Longitudinal Metabolomics Profiling of Parkinson’s Disease-Related α-Synuclein A53T Transgenic Mice

Metabolic homeostasis is critical for all biological processes in the brain. The metabolites are considered the best indicators of cell states and their rapid fluxes are extremely sensitive to cellular changes. While there are a few studies on the metabolomics of Parkinson’s disease, it lacks longitudinal studies of the brain metabolic pathways affected by aging and the disease. Using ultra-high performance liquid chromatography and tandem mass spectroscopy (UPLC/MS), we generated the metabolomics profiling data from the brains of young and aged male PD-related α-synuclein A53T transgenic mice as well as the age- and gender-matched non-transgenic (nTg) controls. Principal component and unsupervised hierarchical clustering analyses identified distinctive metabolites influenced by aging and the A53T mutation. The following metabolite set enrichment classification revealed the alanine metabolism, redox and acetyl-CoA biosynthesis pathways were substantially disturbed in the aged mouse brains regardless of the genotypes, suggesting that aging plays a more prominent role in the alterations of brain metabolism. Further examination showed that the interaction effect of aging and genotype only disturbed the guanosine levels. The young A53T mice exhibited lower levels of guanosine compared to the age-matched nTg controls. The guanosine levels remained constant between the young and aged nTg mice, whereas the aged A53T mice showed substantially increased guanosine levels compared to the young mutant ones. In light of the neuroprotective function of guanosine, our findings suggest that the increase of guanosine metabolism in aged A53T mice likely represents a protective mechanism against neurodegeneration, while monitoring guanosine levels could be applicable to the early diagnosis of the disease.     

Advances in endophenotyping schizophrenia

The search for the genetic architecture of schizophrenia has employed multiple, often converging strategies. One such strategy entails the use of tracing the heritability and neurobiology of endophenotypes. Endophenotypes are quantifiable traits not visible to the eye, which are thought to reflect an intermediate place on the path from genes to disorder. Endophenotype abnormalities in domains such as neurophysiology or neurocognition occur in schizophrenia patients as well as their clinically “unaffected” relatives, and reflect polymorphisms in the DNA of schizophrenia spectrum subjects which create vulnerability to developing schizophrenia. By identifying the single nucleotide polymorphisms (SNPs) associated with endophenotypes in schizophrenia, psychiatric neuroscientists can select new strong inference based molecular targets for the treatment of schizophrenia.     

SPC-Cre-ERT2 Transgenic Mouse for Temporal Gene Deletion in Alveolar Epithelial Cells

Although several Cre-loxP-based gene knockout mouse models have been generated for the study of gene function in alveolar epithelia in the lung, their applications are still limited. In this study, we developed a SPC-Cre-ER^T2 mouse model, in which a tamoxifen-inducible Cre recombinase (Cre-ER^T2) is under the control of the human surfactant protein C (SPC) promoter. The specificity and efficiency of Cre-ER^T2 activity was first evaluated by crossing SPC-Cre-ER^T2 mouse with ROSA26R mouse, a β-galactosidase reporter strain. We found that Cre-ER^T2 was expressed in 30.7% type II alveolar epithelial cells of SPC-Cre-ER^T2/ROSA26R mouse lung tissues in the presence of tamoxifen. We then tested the tamoxifen-inducible recombinase activity of Cre-ER^T2 in a mouse strain bearing TSC1 conditional knockout alleles (TSC1^fx/fx). TSC1 deletion was detected in the lungs of tamoxifen treated SPC-Cre-ER^T2/TSC1^fx/fx mice. Therefore this SPC-Cre-ER^T2 mouse model may be a valuable tool to investigate functions of genes in lung development, physiology and disease.     

SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway

Gastric cancer is a major cause of mortality worldwide. The glutamate/aspartate transporter SLC1A3 has been implicated in tumour metabolism and progression, but the roles of SLC1A3 in gastric cancer remain unclear. We used bioinformatics approaches to analyse the expression of SLC1A3 and its role in gastric cancer. The expression levels of SLC1A3 were examined using RT‐qPCR and Western bolting. SLC1A3 overexpressing and knock‐down cell lines were constructed, and the cell viability was evaluated. Glucose consumption, lactate excretion and ATP levels were determined. The roles of SLC1A3 in tumour growth were evaluated using a xenograft tumour growth model. SLC1A3 was found to be overexpressed in gastric cancer, and this overexpression was associated with poor prognosis. In vitro and in vivo assays showed that SLC1A3 affected glucose metabolism and promoted gastric cancer growth. GSEA analysis suggested that SLC1A3 was positively associated with the up‐regulation of the PI3K/AKT pathway. SLC1A3 overexpression activated the PI3K/AKT pathway and up‐regulated GLUT1, HK II and LDHA expression. The PI3K/AKT inhibitor LY294002 prevented SLC1A3‐induced glucose metabolism and cell proliferation. Our findings indicate that SLC1A3 promotes gastric cancer progression via the PI3K/AKT signalling pathway. SLC1A3 is therefore a potential therapeutic target in gastric cancer.     

野大豆(Glycine soja)叶绿体的光谱及其激子能量转移

野大豆叶绿体在低温(77K)时出现三条荧光发射谱带,它们来源于不同的色素蛋白复合体。 在纳秒脉冲激光激发下,捕光天线色素的相对荧光量子产额,随激光强度的增加有明显下降现象。用激子理论和动力学方程讨论和计算了激子扩散参量。指出激子转移是随机的,非相干的。     

Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

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