter volume in somatosensory and parietal regions in elite skiers compared with other athletes

Nakagawa, K.; Kanosue, K.

2026-05-13 neuroscience 10.64898/2026.05.10.724084 medRxiv
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Elite athletes exhibit sport-specific neural adaptations, yet it remains unclear whether such changes reflect general effects of training or the unique demands of individual sports. Skiing requires postural control and whole-body coordination under dynamically unstable environments, placing high demands on somatosensory processing and sensorimotor integration. The present study aimed to identify structural brain characteristics specific to elite skiers by comparing them with athletes from other sports disciplines and non-athletes. T1-weighted MRI data were analyzed using voxel-based morphometry in 13 skiers, 23 non-ski control athletes and 25 non-athletes. Whole-brain analysis comparing skiers with non-ski athletes revealed a significant cluster showing greater gray matter volume in skiers compared with non-ski athletes in the left postcentral gyrus, extending into the superior parietal lobule. The identified cluster primarily encompassed cytoarchitectonic Areas 2 and 5L. These regions are involved in higher-order somatosensory processing and multisensory integration. Importantly, region-of-interest analysis demonstrated that gray matter volume within this cluster was greater in skiers compared with non-ski athletes and non-athletes, with no difference between non-ski athletes and non-athletes. These findings highlight the relative prominence of structural adaptations within somatosensory-parietal networks, reflecting the unique integration of proprioceptive and other sensory information required for elite skiing. Overall, these findings provide evidence for sport-specific structural brain differences in elite athletes and highlight the importance of somatosensory and parietal regions in sensorimotor integration relevant to skiing. These findings may have implications for understanding neural markers of expertise and may inform future approaches to training and performance evaluation in skiing.

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Peripheral anatomy of the dolphin ear and associated nervous structures: insights from macroscopic dissection, DICE-{micro}CT, histology, and confocal microscopy

De Vreese, S.; Graïc, J.-M.; Mazzariol, S.; Huggenberger, S.; Fogli, M.; Luzzati, F.; Corona, C.; Favole, A.; Cerda-Domenech, M.; Frigola, J.; Andre, M.

2026-05-19 neuroscience 10.64898/2026.05.15.725593 medRxiv
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The peripheral auditory system of dolphins comprises specialised bony, fatty, vascular, and neural structures adapted for underwater hearing and diving physiology. These include the external ear canal, acoustic fat bodies, sinuses, and associated neurovascular networks, which together support sound conduction, protection, and possibly sensory functions. Despite advances in gross anatomical description, the detailed integration of these tissues, particularly the innervation, neurovascular organisation, and their functional implications, remains poorly understood. Previous studies have described the presence of sensory nerve formations and vascular plexuses, but their arrangement, connectivity, and relation to each other are unresolved. Here, we combine macroscopic dissection, DICE-{micro}CT, histology, and high-resolution confocal microscopy to characterise several neurovascular and sensory components of the dolphin peripheral auditory system in several delphinid species. Macroscopic dissection and DICE-{micro}CT revealed the traditional acoustic fat body distribution with detailed morphology of the posterolateral extension that is not well-known. The cranial nerve distribution, and specifically the mandibular nerve branching patterns, are described in detail. Confocal microscopy uncovered a stratified neurovascular plexus around the external ear canal with a complex sensory system comprising lamellar corpuscles, Merkel cell-neurite complexes, and intraepithelial nerve fibres. Notably, the lamellar corpuscles formed a continuous, three-dimensional neural network with frequent merging and splitting of axonal bundles, shared perineuria, and vascular integration, features not observed in previous studies. Our findings demonstrate that the dolphin external ear canal and surrounding structures form a sophisticated, multimodal somatosensory organ, integrating structural, vascular, and neural specialisations likely adapted for proprioceptive mechanosensation in the aquatic environment. This study provides insights into the integration of the various components of the peripheral hearing apparatus. Future studies integrating anatomical, electrophysiological, and biomechanical approaches are needed to fully elucidate these adaptations.

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First hematological and biochemical data in a rehabilitated giant pangolin (Smutsia gigantea) from southern Cameroon

Montblanc, M.; Harvey-Carroll, J.; Vanassche, J.; Donaldson, M.; Connelly, E.; Hywood, L.

2026-05-03 zoology 10.64898/2026.04.29.721582 medRxiv
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Giant pangolin (Smutsia gigantea) is one of the least studied pangolin species worldwide, with no published hematological and biochemical data available. We report the first blood parameters from a rehabilitated adult male from Campo Maan National Park (southern Cameroon). Hematological and biochemical findings are described and discussed in relation to available data from other pangolin species. These preliminary results provide the first reference framework for this species and highlight their relevance for clinical assessment, health monitoring, and conservation management.

6
Comparative morphology of silk-spinning systems in amphipods

McKim, S.; Turner, T. L.

2026-05-12 evolutionary biology 10.64898/2026.05.07.723571 medRxiv
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Silk glands have been found in two groups of amphipods: the Corophiida and the Ampeliscidae. The silk glands in Ampeliscidae, however, have yet to be examined in detail. Here we report, for the first time, the morphology and distribution of pereopodal glands in the Ampeliscidae, in non-thread producing Synopiidae, and in the Paragammaropsidae. In the Ampeliscidae we found two gland types distributed throughout all pereopods which have the ability to create threads. Pereopods three and four have additional silk extrusion morphology at the tip of the dactylus in which silk is transformed into semi-cylindrical threads used for building domiciles. Synopiid outgroup species have one of the gland types but lack silk extrusion morphology. Using ancestral state reconstruction analysis, we find that glands in the Synopiidae are likely ancestral and hypothesize that silk glands in Ampeliscidae are derived from these ancestral glands. Silk-spinning pereopods in the Paragammaropsidae had similarities with both Corophiida and Ampeliscidae but had distinctions. Ampeliscidae silk-spinning systems bear surprising resemblance to the Corophiida which presents one to reconsider the taxonomic placement of Ampeliscidae and the origins of silk-spinning in amphipods. This is the first comprehensive study on the glandular systems of Ampeliscidae, Synopiidae, and Paragammaropsidae using advanced microscopy, providing pertinent morphological data to the study of arthropod silk gland evolution and complex traits.

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Application of modern mathematical methods for species discrimination in the water fleas (Cladocera: Branchiopoda) that appear similar to the human eye: case of Bosmina (Bosmina) longirostris (O.F. Muller, 1776) from European Eurasia and Sakhalin Island

Garibian, P.; Rubleva, V.; Burlakov, A.; Valeyev, V.; Kasatkina, A.; Kirova, V.

2026-05-22 zoology 10.64898/2026.05.20.726562 medRxiv
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Intraspecific morphological variability presents a complex challenge for biological systematics and biomonitoring, particularly for organisms with high phenotypic plasticity, such as zooplankton. Morphological differences between individuals of the water flea species Bosmina longirostris (Crustacea: Cladocera) are difficult to distinguish visually, parthenogenetic females look morphologically uniform within the species; nevertheless, they demonstrate differences attributable to their geographic origin and developmental stage. A reference dataset of microscopic images was created for the study, including populations from two geographically separated regions (seven ones from European Russia and seven ones from Sakhalin Island in the Pacific Ocean (Far East of Russia) and two age groups, demonstrating the ability of a neural network classify to successfully the intraspecific morphological variation. This study demonstrates that deep learning methods are prospective for the detection and understanding of fine morphological intraspecific differences in the cladocerans.

8
Body size and cranial shape differentiation in urban and rural house mice (Mus musculus domesticus)

Kupchella, S. C.; Kort, A. E.; Phifer-Rixey, M.

2026-05-16 zoology 10.64898/2026.05.16.725634 medRxiv
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Cities are characterized by elevated temperatures, increased pollution, and high-density human populations which often are accompanied by changes in available resources, like food. These shifts have the potential to drive phenotypic divergence in urban wildlife. Functional morphological traits, like body size, can mediate interactions between wildlife and habitat and are closely tied to life history and fitness. While examples of functional morphological variation associated with urbanization are increasing, variation in such traits as a response to urbanization remains unexplored for most taxa. Here, we investigated morphological divergence between urban and rural populations of house mice (Mus musculus domesticus). House mice are globally distributed in diverse habitats and are a model system with a wealth of phenotypic data, making them useful for the study of the impacts of urbanization on morphology. Using a paired replicate design, we sampled urban and rural populations in three distinct metropolitan regions in the eastern United States. We found that body size was smaller in urban populations. Using 3D geometric morphometrics, we also analyzed variation in cranial shape across habitats. Differences in cranial shape were largely allometric, that is, driven by differences in body size. However, we also uncovered evidence of cranial shape variation between habitats not explained by size. In contrast, we did not find evidence for habitat-driven differences in cranial capacity independent of size. Overall, our results suggest a key role for body size in mediating morphological responses to urbanization and highlight the potential of house mice as a globally-distributed model for urbanization.

9
A standardized, surgically relevant map of organ-spesific branch emergence in the human vagus nerve

Bahadir, S.; Chen, F. L.; Tamas, I. P.; McGonagle, E. R.; Nassrallah, Z.; Pelcher, I.; Sun, J.; Xing, T.; Titunick, M.; Knutson, S. M.; Levy, T. J.; Chang, E. H.; Hill, R. V.; Zanos, T.; Barbe, M. F.; Zanos, S.

2026-05-12 neuroscience 10.64898/2026.05.08.723047 medRxiv
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IntroductionVagus nerve stimulation modulates laryngeal, cardiac, pulmonary, and gastrointestinal functions. Knowledge of where along the vagal trunk organ-specific branches emerge may support alternative surgical placements of stimulation devices to engage targeted functions while avoiding off-target effects. However, no quantified map of how vagal branches emerge and how they relate to surgically relevant anatomical landmarks exists in humans. MethodsFifty-eight vagus nerves (29 left, 29 right) from 29 embalmed donor bodies (15 females) were dissected from the jugular foramen through the thoracic cavity. Branches were traced to end organs and allocated to seven groups -- sympathetic, muscular, vascular, cardiac, pulmonary, esophageal, and multiple targets -- and several sub-groups. Distances between branch emergence and the jugular foramen (JF) were normalized to three anatomical landmarks: carotid bifurcation, laryngeal prominence, and superior border of clavicle. ResultsBranch emergence follows a proximal-to-distal order: sympathetic (5.28 cm from JF), muscular (9.59 cm), vascular (10.70 cm), cardiac (19.65 cm), pulmonary (25.36 cm), and esophageal (26.57 cm). Vagal branches emerge into two embryological domains separated near the clavicle: pharyngeal arch-targeting branches cluster proximally (9.34 cm) and primitive mediastinum-targeting branches cluster distally (23.74 cm), with sympathetic, muscular, and vascular sub-groups occupying distinct zones within the proximal domain. The largest branch-free intervals occur above the left clavicle (2.33 {+/-} 2.80 cm) and below the left carotid bifurcation (2.58 {+/-} 3.17 cm). Alternate placement regions separating targeted organs from off-targets: sympathetic vs. cervical visceral at 6/8 cm (L/R), cardiac vs. carotid sinus/bifurcation at 14/10 cm, and recurrent laryngeal vs. other cervical visceral at 18/13 cm from JF. Overall, no differences were found between male and female donors. ConclusionsThis study provides a quantified, landmark-registered map of cervical and thoracic vagal branch emergence, offering a standardized anatomical template that may inform strategies for more function-selective vagal neuromodulation.

10
Gluconeogenesis and glycogen metabolism in the epidermis and endoderm of Xenopus tropicalis embryos and larvae.

Aoki, M.; Tsuchida, A.; Tamura, K.; Baba, O.; Yoshitake, K.; Furukawa, F.

2026-05-12 developmental biology 10.64898/2026.05.08.723674 medRxiv
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In many oviparous animals, egg yolk is the sole source of nutrition until feeding begins, and carbohydrates are present in only small amounts in the yolk. Glucose plays an important role in the developmental processes of various animals. In addition, gluconeogenesis has been reported to occur in the yolk syncytial layer (YSL) of cartilaginous fish and teleosts. In contrast, the role of gluconeogenesis in tetrapods remains unclear. In this study, we used Xenopus tropicalis, an anuran amphibian, which lacks YSL, and therefore provide an opportunity to examine the evolutionary conservation of gluconeogenic mechanisms among vertebrates. In X. tropicalis, liquid chromatography/mass spectrometry revealed that glucose levels increased before liver formation. Subsequent tracer experiments using 13C-labeled metabolic substrates detected gluconeogenesis activity from glycerol and lactate. Expression analyses showed that gluconeogenic genes are expressed in the epidermis and endoderm. Consistently, G0 knockout of fbp1, a key gluconeogenic gene, resulted in a significant reduction in glucose levels, affecting brain development. These findings first demonstrate that gluconeogenesis supports development of X. tropicalis. To the best of our knowledge, gluconeogenesis in developing epidermis has not been reported, highlighting previously unrecognized diversity in tissue-specific metabolism during vertebrate development. Comparative analyses across species will provide further insights into the evolution and functional significance of embryonic gluconeogenesis and nutrient metabolism.

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The lost vultures of Romania: reconstructing two centuries of decline from historical records (Gyps fulvus, Aegypius monachus, Neophron percnopterus, Gypaetus barbatus)

Osvath, G.; Denes, A. L.; Kovacs, Z.; Birau, A. C.; Papp, E.; Jako, G. V.; Zeitz, R.

2026-05-18 zoology 10.64898/2026.05.13.723308 medRxiv
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Romania represents one of the few European Union member states in which all four Old World vulture species historically maintained breeding populations: the Griffon Vulture (Gyps fulvus), Cinereous Vulture (Aegypius monachus), Egyptian Vulture (Neophron percnopterus) and Bearded Vulture (Gypaetus barbatus). Until the 2026 reintroduction efforts initiated by Foundation Conservation Carpathia and Rewilding Romania, Romania remained the last EU country whose former vulture guild had not been targeted for active recovery. Despite this exceptional significance in a European conservation context, no comprehensive synthesis of the historical and contemporary distribution of these species in Romania has been undertaken. We conducted a comprehensive review to gather all available vulture occurrence data and present a fully georeferenced database of 1,170 occurrence records spanning 1818-2025. We systematically searched museum collections, historical ornithological literature, modern field surveys and citizen-science platforms. The database documents substantial breeding populations across the Carpathian arc and Dobrogea until the early twentieth century, followed by near-total breeding collapse between the 1920s and 1960s driven by persecution, secondary poisoning and agrarian transformation. In total, 149 confirmed or probable breeding records have been documented for the four species combined, with the most recent confirmed breeding records dating to 1929 (Gyps fulvus), 1929 (Gypaetus barbatus), 1942 (Aegypius monachus) and 1966 (Neophron percnopterus). Non-breeding occurrences increase markedly after 2010, consistent with dispersal from expanding Balkan source populations. The F[a]g[a]ra {square} and Retezat Mountains emerge as the historically most important breeding strongholds for all four species. Our dataset constitutes the most detailed historical baseline currently available for vulture conservation in Romania and is intended to identify key historical sites with high potential for future reintroduction and recovery. Our results show that Romania historically supported the full guild of European obligate scavengers, and that its collapse occurred within barely four decades (1920s-1960s). The dataset highlights the value of reconstructing historical baselines in regions where functional extinction preceded the onset of modern monitoring, and provides an empirical foundation for reassembling a keystone scavenger guild at a continental scale.

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First record of the subfamily Eucerotinae (Hymenoptera: Ichneumonidae) from the mainland Afrotropics, with a description of a new species

Hopkins, T.; Nascimento, A.; Santos, B. F.; Hovorka, T.; Sääksjärvi, I. E.; Österman, E. M.

2026-05-14 zoology 10.64898/2026.05.11.724332 medRxiv
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The ichneumonid subfamily Eucerotinae has been thought to be almost absent from the tropics, with the only known Afrotropical species found in Madagascar. We report the subfamily to be present in the mainland Afrotropics, and describe a new species, Euceros species 1 from Uganda and Cameroon (name not yet shown in preprint). The subfamily had likely not been observed in the mainland Afrotropics before due to low abundances and insufficient sampling. More Eucerotinae likely remain to be discovered in tropical Africa and Asia, although tropical America may genuinely have few eucerotine species. Much more extensive sampling will be needed before it is possible to make confident estimates of how eucerotine diversity is distributed globally.

13
Non Newtonian Blood Rheology Significantly Alters Hemodynamic Predictions During Cardiac Looping: A Computational Study

Watson, M. C.; Kemmerling, E. C.; Black, L. D.

2026-05-19 developmental biology 10.64898/2026.05.15.725470 medRxiv
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Hemodynamic forces play a key role in early cardiac morphogenesis, yet many computational studies assume Newtonian blood behavior. Here, we evaluate the impact of nonNewtonian shearthinning rheology on flow patterns, pressure distributions, and wall shear stress (WSS) during cardiac looping using idealized threedimensional models of the embryonic heart tube. Five geometries representing progressive looping stages, from a linear tube to an Sshaped configuration with ventricular ballooning, were analyzed under pulsatile flow using both Newtonian and powerlaw viscosity models. Across all stages, Reynolds numbers (Re {approx} 1-7) and Womersley numbers (Wo {approx} 0.3) indicated laminar, quasisteady flow consistent with embryonic conditions. Incorporating shearthinning rheology produced substantial deviations from Newtonian predictions, with peak systolic WSS differing by up to [~]40% and pressure drops by up to [~]20%. These effects were most pronounced in regions of increased curvature and geometric complexity. These findings demonstrate that nonNewtonian rheology significantly influences predicted hemodynamic environments during cardiac looping and should be incorporated into computational models aimed at understanding mechanobiological regulation of early heart development.

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Integrative taxonomy of Trichiurus (Scombriformes: Trichiuridae) reveals a new cutlassfish species from Java, Indonesia

Wu, T.; Li, C.

2026-05-08 zoology 10.64898/2026.05.05.722933 medRxiv
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The genus Trichiurus is the most economically valuable fish in the family Trichiuridae, currently recognized to include 10 valid species. However, historically numerous morphologically similar congeners have been erroneously assigned as synonyms or subspecies of T. lepturus. In this study, we examined 16 hairtail specimens collected from the southern waters of Java Island, Indonesia. Integrated morphological and mitochondrial phylogenetic analyses (COX1 and 16S rRNA), compared against global Trichiurus sequences, revealed that these specimens form an independent lineage that diverged early from other congeners. Consequently, we describe this lineage as a previously undescribed cryptic species. Diagnostic characters include: first anal-fin spine below 36th-37th dorsal-fin rays; anus below 35th-36th dorsal-fin rays; anteriormost tip of supraoccipital well posterior to posterior distal margin of eye; anterior margin of the pectoral-fin spine non-serrated; fangs on both jaws with barb-like processes; upper jaw long, mean 16.6% (15.5-17.6%) of preanal length; snout short, 12.0% (10.9-13.1%) of preanal length; eye small, diameter 5.3% (4.3-5.7%) of preanal length; and absence of hyperostosis on dorsal cranium. We herein propose the name Trichiurus javaensis sp. nov., and provide a formal morphological description and diagnostic characterization of this species.

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Ancient nervous system architecture in a living ctenophore

Ferraioli, A.; Miramon-Puertolas, P.; Altenkirch, P. E.; Jan, A.; Colgren, J.; Vinther, J.; Burkhardt, P.

2026-05-22 neuroscience 10.64898/2026.05.20.726345 medRxiv
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The evolutionary origin of nervous systems in animals remains elusive and is largely hidden from the fossil record. Ctenophores, one of the earliest-branching animals possessing neurons, are instrumental to our understanding of nervous system origin, and a few rare ctenophore fossils preserve traces of nervous tissue as carbonaceous remains. Cambrian ctenophores appear to exhibit a more diverse neuroanatomy than that of modern species, suggesting secondary loss in extant ctenophores. However, much remains unknown about the origin and ontogeny giving rise to the structural organization of modern ctenophore nervous systems. Here, by investigating the neural anatomy of the ctenophore Mnemiopsis leidyi during development, we identified a ladder-like nerve net (LNN) beneath the comb rows that converges into condensed neurites and connects to the aboral organ. Examination of carbon-rich areas of Ctenorhabdotus capulus, an extinct ctenophore from the Burgess Shale, reveals a pattern similar to that of M. leidyi, consistent with a shared neural organization. Furthermore, M. leidyi exhibits a condensed comb nerve, resembling the longitudinal nerve preserved in the Cambrian ctenophore Fasciculus vesanus and the giant axon of extant Euplokamis dunlapae. Our study reveals conserved evolutionary constraints shaping nervous system architectures linked to locomotory organs and indicates that the different modes of nervous system organization observed in Cambrian ctenophores are variably retained in modern species.

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Computational modeling of neurovascular coupling at the gliovascular interface

Dupeuble, F.; Berry, H.; Denizot, A.

2026-05-18 neuroscience 10.64898/2026.05.15.725343 medRxiv
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A growing number of studies indicate the possible involvement of astrocytes in triggering or modulating neurovascular coupling (NVC), i.e. the local dilation of blood vessels in the brain in response to neuronal activity. Astrocytes possess specialized subcellular compartments, named endfeet, that surround arterioles and capillaries, ideally positioned to mediate NVC. Various vasodilators have been shown to contribute to NVC, such as epoxyeicosatrienoic acid (EET), nitric oxide (NO), or prostaglandin E2 (PGE2), but the precise mechanisms underlying NVC and their variability remain to be fully elucidated. In particular, the involvement of astrocytes in this process is controversial. Recent translatome and proteomics data reveal that astrocytes and in particular endfeet are enriched in the proteins of the PGE2 pathway. However, how the latter could contribute to NVC remains to be characterized. Here, we develop a computational model of astrocyte-mediated NVC that recapitulates these findings and describes Ca2+ and PGE2 signaling in astrocytes, NO release by neurons, and arteriole diameter dynamics using ordinary differential equations. The model successfully reproduces the dynamics of arteriole diameter change during hyperemia from in vivo neocortical recordings in awake mice. Our simulations suggest that the astrocyte PGE2 pathway could be responsible for the late response of NVC at the arteriolar level. We further observe that PIP2-derived diacylglycerol plays a major role in driving arteriole diameter dynamics in our model, while phosphatidic acid-derived diacylglycerol, which is calcium-dependent, mainly acts as an amplifier of this response. Finally, a spatial implementation of the model using a simplified astrocyte geometry suggests that NVC is more efficient when synaptic stimulation occurs at the endfoot level rather than at other astrocytic compartments. Overall, this computational study suggests a partial role for astrocyte-mediated PGE2 release in NVC and points to astrocyte perivascular processes as sub-compartments that are ideally positioned and equipped to mediate NVC. Author summaryIn the brain, the local blood flow is regulated to meet neuronal energy demand by modulating the dilation of neighboring blood vessels. The mechanisms driving this process, known as neurovascular coupling (NVC), remain debated and are likely to differ depending on the physiological context. Recent evidence points to astrocytes, a cell type possessing specialized protrusions called "endfeet", that envelop the entire brain vascular tree. Contacts between synapses and endfeet have recently been reported, positioning the latter as ideal mediators of NVC. Here, we developed a computational model that simulates the signaling between neurons, astrocytes, and blood vessels. Our model successfully reproduces experimental recordings of blood vessels dilation in the brains of awake mice. Our simulations suggest that a specific signaling pathway in astrocytes, involving a molecule called prostaglandin E2, is a key driver of the late phase of NVC, occurring a few seconds after neuronal activity. Furthermore, our model indicates that the location of the stimulated synapses matters: signals sent to the astrocyte endfeet are particularly effective at controlling blood flow. This work helps clarify the active role of astrocytes in brain blood flow regulation, a process critical for healthy brain function.

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The direct conversion of human somatic cells into neural-like cells involves a transition through a transient intermediate state.

Bueno, C.; Martinez-Morga, M.; Rodriguez-Lozano, F. J.; Garcia-Bernal, D.; Martinez, S.; Moraleda, J. M.; Blanquer, M.

2026-05-18 neuroscience 10.64898/2026.05.14.725118 medRxiv
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BackgroundDirect conversion of human somatic cells into functional neurons could offer a faster way to generate patient-specific neurons for use in regenerative medicine, disease modelling, and drug development. Although it has been reported that neuronal direct reprogramming bypasses the intermediate pluripotent state, no reports have included time-lapse experiments, potentially overlooking transient intermediate states. Recent studies have shown that the conversion of human mesenchymal stromal cells (hMSCs) into neuron-like cells involves a transition through a transient intermediate state. Therefore, further research is needed to fully understand the process by which human somatic cells can become neurons without cell division. In this study we investigates whether direct neuronal reprogramming of human bone marrow-derived MSC (hBM-MSCs), dental pulp-derived MSC (hDP-MSCs), and adult human dermal fibroblasts (HDFa), involves a transient intermediate state, and sought to further validate the neuronal identity of hMSC-derived induced neurons. MethodsIn this study, we conducted time-lapse experiments to observe the transformation of hBM-MSCs, hDP-MSCs and HDFa, into neurons using a small-molecule-based direct reprogramming protocol. Cellular and ultrastructural changes were further characterized by confocal and electron microscopy. ResultsDirect conversion of hBM-MSCs, hDP-MSCs and HDFa into neuron-like cells occurred rapidly and in absence of cell division. Time-lapse analyses revealed that reprogramming proceeds through a transient intermediate state characterized by distinct morphological changes and dynamic nuclear remodelling. Furthermore, we found that neuron-like cells derived from hBM-MSCs and hDP-MSCs exhibit neuronal polarization, expressed specific neuronal and synaptic markers, formed interconnected cellular networks, and exhibited functional plasticity, providing further evidence that hMSCs can become functional neurons. ConclusionsThis study provides clear evidence that the direct neuronal reprogramming process involves a transition through an intermediate, transient state. Our findings also provide further evidence that hMSCs can become functional neurons. In summary, our work provides new insights into the direct neuronal reprogramming process, which is essential for advancing both developmental biology and regenerative medicine.

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Sex-related differences in healthy aging: changes in neuroelectric brain activity reconstructed from resting-state MEG

Ustinin, M.; Boyko, A.; Rykunov, S.

2026-05-11 neuroscience 10.64898/2026.05.06.723197 medRxiv
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Sex-related differences in the aging of the human brain were studied using large array of experimental data. The open archive CamCan was used as a source of data: the magnetic encephalograms, co-registered with magnetic resonance images of the head, were obtained for each of 434 subjects (ages 18-87 years, mean age 54.7 {+/-}18.4): 217 females (ages 18-87 years, mean age 54.5 {+/-}18.4) and 217 males (ages 18-84 years, mean age 54.8 {+/-}18.3). Recordings were split in 10-year age cohorts, each cohort consisted of equal number of men and women to calculate average intersex characteristics correctly. By massively solving the inverse problem, functional tomograms were calculated - the spatial distribution of elementary spectral components. Physiological noise was eliminated by joint analysis of MEG-based functional tomogram and magnetic resonance image for each subject. Then multichannel spectra were transformed into time series of the power of elementary current dipoles. Summary electric powers were calculated in six conventional frequency bands (1-4 Hz - delta; 4-8 Hz - theta; 8-13 Hz - alpha; 13-21 Hz - beta1; 21-30 Hz - beta2; 30-48 Hz - gamma), and sex differences in age-related changes were examined. It was found that in the youngest age cohort (18-29 years) the summary electrical power of the brain for males is 1.5 times greater than such power for females. For adults (30-69 years), male and female powers are approximately equal, while in older cohorts (70-87 years), male total brain power is greater. Age dependencies in various frequency bands are generally different for men and women, excluding higher frequencies 21-48 Hz. Basic conclusion can be made that after intersex averaging total electric power of the human brain is invariant through the lifespan from 18 to 87 years. The proposed method of joint MEG and MRI analysis can be used for further study of the sex-related details of brain sources in their connection with age changes.

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Photoprotective demands predict external eye pigmentation in terrestrial mammals

Streiferdt, C. S.; Caspar, K. R.

2026-05-19 zoology 10.64898/2026.05.16.725635 medRxiv
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The evolution of eye coloration in mammals and its potential ecological significance remain understudied. Evidence from anthropoid primates suggests that photoprotective demands are crucial determinants of pigmentation in the peri-iridal tissues, which encompass the conjunctiva and portions of the sclera peripheral to the iris. However, it is unclear to what extent these findings can be generalized. Here, we quantify peri-iridal brightness in a photographic sample of 62 terrestrial non-primate mammal species (n = 930). Phylogenetically-controlled analyses revealed significant effects of eye size as well as ecology on ocular pigmentation. Peri-iridal brightness exhibits a notable phylogenetic signal, correlates negatively with eye size and hence exposure to UV light, and is more pronounced in nocturnal species. Significant interspecific effects of latitude on peri-iridal brightness were not recovered, but tentative evidence for non-negligible impacts of this variable at the intraspecific level were found. Overall, these results align with and help to contextualize findings on primates and suggest that photoprotective demands importantly shape ocular appearance across the mammalian radiation. Furthermore, they have implications for hypotheses tying eye pigmentation chiefly to gaze signaling and provide a broad evolutionary framework for the emergence of human eye appearance.

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The role of the roof plate for mesencephalic trigeminal neuron

Lumper, C.; Koumoundourou, A.; Neukum, M.; Rauchfuss, S.; Kohler, U.; Hirt, B.; Graham, A.; Wizenmann, A.

2026-05-07 developmental biology 10.64898/2026.05.04.722596 medRxiv
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The mesencephalic trigeminal nucleus (MTN) contains the proprioceptive sensory neurons that innervate mechanoreceptors in the jaw closing muscles. In the chick embryo, MTN neurons are the first neurons generated in the mesencephalon. They arise bilaterally adjacent to the roof plate and then extend their axons ventrally before projecting caudally towards the rhombencephalon. MTN axons remain in a mid - dorsoventral position and pioneer the lateral longitudinal fasciculus. Notably, MTN axons never cross the roof plate, raising the question of which mechanisms underlie this restriction. Here, we investigated the effects of tissue transplants on the guidance of MTN axons. We found that both the diencephalon and the notochord exert repulsive effects on MTN axons, which could partially explain their early trajectory. We have also analysed the potential roles of the guidance cues BMP2/4, GDF7, SLIT and NETRIN in MTN axon navigation, both in vivo and in vitro. We found no evidence for a role of BMP2/4 or GDF7 in directing MTN axons. However, SLIT-ROBO signaling was found to play a significant role. SLIT proteins are repulsive guidance cues expressed by roof and floor plate. Loss or reduced expression of ROBO2 led to aberrant axon meandering within the dorsal midbrain. Most axons eventually reoriented posteriorly, and only a small fraction crossed the roof plate. Unexpectedly, in the absence of ROBO2, MTN somata migrated into the roof plate, resulting in the loss of a defined roof plate region. Taken together, these results suggest that SLIT2-ROBO2 signaling not only prevents MTN axons from crossing the roof plate but also maintains MTN cell bodies adjacent to the roof plate. With regards to MTN neuron guidance, we conclude that additional roof plate - derived factors are likely to co-operate with SLIT proteins to prevent crossing of the roof plate. Another possibility could be that SLIT might signal through additional receptors.