Structural and biochemical insights into small RNA 3' end trimming by Arabidopsis SDN1.

A family of DEDDh 3'→5' exonucleases known as Small RNA Degrading Nucleases (SDNs) initiates the turnover of ARGONAUTE1 (AGO1)-bound microRNAs in Arabidopsis by trimming their 3' ends. Here, we report the crystal structure of Arabidopsis SDN1 (residues 2-300) in complex with a 9 nucleotide single-stranded RNA substrate, revealing that the DEDDh domain forms rigid interactions with the N-terminal domain and binds 4 nucleotides from the 3' end of the RNA via its catalytic pocket. Structural and biochemical results suggest that the SDN1 C-terminal domain adopts an RNA Recognition Motif (RRM) fold and is critical for substrate binding and enzymatic processivity of SDN1. In addition, SDN1 interacts with the AGO1 PAZ domain in an RNA-independent manner in vitro, enabling it to act on AGO1-bound microRNAs. These extensive structural and biochemical studies may shed light on a common 3' end trimming mechanism for 3'→5' exonucleases in the metabolism of small non-coding RNAs

Corticomuscular Coherence for Upper Arm Flexor and Extensor Muscles During Isometric Exercise and Cyclically Isokinetic Movement

Cortical-muscular functional coupling reflects the interaction between the cerebral cortex and the muscle activities. Corticomuscular coherence (CMC) has been extensively revealed in sustained contractions of various upper- and lower-limb muscles during static and dynamic force outputs. However, it is not well-understood that the CMC modulation mechanisms, i.e., the relation between a cerebral hemisphere and dynamic motor controlling limbs at constant speeds, such as isokinetic movement. In this paper, we explore the CMC between upper arm flexors/extensors movement and motor cortex during isometric exercise and cyclically isokinetic movement. We also provide further insights of frequency-shift and the neural pathway mechanisms in isokinetic movement by evaluating the coherence between motor cortex and agonistic or antagonistic muscles. This study is the first to investigate the relationship between cortical-muscular functional connections in elbow flexion-extension movement with constant speeds. The result shows that gamma-range coherence for isokinetic movement is greatly increased compared with isometric exercise, and significant CMC is observed in the entire flexion-extension stage regardless the nature of muscles contraction, although dominant synchronization of cortical oscillation and muscular activity resonated in sustained contraction stage principally. Besides, the CMC for extensors and flexors are explicitly consistent in contraction stage during cyclically isokinetic elbow movement. It is concluded that cortical-muscular coherence can be dynamically modulated as well as selective by cognitive demands of the body, and the time-varying mechanisms of the synchronous motor oscillation exist in healthy individuals during dynamic movement

Study on Differences in the Pathology, T Cell Subsets and Gene Expression in Susceptible and Non-Susceptible Hosts Infected with Schistosoma japonicum

More than 40 kinds of mammals in China are known to be naturally infected with Schistosoma japonicum (S. japonicum); Microtus fortis (M. fortis), a species of vole, is the only mammal in which the schistosomes cannot mature or cause significant pathogenic changes. In the current study, we compared the differences in pathology by Hematoxylin-eosin staining and in changes in the T cell subsets with flow cytometry as well as gene expression using genome oligonucleotide microarrays in the lung and liver, before challenge and 10 days post-infection with schistosomes in a S. japonicum-susceptible mouse model of infection, a non-susceptible rat model and the non-permissive host, M. fortis. The results demonstrated that S. japonicum promoted a more intensive immune response and more pathological lesions in M. fortis and rats than in mice. Hematoxylin-eosin staining revealed that the immune effector cells involved were mainly eosinophilic granulocytes supplemented with heterophilic granulocytes and macrophages. The analysis of splenic T cell subsets showed that CD4+ T cell subsets and the CD4+/CD8+ ratio were increased, while the CD8+ T cell subsets decreased remarkably in rats; whereas the CD8+ T cell subsets were increased, but the CD4+/CD8+ ratio was decreased significantly in mice. The analysis of the pattern of gene expression suggested that some immune-associated genes and apoptosis-inducing genes up-regulated, while some development-associated genes were down-regulated in the infected M. fortis compared to the uninfected controls; the three different hosts have different response mechanisms to schistosome infection. The results of this study will be helpful for identifying the key molecules in the immune response to S. japonicum in M. fortis and for understanding more about the underlying mechanism of the response, as well as for elucidating the interaction between S. japonicum and its hosts