VictorJuiz/thesis huggingface dataset:
Role of Rho small GTPases in the invasion of Lung Epithelial Cells by Legionella pneumophila
Keywords: Cdc42
invasion
Legionella pneumophila
lung epithelial cells
Rac1
RhoA

Legionella pneumophila is the main cause of Legionnaires' Disease, a fatal pneumonia. The filamentous form of Legionella (FLp) is capable of invading human lung epithelial cells through unique cell surface rearrangements. These unique structures curve around the bacteria, entrapping it at the host cell surface, favoring subsequent invasion. This requires cytoskeleton rearrangements mediated by bacterial activation of E-cadherin and β1-integrin receptors. We investigated the roles of the small GTPases Rac1, RhoA, and Cdc42 (actin regulators) in the attachment and internalization of FLp to lung epithelium. We found Rac1, Cdc42, RhoA, and their downstream effectors, are involved in attachment, but not in internalization of FLp. Internalization was instead dependent on a T4SS-delivered toxin. This indicates that bacterial attachment is dependent on host cell receptors activating downstream small GTPases, causing actin reorganization and bacterial entrapment, but internalization is dependent on a bacterial toxin that polymerizes actin independently of Rho small GTPases.
Coccolithophore Evolutionary Response to the Youngest Toba Eruption (75.0 ± 0.9 ka)
Keywords: Arabian Sea
Coccolithophores
Florisphaera profunda
Monsoons
Super eruptions
Toba

The impact of the recent super eruption, Toba, ~ 74 ka on the marine environment is unknown. For the first time it is compared to coccolithophore assemblage relative abundances, with samples taken from core SO130-289KL, located in an oxygen minimum zone in the northeast Arabian Sea. No long term evolutionary implications associated with temporally close biohorizons can be linked to the super eruption, however climatic changes associated with global cooling following the eruption have been identified indirectly through the relative abundance decrease of the species Florisphaera profunda. F. profunda relative abundance decreases are linked to an increase in primary productivity levels associated with a deepened mixed layer and are seen during the Northeast monsoon season. Northeast monsoon intensity is known to increase during cooler global periods and are here attributed to the lowered F. profunda relative abundances following the eruption.
Effect of Nuts on Markers of Cancer and Coronary Heart Disease Risk in Type 2 Diabetes: A Dose Response Study
Keywords: Cancer
Diabetes
Heart Disease
Monounsaturated Fat
Nuts
Oxidative Stress

Nuts have been shown to reduce coronary heart disease (CHD) risk and possibly cancer development. However, the mechanisms are not clear, and the small but consistent LDL-C reduction does not explain the 18-51% CHD risk reduction observed. Therefore, the effect of nuts was assessed on serum fatty acids, measures of oxidative stress, and prostate cancer (LNCaP) cell growth as part of a secondary analysis of a 12-week feeding trial (100 participants) in type 2 diabetes to explore possible mechanisms. Nuts increased serum oleic acid and monounsaturated fatty acids in the phospholipid fraction and this change related inversely to Framingham Risk Score. However, no associations were seen with markers of oxidative stress or in vitro LNCaP cell growth. It is concluded that intake of monounsaturated fat associated with the Mediterranean diet reduces CHD risk, but the beneficial effect of nuts on CHD and possible effects on cancer remain to be explained mechanistically.
Proteomic Analysis of Endothelial, Smooth Muscle, Myocytes and Fibroblasts Derived from Human Cardiac Tissue Identified Cell Type Specific Exprsession Signatures
Keywords: Cardiomyocyte
Endothelial Cell
Fibroblast
Heart
Mass Spectrometry
Smooth Muscle Cell

The heart is composed of multiple constituent cell types; the primary cells being fibroblasts, cardiomyocytes, endothelial and smooth muscle cells. Here, I employed membrane isolation procedures to attain membrane enriched and depleted proteins from in vitro human fibroblasts, cardiomyocytes, coronary endothelial and coronary smooth muscle cells, obtained from human cardiac biopsy tissues. Shotgun proteomics identified a total of 2320 fibroblast, 2310 cardiomyocyte, 2209 smooth muscle and 2247 endothelial cell proteins. Statistical analysis identified 367 fibroblast-enriched, 97 cardiomyocyte-enriched, 340 endothelial-enriched and 52 smooth muscle cell-enriched proteins. I further ranked these proteins by staining in the Human Protein Atlas database. Finally, comparison of these proteins with a mouse model of dilated cardiomyopathy demonstrated that many single cell type enriched proteins were also differentially expressed in disease. Two fibroblast enriched proteins, GRB2 and PRDX1, were examined in a myocardial infarction mouse model, and demonstrated increased immunofluorescence in the fibroblast enriched, infarct- and adjacent border-zones.
Automatic Classification of Children's Antisocial and Prosocial Lies Using Facial Expressions
Keywords: Antisocial lies
Deception
Facial Expressions
Lying
Prosocial lies

Research on the nonverbal facial expressions of children during lie-telling is extremely limited. As such, it is unknown whether the nonverbal behaviours of children telling an antisocial lie are the same or different when they tell a prosocial lie. The current study is the first to concurrently examine the facial movements of children during antisocial and prosocial lying. Through the use of the Computer Recognition Toolbox (Littlewort et al., 2011), an automated computer vision program using the Facial Action Coding System (Ekman Friesen, 1978), children's nonverbal behaviours were shown to be significantly different in terms of 8 different facial actions. Furthermore, linear support vector machine (SVM) analysis was successful in classifying children's lies with an average accuracy of 72.68%, significantly above chance levels. Implications and limitations are discussed.
Pragmatics, Phonological Processing, and Reading: Language Abilities in 'Unaffected' School-Aged Siblings of Children with Autism Spectrum Disorder
Keywords: Autism Spectrum Disorder
High-risk siblings
Language development
Phonological processing
Pragmatics
Reading

Siblings of children with Autism Spectrum Disorder (ASD) who do not have ASD outcomes are more likely than their peers to experience delays in language acquisition as preschoolers. However, less is known about how these siblings are faring when they are school-aged. We examined language-related abilities of 17 non-ASD siblings, aged 8-11. On average, the non-ASD siblings performed more poorly than the normative sample on measures of phonological memory and phonological awareness. In contrast, word-level reading was intact. No impairments relative to norms were found on a direct child assessment and parent-report measure of pragmatic language; however, recommendations for further research in this area are made. The two pragmatic measures demonstrated weak convergent validity; questions were raised regarding the influence of having an older child with ASD and the effects on parents' frame of reference. Comparing two direct language assessments, this sample performed more poorly in pragmatics than structural language.
Effective Mitigation of Shock Loads of Embedded Electronics in Smart Ammunitions by Polymeric Encapsulation
Keywords: Bilayer potting
Embedded electronics
FEM
Polymeric encapsulation
Shock attenuation system

Short duration impulse and long duration shock loads can lead to the failure of embedded electronics typically used in smart ammunitions. The objective of this work is to develop the means to protect the printed circuit board (PCB) using polymeric encapsulating materials. Three aspects of the work were considered using finite element (FE) simulations. The first is concerned with the development of a micromechanical modelling scheme of a multilayered PCB to determine its equivalent elastic properties. The second is concerned with the determination of the mechanical integrity of the embedded electronics subjected to short duration impulse. The third is concerned with the dynamic behavior of the PCB subjected to long duration shock loads. The effectiveness of different encapsulation designs to attenuate the shock loads are examined. Our results reveal the remarkable effectiveness of a novel bilayer potting approach over the commonly adopted single potting attenuation strategy.
Okapi (Oka), a Novel FERM Domain Protein Essential for Drosophila Oogenesis
Keywords: Crumbs
Drosophila
Epithelia
FERM
Oogenesis
Ovary

FERM proteins are a class of important adaptors in animal tissues. They are ubiquitous in the cytocortex, linking the plasma membrane to cytoskeletal components, and are involved in structural, transport, and signaling functions. FERM proteins interact with numerous binding partners, including the transmembrane protein Crumbs (Crb), a key regulator of cell polarity in epithelial cells. In
Implementing a Manualized Group Intervention for Bereaved Siblings: An Analysis of Feasibility and Barriers
Keywords: Bereavement
Cancer
Children
Intervention
Siblings

The current study, conducted in two segments, assessed the feasibility of implementing a manualized support group for siblings who had experienced the death of a brother or sister from cancer. Part 1 was carried out with a convenience sample of 10 children, aged 6 - 14 years, who attended the program. With respect to acceptability, retention rates, and treatment fidelity, positive outcomes were obtained. Results of standardized questionnaires completed by parents indicated significant improvements in overall, emotional, and social quality of life, and trend-level reductions in problem behaviours and distress symptoms. Outcomes of siblings' self-report questionnaires reflected borderline decreases in problem behaviours. Part 2 of the investigation revealed significant recruitment barriers that impeded enrolment when rigorous sampling procedures were utilized. A qualitative analysis of phone recruitment interviews with parents yielded important themes explaining families' participation declines, including impediments to enrolment, communication with surviving children, and coping with grief.
Dissecting the Role of Nucleosome Assembly Protein-1 (NAP-1) in Small RNA-mediated Chromatin Modulation in Caenorhabditis elegans
Keywords: C. elegans
Chromatin modulation
CSR-1 Small RNA Pathway
Nucleosome Assembly Protein-1
RNA interference

Small RNA-mediated gene-silencing pathways are critical regulators of gene expression throughout development. Some of the least understood roles for these small RNA pathways are in chromatin modulation and genome organization. Chromatin-modifying factors have recently been implicated as playing key roles in small RNA-mediated pathways. This study reveals a new role for the highly conserved histone chaperone, Nucleosome Assembly Protein-1 (NAP-1), in the CSR-1 (Chromosome Segregation and RNAi-deficient) small RNA pathway in the nematode,
The Role of Transforming Growth Factor Beta Signalling in Regulating the Sphingolipid Rheostat in Intrauterine Growth Restriction
Keywords: Acid Ceramidase
Intrauterine Growth Restriction
Placenta
Sphingolipids
Sphingosine Kinase
Transforming Growth Factor Betas

Disruptions of sphingolipid metabolism contribute to the onset of several human pathologies. Herein, I examined sphingolipid metabolism in intrauterine growth restriction (IUGR), a pregnancy-related disorder that is commonly due to placental insufficiency. Lipid mass spectrometry revealed increased levels of pro-death sphingosine (SPH) in IUGR placentae relative to pre-term control placentae. This was accompanied by increased acid ceramidase (AC) expression and reduced sphingosine kinase 1 (SPHK1) expression and activity. Exposure of human choriocarinoma JEG3 cells to TGF1 and 3 recapitulated the sphingolipid regulatory enzyme expression profile observed in IUGR. Pharmacological inhibition of activin receptor-like kinase 5 (ALK5) in human villous explants and JEG3 cells reversed the TGF1 and 3 stimulatory effect on AC expression; whereas exposure of JEG3 cells to ALK1 inhibitor, Dorsomorphin, further suppressed SPHK1 expression. Of clinical significance, ALK5 expression and Smad2 activation is increased in IUGR placentae. Hence, altered TGF signalling may contribute to SPH accumulation in IUGR.
Using Intraoperative Audio to Predict the Presence of Surgical Errors in Operating Room Black Box Recordings
Keywords: Safety
Surgery

Recording and review of surgeries can increase safety by allowing researchers to identify errors and analyze their root causes. Watching a surgical can be time consuming. There is a need to make this process more efficient. The research aims to use intraoperative audio to create a machine learning algorithm that can identify times in a surgical recording where an error has been committed. Audio can create effective features due to subtleties in communication, known to change under times of stress. An alternating decision tree is generated using 19 features and a training set of 31 surgeries. The algorithm was tested on 21 surgeries, yielding a sensitivity of 80.8% and overall accuracy of 41.1%. By changing algorithm parameters, an accuracy of 68% was also achieved. The algorithm demonstrates the feasibility of a machine learning algorithm for surgical error prediction. The algorithm should be tested with raters to test its helpfulness.
Investigating the Effects of Temporal Duration Structure on Recognition Memory
Keywords: Duration
Hippocampus
Memory
Rhythm
Temporal Structure
Timing

In order to function optimally within our environment, we continuously extract temporal patterns from our experiences and formulate expectations that facilitate adaptive behavior. Given that our memories are embedded within spatiotemporal contexts, an intriguing possibility is that mnemonic processes are sensitive to the temporal structure of events. To test this hypothesis, we manipulated interval duration at encoding in a series of behavioral experiments. Our findings revealed enhanced recognition memory (d’) for stimuli that were explicitly encoded within a temporally structured versus unstructured framework. Encoding information within a temporally structured framework was also vital in reducing the negative effects of proactive interference and was linked to a greater ability to recollect contextual details associated with the study event. Rhythmic temporal structure also enhanced recognition memory for incidentally encoded information. Collectively, these results support the possibility that we possess a greater capacity to learn and subsequently remember temporally structured information.
Beads: Symbols of Indigenous Cultural Resilience and Value
Keywords: Beads
Beadwork
Cultural Value
First Nations
Indigenous
Resilience

My intention for this paper is to explore the cultural relevance of the influence that beads have had on Indigenous people in North America. By exploring the inherent cultural values that beads possess in Indigenous culture, I hope to illuminate how beads have come to represent Indigenous resiliency after the effects of colonialism and the residential school system. I aim to illustrate how important this art form has been in the past and will continue to be in the future. Beads should not be portrayed as simple trinkets that Indigenous people have sought to trade in the past, instead, they are integral elements to the greater Indigenous society both prior to and concurrent with European contact. Beads are playing an integral role in repairing cultural ties and spiritual beliefs to Indigenous artists. Beadwork has been, and will continue to be significant in representing Indigenous resiliency as well as highlighting the distinct cultural value of Indigenous peoples.
The Role of Toll-like Receptor 4 in the Pathogenesis of Experimental Subarachnoid Hemorrhage
Keywords: Delayed Cerebral Ischemia
Inflammation
Subarachnoid hemorrhage
Toll-like receptor 4

Subarachnoid hemorrhage (SAH) accounts for 5-7% of strokes worldwide and is associated with high mortality and morbidity. In addition to brain damage from the initial hemorrhagic events, secondary complications are observed in patients as well as animal models. Inflammation is being increasingly implicated in the presentation of secondary complications of SAH. This study was designed to investigate the contributions of Toll-like receptor 4 (TLR4) to secondary pathologies after SAH in mice. SAH was induced in TLR4- deficient animals, animals treated with a pharmacological inhibitor of TLR4 (TAK-242) and their respective controls; the degree of behavioral disruption, histological vasospasm, neuronal damage, reactive gliosis and demyelination was assessed. Disruption of TLR4 signaling was found to improve behavioral scores, and reduce neuronal damage and reactive gliosis, but did not affect histological vasospasm and demyelination after SAH. These data suggests that inhibition of TLR4 signaling could be a promising new therapeutic strategy for SAH patients
Regulation of Cisplatin-induced Programmed Cell Death In Vivo
Keywords: Apoptosis
Caspase-3
Cisplatin
DNA damage
Necroptosis
PCD

Cisplatin [ cis-PtCl2 NH3)2 ] is a widely utilized chemotherapeutic agent. Its proposed mechanism of action involves DNA-platinum adduct formation that triggers DNA damage responses, cell cycle arrest and p53-mediated cell death. In vivo treatment of murine embryos with cisplatin caused widespread cellular injury consistent with induction of apoptosis. Caspase-3 knockout embryos exhibit complete inhibition of cell death 24 hours following cisplatin treatment in a variety of tissues. Examination at later time points revealed an alternate form of programmed cell death in the absence of caspase-3 exhibiting features of necroptosis, suggesting coordinated regulation of these disparate pathways is critical to control PCD signaling in vivo. These results demonstrate caspase-3 is necessary and sufficient to regulate cisplatin- mediated PCD in numerous embryonic tissues and could hold implications towards the maintenance of normal and malignant cells in a variety of solid tissues in the presence of cisplatin.
Organic Anion Transporter Blockade to Improve Beta Cell Function in Diabetes
Keywords: Beta Cell
CMPF
Diabetes
OAT3
Organic Anion Transporter
Probenecid

The furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is elevated in Type 2 Diabetes. CMPF delivery to diabetic levels in mice causes glucose intolerance, impairing glucose-stimulated insulin secretion (GSIS). CMPF enters the β cell through Organic Anion Transporters (OATs). Here, we investigate whether OAT blockade represents a therapeutic target for diabetes prevention, blocking CMPF action on the β cell. First, we block CMPF transport in vivo using pharmacological OAT inhibition. CMPF impairs glucose tolerance, and islets isolated from CMPF-treated mice showed impaired GSIS, while co-treatment with pan-OAT inhibitor probenecid rescues glucose tolerance and islet function. Next, we developed Oat3 knockout (Oat3KO) mice which were also protected against the negative effects of CMPF in vivo, and remarkably, Oat3KO mice were more glucose tolerant than Wildtype controls. These novel studies demonstrate the requirement of OAT transport for CMPF to alter β cell function, and highlight potential for OAT inhibition to improve diabetes.
The Spatiotemporal Accumulation of Myeloid Lineage Cells Is Mapping Out Fibrosis in the Liver after Acute and Chronic Injury
Keywords: fibrosis
Kupffer
liver
macrophage
myeloid
serotonin

Liver fibrosis is known to become problematic after persistent injury. However, little is known about its response after an acute insult. Myeloid lineage cells, specifically, macrophages have been implicated in the promotion and resolution of inflammation and fibrosis. We investigated the role of myeloid lineage cells in the liver after acute injury. Our data show that thermal injury in mice induces fibrosis predominantly around portal venules whereas myeloid cells are enriched throughout the liver. The fibrosis peaks 1-2 weeks post injury and resolves by week 3. Depletion of myeloid cells led to lower fibrosis. Microarray analysis revealed an inflammatory signature and modulation of components of the serotonin (5-HT) pathway in myeloid cells. Antagonizing the 5HT2A/2C receptor decreased fibrosis in thermally injured mice, likely through promoting an anti-fibrotic phenotype in macrophages. Treating mice with a 5HT2A/2C receptor antagonist promotes an anti-fibrotic effect, through modulating the phenotype of macrophages.
Phenotypic and Transcriptional Consequences of Shwachman-Bodian-Diamond Syndrome (SBDS) Deficiency during Hematopoietic Development
Keywords: definitive hematopoietic differentiation
human induced pluripotent stem cells (hiPSCs)
RNA-seq
Shwachman-Diamond Syndrome (SDS)

Shwachman-Diamond syndrome (SDS) is a genetic disorder characterized by exocrine pancreatic and hematological dysfunction. As hematological complications are major concerns for mortality with limited treatment options, the mechanisms underlying the SDS hematopoietic defects need to be elucidated to advance the development of effective treatments. We hypothesized that the onset of SDS hematopoietic defects occurred in a certain hematopoietic developmental stage. In this study, definitive hematopoietic differentiation of SDS compared to normal hiPSCs showed reduced CFU-GM and BFU-E formation, increased venous and endothelial potential, and reduced viability in embryoid bodies containing hemogenic and vascular endothelia. Over-representation analysis of dysregulated genes in SDS compared to normal hiPSCs showed enrichment for pathways including histones, glycosaminoglycan metabolism, and WNT signaling. This study offers insight into the onset of SDS hematopoietic defects and potentially disrupted pathways in SDS hiPSCs, and provides patient hematopoietic cell resources for drug screening and the potential to improve patient outcome.
Using the Unpredictable Chronic Mild Stress Model in Mice to Understand the Involvement of DNA/RNA Oxidation in Major Depressive Disorder
Keywords: Behavioral assays
Chronic Stress
Cortical neurons
DNA/RNA Oxidation
Immunohistochemistry
Major Depressive Disorder

Major Depressive Disorder (MDD) is a debilitating illness, associated with chronic development and a highly heterogeneous etiology. Despite unclear mechanisms, chronic stress is implicated in its development and/or progression. Previous studies in patients with MDD have reported chronic stress and elevated levels of oxidative stress, including increased DNA/RNA oxidation in post-mortem analyses in brain regions associated with cognitive and emotional processing. Using a preclinical model of chronic stress, this thesis investigates: 1) whether unpredictable chronic mild stress (UCMS) in mice induces neuronal DNA/RNA oxidation in the frontal cortex (FC) and basolateral amygdala (BLA), and 2) correlations between levels of neuronal DNA/RNA oxidation with depressive-like behaviors. We predicted that mice subjected to UCMS, relative to mice not subjected to the stress would present higher levels of neuronal DNA/RNA oxidation, and this would be associated with anxiety/depressive-like behaviors. This work provides a translational perspective for the involvement of DNA/RNA oxidation in MDD.