Beta cell antigens in type 1 diabetes: triggers in pathogenesis and therapeutic targets

Recognition of pancreatic beta cell antigens by autoreactive T lymphocytes plays a central role in the pathogenesis of insulin-dependent type 1 diabetes. Recent results suggest that non-conventional antigenic epitope processing and presentation may contribute to triggering and maintaining autoreactive responses. Moreover, promising results raise hope that autoantigens may become safe and specific therapeutics for type 1 diabetes in the future

Stair Negotiation Made Easier using Novel Interactive Energy-Recycling Assistive Stairs

Here we show that novel, energy-recycling stairs reduce the amount of work required for humans to both ascend and descend stairs. Our low-power, interactive, and modular steps can be placed on existing staircases, storing energy during stair descent and returning that energy to the user during stair ascent. Energy is recycled through event-triggered latching and unlatching of passive springs without the use of powered actuators. When ascending the energy-recycling stairs, naive users generated 17.4 ± 6.9% less positive work with their leading legs compared to conventional stairs, with the knee joint positive work reduced by 37.7 ± 10.5%. Users also generated 21.9 ± 17.8% less negative work with their trailing legs during stair descent, with ankle joint negative work reduced by 26.0 ± 15.9%. Our low-power energy-recycling stairs have the potential to assist people with mobility impairments during stair negotiation on existing staircases

A comparison of the learning effects between TGfU-SE and TGfU on learning motivation, sport enjoyment, responsibility, and game performance in physical education

BackgroundBoth the Sport Education (SE) model and Teaching Games for Understanding (TGfU) have been connected to the theory of situated learning, which is a game-centered curricular model. TGfU emphasizes tactical awareness, decision making, and skill execution. The SE model provides a complete season during physical education (PE) lessons. Therefore, it is worth exploring the integration of TGfU with SE (TGfU-SE) model in PE courses, and whether the hybrid TGfU-SE model can achieve better learning effects for students than the TGfU model alone.PurposeThe purpose of the study was to compare the difference in learning effects between the TGfU-SE model and the TGfU model on students’ learning motivation, sport enjoyment, responsibility, and game performance.MethodsThis study used a quasi-experimental design to compare different learning effects between the experimental group (TGfU-SE) and the control group (TGfU). The participants lived in Taiwan, including two junior high school PE teachers and four PE classes with a total of 90 students (TGfU-SE group, n = 46; TGfU group, n = 44). Each teacher taught two PE classes, one with an experimental group and one with a control group. This study used four research instruments, including the Responsibility Scale in Physical Education (RSPE), Learning Motivation Scale in Physical Education (LMSPE), Sport Enjoyment Scale in Physical Education (SESPE), and Game Performance assessment instrument (GPAI). Analysis of covariance (ANCOVA) and the independent t-test were used to analyze the data.ResultsThe results of this study showed that the TGfU-SE model had more positive learning effects on students’ learning motivation, sport enjoyment, responsibility, and game performance than the TGfU model.Conclusionwe concluded that the TGfU-SE model had a more positive influence on students’ learning performance than the TGfU model. It is suggested that the hybrid TGfU-SE model could be implemented effectively in the PE curriculum

A quantitative analysis of monochromaticity in genetic interaction networks

<p>Abstract</p> <p>Background</p> <p>A genetic interaction refers to the deviation of phenotypes from the expected when perturbing two genes simultaneously. Studying genetic interactions help clarify relationships between genes, such as compensation and masking, and identify gene groups of functional modules. Recently, several genome-scale experiments for measuring quantitative (positive and negative) genetic interactions have been conducted. The results revealed that genes in the same module usually interact with each other in a consistent way (pure positive or negative); this phenomenon was designated as monochromaticity. Monochromaticity might be the underlying principle that can be utilized to unveil the modularity of cellular networks. However, no appropriate quantitative measurement for this phenomenon has been proposed.</p> <p>Results</p> <p>In this study, we propose the monochromatic index (MCI), which is able to quantitatively evaluate the monochromaticity of potential functional modules of genes, and the MCI was used to study genetic landscapes in different cellular subsystems. We demonstrated that MCI not only amend the deficiencies of MP-score but also properly incorporate the background effect. The results showed that not only within-complex but also between-complex connections present significant monochromatic tendency. Furthermore, we also found that significantly higher proportion of protein complexes are connected by negative genetic interactions in metabolic network, while transcription and translation system adopts relatively even number of positive and negative genetic interactions to link protein complexes.</p> <p>Conclusion</p> <p>In summary, we demonstrate that MCI improves deficiencies suffered by MP-score, and can be used to evaluate monochromaticity in a quantitative manner. In addition, it also helps to unveil features of genetic landscapes in different cellular subsystems. Moreover, MCI can be easily applied to data produced by different types of genetic interaction methodologies such as Synthetic Genetic Array (SGA), and epistatic miniarray profile (E-MAP).</p

Regulation of translation is required for dendritic cell function and survival during activation

In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control antigen processing and presentation. Here, we show that in response to lipopolysaccharides, protein synthesis is rapidly enhanced in DCs. This enhancement occurs via a PI3K-dependent signaling pathway and is key for DC activation. In addition, we show that later on, in a manner similar to viral or apoptotic stress, DC activation leads to the phosphorylation and proteolysis of important translation initiation factors, thus inhibiting cap-dependent translation. This inhibition correlates with major changes in the origin of the peptides presented by MHC class I and the ability of mature DCs to prevent cell death. Our observations have important implications in linking translation regulation with DC function and survival during the immune response

Rapamycin attenuates PLA2R activation-mediated podocyte apoptosis via the PI3K/AKT/mTOR pathway

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults without diabetes. Primary MN has been associated with circulating antibodies against native podocyte antigens, including phospholipase A2 receptor (PLA2R); however, precision therapy targeting the signaling cascade of PLA2R activation is lacking. Both PLA2R and the mammalian target of rapamycin (mTOR) exist in podocytes, but the interplay between these two proteins and their roles in MN warrants further exploration. This study aimed to investigate the crosstalk between PLA2R activation and mTOR signaling in a human podocyte cell line. We demonstrated that podocyte apoptosis was induced by Group IB secretory phospholipase A2 (sPLA2IB) in a concentration- and time-dependent manner via upregulation of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and mTOR, and inhibited by rapamycin or LY294002. Furthermore, aberrant activation of the PI3K/AKT/mTOR pathway triggers both extrinsic (caspase-8 and caspase-3) and intrinsic (Bcl-2-associated X protein [BAX], B-cell lymphoma 2 [BCL-2], cytochrome c, caspase-9, and caspase-3) apoptotic cascades in podocytes. The therapeutic implications of our findings are that strategies to reduce PLA2R activation and PI3K/AKT/mTOR pathway inhibition in PLA2R-activated podocytes help protect podocytes from apoptosis. The therapeutic potential of rapamycin shown in this study provides cellular evidence supporting the repurposing of rapamycin for MN treatment