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Food Research International (Ottawa,... Jul 2024Lipid oxidation limits the shelf-life of dried microencapsulated oils (DMOs), such as infant formula. However, it is poorly understood how lipid oxidation is affected by...
Lipid oxidation limits the shelf-life of dried microencapsulated oils (DMOs), such as infant formula. However, it is poorly understood how lipid oxidation is affected by different types of emulsifiers. To improve our understanding, we prepared DMOs with different emulsifiers (whey protein isolate (WPI), pea protein isolate (PPI), and non-proteinaceous CITREM) and studied lipid oxidation in both the free and encapsulated fat. Only a small difference in oxidation rate was observed between these fat fractions for all formulations. We ascribed this to a non-discrete distribution of the fractions and the subsequent low fractionation selectivity as shown by Raman microscopy. The DMO with PPI showed hardly any oxidation during a 7-week incubation at 40 °C, whereas the DMOs with WPI and CITREM both reached significantly higher contents of oxidation products (lipid hydroperoxides, aldehydes, and epoxides). The enhanced stability of DMO-PPI could not be ascribed to the presence of phytic acid. In conclusion, we demonstrate the potential of using PPI to produce oxidatively stable DMOs.
Topics: Emulsifying Agents; Oxidation-Reduction; Emulsions; Whey Proteins; Pea Proteins; Spray Drying; Drug Compounding; Lipids; Infant Formula
PubMed: 38763662
DOI: 10.1016/j.foodres.2024.114412 -
Journal of the American College of... May 2024Access to magnetic resonance imaging (MRI) in low-and-middle-income countries (LMICs) remains among the poorest in the world. The lack of skilled MRI personnel...
PURPOSE
Access to magnetic resonance imaging (MRI) in low-and-middle-income countries (LMICs) remains among the poorest in the world. The lack of skilled MRI personnel exacerbates access gaps, reinforcing longstanding health disparities. The SWiM Program aims to sustainably create a network of highly skilled MRI technologists in LMICs who will facilitate the transfer of MRI knowledge and skills to their peers and contribute to implementation of highly valuable imaging protocols for impactful clinical and research use.
METHODS
The program introduces a case-based curriculum designed using a novel train-the-trainer approach, integrated with peer collaborative learning to upskill practicing MRI technologists in LMICs. The six-week curriculum uses the Teach-Try-Use approach, which combines self-paced didactic lectures covering the basics of MR image acquisition (teach) with hands-on expert-guided scanning experience (try), and implementation of protocols tailored to provide the best possible images on their infrastructures (use). Each program includes research translation skills training using an established advanced MRI technique relevant to LMICs. A pilot program focused on cardiac MRI (CMR) was conducted to assess the program's curriculum, delivery, and evaluation methods.
RESULTS
Forty-three MRI technologists from 16 LMICs participated in the pilot CMR program and over the course of the training, implemented optimized CMR protocols that reduced acquisition times while improving image quality. The training resources and scanner-specific standardized protocols are published openly for public use on an online repository. In general, at the end of the program, learners reported considerable improvements in CMR knowledge and skills. All respondents to the program evaluation survey agreed to recommend the program to their colleagues, while 87% indicated interest in returning to help train others.
DISCUSSION
The SWiM Program is the first masterclass in MRI acquisition for practicing imaging technologists in LMICS. The program holds the potential to help reduce disparities in MRI expertise and access. The support of the MRI community, imaging societies, and funding agencies will increase its reach and further its impact in democratizing MRI.
PubMed: 38763442
DOI: 10.1016/j.jacr.2024.04.026 -
Radiotherapy and Oncology : Journal of... May 2024Deep learning can automate delineation in radiation therapy, reducing time and variability. Yet, its efficacy varies across different institutions, scanners, or...
PURPOSE
Deep learning can automate delineation in radiation therapy, reducing time and variability. Yet, its efficacy varies across different institutions, scanners, or settings, emphasizing the need for adaptable and robust models in clinical environments. Our study demonstrates the effectiveness of the transfer learning (TL) approach in enhancing the generalizability of deep learning models for auto-segmentation of organs-at-risk (OARs) in cervical brachytherapy.
METHODS
A pre-trained model was developed using 120 scans with ring and tandem applicator on a 3 T magnetic resonance (MR) scanner (RT3). Four OARs were segmented and evaluated. Segmentation performance was evaluated by Volumetric Dice Similarity Coefficient (vDSC), 95 % Hausdorff Distance (HD95), surface DSC, and Added Path Length (APL). The model was fine-tuned on three out-of-distribution target groups. Pre- and post-TL outcomes, and influence of number of fine-tuning scans, were compared. A model trained with one group (Single) and a model trained with all four groups (Mixed) were evaluated on both seen and unseen data distributions.
RESULTS
TL enhanced segmentation accuracy across target groups, matching the pre-trained model's performance. The first five fine-tuning scans led to the most noticeable improvements, with performance plateauing with more data. TL outperformed training-from-scratch given the same training data. The Mixed model performed similarly to the Single model on RT3 scans but demonstrated superior performance on unseen data.
CONCLUSIONS
TL can improve a model's generalizability for OAR segmentation in MR-guided cervical brachytherapy, requiring less fine-tuning data and reduced training time. These results provide a foundation for developing adaptable models to accommodate clinical settings.
PubMed: 38763356
DOI: 10.1016/j.radonc.2024.110332 -
The Journal of Biological Chemistry May 2024Inflammasomes serve as critical sensors for disruptions to cellular homeostasis, with inflammasome assembly leading to inflammatory caspase activation, gasdermin... (Review)
Review
Inflammasomes serve as critical sensors for disruptions to cellular homeostasis, with inflammasome assembly leading to inflammatory caspase activation, gasdermin cleavage, and cytokine release. While the canonical pathways leading to priming, assembly, and pyroptosis are well characterized, recent work has begun to focus on the role of post-translational modifications (PTMs) in regulating inflammasome activity. A diverse array of PTMs, including phosphorylation, ubiquitination, SUMOylation, acetylation, and glycosylation, exert both activating and inhibitory influences on members of the inflammasome cascade through effects on protein-protein interactions, stability, and localization. Dysregulation of inflammasome activation is associated with a number of inflammatory diseases, and evidence is emerging that aberrant modification of inflammasome components contributes to this dysregulation. This review provides insight into PTMs within the NLRP3 inflammasome pathway and their functional consequences on the signaling cascade, and highlights outstanding questions that remain regarding the complex web of signals at play.
PubMed: 38763335
DOI: 10.1016/j.jbc.2024.107386 -
European Journal of Cell Biology May 2024Nuclear receptor Nur77 plays a pivotal role in immune regulation across various tissues, influencing pro-inflammatory signaling pathways and cellular metabolism. While...
Nuclear receptor Nur77 plays a pivotal role in immune regulation across various tissues, influencing pro-inflammatory signaling pathways and cellular metabolism. While cellular mechanics have been implicated in inflammation, the contribution of Nur77 to these mechanical processes remains elusive. Macrophages exhibit remarkable plasticity in their morphology and mechanics, enabling them to adapt and execute essential inflammatory functions, such as navigating through inflamed tissue and pathogen engulfment. However, the precise regulatory mechanisms governing these dynamic changes in macrophage mechanics during inflammation remain poorly understood. To establish the potential correlation of Nur77 with cellular mechanics, we compared bone marrow-derived macrophages (BMDMs) from wild-type (WT) and Nur77-deficient (Nur77-KO) mice and employed cytoskeletal imaging, single-cell acoustic force spectroscopy (AFS), migration and phagocytosis assays, and RNA-sequencing. Our findings reveal that Nur77-KO BMDMs exhibit changes to their actin networks compared to WT BMDMs, which is associated with a stiffer and more rigid phenotype. Subsequent in vitro experiments validated our observations, showcasing that Nur77 deficiency leads to enhanced migration, reduced adhesion, and increased phagocytic activity. The transcriptomics data confirmed altered mechanics-related pathways in Nur77-deficient macrophage that are accompanied by a robust pro-inflammatory phenotype. Utilizing previously obtained ChIP-data, we revealed that Nur77 directly targets differentially expressed genes associated with cellular mechanics. In conclusion, while Nur77 is recognized for its role in reducing inflammation of macrophages by inhibiting the expression of pro-inflammatory genes, our study identifies a novel regulatory mechanism where Nur77 governs macrophage inflammation through the modulation of expression of genes involved in cellular mechanics. Our findings suggest that immune regulation by Nur77 may be partially mediated through alterations in cellular mechanics, highlighting a potential avenue for therapeutic targeting.
PubMed: 38763048
DOI: 10.1016/j.ejcb.2024.151419 -
Cellular & Molecular Biology Letters May 2024The role of the scavenger receptor CD36 in cell metabolism and the immune response has been investigated mainly in macrophages, dendritic cells, and T cells. However,...
BACKGROUND
The role of the scavenger receptor CD36 in cell metabolism and the immune response has been investigated mainly in macrophages, dendritic cells, and T cells. However, its involvement in B cells has not been comprehensively examined.
METHODS
To investigate the function of CD36 in B cells, we exposed Cd36MB1 mice, which lack CD36 specifically in B cells, to apoptotic cells to trigger an autoimmune response. To validate the proteins that interact with CD36 in primary B cells, we conducted mass spectrometry analysis following anti-CD36 immunoprecipitation. Immunofluorescence and co-immunoprecipitation were used to confirm the protein interactions.
RESULTS
The data revealed that mice lacking CD36 in B cells exhibited a reduction in germinal center B cells and anti-DNA antibodies in vivo. Mass spectrometry analysis identified 30 potential candidates that potentially interact with CD36. Furthermore, the interaction between CD36 and the inhibitory Fc receptor FcγRIIb was first discovered by mass spectrometry and confirmed through immunofluorescence and co-immunoprecipitation techniques. Finally, deletion of FcγRIIb in mice led to decreased expression of CD36 in marginal zone B cells, germinal center B cells, and plasma cells.
CONCLUSIONS
Our data indicate that CD36 in B cells is a critical regulator of autoimmunity. The interaction of CD36-FcγRIIb has the potential to serve as a therapeutic target for the treatment of autoimmune disorders.
Topics: Animals; CD36 Antigens; Receptors, IgG; B-Lymphocytes; Autoimmune Diseases; Mice; Germinal Center; Mice, Inbred C57BL; Protein Binding; Mice, Knockout; Autoimmunity
PubMed: 38762740
DOI: 10.1186/s11658-024-00593-7 -
Communications Biology May 2024
PubMed: 38762602
DOI: 10.1038/s42003-024-06302-6 -
Nature Communications May 2024Cross-modal analysis of the same whole brain is an ideal strategy to uncover brain function and dysfunction. However, it remains challenging due to the slow speed and...
Cross-modal analysis of the same whole brain is an ideal strategy to uncover brain function and dysfunction. However, it remains challenging due to the slow speed and destructiveness of traditional whole-brain optical imaging techniques. Here we develop a new platform, termed Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN), for non-destructive, high-speed, 3D imaging of ex vivo rodent, ferret, and non-human primate brains. Using an optimally designed image acquisition scheme and an accompanying machine-learning algorithm, PATTERN extracts signals of genetically-encoded probes from photobleaching-based temporal modulation and enables reliable visualization of neural projection in the whole central nervous system with 3D isotropic resolution. Without structural and biological perturbation to the sample, PATTERN can be combined with other whole-brain imaging modalities to acquire the whole-brain image with both high resolution and morphological fidelity. Furthermore, cross-modal transcriptome analysis of an individual brain is achieved by PATTERN imaging. Together, PATTERN provides a compatible and versatile strategy for brain-wide cross-modal analysis at the individual level.
Topics: Animals; Brain; Photoacoustic Techniques; Ferrets; Imaging, Three-Dimensional; Mice; Algorithms; Machine Learning; Tomography; Image Processing, Computer-Assisted; Rats; Male
PubMed: 38762498
DOI: 10.1038/s41467-024-48393-z -
Biochimica Et Biophysica Acta.... May 2024Peroxisome biogenesis disorders are caused by pathogenic variants in genes involved in biogenesis and maintenance of peroxisomes. However, mitochondria are also often...
Peroxisome biogenesis disorders are caused by pathogenic variants in genes involved in biogenesis and maintenance of peroxisomes. However, mitochondria are also often affected in these diseases. Peroxisomal membrane proteins, including PEX14, have been found to mislocalise to mitochondria in cells lacking peroxisomes. Recent studies indicated that this mislocalisation contributes to mitochondrial abnormalities in PEX3-deficient patient fibroblasts cells. Here, we studied whether mitochondrial morphology is also affected in PEX3-deficient HEK293 cells and whether PEX14 mislocalises to mitochondria in these cells. Using high-resolution imaging techniques, we show that although endogenous PEX14 mislocalises to mitochondria, mitochondrial morphology was normal in PEX3-KO HEK293 cells. However, we discovered that overexpression of tagged PEX14 in wild-type HEK293 cells resulted in its mitochondrial localisation, accompanied by altered mitochondrial morphology. Our data indicate that overexpression of tagged PEX14 alone directly or indirectly cause mitochondrial abnormalities in cells containing peroxisomes.
PubMed: 38762172
DOI: 10.1016/j.bbamcr.2024.119754 -
American Journal of Obstetrics and... May 2024To evaluate the role of maternal age in the incidence of non-chromosomal congenital anomalies (NCAs) and to pinpoint age groups at higher risk to refine screening... (Review)
Review
Very Young and Advanced Maternal Age Strongly Elevates the Occurrence of Non-Chromosomal Congenital Anomalies: A Systematic Review and Meta-Analysis of Population-Based Studies.
OBJECTIVE
To evaluate the role of maternal age in the incidence of non-chromosomal congenital anomalies (NCAs) and to pinpoint age groups at higher risk to refine screening protocols.
DATA SOURCES
Search performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase.
STUDY ELIGIBILITY CRITERIA
Included were population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women, without restrictions on age range, country, or comorbidities.
STUDY APPRAISAL AND SYNTHESIS METHODS
The PRISMA 2020 guideline and Cochrane Handbook informed the systematic review and meta-analysis. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies.
RESULTS
From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (RR 1.31, CI: 1.07-1.61), rising notably after >40 (RR 1.44, CI: 1.25-1.66). The latter changes to 1.25 (CI: 1.08-1.46) if the co-occurrence of chromosomal aberrations is excluded. Specific anomalies like cleft lip/palate (>40, RR 1.57, CI: 1.11-2.20) and circulatory system defects (>40, RR 1.94, CI: 1.28-2.93) were significantly associated with advanced maternal age. Conversely, gastroschisis was linked to mothers <20 (RR 3.08, CI: 2.74-3.47).
CONCLUSIONS
The study confirms that both very young and advanced maternal ages significantly increase the risk of NCAs. There's a pressing need for age-specific prenatal screening protocols to better detect these anomalies, especially considering the current trend of delayed childbearing. Further research is required to fully understand the impact of maternal age on the prevalence of rarer NCAs.
PubMed: 38761840
DOI: 10.1016/j.ajog.2024.05.010