A 41-year-old man presented with generalized tonic-clonic seizures. MRI revealed left subinsular and right frontal cortex lesions (Figure 1). CSF analysis showed 17 white cells/mm3 (lymphocytes 92%), normal protein, and glucose. The infection and autoimmune screening were negative. On day 3, bilateral auricles swelling and episcleritis emerged (Figure 2). Biopsy of left auricle revealed perivascular lymphocytic infiltration (Figure 2), consistent with relapsing polychondritis (RP). The patient's symptoms improved after oral prednisolone.
Elastic optical networks (EON) based on OFDM/SCFDM subbands are proposed in this paper. We verify the ROADM and switching functionality for individual subband on optical superchannel that consists of multi subbands. 400 Gb/s optical superchannel multicasting and flexible superchannel conversion that covers the whole C-band are experimentally demonstrated.
Cockayne syndrome (CS) is a devastating autosomal recessive genetic disorder, mainly characterized by photosensitivity, growth failure, neurological abnormalities, and premature aging. Mutations in CSB (ERCC6) are associated with almost all clinical phenotypes resembling classic CS. Using RNA-seq approach in multiple cell types, we identified Necdin (NDN) as a target of the CSB protein. Supportive of the RNA-seq results, CSB directly binds to NDN and manipulates the remodeling of active histone marks and DNA 5mC methylation on the regulatory elements of the NDN gene. Intriguingly, hyperactivation of NDN due to CSB deficiency does not interfere with nucleotide excision repair (1), but greatly affects neuronal cell differentiation. Inhibition of NDN can partially rescue the motor neuron defects in CSB mouse models. In addition to shedding light on cellular mechanisms underlying CS and pointing to future avenues for intervention, these data substantiate a reciprocal communication between CSB and NDN in the context of general transcription regulation.
This paper introduces the concept of (O, N)-difference, for an overlap function O and a fuzzy negation N. (O, N)-differences are weaker than fuzzy difference constructed from positive and continuous t-norms and fuzzy negations, in the sense that (O, N)-differences do not necessarily satisfy certain properties, as the right neutrality principle, but only weaker versions of these properties. This paper analyzes the main properties satisfied by (O, N)-differences, and provides a characterization of (O, N)-difference.
The BACE1 antisense transcript (BACE1-AS) is a conserved long noncoding RNA (lncRNA). The level of BACE1-AS is significantly increased and the level of the BACE1 mRNA is slightly increased in subjects with AD. BACE1-AS exerts a significant moderating effect on the expression of the BACE1 mRNA and promotes the formation of Aβ. After the administration of Aβ1-42 to SH-SY5Y cells and C57/BL6J mice, we detected the expression of BACE1-AS, BACE1 mRNA, and BACE1 protein, as well as the concentration of Aβ1-40. Then, we silenced the expression of BACE1-AS in SH-SY5Y and 20E2 cells using siRNAs targeting BACE1-AS and detected its effects on the levels of the BACE1 mRNA and BACE1 protein and Aβ1-40 generation.The administration of Aβ1-42 increased the expression of BACE1-AS, BACE1 mRNA and protein, as well as the concentration of Aβ1-40 in SH-SY5Y cells and the brains of C57BL/6J mice. Pretreatment with the BACE1-AS siRNA inhibited the effect of Aβ1-42 on increasing the expression of BACE1-AS and BACE1, as well as the generation of Aβ.The mechanism by which exogenous Aβ1-42 induces BACE1 expression and Aβ generation is mediated by BACE1-AS. BACE1-AS is involved in the mechanism regulating BACE1 expression and Aβ generation in APPsw transgenic cells.
Alzheimer's disease (AD), the most common form of dementia, is highly prevalent in older adults. The main clinical feature is the progressive decline of memory function, which eventually leads to the decline of cognitive function. At present, the pathogenesis of AD is unclear. In the disease process, synaptic changes are the key. Recent studies have shown that the dysregulation of RNA methylation is related to many biological processes, including neurodevelopment and neurodegenerative diseases. N6-methyladenosine (m6A) is the most abundant modification in eukaryotic RNA. In this study, RNA m6A methylation was quantified in APP/PS1 transgenic mice, which is an AD mouse model, and C57BL/6 control mice, and data showed that m6A methylation was elevated in the cortex and the hippocampus of APP/PS1 transgenic mice. Next, the alterations of m6A RNA methylation in AD and in C57BL/6 mice were investigated using high-throughput sequencing. Genome-wide maps of m6A mRNA showed that the degrees of m6A methylation were higher in many genes and lower in others in AD mice. Interestingly, the expression of the m6A methyltransferase METTL3 was elevated and that of the m6A demethylase FTO was decreased in AD mice. The data were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and pathways that might be related to synaptic or neuron development and growth were constructed. The related pathways and genes predicted the potential roles of the differentially expressed m6A methylation RNA in AD. Collectively, our findings demonstrate that the m6A methylation of RNA promotes the development of AD.
Abstract Background Following the sufficient studies of the effects of skin barrier impairment and heightened neural reaction on sensitive skin (SS), many scholars have paid great attention to the roles of superficial microvasculature in SS. Methods By questionnaire survey, lactic acid sting test, and capsaicin test, eligible subjects were classified as normal skin, only lactic acid sting test positive (LASTP), only capsaicin test positive (CATP), and both positive (both LASTP and CATP). D‐OCT was used to photograph images for evaluating the cutaneous vessels features each group. Results Totally 137 subjects completed the study. Compared with LASTN group, the vascular vessels were closer to epidermis in LASTP group. Mesh and branching vessels were more popular in SS than normal skin. High blood vessel density was more prevalent in SS, while low density frequently presented in normal skin. The vascular depth had a closely negative correlation with face flushing and SSS, and vascular shapes had a good positive correlation with face flushing and SSB. Conclusions Our study indicates that there is a significant difference in vascular depth, shape, and density between SS and normal skin which is valuable to explore SS pathologic mechanism and to further investigate cutaneous microvasculature functions in SS.
Abstract Super-enhancers (SEs) govern macrophage polarization and function. However, the mechanism underlying the signal-dependent latent SEs remodeling in macrophages remains largely undefined. Here we show that the epigenetic reader ZMYND8 forms liquid compartments with NF-κB/p65 to silence latent SEs and restrict macrophage-mediated inflammation. Mechanistically, the fusion of ZMYND8 and p65 liquid condensates is reinforced by signal-induced acetylation of p65. Then acetylated p65 guides the ZMYND8 redistribution onto latent SEs de novo generated in polarized macrophages, and consequently, recruit LSD1 to decommission latent SEs. The liquidity characteristic of ZMYND8 is critical for its regulatory effect since mutations coagulating ZMYND8 into solid compartments disable the translocation of ZMYND8 and its suppressive function. Thereby, ZMYND8 serves as a molecular rheostat to switch off latent SEs and control the magnitude of the immune response. Meanwhile, we propose a phase separation model by which the latent SEs are fine-tuned in a spatiotemporal manner.
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