McGill Science Undergraduate Research Journal

Description and Exploration of Mean-Gauss Surfaces

2023-03-21T22:27:57-04:00

In this paper we explore solving the prescribed mean curvature equation for surfaces meeting a new relation given by (H_S) = λ(K_S), where H_S and K_S are the mean and Gaussian curvatures, respectively. We prove several existence theorems for various families of surfaces and state a conjecture for surfaces of revolution. To conclude, we state a weak existence theorem, and a strong conjecture concerning possible solutions. The intention is that by using differential geometry tools which would have likely been seen at the undergraduate level, the paper and its results are more accessible. My hope is that these new theorems find applications in the classification of surfaces in the future, or at the very least serves as an interesting curiosity.

Rho GTPase regulatory proteins contribute to podocyte morphology and function

2023-03-22T12:33:03-04:00

Podocytes are a critical cellular component of the glomerular filtration barrier, whose strict permselectivity prohibits the passage of large proteins and charged species into the urine. Phenotypic variability or injury of these highly specialized cells can lead to proteinuria and has been linked with altered activity of Rho GTPases, which are strongly associated with the actin cytoskeleton. Notable regulators of these intracellular molecular switches are called guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and guanine nucleotide dissociation inhibitors (GDIs). In this study, the roles of several GEFs in podocyte morphology and activity were investigated, including ECT2, ARHGEF2, ARHGEF26, and ARHGEF40. Results from RhoA and Rac1 G-LISA Activation Assays indicated that the absence of ARHGEF40 impairs epidermal growth factor (EGF)-stimulated RhoA and Rac1 activation, whereas knockout of ARHGEF2 and ARHGEF26 may selectively diminish RhoA activation. Furthermore, filopodia formation was hindered for the ARHGEF40 knockout. There are a number of additional investigations underway to understand Rho GTPase regulatory proteins, including the elimination of new sets of GEFs and GAPs in vivo. It is hopeful that these studies can provide insights into potential novel therapeutic strategies for proteinuria.

Comparison of Small Molecule-Responsive RNA Aptazymes for Applications in Gene Control

2023-03-21T17:20:17-04:00

Modelling how genes act in both space and time is critical to understand animal development, which can potentially drive intervention in gene expression. Gene regulation is examined using many techniques; however, challenges such as cell delivery, invasiveness, toxicity, and efficacy limit our ability to fully probe gene networks. Recent advances have led to the development of tunable, titratable, and reversible tools that can be genetically-encoded into animal model systems to modulate genes with temporal and spatial control. This study compares such tools, testing several aptazyme-based switches that can be expressed inside cells and controlled through the addition of non-toxic small molecules. Three switches responsive to different small molecules were compared for switching activity in mammalian cells. The most efficient switches in terms of activity gauged by their modulation of gene expression were then further assayed. Finally, the specificity of the hypoxanthine switch was tested based on chemical structure and classification. The comparisons revealed the importance of both timing and small molecule concentrations on switch activity, while the specificity testing demonstrated switch activity inside the cell correlated to the aptamer binding properties that were measured biochemically. This work demonstrates the suitability of aptazyme-based switches for application in diverse genetic environments, and in controlling and studying gene networks in animals.

Uncovering the Regulators of CRISPR-Cas Immunity

2023-03-22T14:30:03-04:00

The clustered regularly interspaced short palindromic repeats (CRISPR) system and the CRISPR-associated proteins (Cas) make up an adaptive immune mechanism used by many bacteria and archaea to protect themselves from invading genetic material. Despite the immense evolutionary advantage of the CRISPR-Cas system, it must be meticulously regulated as it has the potential to target endogenous genes and damage the host organism. Identifying the main regulators involved in this process and how they are influenced by distinct conditions are of great clinical interest, since this prokaryotic defense system can be exploited for genome editing and therapy development. This review aims to elucidate the regulation of the CRISPR system in bacterial communities—upon quorum sensing and alginate production in biofilms—and in stressed conditions—upon antibiotic treatment or induction of the Rcs response. Despite the intrinsic contradictions of the results gathered in this review, growth rate is identified as a potential unifying regulator of CRISPR immunity. Overall, the regulation of the CRISPR-Cas system is shown to be multi-dimensional and cross-sectional, to greatly vary amongst lineages, and to be highly sensitive to conditional changes.

The Role of Iron in Epidermal Healing and Infection

2023-03-20T10:44:28-04:00

In recent years, the field of iron studies has expanded into sub-domains that investigate the regulation of this metal in various tissues including the heart, mucosal surfaces, tumours, and the skin. Iron homeostasis in the skin and the role of other non-hepatic cells in the regulation of iron are currently incompletely understood. This paper summarizes the role of iron in wound healing, highlights the importance of maintaining iron concentrations within an intermediate range to avoid toxicity or defects; and integrates the antimicrobial role, interactions, and regulation of various cell types. Notably, the autoregulation of hepcidin secretion by keratinocytes and recruited myeloid cells is described. Additionally, the potential therapeutic role of iron chelators in infection control and their mechanisms of action are explored. This paper aims to elucidate the relevance of local iron control in epidermal infections. Although some of the molecular details underlying this condition remain unclear, published data suggest that iron-regulating therapies are a promising treatment for the eradication of skin infections due to their wound-healing and immune-modulating potential.

At Once Friends and Foes

2023-03-20T16:54:40-04:00

Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) disease. In chronic infections such as TB, consistent pro-inflammatory signalling promotes the generation of myeloid-derived suppressor cells (MDSCs). MDSCs are innate immune cells that are further divided into polymorphonuclear (PMN-MDSC) and monocytic (M-MDSC) subtypes on the basis of their morphology. These cells exert immunosuppressive effects on other immune cell types, thereby protecting the integrity of the lung tissue from damage caused by dysregulated Mtb. However, this comes at the expense of containing the Mtb infection. MDSCs’ unique double-edged role makes them an attractive target for host-directed TB therapeutics. This review aims to summarize current knowledge on the role of MDSCs in TB.

Bacterial Interactions Affecting Chemotherapy Effectiveness

2023-03-21T00:20:04-04:00

Chemotherapy resistance is a recurring challenge in cancer treatment, with specific bacteria impairing the effectiveness of certain chemotherapies. This study reviews three bacteria and their impact on chemotherapy drugs: Mycoplasma and gemcitabine, Fusobacterium nucleatum and oxaliplatin, bacterial β-glucuronase and irinotecan. Bacteria can have wide-ranging effects on cancer treatment; for instance, they may affect drug metabolism, alter toxin conversion, and encourage cancer growth. Whilst the presence of these bacteria was found to have a detrimental effect on the efficacy of chemotherapy treatment, we also consider wider interactions and interdependencies of the microbiota with drug treatments. Some cancer therapies depend on the delicate balance of the microbiome whilst simultaneously disrupting it by their very nature, particularly when antibiotics are introduced. Further research into the complex relationship between bacteria and the tumour micro-environment is needed. Treatments that focus on the immune-oncology microbiome axis or that explore genetic predisposition through the use of biomarkers could also support a more personalised approach.

A Review of Pumice Raft Formation Environments, Saturation, and Dispersal Mechanisms

2023-03-20T17:32:32-04:00

Pumice rafting events are a common result of volcanic eruptions occurring near or beneath bodies of water. Such events are frequently associated with hazards such as tsunamis, and drift pumice is known to cause local economic disruptions, damage ships, impede naval traffic, devastate marine populations, and distribute potentially invasive species over long distances. However, our current understanding of the mechanisms that drive the formation and dispersal of drift pumice are extremely limited. This article reviews historical and characteristic pumice raft-forming eruptions, how interactions with water factor into macro- and micro-scale controls on pumice clast formation and dispersal, and current methods for detection and analysis to better track and mitigate hazards associated with explosive volcanic eruptions and pumice rafts.

An Enduring Controversial Story in the Human Brain

2023-03-22T14:12:57-04:00

Adult hippocampal neurogenesis (AHN) is a well-studied phenomenon that involves the derivation of new neurons from neural progenitor cells in the dentate gyrus region of the hippocampus, an area responsible for cognitive functions such as learning and memory storage. Moreover, the hippocampus is known to be implicated in neurological conditions such as Alzheimer's disease. Although AHN has been extensively observed in animal models for twenty years, its existence and persistence in humans have been widely debated in academia, heavily based on post-mortem immunohistochemical markers. Using the search engines PubMed and Google Scholar for “Adult Human Neurogenesis,” 143 articles that were most relevant to the history of AHN discovery, detection in rodents, immunohistochemical studies on post-mortem human sections, and therapeutic development targeting AHN were reviewed. This review article highlights the current understanding of AHN in rodents and humans, its implications in neurodegenerative diseases and therapeutics, and the inconsistencies and methodological variabilities encountered in studying AHN in humans. Furthermore, the correlation between AHN and diseases such as mood disorders and Alzheimer's disease is still not well established, with conflicting findings reported. Standardization of transcriptomic methodologies and increased availability of post-mortem human brain samples are crucial in advancing AHN research. This review article attempts to discover the fascinating and controversial world of adult human neurogenesis and its potential implications in treating neurological disorders. Apart from the discussion on AHN existence, tackling devastating diseases with this supplemental knowledge can lead to therapeutic advancements which greatly rely on understanding not only the presence of AHN but the mechanisms mediating its availability.