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Communications Biology

Springer Science and Business Media LLC

All preprints, ranked by how well they match Communications Biology's content profile, based on 993 papers previously published here. The average preprint has a 0.83% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.

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Physical Activity Shapes Brain Structure, Function, and the Computational Mechanisms of Cognitive Control

Carvajal-Paredes, P.; Davyt-Colo, J.; Figueroa-Vargas, A.; Martinez-Molina, M. P.; Manterola, C.; Stecher, X.; Zamorano, F.; Soto-Icaza, P.; Billeke, P.

2025-12-15 sports medicine 10.64898/2025.12.12.25342075 medRxiv
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BackgroundSedentarism is prevalent and associated with poorer mental and physical health. Whether everyday physical activity (PA) maps onto computational decision strategies and brain structure/function in non-elderly adults remains unclear. MethodsSeventy-one healthy adults (39 women; 18-45 years) completed the Multi-Source Interference Task (MSIT) during fMRI. PA was quantified with the short IPAQ and participants were classified as Active or Sedentary. Behavior (RT, accuracy) was analyzed with frequentist models and a hierarchical Bayesian drift-diffusion model (DDM) estimating drift rate (v), boundary separation (), and non-decision time ({tau}). First-level fMRI modeled congruent/incongruent trials; group-level analyses used FLAME1 with cluster-wise FWE correction (z>3.1, p <.05). Structural MRI was processed with FreeSurfer 7.4.1 (cortical thickness, hippocampal subfields); surface-based GLMs tested group and DDM effects. ResultsActive participants responded faster overall; incongruent accuracy showed a speed- accuracy trade-off (accuracy increased with slower RTs), with a significant RT x group interaction. In the DDM, boundary separation () was higher in sedentary individuals (greater caution), whereas drift rate (v) differed by sex (males > females). Structurally, the active group showed larger left hippocampal subfields and thicker cortex in posterior temporal & anterior cingulate regions that are negatively related to . Functionally, boundary-related BOLD modulation encompassed fusiform, posterior cingulate, superior temporal cortex, and SMA; Active > Sedentary contrasts highlighted left occipital and inferior parietal lobe. ConclusionsEveryday PA aligns with lower decision thresholds, select structural advantages, and more efficient task-engaged networks, suggesting PA fosters adaptive, resource-efficient cognitive control. These mechanistic links support PA-based strategies to mitigate risks of sedentarism.

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Nitric oxide (NO) signaling in Trichoplax and related species: Microchemical characterization and the lineage-specific diversification

Moroz, L. L.; Romanova, D. Y.; Nikitin, M. A.; Sohn, D.; Kohn, A. B.; Neveu, E.; Varoqueaux, F.; Fasshauer, D.

2020-04-12 evolutionary biology 10.1101/2020.04.10.034207 medRxiv
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Nitric oxide (NO) is a free radical gaseous messenger with a broad distribution across the animal kingdom. However, the early evolution of nitric oxide-mediated signaling in animals is unclear due to limited information about prebilaterian metazoans such as placozoans. Here, we analyzed NO synthases (NOS) in four different species of placozoans (haplotypes H1, H2, H4, H13). In contrast to all other invertebrates studied, Hoilungia and Trichoplax have three distinct NOS genes, including PDZ domain-containing NOS. To characterize NOS activity in Trichoplax adhaerens, we used capillary electrophoresis for microchemical assays of NO-related metabolites. Specifically, we quantified nitrites (products of NO oxidation) and L-citrulline (co-product of NO synthesis from L-arginine), which were affected by NOS inhibitors confirming the presence of functional NOS. Next, using fluorescent single-molecule in situ hybridization, we showed that distinct NOSs are expressed in different subpopulations of cells, with a noticeable distribution close to the edge regions of Trichoplax. These data suggest the compartmentalized release of this messenger and a greater diversity of cell types in placozoans than anticipated. We also revealed a dramatic diversification of NO receptor machinery, including identification of both canonical and novel NIT-domain containing soluble guanylate cyclases as putative NO/nitrite/nitrate sensors. Thus, although Trichoplax is considered to be one of the morphologically simplest free-living animals, the complexity of NO-cGMP-mediated signaling is greater to those in vertebrates. This situation illuminates multiple lineage-specific diversifications of NOSs and NO/nitrite/nitrate sensors from the common ancestor of Metazoa. Short AbstractNitric oxide (NO) is a ubiquitous gaseous messenger, but we know little about its early evolution. Here, we analyzed NO synthases (NOS) in four different species of placozoans - one of the early-branching animal lineages. In contrast to other invertebrates studied, Trichoplax and Hoilungia have three distinct NOS genes, including PDZ domain-containing NOS. Using ultra-sensitive capillary electrophoresis assays, we quantified nitrites (products of NO oxidation) and L-citrulline (co-product of NO synthesis from L-arginine), which were affected by NOS inhibitors confirming the presence of functional enzymes in Trichoplax. Using fluorescent single-molecule in situ hybridization, we showed that distinct NOSs are expressed in different subpopulations of cells, with a noticeable distribution close to the edge regions of Trichoplax. These data suggest both the compartmentalized release of NO and a greater diversity of cell types in placozoans than anticipated. NO receptor machinery includes both canonical and novel NIT-domain containing soluble guanylate cyclases as putative NO/nitrite/nitrate sensors. Thus, although Trichoplax and Hoilungia exemplify the morphologically simplest free-living animals, the complexity of NO-cGMP-mediated signaling in Placozoa is greater to those in vertebrates. This situation illuminates multiple lineage-specific diversifications of NOSs and NO/nitrite/nitrate sensors from the common ancestor of Metazoa.

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Comparative Analysis of Human-Chimpanzee Divergence in Brain Connectivity and its Genetic Underpinnings

Wang, Y.; Cheng, L.; Li, D.; Lu, Y.; Wang, C.; Wang, Y.; Gao, C.; Wang, H.; Vanduffel, W.; Hopkins, W.; Sherwood, C.; Jiang, T.; Chu, C.; Fan, L.

2024-06-04 neuroscience 10.1101/2024.06.03.597252 medRxiv
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Chimpanzees (Pan troglodytes) are humans closest living relatives, making them the most directly relevant comparison point for understanding human brain evolution. Zeroing in on the differences in brain connectivity between humans and chimpanzees can provide key insights into the specific evolutionary changes that might have occured along the human lineage. However, conducting comparisons of brain connectivity between humans and chimpanzees remains challenging, as cross-species brain atlases established within the same framework are currently lacking. Without the availability of cross-species brain atlases, the region-wise connectivity patterns between humans and chimpanzees cannot be directly compared. To address this gap, we built the first Chimpanzee Brainnetome Atlas (ChimpBNA) by following a well-established connectivity-based parcellation framework. Leveraging this new resource, we found substantial divergence in connectivity patterns across most association cortices, notably in the lateral temporal and dorsolateral prefrontal cortex between the two species. Intriguingly, these patterns significantly deviate from the patterns of cortical expansion observed in humans compared to chimpanzees. Additionally, we identified regions displaying connectional asymmetries that differed between species, likely resulting from evolutionary divergence. Genes associated with these divergent connectivities were found to be enriched in cell types crucial for cortical projection circuits and synapse formation. These genes exhibited more pronounced differences in expression patterns in regions with higher connectivity divergence, suggesting a potential foundation for brain connectivity evolution. Therefore, our study not only provides a fine-scale brain atlas of chimpanzees but also highlights the connectivity divergence between humans and chimpanzees in a more rigorous and comparative manner and suggests potential genetic correlates for the observed divergence in brain connectivity patterns between the two species. This can help us better understand the origins and development of uniquely human cognitive capabilities.

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Single-cell transcriptomics identifies a p21-activated kinase important for survival of the zoonotic parasite Fasciola hepatica

Puckelwaldt, O.; Gramberg, S.; Ajmera, S.; Koepke, J.; Samakovlis, C.; Haeberlein, S.

2024-03-27 molecular biology 10.1101/2024.03.26.586785 medRxiv
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Knowledge on the cell types and cell-specific gene expression of multicellular pathogens facilitates drug discovery and allows gaining a deeper understanding of pathogen biology. By utilizing single-cell RNA sequencing (scRNA-seq), we analyzed 19,581 cells of a globally prevalent parasitic flatworm, the liver fluke Fasciola hepatica, which causes a neglected tropical disease and zoonosis known as fascioliasis. We identified 15 distinct clusters, including cells of the reproductive tract and gastrodermis, and report the identification and transcriptional characterization of potential differentiation lineages of stem cells within this parasite. Furthermore, a previously unrecognized ELF5- and TRPMPZQ-expressing muscle cell type was discovered, characterized by high expression of protein kinases. Among these, the p21-activated kinase PAK4 was essential for parasite survival. These data provide novel insight into the cellular composition of a complex multicellular parasite and demonstrate how gene expression at single-cell resolution can serve as a resource for the identification of new drug targets.

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Atypical functional connectome in congenitally blind humans

Koba, C.; Falco-Roget, J.; Collignon, O.; Raczy, K.; Bedny, M.; Tian, M.; Szwed, M.; Stroh, A.-L.

2025-03-02 neuroscience 10.1101/2025.02.28.640746 medRxiv
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The human cortex is organized along continuous functional gradients that capture systematic transitions in functional connectivity across the brain. These gradients describe large-scale organizational principles, including hierarchical transitions from unimodal to transmodal regions. Here, we provide the first characterization of cortical gradients in a large sample of congenitally blind (n = 41) and sighted (n = 44) adults to assess the relative contributions of intrinsic (genetic) and experiential factors to cortical gradient organization. Using resting-state fMRI, we compared functional connectome gradients and their association with cortical structure. Both groups exhibited similar principal gradients: unimodal to transmodal, somatosensory to visual, and frontoparietal segregation, demonstrating that the fundamental scaffold of cortical organization emerges largely independently of visual experience. However, blindness altered specific features of the functional connectome: the visual network was more segregated from the sensorimotor network and more integrated with transmodal and frontoparietal networks. Moreover, blind individuals showed reduced canonical hierarchical ordering within early visual areas, weaker structure-function coupling in visual and temporal regions, and altered functional areal boundaries in V1. These findings suggest that the development of large-scale cortical gradients reflects a genetically guided scaffold that is subsequently refined by sensory experience.

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Synchrony of mind and body are distinct in mother-child dyads

Reindl, V.; Wass, S.; Leong, V.; Scharke, W.; Wistuba, S.; Wirth, C. L.; Konrad, K.; Gerloff, C.

2021-02-21 neuroscience 10.1101/2021.02.21.432077 medRxiv
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Hyperscanning studies have begun to unravel the brain mechanisms underlying social interaction, indicating a functional role for interpersonal neural synchronization (INS), yet the mechanisms that drive INS are poorly understood. While interpersonal synchrony is considered a multimodal phenomenon, it is not clear how different biological and behavioral synchrony markers are related to each other. The current study, thus, addresses whether INS is functionally-distinct from synchrony in other systems - specifically the autonomic nervous system (ANS) and motor behavior. To test this, we used a novel methodological approach, based on concurrent functional near-infrared spectroscopy-electrocardiography, recorded while N = 34 mother-child and stranger-child dyads (child mean age 14 years) engaged in cooperative and competitive tasks. Results showed a marked differentiation between neural, ANS and behavioral synchrony. Importantly, only in the neural domain was higher synchrony for mother-child compared to stranger-child dyads observed. Further, ANS and neural synchrony were positively related during competition but not during cooperation. These results suggest that synchrony in different behavioral and biological systems may reflect distinct processes. Mother-child INS may arise due to neural processes related to social affiliation, which go beyond shared arousal and similarities in behavior.

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Targeted saliva multi-omics is a reliable, non-invasive method to capture physiological stress and recovery

Wenzel, C.; Kalaycik, B.; Billig, A.; Trebing, S.; Joisten, N.; Kolodziej, M.; Braun, M.; Lippelt, L.; Gerharz, A.; Millard, M.; Wieder, O.; Kipper, K.; Iebed, A.; Groll, A.; Walzik, D.; Zimmer, P.

2026-01-30 sports medicine 10.64898/2026.01.28.26345066 medRxiv
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Determining physiological stress at high resolution is crucial across diverse settings to enable informed decision-making in the context of health and disease. Saliva-based targeted multi-omics testing provides a powerful, non-invasive method to quantify physiological stress and circadian dynamics at high-frequency. In a laboratory crossover trial with 24-hour sampling comprising 413 saliva samples, we demonstrate high analytical reliability, distinct molecular individuality, and robust acute and delayed responses to physical exercise across proteins, metabolites, and lipids. Moreover, we present the most comprehensive existing dataset describing 24-hour molecular kinetics across these three omics layers. Leveraging this controlled setting, we applied machine learning to single-timepoint saliva samples to accurately predict recent physical exercise both immediately after and 24 hours later. Next, we translated this analytical framework to a real-world longitudinal setting of elite football players monitored over 16 months, comprising over 12,000 saliva samples. Despite increased biological and contextual variability, the model retained robust discrimination between exercise and rest on the following day. Based on prediction probabilities, we introduce a saliva-based internal strain metric, that captures internal load and can be harnessed to monitor physical exercise and recovery. Model robustness was further supported through out-of-sample validation using previously unseen observations. Our findings demonstrate that saliva-based targeted multi-omics reliably captures physical exercise and recovery states in both laboratory and real-world environments, providing a scalable framework for monitoring physical performance. This non-invasive approach holds broad potential for physiological monitoring and can serve as a blueprint for health- and disease-related contexts.

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Human outperform mouse Purkinje cells in dendritic complexity and computational capacity

Masoli, S.; Sanchez-Ponce, D.; Vrieler, N.; Abu-Haya, K.; Lerner, V.; Shahar, T.; Nedelescu, H.; Rizza, M. F.; Benavides-Piccione, R.; DeFelipe, J.; Yarom, Y.; Munoz, A.; D'Angelo, E.

2023-03-09 neuroscience 10.1101/2023.03.08.531672 medRxiv
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Purkinje cells (PC) of the cerebellum are amongst the largest neurons of the brain and have been extensively investigated in rodents. However, their morphological and physiological properties in humans are still poorly understood. Here, we have taken advantage of high-resolution morphological reconstructions and of unique electrophysiological recordings of human PCs ex vivo to generate computational models and estimate computational capacity. An inter-species comparison showed that human PCs had similar fractal structure but were bigger than mouse PCs. Consequently, given a similar spine density (2/m), human PCs hosted about 5 times more dendritic spines. Moreover, human had higher dendritic complexity than mouse PCs and usually emitted 2-3 main dendritic trunks instead than 1. Intrinsic electroresponsiveness was similar in the two species but model simulations revealed that the dendrites generated ~6.5 times (n=51 vs. n=8) more combinations of independent input patterns in human than mouse PCs leading to an exponential 2n increase in Shannon information. Thus, while during evolution human PCs maintained similar patterns of spike discharge as in rodents, they developed more complex dendrites enhancing computational capacity up to the limit of 10 billion times.

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An introgressed galectin-like protein is a candidate driver of the human tropism in the intestinal parasite Cryptosporidium

Bellinzona, G.; Tichkule, S.; Jex, A.; van Oosterhout, C.; Bandi, C.; Sassera, D.; Castelli, M.; Caccio, S. M.

2026-04-09 genomics 10.64898/2026.04.07.716958 medRxiv
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Cryptosporidium spp. are protozoan parasites responsible for diarrheal diseases. In humans, cryptosporidiosis is predominantly caused by the human-specific Cryptosporidium hominis and by Cryptosporidium parvum. This second species has been classically reported as zoonotic, with a host preference for ruminants. However, the recently described subspecies C. parvum anthroponosum has been found to be restricted to humans. Here, we generated novel whole genome sequences from West African samples of C. p. anthroponosum, and analyzed them together with all those already available, originating from East Africa, Europe, North America and Asia. Phylogenomics showed that all C. p. anthroponosum isolates are strongly clustered together, forming the sister clade of the zoonotic C. parvum representatives. The phylogenetic variations within C. p. anthroponosum did not present a clear geographic structure, consistent with C. hominis, primarily transmitted in humans. To elucidate the evolution of host species adaptation in C. p. anthroponosum, we then investigated genetic exchanges with C. hominis, detecting an ancestral introgression present in all C. p. anthroponosum isolates. This introgression involved a single gene, encoding for an extracellular galectin-like protein, which we predicted with high confidence to form a protein complex with the human insulin-degrading enzyme, a key metabolic regulator. Considering the role of host insulin metabolism in the proliferation of parasites as well as its known intrinsic differences between humans and ruminants, this molecular interaction could represent a plausible mechanism for an important role of the galectin-like protein in host-parasite interactions and in the host specificity of C. p. anthroponosum.

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Antibodies halting motility in Mycoplasma pneumoniae reveal the dynamic nature of the adhesion complex

Kawamoto, A.; Vizarraga, D.; Marcos-Silva, M.; Martin, J.; Makino, F.; Miyata, T.; Roel, J.; Marcos, E.; Aparicio, D.; Fita, I.; Miyata, M.; Pinol, J.; Namba, K.; Kenri, T.

2023-07-31 molecular biology 10.1101/2023.07.31.551205 medRxiv
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Mycoplasma pneumoniae is a bacterial wall-less human pathogen and the etiological agent of atypical pneumonia and tracheobronchitis in both adults and children. M. pneumoniae infectivity, gliding motility and adherence to host target respiratory epithelial cells are mediated by adhesin proteins P1 and P40/P90 forming a transmembrane complex that binds to sialylated oligosaccharides human cell ligands. Here we report the cryo-EM structure of P1 bound to the Fab fragment of monoclonal antibody P1/MCA4, which stops gliding and induces detachment of motile M. pneumoniae cells. On the contrary, polyclonal antibodies generated against the N-domain of P1 or against the whole ectodomain of P40/P90 have little or no effects on adhesion or motility. The epitope of P1/MCA4, centred on loop Thr1426-Asp1438 in the small C-terminal domain of P1, is inaccessible to antibodies in the "open" conformation of the adhesion complex, when ready for attachment to sialylated oligosaccharides. Mutations in the highly conserved Engelman motifs found in the transmembrane helix of P40/P90 also alter adhesion and motility. During the attachment/detachment cycle of the adhesion complex, the C-terminal domain of P1 experiences large conformational rearrangements that are hindered by the antibodies against the domain. Interfering with the gliding of mycoplasma cells suggests new ways to confront M. pneumoniae infections.

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Gene expression of macaques infected with malaria species of zoonotic concern

Bergey, C. M.; Trujillo, A. E.

2023-01-20 systems biology 10.1101/2023.01.19.524806 medRxiv
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A multitude of malaria species (genus Plasmodium) infects primates. Due to their public health importance, the human-infective species have garnered the most focus, but increased knowledge of non-human primate malaria species is warranted to improve our evolutionary understanding of host-parasite interactions. Additionally, the broad host tropism of some primate malaria parasites and their realized or theorized zoonotic potential add urgency to understanding of primate-parasite interactions. Here, we use comparative transcriptomics to understand the rhesus macaque (Macaca mulatta) response to two malaria parasites used as analogues to human-infective species of differing severity and which may represent emerging zoonotic threats: P. coatneyi, comparable to human-infective P. falciparum, and P. cynomolgi, comparable to human-infective P. vivax. We first validate our transcriptomics-based proxy of parasite load through comparison to gold-standard microscopy-based measures. We then find that malaria-associated host genes have functional links to immune system regulation and blood cells. Host genes with differing expression by malaria species were more likely to be involved in brain-linked functions, perhaps due to the differential central nervous system involvement of the two parasite species. Such comparative work on primate malaria species may help elucidate the essential and species-specific molecular mechanisms that underlie differing clinical presentations and zoonotic risk.

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Multi-omics analysis reveals cross-organism interactions in coral holobiont

Maruyama, T.; Ito, M.; Wakaoji, S.; Okubo, Y.; Ide, K.; Nishikawa, Y.; Fujimura, H.; Suda, S.; Nakano, Y.; Satoh, N.; Shinzato, C.; Yura, K.; Takeyama, H.

2021-10-26 systems biology 10.1101/2021.10.25.465660 medRxiv
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Corals create an ecosystem, called a holobiont, with intracellular algae (zooxanthellae) and resident bacteria. Zooxanthellae and some bacteria play major roles in the physiological properties of the coral host. However, because of the difficulties in experimental verification of cross-organism interactions, the mechanisms underpinning these interactions are largely unknown. To address this, we here generated and then analyzed multi-omics datasets for corals, zooxanthellae, and bacteria collected at Okinawa, Japan, from November 2014 to September 2016. Using cross-organism co-expression analysis, we successfully characterized the host-alga relationship in the coral holobiont. Specifically, we observed that the coral host dominates the zooxanthellae. The multi-omics analysis also suggested that infection with coral-associated bacteria Endozoicomonas likely involves coral-like ephrin ligands, triggering an immune response of the coral host. This study highlights the potential of the multi-omics approach to elucidate coral-microbe interactions.

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Haplotype-Resolved Cattle Genomes Provide Insights Into Structural Variation and Adaptation

Low, W. Y.; Tearle, R.; Liu, C.; Koren, S.; Rhie, A.; Bickhart, D. M.; Rosen, B. D.; Kroneberg, Z. N.; Kingan, S. B.; Tseng, E.; Thibaud-Nissen, F.; Martin, F. J.; Billis, K.; Ghurye, J.; Hastie, A. R.; Lee, J.; Pang, A.; Heaton, M. P.; Phillippy, A. M.; Hiendleder, S.; Smith, T. P.; Williams, J. L.

2019-08-01 genomics 10.1101/720797 medRxiv
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We present high quality, phased genome assemblies representative of taurine and indicine cattle, subspecies that differ markedly in productivity-related traits and environmental adaptation. We report a new haplotype-aware scaffolding and polishing pipeline using contigs generated by the trio binning method to produce haplotype-resolved, chromosome-level genome assemblies of Angus (taurine) and Brahman (indicine) cattle breeds. These assemblies were used to identify structural and copy number variants that differentiate the subspecies and we found variant detection was sensitive to the specific reference genome chosen. Six gene families with immune related functions are expanded in the indicine lineage. Assembly of the genomes of both subspecies from a single individual enabled transcripts to be phased to detect allele-specific expression, and to study genome-wide selective sweeps. An indicus-specific extra copy of fatty acid desaturase is under positive selection and may contribute to indicine adaptation to heat and drought.

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Posterior integration and thalamo-frontotemporal broadcasting are impaired in disorders of consciousness

Panda, R.; Lopez-Gonzalez, A.; Gilson, M.; Gosseries, O.; Thibaut, A.; Frasso, G.; Cecconi, B.; Escrichs, A.; GIGA group collaborators, ; Deco, G.; Laureys, S.; Zamora-Lopez, G.; Annen, J.

2021-11-10 neuroscience 10.1101/2021.11.08.467694 medRxiv
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The study of the brains static and dynamical activity is opening a valuable source of assistance for the clinical assessment of patients with disorders of consciousness. For example, glucose uptake and dysfunctional spread of naturalistic and synthetic stimuli has proven useful to characterize hampered consciousness. However, understanding of the mechanisms behind loss of consciousness following brain injury is still missing. Here, we study the propagation of endogenous and in-silico exogenous perturbations in patients with disorders of consciousness, based upon directed and causal interactions estimated from resting-state fMRI. We found that patients with disorders of consciousness suffer decreased capacity for neural propagation and responsiveness to events, and that this can be related to glucose metabolism as measured with [18F]FDG-PET. In particular, we show that loss of consciousness is related to the malfunctioning of two neural circuits: the posterior cortical regions failing to convey information, in conjunction with reduced broadcasting of information from subcortical, temporal, parietal and frontal regions. These results seed light on the mechanisms behind disorders of consciousness, triangulating network function with basic measures of brain integrity and behavior. HighlightsO_LIPropagation of neural events and network responses are disrupted in patients with DoC. C_LIO_LILoss of consciousness is related to the malfunctioning of two neural circuits. C_LIO_LIPosterior cortical regions lack to integrate information in altered consciousness. C_LIO_LIBreakdown of information broadcasting of subcortical cortical areas in DoC. C_LIO_LILoss of network responses in DoC patients is related to glucose metabolism. C_LI

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Phylogenomics reveals the evolutionary origin of lichenization in chlorophyte algae

Keller, J.; Puginier, C.; Libourel, C.; Otte, J.; Skaloud, P.; Delaux, P.-M.; Dal Grande, F.

2022-01-07 plant biology 10.1101/2022.01.06.475074 medRxiv
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Mutualistic symbioses have contributed to major transitions in the evolution of life. Here, we investigate the evolutionary history and the molecular innovations at the origin of lichens, which are a symbiosis established between fungi and green algae or cyanobacteria. We de novo sequence the genomes or transcriptomes of 12 lichen algal symbiont (LAS) and closely related non-symbiotic algae (NSA) to improve the genomic coverage of Chlorophyte algae. We then perform ancestral state reconstruction and comparative phylogenomics. We identify at least three independent gains of the ability to engage in the lichen symbiosis, one in Trebouxiophyceae and two in Ulvophyceae, confirming the convergent evolution of the lichen symbioses. A carbohydrate-active enzyme from the glycoside hydrolase 8 (GH8) family was identified as a top candidate for the molecular-mechanism underlying lichen symbiosis in Trebouxiophyceae. This GH8 was acquired in lichenizing Trebouxiophyceae by horizontal gene transfer, concomitantly with the ability to associate with lichens fungal symbionts (LFS) and is able to degrade polysaccharides found in the cell wall of LFS. These findings indicate that a combination of gene family expansion and horizontal gene transfer provided the basis for lichenization to evolve in chlorophyte algae.

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High throughput protein serial crystallography using a grease matrix and a large-area support film

Sugahara, M.; Maki-Yonekura, S.; Inoue, I.; Takaba, K.; Narai, S.; Naitow, H.; Kang, J.; Tono, K.; Numata, K.; Ishikawa, T.; Yabashi, M.; Yonekura, K.

2025-01-31 molecular biology 10.1101/2025.01.31.635837 medRxiv
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Serial femtosecond crystallography (SFX) using ultrashort pulses from X-ray free- electron lasers (XFELs) enables the determination of crystal structures at room temperature while minimizing radiation damage to the samples. This method involves irradiating numerous crystals one by one with XFEL pulses, allowing even the capture snapshots of dynamical structures in biological macromolecules. To achieve this, an efficient sample delivery system is essential for acquiring a large number of diffraction patterns. The most common approach uses a highly viscous grease matrix containing sample crystals, injected into the XFEL path from a narrow nozzle. However, the injection often suffers from clogging issues inside the injector nozzle, resulting in additional challenges such as the need for suitably sized crystals, increased sample consumption and unstable flow rates. Alternatively, a fixed-target approach, which scans a two-dimensional substrate with dispersed samples, can circumvent these issues. However, it must ensure the integrity of biological samples and provide sufficient surface area for efficient data collection. We here present an approach that utilizes a grease matrix and a large-area support film specially designed to address these requirements. This system offers a fast and reliable solution for protein SFX, enabling high-quality structure determination while significantly reducing sample consumption.

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Large-scale population genomics of Malayan pangolins reveals deep diversification and a new species

Li, B.; Lan, T.; Wang, Q.; Shi, M.; Guo, C.; Li, H.; Liu, B.; Liu, S.; Finch, K.; Wang, S.; Yang, S.; Cui, L.; Li, J.; Zhao, X.; Wang, J.; Deng, Z.; Wang, X.; Ma, Y.; Kim, H. J.; Wasser, S. K.; Wang, K.; Lu, H.; Yang, D.; Chen, J.; Guo, H.; Yao, Y.; Xie, H.; Wang, Y.; Fan, J.; Li, W.; Niu, X.; Hou, Y.; Yu, J.; Lu, J.; Li, S.; Qiu, Z.; Zhang, W.; Bai, S.; Han, L.; Wu, Y.; Cai, X.; Huang, Y.; Wang, Z.; Wang, C.; Li, J.; Jiang, Y.; Liu, S.; Wang, J.; Li, L.; Hua, Y.; Liu, H.; Xu, Y.

2023-08-07 genomics 10.1101/2023.08.07.548787 medRxiv
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BackgroundArchipelagos and oceanic islands often present high percentage of endemism due to rapid speciation. The Malayan pangolin is a species distributing at both mainland (southern Yunnan, China) and oceanic islands via Malayan peninsula, which may result in deep differentiation among populations. In-depth investigation of population structure and genetic consequences for such species is of vital importance for their protection and conservation, practically for the critically endangered Malayan pangolin that is suffering from poaching, illegal trade, and habitat loss. ResultsHere we carried out a large-scale population genomic analysis for Malayan pangolins, and revealed three highly distinct genetic populations in this species, two of which are now being reported for the first time. Based on multiple lines of genomic and morphological evidence, we postulate the existence of a new pangolin species (Manis_1). Genetic diversity and recent inbreeding were both at a moderate level for both Malayan pangolins and Manis_1, but mainland Malayan pangolins presented relatively lower genetic diversity, higher inbreeding and fitness cost than island populations. ConclusionsWe found extremely deep and graded differentiation in Malayan pangolins, with two newly discovered genetic populations and a new pangolin species that is closely related to the Philippine pangolin than the typical Malayan pangolin, but a distant relative of the Indian pangolin. Anthropogenic factors did not significantly weaken the basis of genetic sustainability for Malayan pangolins, but mainland Malayan pangolins should be paid more attention for conservation due to higher genetic risks than island populations.

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Natural variability in bee brain size and symmetry revealed by micro-CT imaging and deep learning

Lösel, P. D.; Monchanin, C.; Lebrun, R.; Jayme, A.; Relle, J.; Devaud, J.-M.; Heuveline, V.; Lihoreau, M.

2022-11-30 animal behavior and cognition 10.1101/2022.10.12.511944 medRxiv
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Analysing large numbers of brain samples can reveal minor, but statistically and biologically relevant variations in brain morphology that provide critical insights into animal behaviour, ecology and evolution. So far, however, such analyses have required extensive manual effort, which considerably limits the scope for comparative research. Here we used micro-CT imaging and deep learning to perform automated analyses of 3D image data from 187 honey bee and bumblebee brains. We revealed strong inter-individual variations in total brain size that are consistent across colonies and species, and may underpin behavioural variability central to complex social organisations. In addition, the bumblebee dataset showed a significant level of lateralization in optic and antennal lobes, providing a potential explanation for reported variations in visual and olfactory learning. Our fast, robust and user-friendly approach holds considerable promises for carrying out large-scale quantitative neuroanatomical comparisons across a wider range of animals. Ultimately, this will help address fundamental unresolved questions related to the evolution of animal brains and cognition. Author SummaryBees, despite their small brains, possess a rich behavioural repertoire and show significant variations among individuals. In social bees this variability is key to the division of labour that maintains their complex social organizations, and has been linked to the maturation of specific brain areas as a result of development and foraging experience. This makes bees an ideal model for understanding insect cognitive functions and the neural mechanisms that underlie them. However, due to the scarcity of comparative data, the relationship between brain neuro-architecture and behavioural variance remains unclear. To address this problem, we developed an AI-based approach for automated analysis of brain images and analysed an unprecedentedly large dataset of honey bee and bumblebee brains. Through this process, we were able to identify previously undescribed anatomical features that correlate with known behaviours, supporting recent evidence of lateralized behaviour in foraging and pollination. Our method is open-source, easily accessible online, user-friendly, fast, accurate, and robust to different species, enabling large-scale comparative analyses across the animal kingdom. This includes investigating the impact of external stressors such as environmental pollution and climate change on cognitive development, helping us understand the mechanisms underlying the cognitive abilities of animals and the implications for their survival and adaptation.

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Spontaneous activity changes in large-scale cortical networks in older adults couple to distinct hemodynamic morphology

Sitnikova, T.; Hughes, J. W.; Howard, C. M.; Stephens, K. A.; Woolrich, M. W.; Salat, D. H.

2020-09-03 neuroscience 10.1101/2020.05.05.079749 medRxiv
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Neurovascular coupling is a dynamic core mechanism supporting brain energy demand. Therefore, even spontaneous changes in neural activity are expected to evoke a vascular hemodynamic response (HDR). Here, we developed a novel procedure for estimating transient states in intrinsic activity of neural networks based on source-localized electroencephalogram in combination with HDR estimation based on simultaneous rapid-acquisition functional magnetic resonance imaging. We demonstrate a readily apparent spatiotemporal correspondence between electrophysiological and HDR signals, describing for the first time how features of neurovascular coupling may differ among large-scale brain networks. In the default mode network, the HDR pattern in our older adult participants was associated with a surrogate marker of cerebrovascular deterioration and predicted alterations in temporal structure of fast intrinsic electrophysiological activity linked to memory decline. These results show the potential of our technique for making inferences about neural and vascular processes in higher-level cognitive networks in healthy and at-risk populations.

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Spatial transcriptomics of a parasitic flatworm provides a molecular map of vaccine candidates, drug targets and drug resistance genes

Gramberg, S.; Puckelwaldt, O.; Schmitt, T.; Lu, Z.; Haeberlein, S.

2023-12-11 molecular biology 10.1101/2023.12.11.571084 medRxiv
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The spatial organization of gene expression dictates tissue functions in multicellular parasites. Here, we present the first spatial transcriptome of a parasitic flatworm, the common liver fluke Fasciola hepatica. We identified gene expression profiles and marker genes for eight distinct tissues and validated the latter by in situ hybridization. To demonstrate the power of our spatial atlas, we focused on genes with substantial medical importance, including vaccine candidates (Ly6 proteins), drug targets ({beta}-tubulins, protein kinases) and drug resistance genes (glutathione S-transferases, ABC transporters). Several of these genes exhibited unique expression patterns, indicating tissue-specific biological functions. Notably, the prioritization of tegumental protein kinases identified a PKC{beta}, for which small-molecule targeting caused parasite death. Our comprehensive gene expression map provides unprecedented molecular insights into the organ systems of this complex parasitic organism, serving as a valuable tool for both basic and applied research.