Biology subjects

Rich, A.

Publications and source records attributed to Rich, A..

14 recordsLinked to original sources

bioRxiv2025

Live visualization of extracellular matrix dynamics during development and regeneration in zebrafish

Extracellular matrix (ECM) plays fundamental roles in animal development, regeneration, and disease. The difficulty of tagging endogenous matrix proteins in vertebrates has limited the understanding of ECM composition and dynamics in complex tissues. To visualize vertebrate ECM components, we tagged zebrafish Laminin, gamma 1 (Lamc1), Collagen, type I, alpha 2 (Col1a2), and Transforming growth factor, beta-induced (Tgfbi) using C-terminus in-fusion genome editing. Analysis of these knock-in lines revealed distinct expression of each protein in various tissues during development and regeneration. Fluorescent recover after photobleaching (FRAP) analysis further indicated that Lamc1 is stable in fin fold matrix but more dynamic in myoseptal matrix of developing zebrafish, while Col1a2 and Tgfbi are stable matrix components in myosepta. Strikingly, we found that Col1a2-mScarlet protein accumulates at the amputation plane during tailfin regeneration, where it remains concentrated for several days and distant from the regeneration blastema. This "foundation" region also displayed a distinct transcriptome suggesting active and dedicated events at the base of the regenerating appendage. Our resource enables live capture of ECM dynamics that can identify new events in developing and regenerating zebrafish. Summary statementExtracellular matrix resources for zebrafish development and tissue regeneration.

developmental biology↗

bioRxiv2025

Distinctive associations between plasma p-tau181 levels and hippocampal subfield volume across the Alzheimer's disease continuum

BackgroundPlasma p-tau181 is a promising diagnostic marker of Alzheimers disease (AD) pathology, reflecting amyloid accumulation, tau deposition, and downstream neurodegeneration that leads to cognitive impairment. However, the specificity of plasma p-tau181 to AD-related tau pathology remains unclear. ObjectiveTo assess whether plasma p-tau181 is differentially associated with volumetric changes in distinct hippocampal subfields and whether they mediate the relationship between plasma p-tau181 and cognition across the AD continuum. Methods213 participants with normal cognition (N=57), mild cognitive impairment (N=109), and AD (N=47) from the Alzheimers Disease Neuroimaging Initiative (ADNI) were included for cross-sectional analyses of hippocampal subfield volume that was quantified using the Automatic Segmentation of Hippocampal Subfields (ASHS) software. A subset (n=89) was evaluated for one-year longitudinal changes in hippocampal subfield volume. ResultsHigher plasma p-tau181 levels (pg/mL) were associated with decreased volumes in the CA1 and dentate gyrus, bilaterally, and right entorhinal cortex (ps < 0.05). Additionally, volumes of these subfields partially mediated the relationship between plasma p-tau181 and ADNI memory and executive function composite scores. Baseline plasma p-tau181, however, did not predict longitudinal atrophy of hippocampal subfields across diagnostic groups. ConclusionsPlasma p-tau181 is differentially associated with hippocampal subfields that are closely related to both age- and AD-related neurodegeneration. Elevated plasma p-tau181 levels may reflect tau accumulation, and volumetric changes in CA1 and DG may mediate the detrimental effect of tau pathology on cognition.

neuroscience↗

bioRxiv2025

Decaying and expanding Erk gradients process memory of skeletal size during zebrafish fin regeneration

Regeneration of an amputated salamander limb or fish fin restores pre-injury size and structure, illustrating the phenomenon of positional memory. Although appreciated for centuries, the identity of position-dependent cues and how they control tissue growth are not resolved. Here, we quantify Erk signaling events in whole populations of osteoblasts during zebrafish fin regeneration. We find that osteoblast Erk activity is dependent on Fgf receptor signaling and organized into millimeter-long gradients that extend from the distal tip to the amputation site. Erk activity scales with the amount of tissue amputated, predicts the likelihood of osteoblast cycling, and predicts the size of regenerated skeletal structures. Mathematical modeling suggests gradients are established by the transient deposition of long-lived ligands that are transported by tissue growth. This concept is supported by the observed scaling of expression of the essential epidermal ligand fgf20a with extents of amputation. Our work provides evidence that localized, scaled expression of pro-regenerative ligands instructs long-range signaling and cycling to control skeletal size in regenerating appendages.

developmental biology↗

bioRxiv2024

Characteristics of vicarious touch reports in a general population

Vicarious touch broadly refers to sensory, neural, or affective responses to observing touch on another person. In this study, we focus on the conscious experience of these sensations. We collected vicarious touch reports from 422 undergraduate students who viewed videos from the Validated Touch-Video Database (VTD), a stimulus set systematically rated for hedonic qualities, arousal, and perceived threat levels. A surprisingly large majority (84%) of participants reported vicarious sensations such as touch, tingling, pressure, and pain, predominantly matching the location of touch on the hands observed in the videos. Contrary to previous studies, we found that vicarious touch was more prevalent in women than men. Additionally, while earlier research suggested a correlation between vicarious sensations and emotional reactivity, our data did not support this relationship. The nature and intensity of reported sensations varied strongly with the emotional content of the videos: pleasant touches often evoked ticklish or warm sensations, while unpleasant touches often resulted in pain or pressure. Participants regularly described their sensations as either pleasant or unpleasant, indicating that the affective qualities of observed touch were mirrored in their experiences. Subjective arousal and threat ratings taken from the VTD for each video strongly correlated with the prevalence and intensity of vicarious touch measured here, with painful, highly arousing touches eliciting the strongest responses. Even observing touch on a non-human object occasionally triggered similar vicarious sensations. Using a new clustering approach, we identified three distinct profiles of vicarious touch, each characterised by unique sensory experiences, variations in the localisation and intensity of sensations, and differences in responses to observing touch on another person versus an object. Overall, our results challenge the traditional view that conscious vicarious touch experiences are a rare phenomenon and underscore the diversity of vicarious sensory perception.

neuroscience↗

bioRxiv2023

Apical polarity and actomyosin dynamics regulate Hippo signaling by controlling Kibra subcellular localization

Cell polarity and actomyosin networks are key features that organize cells of epithelial tissues and are known to regulate tissue growth. However, the mechanisms by which polarity cues and actomyosin cytoskeleton influence intracellular signaling cascades that control growth remain poorly understood. The Hippo pathway is an evolutionarily conserved regulator of tissue growth and is known to integrate inputs from both polarity and actomyosin components. An upstream activator of the Hippo pathway, Kibra, localizes into distinct pools at the junctional and medial regions of the apical cortex in epithelial cells, and medial accumulation was shown to promote Kibra activity. Here, we demonstrate that cortical Kibra distribution is controlled by a tug of war between apical polarity and actomyosin dynamics. We show that while the apical polarity network, in part via aPKC, tethers Kibra at the junctional cortex to silence its activity, medial actomyosin flows promote Kibra-mediated Hippo complex formation at the medial cortex, thereby activating the Hippo pathway. This study provides a mechanistic understanding of the relationship between the Hippo pathway, polarity, and actomyosin cytoskeleton and offers novel insights into how fundamental features of epithelial tissue architecture can serve as inputs into signaling cascades that control tissue growth, patterning, and morphogenesis.

cell biology↗

bioRxiv2023

Exploring the noncanonical translatome using massively integrated coexpression analysis

BackgroundRecent studies uncovered pervasive transcription and translation of thousands of noncanonical open reading frames (nORFs) outside of annotated genes. The contribution of nORFs to cellular phenotypes is difficult to infer using conventional approaches because nORFs tend to be short, of recent de novo origins, and lowly expressed. Here we develop a dedicated coexpression analysis framework that accounts for low expression to investigate the transcriptional regulation, evolution, and potential cellular roles of nORFs in Saccharomyces cerevisiae. ResultsOur results reveal that nORFs tend to be preferentially coexpressed with genes involved in cellular transport or homeostasis but rarely with genes involved in RNA processing. Mechanistically, we discover that young de novo nORFs located downstream of conserved genes tend to leverage their neighbors promoters through transcription readthrough, resulting in high coexpression and high expression levels. Transcriptional piggybacking also influences the coexpression profiles of young de novo nORFs located upstream of genes, but to a lesser extent and without detectable impact on expression levels. Transcriptional piggybacking influences, but does not determine, the transcription profiles of de novo nORFs emerging nearby genes. About 40% of nORFs are not strongly coexpressed with any gene but are transcriptionally regulated nonetheless and tend to form entirely new transcription modules. We offer a web browser interface (https://carvunislab.csb.pitt.edu/shiny/coexpression/) to efficiently query, visualize and download our coexpression inferences. ConclusionsOur results suggest that nORF transcription is highly regulated. Our coexpression dataset serves as an unprecedented resource for unraveling how nORFs integrate into cellular networks, contribute to cellular phenotypes, and evolve.

systems biology↗

bioRxiv2021

Mucoricin is a Ricin-Like Toxin that is Critical for the Pathogenesis of Mucormycosis

Fungi of the order Mucorales cause mucormycosis, a lethal infection with an incompletely understood pathogenesis. We now demonstrate that Mucorales fungi produce a toxin that plays a central role in virulence. Polyclonal antibodies against this toxin inhibit its ability to damage human cells in vitro, and prevent hypovolemic shock, organ necrosis, and death in mice with mucormycosis. RNAi inhibition of the toxin in Rhizopus delemar, compromises the ability of the fungus to damage host cells and attenuates virulence in mice. This 17 kDa toxin has structural and functional features of the plant toxin, ricin, including the ability to inhibit protein synthesis by its N-glycosylase activity, the existence of a motif that mediates vascular leak, and a lectin sequence. Antibodies against the toxin inhibit R. delemar- or toxin-mediated vascular permeability in vitro and cross-react with ricin. A monoclonal anti-ricin B chain antibody binds to the toxin and also inhibits its ability to cause vascular permeability. Therefore, we propose the name "mucoricin" for this toxin. Not only is mucoricin important in the pathogenesis of mucormycosis but our data suggest that a ricin- like toxin is produced by organisms beyond the plant and bacterial kingdoms. Importantly, mucoricin should be a promising therapeutic target.

microbiology↗

bioRxiv2021

Dynamic Detection and Reversal of Myocardial Ischemia Using an Artificially Intelligent Bioelectronic Medicine

SummaryMyocardial ischemia is spontaneous, usually asymptomatic, and contributes to fatal cardiovascular consequences. Importantly, biological neural networks cannot reliably detect and correct myocardial ischemia on their own. In this study, we demonstrate an artificially intelligent and responsive bioelectronic medicine, where an artificial neural network (ANN) supplements biological neural networks enabling reliable detection and correction of myocardial ischemia. ANNs were first trained to decode spontaneous cardiovascular stress and myocardial ischemia with an overall accuracy of [~]92%. ANN-controlled vagus nerve stimulation (VNS) reversed the major biomarkers of myocardial ischemia with no side effects. In contrast, open-loop VNS or ANN-controlled VNS following a caudal vagotomy essentially failed to reverse correlates of myocardial ischemia. Lastly, variants of ANNs were used to meet clinically relevant needs, including interpretable visualizations and unsupervised detection of emerging cardiovascular stress states. Overall, these results demonstrate that ANNs can supplement deficient biological neural networks via an artificially intelligent bioelectronic medicine system.

bioengineering↗

bioRxiv2020

Perceptual difficulty modulates the direction of information flow in familiar face recognition

Humans are fast and accurate when they recognize familiar faces. Previous neurophysiological studies have shown enhanced representations for the dichotomy of familiar vs. unfamiliar faces. As familiarity is a spectrum, however, any neural correlate should reflect graded representations for more vs. less familiar faces along the spectrum. By systematically varying familiarity across stimuli, we show a neural familiarity spectrum using electroencephalography. We then evaluated the spatiotemporal dynamics of familiar face recognition across the brain. Specifically, we developed a novel informational connectivity method to test whether peri-frontal brain areas contribute to familiar face recognition. Results showed that feed-forward flow dominates for the most familiar faces and top-down flow was only dominant when sensory evidence was insufficient to support face recognition. These results demonstrate that perceptual difficulty and the level of familiarity influence the neural representation of familiar faces and the degree to which peri-frontal neural networks contribute to familiar face recognition.

neuroscience↗

bioRxiv2020

Rho1 activation recapitulates early gastrulation events in the ventral, but not dorsal, epithelium of Drosophila embryos

Ventral furrow formation, the first step in Drosophila gastrulation, is a well-studied example of tissue morphogenesis. Rho1 is highly active in a subset of ventral cells and is required for this morphogenetic event. However, it is unclear whether spatially patterned Rho1 activity alone is sufficient to recapitulate all aspects of this morphogenetic event, including anisotropic apical constriction and coordinated cell movements. Here, using an optogenetic probe that rapidly and robustly activates Rho1 in Drosophila tissues, we show that Rho1 activity induces ectopic deformations in the dorsal and ventral epithelia of Drosophila embryos. These perturbations reveal substantial differences in how ventral and dorsal cells, both within and outside the zone of Rho1 activation, respond to spatially and temporally identical patterns of Rho1 activation. Our results demonstrate that an asymmetric zone of Rho1 activity is not sufficient to recapitulate ventral furrow formation and indicate that additional, ventral-specific factors contribute to the cell- and tissue-level behaviors that emerge during ventral furrow formation.

developmental biology↗

bioRxiv2019

Competition between kinesin-1 and myosin-V define Drosophila posterior determination

Local accumulation of oskar (osk) mRNA in the Drosophila oocyte determines the posterior pole of the future embryo. Two major cytoskeletal components, microtubules and actin filaments, together with a microtubule motor, kinesin-1, and an actin motor, myosin-V, are essential for osk mRNA posterior localization. In this study, we use Staufen, an RNA-binding protein that colocalizes with osk mRNA, as a proxy for posterior determination. We demonstrate that posterior localization of osk/Staufen is determined by competition between kinesin-1 and myosin-V. While kinesin-1 removes osk/Staufen from the cortex along microtubules, myosin-V anchors osk/Staufen at the cortex. Myosin-V wins over kinesin-1 at the posterior pole due to low microtubule density at this site, while kinesin-1 wins it at anterior and lateral positions because they have high density of cortically-anchored microtubules. As a result, posterior determinants are removed from the anterior and lateral cortex but retained at the posterior pole. Thus, posterior determination of Drosophila oocyte is defined by kinesin-myosin competition, whose outcome is primarily determined by cortical microtubule density.

cell biology↗

bioRxiv2019

Yellow strawberries and red bananas: The influence of object-colour knowledge on emerging object representations in the brain

The ability to rapidly and accurately recognise complex objects is a crucial function of the human visual system. To recognise an object, we need to bind incoming visual features such as colour and form together into cohesive neural representations and integrate these with our pre-existing knowledge about the world. For some objects, typical colour is a central feature for recognition; for example, a banana is typically yellow. Here, we applied multivariate pattern analysis on time-resolved neuroimaging (magnetoencephalography) data to examine how object-colour knowledge affects emerging object representations over time. Our results from 20 participants (11 female) show that the typicality of object-colour combinations influences object representations, although not at the initial stages of object and colour processing. We find evidence that colour decoding peaks later for atypical object-colour combinations in comparison to typical object-colour combinations, illustrating the interplay between processing incoming object features and stored object-knowledge. Taken together, these results provide new insights into the integration of incoming visual information with existing conceptual object knowledge. Significance StatementTo recognise objects, we have to be able to bind object features such as colour and shape into one coherent representation and compare it to stored object knowledge. The magnetoencephalography data presented here provide novel insights about the integration of incoming visual information with our knowledge about the world. Using colour as a model to understand the interaction between seeing and knowing, we show that there is a unique pattern of brain activity for congruently coloured objects (e.g., a yellow banana) relative to incongruently coloured objects (e.g., a red banana). This effect of object-colour knowledge only occurs after single object features are processed, demonstrating that conceptual knowledge is accessed relatively late in the visual processing hierarchy.

neuroscience↗

bioRxiv2018

Seeing versus Knowing: The Temporal Dynamics of Real and Implied Colour Processing in the Human Brain

Colour is a defining feature of many objects, playing a crucial role in our ability to rapidly recognise things in the world around us and make categorical distinctions. For example, colour is a useful cue when distinguishing lemons from limes or blackberries from raspberries. That means our representation of many objects includes key colour-related information. The question addressed here is whether the neural representation activated by knowing that something is red is the same as that activated when we actually see something red, particularly in regard to timing. We addressed this question using neural timeseries (magnetoencephalography, MEG) data to contrast real colour perception and implied object colour activation. We applied multivariate pattern analysis (MVPA) to analyse the brain activation patterns evoked by colour accessed via real colour perception and implied colour activation. Applying MVPA to MEG data allows us here to focus on the temporal dynamics of these processes. Male and female human participants (N=18) viewed isoluminant red and green shapes and grey-scale, luminance-matched pictures of fruits and vegetables that are red (e.g., tomato) or green (e.g., kiwifruit) in nature. We show that the brain activation pattern evoked by real colour perception is similar to implied colour activation, but that this pattern is instantiated at a later time. These results suggest that a common colour representation can be triggered by activating object representations from memory and perceiving colours.

neuroscience↗

bioRxiv2018

Decoding digits and dice with Magnetoencephalography: Evidence for a shared representation of magnitude

Numerical format describes the way magnitude is conveyed, for example as a digit ( 3) or Roman Numeral ( III). In the field of numerical cognition, there is an ongoing debate of whether magnitude representation is independent of numerical format. Here, we examine the time course of magnitude processing when using different symbolic formats. We presented participants with a series of digits and dice patterns corresponding to the magnitudes of 1 to 6 while performing a 1-back task on magnitude. Magnetoencephalography (MEG) offers an opportunity to record brain activity with high temporal resolution. Multivariate Pattern Analysis (MVPA) applied to MEG data allows us to draw conclusions about brain activation patterns underlying information processing over time. The results show that we can crossdecode magnitude when training the classifier on magnitude presented in one symbolic format and testing the classifier on the other symbolic format. This suggests similar representation of these numerical symbols. Additionally, results from a time-generalisation analysis show that digits were accessed slightly earlier than dice, demonstrating temporal asynchronies in their shared representation of magnitude. Together, our methods allow a distinction between format-specific signals and format-independent representations of magnitude showing evidence that there is a shared representation of magnitude accessed via different symbols.

neuroscience↗