Congenital disorders of glycosylation (CDG) and mitochondrial disorders are multisystem disorders with overlapping symptomatology. Pathogenic variants in the PMM2 gene lead to abnormal N-linked glycosylation. This disruption in glycosylation can induce endoplasmic reticulum stress, contributing to the disease pathology. Although impaired mitochondrial dysfunction has been reported in some CDG, cellular bioenergetics has never been evaluated in detail in PMM2-CDG. This prompted us to evaluate mitochondrial function and autophagy/mitophagy in vitro in PMM2 patient-derived fibroblast lines of differing genotypes from our natural history study. We found secondary mitochondrial dysfunction in PMM2-CDG. This dysfunction was evidenced by decreased mitochondrial maximal and ATP-linked respiration, as well as decreased complex I function of the mitochondrial electron transport chain. Our study also revealed altered autophagy in PMM2-CDG patient-derived fibroblast lines. This was marked by an increased abundance of the autophagosome marker LC3-II. Additionally, changes in the abundance and glycosylation of proteins in the autophagy and mitophagy pathways further indicated dysregulation of these cellular processes. Interestingly, serum sorbitol levels (a biomarker of disease severity) and the CDG severity score showed an inverse correlation with the abundance of the autophagosome marker LC3-II. This suggests that autophagy may act as a modulator of biochemical and clinical markers of disease severity in PMM2-CDG. Overall, our research sheds light on the complex interplay between glycosylation, mitochondrial function, and autophagy/mitophagy in PMM2-CDG. Manipulating mitochondrial dysfunction and alterations in autophagy/mitophagy pathways could offer therapeutic benefits when combined with existing treatments for PMM2-CDG.
<p>Where progression towards gender equality is concerned, Japan lags behind most other developed countries with its culture which heavily values tradition. However, its traditional gender roles may be changing as the birth-rate declines and women take up the increasing opportunities opening up for them in the workplace. Within the contexts of these tensions between traditionalism and change, this study investigated the constructions of femininity in popular Japanese manga, one of the most consumed forms of media in Japan which also enjoys global popularity. As such, this study approached manga as a potentially important resource for identifying the available meanings of being a young Japanese woman in contemporary Japanese society. To date, little research has examined manga, and much of the available literature has used content analysis or focused solely on superheroine characters and the romantic interest. As a point of difference, this research implemented discursive analyses and sought to identify a range of femininities made available to readers in manga. It examined four titles within two genres of manga: the shounen genre targeted to male audiences and the shoujo manga, targeted at a female audience. The research employed a feminist, poststructuralist framework to identify the ways in which constructions of femininity in manga drew on dominant Japanese discourses of femininity as well as more globally produced postfeminist discourses associated with popular culture. The study found that manga overall produced femininities within both traditional and contemporary postfeminist discourses. Analyses also highlighted the limited meanings of femininity made available to young female audiences of shoujo manga through dominant postfeminist, empty representations of ‘empowerment’ whilst also underlining the problematic dominance of sexist portrayals of young women in shounen manga. Further, the storylines of shoujo manga were found to be replete with romantic narratives, prioritising romance and marriage as a means to happiness. These findings may identify the implications of such femininities on how young Japanese women view themselves, and are viewed by others globally.</p>
Glucagon has been shown effective for the treatment of insulinoma-associated hypoglycemia. However, its use has been limited to preoperative supportive care and emergency treatment of hypoglycemic crisis because of the need of constant intravenous infusion administration. Here, we report a case of insulinoma in a dog managed with subcutaneous saline-diluted glucagon and a continuous glucose monitoring system (CGMS), which were effective in glycemic control allowing longterm home treatment. A 14-year-old spayed female Lakeland terrier presented with hypoglycemic crisis, unresponsive to prednisolone and diet.The dog was diagnosed with insulinoma based on hyperinsulinemia and computed tomography ndings. Treatment with subcutaneous diluted glucagon along with CGMS monitoring allowed the patient to remain at home with controlled glycemia for approximately 4 months. Therefore, a combination of subcutaneous diluted glucagon and CGMS might be an effective long-term supportive care of insulinoma in dogs.
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