Extraocular Muscle Characteristics Related to Myasthenia Gravis Susceptibility

Background

The pathogenesis of extraocular muscle (EOM) weakness in myasthenia gravis might involve a mechanism specific to the EOM. The aim of this study was to investigate characteristics of the EOM related to its susceptibility to myasthenia gravis.

Methods

Female F344 rats and female Sprague-Dawley rats were assigned to experimental and control groups. The experimental group received injection with Ringer solution containing monoclonal antibody against the acetylcholine receptor (AChR), mAb35 (0.25 mg/kg), to induce experimental autoimmune myasthenia gravis, and the control group received injection with Ringer solution alone. Three muscles were analyzed: EOM, diaphragm, and tibialis anterior. Tissues were examined by light microscopy, fluorescence histochemistry, and transmission electron microscopy. Western blot analysis was used to assess marker expression and ELISA analysis was used to quantify creatine kinase levels. Microarray assay was conducted to detect differentially expressed genes.

Results

In the experimental group, the EOM showed a simpler neuromuscular junction (NMJ) structure compared to the other muscles; the NMJ had fewer synaptic folds, showed a lesser amount of AChR, and the endplate was wider compared to the other muscles. Results of microarray assay showed differential expression of 54 genes in the EOM between the experimental and control groups.

Conclusion

Various EOM characteristics appear to be related to the increased susceptibility of the EOM and the mechanism of EOM weakness in myasthenia gravis.     

Characterization of Tat Antibody Responses in Chinese Individuals Infected with HIV-1

HIV-1 Tat is an important regulatory protein involved in AIDS pathogenesis. However, the immunoprofiles of anti-Tat responses remain unclear. We analysed the immunoprofiles of the anti-Tat antibody responses and the neutralizing activities. Out of 326 HIV-1-seropositive individuals, 12.9% were positive for anti-Tat antibodies. We found six different immunological profiles of anti-Tat antibody responses: full-potential response, combined response, N-specific response, C-specific response, full-length Tat-specific response and Tat-related response. These responses represent two types of anti-Tat responses: the major complete response and the alternative C-prone response. A Tat-neutralizing activity is significantly higher in anti-Tat-seropositive samples than anti-Tat-negative or healthy blood-donor samples, and significantly correlates with the anti-Tat reactivities. The data here could contribute to a better understanding of the significance of anti-Tat responses in preventing HIV pathogenesis and could be useful for designing more effective vaccines in the future.     

The Association between Subclinical Atherosclerosis and Uterine Fibroids

Objective(s)

To explore the atherogenic hypothesis of uterine fibroids among Chinese women.

Methods

In a case-control study, 335 patients confirmed by ultrasound or hysterectomy surgery and 539 controls were enrolled between October 1, 2009 and April 1, 2012. Unconditional logistic regressions were used to calculate the odds ratios (ORs) for the associations of subclinical atherogenic and cardiovascular risk parameters with uterine fibroids in the overall case group and hysterectomy-confirmed case group, respectively.

Results

Higher level of ankle-brachial index (ABI) was independently associated with increased odds of uterine fibroids. The odds of UF among women in the highest tertile of ABI were 1.88 times higher (95%CI: 1.17, 3.02, P_trend = 0.008) compared to those in the lowest tertile. The serum concentration of homocysteine was inversely related to fibroids (middle vs. low: OR 0.56, 95%CI: 0.36, 0.85; high vs. low: OR 0.50, 95% CI: 0.32, 0.79; P_trend = 0.002). In the hysterectomy-confirmed group, an inverse association was suggested between high-density lipoprotein cholesterol (HDL-C) and fibroids (OR 0.46, 95% CI: 0.25, 0.84, P_trend = 0.014). Moreover, the effect of homocysteine concentration was not observed in this group.

Conclusion(s)

These findings suggest that women with uterine fibroids might have an increased risk of subclinical atherosclerosis.     

Homeostatic Properties and Phenotypic Maturation of Murine CD4+ Pre-Thymic Emigrants in the Thymus

After a tightly regulated developmental program in the thymus, “mature” single positive (SP) thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs) are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4⁺ pre-RTEs, a population of CD4⁺ SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4⁺ pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs’ better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4⁺ pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4⁺ pre-RTEs is independent of MHC class II and Aire molecules.     

Antisense-Oligonucleotide Mediated Exon Skipping in Activin-Receptor-Like Kinase 2: Inhibiting the Receptor That Is Overactive in Fibrodysplasia Ossificans Progressiva

Fibrodysplasia ossificans progressiva (FOP) is a rare heritable disease characterized by progressive heterotopic ossification of connective tissues, for which there is presently no definite treatment. A recurrent activating mutation (c.617G→A; R206H) of activin receptor-like kinase 2 (ACVR1/ALK2), a BMP type I receptor, has been shown as the main cause of FOP. This mutation constitutively activates the BMP signaling pathway and initiates the formation of heterotopic bone. In this study, we have designed antisense oligonucleotides (AONs) to knockdown mouse ALK2 expression by means of exon skipping. The ALK2 AON could induce exon skipping in cells, which was accompanied by decreased ALK2 mRNA levels and impaired BMP signaling. In addition, the ALK2 AON potentiated muscle differentiation and repressed BMP6-induced osteoblast differentiation. Our results therefore provide a potential therapeutic approach for the treatment of FOP disease by reducing the excessive ALK2 activity in FOP patients.     

Recent Geological Events and Intrinsic Behavior Influence the Population Genetic Structure of the Chiru and Tibetan Gazelle on the Tibetan Plateau

The extent to which a species responds to environmental changes is mediated not only by extrinsic processes such as time and space, but also by species-specific ecology. The Qinghai-Tibetan Plateau uplifted approximately 3000 m and experienced at least four major glaciations during the Pleistocene epoch in the Quaternary Period. Consequently, the area experienced concurrent changes in geomorphological structure and climate. Two species, the Tibetan antelope (Pantholops hodgsonii, chiru) and Tibetan gazelle (Procapra picticaudata), both are endemic on the Qinghai-Tibetan Plateau, where their habitats overlap, but have different migratory behaviors: the chiru is inclined to have female-biased dispersal with a breeding migration during the calving season; in contrast, Tibetan gazelles are year-round residents and never migrate distantly. By using coalescence methods we compared mitochondrial control region DNA sequences and variation at nine microsatellite loci in these two species. Coalescent simulations indicate that the chiru and Tibetan gazelle do not share concordant patterns in their genealogies. The non-migratory Tibetan gazelle, that is more vulnerable to the impact of drastic geographic changes such as the elevation of the plateau, glaciations and so on, appears to have a strong population genetic structure with complicated demographic history. Specifically, the Tibetan gazelle population appears to have experienced isolation and divergence with population fluctuations since the Middle Pleistocene (0.781 Ma). However, it showed continued decline since the Upper Pleistocene (0.126 Ma), which may be attributed to the irreversible impact of increased human activities on the plateau. In contrast, the migratory chiru appears to have simply experienced population expansion. With substantial gene flow among regional populations, this species shows no historical population isolation and divergence. Thus, this study adds to many empirical studies that show historical and contemporary extrinsic and intrinsic processes shape the recent evolutionary history and population genetic structure of species.     

Effects of Nanoparticle Shape and Size on Optical Properties of LaB<Subscript>6</Subscript>

The optical response of lanthanum hexaboride (LaB₆) nanoparticles has been investigated by both theoretically and experimentally. The LaB₆ nanoparticles obtained by solid-state reaction could avoid serious surface oxidization and exhibit excellent optical performance. The discrete dipole approximation (DDA) has been used to investigate the optical response of LaB₆ nanoparticles with different sizes and different shapes. The calculation results coincide with the experimental results and reveal that the largest extinction peak value appears at 60 nm for cubic particles and 40 nm for spherical particles, respectively. Our calculation results show that the existence of the largest extinction peak value is not only due to the surface oxides but also relate to the particle shape of LaB₆ compound. In addition, the LaB₆ nanoparticles with cubic and spherical shapes exhibit different optical responses, and the cubic particles exhibit stronger near infrared (NIR) extinction than spherical particles. With increasing particle size, the extinction peak value of spherical particle decreases more rapidly than that of cubic ones.     

Tailoring of Localized Surface Plasmon Resonances of Core-Shell Au@Ag Nanorods by Changing the Thickness of Ag Shell

We report the synthesis and the characterization of core-shell Au@Ag nanorods through reduction by the wet chemical method. UV-visible absorption spectra of core-shell Au@Ag nanorods demonstrate the longitudinal mode of localized surface plasmon resonances (LSPRs) can be tailored from 724 to 786 nm by controlling the thickness of the silver shell, as is assessed by transmission electron microscope (TEM). Furthermore, the tunable and well-controlled LSPRs of core-shell Au@Ag nanorods are also investigated by numerical simulation using the finite difference time domain (FDTD) method, which strongly supports the experimental observations. The growth mechanism for core-shell Au@Ag nanorods is proposed, according to experimental observations and numerical calculations.     

Analysis of Mid-Infrared Surface Plasmon Modes in a Graphene-Based Cylindrical Hybrid Waveguide

A graphene-based cylindrical hybrid surface plasmon polariton waveguide, composed of a silicon nanowire core surrounded by a silica layer and then a graphene layer, is investigated using the finite-difference time-domain method. The analytical solutions and the numerical simulation show that an ultra-small mode area and a large propagation length can be achieved with this waveguide. Utilizing the perturbation theory of coupled mode, we demonstrate that the six lowest-order coupling modes originate from the coupling of the three lowest-order single-waveguide modes, and the m?=?1 order yy-coupling mode possesses the maximum coupling length and the minimum crosstalk. This waveguide can be used for photonic integrated circuits in the mid-infrared range.