VictorJuiz/thesis huggingface dataset:
Feeding in the Blood-gorging Bug Rhodnius prolixus: The Role of Sulfakinin Signaling

Sulfakinins (SKs) are neuropeptides that have been shown to function as feeding satiety factors in insects. We confirmed the presence of two SKs (Rhopr-SK-1 and Rhopr-SK-2) in Rhodnius prolixus. Reverse transcriptase quantitative PCR (RT-qPCR) demonstrated that the Rhopr-SK transcript is mainly expressed in the central nervous system (CNS) in unfed fifth-instar R. prolixus. Fluorescent in situ hybridization (FISH) showed transcript expression only in neurons in the brain. Immunohistochemical staining of SK-like peptides was observed in the same neurons in the brain and in processes extending throughout the CNS, as well as over the posterior midgut and anterior hindgut. Rhopr-SK-1 induced contractions of the hindgut in a dose-dependent manner, but had no effect on heartbeat frequency. Injection of Rhopr-SK-1 significantly decreased the overall size of the blood meal consumed, suggesting SK’s role as a satiety factor in R. prolixus. Two seven-transmembrane Rhopr-SK G protein-coupled receptors (GPCRs), Rhopr-SKR-1 and Rhopr-SKR-2, were cloned and characterized. RT-qPCR of the two Rhopr-SKR transcripts revealed that the target tissues for Rhopr-SK-1 and Rhopr-SK-2 are located in the CNS, heart, gut, salivary glands, Malpighian tubules, fat body, as well as, male and female reproductive systems. Rhopr-SK-1 inhibits contractions of the oviduct and ejaculatory duct in adult R. prolixus, whilst having no effect on contractions of the bursa. A functional receptor assay that utilized Human Embryonic Kidney (HEK)-293 cells stably expressing a modified cyclic nucleotide-gated (CNG) channel (HEK293/CNG) characterized the two Rhopr-SK receptors. Modified HEK293/CNG assays showed that the PLC/IP3 pathway, and not the cAMP pathway, is solely initiated upon the activation of either Rhopr-SK receptor. Nonsulfated Rhopr-SK-1 was not able to activate either Rhopr-SK receptor. Both Rhopr-SKRs were exclusively activated via Rhopr-SK-1 and Rhopr-SK-2. The importance of the SK signaling pathway in the modulation of feeding was demonstrated by the knockdown of the transcripts for Rhopr-SKs and Rhopr-SKRs, which led to an increase in the overall intake of blood during feeding.

Keywords: Chagas Disease
Feeding
Molecular
Receptor Assay
Satiety
Sulfakinin
Advisor: Lange, Angela B
Orchard, Ian
Insights into Glomerular Cell Biology in Health and Disease

The integrity of the kidney glomerular filtration barrier relies on the health of its components, which include podocytes forming the final layer of the filtration barrier, and endothelial cells lining the glomerular capillaries. Both cell types are important for kidney development and normal kidney homeostasis, and their injury is implicated in a range of kidney diseases, notably diabetic kidney disease, the most common cause of kidney failure. Here, I used podocytes to explore novel autophagic regulation and paracrine communication mechanisms. By examining the phenotypic effects of JAK2 absence in podocytes, I identified a role for JAK2 in regulating podocyte autophagy completion, specifically through regulating the expression of a master regulator of lysosomal gene expression known as transcription factor TFEB. Since JAK2 has garnered attention as a promising therapeutic target for the treatment of diabetic kidney disease, I explored the effects of systemic JAK2 inhibition, and JAK2 deletion from podocytes in experimental models of diabetes. Pharmacological inhibition of JAK2 prevented progression of albuminuria and reduced urine excretion of the chemokine CCL2. Likewise, podocyte-specific JAK2 knockout resulted in a marked reduction in urine excretion of CCL2, which was also enriched in culture media conditioned by podocytes exposed to high glucose. Podocyte secreted CCL2 signaling via its receptor CCR2 induced glomerular endothelial activation, characterized by VCAM-1 upregulation, through a pathway regulated by p38 MAPK, MSK1/2, and phosphorylation of histone protein H3 on serine residue 10 (phospho-histone H3Ser10). Moreover, increased phospho-histone H3Ser10 levels were observed in the kidneys of diabetic endothelial nitric oxide synthase knockout mice and in the glomeruli of humans with diabetic kidney disease. Collectively, these findings: i) identified the homeostatic actions of JAK2 in podocyte autophagy, also raising the possibility that therapeutically modulating TFEB activity may improve podocyte health in glomerular disease; ii) highlight the anti-inflammatory effects of JAK2 inhibition and podocyte-specific JAK2 deletion in diabetes; and iii) demonstrate the influence that histone protein phosphorylation may have on gene activation in diabetic kidney disease.

Advisor: Advani, Andrew
Musical Bridges––Crossing the Divide of Where Fear Meets Music: How Autoethnography Contributes to an Evolving Cultural Identity Through Multiple Musical Worlds

This research explores the presence of rich, multi-layered political, socio-economic Levantine identities within three musical narratives which challenge and inform views about the relationship between politics and music. The dissertation draws on auto-ethnography and narrative research as a pedagogy for cultivating empathy, courage, and social justice in music education settings. The purpose of the study is to explore the function of music in diverse socio-political global contexts as a means of understanding ourselves in local contexts. Additionally, the stories demonstrate how music has played a role in reconciling multiple identities and connecting people of disparate backgrounds and experiences, and how music has played a role in disconnecting people (including myself) through the socio-political forces that at times may have been too strong. Through narrative analysis, personal reflection, and musical inquiry of three stories, I investigate the standard narratives of the positive role of music, the political acts of forming solidarity and moments of resistance in musical contexts, and the political interactions in a Canadian context that question music’s capacity for inclusivity within a pluralist society. This study joins a vibrant conversation in music education about the inextricable link between politics and music, as well as discussions about the need to develop empathy and courage in presenting, performing, and educating in, through and about music from diverse cultural contexts. I argue that music is political and can be difficult to negotiate in the rehearsal room, but that difficult elements such as empathy and courage can bring people together and change the narrative. Empathizing by acknowledging the humanity of others raised to think differently, as well as courage to overcome fear, can stir to action, embracing true inclusivity in a Canadian context.

Advisor: Dolloff, Lori
Al-'Asabiyya in Context: Choice and Historical Continuity in Al-Muqaddima of Ibn Khaldūn

The purpose of this dissertation is to understand the meaning of the term Al-'Aṣabiyya in Al-Muqaddima of Ibn Khaldūn in context. In Al-Muqaddima, he constructs a method for the scientific study of history, the subject matter of which is human association. Human association is necessary for human beings, but by its nature, it requires political authority and economic organization. By order of existence, political authority is acquired only by al-‘aṣabiyya. Therefore, al-‘aṣabiyya is an “essential condition” in the world, and it can be perceived by the senses and the intellect. It is a power that “secures” political victory, and as such, it becomes the source that enables protection and the preservation of human life, the development of urban culture through the management of economic cooperation, and social harmony. In this study, I use a linguistic-contextual method to show that the form of al-'aṣabiyya that secures political authority is not natural, irrational, or aggressive. Rather, it is the fruit of the labour of unity and agreement between individuals and groups (‘aṣabiyyāt). It is a power that individuals manufacture intentionally either by way of descent, alliance, or allegiance to gain political authority. They are ahl al-‘aṣabiyya who achieve their goal “in the ordinary way,” that is, by overcoming others by their power of unity, and praiseworthy qualities. This study also shows that there is no organic connection between al-‘aṣabiyya and the form or quality of rulership. In fact, Ibn Khaldūn’s rejection of hereditary rule, condemnation of tyranny, and argument against the necessity of prophecy show that rational politics suffices for the management of human association. His statement on the science of physics, the use of the term “matter” in an economic sense to mean money, and the connection between injustice and economic policies show that the decline of the polity is not natural but a matter of choice between moderation and excessiveness. The detailed exposition of these various elements shows that the pattern of history in Al-Muqaddima is not cyclical. Instead, history is a narrative about cultural transmission, political and historical continuity, the expansion of one power, and the contraction of another.

Keywords: Al-'Aṣabiyya
Al-Muqaddima
Economic policies and Injustice
Historical and Political Continuity
Ibn Khaldūn
Linguistic-Contextual Method of Interpretation
Advisor: Williams, Melissa S.
Dying as a Process – A Temporal Look at the Ordered Events that Occur at an Organellar Level in Saccharomyces cerevisiae

Cell death is a dynamic, complex process. In this thesis, I describe the development of an automated imaging pipeline for detecting the changes in subcellular morphology that cells undergo through time as they are dying, known as a terminal phenotype. I captured terminal phenotypes over a 24-hour time course, for 352 temperature sensitive mutants of essential genes each expressing a panel of diagnostic GFP markers, representing 21 major subcellular compartments and structures. The pipeline used an unsupervised One-Class support vector machine outlier detection method to calculate single-cell penetrance, the percentage of cells for a given mutant population that look different from wild-type. Penetrance was calculated for each mutant and consisted of 9 timepoints for 21 GFP markers, for a total of 189 measured variables per terminal phenotype profile. A logistic function was fitted to the time-course data to extract the time at which half of the maximum penetrance occurred, which served as a marker for first-occurrence of a phenotypic change for a given GFP marker. Clustering of half-max times revealed grouping of terminal phenotypes according to biological process, and ordering of half-max times for each functional class revealed 9 divergent terminal phenotype trajectories that differ in compartments affected, and timing.

Keywords: cell death
confocal fluorescence microscopy
high-content screening
high-throughput microscopy
terminal phenotype
yeast
Advisor: Andrews, Brenda
Boone, Charles
Reconstructing the Evolution of Xylose Fermentation in Scheffersomyces Stipitis

Lignocellulose is a renewable feedstock that can be fermented to biofuels and biochemicals, but its use is limited by several techno-economic challenges, including xylose fermentation. Scheffersomyces stipitis has been identified as an efficient xylose fermenter, but does not ferment well in industrial conditions. The scientific community has been engineering Saccharomyces cerevisiae, the preferred yeast for industrial biotechnology, to ferment xylose to ethanol with the xylose reductase (XR)-xylitol dehydrogenase (XDH) genes from Sch. stipitis for 30 years; however, recombinant Sac. cerevisiae's titres, rates, and yields for ethanol from xylose lags Sch. stipitis. This performance gap may be due to aspects of Sac. cerevisiae's metabolism that hinders xylose fermentation, aspects of Sch. stipitis' metabolism that enables xylose fermentation, or a combination of both. The focus of this thesis is to improve our understanding of budding yeast metabolism beyond Sac. cerevisiae, and ultimately reverse engineer how Sch. stipitis' metabolism has evolved to ferment xylose to ethanol efficiently with improved genome annotations and metabolic modelling. To obtain higher-quality genome annotations, ortholog groups in 33 yeasts and fungi spanning 600 million years in Dikarya were predicted using OrthoMCL. Over 500 enzyme families were curated with phylogenetic reconstruction to resolve inconsistencies. These ortholog assignments are more accurate than existing ortholog databases, and span diverse yeasts. Next, the gains and losses of metabolic genes were reviewed to identify important and reoccurring events in the evolution of metabolism in budding yeasts. Duplications were found to play an important role in the evolution of metabolism, including changes in enzyme cofactor preference and localization. The curated pan-genome and functional annotations were used to reconstruct genome-scale metabolic networks of the 33 species; the reconstructions have more genomic and metabolic coverage than those made with previous methods. Finally, the Sch. stipitis metabolic network was used to simulate xylose fermentation. NADH kinase and NADP phosphatase (NADPase), an orphan enzyme in eukaryotes, were found to be critical to xylose fermentation in these metabolic flux simulations. Pho3.2p was the sole NADPase candidate showing expression during xylose fermentation; its activity was confirmed in vitro. Xylose fermentation evolved in the Scheffersomyces-Spathaspora clade following genes duplications for XR and an acid phosphatase. This thesis provides a foundation for unravelling how metabolism has evolved in the yeast pan-genome.

Keywords: biotechnology
evolution
flux balance analysis
metabolism
xylose
yeast
Advisor: Mahadevan, Radhakrishnan
Microtruss Design for Strength and Energy Absorption

The question of information flow within an inverse design problem is tackled with focus on thermodynamically irreversible phenomena, i.e. strength and energy absorption. Microtruss materials are used as a platform for the study as their individual building units, i.e. struts, possess uniform geometry, known properties, and can be tuned to achieve a desired level of performance; a much simpler task than attempting to design bulk microstructure. Elements of compositing are utilized to alter the performance of the microtrusses, namely nanocrystalline nickel electroplating and carburizing. In terms of strength, both compositing approaches produced microtrusses with superior performance. Additionally, the strength property was optimized using classical optimization approaches since the strength is determined by the onset of the first failure mechanism to be activated; a task that can be completed using conventional analytical models, such as the Shanley-Engesser buckling equation. The problem becomes more complicated for energy absorption since the onset and progression of the deformation and damage need to be readily describable analytically, which is not possible due to the distortion and deformation of the collapsing struts, i.e. geometrical and material non-linearities need to be considered. A primarily experimental approach is therefore followed to first identify the active failure mechanisms and their influence on the energy absorption property. The carburized microtrusses were modified with post-carburizing heat treatments such as tempering and decarburizing to enhance their post-buckling behavior and energy absorption capability. The nickel-coated microtrusses were plated using various plating conditions to control the hardness, thickness, composition, and adhesion of the coatings. With the proper plating parameters, nickel-phosphorous coatings introduced pre-buckling damage that nearly eliminated the post-peak softening in conventionally buckled microtrusses and resulted in an enhanced energy absorption response placing these hybrid microtrusses ahead with the top commonly reported energy absorbers in literature, such as foams and honeycombs.

Keywords: Carburizing
Electroplating
Energy Absorption
Microtruss
Optimization
Strength
Advisor: Hibbard, Glenn D
School choice in deindustrialized cities: A mixed method comparison of charter and public schools on safety and parental involvement in Detroit, Michigan

Charter schools have rapidly expanded in deindustrialized American cities over the past twenty-five years where they have been touted as a solution to pressing school safety problems, low parent participation, and educational underperformance. Yet, research on charter schools has focused on student achievement, largely overlooking school safety and parental involvement. This thesis compares charter and public schools on perceived school safety and parental involvement in Detroit, Michigan in three studies in the sandwich format. With its large charter school sector, Detroit is a highly relevant setting, embodying the social and economic challenges of deindustrialized cities that have undergone charter school reforms. In the first study, charter schools exhibited statistically higher perceived school safety, net of controls for neighborhood, school, and demographic characteristics. However, this relationship was largely diminished after accounting for parent-related characteristics. In the second study, non-profit managed charter schools elicited statistically higher parental involvement than for-profit managed charter and public schools while public schools reported greater parent decision-making, net of controls. The third study examined the mechanisms underlying the statistical results by conducting site observations (n = 40), interviews with parents (n = 20) and teachers (n = 20), and numerous informal interviews with different groups of stakeholders. Findings indicated that although charter school strategies were partly attributable to school performance, distinguishing attributes of school choosers conferred a self-selection advantage to charter schools. Overall, charter schools in deindustrialized cities appear to offer a modest improvement on perceived school safety and parental involvement, but they are not accessed by the most disadvantaged students. Extending access to information and transportation may enable greater access, but policy remedies beyond school choice may be needed to address challenges in neighborhood public schools where extraordinarily disadvantaged students are likely to remain enrolled. Additionally, relationship-building and a parent presence in school may be strategies for improving perceived school safety. This thesis furthers existing scholarship by demonstrating the following: the importance of safety to school choice processes in deindustrialized cities; distinguishing features of school choosers among demographically similar families; and differences in safety and parental involvement strategies by school type.

Keywords: Charter schools
Detroit
Parental involvement
School choice
School safety
Advisor: Davies, Scott
Umanesimo volgare nellâ Italia del Cinquecento: la vita e le opere di Lattanzio Benucci (1521-1598)

In the sixteenth century the Republic of Siena played an important role in the development of the Renaissance. The contribution Sienese writers made to Italian literature and history is still to be written, but it is impressive to see how many men, and women were part of it. One such case is represented by the scholar and writer Lattanzio Benucci, born near Siena in 1521. A cultured member of the nobility, Benucci studied at the local university and then served his city as ambassador to Florence, where he entered the salon of the poet and courtesan Tullia d’Aragona. Subsequently, Benucci moved to Rome where he was a courtier first of Cardinal Antonio Trivulzio and then of Cardinal Alfonso Carafa. In 1565 Benucci returned to Siena. Duke Cosimo de’ Medici employed him in Florence, where he died in 1598. The details of his biography are analyzed in the first chapter of this thesis. Over the centuries, some of Benucci’s literary works were lost. What has survived, however, is very revealing of his learning and letters: at least three poetry collections (see the second chapter), together with some others transcribed after his death (analyzed in the third chapter), a Dialogo de la lontananza (“Dialogue on Distance”), and a commentary (Osservazioni) on Dante’s Divine Comedy (both examined in the fourth chapter). All these works are still unpublished: in the second volume of this thesis, most of them have been transcribed in five appendices with philological apparatuses. This dissertation aims not only to increase our knowledge of a productive and well-connected intellectual of the sixteenth century, but also at offering a much more nuanced understanding of the complexity of late Renaissance Humanism. In so doing, it helps to shift the traditional focus away from much-examined Florence, Rome, and Venice, in order to place it on another crucially important city, Siena, and thereby widen our views on Renaissance Italy.

Keywords: Humanism
Italian Studies
Poetry
Renaissance
Advisor: Eisenbichler, Konrad
Pharmacological Manipulation of Long-term Potentiation and Cortical Inhibition from the Dorsolateral Prefrontal Cortex, a Model to Understand Cognitive Deficits of Schizophrenia

Several studies have assessed the pharmacological modulation of cortical inhibition (CI) and long-term potentiation (LTP) using transcranial magnetic stimulation (TMS) from the motor cortex and recorded these effects through surface electromyography (EMG). However, recording CI and LTP from the dorsolateral prefrontal cortex (DLPFC), a cortical region that is more closely associated with the pathophysiology of severe psychiatric disorders including schizophrenia were previously not done. Objectives: This study, therefore, was designed to investigate whether CI, indexed by long interval cortical inhibition (LICI), and LTP measured using paired associative stimulation (PAS) could be modulated and measured from the DLPFC in healthy participants through the use of TMS combined with electroencephalography ( EEG ) using a placebo-controlled, randomized double-blinded crossover study design. Methods: 12 healthy participants were given a single oral dose of baclofen, a GABAB agonist, dextromethorphan, a NMDA antagonist, L-DOPA, a dopamine precursor, rivastigmine, an acetylcholine esterase inhibitor for each arm of the study. Results: LICI was enhanced and suppressed by increasing GABAergic tone and cholinergic tone, respectively. LTP was increased by enhancing cholinergic tone and dopaminergic tone and abolished when NMDA receptors were blocked. Conclusion: These results are important and have the potential for therapeutic application in manipulating neural plasticity and CI in the DLPFC to treat a variety of conditions, including depression, Parkinson's disease, and schizophrenia.

Keywords: brain stimulation
lon-term potentiation
neuroimaging
schizophrenia
Advisor: Daskalakis, Zafiris Z
Rajji, Tarek K