Almost all organisms exhibit ~24-h rhythms, or circadian rhythms, in a plentitude of biological processes.These rhythms are driven by endogenous molecular clocks consisting of a series of transcriptional and translati...Almost all organisms exhibit ~24-h rhythms, or circadian rhythms, in a plentitude of biological processes.These rhythms are driven by endogenous molecular clocks consisting of a series of transcriptional and translational feedback loops. Previously, we have shown that the inner nuclear membrane protein MAN1 regulates this clock and thus the locomotor rhythm in flies, but the mechanism remains unclear. Here, we further confirmed the previous findings and found that knocking down MAN1 in the pacemaker neurons of adult flies is sufficient to lengthen the period of the locomotor rhythm. Molecular analysis revealed that knocking down MAN1 led to reduced m RNA and protein levels of the core clock gene period(per),likely by reducing its transcription. Over-expressing per rescued the long period phenotype caused by MAN1 deficiency whereas per mutation had an epistatic effect on MAN1, indicating that MAN1 sets the pace of the clock by targeting per.展开更多
分析1例骨斑点症患者的临床特点并检测LAP2-emerin-MAN1 domain-containing protein 3(LEMD3)基因突变,结合文献探讨骨斑点症的发病机制、临床表现、病理特征及影像学特点。患者,女性,37岁,汉族,因体检X线胸片发现肩关节异常就诊。父母...分析1例骨斑点症患者的临床特点并检测LAP2-emerin-MAN1 domain-containing protein 3(LEMD3)基因突变,结合文献探讨骨斑点症的发病机制、临床表现、病理特征及影像学特点。患者,女性,37岁,汉族,因体检X线胸片发现肩关节异常就诊。父母非近亲结婚,家族中无类似病史。体格检查示四肢关节活动自如,无压痛。X线片检查发现肱骨、锁骨、肩胛骨及部分肋骨、骨盆、双膝关节和双踝关节骨内多发边缘清晰、密度均匀的圆形或卵圆形钙化点。实验室生化检查未见异常。基因组DNA进行LEMD3基因突变检测,结果显示在12号外显子上存在1个杂合错义突变,即c. 2569G>A,导致p. Gly858Arg。骨斑点症是一种罕见的良性骨质硬化性疾病,临床症状常不明显。临床上对骨斑点症应常规检测LEMD3基因突变。展开更多
Protein N-glycosylation plays very important roles in immunity and α-mannosidase is one of the key enzymes in Nglycosylation. This paper reports that inhibition of α-mannosidase Man2c1 gene expression enhances adhes...Protein N-glycosylation plays very important roles in immunity and α-mannosidase is one of the key enzymes in Nglycosylation. This paper reports that inhibition of α-mannosidase Man2c1 gene expression enhances adhesion of Jurkat T cells. In comparison to the controls with normal expression of the enzyme, Jurkat cells with the inhibition of Man2c1 gene expression （AS cell） formed larger aggregates in culture, indicating an enhancement of adhesion between the cells. mRNA differential display analysis discovered up-regulation of several adhesion molecule genes in the AS cell. Because of the pivotal role played by CD54-LFA-1 interaction in immune cell interaction, this study focused on the contribution of enhanced expression of CD54 and LFA-1 to the enhanced adhesion of AS Jurkat cells. These facts, including increased binding of AS cells to ICAM-1-Fc, Mg^2＋ activation of the binding of AS cells to ICAM-1-Fc and enhanced aggregation of AS cells, together with the inhibiting effect of a blocking CD1 la mAb on the binding to ICAM-1-Fc and aggregation of the cells demonstrate an important contribution of enhanced CD54-LFA-1 interaction to increased adhesion between AS cells. The enhanced CD54-LFA-1 interaction also resulted in increased adhesion between AS Jurkat T cells and Raji B cells. In addition, AS cells showed cytoskeletal rearrangement. The data imply a biological significance of MAN2C1 in T-cell functioning.展开更多
基金supported by grants from the National Natural Science Foundation of China (31471125 and 31671215)‘‘1000 Talents’’ Program of China
文摘Almost all organisms exhibit ~24-h rhythms, or circadian rhythms, in a plentitude of biological processes.These rhythms are driven by endogenous molecular clocks consisting of a series of transcriptional and translational feedback loops. Previously, we have shown that the inner nuclear membrane protein MAN1 regulates this clock and thus the locomotor rhythm in flies, but the mechanism remains unclear. Here, we further confirmed the previous findings and found that knocking down MAN1 in the pacemaker neurons of adult flies is sufficient to lengthen the period of the locomotor rhythm. Molecular analysis revealed that knocking down MAN1 led to reduced m RNA and protein levels of the core clock gene period(per),likely by reducing its transcription. Over-expressing per rescued the long period phenotype caused by MAN1 deficiency whereas per mutation had an epistatic effect on MAN1, indicating that MAN1 sets the pace of the clock by targeting per.
基金This work was supported by the National Basic Research Program of China （No. 2001CB510004） by the National Natural Science foundation of China （No. 31070868）.
文摘Protein N-glycosylation plays very important roles in immunity and α-mannosidase is one of the key enzymes in Nglycosylation. This paper reports that inhibition of α-mannosidase Man2c1 gene expression enhances adhesion of Jurkat T cells. In comparison to the controls with normal expression of the enzyme, Jurkat cells with the inhibition of Man2c1 gene expression （AS cell） formed larger aggregates in culture, indicating an enhancement of adhesion between the cells. mRNA differential display analysis discovered up-regulation of several adhesion molecule genes in the AS cell. Because of the pivotal role played by CD54-LFA-1 interaction in immune cell interaction, this study focused on the contribution of enhanced expression of CD54 and LFA-1 to the enhanced adhesion of AS Jurkat cells. These facts, including increased binding of AS cells to ICAM-1-Fc, Mg^2＋ activation of the binding of AS cells to ICAM-1-Fc and enhanced aggregation of AS cells, together with the inhibiting effect of a blocking CD1 la mAb on the binding to ICAM-1-Fc and aggregation of the cells demonstrate an important contribution of enhanced CD54-LFA-1 interaction to increased adhesion between AS cells. The enhanced CD54-LFA-1 interaction also resulted in increased adhesion between AS Jurkat T cells and Raji B cells. In addition, AS cells showed cytoskeletal rearrangement. The data imply a biological significance of MAN2C1 in T-cell functioning.
