30921 research outputs found
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Monitoring beluga whales from space: estimating abundance and evaluating social structure using VHR satellite imagery
No full textImproving monitoring efforts of Arctic species is becoming increasingly important given the rate of change in Arctic marine ecosystems and the presumed impact on Arctic marine mammals, such as beluga whales (Delphinapterus leucas). Very High Resolution (VHR) satellite imagery is emerging as a promising tool for efficiently monitoring beluga whale populations, which can be logistically challenging with current methods. Here we use VHR satellite imagery to investigate two conservation relevant aspects of beluga whale populations: abundance and social dynamics. First we determined two missing pieces of information required to estimate beluga whale abundance in VHR satellite imagery: 1) depths that beluga whales are visible in VHR satellite images, which are used to define availability bias correction factors, and 2) a comparison of abundance estimates in VHR satellite imagery to current aerial methods. We determined that beluga whales can be detected only at the surface in turbid water and at depths of 0 – 2 m in clear water in 0.31 m resolution VHR imagery, and that beluga whale availability bias corrected abundance estimates made from synchronous VHR satellite imagery and drone surveys were comparable. We further used VHR imagery to describe beluga whale group size, composition, and cohesion in beluga whale populations from Cumberland Sound, Eastern High Arctic – Baffin Bay, and Western Hudson Bay in relation to anthropogenic disturbance, density, and social context. We found that group size decreased with harvest, which seemingly reflects population decline or removal of key social individuals, while recent increases in vessel traffic were associated with larger group sizes and greater spatial cohesion, possibly suggesting an adaptative response to increase vigilance to vessel disturbance. Beluga whale social cohesion was mainly influenced by the presence of juvenile whales, with adult-juvenile mixed groups having smaller inter-individual distances than groups with adults only. Future beluga whale management efforts may benefit from incorporating VHR imagery into research programs and continuing to assess beluga whale social group dynamics alongside traditional abundance estimates; particularly given the expansion of anthropogenic disturbance in the Arctic.October 202
Galactic scale radio-mode feedback in compact radio galaxies
No full textIn the early stages of radio galaxy evolution, where the nuclear jets reside entirely within the host galaxy, the interaction of an expanding radio source with the surrounding interstellar medium is likely to be the most pronounced. These kpc-scale jets will cause nearby clouds to collapse and trigger starbursts in a direct consequence of radio-mode feedback from Active Galactic Nuclei (AGN).
In this thesis, I present the first systematic search for ultraviolet emission signatures from radio source-driven AGN feedback in Compact Steep Spectrum (CSS) radio galaxies. Owing to their characteristic sub-galactic jets (1-20 kpc projected linear sizes), CSS hosts are excellent laboratories for probing galaxy- scale feedback via jet-triggered star formation. The sample consists of 7 powerful CSS galaxies, and 2 galaxies host to radio sources >20 kpc as control, at low to intermediate redshifts (z<0.6). Imaging with the Hubble Space Telescope shows extended UV continuum emission in six out of seven CSS galaxies; with five CSS hosts exhibiting UV knots co-spatial and aligned along the radio-jet axis. Young, massive stellar populations are likely to be the dominant source of the blue excess emission in radio galaxies at these redshifts, hence the radio-aligned UV regions could be attributed to jet-induced starbursts. Lower near-UV star formation rates compared to other indicators suggest low scattered AGN light contribution to the observed UV. Dust attenuation of UV emission appears unlikely from high internal extinction correction estimates in most sources. Comparison with evolutionary synthesis models shows that the observations are consistent with recent (1-8 Myr) activity likely triggered by current or an earlier episode of radio emission, or by a confined radio source that has frustrated growth due to a dense environment. While follow-up spectroscopic and polarized light observations are needed to constrain the activity-related components in the observed UV, the detection of jet-induced star formation is a confirmation of an important prediction of the jet feedback paradigm.October 202
Counteracting temozolomide (TMZ)-resistant glioblastoma (GBM) via inhibition of the cellular base excision repair pathway (BER)
No full textBackground
Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the standard of care treatment of surgery, radiation therapy and Temozolomide (TMZ) chemotherapy, GBM frequently recurs in a drug-resistant form. This work investigates how inhibition of the hyperactive Base Excision Repair (BER) pathway, with existing or newly developed inhibitors, could be beneficial to resensitize resistant GBM to the DNA alkylation damage of TMZ.
Methods and Materials
Patient-derived Brain Tumour Initiating Cells (BTICs) were used as our GBM model. BTICs were cultured and treated with increasing concentrations of Temozolomide (TMZ) alone or in combination with various inhibitors targeting the Base Excision Repair (BER) pathway. DNA damage was assessed using our novel high-throughput alkaline 3-D comet assay, while self-renewal and proliferation capacities were evaluated through sphere formation, cell viability, and serial-replating assays.
Results
A novel high-throughput alkaline 3D comet assay was developed and optimized to measure DNA damage specifically in BTICs. Using this assay, resistant BTICs were re-sensitized to TMZ damage with BER inhibitors Pamiparib, Olaparib, and the novel compound B9 which targets the scaffolding protein XRCC1 within the BER. Self-renewal and cell proliferation assays confirmed that BER inhibition impaired growth and sphere-formation capacity of resistant BTICs when combined with TMZ. Serial re-plating assay showed that BER inhibitors reduced long-term self-renewal and proliferation potentials of TMZ treated BTICs, as they failed to form spheres and showed reduced proliferation after being moved to drug-free conditions post-treatment.
Conclusion
This study shows that targeting the BER repair pathway can effectively re-sensitize TMZ-resistant BTICs, which provides a promising strategy to overcome therapeutic resistance in GBM. Our Novel compound B9 shows significant potential, making XRCC1 inhibition and biomarker analysis important objectives of our work. Furthermore, our novel high-throughput 3D comet assay platform represents a valuable tool for DNA damage analysis in tumorspheres, which could facilitate large-scale drug screening in GBM as well as other diseases.February 202
Mapping of quantitative trait loci (QTLs) in Thinopyrum intermedium for Fusarium graminearum tolerance and agronomic traits
No full textDespite the significant benefits that intermediate wheatgrass (Thinopyrum intermedium) provides for soil health and carbon sequestration, its potential in Canada's commercial production landscape is yet to be fully realized. As a result, the University of Manitoba's perennial grains breeding program is focused on developing IWG cultivars with increased grain yields and greater resistance to Fusarium graminearum. Genetic analysis was performed to improve our understanding of these traits in IWG. A genetic map consisting of 865 markers covering 20 linkage groups was developed in R using the package OneMap (Margarido et al., 2007). The map was developed using genetic and phenotypic data from 150 F1 progeny and two parents (UM2014-0001 and UM2014-0044) from cycle two UMB selections. The JGI public access intermediate wheatgrass consensus map (v3.1) was used as a reference. Quantitative trait locus (QTL) analysis was performed using composite interval mapping (CIM) in the R package fullsibQTL (Gazaffi et al., 2014) with a LOD threshold of 3. The results revealed 52 QTLs associated with Fusarium head blight (FHB) severity and incidence measurements and 52 QTLs associated with various agronomic traits. One large effect QTL for seed number and two large effect QTLs associated with FHB severity and incidence were identified. The future use of marker assisted selection in the UMB population is discussed in relation to 13 relevant QTLs. Broad-sense heritability estimates revealed plant height, thousand kernel weight, and seed number were highly heritable traits, while tiller number and crown diameter were largely controlled by environmental factors. Among this population, reciprocal crosses involving UM2014-0001 exhibited significantly larger seed masses, while UM2014-0002 parents produced 22.8% more seeds. UM2014-0044 parents displayed superiority in forage related traits (crown diameter and plant height). Trait relationships and genetic analysis of agronomic and FHB resistance traits has provided insights to advance future IWG breeding programs. This research enables marker-assisted selection to breed for IWG crops that meet the demands of our food system while addressing the environmental challenges this system has created.University of Manitoba Collaborative Research Program (UCRP) Canadian Agricultural Partnership The Land InstituteMay 202
Traditional stand-up dumbbell curls induced uniform elbow flexors regional hypertrophy in untrained individuals
No full textContext: Skeletal muscle plays a crucial role in daily motion, athletic performance, health, and longevity. However, aging- or disuse-induced muscle loss can lead to functional disorders, vulnerability to injury, and increased risks of chronic diseases if left unattended. Resistance training, a type of physical exercise where skeletal muscle contracts against an external resistance to improve function and aesthetics, has been widely considered the most effective extraneous means to increase muscle mass and prevent the health-related risk of muscle atrophy. Recent evidence suggests that a muscle could increase its anatomical cross-sectional area and muscle thickness of a particular region to a greater degree than others, referred to as regional muscle hypertrophy (RMH).
Objective: This study examined the change in muscle thickness (MT) at three regions of elbow flexors (EF) and its RMH pattern to eight-week standing dumbbell curl (SDC) training.
Method: 22 untrained individuals (age: 23.4±3.9 years) were recruited to participate in the study. Participants completed 24 sessions (eight weeks, 3 sessions/week) of unilateral SDC training with a dumbbell equivalent to 70% of their one repetition maximum. MT of the proximal, middle, and distal elbow flexor of each participant was assessed before and after training using B-mode ultrasonography. A paired sample t-test was used to assess the pre-post MT changes of each of the three regions. A one-way repeated measure analysis of variance was conducted to compare the percent change in MT between regions.
Result: Paired sample t-tests found significant differences between pre- and post-MT of all three regions (Proximal: p<0.001, d=1.63, Middle: p<0.001, d=1.21, Distal: p<0.001, d=2.06). No significant differences were found among regions.
Conclusion: The current study showed significant increases in MT of all three regions of the EF in untrained participants in response to eight weeks of SDC RT. Further, no significant differences were observed between regions, suggesting that SDC training induced uniform muscle growth across the long axis of the EF.October 202
Investigating the Roles of Homeobox Proteins and TEAD in Small Cell Lung Cancer
No full textLung cancer remains a significant global health concern, responsible for a substantial number of cancer-related deaths annually. Small cell lung cancer (SCLC), one of its subtypes, is particularly aggressive and resistant to treatment, leading to a poor prognosis for patients. Unfortunately, treatment options for SCLC remain limited and have not been advanced for decades. This highlights the urgent need for a deeper understanding of the molecular mechanisms underlying the pathogenesis of SCLC in order to identify novel therapeutic strategies for this disease. DNA-bind proteins, TEADs, play a crucial role in promoting SCLC survival. TEADs are best recognized for their role in interacting with transcriptional activators, YAP and TAZ, however, it was found that the function of TEADs in SCLC is completely independent of YAP and TAZ. Beyond this however, the mechanisms underlying the critical function of TEAD in SCLC is unknown. Preliminary data gathered by the Pearson lab identified the presence of homeobox proteins PROX1, NKX2-1 and NKX2-2 with the TEAD complex in SCLC, prompting the hypothesis that TEAD interacts with these proteins to silence TEAD target genes in SCLC, promoting the cancerous state. Using co-immunoprecipiation, the association of TEAD with PROX1 and NKX2-1 were confirmed. Additionally, CRISPR interference was used to knockdown PROX1, NKX2-1 and NKX2-2 in SCLC cells, to assess their role in TEAD-mediated gene regulation. This resulted in an increase in controlled cell regulation and differentiation genes, and a decrease in SCLC biomarkers, consistent with the hypothesis. However, contrasting the hypothesis, protein knockdowns showed a decrease of cell adhesion genes. Nevertheless, these findings bring light to a novel pathway in SCLC pathogenesis. Understanding the exact mechanisms behind these homeobox proteins and their interaction with TEADs could lead to the development of more effective treatment for SCLC
L’éducation artistique dans les écoles francophones et d’immersion française au Manitoba : le vécu des enseignants généralistes (de la maternelle à la 6e année)
No full textCette étude qualitative examine l’expérience vécue de cinq enseignantes généralistes de la maternelle à la 6e année des programmes français et d’immersion française au Manitoba à l’égard de l’éducation artistique. Dans le contexte minoritaire francophone, les arts et la culture sont indispensables à l’épanouissement des communautés francophones, conséquemment, l’éducation artistique doit avoir une place de choix dans le milieu scolaire. Parallèlement aux spécialistes des arts, les enseignants généralistes sont appelés à jouer un rôle dans la mise en œuvre de l’éducation artistique. Cette étude phénoménologique de cas multiples inspirée par une approche axée sur les arts donne une voix à cinq enseignantes généralistes et permet d’explorer et de comprendre leur expérience, leurs perceptions et leurs croyances, ainsi qu’à clarifier leur rôle et leurs besoins d’apprentissage professionnel dans ce domaine.
Des recommandations pour l’administration scolaire, le ministère de l’Éducation, les facultés d’éducation des universités et les organismes artistiques ont émergé à partir des réflexions des participantes et de l’analyse des données de cette étude axée sur le Programme français et le Programme d’immersion française au Manitoba.
This qualitative study examines the lived experience of five Kindergarten to Grade 6 generalist teachers in Manitoba's Français and French immersion programs in relation to arts education. Arts and culture are essential to the flourishing of minority Francophone communities, and consequently, arts education must be prominent in the school environment. Alongside arts specialists, generalist teachers are called upon to play a role in providing arts education. This phenomenological multiple case study, inspired by arts-based methodology, gives a voice to five generalist teachers, and allows for exploration and understanding of their experiences, perceptions, and beliefs, along with the clarification of their teaching role and professional needs.
Recommendations for school administrators, the Department of Education, University Faculties of Education, and arts organizations emerged from the participants' perspectives and the data analysis from this study that focused on the Français and French Immersion programs in Manitoba.February 202
A one health approach to investigating the genetic diversity of the opportunistic and multi-drug resistant pathogenic genus, Acinetobacter spp.
No full textAcinetobacter spp. are a group of Gram-negative bacteria found in a variety of different environments such as hospitals, food, soil and water sources. In fact, investigation of Acinetobacter spp. has been declared a One Health crisis. highlighting that not just clinical, but also animal and environmental samples are important to our understanding and resolution of these infections. Many strains of the most notorious member, Acinetobacter baumannii are multi-drug resistant (MDR), and virulent, causing infections in humans including soft tissue and wound infections, ventilator-associated pneumonia and even bacteremia. Various antibiotic resistance genes (ARGs) are common in Acinetobacter spp. In Chapter 3, the diversity of Acinetobacter spp. is highlighted with the discovery of novel sequence types and therefore novel clonal complexes from non-clinical sources. We found that the most common ARGs are efflux pumps and the presence of ARGs did not necessarily determine antibiotic susceptibility. There was also no correlation between virulence and geographic origin or isolation source. In Chapter 4, we explore clinical MICs of colistin resistance observed in clinical isolates of Acinetobacter courvalinii and Acinetobacter pittii, and in non-clinical isolates of Acinetobacter seifertii. Again, with Chapter 3 as a basis, Chapter 5 describes the discovery of an ADC-5 cephalosporinase encoding gene from a tank milk isolate of A. baumannii, the first to be observed in a non-clinical isolate. Efflux pumps were the most commonly detected ARG and this was studied in more detail in Chapter 6. Determinants of substrate selectivity using molecular genetic techniques. Finally, because of the classification of A. baumannii as a One Health challenge. understanding the impact of a wide-spread environmental non-antibiotic compound, SA, and its effects on antibiotic susceptibility and virulence are explored in Chapter 7. Studying the impact of SA on ARGs and virulence genes (VGs) using a proteomic approach revealed changes in membrane specific structures such as efflux pumps and porins thereby affecting antibiotic susceptibility. By taking a One Health approach to studying ARGs and VGs in non-clinical and clinical Acinetobacter spp, this study greatly contributes to the understanding of resistance and virulence mechanisms and non-antibiotic triggers thereby contributing to prevention and treatment of such infections.October 202
Synthesis and exploration of boron-containing heterocycles as potential PARP inhibitors
No full textThe 18 members of the poly (ADP-Ribose) Polymerase (PARP) family of enzymes are involved in a variety of biological processes, such as apoptosis and DNA repair. The PARP enzyme consumes NAD+ as a substrate, and competitive inhibitors are used to mimic the natural NAD+ substrate and prevent PARylation. Inhibiting PARP is therapeutically utilized in anticancer treatment. These inhibitors have the potential to function as sensitizers, so they can increase the effectiveness of anticancer therapies, including radiation therapy and chemotherapy medications. Since PARP inhibitors cause synthetic lethality in homologous recombination-dysfunction cells, they are also used as single-agent treatments in individuals with BRCA-deficient breast, ovarian, or prostate cancer. Organoboron compounds can be described as Lewis acids due to their empty p-orbital, which accepts lone pair electrons (Lewis Base) and changes hybridization. This unique feature makes organoboron compounds preferred drug candidates, leading to an increase in the number of functional groups, including boronic acid, in medicinal chemistry. Boron-containing heterocyclic rigid structures improve drug-enzyme interactions based on forming tertiary complexes between boronic acids and responsible amino acids such as serine. For this reason, we created a boron-containing heterocyclic library that includes 21 benzoxazaborinin derivatives, and their yields range from 20% to 99%. Those compounds are characterized by utilizing NMR spectroscopy and HRMS and tested with a PARP-1 screening assay, which is cost-effective and does not require special laboratory equipment. This assay quantifies leftover NAD+ substrate by converting it to a fluorophore group that makes excitation (372 nm) and emission (444 nm). Overall, we were able to synthesize benzoxazaborinin-based PARP inhibitors, with the lowest IC50 value of 31 M for structure 15A.The student was funded by the Republic of Turkey and its Ministry of National Education.February 202
Little Kapwa, redefining the cultural centre
No full textLittle Kapwa is a cultural hub for second-generation Filipinx Canadians who share a “Third Culture” formed through their
traditional Filipinx and modern Canadian experiences. The centre’s interior design utilizes the essence of “home” to support
its primary users in celebrating and practicing the third culture they are cultivating. To achieve the feeling of “home” in Little
Kapwa’s design, this practicum proposes unique programming and interior features which explore identity, culture, and
placemaking.
At the same time, Little Kapwa introduces a cultural centre that recognizes the multitude of layers within a cultural community.
Little Kapwa breaks through multicultural ideas of a culture–which captures a surface-based notion of its diverse community.
Instead, Little Kapwa’s interior design allows the growth of culture, creating space for future generations, like second-generation
Filipinxs who plant new seeds of cultural practice as time passes.May 202