Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4,045 Japanese individuals (2,060 cases and 1,985 healthy controls). A susceptibility locus on chromosome 3q13.33 (including ARHGAP31, TMEM39A, POGLUT1, TIMMDC1, and CD80) was previously identified both in the European and Chinese populations and was replicated in the Japanese population (OR = 0.7241, P = 3.5 × 10−9). Subsequent in silico and in vitro functional analyses identified rs2293370, previously reported as the top-hit SNP in this locus in the European population, as the primary functional SNP. Moreover, e-QTL analysis indicated that the effector gene of rs2293370 was Protein O-Glucosyltransferase 1 (POGLUT1) (P = 3.4 × 10−8). This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of PBC.
Eukaryotic communities in aerobic wastewater treatment processes are well characterized, but little is known about them in anaerobic processes. In this study, abundance, diversity and morphology of eukaryotes in anaerobic sludge digesters were investigated by quantitative real-time PCR (qPCR), 18S rRNA gene clone library construction and catalyzed reporter deposition-fluorescence in situ hybridization (CARD-FISH). Samples were taken from four different anaerobic sludge digesters in Japan. Results of qPCR of rRNA genes revealed that Eukarya accounted from 0.1% to 1.4% of the total number of microbial rRNA gene copy numbers. The phylogenetic affiliations of a total of 251 clones were Fungi, Alveolata, Viridiplantae, Amoebozoa, Rhizaria, Stramenopiles and Metazoa. Eighty-five percent of the clones showed less than 97.0% sequence identity to described eukaryotes, indicating most of the eukaryotes in anaerobic sludge digesters are largely unknown. Clones belonging to the uncultured lineage LKM11 in Cryptomycota of Fungi were most abundant in anaerobic sludge, which accounted for 50% of the total clones. The most dominant OTU in each library belonged to either the LKM11 lineage or the uncultured lineage A31 in Alveolata. Principal coordinate analysis indicated that the eukaryotic and prokaryotic community structures were related. The detection of anaerobic eukaryotes, including the members of the LKM11 and A31 lineages in anaerobic sludge digesters, by CARD-FISH revealed their sizes in the range of 2–8 μm. The diverse and uncultured eukaryotes in the LKM11 and the A31 lineages are common and ecologically relevant members in anaerobic sludge digester.
Magnetic resonance image features of heterogeneity and smaller volume in the submandibular gland are reliable for predicting hyposalivation related to the progression of Sjögren's syndrome.
Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is a member of the osteonectin family of proteins. In this study, immunohistochemistry for SPARCL1 was performed to obtain its distribution in the human brainstem, cervical spinal cord, and sensory ganglion. SPARCL1-immunoreactivity was detected in neuronal cell bodies including perikarya and proximal dendrites, and the neuropil. The motor nuclei of the IIIrd, Vth, VIth, VIIth, IXth, Xth, XIth, and XIIth cranial nerves and spinal nerves contained many SPARCL1-immunoreactive (-IR) neurons with medium-sized to large cell bodies. Small and medium-sized SPARCL1-IR neurons were distributed in sensory nuclei of the Vth, VIIth, VIIIth, IXth, and Xth cranial nerves. In the medulla oblongata, the dorsal column nuclei also had small to medium-sized SPARCL1-IR neurons. In addition, SPARCL1-IR neurons were detected in the nucleus of the trapezoid body and pontine nucleus within the pons and the arcuate nucleus in the medulla oblongata. In the cervical spinal cord, the ventral horn contained some SPARCL1-IR neurons with large cell bodies. These findings suggest that SPARCL1-containing neurons function to relay and regulate motor and sensory signals in the human brainstem. In the dorsal root (DRG) and trigeminal ganglia (TG), primary sensory neurons contained SPARCL1-immunoreactivity. The proportion of SPARCL1-IR neurons in the TG (mean ± SD, 39.9 ± 2.4%) was higher than in the DRG (30.6 ± 2.1%). SPARCL1-IR neurons were mostly medium-sized to large (mean ± SD, 1494.5 ± 708.3 μm(2); range, 320.4-4353.4 μm(2)) in the DRG, whereas such neurons were of various cell body sizes in the TG (mean ± SD, 1291.2 ± 532.8 μm(2); range, 209.3-4326.4 μm(2)). There appears to be a SPARCL1-containing sensory pathway in the ganglion and brainstem of the spinal and trigeminal nervous systems.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.