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Communications Biology

Springer Science and Business Media LLC

Preprints posted in the last 30 days, 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.

1
A multi-omics view of wax synthesis in the wild cochineal bug, Dactylopius opuntiae

Dessert, J.; Marcotte, E. M.; Ochman, H.

2026-08-18 molecular biology 10.64898/2026.08.13.744733 medRxiv
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This study establishes a comprehensive genomic, transcriptomic, and proteomic foundation for the wild cochineal bug, Dactylopius opuntiae, a scale insect and agricultural pest of prickly pear cacti notable for its dense white waxy covering. Although fatty acyl reductases (FARs) are central to insect epicuticular wax biosynthesis, the genes underlying wax production in cochineal insects are largely unexplored due to a lack of genomic resources. We report a 359-Mb de novo genome assembly in which we identify 26 FAR genes. Through phylogenetic reconstruction of Coccoidea FAR enzymes we reveal lineage-specific expansions of tandemly arranged D. opuntiae FAR genes, and discuss these enzymes roles in the development of this insects epicuticular waxy coating.

2
Denisovan leg bones from Taiwan reveal large body size

Kaifu, Y.; Chang, C.-H.; Tarusawa, Y.; Sawafuji, R.; Yonemoto, S.; Shimamura, S.; Takai, M.; Kono, R. T.; Sun, C.-H.; Tsai, C.-H.; Yoneda, M.; Tsutaya, T.

2026-08-08 paleontology 10.64898/2026.08.07.743438 medRxiv
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Denisovans are an extinct archaic Homo group whose lineage diverged from the Neanderthal lineage approximately 550,000 years ago and were widely distributed across eastern Asia until [~]45,000 years ago1-7. Their morphological features are known directly from the existing cranio- dental and phalangeal remains1,2,8-12. However, the body size and postcranial morphology of the Denisovans remain largely unknown. We here report that hominin femoral and tibial fossils recovered from the Penghu Channel, Taiwan, are Denisovans in their proteomic profiles. Morphologically, these specimens are among the largest leg bones known in Pleistocene Homo. They exhibit generally archaic features, but also show some modern human-like morphology, including a strong femoral pilaster. Our findings demonstrate that the Denisovan population at the northern circle had larger body size than earlier Homo erectus as well as Late Pleistocene Homo sapiens in eastern Asia. This challenges the generally held expectation that Pleistocene Homo followed Bergmanns rule that anticipates latitudinal decline of body size, and suggests that the large Denisovan brain resulted from their large body size at least partly. The strong pilaster developed in the Penghu femur suggests some behavioral similarities between the Denisovans and the Upper Palaeolithic modern humans and/or gene flow from the latter to the former.

3
Genuinely Blind Identification of Sleep Spindles through Trispectral Modulation Analysis

Kovach, C. K.; Gliske, S. V.; West, L. C.; Liu, J.; Summers, M. O.; Kumar, S.; Gonzales, J. A.; Cox, O.; Tsang, E. W.; Thompson, J. A.; Kushida, C. A.; Abosch, A.

2026-08-27 neuroscience 10.64898/2026.08.24.746784 medRxiv
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Sleep spindles, transient 11-16 Hz oscillatory bursts, are a defining electrographic feature of non-rem (NREM) sleep and a key biomarker of sleep physiology. A need for efficient and reliable identification of spindles motivates a large literature on automated detection algorithms. In this literature, annotation by trained sleep specialists remains the gold standard against which automated methods are trained, tuned and evaluated. However, inter-scorer agreement among experts is modest, which leaves a significant role for subjective judgment in the definition of a spindle. Finding objective, scorer-independent, criteria for identifying spindles remains an unresolved challenge. We report here a robust, highly specific, and previously unrecognized signature of spindle activity in the fourth-order spectrum (trispectrum), from which we identify the presence of spindles, characterize their waveforms, and obtain an optimal detection filter through a decomposition of the trispectrum (HOSD). Although it is a strictly blind, data-driven method, HOSD-based spindle identification and detection agrees well with expert annotation (median AUROC ~0.9), yet identifies many more events at the native threshold than both human scorers and comparison detectors. Many of these additional detections are confirmed as meeting AASM spindle criteria by four blinded specialists, demonstrating that spindle-like oscillatory bursting is prevalent below conventional human and automated detection thresholds. We observe that N2 sleep is distinguished principally by high-amplitude bursts, while low-amplitude bursting persists throughout NREM sleep, being globally suppressed only in REM sleep. We also describe robust identification of recording-specific spindle waveform properties such as frequency deceleration.

4
The Movie After-Effect: widespread adaptation of human cortex following naturalistic sensory experience

Simony, E.; Yahav, N.; Malach, R.

2026-08-22 neuroscience 10.64898/2026.08.13.744606 medRxiv
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Neural systems adapt to prolonged sensory input through mechanisms such as gain control or homeostatic plasticity to maintain stable operating ranges. However, this phenomenon has so far been documented under extreme, non-ecological stimuli targeting specific sensory systems. Here, we reveal a widespread adaptation process across diverse human cortical regions following naturalistic movie watching conditions. The effect was evident in 218 out of 251 cortical regions (87%) that exhibit significant stimulus-driven activations. Analyzing the HCP fMRI data set in which 170 participants watched 14 movie clips, followed by rest periods - we found robust evidence for a movie-induced adaptation process, revealed in the post-movies rest periods. Within a region, voxels highly activated at the end of movies subsequently reduced their activity below baseline during rest, with the magnitude of this drop proportional to initial activation levels, manifested as a consistent voxel-population inversion effect. Conversely, persistently movie-inactivated voxels exhibited increased activation above baseline. Importantly, this Movie After-Effect (MvAE) enabled successful decoding of the specific rest periods following individual movie clips. Our findings suggest that under naturalistic conditions, cortical neurons dynamically change their gain to achieve homeostatic balance in a process akin to batch instance normalization in artificial neural networks. Whether this ubiquitous MvAE has additional cognitive and memory-related implications remains to be explored.

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Genome-Wide Selection Signatures in Nili-Ravi Buffalo (Bubalus bubalis) Reveal a T-Cell Costimulatory and Cytokine-Signaling Gene Network Distinct from Classical Bovine Tuberculosis Candidate Genes

Ahmad, A.; bakar, A.; Laeeque, S. M.; Khan, W. A.; Kaul, H.; Manan, A.; mustafa, h.

2026-08-11 genomics 10.64898/2026.08.10.743898 medRxiv
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Genomic signatures of selection can reveal loci underlying adaptation and disease resistance in livestock populations, but such analyses in water buffalo (Bubalus bubalis) have historically been constrained by the absence of a chromosome-level, species-native reference genome for SNP array data. We re-analyzed genotype data from 85 Nili-Ravi buffalo (Axiom Buffalo Genotyping 90K array, originally positioned using bovine (Bos taurus, UMD3.1) proxy coordinates, by performing a full coordinate liftover to the buffalo-native UOA_WB_1 assembly using an independently published SNP remapping resource. Following quality control (51,209 markers retained), haplotype phasing, and genome-wide integrated haplotype score (iHS) and Wrights Fst (case/control) selection scans, we evaluated 14 classical bovine-tuberculosis (bTB) candidate genes and identified six additional genes with putative immune function through an unbiased genome-wide screen. None of the 14 classical candidates (including SLC11A1, the Toll-like receptors, and IFNG) reached genome-wide significance in either scan. In contrast, six novel loci TNFSF18, IL2RB, TNFRSF19, IRF2, IL15, and CD28 showed significant iHS or Fst signals, four of which (TNFSF18, IL2RB, IL15, CD28) converge functionally on T-cell costimulation and cytokine receptor signaling (KEGG pathways map04660 and map04060, Bos taurus proxy annotation). Using extended haplotype homozygosity (EHH) decay, haplotype furcation structure, and per-marker haplotype counts as three independent lines of corroborating evidence, we classified these six genes into confidence tiers: TNFSF18 and IL2RB showed the strongest, most balanced support, while CD28 and IL15 signals were driven by very few haplotypes (3 and 5 of 30, respectively) and should be interpreted cautiously pending replication. These findings suggest that adaptive, cell-mediated immune signaling rather than the innate/macrophage-centred mechanisms emphasized by existing bTB candidate gene panels may be a more productive avenue for future selection studies in Nili-Ravi buffalo, while underscoring the value of buffalo-native coordinate systems for accurate genomic inference in this species.

6
Distributed Genetic Effects on Human Brain Structure Emerge Across Multiple Spatial Scales

Gleave, E. J.; Garcia-Marin, L. M.; Ceja, Z.; Renteria, M. E.; Chattopadhyay, T.; Gaser, C.; Rajagopalan, P.; Thompson, P. M.

2026-08-21 neuroscience 10.64898/2026.08.17.745237 medRxiv
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Genome-wide association studies (GWAS) have identified hundreds of common genetic variants associated with regional brain volumes, enabling the construction of polygenic scores (PGS) that summarize genetic predisposition for variation in specific neuroanatomical traits. To investigate how these genetic influences are exerted spatially throughout the brain, we computed PGS for ten brain volume phenotypes, including nine major subcortical structures and intracranial volume. Each locus was weighted by its estimated GWAS effect size on regional volume in the original GWAS. In an independent, non-overlapping sample of 2,830 UK Biobank participants, we performed whole-brain voxel-based morphometry (VBM) analyses of 3D volumetric brain MRI to reveal voxel-wise associations between each PGS and modulated gray matter volume (GMV). To probe genetic effects across multiple spatial scales, analyses were repeated across Gaussian smoothing kernels ranging from 2-mm to 12-mm full-width at half-maximum (FWHM). Several PGS demonstrated highly significant associations with GMV, including localized effects in the hippocampus, amygdala, thalamus, and basal ganglia, whereas the brainstem PGS showed more widespread associations throughout the brain. For most of the PGS, the fraction of voxels surviving the false discovery rate (FDR) correction increased with increasing FWHM. Peak voxel-wise significance was often strongest at intermediate smoothing levels. Hippocampal significance maps showed progressively larger regions of significant signal at higher smoothing levels, and subsampling showed that detectable signal remained present even with substantial reductions in sample size. These findings suggest that genetic influences on brain morphology are expressed across multiple spatial scales, with consequences that may help to guide the design of deep learning methods to discover genomic loci associated with brain structure and brain diseases.

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Maturation of Sleep EEG Complexity in Preterm Newborns: Insights from Lempel-Ziv and Joint Lempel-Ziv Analyses

Devera, A.; Catanzariti, M.; Legnani, M.; Mezquita, C.; Gonzalez, J.; Urban, L.; Hackembruch, H.; Blasina, F.; Torterolo, P.; Mateos, D. M.

2026-08-19 neuroscience 10.64898/2026.08.10.742446 medRxiv
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The development of the sleep-wake cycle reflects the progressive structural and functional maturation of the brain. However, the organization of neural dynamics during prematurity remains incompletely understood. In this study, we analyzed the EEG from 54 polysomnographic recordings obtained from 39 preterm infants, grouped according to postmenstrual age (PMA) into three categories: 30-31, 32-33 and 34-35 weeks. Lempel-Ziv Complexity (LZC) and Joint Lempel-Ziv Complexity (JLZC) of the electroencephalogram (EEG) were analyzed during active sleep (AS), quiet sleep (QS), and indeterminate sleep (IS). LZC computed from the raw, unfiltered recordings were significantly higher during QS than during AS and increased with PMA during AS. To further refine the analysis, LZC was also evaluated separately in the low-frequency (1-15.5 Hz) and high-frequency (16-30 Hz) EEG bands. In the low-frequency band, LZC was consistently higher during QS than during AS, an effect that was most pronounced in more immature groups. Furthermore, LZC increased with maturation particularly during AS. Sleep-state comparisons of LZC in the high-frequency EEG band also revealed higher values during QS than during AS across all PMA groups. Moreover, in contrast to the low-frequency band, LZC progressively decreased with advancing PMA both in AS and QS, suggesting that the neural mechanisms underlying low- and high-frequency EEG activity follow distinct maturational trajectories. Interestingly, larger LZC in the temporal cortex and interhemispheric differences were detected in the 32-33 PMA group. On the other hand, JLZC analysis revealed greater joint spatiotemporal dynamics across EEG channels during QS than during AS, with consistently higher JLZC values in temporal regions and lower in occipital regions. Together, these findings show that these complexity metrics distinguishes sleep states and captures maturational changes in EEG activity in preterm infants. These results provide novel insights into early brain development and suggest potential quantitative biomarkers of neonatal brain maturation.

8
Mice sense Moon and Sun

Barde, W.; Grayver, A.; Runker, A. E.; Izumo, M.; Acosta Rodriguez, V. A.; Takahashi, J. S.; Kempermann, G.

2026-08-20 neuroscience 10.64898/2026.08.17.745150 medRxiv
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Life on earth has always been exposed to the fluctuating Earth's magnetic field, but a magnetic sense affecting behavior has been debated for mammals. We here report that mice, kept under constant laboratory conditions, showed fluctuations in spontaneous behavioral activity with a periodicity of ~14 and ~28 days. This was confirmed in nine cohorts from four facilities on two continents, covering 3 to 41 months. Such oscillations were also maintained in brain Bmal1 knockout mice lacking circadian rhythms, suggesting independence of the circadian clock. The behavioral activity peaked around full and new Moon, and showed a strong alignment with the periodic geomagnetic fluctuations originating in the Earth's iono- and magnetosphere that are modulated by solar rotation and the orbital motion of the Moon. In the ultradian range, this alignment persisted in CRY1/2 knockout mice, suggesting that solar-lunar-driven geomagnetic fluctuations can modulate behavior rhythms independently of CRY1/2.

9
The BEAC, an epigenetic clock for birds

Hukkanen, M.; Jarman, S.; Budd, A.; Nitta Fernandes, F. A.; Ambrosini, R.; Anderson, C.; Bardon, G.; Berry, O.; Bitton, P.-P.; Bugnyar, T.; Caprioli, M.; Carlile, N.; Cecere, J. G.; Cossin-Sevrin, N.; Costanzo, A.; Corregidor-Castro, A.; Davis, L. R.; van Dijk, E.; Elsner, M.; Elliott, K. H.; Ferrer Obiol, J.; Frigerio, D.; Gardoni, N.; Helsen, P.; Hofer, M.; Kleindorfer, S.; Lammers, J.; Leandri-Breton, D.-J.; Massen, J.; McIvor, G. E.; Meyer, B. S.; Morel, A.; Morganti, M.; Paciello, E.; Paris, J.; Pilastro, A.; Pihlflyckt, L.; Plaza, P.; Polanowski, A. M.; Puhakka, A.; Roman, L.; Romano, A.

2026-08-19 molecular biology 10.64898/2026.08.14.744821 medRxiv
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Epigenetic clocks are powerful tools for estimating both chronological and biological age, enabling the integration of age information into population monitoring, demographic modelling, and research on the ecophysiology and evolution of ageing. Most epigenetic clocks so far have been developed for mammals: here, we present the Bird Epigenetic Ageing Clock (BEAC) for estimating chronological age in avian species. BEAC was established based on genome-wide enzymatic methylation sequencing data of known-age king penguins (Aptenodytes patagonicus), and validated in nine other bird species. The BEAC collects age-informative signals into a bisulfite amplicon sequencing panel of 24 primer pairs, providing a highly accurate and cost-effective alternative to sequencing-intensive approaches. It achieved strong predictive performance in independent king penguin training (R{superscript 2}=0.88; MAE=1.7 years, n=78) and testing data (R{superscript 2}=0.79; MAE=2.3 years, n=41), with negligible batch effects, high longitudinal consistency, and resilience to reduced sample size or missing loci. Importantly, cross-species validation across 180 samples showed that BEAC reliably captures age-associated methylation signals in nine additional bird species across seven clades, demonstrating that a single set of loci can be predictive of ageing across multiple different bird species. BEAC offers a flexible, empirically validated tool and a transferable framework for developing epigenetic clocks in avian species, providing a highly valuable resource for eco-evolutionary studies of ageing in wild species.

10
Temporal persistence and structural organization of neuronal avalanche dynamics

Cafaro, G.; Angiolelli, M.; Demuru, M.; Casagrande, G.; Quarantelli, M.; Granata, C.; Depannemaecker, D.; Duma, G. M.; Scarpetta, S.; Sorrentino, P.

2026-08-19 neuroscience 10.64898/2026.08.10.743923 medRxiv
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Brain activity can be understood as a sequence of neuronal avalanches, i.e., transient episodes of coordinated activation that emerge across scales, from individual neurons and local networks to whole-brain dynamics. Avalanches are typically characterized by features such as size, duration, number of active components, and the silent time separating consecutive events. Although these features have been extensively characterized through their marginal distributions, their temporal organization and dependence on the underlying brain architecture remain poorly understood, leaving us without a framework for embedding fast neuronal avalanches within slower brain dynamics. Here, we analyzed eyes-closed resting-state magnetoencephalography recordings and the corresponding structural connectomes from 30 healthy participants to investigate the dynamics of avalanche sizes. We found that large avalanches preferentially followed short silent times, whereas small avalanches were more likely to occur after long silent periods. Based on the empirical joint distributions of avalanche size and silent time, we could define four types of events occurring above chance levels (avalanche large or small, preceding pause long or short). Mixed categories--combining a small value of one feature with a large value of the other--occurred more frequently than expected, while same-category events happened less often than chance. Furthermore, consecutive events tended to remain in the same category, a phenomenon referred to as persistence. We next investigated whether a brain regions connectivity profile shapes its propensity to participate in avalanches of different sizes. More strongly connected regions participated most often in small avalanches, whereas weakly connected regions were preferentially recruited during large avalanches. This pattern may reflect the greater sensitivity of highly connected hubs to fluctuations propagating through the network, resulting in frequent but spatially contained events. By contrast, the recruitment of more peripheral regions may require broader and stronger collective activity, occurring only during rarer, large-scale avalanches. In contrast, regional participation showed no clear association with the silent time preceding an avalanche. Together, these findings show that neuronal avalanches are neither temporally independent nor anatomically unconstrained: their sequence retains a memory of preceding events, while structural topology shapes which regions are recruited as avalanches grow. By connecting fast avalanche dynamics with slower temporal organization and the structural connectome, our results provide a multiscale framework for understanding how transient events are embedded within ongoing brain activity.

11
Evolution profile of 13415 SNVs in 33 language/cognition genes measured by five types of distance calculation

Zhang, Z.; Xu, Y.

2026-08-23 molecular biology 10.64898/2026.08.19.745865 medRxiv
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This study aims to quantify the genetic similarity of different species (from fish to humans) to the human reference genome (pp6, Homo sapiens.GRCh38) based on the allele presence/absence patterns of 33 language/cognition related gene SNV loci, identify key breakpoints during evolution, and evaluate the enrichment of language and cognition genes at these breakpoints. We designed a similarity calculation method relying on binary features (four columns for A/T/C/G), adopted five difference/distance measures (Sorensen, Rogers, Nei, Reynolds, and Hellinger), and converted them into similarity values (1/(1+distance)). For each method, samples were independently ranked, the first derivative of similarity was computed, and the top 12 peaks were selected as candidate breakpoints. Results show that the similarity curves from the five methods are highly consistent (correlation coefficients >0.9), with major peaks concentrated at positions 355, 363, 381, 382, 390, 400, etc., where the corresponding samples are predominantly ancient hominins and primates. Furthermore, we defined 13 peak groups (starting positions 355-401). For each peak within a group, pairwise SNV differences between the peak apex sample and its immediate left neighbor were compared, and the intersection F_INTERSECTION (shared differential loci) was obtained. For each F_INTERSECTION, we calculated the proportions of language genes and cognition genes. In addition, we computed the differential sets between adjacent groups' F_INTERSECTION to trace the gradual emergence of new loci. In F_INTERSECTION, language genes accounted for an average of 59.5%, and cognition genes for an average of 62.9%. The proportion of language genes reached a peak at position 383 (61.2%), while cognition genes peaked at position 386 (64.9%). High frequency peak samples include c25, c27, and ja2, suggesting that language cognition genes may have undergone independent intensification during Eurasian evolution. Differential analysis between adjacent F_INTERSECTION revealed a stepwise acquisition of new loci from position 355 to 401, with three bursts of newly added loci along the entire evolutionary axis. This study provides a quantitative framework based on similarity curves, offers a novel molecular perspective for understanding the evolution of language and cognitive abilities, and highlights the potential importance of East Asian archaic hominins in the evolution of language cognition genes.

12
Evolution of the motor cortex microstructure and its lateralization: a comparative study of chimpanzees and humans

Chauvel, M.; Kirilina, E.; Lipp, I.; Buettner, F.; Jaeger, C.; Pine, K.; Edwards, L.; Ebel, S.; Kopp, K.; Helbling, S.; McColgan, P.; Rose, D.; Graessle, T.; McElreath, R.; Chaimow, D.; Crockford, C.; Wittig, R.; Weiskopf, N.

2026-08-22 neuroscience 10.64898/2026.08.20.745984 medRxiv
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Human hand coordination exceeds that of other species, including great apes, and is marked by pronounced right-hand dominance. This specialization parallels an expansion of its cortical representation, forming the hand-knob in the motor cortex. In humans, this region shows high myelination on quantitative MRI (qMRI), but whether this feature is shared with great apes remains unclear. It is also unknown whether increased right-hand dominance in humans is mirrored by greater hemispheric asymmetry in cortical microstructure. Using high-resolution qMRI, we compared motor cortex subdivisions controlling the leg, hand, and face in humans and chimpanzees. We found consistently higher myelin and iron content in the hand-knob in both species, suggesting an evolutionarily conserved role. However, only humans showed enhanced rightward lateralization. These results highlight both conserved and species-specific features of the motor cortex, offering insights into the evolution of manual dexterity and handedness.

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Neural Signatures of Conscious Experience During Sleep: A Serial Awakening Study Using High-Density EEG

Selte, A.; Haworth, S. E.; Vannasse, T. J.; Alauddin, T.; Gjini, K.; Philibert-Rosas, S.; Brace, C.; Sevak, B.; Riedner, B.; Kalkach-Aparicio, M.; Tononi, G.; Boly, M.; Struck, A. F.

2026-08-20 neuroscience 10.64898/2026.08.16.745040 medRxiv
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Identifying neural signatures of consciousness remains a central challenge in neuroscience. Sleep offers a tractable model for comparing brain activity in the presence or absence of subjective experience while minimizing behavioral responsiveness confounds. Using overnight 256 electrode high-density EEG in 140 participants and a serial-awakening paradigm, we analyzed 699 non-rapid eye movement (NREM) sleep stage 2 and 3 awakenings (351 dreaming experience, 348 no experience). Features from the 60s preceding awakening included regional spectral power, lagged-coherence connectivity, graph-theoretic metrics and gamma-to-alpha power ratios. Dreaming experiences were associated with shifts in posterior spectral balance, particularly reduced alpha and delta power and increased gamma-related measures, together with altered large scale network organization. In participant-level cross-validated machine-learning analyses, all classifiers performed above chance, with the best ensemble model reaching an ROC-AUC of 0.80 and average precision of 0.80. These findings identify reproducible posterior electrophysiological and network-level signatures of conscious states during NREM sleep.

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Cryo-EM structures of apo human Factor XIa reveal catalytic-domain flexibility and exposure of the Factor IX-binding site

Siutkina, A. I.; Neuhaus, A.; Taterra, M.; Bermudez, M.; Gatsogiannis, C.; Kalinin, D. V.

2026-08-26 biochemistry 10.64898/2026.08.25.744604 medRxiv
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Factor XI (FXI) is a key coagulation protease of the intrinsic pathway of blood coagulation and an emerging antithrombotic target. However, the structural transition from zymogen to active Factor XIa (FXIa) has remained poorly understood. Using cryo-EM, we demonstrate that FXI activation results in a global reorganization of the homodimer, extending beyond the activation loop to include a significant reorientation of the catalytic domain (CD) relative to the apple-domain (AD) platform. The CD displays pronounced conformational heterogeneity; we identify three distinct conformers, suggesting that FXIa exists as a dynamic ensemble rather than a single rigid state. MD analysis indicates that activation disrupts the inter-CD allosteric communication present in the zymogen, thereby facilitating this flexibility. CD plasticity allows for the dynamic exposure of the A3 exosite, facilitating the binding of Factor IX. Comparison with plasma kallikrein (PKa) suggests that such structural flexibility may be a shared feature of apple-domain-containing contact-system proteases. Our results reveal that FXIa functions as a dynamic ensemble, providing a structural framework for understanding substrate recognition and identifying novel, non-catalytic sites for the development of specific FXIa inhibitors.

15
Network Topology reveals disrupted AMPA receptor stabilization leads to an impaired LTD in epileptic synapses

Meghna, P.; Kateriya, S.; Punnakkal, P.

2026-08-19 neuroscience 10.64898/2026.08.10.743452 medRxiv
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Cognitive comorbidities in epilepsy patients may be the result of synaptic alterations and impaired synaptic signalling. Electrophysiological evidence demonstrates that epileptic synapses undergo a GluN2B-dependent metaplastic shift, where a low-frequency stimulation protocol unexpectedly induced long-term potentiation (LTP) rather than long-term depression (LTD). However, the downstream postsynaptic structural cascade responsible for this functional impairment remains unresolved. To elucidate the molecular architecture driving this shift, this study employed an in silico protein-protein interaction network approach using Cystoscape. A baseline intersection network of LTD and epilepsy-associated genes were constructed, anchored with GRIN2B, and topologically ranked to identify hub proteins. This analysis identified a core module biased toward synaptic potentiation, dominated by the kinase CAMK2A, AMPA receptor subunits, and auxiliary Transmembrane AMPA Receptor Regulatory Proteins (TARPs) and CNIH2. These provided a structural basis for the prolonged receptor retention and delayed deactivation kinetics characteristic of epileptic synapses. Mapping the LTD-execution machinery against this interactome revealed that calcineurin was topologically segregated and lacks direct connectivity from the central AMPA receptor complex. Further studies would be required to test and confirm the involvement of these proteins. To experimentally validate these in silico findings, human transcriptomic data from cortical and hippocampal tissues of drug-resistant epilepsy patients was also analyzed which confirmed the significant upregulation of CNIH2 and CACNG2 in both tissue types. The cross-validation with patient transcriptomic data, demonstrated that the epileptic synapse undergoes a pathological shift. Hence, the upregulation of the auxiliary proteins functionally overpowers the established LTD machinery and prevents LTD consolidation.

16
Symbiont effectors modulate plant signalling to increase host stress resilience

Rehneke, L.; Osborne, R.; Lehmann, S.; Zhang, Y.; Roberts, J.; Altmann, S.; Köpff, E.; Eichmann, R.; Falter-Braun, P.; Shan, W.; Schäfer, P.

2026-08-19 plant biology 10.64898/2026.08.17.744369 medRxiv
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Plant colonizing mutualistic symbionts confer beneficial effects to their hosts, which often includes increased growth, and biotic and abiotic stress resilience. How these benefits are activated on a molecular level is mostly unknown. Here, we describe effector candidates of the fungal symbiont Serendipita indica (Si), which modulate plant stress signalling pathways. By analyzing the Si effector interactome, we reveal frequent targeting of stress related host proteins, which are linked to the identified effector signalling functions. Moreover, functional data indicate that Si effectors modulate abiotic stress response of Arabidopsis, as well as resistance to pathogen infection. Analysis of symbiont effectors might not only uncover previously unreported molecular mechanisms that increase plant fitness but might also be used to identify potential genetic traits for crop improvement under changing climates.

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Cholesterol transport cycle of human ABCA2

Tan, S. M.; Schnelle, K.; Voskoboynikova, N.; Nowacki, M.; Esch, B. M.; Froehlich, F.; Holtmannspoetter, M.; Piehler, J.; Shvarev, D.; Parey, K.; Januliene, D.; Moeller, A.

2026-08-25 molecular biology 10.64898/2026.08.25.746927 medRxiv
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Cholesterol is a key component of cellular membranes and is critical for brain function, particularly axon myelination. Among the 48 human ATP-binding cassette (ABC) transporters, ABCA2 exhibits the highest expression in the brain and is involved in cholesterol metabolism, primarily in oligodendrocytes. Notably, ABCA2 has been associated with myelin sheath integrity and maintenance, as well as Alzheimer's disease. Here, we report cryo-EM structures of human ABCA2 that reveal critical endogenous lipid-binding sites unique to ABCA2. Our five distinct conformations include a previously uncharacterized intermediate between the closed and apo states of ABCA subfamily transporters. Most importantly, we elucidated the cholesterol transport mechanism of ABCA2, which involves novel interdependent rotations of the exocytoplasmic domains (ECDs) and regulatory domains (RDs). Our structural findings provide a new perspective on ABCA transporter function and highlight the role of ABCA2 in facilitating efficient cholesterol recycling and transport in the brain.

18
Host ecological context influences taxonomic diversity and functional conservation of gut microbiome across anthropogenic habitats in macaques

Kulkarni, V.; Karanth, P.; Radhakrishna, S.

2026-08-25 ecology 10.64898/2026.08.24.746638 medRxiv
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Gut microbiome responses to anthropogenic disturbance vary across wildlife species, even within similarly disturbed landscapes. What drives this variation is unclear: whether it reflects anthropogenic exposure itself or broader ecological differences among hosts. We tested this using three macaque species with contrasting ecology, Bonnet, Rhesus, and Lion-tailed macaques, sampled across 12 sites in southern India spanning contrasting anthropogenic exposure, using 16S rRNA gene sequencing (n = 127) and shotgun metagenomics on a subset of samples. The two synurbanized species exhibited a similar magnitude of microbiome restructuring but differed in the taxa underlying these changes; no differentially abundant amplicon sequence variants were shared across all three species, indicating that shared anthropogenic exposure did not produce uniform microbial responses across hosts. The specialist Lion-tailed macaque showed a more extensive response, characterized by reduced diversity and phylogenetically structured compositional change. The Bonnet macaque showed greater microbial similarity with the Rhesus macaque than with the Lion-tailed macaque during sympatric co-occurrence. Despite taxonomic divergence, functional pathway architecture was broadly conserved across species and habitats, with selective shifts in pathways including vitamin B6 biosynthesis and fermentation. Together, these findings show that microbiome responses to anthropogenic environments are jointly shaped by ecological context and host ecology, with host differences in diet, habitat use, and ecological history influencing the magnitude and nature of microbial restructuring. These findings show that taxonomic diversity and functional potential respond as partially decoupled axes under anthropogenic pressure, with implications for assessing microbiome resilience across ecologically heterogeneous wildlife.

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A Stickiness Response System in Rats

Tan, S.; Rencken, S.; Childs, T.; Stone, J.; Tiesman, A.; Anderson, P.; Brecht, M.; Clemens, A. M.

2026-08-12 neuroscience 10.64898/2026.08.06.742745 medRxiv
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The perception of stickiness is known to everyone who interacts with the world. While eating, walking, and navigating diverse environments including crowded subways, forests, fields and lunchrooms, stickiness is a common and old sensation. Responses to sticky stimuli have been measured in animal and human brains; however, precise behavioral responses and the underlying neural mechanisms are not well understood. We applied sticky stimuli to three-week-old rat pups and found the effects vary greatly across the animals body: Sticky stimuli are quickly removed from forepaws and nose, but often evoke only little reaction from hindpaws. When we applied sticky (marshmallow, mochi) and non-sticky stimuli (water, oil) to forepaws, we observed stimulus unspecific behaviors (licking and grooming) with variable response onsets as well as three fast-onset sticky-specific behaviors. Sticky-specific behaviors were exclusively triggered by sticky stimuli and included paw shaking and paw swiping (behaviors presumably aiming at stickiness removal) and paw tapping. In tapping, animals gently tap their forepaws onto each other or on the ground; we wondered if the resulting paw-substrate detachments serve stickiness sensing. Blocking of forepaw skin sensation reduced sticky-specific responses to sticky stimuli compared to control conditions (Ringers injections). To assess central representations of stickiness, we obtained in vivo whole-cell recordings of neurons in forepaw-somatosensory-cortex while presenting sticky and non-sticky stimuli to anesthetized rat pups. While responses were heterogeneous across the population, we observed individual neurons that had significantly different responses to stimulus detachment for sticky and non-sticky stimuli. In summary, we describe a fast-onset, body-part-specific stickiness response system in rats, which is strongly driven by forepaw skin afferents. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/742745v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@2ad341org.highwire.dtl.DTLVardef@1936c2forg.highwire.dtl.DTLVardef@1a39d23org.highwire.dtl.DTLVardef@a196e9_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Habitat and feeding ecology of a Denisovan from Late Pleistocene Taiwan

Yoneda, M.; Chang, C.-H.; Itahashi, Y.; Tsutaya, T.; Sun, C.-H.; Tsai, C.-H.; Kaifu, Y.

2026-08-08 paleontology 10.64898/2026.08.07.743455 medRxiv
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Denisovans, originally identified from ancient genome from Denisova Cave in Altai, were a sister group to the Neanderthals and were once widely distributed across diverse terrains in the north and south of eastern Asia1-5. Genomic studies suggest that there were multiple events of interbreeding between modern humans (Homo sapiens) and Denisovans somewhere in Asia6. However, little is known about Denisovan living environments, diet, ecological niche, the timing of their disappearance, and the possible coexistence with modern humans in different regions. Here we report the radiocarbon age and stable isotopic signature of Penghu 3, a large Denisovan tibia from Penghu Channel, Taiwan7. The results showed that Penghu 3 dates to approximately 45,000 years ago, the time when modern humans were already widespread in southern parts of Asia. This Denisovan individual inhabited a C4-dominated ecosystem, open environments such as savannahs and floodplains, or a mixture of both, and consumed a high proportion of animal protein similar to some European Neanderthals8-10, with no clear evidence for the use of aquatic resources. These findings have implications for the behavioral flexibility, large body size7, and eventual disappearance of the Denisovans.