McGill Science Undergraduate Research Journal

Antimicrobial Resistance Mechanisms of Gram-Positive and Gram-Negative Bacteria

2024-03-26T23:55:30-04:00

The discovery of antibiotics has long helped humans in the battle against bacteria. However, the misuse of antibiotics in industries and medical systems has unintentionally provided an ideal environment for bacteria to develop resistance mechanisms through mutations and gene transfer, resulting in the emergence of antimicrobial-resistant bacteria. This has proven to be an urgent and pressing issue in the global healthcare system, resulting in increased mortality. Therefore, increasing resources are invested to study their different resistance mechanisms and develop corresponding novel drugs and treatment methods. This review briefly introduces several key resistance mechanisms with examples from both Gram-negative and Gram-positive bacteria, the current and novel methods for treating multiple drug-resistant bacteria as well as the potential actions that could be done to improve the situation.

Endocrine Resistance in Breast Cancer: The Role of mTOR Signaling in Mediating Resistance to Selective Estrogen Receptor Modulators

2024-01-21T16:01:30-05:00

Selective estrogen receptor modulators (SERMs) have been widely prescribed and effective as a first-line endocrine therapy to treat ER+ breast cancer. Tamoxifen, the most used SERM in the treatment of breast cancer, has been shown to be effectively anti-proliferative in breast tissue and has made a tremendous contribution to reducing breast cancer mortality. Vast experimental evidence from seven sources supports tamoxifen’s ability in repressing the expression of estrogen-responsive genes involved in cancer growth. The binding of tamoxifen to the estrogen receptor prevents the recruitment of coactivators to the complex and instead promotes the recruitment of corepressors and histone deacetylases, thus inhibiting transcriptional activation of target genes. However, the issue of endocrine resistance remains a predominant problem with this therapy. Sources have found that endocrine resistance can arise due to dysregulations in the mTOR signaling pathway. Experiments have revealed some hope regarding a mechanism by which we can re-sensitize the breast cancer cells to the therapy, notably by knocking down YAP/TAZ or PSAT1 in the mTOR pathway. Despite this discovery, endocrine resistance prevails due to irregularities in additional pathways. Therefore, subsequent research is crucial to identify more targets that, when knocked down, enable re-sensitization of resistant cells, restoring full therapeutic ability of SERMs in afflicted women.

The Use of Leishmania-Derived Extracellular Vesicles as a Vaccine Platform Against Emerging Viral Diseases

2024-01-09T09:52:18-05:00

Extracellular vesicles (EVs) are small membrane-bound “vehicles” responsible for transporting biological materials from source cells to target cells. EVs are thus indirectly capable of inducing changes in the physiological state and behavior of target cells once their contents are successfully released or received. Both prokaryotic and eukaryotic species utilize EVs for a variety of purposes. For example, Leishmania, a protozoan parasite, has demonstrated the ability to secrete immunomodulatory EVs. Various studies have shown that it is not these EVs in themselves, but rather the contents of these EVs that are directly involved in the parasite’s colonization and replication inside host cells. Although using Leishmania as an expression system for recombinant proteins has been explored (investigations have yielded successful and promising results), the use of Leishmania-derived EVs is a burgeoning field of research. In fact, considering extant research on EV-based vaccines, substantial potential lies in exploiting Leishmania-derived EVs as a novel vaccine platform. Hence, this study aims to discuss the immunomodulatory capabilities of Leishmania-derived EVs and their potential application in vaccine development. Lastly, in piecing together the nature of Leishmania-derived EVs and the general therapeutic potential of engineered EVs, it is further hypothesized that Leishmania may be an effective expression system for EVs that harbour desired viral antigens as a part of more efficient vaccine designs.

An Optimization of Experimental Conditions to Characterize Perineuronal Nets in the Human Cerebellum

2024-01-16T12:05:04-05:00

During childhood and adolescence, the brain is highly responsive to external stimuli compared to adulthood. Perineuronal nets (PNNs), play a crucial role during this period by reducing neuroplasticity. These mesh-like structures protect and fortify neural connections between cells. Child abuse includes physical, emotional, and sexual abuse and/or neglect1. It is consistently associated with negative mental and physical health outcomes, underscoring the importance of identifying risk and resilience factors for effective prevention of such outcomes. Our laboratory focuses on understanding the cellular and molecular neuroanatomy of major depression and the lasting impact of child abuse (CA) on the brain. However, the impact of CA on PNNs remains relatively unexplored. How does CA influence the brain, potentially contributing to negative outcomes in the future? Samples from post-mortem human brain cerebellum were dissected and then used to perform RNAscope experiments to label glutamatergic, GABAergic, and parvalbumin-positive cells, following a brief IF protocol using Wisteria Floribunda Lectin (WFL) to visualize PNNs. The RNAscope protocol was successfully optimized by the addition of normal donkey serum (NDS), manipulation of incubation time, and WFL concentration. PVALB+ mRNA expression was positively identified in Purkinje cells, molecular layer interneurons, and deep cerebellar nucleus (DCN) neurons. SLC17A7+ mRNA expression was evident in granule cells and excitatory projection DCN neurons. GAD1+ mRNA expression was detected in Purkinje cells and inhibitory DCN neurons. These results provide an experimental protocol for future studies investigating the role of PNNs in the human cerebellum. We propose that CA alters the recruitment of PNNs, influencing circuitry and potentially increasing susceptibility to various mental illnesses, including major depressive disorder (MDD). MDD, also called clinical depression, causes a persistent feeling of sadness and loss of interest. This study aims to optimize fluorescent in situ hybridization (FISH, RNAscope) and immunofluorescence (IF) markers for the localization and phenotyping of PNN-enwrapped neurons in the human cerebellum. This article describes problems we encountered when running experiments and ways to optimize them. As this work is preliminary, it will help develop future protocols for exploring the effects of depression on PNNs and the phenotype of the cells they encircle. Comparing depressed individuals with and without a history of CA with neurologically and psychiatrically healthy controls will allow us to determine whether a history of CA impacts the distribution and density of PNNs.

Orthopedics in Space Travel: Developing Procedures to Evaluate the Safety of Implants Amidst the Rise of Commercial Space Tourism

2024-01-13T18:21:43-05:00

With the rise of commercial space tourism, the barrier of entry into space lowers. Therefore, passengers with more complex medical conditions are predicted to enter space. This report aims to initiate the development of procedures assessing the safety of space travel for individuals with orthopedic implants. In preparation for the 2023 sounding rocket launch by McGill Rocket Team, the Payload subteam developed a bone model, a human model, a finite element analysis model, and a testing model for determining the safety of orthopedic implants under the harsh conditions of spaceflight. Measuring the dynamic forces of the MRT's Portho's rocket in flight yielded vibrations in the 300-2750 Hz range, which is valuable for creating better models of the loading conditions on orthopedic implants in silico. Three point bending testing revealed high precision but low accuracy in measuring the mechanical strength of the models. Ultimately, the study recommends adjusting the human, bone, and testing models to prevent oversimplification. Further, future work should analyze bone screw interfaces on a microscopic level to detect small changes in implant stresses. By implementing these changes, procedures can accurately describe the safety of spaceflight for those with orthopedic implants.

Properties of Accretion Discs Around Black Holes Through Modelling

2024-01-21T16:59:23-05:00

We examine accretion discs within the context of Einstein's general relativity. We use the metrics corresponding to the four black hole solutions proposed by Einstein, with the Shakura-Sunyaev model of the disc. Starting from the definition of the "no-hair theorem" that a black hole only stores information about three main parameters — mass, angular momentum and charge — we tested the impact of varying these parameters, emphasising the relations between them. Moreover, the research we present here captures and illustrates two pivotal aspects predicted by general relativity: the circular photon ring and the frame-dragging effects of the ergosphere. Our research delves into emissivity profiles, exploring both the well-established lamp post model and the beamed point source model. We reproduced the results from the literature and noted the inconsistencies between the works and our results while also providing an alternative source supporting our results. Altogether, this work presents a comprehensive exploration of accretion disc dynamics around central compact objects within the framework of Einstein's general relativity, shedding light on intricate phenomena that continue to captivate the scientific community.

The Effects of Climate Change on Oceanic Sonar Use in the Upper European Continental Shelf

2023-12-09T14:43:46-05:00

As the global effects of climate change become more known year by year, it becomes ever-more pertinent to examine the effects this may bring for every aspect of modern life we rely on. One topic of focus is that of multi-frequency sonar communication and navigational systems, which rely on well-established relationships relating to wave speed, signal intensity, and attenuation. We compiled data on oceanic temperature, acidity, and salinity in the Upper European Shelf, which includes the North Sea and Mediterranean Sea, from 2006 to 2072 using the CMIP5 future climate model in the RCP8.5 scenario. We calculate that the speed of sound in the northern European oceanic area will decrease by almost 18 m/s by 2072, with an average yearly decrease in sound speed by 0.37 m/s. The attenuation of sound through water will change year by year, calculated based on a higher-order polynomial regression dependent on the frequency of sonar used. The maximum operating ranges of active low-frequency, mid-frequency, and high-frequency sonar systems would theoretically change by +0.06%, -0.19%, and +0.71%, respectively per year, if no other factors are affected. Due to increased sound propagation, the ambient noise level of the ocean would also increase and have some counter-effect to the increased detection range however that increase in noise level was not quantitatively analyzed in this study.

Cinnamomum cassia and Origanum compactum Essential Oils as Antifungal Candidates for the Treatment of Aspergillosis

2024-03-27T00:04:13-04:00

Aspergillosis is a disease that usually affects the respiratory system. While most patients develop mild symptoms, aspergillosis can become a serious health threat in immunocompromised populations and patients with pre-existing respiratory conditions. Aspergillosis is caused by fungi of the Aspergillus genus. Existing treatments include drugs such as azoles, ergosterol interfering agents (Amphotericin B), and echinocandins (Caspofungin), which usually come with various drawbacks. Numerous studies have shown the antifungal properties of certain essential oils (EOs), which represent potential alternative treatments against fungal infections. Here, we screened the antifungal properties of five EOs against Aspergillus oryzae: Melaleuca alternifolia, Mentha x piperita, Thymus zygis, Origanum compactum, and Cinnamomum cassia. Of the five EOs, two demonstrated antifungal activity: Origanum compactum acted as a fungistatic, while Cinnamomum cassia showed both fungistatic and fungicidal effects against A. oryzae. Therefore, both EOs represent potential alternative treatments against Aspergillosis.

Elevated Ambient Carbon Dioxide Levels Induce Attraction but Not Attachment of Adult Ixodes scapularis in Artificial Membrane Feeding

2024-01-12T19:35:36-05:00

Numerous feeding studies on tick species have explored disease transmission, vector interactions, and acaricide testing. Traditionally, these studies used animals for feeding. However, artificial membrane feeding offers several advantages including increased standardization of experiments, decreased costs, and improved animal welfare. In vitro conditions must closely mimic natural environments to promote successful feeding attachment. Kairomones produced by the host are strong stimulants that encourage attachment. An important kairomone detected by ticks is carbon dioxide (CO₂). Previous studies have shown elevated CO₂levels stimulate host identification and attraction and potentially improve artificial feeding rates in some tick species. The objective of this study was to use an artificial membrane feeding chamber prototype to explore the effects of ambient CO₂ in inducing Ixodes scapularis attachment. Differences in attachment rate were explored at an air-typical ambient CO₂ level of 0.04% and an elevated CO₂level of 4.0%. Tick attachment was not detected in either ambient CO₂condition during the incubation period, indicating ambient CO₂does not impact the attachment rate under the presented condition. However, I. scapularis contact with the artificial membrane occurred at an increased rate of 0.014 female ticks in contact with the membrane per hour in the elevated CO₂ condition (4%) compared with a rate of 0.01 ticks per hour in the air-typical CO₂ condition (0.04%) (p = 0.048) suggesting that the ambient CO₂ level affects attraction to the blood but does not directly stimulate attachment of I. scapularis.

A Replication Study to Evaluate the Effects of Awe on Humility

2024-01-21T22:59:57-05:00

This paper replicates Stellar and Colleagues’ 2018 study involving an experimental manipulation of awe using standardized video induction, as well as proposing and testing out an additional hypothesis. The previous study hypothesized that watching an awe-inducing video would lead participants to write fewer strengths before writing their weaknesses. In addition to the replication, we hypothesized that participants with higher scores of depressive symptomatology (DS) would list fewer strengths due to diminished self-concept and self-efficacy. Ninety-four undergraduate psychology students were recruited from McGill University ranging from 18 to 35 years of age. Participants were randomly assigned to either the awe-inducing or neutral video condition, and then filled out measures of humility, emotional reactions, and DS. In contradiction with the original study, participants in the awe condition and the neutral condition did not significantly differ in their ratio of disclosed strengths to weaknesses, therefore no significant correlations were found between awe and humility or humility and depression. Additionally, results indicated that participants with greater DS did not list fewer strengths compared to those scoring lower on the CES-D. We were unable to directly replicate the original study and thus rejected our alternate hypothesis. This study had various potential limitations, among which are the possibilities of self-report bias, issues regarding convenience sampling, and bias due to time constraints. The current study advances the literature by including depression relating to awe and humility. Further research is needed, to differentiate lab-induced awe from natural experiences of awe and identify possible moderating factors on humility.