The Anti-Desmoglein 1 Autoantibodies in Pemphigus Vulgaris Sera are Pathogenic

Pemphigus vulgaris and pemphigus foliaceus are two closely related, but clinically and histologically distinct, autoimmune skin diseases. The autoantigens for pemphigus vulgaris and pemphigus foliaceus are desmoglein 3 and desmoglein 1, respectively. The anti-desmoglein 1 antibodies in pemphigus foliaceus and anti-desmoglein 3 antibodies in pemphigus vulgaris are pathogenic as determined by immunoglobulin G passive transfer animal models. More than 50% of pemphigus vulgaris sera also contain anti-desmoglein 1 autoantibodies; however, the pathogenicity of the anti-desmoglein 1 autoantibodies in pemphigus vulgaris remains unknown. In this study, we used soluble recombinant extracellular domains of desmoglein 1 and desmoglein 3 to obtain affinity-purified anti-desmoglein 1 and anti-desmoglein 3 autoantibodies from pemphigus vulgaris sera and examined the pathogenicity of each fraction separately using the passive transfer mouse model. By immunoprecipitation, the purified anti-desmoglein 1 and anti-desmoglein 3 showed no cross-reactivity. The anti-desmoglein 1 autoantibodies in pemphigus vulgaris induced typical pemphigus foliaceus lesions in neonatal mice, whereas the anti-desmoglein 3 fraction induced pemphigus vulgaris-like lesions. In addition, the pathogenic anti-desmoglein 1 and anti-desmoglein 3 autoantibodies in pemphigus vulgaris had predominant IgG4 subclass specificity. These findings suggest that the anti-desmoglein 1 antibodies in pemphigus vulgaris are pathogenic

7-(1,3-Dioxolan-2-ylmeth­yl)-1,3-di­methyl­purine-2,6(1H,3H)-dione trichloro­acetic acid solvate

In the title compound, C11H14N4O4·C2HCl3O2, the dioxolane ring adopts an envelope conformation. Doxophylline [7-(1,3-dioxolan-2-yl-meth­yl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione] and trichloro­acetic acid mol­ecules are linked by O—H⋯N and C—H⋯O hydrogen bonds

The caudal pedunculopontine tegmental nucleus may be involved in the regulation of skeletal muscle activity by melanocortin-sympathetic pathway: a virally mediated trans-synaptic tracing study in spinally transected transgenic mice

Understanding neuroanatomical sympathetic circuitry and neuronal connections from the caudal pedunculopontine tegmental nucleus to skeletal muscle is important to the study of possible mechanisms of pedunculopontine tegmental nucleus (PPTg) and cuneiform nucleus (CnF) that are involved in the regulation of skeletal muscle activity of the sympathetic pathway. The aim of this study was to use virus PRV-614 to trace the melanocortin-sympathetic neural pathways from PPTg and CnF to a hindlimb muscle (gastrocnemius) in spinally transected MC4R-GFP transgenic mice. PRV-614 was injected into the gastrocnemius muscle after receiving a complete spinal cord transection below the L2 level. PRV-614/MC4R-GFP and PRV-614/TPH dual-labeled neurons were found in the dissipated parts of PPTg (dpPPTg), but not between the compact parts of PPTg (cpPPTg) and CnF. It is proposed that a hierarchical pathway of neurons within the caudal pedunculopontine tegmental nucleus sends projections to the RVLM, which in turn projects onto the IML sympathetic preganglionic neurons that regulate muscle blood flow through melanocortin-sympathetic signals. Our results collectively indicate that MC4Rs expressed in caudal pedunculopontine tegmental nucleus may be involved in skeletal muscle activity of melanocortin-sympathetic pathways

Seeing Differently, Acting Similarly: Imitation Learning with Heterogeneous Observations

In many real-world imitation learning tasks, the demonstrator and the learner have to act in different but full observation spaces. This situation generates significant obstacles for existing imitation learning approaches to work, even when they are combined with traditional space adaptation techniques. The main challenge lies in bridging expert's occupancy measures to learner's dynamically changing occupancy measures under the different observation spaces. In this work, we model the above learning problem as Heterogeneous Observations Imitation Learning (HOIL). We propose the Importance Weighting with REjection (IWRE) algorithm based on the techniques of importance-weighting, learning with rejection, and active querying to solve the key challenge of occupancy measure matching. Experimental results show that IWRE can successfully solve HOIL tasks, including the challenging task of transforming the vision-based demonstrations to random access memory (RAM)-based policies under the Atari domain.Comment: 17 pages, 25 figure

Retinal nerve fiber layer thickness measured by optical coherence tomography in Chinese teenagers aged from 13 years old to 18 years old

AIM: To establish a reference range of retinal nerve fiber layer(RNFL)thickness by optical coherence tomography(OCT)in Chinese teenagers aged from 13 to 18 years old, and investigate its relationship with age, eye side, gender, and ethnic group.<p>METHODS: A total of 402 eyes from 201 normal Chinese aged from 13 to 18 years old were recruited for this study. Optic disk with 3.4mm diameter circle in different global average, quadrant and part-time bit retinal nerve fiber layer thickness(RNFLT)was measured by RNFL thickness average analysis program. Their RNFLT at different part-time bit, quadrant and global average RNFLT around the disc were measured by OCT with 3.4mm diameter circle, using the RNFL thickness average analysis program. The data was analyzed with SPSS statistical 19.0. The influences of several factors(such as age, eye side, gender, and ethnic group)on RNFLT were also analyzed.<p>RESULTS: The global average RNFLT at 13, 14, 15, 16, 17, 18 years old was 108.32±9.42μm, 109.23±9.67μm, 110.36±11.14μm, 111.27±10.21μm, 109.23±9.67μm, 112.11±8.83μm respectively. RNFLT of right eyes was 109.82±8.93μm and of left eyes was 110.33±9.89μm. All of the male's average RNFLT was 110.14±10.02μm, and all of the female's average RNFLT was 109.96±11.22μm. The average RNFLT of Han nationality was 110.22±9.31μm and of non-Han nationality was 109.87±8.65μm. The average RNFLT of all was 110.02±9.87μm, the RNFLT at the superior, nasal, inferior and temporal quadrant was 146.56 ±18.88μm, 76.49±13.28μm, 136.64±16.29μm, 82.01±12.55μm respectively. There was no significant difference in gender, eye side, and ethnic group(all <i>P</i><0.05), but the difference was significant compared with adult's data of the database. <p>CONCLUSION: This study has established a normal standard reference of RNFLT and its related indexes by OCT in Chinese teenagers aged 13-18 years old. Gender, age, eye side, and ethnic group have no effect on their RNFLT, which has significant difference with adult's data. And for the diagnosis and follow-up of diseases involving in RNFL changes, the adult's data can not be used

Linking nutrient strategies with plant size along a grazing gradient: Evidence from Leymus chinensis in a natural pasture

AbstractStudying the changes in nutrient use strategies induced by grazing can provide insight into the process of grassland degradation and is important for improving grassland quality and enhancing ecosystem function. Dominant species in meadow steppe can optimize their use of limiting resources; however, the regulation of nutrient use strategies across grazing gradients is not fully understood. Therefore, in this study, we report an in situ study in which the impact of grazing rates on nutrient use strategies of Leymus chinensis, the dominant plant species in eastern Eurasian temperate steppes, was investigated. We conducted a large randomized controlled experiment (conducted continuously for five years in grassland plots in a natural pasture in Hailar, eastern Mongolia Plateau, China) to assess the effects of grazing rate treatments (0.00, 0.23, 0.34, 0.46, 0.69, and 0.92 adult cattle unit (AU) ha−1) on L. chinensis along a grazing gradient and employed a random sampling approach to compare the accumulation, allocation, and stoichiometry of C, N, and P in leaves and stems. Our findings demonstrated the follows: (i) The height of L. chinensis decreased with an increase in the grazing gradient, and the concentrations of C, N, and P significantly increased; (ii) the accumulation of C, N, and P per individual was negatively correlated with the concentration of aboveground tissues, suggesting that there was a tradeoff in L. chinensis between nutrient accumulation and concentration at the individual scale; (iii) the leaf-to-stem ratio of C, N, and P accumulation increased with grazing intensity, indicating a tradeoff in nutrient allocation and plant size at the individual plant level; and (iv) grazing rates were negatively correlated with the ratios of C:N and C:P in the stem; however, these ratios in leaves significantly increased with grazing intensity. Our findings suggest that L. chinensis in meadow steppe adapts to grazing disturbance through tradeoffs between plant size and nutrient use strategies. Moreover, our results imply that grazing produces a compensatory effect on nutrient use efficiency between the stems and leaves of L. chinensis