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Objective To explore whether the variants in non MHC proteasome gene are associated with AS and explain the role of the variant in the disease. Material and methods Case-control analysis to identify AS predisposition genes; dual-luciferase reporter assay, immunoblot analysis and osteoclastogenesis assays to detect the function of the positive variant. Affected individuals were diagnosed according to the modified New York Criteria by at least two experienced rheumatologists, and rechecked by another rheumatologist. Results The study included 1037 AS patients and 1014 no rheumatic and arthritis disease controls. The main age of AS onset is between 16 and 35 years old. HLA-B27-positive subjects comprised 90.0% of patients. A nonsynonymous SNP rs12717 in proteasome gene PSMB1 significantly associated with AS. Individuals with CC genotype had a higher onset risk compared with those with GG/GC genotypes (OR = 1.89, P  = 0.0047). We also discovered that PSMB1 regulates the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) signalling pathway and the disease-associated variant PSMB1-Pro11 significantly inhibits RANKL-induced NF-κB pathway in osteoclast differentiation via the degradation of IKK-β compared with PSMB1-Ala11. RANKL induced osteoclast differentiation was significantly lower in primary monocyte osteoclast precursor from individuals with genotype PSMB1 31C/31C compared with individuals with genotype PSMB1 31G/31G . Conclusions These results reveal a novel understanding of the bone formation and reabsorbing imbalance in AS. The new bone formation phenotype can be attributed to the inhibition of osteoclast differentiation by a more functional PSMB1 gene. [ABSTRACT FROM AUTHOR]

Lake Group of Badain Jaran Desert and the recharge sources are hot issues in the academic community. The Mega Dune links the atmospheric precipitation and the lake water. Studying its hydrological characteristics could deepen the understanding of regional lake water cycle, while the plant distribution is an important indicator of the hydrological characteristics of the Mega Dune. This paper took the Tamarix laxa as the research object, measured the water content by drying method, analysed the spatial and temporal variation characteristics of the water content, then explored the indicative significance to the hydrological characteristics of the Mega Dune. The results showed: the soil profile of Tamarix laxa distribution area can be divided into moisture rapid change layer(0 to 60 cm), moisture active layer(60 to 120 cm) and moisture relatively stable layer(120 to 200 cm) according to its moisture characteristics, and the moisture content tends to decrease with increasing depth, and the average moisture content of rapid change layer is 1.69%, which is significantly higher than the other two layers. The water content of the distribution area is 95.83% in the range of 0.50% to 3.00% and the observed maximum value was 4.88%, all of them are less than the field water capacity(5.00%), which indicated that it was difficult to form gravity water in the Tamarix laxa distribution area at the leeward slope of the Mega Dune, but also indicated that the precipitation is difficult to quickly infiltrate to replenish lake water as gravity water for the leeward slope of the Mega Dune. The "arborization" growth characteristics of Tamarix laxa and its special distribution position are not only conducive to its root tiller propagation, but also to the storage and maintenance of water, which maintains its survival and development. [ABSTRACT FROM AUTHOR]

It is of great significance to study the effects of precipitation events on carbon exchange in the ecosystem for an accurate understanding of the carbon cycle. However, the response of net ecosystem CO2 exchange (NEE) in the desert to precipitation events is elusive. In this study, the NEE in response to precipitation events of varying intensities in the Badain Jaran Desert (BJD) in China was continuously monitored using the eddy covariance (EC) technique. The following results were obtained: (1) The BJD ecosystem was a net CO2 sink throughout the study period, with NEE values of -113.4, -130.7, and -175.4 g C m-2a-1 in 2016, 2018, and 2019, respectively. The total precipitation yielded a higher carbon sequestration capacity in 2019 than in the other two years. In addition, the intensity, time, and frequency of precipitation had significant impacts on CO2; (2) the threshold value of the NEE response to precipitation was ~1.4 mm, indicating the extreme sensitivity of the BJD to precipitation events; (3) the variations in the NEE response to precipitation events conformed to a dual exponential model. The analytical results of the model indicate that precipitation intensity was positively correlated with the carbon sequestration capacity of the desert. The model revealed that the greater the precipitation intensity, the longer it takes the NEE to reach the maximum, and the lengthier the duration of the residual effects. With an increase in the total precipitation and frequency of extreme precipitation events under warm and humidification climates, the carbon sequestration capacity of the BJD will likely be enhanced. The results of this study are of great significance for revealing the carbon cycle mechanism of the desert ecosystem. [ABSTRACT FROM AUTHOR]

Oculopharyngodistal myopathy is a late-onset degenerative muscle disorder characterized by ptosis and weakness of the facial, pharyngeal, and distal limb muscles. A recent report suggested a non-coding trinucleotide repeat expansion in LRP12 to be associated with the disease. Here we report a genetic study in a Chinese cohort of 41 patients with the clinical diagnosis of oculopharyngodistal myopathy (21 cases from seven families and 20 sporadic cases). In a large family with 12 affected individuals, combined haplotype and linkage analysis revealed a maximum two-point logarithm of the odds (LOD) score of 3.3 in chromosomal region chr19p13.11-p13.2 and narrowed the candidate region to an interval of 4.5 Mb. Using a comprehensive strategy combining whole-exome sequencing, long-read sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal CGG repeat expansion in the 5' UTR of the GIPC1 gene that co-segregated with disease. Overall, the repeat expansion in GIPC1 was identified in 51.9% independent pedigrees (4/7 families and 10/20 sporadic cases), while the repeat expansion in LRP12 was only identified in one sporadic case (3.7%) in our cohort. The number of CGG repeats was <30 in controls but >60 in affected individuals. There was a slight correlation between repeat size and the age at onset. Both repeat expansion and retraction were observed during transmission but somatic instability was not evident. These results further support that non-coding CGG repeat expansion plays an essential role in the pathogenesis of oculopharyngodistal myopathy. [ABSTRACT FROM AUTHOR]

Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Thus far, although two loci for DSAP have been identified, the genetic basis and pathogenesis of this disorder have not been elucidated yet. In this study, we performed a genome-wide linkage analysis in three Chinese affected families and localized the gene in an 8.0 cM interval defined by D12S330 and D12S354 on chromosome 12. Upon screening 30 candidate genes, we identified a missense mutation, p.Ser63Asn in SSH1 in one family, a frameshift mutation, p.Ser19CysfsX24 in an alternative variant (isoform f) of SSH1 in another family, and a frameshift mutation, p.Pro27ProfsX54 in the same alternative variant in one non-familial case with DSAP. SSH1 encodes a phosphatase that plays a pivotal role in actin dynamics. Our data suggested that cytoskeleton disorganization in epidermal cells is likely associated with the pathogenesis of DSAP. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Oculopharyngodistal myopathy is a late-onset degenerative muscle disorder characterized by ptosis and weakness of the facial, pharyngeal, and distal limb muscles. A recent report suggested a non-coding trinucleotide repeat expansion in LRP12 to be associated with the disease. Here we report a genetic study in a Chinese cohort of 41 patients with the clinical diagnosis of oculopharyngodistal myopathy (21 cases from seven families and 20 sporadic cases). In a large family with 12 affected individuals, combined haplotype and linkage analysis revealed a maximum two-point logarithm of the odds (LOD) score of 3.3 in chromosomal region chr19p13.11-p13.2 and narrowed the candidate region to an interval of 4.5 Mb. Using a comprehensive strategy combining whole-exome sequencing, long-read sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal CGG repeat expansion in the 5' UTR of the GIPC1 gene that co-segregated with disease. Overall, the repeat expansion in GIPC1 was identified in 51.9% independent pedigrees (4/7 families and 10/20 sporadic cases), while the repeat expansion in LRP12 was only identified in one sporadic case (3.7%) in our cohort. The number of CGG repeats was <30 in controls but >60 in affected individuals. There was a slight correlation between repeat size and the age at onset. Both repeat expansion and retraction were observed during transmission but somatic instability was not evident. These results further support that non-coding CGG repeat expansion plays an essential role in the pathogenesis of oculopharyngodistal myopathy., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Charcot-Marie-Tooth disease (CMT) is the most common type of inherited peripheral neuropathy and has a high degree of genetic heterogeneity. CMT with concurrent diabetes mellitus (DM) is rare. The purpose of this study is to explore the genetic, clinical and pathological characteristics of the patients with CMT and concurrent DM., Methods: We investigated gene mutations (the peripheral myelin protein 22 gene, myelin protein zero gene, lipopolysaccharide-induced tumor necrosis factor-α factor gene, early growth response gene and the neurofilament light chain gene loci) of a relatively large and typical Chinese family with CMT1 and concurrent DM2. From the literature, we also retrieved all reported families and single cases with CMT and concurrent DM. We comprehensively analyzed the characteristics of total 33 patients with CMT and concurrent DM, and further compared these characteristics with those of patients of diabetic peripheral neuropathy (DPN)., Results: Patients with CMT and concurrent DM had some relatively independent characteristics and pathogenic mechanisms. So we designated that kind of characteristic demyelinating CMT which accompanies DM as Yu-Xie syndrome (YXS), a new specific clinical subtype of CMT., Conclusion: CMT is an etiologic factor of DM, even though the intrinsic association between CMT and DM still remains further exploration.