Changes in protein fluxes and gene expression in non-injured muscle tissue distant from an acute myotoxic injury in male mice.

The response to acute myotoxic injury requires stimulation of local repair mechanisms in the damaged tissue. However, satellite cells in muscle distant from acute injury have been reported to enter a functional state between quiescence and active proliferation. Here, we asked whether protein flux rates are altered in muscle distant from acute local myotoxic injury and how they compare to changes in gene expression from the same tissue. Broad and significant alterations in protein turnover were observed across the proteome in the limb contralateral to injury during the first 10 days after. Interestingly, mRNA changes had almost no correlation with directly measured protein turnover rates. In summary, we show consistent and striking changes in protein flux rates in muscle tissue contralateral to myotoxic injury, with no correlation between changes in mRNA levels and protein synthesis rates. This work motivates further investigation of the mechanisms, including potential neurological factors, responsible for this distant effect. KEY POINTS: Previous literature demonstrates that stem cells of uninjured muscle respond to local necrotic muscle tissue damage and regeneration. We show that muscle tissue that was distant from a model of local necrotic damage had functional changes at both the gene expression and the protein turnover level. However, these changes in distant tissue were more pronounced during the earlier stages of tissue regeneration and did not correlate well with each other. The results suggest communication between directly injured tissue and non-affected tissues that are distant from injury, which warrants further investigation into the potential of this mechanism as a proactive measure for tissue regeneration from damage.

Changes in protein fluxes in skeletal muscle during sequential stages of muscle regeneration after acute injury in male mice.

Changes in protein turnover play an important role in dynamic physiological processes, including skeletal muscle regeneration, which occurs as an essential part of tissue repair after injury. The inability of muscle tissue to recapitulate this regenerative process can lead to the manifestation of clinical symptoms in various musculoskeletal diseases, including muscular dystrophies and pathological atrophy. Here, we employed a workflow that couples deuterated water (2H2O) administration with mass spectrometry (MS) to systematically measure in-vivo protein turnover rates across the muscle proteome in 8-week-old male C57BL6/J mice. We compared the turnover kinetics of over 100 proteins in response to cardiotoxin (CTX) induced muscle damage and regeneration at unique sequential stages along the regeneration timeline. This analysis is compared to gene expression data from mRNA-sequencing (mRNA-seq) from the same tissue. The data reveals quantitative protein flux signatures in response to necrotic damage, in addition to sequential differences in cell proliferation, energy metabolism, and contractile gene expression. Interestingly, the mRNA changes correlated poorly with changes in protein synthesis rates, consistent with post-transcriptional control mechanisms. In summary, the experiments described here reveal the signatures and timing of protein flux changes during skeletal muscle regeneration, as well as the inability of mRNA expression measurements to reveal changes in directly measured protein turnover rates. The results of this work described here provide a better understanding of the muscle regeneration process and could help to identify potential biomarkers or therapeutic targets.

"This is not built for me": A qualitative study of adult-sized changing tables and public restroom accessibility.

BACKGROUND: Adult-sized changing tables allow individuals with disabilities or medical conditions related to toileting to change with or without assistance. These tables are rarely found in public restrooms, and as a result, those who need them are often changed on floors, in vehicles, or are unable to stay in public spaces for more than a few hours. OBJECTIVE: This study aimed to understand how individuals who utilize adult-sized changing tables, or self-advocates, and caregivers for disabled people, access public restrooms and to report recommendations to improve inclusivity of public restrooms. METHODS: We virtually interviewed five self-advocates and sixteen caregivers in February and March 2023. We performed a qualitative analysis of the interview transcripts using MAXQDA 2022. RESULTS: Four major themes arose during interviews: social consequences, health effects, caregiver effects, and inaccessibility of restrooms in the healthcare setting. All caregivers have changed disabled individuals in vehicles, and 11 on public restroom floors, experiencing guilt and stress, and often receiving injuries. Several respondents reported limiting intake of fluids or using suppositories to prevent the need to toilet during unavoidable outings. Respondents most need height adjustable changing tables in healthcare settings, airports, and large recreational facilities. CONCLUSIONS: Without adult-sized changing tables, individuals with disabilities are forced to risk their health and dignity to utilize public spaces.

Weighting Methods for Rare Event Identification From Imbalanced Datasets.

In machine learning, we often face the situation where the event we are interested in has very few data points buried in a massive amount of data. This is typical in network monitoring, where data are streamed from sensing or measuring units continuously but most data are not for events. With imbalanced datasets, the classifiers tend to be biased in favor of the main class. Rare event detection has received much attention in machine learning, and yet it is still a challenging problem. In this paper, we propose a remedy for the standing problem. Weighting and sampling are two fundamental approaches to address the problem. We focus on the weighting method in this paper. We first propose a boosting-style algorithm to compute class weights, which is proved to have excellent theoretical property. Then we propose an adaptive algorithm, which is suitable for real-time applications. The adaptive nature of the two algorithms allows a controlled tradeoff between true positive rate and false positive rate and avoids excessive weight on the rare class, which leads to poor performance on the main class. Experiments on power grid data and some public datasets show that the proposed algorithms outperform the existing weighting and boosting methods, and that their superiority is more noticeable with noisy data.

Online couples mindfulness-based intervention for young breast cancer survivors and their partners: A randomized-control trial.

PURPOSE: Young breast cancer survivors (YBCS) face unique challenges in coping with disease, distress, and relationship concerns. The purposes of this study were to understand the acceptability and feasibility of an online Mindfulness-Based Intervention (MBI) for YBCS and their partners (i.e., Couples Mindfulness-Based Intervention: C-MBI) and to compare the effectiveness of the C-MBI to a closely-matched control, an online MBI for individuals (I-MBI). METHODS: YBCS and their partners were recruited. Couples were randomly assigned to an 8-week C-MBI (couples = 41) or to I-MBI (couples = 36), which included one-hour video modules, a manual, and guided-meditation audios. Both couple members participated in the C-MBI; only the YBCS participated in the control I-MBI. Participants answered surveys about individual- and couple-level functioning at baseline and post-intervention. RESULTS: Online delivery was shown to be feasible and acceptable. For YBCS and their partners, levels of perceived stress, anxiety, depression, and fatigue were lower after the intervention, in both conditions. Unexpectedly, however, participating in the C-MBI appeared to have detrimental effects on dyadic adjustment and relationship quality. CONCLUSION: Although YBCS and their partners reported online delivery was acceptable and benefited well-being, for couple-based MBIs to have benefits for relationship functioning, it may be necessary for couples to have the support of other couples and an instructor. Online delivery may be particularly acceptable and effective for clinical populations, including YBCS. Medical professionals may be more likely to recommend online-MBI programs to cancer survivors, because the programs are of little or no cost.

A mathematical formulation of DNA computation.

DNA computation is to use DNA molecules for information storing and processing. The task is accomplished by encoding and interpreting DNA molecules in suspended solutions before and after the complementary binding reactions. DNA computation is attractive, due to its fast parallel information processing, remarkable energy efficiency, and high storing capacity. Challenges currently faced by DNA computation are: 1) lack of theoretical computational models for applications and 2) high error rate for implementation. This paper attempts to address these problems from mathematical modeling and genetic coding aspects. The first part of this paper presents a mathematical formulation of DNA computation. The model may serve as a theoretical framework for DNA computation. In the second part, a genetic code based DNA computation approach is presented to reduce error rate for implementation, which has been a major concern for DNA computation. The method provides a promising alternative to reduce error rate for DNA computation.