Hutchinson–Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain. In an attempt to clarify the origin of this phenomenon, we have developed an inducible transgenic mouse model with expression of the most common HGPS mutation in brain, skin, bone and heart to investigate how the mutation affects these organs. Ultrastructural analysis of neuronal nuclei after 70 weeks of expression of the LMNA c.1824C>T mutation showed severe distortion with multiple lobulations and irregular extensions. Despite severe distortions in the nuclei of hippocampal neurons of HGPS animals, there were only negligible changes in gene expression after 63 weeks of transgenic expression. Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology. Our results suggest that certain tissues are protected from functional deleterious effects of progerin.
Even though K63-linked polyubiquitin chains do not target proteins for proteasomal degradation, they play nevertheless a complementary protective role in maintaining protein homeostasis by directing malfunctioning proteins and organelles to inclusion bodies or autophagosomes. A paradigm for this process is the sequestration and autophagic degradation of dysfunctional mitochondria. Although studies have shown that K63-ubiquitylation of mitochondrial proteins by the ubiquitin ligase Parkin is important in this process, it is presently not clear if this modification also suffices to initiate this cascade of events. To address this question, we have engineered the ubiquitin ligase ProxE3, which in an inducible manner synthesizes K63-linked ubiquitin chains on the surface of mitochondria. We found that the presence of K63-linked ubiquitin chains on mitochondria resulted in the recruitment of the ubiquitin adaptor p62 and induced a dramatic redistribution of mitochondria, which was reminiscent to the Parkin-facilitated sequestration in response to mitochondrial uncoupler. However, ProxE3 did not induce autophagic degradation of mitochondria. Our data show that K63-linked ubiquitin chains at the mitochondrial membrane are sufficient for the induction of mitochondrial sequestration, but not mitophagy, without the need of extrinsically inflicting mitochondrial dysfunction.
Background & Aims Previous investigations have aimed at investigating parameters affecting age perception on several ethnicities. Perceived health has been a newer focus on Caucasian skin, yet little is known on the skin features used to estimate the health status of Chinese women and we aimed to investigate whether these cues are the same as those used for age perception. Methods Age and health appearance of 276 Chinese female volunteers were estimated from their photographs by 1025 female naïve Chinese graders 20–69 years old. Models were built to predict perceived age and health from topographic, colour and biophysical measured variables, in two subsets of the studied volunteers: below and above 50 years. Machine learning‐based predictive models for age and health perception were built on the collected data, and the interpretability of the models was established by measuring feature importance. Results Age perception was mostly driven by topographic features, particularly eye bags and eyelid sagging in the group below 50 years old. Wrinkles, notably from the lower part of the face and oval of the lower face, were found to be more relevant in the group above 50 years. Health appearance was primarily signalled by skin imperfections and global pigmentation in the subset below 50 years, whereas colour‐related parameters and skin hydration acted as health cues for the subset above 50 years. Conclusion Distinct skin features were acting as cues for age perception and/or health perception and varied per age subset. Their contribution should be borne in mind when designing products for ‘younger looking skin’ and ‘healthier looking skin’.
A free sorting task was applied to sort chocolate proteins bars by trained and untrained panelists. Trained and untrained panelists sorted the nine chocolate proteins bars samples into groups. They were then asked to describe in their own words after the sorting was done. Multidimensional Scaling and Correspondence Analysis were performed on these data. Results showed that trained and untrained panels sorted the chocolate proteins bars in a similar way (RV coefficient value). The results also show that the trained panel was significantly more objective than the untrained panel. However, comparable terms were used similarly by both panels and statistical results indicated that untrained and trained panels could be used for free sorting tasks as both panels were able to perform the test being discriminative. Practical ApplicationsThe free sorting task method was used for the first time to differentiate a complex food product with trained and untrained panelists. This task associated with word association was a success and enable the use of this sensory method to potentially understand a strategic local market with consumer feedback.
Introduction: Acne is one of the most common skin concerns of unknown etiology, often connected to the menstrual cycle in women, and possibly to the microbial profile and function. Objective:We aimed to investigate how hormonal fluctuation affects hormonal acneprone skin in different populations in relation to skin clinical parameters and microbial profiles. Methods:We evaluated skin features by using biophysical and topographical tools.For microbial profiling, we sequenced facial skin microbiota and associated the findings with the skin clinical parameters during the different phases of the menstrual cycle.Results: We identified differences between and within hormonal phases in women of Chinese and Caucasian origin. Changes were discovered in transepidermal water loss (TEWL), sebum level, hydration level, and pore volume. The most abundant identifiable genera in both ethnicities were Cutibacterium, Staphylococcus, and Streptococcus, without any significant abundant differences within the menstrual cycle. Interestingly, 11 bacterial metabolic pathways were downregulated in Chinese compared to Caucasian skin during the follicular phase. The majority of these pathways were associated with skin redox balance, perhaps indicating a weaker oxidative stress response in Chinese versus Caucasian skin. Novosphingobium taxa were increased in the Chinese skin microbiome, which has been reported to protect skin from pollution-mediated oxidative stress. Conclusion:Thus, this pilot study explored some of the clinical and metagenomic changes in acne-prone skin, and provide guidance to tailor-personalized skin care regimes during the menstrual cycle. Also, the skin redox status in acne-prone skin, provides more opportunity to tailor-personalized skin care regimes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.