30921 research outputs found
Sort by
Characterizing sex-related differences in brown adipose tissue from Phb1 Knock-In mouse models
Full text linkBrown adipose tissue (BAT) functions as a heat-producing organ that contributes to whole-body energy balance. The amount and activity of BAT differ between sexes: females typically display greater mitochondrial content and thermogenic responsiveness than males, largely influenced by estrogen signaling. Although sex steroids are known to affect BAT physiology, the intracellular mechanisms that connect hormonal input to metabolic outcomes remain incompletely understood. Prohibitin-1 (PHB1) is an evolutionarily conserved scaffold protein that supports mitochondrial organization and coordinates metabolic and hormonal signaling, including estrogen, androgen, and insulin pathways. Through various post-translational modifications (PTMs), PHB1 can relocate among subcellular compartments and influence multiple pathways, including those involved in lipid handling and insulin responses. Among its modification sites, two residues, Cys69 and Tyr114, appear particularly important for regulating PHB1 function, yet their physiological relevance in living systems has not been defined.
To explore this, two CRISPR-engineered knock-in mouse models were generated, Phb1-KiC69A and Phb1-KiY114F, each lacking one of these critical sites. Analyses of glucose and insulin tolerance tests (GTT and ITT), along with histological evaluation of BAT morphology and mitochondrial density, revealed distinct and sex-dependent consequences for BAT architecture, mitochondrial quality, and metabolic regulation including glucose homeostasis and insulin sensitivity regulation. Phb1-KiC69A females showed enlarged BAT depots and hypertrophic adipocytes, while males exhibited disrupted mitochondrial ultrastructure. In contrast, Phb1-KiY114F males displayed modest BAT expansion with relatively intact mitochondria, and females maintained small, densely structured adipocytes. Gonadectomy further indicated that endocrine status modifies these traits: loss of testosterone enhanced insulin sensitivity in Phb1-KiC69A males, whereas estrogen withdrawal slightly impaired glucose handling in Phb1-KiY114F females.
Together, the results indicate that mutating Cys69 and Tyr114 sites in PHB1 influence BAT structure and metabolic function in a sex-dependent manner, providing evidence that PHB1 could participate in the hormonal regulation of energy metabolism.February 202
A systematic X-ray spectroscopic study of thermonuclear supernova remnants
Full text linkThermonuclear supernovae (SNe) are catastrophic explosions that occur when white dwarfs -- the compact remnants of low-mass stars -- experience runaway nuclear burning. While it is commonly believed that these explosions emerge from white dwarf stars in binary systems, the exact mechanisms by which these explosions proceed are not fully understood. It is possible, however, to determine a number of the properties of one of these explosions by examining its supernova remnant (SNR). In the interest of connecting these supernova remnants to their supernova progenitors, we perform a systematic spatially-resolved X-ray spectroscopic study of a selection of 15 SNRs that are known to be, believed to be, or which have been suspected of being of a thermonuclear origin. We make use primarily of data from the XMM-Newton space telescope, whose sensitivity -- combined with its strong spectral and angular resolution -- affords us a powerful tool to study the spectra of these objects. For one remnant, we instead make use of data from the Chandra space telescope, whose superior angular resolution allows us to examine more closely the thermal-emitting regions for one of our smallest and youngest targets.
To remove possible sources of bias, we make use of an algorithm that generates regions based on surface brightness to determine the extent and distribution of the regions used in this study. Using one- or two-component models of thermal plasmas, we determine a variety of physical parameters for each of these regions, including the abundances for a variety of elements between O and Fe. We then compare these abundances to a collection of 335 individual models from 11 sets of simulations of supernova nucleosynthesis yields. We find a wide range of agreement between our observations and the models: while for some objects there is strong agreement between the models and observations, in general, the observed abundances do not match the entirety of the predicted yields for any of the models. Despite this, we present our best estimates for the progenitor details of each SNR based on the models that best reproduce their observed abundances, additionally addressing the progenitor classification for several objects for which this has long been debated. We also discuss a number of limitations present in the current models that may have lead to these disagreements, identifying reaction rates, dimensionality, metallicity, and explosion energy as four possible areas for future simulations to consider. We close by considering the possibility of future work, addressing additional tools, targets, and methods that could lend themselves to such a study.February 202
Prevalence, Position and Diameter of The Posterior Superior Alveolar Neurovascular Bundle on Cone-Beam Computed Tomography Scans - A Retrospective Study
No full textPurpose: This retrospective study aimed to assess the prevalence, anatomical position, and diameter of the posterior superior alveolar neurovascular bundle (PSAN) canal in relation to maxillary alveolar landmarks using cone-beam computed tomography (CBCT) scans in a retrospective study design. Additionally, the influence of sex, side, age, and dentition status on these parameters was evaluated to aid clinicians in minimizing the risk of PSAN injury
during surgical procedures.
Methods: A total number of 275 randomly selected and anonymized CBCT scans were reviewed, with 218 cases meeting the inclusion criteria. The PSAN canal was assessed in the premolar, first molar and second molar regions for: (a) prevalence, (b) canal location, (c) distance to alveolar crest, (d) distance to sinus floor, (e) alveolar height, (f) distance to medial sinus wall, and (g) canal diameter.
Results: PSAN canal prevalence was 91.71% in premolar, 79.13% in first molar, 79.61% in second molar region. The canal was most commonly intraosseous in the premolar region (80.7%), but predominantly intrasinus in the first (57.7%) and second molar region (67.1%). Mean distances from the PSAN canal to the alveolar crest were 26.16±5.66 mm (PM), 17.78±5.14 mm (M1), and 17.03±4.18 mm (M2). Distances to the sinus floor were
12.53±5.36 mm (PM), 10.67±4.46 mm (M1), and 9.69±3.81 mm (M2). Alveolar heights measured 13.76±5.15 mm (PM), 7.99±3.11 mm (M1), and 8.26±2.80 mm (M2). Canal-to-medial wall distances were 7.70±2.50 mm (PM), 13.70±3.70 mm (M1), and 16.04±3.01 mm (M2). Canal diameters were consistent across regions: 1.36±0.39 mm (PM), 1.36±0.38 mm (M1), and 1.33±0.40 mm (M2). No significant differences were observed based on sex, side,
age, or dentition status (p > 0.05).
Conclusion: The PSAN canal exhibits consistent anatomical patterns in prevalence, position, and diameter across regions, which may assist clinicians in avoiding neurovascular injury during surgical interventions.This study suggests that demographic and anatomical variables such as age, sex, side, and dentition status do not significantly impact these measurements
Synthesis, characterization, and development of boron-based pyrazoles that can serve as potential therapeutic redox regulators in amyotrophic lateral sclerosis (ALS): introducing Borsantrazole™
Full text linkAmyotrophic lateral sclerosis (ALS) is a heterogeneous and fatal motor neurodegenerative disease. Since ALS was discovered in 1869, only two FDA-approved drugs, Edaravone (EDR) and Riluzole, have had clinically validated impacts on disease progression. However, preclinical studies of these approved drugs in SOD1 ALS mouse models haven't shown any survival benefits. Here, we report the discovery and development of a boron-based improved version of FDA-approved EDR, which could modify motor disease phenotypes in SOD1 ALS mice models, demonstrating target engagement. Using a novel green chemistry approach, we synthesized four boron-based EDR analogues and EDR prodrugs (B5-EDR). All six compounds showed excellent safety and efficacy in vitro. Single and daily doses of NS-1-2 (10mg/kg) (BorsantrazoleTM) caused no tissue toxicity in wild-type mice; furthermore, presymptomatic NS-1-2 treatment in G37R (42) mice effectively modified clinical motor disease phenotypes. Moreover, the untargeted biomarker analysis showed differential protein expression in the brain and spinal cord of SOD1 ALS mice, supporting the therapeutic potential of NS-1-2. Furthermore, the lead compound NS-1-2 is registered as a trademark under the name BorsantrazoleTM (BSZ) and is protected by a patent. It is supported by a comprehensive international search report from the World Intellectual Property Organization, PCT/CA2023/051352 (WO/2024/103151), which affirms its novelty, inventive step, industrial utility, and industrial applicability.Natural Sciences and Engineering Research Council of Canada (NSERC): grant number is RGPIN-2017-05938
2017 Research Manitoba New Investigator Operating GrantFebruary 202
Identifying challenges and enablers to engaging patients in preclinical laboratory research: an interview study
Full text linkBackground: Patient engagement in research enriches study design, conduct, and dissemination by integrating lived experiences of patients into the research process. Although patient engagement is becoming more popular in clinical research settings, it remains comparatively rare in preclinical (i.e. laboratory based) research. To explore this gap, we conducted an interview study to understand how researchers and patients have implemented patient engagement in this area, focusing on the challenges and benefits of their approach.
Methods: We conducted semi-structured interviews of patients (n = 15) and researchers (n = 14) with previous preclinical patient engagement experience. Interviews were transcribed and reviewed using an inductive, thematic content analysis, which allowed for bottom-up analysis of interview data. Our team identified, reviewed and refined emerging themes. Our team members include preclinical, clinical and patient engagement researchers and patient partners, which allowed for various perspectives to contribute to the final interpretation of the findings and drafting of the manuscript.
Results: We identified five themes. Theme 1: Researchers and patients highlighted the necessity to adopt a thoughtful and tailored approach for each preclinical engagement initiative. This includes taking time to cultivate personal relationships and co-developing engagement activities to meet patient and researcher preferences and needs. Theme 2: Clear communication was deemed critical, suggesting the need for a clear and shared vocabulary without technical jargon. Theme 3: Varied goals for engagement in preclinical research between researchers and patients were underscored, indicating the need to discuss aims and motivations early and often as well as to co-develop mutually beneficial strategies. Theme 4: Researchers and patients also discussed how their communities require a better understanding of the value of preclinical patient engagement. This could be fostered through education and illustrative case examples. Theme 5: Finally, a shift in research culture was deemed necessary and called for stronger institutional support, efficient channels to connect preclinical researchers and patients, as well as initiatives that recognize and champion preclinical patient engagement.
Conclusion: Our study identified five common themes in preclinical patient engagement which can help the research community facilitate meaningful engagement of patients in preclinical laboratory research.Plain English summary: Engaging patients as partners in clinical research, known as patient engagement, is a growing practice that has numerous benefits. However, uptake in preclinical laboratory research (e.g. cell and animal studies) has been limited. Nevertheless, incorporating patients as active collaborators at this discovery stage of biomedical research may be beneficial. To better understand how patient engagement fits into preclinical research, we conducted interviews with patient partners and preclinical researchers who have implemented this practice. Five key themes emerged. First, both groups emphasized the need for adopting a thoughtful and tailored approach since preclinical research is not typically patient facing. Second, shared vocabulary was important to facilitate communication. Third, setting clear expectations and outlining varied goals for engagement was considered critical. Fourth, understanding the value of preclinical research helped ground engagement efforts. Finally, interviewees felt a cultural shift is needed for this practice to be accepted more widely. These themes are important factors to consider when engaging patients in preclinical laboratory research; they may be used to inform and support future preclinical patient engagement efforts
The benefits of using biophilic design in post-secondary design studio classrooms
Full text linkPost-secondary design students spend a significant portion of their professional education engaging in creative project work in design studio classrooms. This Master of Interior Design (MID) thesis examines the impact of incorporating biophilic elements into the interior design of a studio classroom to create a more supportive, less stressful learning environment for design students. Additionally, this thesis study examines the needs and preferences of design students within studio settings. Biophilic design is supported by prior research demonstrating positive health outcomes among office workers, hospital patients, and middle school students (Mahrous et al., 2024). However, given the limited research on the effects of biophilic design on students in design studio classroom settings, this study helps bridge the gap between past and current research. A unique mixed-methods approach, including augmented reality (AR), was employed. AR enabled interior design students (n = 20) to experience an overlay of biophilic design within their current studio environment, permitting them to walk around and perform typical tasks through a cognitive walkthrough. After experiencing the biophilic studio classroom, semi-structured interviews gathered participants’ perceptions of the virtual biophilic environment compared to their current space. An online follow-up survey was also conducted to assess stress levels by comparing experiences in the current studio classroom with those in the AR-viewed biophilic environment. This thesis study highlights the advantages of utilizing augmented reality (AR) technology in environmental and behavioural (EB) research, and its findings support incorporating biophilic design elements into post-secondary studio classrooms to improve comfort and reduce stress.February 202
RAMEN: Dissecting individual, additive and interactive gene-environment contributions to DNA methylome variability in cord blood
Full text linkGenetic variation and environmental exposures are amongst the main factors associated with inter-individual DNA methylation variability. However, the prevalence and genomic context of individual, additive, and interactive gene-environment effects remains unclear. We present RAMEN, an R package that dissects genome-exposome contributions to microarray Variably Methylated Loci using machine learning and statistical techniques. Analyzing cord blood samples from CHILD and PREDO (overall n = 1662), we identify genetic variants as key contributors to DNA methylation variability, usually in additive and interactive combinations with the environment. We provide a detailed catalogue of cord blood Variably Methylated Loci and the gene-environment contribution to their variability
Inter-generational playground design: an exploration into play, familiarity, and place attachment
Full text linkThis practicum explores the possibility of creating an intergenerational park in the town of Swan River, Manitoba, a community which, like many in the Parklands Region, continues to have a larger older adult population when compared to the provincial average (Statistics Canada 2017). Like many communities in Manitoba, both rural and urban, Swan River has seen many changes in the last 75 years, largely due to the immense technological and industrial development we’ve seen since the beginning of the post war period. While these changes have largely improved living conditions in said communities by providing electricity, refrigeration, indoor plumbing, and the like, it has also drastically changed the way we live our day to day lives and created a reality that is unrecognizable and unfamiliar to many older adults. Additionally, with these changes, the communities they call home have also changed and the places, structures, and landscapes that they once felt connected to may no longer exist. This lack of familiarity can lead to a disconnection from the places we call home, which minimizes our sense of belonging within our community and can have a negative impact on our wellbeing, especially as we age.
Creating supportive, understanding, and empathetic communities begins by encouraging discussion, meaningful interaction and connections between different ‘groups’ of people. By supporting and encouraging connections between community members of all ages through intergenerational design, we can create strong, resilient, and inclusive communities that will continue to support their populations, no matter their age or functional ability.February 202
Car park feasibility: Crescent Drive Park / Crescent Drive Golf Course / Thermea
Full text linkThe practicum is a car park feasibility study of Crescent Drive Park/ Thermea/ Crescent Drive golf course in Winnipeg, Manitoba. The intention is to thoroughly investigate and propose solutions to the neighborhood’s multi-layered concerns. These include providing designs for convenient parking for Thermea, reducing safety concerns in the neighborhood, controlling street parking, enhancing the entrance of the park, the golf course, and Thermea, retaining the mature and healthy tree canopies, and reducing car traffic in the neighborhood.February 202
Nanopore sequencing and phylogenetic analysis of treponema pallidum from clinical specimens in Manitoba.
Full text linkSyphilis is a systemic infection caused by the bacteria Treponema pallidum subspecies pallidum (TPA) that became largely controlled in Canada following the introduction of penicillin treatment in the mid 20th century. Up until the 2000s, syphilis incidence remained below 1 case per 100,00 people but since then there has been a nationwide resurgence. Manitoba has some of the highest rates in the country, reaching 136.4 cases per 100,000 people in 2022, nearly four times the national average. This epidemic has also seen a demographic shift, with women now representing more than 50% of new cases along with the re-emergence of congenital syphilis. Given these rates and the return of previously rare outcomes, understanding the genomic diversity of TPA could enhance surveillance, identify transmission networks and guide public health responses.
This project established a workflow for sequencing TPA directly from clinical swabs collected in Manitoba using Oxford Nanopore Technology (ONT). Screening specimens with a tp47 PCR and implementation of a multiplex Lesion Panel assay improved diagnostic efficiency and enabled prioritization of samples for downstream genomic analysis. Extraction and amplification methods were evaluated, with total nucleic acid extraction and selective whole-genome amplification (SWGA) providing the best recovery of TPA DNA. Sequencing optimizations enhanced read depth and assembly quality by incorporating adaptive sampling, flow cell reloading and sample multiplexing. Reference-guided assembly and quality assessment produced thirteen high-quality Manitoba genomes.
iii
The results of the phylogenetic analysis aligned with a previous study that included specimens from British Columbia and Alberta, Manitoba genomes clustered within the SS14 lineage. Further in-silico analysis confirmed the genetic stability of key diagnostic targets and the presence of macrolide resistance. Overall, this study demonstrates the feasibility of producing TPA genomes from metagenomic clinical samples and highlights the potential of Nanopore sequencing for the genomic surveillance of syphilis in Canada.February 202