The mammalian 5.8S rRNA contains a partially 2′-0-methylated uridylic acid residue at position 14 which is largely or entirely methylated in the cytoplasm (Nazar, R.N., Sitz, T.O. and Sommers, K.D. (1980) J. Mol. Biol. 142, 117–121). The effect of this methylation on the 5.8S RNA structure and 5.8–28S rRNA junction was investigated using both chemical and physical approaches. Electrophoretic studies indicated that the free 5.8S rRNA can take on at least two different conformations and that the 2′-0-methylation at U14 restricts the molecule to the more hydrodynamically open form. Structural studies using limited pancreatic or T1 ribonuclease digestion indicated that the methylated conformation was more susceptible to digestion, consistent with a more open tertiary structure. Modification-exclusion studies indicated that the first 29 nucleotides at the 5′ end and residues 140 through 158 at the 3′ end affect the 5.8S–28S rRNA interaction, supporting previous suggestions that the 5.8S RNA interacts with its cognate high molecular weight component through its termini. These results also suggested that the 2′-0-methylated uridylic acid residue plays a role in the 5.8S–28S rRNA interaction and thermal denaturation studies confirmed this by showing that methylation destabilizes the 5.8S–28S rRNA junction. The 5.8–28S rRNA interaction appears to be more complex than previously believed.
Retinal ischaemia is a common feature shared by numerous eye diseases. Ischaemic insult leads to retinal dysfunction and neuronal death. Lycium barbarum polysaccharides are well known for eyesight preservation. We have previously reported the effect of Lycium barbarum polysaccharides on cell death, blood ocular barrier and oxidative stress within 24 h retinal ischaemia. This study focuses on retinal function and looks for ultrastructural and cellular correlates after a relatively long period of reperfusion for 7 days.Two-hour ischaemia was induced by intraluminal occlusion of the internal carotid artery. Either Lycium barbarum polysaccharides or phosphate-buffered saline was orally pre-administered daily for 7 days before ischaemia and continued for 1, 3 and 7 days after reperfusion. Electroretinogram was performed to evaluate visual function. Paraffin-embedded retinal sections were prepared 7 days after reperfusion and utilized for histological and immunohistochemical analyses.Ischaemia led to sustained inhibition of b-wave amplitude and oscillatory potentials. Lycium barbarum polysaccharide-treated mice exhibited greater b-wave and oscillatory potential responses from days 1 to 7 after reperfusion. In addition, increased number of viable cells and calretinin-positive cells, as well as enhanced immunoreactivity of protein kinase C alpha and attenuated glial fibrillary acidic protein expression, was noted in Lycium barbarum polysaccharide-treated retina.Daily consumption of Lycium barbarum polysaccharides effectively alleviated ischaemia-induced retinal dysfunction as well as reduced correlated neuronal death and glial activation. This prolonged effect could last at least 7 days. It suggested that Lycium barbarum polysaccharides might serve as a neuroprotective agent in ischaemic retinopathies.
Abstract: We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system. One Sentence Summary: We report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.
Abstract Hashimoto disease ( HD ) is an autoimmune thyroid disease resulting from complex interactions between genetic and environmental factors. The human leukocyte antigen ( HLA ) gene has been established to be involved in the susceptibility to HD . We aim to investigate the associations between HLA ‐B alleles and Han Chinese children with HD by both case‐control and family‐based studies. A total of 108 unrelated children with HD , 380 unrelated healthy controls, 58 trios of affected patients and their parents, and 75 trios of unaffected siblings and their parents were recruited. HLA ‐B genotyping was performed by polymerase chain reaction and detected with a sequence‐specific oligonucleotide probes system. We found that B*46:01 allele ( OR = 2.31, 95% CI 1.60–3.34, P c = 9.99 × 10 −5 ) and carrier ( OR = 3.28, 95% CI 2.10–5.11, P c = 1.35 × 10 −6 ) were associated with HD risk. Transmission/disequilibrium test further confirmed an overtransmission of the B*46:01 ( OR 2.55, 95% CI 1.36–6.10, P = 6.5 × 10 −3 ). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA ‐B*46:01 confers susceptibility to HD in Han Chinese children. Further studies with larger children cohort are required to confirm the role of B*46:01 in the development of HD .
Elevated intraocular pressure (IOP) is the main risk factor of glaucoma. In this study, an elevated IOP was introduced into the right eye balls of Sprague-Dawley rats, while their left eye balls were kept at a normal state. Nanoindentation showed that the elastic modulus of normal corneas was 2.75-3.33 MPa, whereas that of elevated IOP group was higher at 4.89-5.58 MPa. Scanning electron microscopy imaging suggested that the collagen fibrils subjected to the elevated IOP became thinner and with random directionality. It is believed the observed increase in elastic modulus should due to the strain-stiffening effects of collagen fibrils.
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