Design and Validation of a Novel Patterned Microfluidic Culture Platform for hiPSC-CM Maturation

Adult cardiomyocytes (CMs) are among the most challenging cells to culture in vitro, given their poor adherence to plastic culture wells and poor maturation outside the native extracellular matrix (Narkar et al., 2022). Human induced pluripotent stem cell-derived CMs (hiPSC-CMs) offer a viable alternative to study heart development and disease progression. While not comparable to adult CMs in their maturity (Narkar et al., 2022), they mimic the clinical phenotypes of heart failure and are more feasible to culture. Nevertheless, hiPSC-CMs require specialized culture conditions that cannot be achieved with 2D static culturing, which fail to replicate native tissue environments (X. Huang et al., 2022). Instead, microfluidic culturing may enhance the maturation profiles of hiPSC-CMs, given the ability to tune media flow rates to match cell shear stress values. Additionally, microfluidic culture may be enhanced through substrate micropatterning, which directs specific cell attachment toward the desired mature cell profiles. While previous research has outlined the impact of microfluidic media flow and micropatterning on hiPSC-CM maturation, little work has analyzed how dynamic media flow influences cells inside micropatterns, or how biomimetic-driven micropatterns can support maturation in combination with dynamic media flow. This work hypothesizes that dynamic flow combined with biomimetic-inspired micropatterns will improve hiPSC-CM maturation. Functional validation will include an analysis of cell morphology and gene expression compared to static culture. Through the intersection of advanced microfabrication and biological testing, this work will provide key insight into the impact of biomimetic culture on hiPSC-CM development, potentially establishing a new paradigm for cell culture

WATERMAN FUND ESSAY WINNER: Old Friends in the Alpine: Field Scientists on Vermont\u27s Highest Peak

In this winning essay of the annual contest sponsored by the Waterman Fund, a young scientist meets Bill Howland, who studied the same vegetation in 1991, at their study site high on Vermont’s Mount Mansfield

Skyline Sketches: Survival of the Timid

A mother and daughter retreat in bad weather, showing that timidity saves lives

Neural representations of valence and arousal in Kung Fury

Emotions are a core component of human experience and behavior, yet after decades of scientific research, it is still difficult to uncover the neural substrates related to emotion. Recent advances in neuroscience have examined how we interpret emotional signals from static images of facial expressions, but less work has sought to understand how the brain constructs our emotional experiences (Chen, 2020). To investigate such idiosyncratic experiences across participants, we employed naturalistic stimuli to model the real-time, reliable changes in activity that correspond to changes in emotional experience. A primary element of emotional experience is core affect, defined as the mental representation of bodily changes, which when experienced as feelings (or with conscious awareness), constitute a degree of hedonic valence and arousal (Lindquist et al., 2012). Previous studies in affective neuroscience have discovered neural representations of valence and arousal with findings linked to amygdala, insula, thalamus, orbitofrontal cortex, cingulate cortex, and subsections of the prefrontal cortex, but no previous study has utilized the movie Kung Fury in uncovering rich and reliable brain responses. Do neural representations of emotions generalize to unseen movies? Our results suggest that valence elicits robust activity in visual cortices, the intraparietal sulcus, and the cuneus, while arousal elicits activity in the precuneus, posterior cingulate cortex, and intraparietal sulcus, both subsets of regions implicated in the saliency and default mode network respectively. Our findings suggest that our brain utilizes a constellation of brain regions to construct our everyday emotional experiences

INVESTIGATING THE HUMAN FACE PROCESSING NETWORK: INSIGHTS FROM ACQUIRED PROSOPAGNOSIA AND HYPERFAMILIARITY FOR FACES

Human faces provide essential social cues that we interpret rapidly, allowing us to recognize identities, interpret emotions, and gauge familiarity. This thesis explores face processing disruptions in four case studies, each offering new insights into the brain’s face recognition mechanisms. Chapter one presents Annie, a 28-year-old woman who acquired prosopagnosia (face blindness) following COVID-19. After recovering from the severe symptoms of the infection, Annie experienced significant difficulty in recognizing familiar faces and navigating familiar environments. Testing confirmed her impairment in face recognition but showed her preserved cognitive and basic visual processing abilities. Annie was still able to recognize objects and scenes, pointing to a selective impact on face processing. A survey of individuals with long COVID revealed deficits with visual processing, highlighting a need for further exploration of long COVID’s cognitive and perceptual effects. Chapter two thoroughly explores face processing abilities in two participants, Alma-Jean and Rose, who acquired prosopagnosia due to extensive damage to their right temporal lobes. Both participants exhibited severe impairments in face identity recognition while retaining the ability to recognize facial expressions, suggesting a dissociation between identity and expression processing. Alma-Jean also displayed intact facial sex recognition. Our findings provide evidence for separate processing pathways for facial identity and expression, as well as facial identity and sex. Chapter three describes Nell who developed hyperfamiliarity for faces after a severe migraine. Nell experiences false feelings of familiarity with unfamiliar faces, names, and some object categories while retaining accuracy in recognizing actually familiar faces, names, and objects. Her prolonged response times on face tests suggest disruptions in familiarity mechanisms that interfere with processing efficiency. Together, these cases reveal how distinct disruptions in face processing can stem from varied etiologies and increase our understanding of mechanisms underlying the complex neural systems that support social cognition and recognition