Biology subjects

Clancy, K.

Publications and source records attributed to Clancy, K..

5 recordsLinked to original sources

bioRxiv2021

The role of extracellular matrix biomolecules on endometrial epithelial cell attachment and cytokeratin 18 expression on gelatin hydrogels

The endometrium undergoes profound changes in tissue architecture and composition, both during the menstrual cycle as well as in the context of pregnancy. Dynamic remodeling processes of the endometrial extracellular matrix (ECM) are a major element of endometrial homeostasis, including changes across the menstrual cycle. A critical element of this tissue microenvironment is the endometrial basement membrane, a specialized layer of proteins that separates the endometrial epithelium from the underlying endometrial ECM. Bioengineering models of the endometrial microenvironment that present an appropriate endometrial ECM and basement membrane may provide an improved environment to study endometrial epithelial cell (EEC) function. Here, we exploit a tiered approach using two-dimensional high throughput microarrays and three-dimensional gelatin hydrogels to define patterns of EEC attachment and cytokeratin 18 (CK18) expression in response to combinations of endometrial basement membrane proteins. We identify combinations (collagen IV + tenascin C; collagen I + collagen III; hyaluronic acid + tenascin C; collagen V; collagen V + hyaluronic acid; collagen III; collagen I) that facilitate increased EEC attachment, increased CK18 intensity, or both. We also identify significant EEC mediated remodeling of the GelMA matrix environment via analysis of nascent protein deposition. Together, we report efforts to tailor the localization of basement membrane-associated proteins and proteoglycans in order to investigate tissue engineered models of the endometrial microenvironment.

bioengineering↗

bioRxiv2019

Impaired early visual categorization of fear in social anxiety

Social anxiety is associated with biased social perception, especially of ambiguous cues. While aberrations in high-level processes, including cognitive appraisal and interpretation of social signals, have been implicated in such biases, contributions of early, low-level stimulus processing remain unclear. Categorical perception is known to be an efficient process to resolve signal ambiguity, and categorical emotion perception can swiftly classify sensory input, \"tagging\" biologically important stimuli at early stages of processing to facilitate ecological response. However, early threat categorization could be disrupted by exaggerated threat processing in anxiety, resulting in biased perception of ambiguous signals. We tested this hypothesis among individuals with low and high trait social anxiety (LSA and HSA), who performed a 2-alternative-forced-choice (fear or neutral) task on facial expressions parametrically varied along a neutral-fear continuum. Clear divergence between the groups emerged in the profiles of reaction time (RT) and early visual response along the neutral-fear continuum. The LSA group exhibited a RT profile characteristic of categorical perception with drastically increased RT from neutral to intermediate (boundary) fear intensities, contrasting monotonous, non-significant RT changes in the HSA group. Neurometric analysis along the continuum identified an early fear-neutral categorization operation (arising in the P1, an early visual event-related potential/ERP at 100 ms) in the LSA (but not HSA) group. Absent group differences in higher-level cognitive operations (identified by later ERPs), current findings highlight a dispositional cognitive vulnerability in early visual categorization of social threat, which could precipitate further cognitive aberrations and, eventually, the onset of social anxiety disorder.

neuroscience↗

bioRxiv2019

A Gelatin Hydrogel to Study Endometrial Angiogenesis and Trophoblast Invasion

As the lining of the uterus and site of blastocyst implantation, the endometrium is a dynamic tissue that undergoes rapid cycles of growth, breakdown, and remodeling each menstrual cycle. Significant vascular remodeling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodeling enhance blood flow to the embryo ahead of placentation. Insight into endometrial vascular remodeling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective for this study was to develop a tissue engineering platform to investigate processes of endometrial angiogenesis and trophoblast invasion in a 3D environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue. Further, the hydrogel supports the formation of stable endometrial endothelial cell networks and attachment of a stratified endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment, and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.

bioengineering↗

bioRxiv2018

Locomotion-dependent remapping of distributed cortical networks

The interactions between areas of the neocortex are fluid and state-dependent, but how individual neurons couple to cortex-wide network dynamics remains poorly understood. We correlated the spiking of individual neurons in primary visual (V1) and retrosplenial (RSP) cortex to activity across dorsal cortex, recorded simultaneously by calcium imaging. Individual neurons were correlated with distinct and reproducible patterns of activity across the cortical surface; while some fired predominantly with their local area, others coupled to activity in subsets of distal areas. The extent of distal coupling was predicted by how strongly neurons correlated with the local network. Changes in brain state triggered by locomotion re-structured how neurons couple to cortical activity patterns: running strengthened affiliations of V1 neurons with visual areas, while strengthening distal affiliations of RSP neurons with sensory cortices. Thus, individual neurons within a cortical area can independently engage in different cortical networks depending on the animal's behavioral state.

neuroscience↗

bioRxiv2017

Human olfactory cortex contributes to emotional and perceptual aspects of aversive associative learning and memory

The role of the sensory cortex, beyond the amygdala, has been increasingly recognized in animal associative learning and memory. Here, we examined olfactory cortical plasticity in human olfactory associative learning and memory, while elucidating related changes in emotional and perceptual responses. Psychophysical and neurometric analyses were conducted across an odor-morphing continuum, with the two extreme levels differentially conditioned with aversive and neutral stimuli. Conditioned odors acquired distinct emotional values, tracked by ensemble response patterns in the orbitofrontal (high-level) olfactory cortex. Also observed were enhanced perceptual discrimination and divergent ensemble neuronal response patterns in the anterior and posterior piriform (low-to-intermediate-level) olfactory cortices. Whereas emotional-learning-related changes, both behavioral and neural, maintained 8 days later, perceptual-learning-related changes, also both behavioral and neural, recovered by then, highlighting the human aptitude of forming persistent emotional memory and related sensory cortical plasticity in contrast to transient perceptual alterations of sensory stimuli associated with mild aversive experiences.

neuroscience↗