Coupling between NMDA Receptor and Acid-Sensing Ion Channel Contributes to Ischemic Neuronal Death

SummaryAcid-sensing ion channels (ASICs) composed of ASIC1a subunit exhibit a high Ca2+ permeability and play important roles in synaptic plasticity and acid-induced cell death. Here, we show that ischemia enhances ASIC currents through the phosphorylation at Ser478 and Ser479 of ASIC1a, leading to exacerbated ischemic cell death. The phosphorylation is catalyzed by Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, as a result of activation of NR2B-containing N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) during ischemia. Furthermore, NR2B-specific antagonist, CaMKII inhibitor, or overexpression of mutated form of ASIC1a with Ser478 or Ser479 replaced by alanine (ASIC1a-S478A, ASIC1a-S479A) in cultured hippocampal neurons prevented ischemia-induced enhancement of ASIC currents, cytoplasmic Ca2+ elevation, as well as neuronal death. Thus, NMDAR-CaMKII cascade is functionally coupled to ASICs and contributes to acidotoxicity during ischemia. Specific blockade of NMDAR/CaMKII-ASIC coupling may reduce neuronal death after ischemia and other pathological conditions involving excessive glutamate release and acidosis

Allele frequency analysis of Chinese chestnut (Castanea mollissima) populations using fluorescent simple sequence repeats (SSR) analysis

The aim of this study was to establish a method for allele frequency detection in bulk samples. The abundance of polymerase chain reaction (PCR) products in bulk leaf samples was detected using fluorescent labeled Simple sequence repeat (SSR) primers and an Applied biosystems (AB) automatic DNA analyzer. Compared with the conventional SSR technique based on polyacrylamide gel electrophoresis (PAGE) and silver staining, fluorescent SSR was much more sensitive. A total of 78 alleles, an average of 4.6 alleles per locus, were detected among 17 chestnut populations with the primer CmTCR10 (NED) and a total of 41 alleles, an average of 2.4 alleles per locus, were detected with the primer CmTCR24 (6-FAM). Multiplexing the PCR reaction by combining the primer pairs of CmTCR10 and CmTCR24, using different fluorescent dyes for different primers, showed that the alleles could be discriminated and the sizes of the amplified segments were similar. Furthermore, the exact sizes of the amplified fragments and the abundance of the PCR products were determined by fluorescent SSR. After data analysis with GeneScan software and allele calling and output with Genotyper software, allele frequencies were calculated for equal pooled samples in each population using the FREQS-R module in the R statistical computing language. The results indicate that it is feasible to determine allele frequencies in bulked samples based on the detection of SSR-PCR products. The advantages and additional applications of this method are also discussed. The abundance of the PCR products can be used to determine the allele frequencies in bulk samples of chestnut populations.Keywords: Fluorescent simple sequence repeats (SSR), chestnut population, bulk sampling, allele frequencie

Epidemiological survey of school-age children with low vision in Zhouqu County of Gannan Tibetan autonomous prefecture of Gansu province

AIM: To have a detailed picture of school-age children's eyesight status, and the main factors that caused their low vision in Zhouqu County of Gannan Tibetan autonomous prefecture of Gansu province. METHODS: The census work of knowing school-age children's eyesight status was implemented through visual inspection, conventional ophthalmic examination, optometry checks, etc. The results were compared with other domestic epidemiological data. RESULTS: Altogether 536 people with low vision were identified through survey and the rate was 21.12%. Among those people, the number of myopia patients accounted for 80.59% and the prevalence rate was 17.02%. Besides, the prevalence rate of presbyopia was 2.05%, amblyopia 2.76%, strabismus 1.02%, ocular trauma 0.95%, and congenital eye disease 0.71%. CONCLUSION: The prevalence rate of low vision was related with several factors such as gender and nationality. The rate increases with age and the myopia is the primary element that causes low vision

Evidence for chiral superconductivity in Kagome superconductor CsV3Sb5

The interplay among frustrated lattice geometry, nontrivial band topology and correlations yields rich quantum states of matter in Kagome systems. A class of recent Kagome metals, AV3Sb5 (A= K, Rb, Cs), exhibit a cascade of symmetry-breaking transitions, involving 3Q chiral charge ordering, electronic nematicity, roton pair density wave and superconductivity. The interdependence among multiple competing orders suggests unconventional superconductivity, the nature of which is yet to be resolved. Here, we report the electronic evidence for chiral superconducting domains with boundary supercurrent, a smoking-gun of chiral superconductivity, in intrinsic CsV3Sb5 akes. Magnetic field-free superconducting diode effects are observed with its polarity modulated by thermal histories, unveiling a spontaneous time-reversal-symmetry breaking within dynamical order parameter domains in the superconducting phase. Strikingly, the critical current exhibits double-slit superconducting interference patterns, when subjected to external magnetic field. This is attributed to the periodic modulation of supercurrent owing along chiral domain boundaries constrained by fluxoid quantization. Our results provide the direct demonstration of a time-reversal symmetry breaking superconducting order in Kagome systems, opening a potential for exploring exotic physics, e.g. Majorana zero modes, in this intriguing topological Kagome system.Comment: 16 pages,13 figure

Exopolysaccharide, Isolated From a Novel Strain Bifidobacterium breve lw01 Possess an Anticancer Effect on Head and Neck Cancer – Genetic and Biochemical Evidences

Probiotic bacteria exopolysaccharides (EPS) have been recognized as molecules that regulate immune development and have anti-inflammation and anticancer effects. Yet, these bioactivities are of interspecies diversity; thus, examining the gene clusters of EPS and biosynthesis pathways are essential for selecting the better application of specific EPS. In this study, we isolated a new Bifidobacterium strain, named B. breve lw01. A complete genome of B. breve lw01 was sequenced revealing a circular 2,313,172 bp chromosome. Furthermore, a deep excavation of genome sequence from different database based on the comparison-selected results was performed to explore the gene cluster responsible for EPS synthesis. We found that B. breve lw01 harbors a new EPS-encoding cluster with 14 predicted genes, which could be divided into three groups according to the biosynthesis pathway hypothesis. Using tertiary purification, high purity EPS were obtained. EPS is composed of rhamnose (Rha), arabinose (Ara), galactose (Gal), glucose (Glc), and mannose (Man) in a molar ratio of 0.35:0.44:1.38:0.67:1.65. With reference to its bioactivity, it showed to possess anticancer activity against Head and Neck Squamous Cell Carcinoma cell line by regulating cell cycle arrest and cell apoptosis promotion. To sum up, this study examined the biosynthesis and bioactivity of EPS using a new isolated B. breve strain, which could be used to clarify its further application in functional food or drug industry