iScience

Fractal scaling governs the complex behavior of various animal species and, in humans, can be altered by neurodegenerative diseases and aging1. However, the mechanism underlying fractal scaling remains unknown. Here, we videorecorded C. elegans that had been cultured in a microfluidic device for 3 days and analyzed temporal patterns of C. elegans actions by fractal analyses. The residence-time distribution of C. elegans shared a common feature with those of human and mice2-4. Specifically, the residence-time power-law distribution of the active state changed to an exponential-like decline at a longer time scale, whereas this change did not occur in the inactive state. The exponential-like decline disappeared in starved C. elegans but was restored by culturing animals with glucose. The exponential-like decline similarly disappeared in insulin-signaling daf-2 and daf-16 mutants. Therefore, we conclude that insulin signaling regulates fractal scaling of C. elegans behavior. Our findings indicate that neurosensory modulation of C. elegans behavior by insulin signaling is achieved by regulation of fractal scaling. In humans, diabetes mellitus is associated with depression, bipolar disorder, and anxiety disorder5, which affect daily behavioral activities. We hypothesize that comorbid behavioral defects in patients with diabetes may be attributed to altered fractal scaling of human behavior.

The sauropod hind limb was the main support that allowed their gigantic body masses and a wide range of dynamic stability adaptations. It was closely related to the position of the centre of masses of their multi-ton barrel-shaped bodies, and experienced one of the most noticeable posture changes during macronarian evolution. Deeply branched macronarians achieved increasingly arched hind limbs in what is known as wide-gauge posture. However, it is not clear if this evolutionary trend is related to the evolutionary cascade toward gigantism even though some titanosaurians were the largest terrestrial vertebrates that ever existed. We tested evolutionary changes in hind limb morphology in the Macronaria phylogenetic tree by 3D geometric morphometrics. The macronarian hind limb does become progressively more arched toward deeply-branched groups, specifically Saltasauridae. However, there is morphological convergence between different macronarian subclades. Wide-gauge posture does not correlate with changes in body size deeper in the macronarian evolutionary tree, and acted as an exaptation to gigantism. Despite some titanosaurian subclades becoming some of the largest vertebrates, there is not a statistically-significant trend toward a particular body size but we identify a phyletic body size decrease in Macronaria.

The discovery of a diverse repertoire of ultrasonic vocalizations (USVs) sparked interest in understanding their role in mouse social behavior. Social communication in mice is not just vocal, but multimodal and occurs mostly in close proximity. Aiming to unravel the impact direct physical interaction has on the vocal communication of same-sex mouse dyads, we separated mice through a divider preventing direct physical interaction, but allowing visual, olfactory and some tactile interaction through holes. Separated dyads emitted a distinct call repertoire consisting mainly of calls in or just above the human audible range (but not squeaks) as well as Noisy calls, and only to a lesser degree of USVs. Increasing the possibility for direct interaction through larger holes in the divider led to an adaption of the call repertoire. The separation-induced call repertoire was neither affected by sex, nor was it mouse strain specific, even though differences in spectro-temporal parameters and call class proportion occurred. Lastly, buspirone treatment showed no observable effect, suggesting anxiety to not be the main driver underlying the separation-induced call repertoire. We show that separated same-sex mouse dyads predominantly emit a call repertoire that until now has only been observed in isolation or during aversive stimulation.

Courtship behaviors consist of two phases, namely the appetitive and consummatory states. Despite the long history of the concept, few studies have been done regarding the genetic contribution on those two different phases. Male mice are known to produce distinct ultrasonic vocalizations (USVs) as they progress through courtship states1-14, and these courtship sounds also show strain-specific differences15-18. Here, we delved into USV syllable patterns emitted during specific courtship actions using inbred mouse strains and their progeny: C57BL/6J (B6) mice, 129S4/SvJae (129) mice, and their second filial generation (F2) offspring of mixed genetic backgrounds. B6, 129, and F2 mice generated similar USV syllables during mounting behavior. In contrast, B6 and 129 mice showed different USV syllable patterns during body and anogenital sniffing behavior, and the USV syllable usage of F2 mice in this courtship state diverged according to the degree of genetic similarity with B6 or 129 mice. From these results, we propose that differential selection pressures19-20 favored diversity in appetitive behavior but conservation in consummatory behaviors.

The proper balance and transition between cellular quiescence and proliferation are critical to tissue homeostasis, and their deregulations are commonly found in many human diseases, including cancer and aging. Recent studies showed that the reentry of quiescent cells to the cell cycle is subjected to circadian regulation. However, the underlying mechanisms are largely unknown. Here, we report that two circadian proteins, Cryptochrome (Cry) and Rev-erb, deepen cellular quiescence in rat embryonic fibroblasts, resulting in stronger serum stimulation required for cells to exit quiescence and reenter the cell cycle. This finding was opposite from what we expected from the literature. By modeling a library of possible regulatory topologies linking Cry and Rev-erb to a bistable Rb-E2f gene network switch that controls the quiescence-to-proliferation transition and by experimentally testing model predictions, we found Cry and Rev-erb converge to downregulate Cyclin D/Cdk4,6 activity, leading to an ultrasensitive increase of the serum threshold to activate the Rb-E2f bistable switch. Our findings suggest a mechanistic role of circadian proteins in modulating the depth of cellular quiescence, which may have implications in the varying potentials of tissue repair and regeneration at different times of the day.

The Great Ordovician Biodiversification Event (GOBE) embodies the most dramatic increase of marine biodiversity and escalation of macroecological complexity during the early Phanerozoic. Despite its critical role, the precise timing and duration of the GOBE remain controversial. Numerous palaeobiological studies have attempted to quantify the GOBE based on estimates of species richness through time for various groups of marine organisms. However, these studies use fossil data restricted to specific geographic regions or employ disparate methodologies that preclude direct analytical comparisons. We present a meta-analysis of Ordovician biodiversity that integrates information from multiple temporal, geographic, and ecological scales. We collate 98 datasets from 54 publications to analyze temporally standardized rates of marine species biodiversity accumulation between the latest Cambrian and throughout the entire Ordovician using an effect-size approach. Our results indicate statistically significant high rates of sustained species accumulation that can be traced from the late Cambrian and until the Middle Ordovician, stabilization during the Late Ordovician and then a precipitous decline caused by the Late Ordovician Mass Extinction. Geographic scale (global vs regional) has no significant bearing on rates of biodiversification, with the only exception observed during the Dapingian-Darriwilian transition, supporting the hypothesis of mass dispersal of generalists during the Early Ordovician. Benthic and suspension-feeding organisms show high rates of biodiversity accumulation throughout most of the Ordovician (Tremadocian-Sandbian), whereas the diversification of nektonic, pelagic and predatory/scavenger organisms was mostly restricted to the Early Ordovician.

Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potential beneficial as well as detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be re-activated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Understanding the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be deconvoluted by surface-based assays like enzyme-linked immunosorbent assays (ELISAs) which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody-affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory re-activation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2.

Single cell spatial interrogation of the immune-structural interactions in COVID -19 lungs is challenging, mainly because of the marked cellular infiltrate and architecturally distorted microstructure. To address this, we developed a suite of mathematical tools to search for statistically significant co-locations amongst immune and structural cells identified using 37-plex imaging mass cytometry. This unbiased method revealed a cellular map interleaved with an inflammatory network of immature neutrophils, cytotoxic CD8 T cells, megakaryocytes and monocytes co-located with regenerating alveolar progenitors and endothelium. Of note, a highly active cluster of immature neutrophils and cytotoxic CD8 T cells, was found spatially linked with alveolar progenitor cells, and temporally with the diffuse alveolar damage stage. These findings provide new insights into how immune cells interact in the lungs of severe COVID-19 disease. We provide our pipeline [Spatial Omics Oxford Pipeline (SpOOx)] and visual-analytical tool, Multi-Dimensional Viewer (MDV) software, as a resource for spatial analysis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=190 HEIGHT=200 SRC="FIGDIR/small/22283654v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@f1332forg.highwire.dtl.DTLVardef@1576abcorg.highwire.dtl.DTLVardef@208c84org.highwire.dtl.DTLVardef@e93975_HPS_FORMAT_FIGEXP M_FIG C_FIG

Glucose-induced pancreatic islet hormone release is tightly coupled with oscillations in cytoplasmic free Ca2+ concentration of islet cells, which is regulated by a complex interplay between intercellular and intracellular signaling. {delta} cells, which entangle with cells located at the islet periphery, are known to be important paracrine regulators. However, the role of {delta} cells in regulating Ca2+ oscillation pattern remains unclear. Here we show that {delta}- cell-to-cell interactions are the source of variability in glucose-induced Ca2+ oscillation pattern. Somatostatin secreted from {delta} cells prolonged the islets oscillation period in an cell mass-dependent manner. Pharmacological and optogenetic perturbations of {delta}- interactions led islets to switch between fast and slow Ca2+ oscillations. Continuous adjustment of {delta}- coupling strength caused the fast oscillating islets to transition to mixed and slow oscillations. We developed a mathematical model, demonstrating that the fast-mixed-slow oscillation transition is a Hopf bifurcation. Our findings provide a comprehensive understanding of how {delta} cells modulate islet Ca2+ dynamics and reveal the intrinsic heterogeneity of islets due to the structural composition of different cell types. HighlightsO_LISomatostatin slows down islet Ca2+ oscillations in an cell mass-dependent manner. C_LIO_LIPharmacological and optogenetic perturbations of {delta}- interaction cause islet Ca2+ oscillation mode switching. C_LIO_LIContinuous tuning of {delta}- interaction strength induces fast-mixed-slow oscillation transition successively. C_LIO_LIMathematical modeling shows the fast-mixed-slow oscillation transition as a Hopf bifurcation. C_LI

Osteohistological investigations of fossilized bone can reveal details about the specimens biological, geological and environmental conditions. Micro-to-nanoscale imaging provides insight into the structural organization of bone and can also reveal indicators of the fossilization process. We examined a petrographic thin section of the left fibula of a [~]71.5 million-year-old Albertosaurus sarcophagus (Canadian Museum of Nature [CMN] catalogue number FV 11315) using nanoscale scanning electron microscopy (SEM) and focused ion beam (FIB)-SEM tomographic imaging to study the arrangement of mineral and organic components of fossil bone in multidimensions. Here, we present evidence of permineralization in Haversian canals by energy dispersive X-ray spectroscopy. Nanoscale 3D FIB-SEM imaging revealed that the characteristic 67 nm banding periodicity of collagen fibrils was remarkably well preserved over 70M years, and 3D imaging allowed for the detection of collagen fibril bundles in parallel fibered and lamellar bone arrangements. A newly discovered structure in modern bone, the ellipsoidal mineral cluster, was tiled throughout the 3D space of fibrolamellar fossil bone. These observations, afforded by the high-resolution and site-specific nature of FIB-SEM, link key fossilized features with the micro-nanoscale structure of modern-day bone. This investigation highlights the persistence of bone formation and organization persisting for over millions of years.

Intraspecies aggression has profound ecological and evolutionary consequences, as recipients can suffer injuries, decreases in fitness, and become outcasts from social groups. Although animals implement diverse strategies to avoid hostile confrontations, the extent to which social influences affect escape tactics is unclear. Here, we used computational and machine-learning approaches to analyze complex behavioral interactions as mixed-sex groups of mice, Mus musculus, freely interacted. Mice displayed a rich repertoire of behaviors marked by changes in behavioral state, aggressive encounters, and mixed-sex interactions. A prominent behavioral sequence consistently occurred after aggressive encounters, where males in submissive states quickly approached and transiently interacted with females immediately before the aggressor engaged with the same female. The behavioral sequences were also associated with substantially fewer physical altercations. Furthermore, the males behavioral state and the interacting partners could be predicted by distinct features of the behavioral sequence, such as kinematics and the latency to and duration of male-female interactions. More broadly, our work revealed an ethologically relevant escape strategy influenced by the presence of females that may serve as a mechanism for de-escalating social conflict and preventing consequential reductions in fitness.

The effects of hormone stimulation on the cell translational profile remain poorly understood. Here, using polysome profiling combined to RNA sequencing, we analyzed the translational response to follicle-stimulating hormone (FSH) of primary rat Sertoli cells, that exhibit an active anabolic activity regulated by reproductive hormones in the male gonad. We first established that mRNA distribution to polysomes follows a bimodal pattern, with 15% of mRNAs enriched in polysomes and exhibiting high expression. Critically, this basal polysomal enrichment had a major impact on FSH-induced mRNA recruitment to the polysomes, since FSH stimulation promoted the release of polysome-enriched mRNAs, while mRNAs that were the least associated to polysomes were preferentially recruited to polysomes upon stimulation. The FSH signal did not alter the core biological functions of Sertoli cells, but shifted the proteins involved in these functions, suggesting a molecular rewiring of the FSH-induced gene expression. These findings underscore how ribosomal reallocation dynamically adapts the cellular translatome to microenvironmental changes, enabling cells to fine-tune protein production in response to external stimuli. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/629416v1_ufig1.gif" ALT="Figure 1000"> View larger version (19K): org.highwire.dtl.DTLVardef@27334forg.highwire.dtl.DTLVardef@199c630org.highwire.dtl.DTLVardef@a28b92org.highwire.dtl.DTLVardef@1794172_HPS_FORMAT_FIGEXP M_FIG C_FIG Bullet points* In Sertoli cells, most mRNAs distribute similarly between monosomes and polysomes, but a sub-population is specifically enriched in polysomes * Basal polysomal enrichment level has a major impact on FSH-induced mRNA recruitment or release from the polysomes * The FSH signal induced a global rewiring of the proteins involved in Sertoli cell basal activity * FSH-induced reassignment of ribosomes to specific mRNAs has to comply with a tightly maintained mRNA distribution landscape

Cell-to-cell communication plays a cardinal role in the biology of multicellular organisms. H2O2 is an important cell-to-cell signaling molecule involved in the response of mammalian cells to wounding and other stimuli. We previously identified a signaling pathway that transmits wound-induced cell-to-cell H2O2 signals within minutes over long distances, measured in centimeters, in a monolayer of cardiomyocytes. Here we report that this long-distance H2O2 signaling pathway is accompanied by enhanced accumulation of cytosolic H2O2 and altered redox state in cells along its path. We further show that it requires the production of superoxide, as well as the function of gap junctions, and that it is accompanied by changes in the abundance of hundreds of proteins in cells along its path. Our findings highlight the existence of a unique and rapid long-distance H2O2 signaling pathway that could play an important role in different inflammatory responses, wound responses/healing, cardiovascular disease, and/or other conditions. HighlightsO_LIWounding induces an H2O2 cell-to-cell signal in a monolayer of cardiomyocytes. C_LIO_LIThe cell-to-cell signal requires H2O2 and O2{middle dot}- accumulation along its path. C_LIO_LIThe signal propagates over several centimeters changing the redox state of cells. C_LIO_LIChanges in the abundance of hundreds of proteins accompanies the signal. C_LIO_LIThe cell-to-cell signal requires paracrine and juxtacrine signaling. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=70 SRC="FIGDIR/small/572374v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@3b3806org.highwire.dtl.DTLVardef@1db37fcorg.highwire.dtl.DTLVardef@138bdd7org.highwire.dtl.DTLVardef@377402_HPS_FORMAT_FIGEXP M_FIG C_FIG

Graptolites are fossils from the mid-Cambrian to lower Carboniferous periods that inform both our understanding of evolution and the exploration of shale gas [1-4]. The identification of graptolite species remains a visual task carried out by experienced taxonomists because their fine-grained morphologies and incomplete preservation in multi-fossil samples have hindered automation. Artificial intelligence (AI) holds great promise for transforming such meticulous tasks, and has already proven useful in applications ranging from animal classification to medical diagnostics [5-15]. Here we demonstrate that graptolites can be identified with taxonomist accuracy using a deep learning model [16-18]. We develop a convolutional neural network to classify macrofossils, and construct a comprehensive dataset of >34,000 images of 113 graptolite species annotated at pixel-level resolution to train the model. We validate the models performance by comparing its ability to identify 100 images of graptolite species that are significant for rock dating and shale gas exploration with 21 experienced taxonomists from research institutes and the shale gas industry. Our model achieves 86% and 81% accuracy when identifying the genus and species of graptolites, respectively; outperforming taxonomists in terms of accuracy, time, and generalization. By investigating the decisions made by the neural network, we further show that it can recognise fine-grained morphological details better than taxonomists. Our AI approach, providing taxonomist-level graptolite identification, can be deployed on web and mobile apps to extend graptolite identification beyond research institutes and improve the efficiency of shale gas exploration.

HLA, the coding genes of human major histocompatibility (MHC) proteins, play a crucial role in the human adaptive immune system by presenting antigenic peptides to T cell receptors on T cells. HLA-A, HLA-B and HLA-C, these 3 Class I HLA genes are one of the most polymorphic loci in the human genome. For decades, HLA typing has been performed prior to tissue and stem cell transplantation. However, beyond the role in tissue matching, HLA has also been implicated in a wide array of autoimmune diseases and HLA genotypes and expression levels are closely associated with cancer patients prognosis as recent studies have revealed. Recently methods have been developed to perform HLA typing and HLA expression quantification together by using RNA-seq techniques. However, these bulk RNA-seq experiments are measuring an averaged signal of cell populations. Single-cell RNA-seq (scRNA-seq) has regained its popularity due to its power to reliably resolve single RNA transcriptomes at large scales. In our present study, we did HLA typing using three independent scRNA-seq datasets. Interestingly, we found that single cells from the same donor could be classified into different groups where each group has a distinct expressed HLA genotype (e.g., HLA-A, heterozygous or homozygous); in other words, HLA class I genes show abundant allele specific expression in single cells. This phenomenon has been repeatedly observed in a total of 14 donors from 3 independent datasets (one is breast epithelium, another two are multiple myeloma). Our systematic analysis of HLA class I gene expression using multiple scRNA-seq datasets has uncovered a putative mechanism, where by fine tuning HLA class I expressions both at the quantity and allele levels, our immune system is able to handle various internal challenges through single cells equipped with extraordinary diverse HLA expression patterns.

SummaryEstimating deep-time diversification patterns and the establishment of extant biodiversity represent major challenges in macroevolution. Fossil record data provide essential information to address these topics, but their heterogeneous temporal and geographical distributions require using analytical approaches to process these data. Gardiner et al.1 (hereafter GEA) used a deep-learning model2 and a fossil-occurrences dataset3 to estimate neoselachian richness over the last 145 myr. Results and DiscussionGEA1 found that neoselachian diversity increased throughout the Cretaceous, was little impacted by the Cretaceous-Paleogene (K/Pg) mass extinction ([~]10% species loss), and peaked in the mid-Eocene but declined until the Present. While the Cretaceous increase in neoselachian richness is well known4, the other findings of GEA1 are at odds with current knowledge. With the exception of lamniform sharks, the perceived decrease in species richness in the recent past is most likely due to a drop in available fossil record data combined with difficulties in identifying extant species in the fossil record5. Similarly, all previous analyses of the impact of the K/Pg mass extinction on elasmobranch diversification have reported high extinction rates, a marked diversity drop, and delayed recovery6-7, despite heterogeneity across clades, ecology, and geographical distribution7. Taking the K/Pg as an example, we demonstrate that the discrepancies between GEA1s results and current consensus is most likely due to a combination of incomplete, unverified, and incorrect fossil-occurrence data with inappropriate methodology.

In the Drosophila olfactory system most odorants are encoded in the antennal lobe in a combinatory way, activating several glomerular circuits. However, odorants of particular ecological role for the fly are encoded through activation of a single specialized olfactory pathway. Comparative analyses of densely reconstructed connectomes of one broadly tuned glomerulus (DL5) and one narrowly tuned glomerulus (DA2) gained detailed insight into the variations of synaptic circuitries of glomeruli with different computational tasks. Our approach combined laser-branding of glomeruli of interest with volume based focused ion beam-scanning electron microscopy (FIB-SEM) to enable precise targeting and analysis of the two glomeruli. We discovered differences in their neuronal innervation, synaptic composition and specific circuit diagrams of their major cell types: olfactory sensory neurons (OSNs), uniglomerular projection neurons (uPNs) and multiglomerular neurons (MGNs). By comparing our data with a previously mapped narrowly tuned glomerulus (VA1v), we identified putative generic features of narrowly tuned glomerular circuits, including higher density of neuronal fibers and synapses, lower degree of OSN lateralization, stronger axo-axonic connections between OSNs, dendro-dendritic connections between many uPNs, and lower degree of presynaptic input on OSN axons. In addition, this work revealed that the dendrites of the single uPN in DL5 contain a substantial amount of autapses interconnecting distant regions of the dendritic tree. The comparative analysis of glomeruli allows to formulate synaptic motifs implemented in olfactory circuits with different computational demands.

In recent years, many women have delayed childbearing, thus increasing the necessity for assisted reproductive technology (ART) for older women1-3. Despite advances in ART4, its success rate in advanced-age women is still very low3,4. As time-lapse imaging became available, morphological features of the developing pre-implantation embryo, in-vitro, are heavily used to assess its potency5-9. Timing of embryo cleavage is also an important factor that correlates with blastocyst formation and pregnancy rates8,10-14. Yet, our understanding of the interplay between embryos morphology, viability, and maternal age is limited, as manual approaches to infer embryo morphokinetics are time-consuming, subjective, and prone to errors. Machine learning15-18 was recently harnessed to predict embryo developmental potential19,20, however, with limited success. Here, we develop an artificial intelligence (AI) platform that infers the embryos developmental stage and captures tens of morphological properties and developmental dynamics. We show that developmental timing is the most informative and predictive morphokinetic property, particularly for embryos from maternally aged females. Analyzing the timing distributions reveals that viable embryos are confined into an age-independent temporal corridor while non-viable embryos deviate from it towards slower transition times. Yet, the deviation of non-viable embryos from the temporal corridor is age-dependent. Furthermore, there is a significant correlation between consecutive developmental stages transition times that diminishes in maternally old embryos. Overall, our results suggest that maternally old embryos most apparent morphokinetic property is the loss of temporal regulation. Our results and platform pave the way for a more accurate, maternally-age-dependent, assisted reproductive technology.

Marmoset monkeys have attracted much attention as a non-human primate model for studying vocal communication, but the call pattern and its meaning in marmoset communication are largely unknown. Here, we analyze sounds produced by hundreds of marmosets either in isolation or in pairs and reveal distinct call patterns in marmoset communication. The most prominent phee calls could be categorized into multiple grades based on the number of comprising phee syllables. Call transitions exhibited non-random patterns, favoring transition to the same or adjacent grade, with long sequences limited within two adjacent grades. The interval, composition, and temporal distribution of calls were significantly different between isolated and paired marmosets. Notably, different patterns of phee calls correlated with the heart rates and emotional states of marmoset, with the higher call grade reflecting a more agitated state. Antiphonal calling also exhibited distinct patterns and phee calls directly affected the heart rate of the listener in a manner depending on the grade of phee calls. Thus, phee call patterns in marmosets could encode emotional states and transmit emotion between turn-taking marmosets. How emotional expression in animals evolves into semantic communication in humans remains a mystery. Such complex call patterns in marmoset vocalization could represent the evolutionary prelude to semantic communication in primates.

In addition to frequently occurring stable all-or-none responses, live cells can display more complex response dynamics, e.g., oscillations in the activity/concentration of biomolecules. While the emergence and function of oscillatory dynamics have been heavily investigated, fewer efforts have been spent on whether cells can fine-tune different aspects of an oscillatory signal (e.g., peakwidth, duty cycle, and frequency) and whether this fine-tuning can allow oscillatory signals to convey different information. In this study, we investigate glucose-induced calcium (Ca2+) oscillation in MIN6 cells, finding that the spontaneous or induced changes in the phosphatidylinositol 4,5-bisphosphate (PIP2) level during Ca2+ oscillation can modulate the peakwidth of individual Ca2+ spikes. Additionally, using a combination of optogenetics and Ca2+ imaging, we demonstrate that variation of the widths and frequencies of Ca2+ spikes can exert strong influence on coupling between neighboring MIN6 cells.