Communications Biology
○ Springer Science and Business Media LLC
Preprints posted in the last 90 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.
Kizilaslan, Z.; Townsend Graybeal, J.; Huffman, C.; Mejia, A.; Penagaricano, F.; Kizilaslan, M.; Ahsan, N.; Khatib, H.
Show abstract
Evolutionary success in mammals requires coordinated regulation of cognitive functions and reproductive capacity. Such coordination must involve shared genes and molecular pathways between the brain and germ cells, yet direct evidence linking cognition to reproduction across species remains limited. Here, proteomic and transcriptomic analyses were performed experimentally in Ovis aries and Rattus norvegicus, while transcriptomic datasets from Mus musculus, Macaca mulatta, and Homo sapiens were analyzed in silico. We identified 8,464 protein-coding genes shared between the brain and sperm/testis and conserved across five species. In rats, 8,444 of these genes were also shared between the brain and the ovary. Functional annotation classified 3,890 genes as associated with both neurological and reproductive functions, and 1,752 as uncharacterized in these contexts, highlighting candidates for future studies on reproductive and neurological disorders. These findings reveal a deeply conserved genetic network linking neurological and reproductive systems, underscoring the evolutionary interplay that supports mammalian fitness.
Dessert, J.; Marcotte, E. M.; Ochman, H.
Show abstract
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.
Ziaikin, E.; Niv, M. Y.
Show abstract
Bitterness is a key taste modality mediated in vertebrates by TAS2R G-protein-coupled receptors, which also function in diverse extraoral tissues. Recent cryo-EM structures have revealed a non-classical intracellular pocket in TAS2R14, raising the question of whether ligand pocket choice can be predicted computationally and what sequence features control it. Here we evaluate the Boltz-2 co-folding framework on all currently available agonist-TAS2R cryo-EM complexes and show that it correctly identifies the experimentally observed binding pocket for 12 of 15 pairs, including intracellular binding that docking into predicted receptor models fails to reproduce. Focusing on aristolochic acid, which binds intracellularly to TAS2R14 and extracellularly to TAS2R43, we use a series of in silico morphing experiments to pinpoint transmembrane helices 3 and 7, and specific residues within them, as key determinants of pocket preference. Extending the analysis to [~]1,500 agonist-receptor associations from BitterDB, we find that while most receptors are predicted to bind agonists predominantly in the extracellular pocket, several TAS2Rs may have both extracellularly and intracellularly binding ligands. Finally, by fine-tuning the Boltz-2 affinity module on [~]7,000 positive and negative experimental data points, we obtain a TAS2R-specific classifier that improves AUROC from 0.54 to 0.82 and average precision from 0.24 to 0.58 on a validation set.
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.
Show abstract
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.
Pathak, A.; Quek, S.; Sharma, R.; Shiau, J.; Thomas, M.; Hughes, G.; Murdock, C.
Show abstract
Temperature is a key determinant of malaria transmission, influencing both parasite development and mosquito physiology, yet the underlying mechanisms remain poorly understood. Here, we examined how temperature and time modulate gene expression in Anopheles stephensi infected with Plasmodium falciparum. Using RNA-sequencing over 1-19 days post-blood meal and three temperature regimes (20, 24, and 28{degrees}C with diurnal fluctuations of 9{degrees}C), we characterize transcriptome responses to infection with P. falciparum at the site of infection in the midgut, and systemically, in the carcasses. Oocyst prevalence and density declined over the thermal gradient, albeit with distinct, non-linear temporal dynamics in parasite development rates. Although infection contributed minimally to global variation in gene expression relative to temperature and time, infection-associated genes in the midgut showed coordinated transcriptional responses enriched in canonical Plasmodium associated extracellular, proteolytic, immune, and metabolic functions; notably, decline in oocyst infections in the midguts over the thermal gradient was reflected in reduced expression of immune genes known to regulate P. falciparum. Network analysis demonstrated that these genes participate in a significantly interconnected protein-protein interaction network, within which a small number of high betweenness centrality proteins act as bottlenecks linking immune, metabolic, reproductive and behavioral processes. Our results suggest responses to infection may be mediated through coordinated physiological networks rather than large-scale transcriptional changes. Our findings also indicate that differences in thermal conditions may be an important factor when comparing mechanisms of vector- parasite interactions between Plasmodium species. Together, our results highlight the importance of integrating thermal context into mechanistic studies of vector-parasite interactions.
Kuwamizu, R.; Yamamoto, N.; Otani, K.; Moriguchi, Y.
Show abstract
The Stroop effect is a canonical measure of executive control, yet its neural architecture has been defined largely in literate children and adults, where left frontal mechanisms have long been implicated in resolving verbal conflict. How the developing brain supports Stroop-like interference control before literacy and stable verbal responding are established remains unknown. Here we show that successful interference control in early childhood is associated with the selective engagement of right lateral prefrontal regions. We used multichannel functional near-infrared spectroscopy to measure prefrontal hemodynamics in 94 children aged 35-79 months during a color-pointing Stroop-like task, in which children pointed to colors in response to spoken color names. Stroop-like conflict elicited broad activation across bilateral lateral prefrontal regions, a conflict response already present from around 3 years of age and did not show a detectable age-related increase. By contrast, individual differences in accuracy under conflict were selectively associated with greater activation in the right dorsolateral and right rostrolateral prefrontal cortices, independent of age. These findings suggest that right lateral prefrontal regions play an important role in successful interference control in early childhood, indicating that preschool Stroop-like control is not merely a weaker form of the adult left-lateralized system.
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.
Show abstract
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.
Fujiwara, J.; Tobler, P. N.; Tsutsui, K.-I.; Ugawa, Y.; Eifuku, S.; Taira, M.
Show abstract
We conform not only to the opinions and behaviors of others but also to those of ourselves, suggesting that the motivation to appear consistent leads us to treat ourselves like others. However, the neural mechanisms of self-conformity remain unclear. We used a sequential facial attractiveness-rating task with ostensible reminders of participants own previous ratings to investigate self-conformity and compare it against group conformity. Rating data showed that participants on average conformed to both themselves and the group. While some individuals conformed excessively (over-conformity), others went against their previous behavior (anti-conformity), similarly in self and group conditions. Neurally, dorsomedial and ventrolateral prefrontal cortex activity correlated with both self- and group conformity. Moreover, self-versus group conformity engaged more medial versus lateral prefrontal regions, and over-versus anti-conformity more ventral versus dorsal regions. These results suggest that self- and group conformity rely on both common and dedicated neural mechanisms.
Bozdech, Z.;Boentoro, J.;Kucharski, M.;Nayak, S.
Show abstract
The parasite Plasmodium falciparum causes malaria, the deadliest human parasitic disease, which remains fatal when not promptly treated. Evolving parasite resistance to frontline artemisinin-based therapies threatens vulnerable populations and decades of progress toward malaria elimination. Yet the mode of action of dihydroartemisinin (DHA), the active metabolite of these treatments, remains incompletely understood. Here we applied dose-response transcriptomics across the three intraerythrocytic stages - rings, trophozoites, and schizonts, revealing a two-tier transcriptional response to DHA, with low- and high-dose programs consistent with specific drug action and cytotoxic damage. The trophozoite stage mounts the strongest and most coordinated response, including a striking reversal of the developmental cascade in which protein synthesis machinery is broadly downregulated and a ring-like transcriptional profile is reactivated - reminiscent of drug-induced quiescence. Coordinated regulation of multiple protein complexes, most notably Kelch13 and its interacting partners (KIC), points to organized transcriptional control of the parasites drug response. This work provides a stage- and dose-resolved view of DHA action in P. falciparum and a template for future antimalarial mechanism-of-action studies.
Lin, S.; Ball, D. A.; Fazel, M.; Karpova, T. S.; Ho, M.
Show abstract
Glypican-3 (GPC3) is a heparan sulfate proteoglycan that is highly expressed in hepatocellular carcinoma and promotes tumor progression through Wnt3a/{beta}-catenin signaling. However, how the nanoscale organization of GPC3 at the cell surface controls signaling remains unclear. Here, we combined nano-resolution MINFLUX imaging, single-molecule tracking, and functional assays to define the spatial architecture and dynamics of GPC3 on hepatoma cells. We found that GPC3 exists as both single molecules and nanoscale clusters and switches between confined and free diffusions on the plasma membrane. Heparan sulfate (HS) chains create nanoscale corrals that limit GPC3 movement, whereas removal of HS increases diffusive heterogeneity and disrupts confinement. Wnt3a stimulation induces the formation of higher-order GPC3 assemblies and enhances {beta}-catenin signaling, while loss of HS markedly reduces this response. MINFLUX DNA-PAINT further revealed that HS chains orchestrate the spatial distribution of Wnt3a and promote its association with the Wnt receptor, Frizzled-1, an essential step for pathway activation. Collectively, these findings reveal that HS controls the nanoscale organization and dynamics of GPC3 to promote Wnt receptor assembly and efficient {beta}-catenin signaling in hepatoma cells.
Akinmusola, R. Y.; Minhas, R.; O'Neill, P.; Kon-Nanjo, K.; Kon, T.; Shimada, Y.; Ramsdale, M.; Kudoh, T.
Show abstract
The Arabian killifish (Aphaniops dispar) is new tractable vertebrate model system for developmental, ecological and biomedical research, including drug screening, pharmacological and infection biology studies. It is a relatively small euryhaline teleost with broad thermal tolerance and adaptability across a wide range of salinities from freshwater to hypersaline habitats. The embryos and early larvae are tolerant to environmental stressors and exhibit a delayed period of nutritional independence before hatching. This advantage offers an extended window for experimenting on the early developmental processes. Here, we describe time-course gene expression profiling of Arabian killifish embryos across nine developmental time points, from the 1-cell stage to the larval pre-hatching stage. Clustering of dynamic expression profiles for 27,564 Trinity genes revealed coordinated transcriptional modules corresponding to the maternal, blastula, maternal-to-zygotic transition (MZT)-related, gastrulation, organogenesis and larval maturation stages. The maternal stage displayed a highly distinct expression profile, dominated by maternal-specific transcripts that are rapidly degraded during the MZT. The later stages, from 48 hpf onward, revealed a shift from early regulatory mechanisms to the expression of organogenesis-related genes. The ZGA stage showed the conserved up-regulation of many zinc finger-associated genes, consistent with zebrafish and other teleost genomes. Overall, embryo development in A. dispar is slower than in zebrafish, with equivalent stages occurring several hours later. We propose a delayed onset of zygotic genome activation (ZGA) in the blastula stage, corresponding to 6 hpf in the Arabian killifish. Taken together, this study provides a transcriptomic resource for mining embryo development-related genes in the Arabian killifish.
Simony, E.; Yahav, N.; Malach, R.
Show abstract
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.
Tupe, C.; Goyal, B.; De, T. D.; Bhatt, D.; Dixit, B.; pandey, K. C.; Na, B. K.; Emami, S. N.; Chakraborti, S.
Show abstract
Iron homeostasis is essential for both the Plasmodium parasite and its hosts, the mosquito and human; however, the molecular mechanisms governing intracellular iron trafficking remain poorly understood. In mammals, poly(rC)-binding proteins (PCBPs) function as major iron chaperones by delivering Fe2+ to ferritin and other iron-dependent proteins, yet their role in insects has not been investigated. Here, we provide the first structural and functional characterization of the PCBP from a major malaria vector, Anopheles stephensi. Comparative structural and evolutionary analyses showed that insect PCBPs are most closely related to human PCBP3. Coordinated expression and co-localization of AsPCBP with ferritin following blood feeding suggested a conserved role in mosquito iron homeostasis. Functional analyses demonstrated that KH2-KH3 linker and KH3 domain of PCBP, plays an important role in the AsPCBP-ferritin interaction and that deletion of these regions, unexpectedly increased ferritin binding affinity but impaired iron delivery, indicating that these regions are dispensable for complex formation but essential for efficient iron transfer. Collectively, our results identify PCBP as a key component of mosquito iron homeostasis that could be exploited for the development of novel antimalarial strategies.
Olaciregui-Dague, K. R.; Acero-Pousa, I.; Berjaga-Buisan, T.; Kaller, M. S.; Sitt, J.; Deco, G.; Kringelbach, M. L.
Show abstract
BackgroundConsciousness is increasingly understood as an emergent property of large-scale brain dynamics that depend upon flexible interactions among distributed cortical and subcortical systems. Although disorders of consciousness (DOC) have traditionally been associated with impaired integration and reduced network complexity, the role of hierarchical brain organization in supporting conscious awareness remains poorly understood. Here, we investigated how hierarchical organization relates to behavioral responsiveness in DOC by combining trophic-level analysis, trophic coherence, and whole-brain dynamical metrics. MethodsResting-state functional MRI data were analyzed from healthy controls (CNT), minimally conscious state (MCS) patients, and unresponsive wakefulness syndrome (UWS) patients drawn from a previously published DOC cohort. Static global and regional measures of functional hierarchy were computed from directed effective-connectivity networks. Dynamic trophic states were identified using time-resolved phase-coupling analyses and clustering of recurrent coordination patterns. State occupancy, dwell time, metastability, synchrony, and behavioral associations with Coma Recovery Scale-Revised (CRS-R) scores were evaluated. ResultsRegional trophic levels were positively associated with behavioral responsiveness, with higher frontal and thalamic trophic levels and lower insular trophic levels predicting higher Coma Recovery Scale-Revised (CRS-R) scores. Dynamic trophic-state analysis identified a pathological hyper-hierarchical state, defined by elevated frontal, thalamic, and insular trophic levels, that exhibited progressively greater occupancy and longer dwell times from healthy controls to minimally conscious state and unresponsive wakefulness syndrome patients. In contrast, occupancy and dwell time of this state distinguished diagnostic groups but were not significantly associated with behavioral responsiveness. Independent analyses demonstrated significant reductions in metastability and global synchrony across disorders of consciousness. Anatomical mapping localized elevated trophic levels within the pathological state predominantly to fronto-thalamo-limbic systems. ConclusionsDisorders of consciousness are characterized not simply by loss of hierarchical organization but by prolonged stabilization within recurrent hyper-hierarchical brain states. Conscious awareness appears to depend not only on hierarchical organization itself but also on the capacity to flexibly transition between distinct brain states. Severe disorders of consciousness are associated with persistent occupation of pathological hyper-hierarchical states, potentially restricting the dynamical repertoire available for conscious processing.
Ahmad, A.; bakar, A.; Laeeque, S. M.; Khan, W. A.; Kaul, H.; Manan, A.; mustafa, h.
Show abstract
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.
Breit, A. M.; Takeshita, R. S. C.; Ehmke, E.; Walls, C.; Billington, C.; Larsen, P.; McLain, A.; Faulk, C.
Show abstract
Madagascars dwarf lemurs (genus Cheirogaleus) are the only obligate-hibernating primates and closest relative to humans capable of hibernation. Endemic to the increasingly fragmented dry forests of Madagascar, the fat tailed dwarf lemur (Cheirogaleus medius) represents a unique model for understanding primate physiology and tropical hibernation. Here we present FatTail1, a highly contiguous diploid genome assembly generated from a male C. medius at the Duke Lemur Center using Oxford Nanopore Technologies PromethION sequencing. The assembly spans 2.3 Gb, with an N50 of 103Mb, L50 of 10, and a BUSCO completeness score of over 99%. In addition to a complete mitogenome, we generated allele-specific DNA methylation profiles and annotated 23,925 genes using NCBIs EGAPX. FatTail1 exceeds the gap-free contiguity of previously published strepsirrhine genomes, representing the first telomere-to-telomere genome of a Strepsirrhine primate, and providing a foundation for future studies of primate hibernation, epigenetic regulation, and conservation genomics. ARTICLE SUMMARYDwarf lemurs are the only primates and closest relative to humans capable of months-long hibernation, making them an important model for understanding metabolic adaptations with relevance to human physiology. Here we present FatTail1, the first telomere-to-telomere genome assembly of a strepsirrhine primate, generated from a fat-tailed dwarf lemur (Cheirogaleus medius) using Oxford Nanopore Technologies PromethION sequencing. In addition to a highly complete nuclear genome, we assembled the mitogenome, identified allele-specific DNA methylation profiles and annotated 23,925 genes. FatTail1 exceeds the gap-free contiguity of previously published strepsirrhine genomes and provides an improved genomic resource for studies of hibernation, comparative genomics, epigenetic regulation, evolutionary biology, and conservation of this threatened primate.
Ge, Z.; Dou, W.
Show abstract
Deep brain systems involved in arousal, autonomic regulation, sensory integration, and homeostatic control remain underrepresented in conventional whole-brain neuroimaging frameworks. In particular, diencephalic and brainstem nuclei are often insufficiently represented in cortex-centered analyses, limiting the normative references needed to interpret systems-level variation in health and disease. To address this gap, we developed a unified multiscale framework with explicit representation of deep nuclei. By integrating cerebral, cerebellar, diencephalic, and brainstem atlases in standard space, we constructed a 220-region whole-brain parcellation and extracted complementary features at three analytical scales: nodal properties, edge-wise connectivity, and persistent-homology-based topological descriptors. We applied this framework to healthy adults from the Human Connectome Project-Aging cohort to characterize normative multiscale organization and test sex- and age-related variation. Applied to this cohort, our framework revealed pronounced heterogeneity across anatomical systems. Brainstem and diencephalic nuclei showed multiscale feature profiles distinct from those of cerebral and cerebellar regions across nodal, edge-wise, and higher-order topological scales. Sex comparisons identified selective differences across different scales, whereas age modeling revealed widespread but feature- and system-dependent variation across adulthood. Together, these findings show that normative whole-brain organization in this deep-system-aware space is structured by system-specific rather than globally uniform patterns. These findings establish a normative multiscale framework for characterizing brainstem-diencephalic-cerebellar-cerebral organization in healthy adults and provide a quantitative reference for future translational studies of disease-related abnormalities in deep regulatory systems.
Wang, R.; Keerativittayayut, R.; Morioka, S.; Takeda, M.; Jimura, K.; Hasegawa, I.; Nakahara, K.
Show abstract
The standard model of memory consolidation posits a temporary role for the hippocampus. We challenge this view by combining a novel face-name associative memory task with cross-modal decoding of fMRI data. We demonstrate that the hippocampus remains persistently engaged in representing both recent and remote memories, with distinct subregional contributions: recent memories were represented in the right posterior hippocampus, whereas remote memories additionally recruited the left anterior hippocampus. This sustained hippocampal involvement occurred alongside a large-scale network reorganization. Remote memory retrieval was accompanied by increased global connectivity among semantic regions, yet the hippocampus itself did not emerge as a major hub. Instead, network hubs shifted from the medial prefrontal cortex (mPFC) for recent memories to the mPFC and bilateral inferior parietal lobule for remote memories. These findings reveal a dynamic process in which the hippocampus preserves long-lasting representational functions while the broader memory network undergoes extensive reorganization.
Gleave, E. J.; Garcia-Marin, L. M.; Ceja, Z.; Renteria, M. E.; Chattopadhyay, T.; Gaser, C.; Rajagopalan, P.; Thompson, P. M.
Show abstract
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.
Pankratov, V.; Meyer Pedersen, B.; Fogh Sorensen, E.; Munch, K.; Bataillon, T.; Schierup, M. H.; Bergman, J.
Show abstract
BackgroundPrimates constitute one of the most phylogenetically and ecologically diverse Eutherian mammalian orders, with a central role in advancing our knowledge of human evolution, speciation processes and conservation biology. While thousands of whole-genome sequences have been generated across a multitude of primate taxa, discrepancies in data processing - particularly the lack of ploidy-aware variant calling in sex-linked regions - have limited the utility of existing datasets for large-scale comparative analyses. ResultsHere, we utilized publicly available short-read sequencing data of non-human primates, recently published primate genome assemblies and a ploidy-aware variant calling procedure to generate a genome-scale nucleotide diversity panel comprising 3,240 individuals from 269 species and 71 genera. To further facilitate cross-species comparisons, we generated a multiple-genome alignment of primate assemblies used for variant calling. ConclusionThis curated resource of non-human primate diversity provides a foundation for future research in primate evolutionary biology, speciation, and sex chromosome evolution (https://pure.au.dk/portal/en/datasets/primate-diversity-panel/).