Pursuing Natural Unity, Consciousness Included

An ontological exploration of consciousness and how it is related to the body and other aspects of physical reality. Framed by David Chalmers\u27 conception of The Hard Problem , we begin from a physicalist perspective to discuss the problem of mental causation, which is the inquiry of how the mind communicates and interacts with the body. From here we examine the employment of identity reduction to functionalize and therefore physically explain mentality. We find that reductionist methods, the backbone of scientific investigation, do not work to explain conscious experience, because conscious experience is not quantifiable--it is qualitative. Thus we are left with looking for alternatives to our physicalist world-view in order to explain consciousness\u27s place in reality. Perhaps a major conceptual revolution of how we see and understand the world is on the horizon that will allow us to finally explain consciousness

Neural correlates of abnormal sensory discrimination in laryngeal dystonia

AbstractAberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder

A Pansychistic, Photographic View on Nature and the Body

Through an emphasis on the formal similarities in black and white photographs of human bodies and rocks, I attempt to shift my viewer’s existential conception of the “self” by communicating a pansychistic and ecofeminist message which inspires humility in one’s place in the world and justification for the necessity of compassion for nature

Race Information Influences Cognitive Processes in Brain and Behavior in Black and White Individuals

Race is a prevailing social category in the United States, and physical cues that indicate race are often used as a heuristic to distinguish in- and out-group members. The salience of race can influence our cognitive processes and contribute to racially-biased behavior. The present dissertation examines the contexts in which race information biases behavior and investigates the underlying cognitive and neurobiological processes that contribute to racially-biased behavior. Furthermore, the present dissertation studies illustrate the importance of implementing diversity in participant samples and experimental stimuli in psychological research. Chapter 1 reviews the importance of race as a social group in the United States, how it can uniquely impact cognitive processes, and highlights gaps in the literature due limited representation in experimental paradigms. Chapter 2 examines how task-irrelevant race information impacts cognitive control and illustrates how representative samples can nuance our understanding of cognitive and neurobiological processes underlying biased behavior. Chapter 3 builds upon the previous chapter by investigating the effects of perceived threat on impulse control to task-irrelevant race information and the representation of race information in the brain. Chapter 4 leverages a large open-access dataset to demonstrate the importance of diverse racial representation in experimental samples and stimuli by demonstrating the effects of race information on a series of cognitive processes in youth. Together, these studies examine the contexts in which race information influences cognition and elucidates the neurobiological processes that contribute to racially-biased behavior. Lastly, Chapter 5 highlights the implications of the current work and discusses the opportunity and responsibility researchers have to improve future psychological research work by implementing diverse and representative experimental designs

RNA Phase Separation in Cancer: Investigating HSATII RNA folding and function

As the study of genome regulation is moving to understand the essential functions performed by long non-coding RNAs (lncRNAs), once written off as “junk”, and biophysical studies are revealing the role of phase-separated condensates in nuclear organization, Human Satellite II (HSATII) RNAs present an advantageous opportunity to synthesize these complementary approaches. HSATII DNA, found on the heterochromatic pericentromeres of many human chromosomes, is transcriptionally repressed in normal cells, but misregulation of these genomic regions in a variety of cancer cell lines allows for their aberrant transcription. These highly repetitive HSATII RNAs aggregate into large focal accumulations immediately adjacent to their sites of transcription and bind to gene expression regulatory proteins such as methyl-CpG binding protein 2, MeCP2. Here, I present evidence that HSATII RNAs possess folded secondary structures which allow them to self-assemble into spherical droplets via liquid-liquid phase separation in vitro. Further, I show how these structures can be disrupted in vivo, providing a platform for testing key hypotheses regarding HSATII RNA droplet structure and their ability to sequester nuclear proteins such as MeCP2. Future work on HSATII RNA folding and their ability to form multivalent RNA-RNA, RNA-protein interactions in vivo will build upon a growing understanding of lncRNAs’ regulatory capacity and their role as organizers of liquid-like nuclear compartments

Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic – Neutral Hydrophilic Block Polymers

Polyelectrolyte complex micelles (PCMs, core-shell nanoparticles formed by complexation of a polyelectrolyte with a polyelectrolyte-hydrophilic neutral block polymer) offer an attractive solution to the critical problem of delivering therapeutic nucleic acids, but few structure-property studies have been carried out to date. We present data comparing oligonucleotide PCMs formed with poly(vinylbenzyl trimethylammonium) as the cationic block to those using poly(lysine), which is more commonly used. Despite its higher charge density, increased hydrophobicity, and permanent charge, pVBTMA appears to complex DNA more weakly than does poly(lysine). Using small angle X-ray scattering and electron microscopy, we find that, at physiological ionic strength, PCMs formed from both cationic blocks exhibit very similar structure-property relationships, with PCM radius determined by the cationic block size and shape controlled by the hybridization state of the oligonucleotides. These observations narrow the design space for optimizing therapeutic PCMs and provide new insights into the rich polymer physics of polyelectrolyte self-assembly. <br /

RNA-Protein Phase Separation In Cancer: Investigating Human Satellite II RNA Structure And Function

Human Satellite II, a tandemly repeated stretch of DNA found near the centromeres of most human chromosomes, is not transcribed into RNA in normal human cells, but is expressed in many human cancer cell lines and tissues. HSATII transcripts accumulate in the nucleus adjacent to their sites of transcription and recruit nuclear regulatory proteins within these large nuclear foci. Recent evidence suggests that RNA and proteins within the nuclear environment can phase separate into liquid-like droplets, creating abberant structures, some of which are known to contribute to pathological effects. Here, we present evidence that HSATII RNA folds on itself to form defined secondary structures, which could enable HSATII RNA to participate in a variety of RNA-RNA or RNA-protein interactions. Indeed, we show that HSATII RNA phase separates into liquid-like droplets, a process that is dependent on the size and sequence of the individual transcripts. A dependence on length suggests that HSATII RNA phase separation requires either a certain complexity of secondary structure or minimum number of contacts between single molecules. We hypothesize that HSATII RNA droplets differentially solubilize specific proteins via RNA-protein interactions, which could explain the observed sequestration of genomic regulatory proteins to nuclear HSATII RNA accumulations. Phase separation offers a powerful lens through which to begin to understand how misregulation of transcription, via the creation of liquid-like droplets, can disrupt regulatory processes, whose slight alterations can tip the balance in favor of further misregulation

Neural correlates of dystonic tremor: a multimodal study of voice tremor in spasmodic dysphonia

Tremor, affecting a dystonic body part, is a frequent feature of adult-onset dystonia. However, our understanding of dystonic tremor pathophysiology remains ambiguous as its interplay with the main co-occurring disorder, dystonia, is largely unknown. We used a combination of functional MRI, voxel-based morphometry and diffusion-weighted imaging to investigate similar and distinct patterns of brain functional and structural alterations in patients with dystonic tremor of voice (DTv) and isolated spasmodic dysphonia (SD). We found that, compared to controls, SD patients with and without DTv showed similarly increased activation in the sensorimotor cortex, inferior frontal (IFG) and superior temporal gyri, putamen and ventral thalamus, as well as deficient activation in the inferior parietal cortex and middle frontal gyrus (MFG). Common structural alterations were observed in the IFG and putamen, which were further coupled with functional abnormalities in both patient groups. Abnormal activation in left putamen was correlated with SD onset; SD/DTv onset was associated with right putaminal volumetric changes. DTv severity established a significant relationship with abnormal volume of the left IFG. Direct patient group comparisons showed that SD/DTv patients had additional abnormalities in MFG and cerebellar function and white matter integrity in the posterior limb of the internal capsule. Our findings suggest that dystonia and dystonic tremor, at least in the case of SD and SD/DTv, are heterogeneous disorders at different ends of the same pathophysiological spectrum, with each disorder carrying a characteristic neural signature, which may potentially help development of differential markers for these two conditions