Crucial Cue Research Articles

Tissue shear as a cue for aligning planar polarity in the developing Drosophila wing

Planar polarity establishment in epithelia requires interpretation of directional tissue-level information at cellular and molecular levels. Mechanical forces exerted during tissue morphogenesis are emerging as crucial tissue-level directional cues, yet the mechanisms by which they regulate planar polarity are poorly understood. Using the Drosophila pupal wing, we confirm that tissue stress promotes proximal-distal (PD) planar polarity alignment. Moreover, high tissue stress anisotropy can reduce the rate of accumulation and lower the stability on cell junctions of the core planar polarity protein Frizzled (Fz). Notably, under high tissue stress anisotropy, we see an increased gradient of cell flow, characterised by differential velocities across adjacent cell rows. This promotes core protein turnover at cell-cell contacts parallel to the flow direction, possibly via dissociation of transmembrane complexes by shear forces. We propose that gradients of cell flow play a critical role in establishing and maintaining PD-oriented polarity alignment in the developing pupal wing.

Fast Recurrent Field Transforms for Optical Flow on Edge GPUs

Abstract Optical flow reflects motion information in videos, serving as a crucial visual cue. However, high computational demands make dense optical flow estimation challenging to deploy on mobile platforms. We address this by introducing EdgeFlow, an optical flow network designed explicitly for edge GPUs. To enable efficient feature extraction, we propose a novel Low Memory Access Cost Net (LMAC-Net). Furthermore, we design a Convolutional Gated Core (CGC) for optical flow update, capable of obtaining high-quality features at low computational cost. During training and inference, we decouple the upsampling procedure. Inference speed is increased by only upsampling the final update outputs, reducing unnecessary computations. Our model demonstrates significant efficiency, utilizing only 52% of the parameters required by the baseline model. In generalization tests conducted on the Sintel dataset, EdgeFlow outperforms the baseline by achieving an 13% reduction in error rate. Additionally, the processing speed of EdgeFlow deployed on the Jetson Xavier NX platform is 7.5 times faster than the baseline. Finally, after using TensorRT to accelerate the model (with 3 recurrent updates), the inference speed is 98.67 FPS at 640×480 resolution. Source code is available at https://github.com/sklibra/EdgeFlow/tree/master.

Long-day induced flowering requires DNA hypermethylation in orchardgrass.

Flowering, a pivotal plant lifecycle event, is intricately regulated by environmental and endogenous signals via genetic and epigenetic mechanisms. Photoperiod is a crucial environmental cue that induces flowering by activating integrators through genetic and epigenetic pathways. However, the specific role of DNA methylation, a conserved epigenetic marker, in photoperiodic flowering remains unclear. This study integrated methylome, transcriptome, and gene expression analyses in orchardgrass (Dactylis glomerata) to elucidate the molecular mechanisms underlying long-day (LD) flowering. We found that LD treatment led to CHH hypermethylation, which was associated with the increased expression of RNA-dependent DNA methylation pathway components. LD-induced CHH hypermethylation in promoters correlated with upregulated photoperiod pathway genes and down-regulated miRNAs. The suppression of DNA methylation under LD conditions delays flowering, highlighting the critical role of hypermethylation. Additionally, the novel-miR1736-3p was identified as a negative regulator of DgFT. These findings elucidate the promotion of flowering through LD-induced CHH hypermethylation and provide insights into using epigenetic techniques to control plant flowering time.

Multi-modal Sarcasm Detection on Social Media via Multi-Granularity Information Fusion

The rising popularity of diverse social media platforms, commonly utilized by individuals to articulate their emotions in everyday interactions, has spurred a growing interest in the task of multi-modal sarcasm detection (MSD). Nonetheless, due to the unique nature of sarcasm, there remain two main challenges to achieving robust MSD. Firstly, prevailing methodologies often overlook the issue of weak multi-modal correlation, thereby neglecting the crucial sarcasm cues that are inherent in each uni-modal source. Secondly, there are inefficiencies in modeling cross-modal interactions in unaligned multi-modal data. To tackle these challenges, we introduce a multi-granularity information fusion network for multi-modal sarcasm detection. Specifically, we design a multi-task CLIP framework that can utilize multi-granularity cues from multiple tasks (i.e., text, image, and text-image interaction tasks) for multi-modal sarcasm detection. Furthermore, we devise a global-local cross-modal interaction learning method that uses discourse-level representations from each modality as the global multi-modal context to engage with local uni-modal features. This enables the global multi-modal context and local uni-modal features to mutually enhance and progressively improve through a multi-layer superposition. Following extensive experimental results and thorough analysis, our model achieves state-of-the-art performance in multi-modal sarcasm detection.

Probabilistically constrained vector summation of motion direction in the mouse superior colliculus.

Visual motion is a crucial cue for the brain to track objects and take appropriate actions, enabling effective interactions with the environment. Here, we study how the superior colliculus (SC) integrates motion information using asymmetric plaids composed of drifting gratings of different directions and speeds. With both invivo electrophysiology and two-photon calcium imaging, we find that mouse SC neurons integrate motion direction by performing vector summation of the component gratings. The computation is constrained probabilistically by the possible physical motions consistent with each grating. Excitatory and inhibitory SC neurons respond similarly to the plaid stimuli. Finally, the probabilistically constrained vector summation also guides optokinetic eye movements. Such a computation is fundamentally different from that in the visual cortex, where motion integration follows the intersection of the constraints. Our studies thus demonstrate a novel neural computation in motion processing and raise intriguing questions regarding its neuronal implementation and functional significance.

CAR-T cells are more affected than T lymphocytes by mechanical constraints: A microfluidic-based approach.

CAR-T cell therapy has attracted considerable attention in recent years owing to its well-known efficacy against haematopoietic malignancies. Nevertheless, this immunotherapy fails against solid tumours due to hostile conditions found in the tumour microenvironment. In this context, many relevant biochemical factors have been thoroughly studied, but crucial mechanical cues have been underestimated. We developed an innovative approach using microfluidic devices, which recreate the biomechanical aspects of solid tumours. Using these platforms, we quantified immune cell migration (T and CAR-T cells) under different confinement conditions. We found that both CAR-T cell and T cell velocities are affected by the biomechanical and chemical cues studied, which are closely related to those found in solid tumours. Under biochemical stimulus-free conditions, the velocity of T cells is independent of the width of the microchannel, whereas the velocity of CAR-T cells is greatly reduced in the highest confinement channels. When chemoattractants or tumour cells are added, immune cells display increased confined migration velocity. However, in the presence of immunosuppressive chemokines, T cells become slower, whereas CAR-T cells significantly increase their velocity via a chimeric cytokine receptor. Our approach contributes to a better understanding of immune cell migration and the influence of mechanical constraints, which will allow the testing of new ways to improve CAR-T cell trafficking into solid tumours. Therefore, our study revealed that the migratory behaviour of CAR-T cells differs from that of T cells under confined conditions and that biomechanical cues, such as cell deformability caused by confinement, can influence the correct infiltration of immune cells into solid tumours during the immune response.

Images of ingredients or finished products on food packages: the effects of food readiness and purchasing motivations

PurposeThis study explores the impact of packaging images (ingredients vs finished products), degree of food readiness (ready-to-heat vs ready-to-cook) and purchasing motivations (utilitarian vs hedonic) on consumer preferences.Design/methodology/approachTwo 2 × 2 between-subject experiments were conducted to investigate the interactive effects of package image type and food readiness (Study 1) as well as their individual impacts (Study 2). Data analysis and hypothesis testing were performed using SPSS software.FindingsConsumers initially preferred packaging images of finished products over ingredients when selecting ready-to-eat foods. However, their attitudes declined upon learning about specific food content. When motivated by hedonic factors, consumers favored images of finished products for ready-to-cook foods, whereas utilitarian motivations led to a preference for ingredient images. After purchasing, ingredient images were favored across both motivational contexts.Originality/valueFood packaging images serve as crucial cues in consumer purchase decisions, though no consensus currently exists on whether these images should feature ingredients or finished products. This study offers valuable insights into how these visual factors affect consumer behavior and decision-making, providing manufacturers with guidance on enhancing product evaluations by consumers.

Charge Modulation at the Liquid Crystal Droplet-Aqueous Interface Enables Ultrasensitive, Nonspecific Protein Detection.

Thermotropic nematic liquid crystals (LC) have been utilized to sense/detect various analytes such as polymers, surfactants, lipids, etc. However, their use for protein detection depends on pre-adsorbed molecules, co-nematogens, or biomolecular agents for specificity.This approach impedes the platform's sensitivity with a detection limit for the folded proteins generally reported in the micromolar concentration range. Here, this work provides fundamental insights into the type of molecular interactions and their modulation that can drive ultrasensitive protein detection at an LC microdroplet/aqueous interface formed without adding an auxiliary co-nematogen. Using ultraviolet (UV) light treated 4-cyano-4'-pentylbiphenyl (5CB) LC and a flow-focused microfluidic device, we prepared different populations of monodisperse and highly negatively charged microdroplets in water. Adding an aqueous solution of various model proteins(α-synuclein, α-chymotrypsin, myoglobin, or bovine serum albumin, BSA) with different secondary structures and surface charges triggers a rapid radial- to bipolar-defect transition in these microdroplets. Isothermal titration calorimetry measurement and molecular dynamic simulation studies attribute this to the dominant electrostatic force-mediated adsorption of proteins at the LC/aqueous interface.Further, bioconjugation-based variation of protein surface charge allows tuning their detection limit.These findings can provide crucial physical cues for designing responsive LC systems and establishing a foundation for developing versatile, molecularly tailored, and highly specific biomolecular detection platforms.

Fine-grained gaze estimation based on the combination of regression and classification losses

Human gaze is a crucial cue used in various applications such as human-robot interaction, autonomous driving, and virtual reality. Recently, convolution neural network (CNN) approaches have made notable progress in predicting gaze angels. However, estimating accurate gaze direction in-the-wild is still a challenging problem due to the difficulty of obtaining the most crucial gaze information that exists in the eye area which constitutes a small part of the face images. In this paper, we introduce a novel two-branch CNN architecture with a multi-loss approach to estimate gaze angles (pitch and yaw) from face images. Our approach utilizes separate fully connected layers for each gaze angle prediction, allowing explicit learning of discriminative features and emphasizing the distinct information associated with each gaze angle. Moreover, we adopt a multi-loss approach, incorporating both classification and regression losses. This allows for joint optimization of the combined loss for each gaze angle, resulting in improved overall gaze performance. To evaluate our model, we conduct experiments on three popular datasets collected under unconstrained settings: MPIIFaceGaze, Gaze360, and RT-GENE. Our proposed model surpasses current state-of-the-art methods and achieves state-of-the-art performance on all three datasets, showcasing its superior capability in gaze estimation.

Motion blur microscopy: in vitro imaging of cell adhesion dynamics in whole blood flow

Imaging and characterizing the dynamics of cellular adhesion in blood samples is of fundamental importance in understanding biological function. In vitro microscopy methods are widely used for this task but typically require diluting the blood with a buffer to allow for transmission of light. However, whole blood provides crucial signaling cues that influence adhesion dynamics, which means that conventional approaches lack the full physiological complexity of living microvasculature. We can reliably image cell interactions in microfluidic channels during whole blood flow by motion blur microscopy (MBM) in vitro and automate image analysis using machine learning. MBM provides a low cost, easy to implement alternative to intravital microscopy, for rapid data generation where understanding cell interactions, adhesion, and motility is crucial. MBM is generalizable to studies of various diseases, including cancer, blood disorders, thrombosis, inflammatory and autoimmune diseases, as well as providing rich datasets for theoretical modeling of adhesion dynamics.

Why leave items in the shopping cart? The impact of consumer filtering behavior

Online product information provides crucial cues for consumer shopping behavior; however, the impact of consumer-side information manipulation on non-purchase behavior (e.g., shopping cart abandonment) remains unclear. Filtering, a common manipulation strategy, was initially considered synonymous with searching, both of which contribute to consumer purchase behavior. However, recent research suggests significant differences, particularly in terms of cost and product matching. This study explores how such differences affect information manipulation and subsequently shape shopping cart abandonment, drawing on information foraging theory. Based on the premise that a forager's interaction with the environment is mediated by cognition, we find that consumer filtering behavior influences perceptions of serendipity (i.e., discovering unexpected items) and similarity (i.e., encountering similar items), thereby influencing shopping cart abandonment. Mediation analyses reveal that perceived serendipity and similarity are equally potent mediators. Marginal effects analyses demonstrate that a one standard deviation increase in consumer perceptions of serendipity (similarity) in filtering results increases the likelihood of shopping cart abandonment by 32.2% (22.1%). Theoretical contributions and practical insights for information behavior researchers and digital marketers are also provided.

VOC Characterization of Byasa hedistus (Lepidoptera: Papilionidae) and Its Visual and Olfactory Responses during Foraging and Courtship.

Color and odor are crucial cues for butterflies during foraging and courtship. While most sexual dimorphic butterflies rely more on vision, our understanding of how butterflies with similar coloration use different signals remains limited. This study investigated the visual and olfactory behavioral responses of the similarly colored butterfly Byasa hedistus during foraging and courtship. While visiting artificial flowers of different colors, we found that B. hedistus exhibits an innate color preference, with a sequence of preferences for red, purple, and blue. The frequency of flower visits by B. hedistus significantly increased when honey water was sprayed on the artificial flowers, but it hardly visited apetalous branches with honey water. This proves that locating nectar sources by odor alone is difficult in the absence of floral color guides. During courtship, males are active while females hardly chase; only two models were observed: males chasing males and males chasing females. The courtship process includes four behaviors: slowing approach, straight chasing, hovering, and spinning. B. hedistus cannot distinguish between sexes based on color, as there is no significant difference in color and shape between them. Twenty-three VOCs (>1%) were identified in B. hedistus, with 21 shared by both sexes, while ketones are specific to males. These VOCs are principally represented by cineole, β-pinene, and linalool. When cineole was added to butterfly mimics, many butterflies were attracted to them, but the butterflies did not seem to distinguish between males and females. This suggests that cineole may be the feature VOC for identifying conspecific groups. Adding β-pinene and linalool to mimics induced numerous butterflies to chase, hover, spin around, and attempt to mate with them. This suggests that β-pinene and linalool are crucial cues indicating the presence of females.

DEM super-resolution guided by shaded relief using attention-based fusion

Deep-learning based approaches have been proven effective for Digital Elevation Model (DEM) super-resolution (SR) tasks. Previous networks typically treat DEM elevation values as single-channel image for input. However, DEM images alone cannot fully capture spatial and terrain features. Shaded relief images (SRIs), derived from DEMs, serve as crucial visual cues that intuitively convey terrain characteristics, addressing the limitations of DEM images and providing synergistic benefits for training DL models. The primary challenge in utilizing SRIs for guiding DEM SR lies in accurately selecting a consistent structure to extract and effectively integrate features from SRIs and DEMs. In this study, we propose an Attention-based Hierarchical Terrain Fusion (AHTF) framework for guided DEM SR. Specifically, an Attention-based Feature Fusion Module (AFFM) is designed to efficiently fuse relevant information from LR DEM and SRI, which includes a feature enhancement block to select valuable features and a feature recalibration block to fuse diverse terrain features. Additionally, we optimize the loss function from the perspectives of terrain analysis and visual effects. We validate AHTF on our newly constructed real-world Shade-DEM SR dataset and two open-source DEM SR datasets. Compared to the current state-of-the-art methods, our AHTF achieves the best results in terms of root mean square error (RMSE) for elevation, slope, and aspect. Furthermore, the extracted stream networks are closer to real-world conditions. This study offers new insights and methods for further research and application in the field of DEM super-resolution. Our dataset can be obtained at https://doi.org/10.6084/m9.figshare.25590945.

Control over self and others’ face: exploitation and exploration

The face serves as a crucial cue for self-identification, while the sense of agency plays a significant role in determining our influence through actions in the environment. The current study investigates how self-identification through facial recognition may influence the perception of control via motion. We propose that self-identification might engender a belief in having control over one’s own face, leading to a more acute detection and greater emphasis on discrepancies between their actions and the sensory feedback in control judgments. We refer to the condition governed by the belief in having control as the exploitation mode. Conversely, when manipulating another individual’s face, the belief in personal control is absent. In such cases, individuals are likely to rely on the regularity between actions and sensory input for control judgments, exhibiting behaviors that are exploratory in nature to glean such information. This condition is termed the explorative mode. The study utilized a face-motion mixing paradigm, employing a deep generative model to enable participants to interact with either their own or another person’s face through facial and head movements. During the experiment, participants observed either their own face or someone else’s face (self-face vs. other-face) on the screen. The motion of the face was driven either purely by their own facial and head motion or by an average of the participant’s and the experimenter’s motion (full control vs. partial control). The results showed that participants reported a higher sense of agency over the other-face than the self-face, while their self-identification rating was significantly higher for the self-face. More importantly, controlling someone else’s face resulted in more movement diversity than controlling one’s own face. These findings support our exploration–exploitation theory: When participants had a strong belief in control triggered by the self-face, they became highly sensitive to any sensorimotor prediction errors, leading to a lower sense of agency. In contrast, when the belief of control was absent, the exploration mode triggered more explorative behaviors, allowing participants to efficiently gather information to establish a sense of agency.

Nitrogen-fixing bacteria boost floral attractiveness in a tropical legume species during nutrient limitation.

Legumes establish mutualistic interactions with pollinators and nitrogen (N)-fixing bacteria that are critical for plant reproduction and ecosystem functioning. However, we know little about how N-fixing bacteria and soil nutrient availability affect plant attractiveness to pollinators. In a two-factorial greenhouse experiment to assess the impact of N-fixing bacteria and soil types on floral traits and attractiveness to pollinators in Chamaecrista latistipula (Fabaceae), plants were inoculated with N-fixing bacteria (NF+) or not (NF-) and grown in N-rich organic soil (+N organic soil) or N-poor sand soil (-N sand soil). We counted buds and flowers and measured plant size during the experiment. We also measured leaf, petal, and anther reflectance with a spectrophotometer and analyzed reflectance curves. Using the bee hexagon model, we estimated chromatic contrasts, a crucial visual cues for attracting bees that are nearby and more distant. NF+ plants in -N sand soil had a high floral display and color contrasts. On the other hand, NF- plants and/or plants in +N organic soil had severely reduced floral display and color contrasts, decreasing floral attractiveness to bee pollinators. Our findings indicate that the N-fixing bacteria positively impact pollination, particularly when nutrients are limited. This study provides insights into the dynamics of plant-pollinator interactions and underscores the significant influence of root symbionts on key floral traits within tropical ecosystems. These results contribute to understanding the mechanisms governing mutualisms and their consequences for plant fitness and ecological dynamics.

Design and Evaluation of a Wearable Fingertip Device for Three-Dimensional Skin-Slip Display.

Skin-slip provides crucial cues about the interaction state and surface properties. Currently, most skin-slip devices focus on two-dimensional tactile slip display and have limitations when displaying surface properties like bumps and contours. In this article, a wearable fingertip device with a simple, effective, and low-cost design for three-dimensional skin-slip display is proposed. Continuous multi-directional skin-slip and normal indentation are combined to convey the sensation of three-dimensional geometric properties in virtual reality during active finger exploration. The device has a tactile belt, a five-bar mechanism, and four motors. Cooperating with the angle-mapping strategy, two micro DC motors are used to transmit continuous multi-directional skin-slip. Two servo motors are used to drive the five-bar mechanism to provide normal indentation. The characteristics of the device were obtained through the bench tests. Three experiments were designed and sequentially conducted to evaluate the performance of the device in three-dimensional surface exploration. The experimental results suggested that this device could effectively transmit continuous multi-directional skin-slip sensations, convey different bumps, and display surface contours.

A Sino‒Thai Blue-and-White Porcelain at UMMA

A blue-and-white porcelain lidded bottle housed at the University of Michigan Museum of Art stands as a significant representative from a collection of late 19th-century tea sets crafted in China for the Siamese court. This brief examination delves into crucial visual cues, such as the bottle’s distinct ringed-neck shape, incorporation of typical Chinese auspicious motifs, depictions of Siamese coinage and royal monograms from the Rama V period in its decorative patterns, and the presence of a Chinese-language hallmark on its base. These visual elements and inscriptions collectively unveil insights into the bottle’s purpose, origins, and its broader significance within the realm of Sino–Thai ceramics.

Object Detection for the Visually Impaired

This paper presents the design and development of a mobile application, built using Flutter, that leverages object detection to enhance the lives of visually impaired individuals. The application addresses a crucial challenge faced by this community – the lack of real-time information about their surroundings. We propose a solution that utilizes pre-trained machine learning models, potentially through TensorFlow Lite for on-device processing, to identify objects within the user's field of view captured by the smartphone camera. The application goes beyond simple object recognition. Detected objects are translated into natural language descriptions through text-to-speech functionality, providing crucial auditory cues about the environment. This real-time information stream empowers users to navigate their surroundings with greater confidence and independence. Accessibility is a core principle of this project. The user interface will be designed with compatibility for screen readers, ensuring seamless interaction for users who rely on assistive technologies. Haptic feedback mechanisms will be incorporated to provide non-visual cues and enhance the user experience. The ultimate goal of this project is to create a user-friendly and informative application that empowers visually impaired people to gain greater independence in their daily lives. The application has the potential to improve spatial awareness, foster a sense of security, and promote overall inclusion within society

Rate dependent neural responses of interaural-time-difference cues in fine-structure and envelope.

Advancements in cochlear implants (CIs) have led to a significant increase in bilateral CI users, especially among children. Yet, most bilateral CI users do not fully achieve the intended binaural benefit due to potential limitations in signal processing and/or surgical implant positioning. One crucial auditory cue that normal hearing (NH) listeners can benefit from is the interaural time difference (ITD), i.e., the time difference between the arrival of a sound at two ears. The ITD sensitivity is thought to be heavily relying on the effective utilization of temporal fine structure (very rapid oscillations in sound). Unfortunately, most current CIs do not transmit such true fine structure. Nevertheless, bilateral CI users have demonstrated sensitivity to ITD cues delivered through envelope or interaural pulse time differences, i.e., the time gap between the pulses delivered to the two implants. However, their ITD sensitivity is significantly poorer compared to NH individuals, and it further degrades at higher CI stimulation rates, especially when the rate exceeds 300 pulse per second. The overall purpose of this research thread is to improve spatial hearing abilities in bilateral CI users. This study aims to develop electroencephalography (EEG) paradigms that can be used with clinical settings to assess and optimize the delivery of ITD cues, which are crucial for spatial hearing in everyday life. The research objective of this article was to determine the effect of CI stimulation pulse rate on the ITD sensitivity, and to characterize the rate-dependent degradation in ITD perception using EEG measures. To develop protocols for bilateral CI studies, EEG responses were obtained from NH listeners using sinusoidal-amplitude-modulated (SAM) tones and filtered clicks with changes in either fine structure ITD (ITDFS) or envelope ITD (ITDENV). Multiple EEG responses were analyzed, which included the subcortical auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs) elicited by stimuli onset, offset, and changes. Results indicated that acoustic change complex (ACC) responses elicited by ITDENV changes were significantly smaller or absent compared to those elicited by ITDFS changes. The ACC morphologies evoked by ITDFS changes were similar to onset and offset CAEPs, although the peak latencies were longest for ACC responses and shortest for offset CAEPs. The high-frequency stimuli clearly elicited subcortical ASSRs, but smaller than those evoked by lower carrier frequency SAM tones. The 40-Hz ASSRs decreased with increasing carrier frequencies. Filtered clicks elicited larger ASSRs compared to high-frequency SAM tones, with the order being 40 > 160 > 80> 320 Hz ASSR for both stimulus types. Wavelet analysis revealed a clear interaction between detectable transient CAEPs and 40-Hz ASSRs in the time-frequency domain for SAM tones with a low carrier frequency.

Bacterial c-di-GMP signaling gene affects mussel larval metamorphosis through outer membrane vesicles and lipopolysaccharides

Biofilms serve as crucial cues for settlement and metamorphosis in marine invertebrates. Within bacterial systems, c-di-GMP functions as a pivotal signaling molecule regulating both biofilm formation and dispersion. However, the molecular mechanism of how c-di-GMP modulates biofilm-induced larval metamorphosis remains elusive. Our study reveals that the deletion of a c-di-GMP related gene in Pseudoalteromonas marina led to an increase in the level of bacterial c-di-GMP by knockout technique, and the mutant strain had an enhanced ability to produce more outer membrane vesicles (OMVs) and lipopolysaccharides (LPS). The mutant biofilms had higher induction activity for larval metamorphosis in mussels Mytilus coruscus, and OMVs play a major role in the induction activity. We further explored the function of LPS in OMVs. Extracted LPS induced high larval metamorphosis rate, and LPS content were subject to c-di-GMP and LPS-biosynthesis gene. Thus, we postulate that the impact of c-di-GMP on biofilm-induced metamorphosis is mediated through OMVs and LPS.