NLRX1 inhibits the early stages of CNS inflammation and prevents the onset of spontaneous autoimmunity.

Nucleotide-binding, leucine-rich repeat containing X1 (NLRX1) is a mitochondria-located innate immune sensor that inhibits major pro-inflammatory pathways such as type I interferon and nuclear factor-κB signaling. We generated a novel, spontaneous, and rapidly progressing mouse model of multiple sclerosis (MS) by crossing myelin-specific T-cell receptor (TCR) transgenic mice with Nlrx1-/- mice. About half of the resulting progeny developed spontaneous experimental autoimmune encephalomyelitis (spEAE), which was associated with severe demyelination and inflammation in the central nervous system (CNS). Using lymphocyte-deficient mice and a series of adoptive transfer experiments, we demonstrate that genetic susceptibility to EAE lies within the innate immune compartment. We show that NLRX1 inhibits the subclinical stages of microglial activation and prevents the generation of neurotoxic astrocytes that induce neuronal and oligodendrocyte death in vitro. Moreover, we discovered several mutations within NLRX1 that run in MS-affected families. In summary, our findings highlight the importance of NLRX1 in controlling the early stages of CNS inflammation and preventing the onset of spontaneous autoimmunity.

Tissue histology on the correlation between fracture energy and elasticity.

PURPOSE: Preemptively estimating tissue damage is crucial for a safe surgical procedure. We previously investigated the possibility of estimating the fracture energies of biological tissues based on their elasticities. However, the reason behind the presence of these correlations is poorly understood. In this study, we investigate the effect of a tissue's histology on the correlation between the fracture energy and elasticity. We hypothesize that two tissues with similar fibrous structure will show a similar correlation between the fracture energy and elasticity. METHODS: Porcine duodenum were used for this study. Two tensile tests were performed for each porcine duodenum specimen to determine its elasticity and tearing energy. The correlation between fracture energy and elasticity was then investigated using the results from the mechanical tests. Furthermore, duodenum specimens were fixed in 10% formalin while under tension. Microscopic images were then taken to visualize the fibrous structure within the duodenum tissues under tension. RESULTS: The results from the tensile test showed that the fracture energy had an isotropic positive and linear correlation with the elasticity to the negative 0.5th power (R2 = 0.89), which was also previously reported in small intestinal (jejunum) specimens. Furthermore, the tearing patterns of the duodenum were identical to the ones reported in the jejunum. Hematoxylin and eosin staining on tissues fixed under tension showed that the endomysium fibers are involved in providing resistance toward traction. CONCLUSION: Through mechanical tests, we showed that porcine duodenum tissues also have a correlation between its fracture energy and elasticity. We also discussed that the histological structure of a tissue is an important factor that dictates how the tearing energy of a tissue will correlate to the elasticity. We understood that since the tearing mechanism between the duodenum and jejunum was similar, the correlations between their fracture energies and elasticities were also similar.

Tissue damage force estimation in porcine small intestine from its elasticity.

PURPOSE: Post-surgical complications are correlated to the surgeon's technical skill level. Thus, efforts are being put in finding ways to improve the surgeon's technical skills, such as not causing unwanted damage to tissues during surgery. In this study, we aim to investigate the possibility of estimating biological tissue damage, in view of preventing unwanted damage during surgery. METHODS: A series of tensile tests were performed on porcine small intestinal tissue to determine the elasticity and the tearing force. The tissue was then microscopically observed to investigate the influence of fibrous protein configuration in the tissue's mechanical properties. RESULTS: The results from the tensile test showed that the fracture energy had a positive and linear correlation with the elasticity to the negative 0.5th power (R2 = 0.897), which was also suggested by an existing damage model for polymeric materials (Lake-Thomas model). The results from the microscopic observations also showed a resembling influence of fiber configuration on the elasticity as suggested in polymer mechanics (affine network model). CONCLUSION: We showed that the fracture energy had a correlation with the elasticity in porcine small intestinal tissues, which was also suggested in polymer mechanics, thus being a promising avenue toward the ability to estimate the maximum applicable force onto a biological tissue without causing damage during surgery. Attention should also be pointed, however, towards investigating the extent at which polymer mechanics and biomechanics overlap.

Bacterial adhesion and antibacterial property of coating materials containing theobromine and S-PRG filler.

Theobromine (TB) has been reported to promote tooth remineralization, strengthen tooth substance, and relieve dentin hypersensitivity. This study aimed to evaluate experimental tooth coating materials containing TB and surface pre-reacted glass-ionomer (S-PRG) fillers by examining the effects on bacterial adhesion and antibacterial properties. In addition, the amount of TB eluted from the coating material was measured. There was no significant difference in bacterial adhesion depending on the presence or absence of TB in the coating material, however, a significant decrease in the amount of bacterial adhesion was observed when S-PRG fillers were added to the coating material. The amount of eluted TB did not differ depending on the type of the filler in the coating material. It was suggested that TB could be used to develop a new dental material with the potential ability to inhibit the initiation and progression of dental caries.

Exhaustive Multi-Parametric Assessment of the Behavioral Array of Daily Activities of Mice Using Cluster and Factor Analysis.

Using automated supervised behavioral assessment software, we recorded and analyzed 24 h non-interrupted recordings of mice for a duration of 11 days. With the assistance of free R programming, we used correlation matrix-based hierarchical clustering and factor analysis to separate the 33 activities into meaningful clusters and groups without losing the exhaustive nature of the findings. These groups represent novel meaningful behavioral patterns exhibited by mice in home cage. Thirty-three activities were separated into 5 clusters based on dissimilarity between activities and 6 factors based on statistical modeling. Using these two methods, we describe and compare behavioral arrays of two groups of animals: 1. Continuously recorded for 11 days in social isolation and 2. Intermittently socially isolated for recording on days 1, 3, 5, 8, and 10, while socializing on the other days. This is the first work to our knowledge that interprets mouse home cage activities throughout a 24 h period and proposes a base line of a daily routine of a healthy C57Bl/6J mouse that can be used for various experimental paradigms, including disease, neuroinflammation, or drug testing to trace behavioral changes that follow intervention. In this work, we defined the necessary acclimatization period for the 24 h recording paradigm of home cage behavior. We demonstrated the behavioral changes that are associated with the effect of social isolation, intermittent socialization, and re-introduction to a familiar home cage. We provide the full description of the codes used in R.