Study on the role of gga-miRNA-200a in regulating cell differentiation and proliferation of chicken breast muscle by targeting Grb2

Growth factor receptor-bound protein 2 (Grb2) have been proved by a lot of studies playing a major role in cell proliferation and cell differentiation. However, the regulation of Grb2 expression by microRNAs (miRNAs) in chicken breast muscle still remains unknown. The expression profile of Grb2 was checked based on our previous RNA sequencing data and the Grb2 relative expression level in breast muscle of aged hens (55-week-old) was validated significantly higher than juvenile hens (20-week-old) using qRT-PCR. miRNAs that interact with Grb2 have been predicted in chicken and the relationship between the potential miRNA and Grb2 was verified using dual luciferase reporter assay in chicken DF1 cells. Dual-luciferase reporter assays results demonstrated that the expression of luciferase reporter gene linked with part sequence of the 3′UTR of chicken Grb2 gene was down-regulated by the overexpression of gga (Gallus Gallus)-miR-200a-3p in the DF1 cells, and the down-regulation behavior was abolished when the gga-miR-200a-3p binding site in 3′UTR of Grb2 was mutated, indicating that gga-miR-200a can suppress the expression level of its target gene Grb2. Therefore, we concluded that the significantly increased expression level of Grb2 in the breast muscle of aged chicken can (at least partly can) be explained by the decreased expression of miR-200a, which reduced the inhibitory effect on Grb2. Taken together, these findings suggest that gga-miR-200a can suppress the expression level of its target gene Grb2 and might be involved in the cell differentiation and proliferation of chicken breast muscle through binding with the 3’UTR of Grb2.     

Factor Xa: at the crossroads between coagulation and signaling in physiology and disease

Activated factor Xa (FXa) is traditionally known as an important player in the coagulation cascade responsible for thrombin generation. Long considered a passive bystander, it is now evident that FXa exerts direct effects on a wide variety of cell types via activation of its two main receptors, protease-activated receptor-1 (PAR-1) and PAR-2. Recent findings suggest that PAR-2 plays a crucial role in fibro-proliferative diseases such as fibrosis, tissue remodeling and cancer and point towards FXa as the important mediator coordinating the interface between coagulation and disease progression. Here, we provide an overview of the FXa signaling pathways that mediate its effects in pathophysiology and explore the potential therapeutic implications of targeting FXa; in terms of arresting disease progression, the modulation of FXa activity might be more important than the modulation of FVIIa or thrombin.     

Transient induced gamma-band response in EEG as a manifestation of miniature saccades

The induced gamma-band EEG response (iGBR) recorded on the scalp is widely assumed to reflect synchronous neural oscillation associated with object representation, attention, memory, and consciousness. The most commonly reported EEG iGBR is a broadband transient increase in power at the gamma range approximately 200-300 ms following stimulus onset. A conspicuous feature of this iGBR is the trial-to-trial poststimulus latency variability, which has been insufficiently addressed. Here, we show, using single-trial analysis of concomitant EEG and eye tracking, that this iGBR is tightly time locked to the onset of involuntary miniature eye movements and reflects a saccadic "spike potential." The time course of the iGBR is related to an increase in the rate of saccades following a period of poststimulus saccadic inhibition. Thus, whereas neuronal gamma-band oscillations were shown conclusively with other methods, the broadband transient iGBR recorded by scalp EEG reflects properties of miniature saccade dynamics rather than neuronal oscillations.     

大鼠尾壳核头部生长抑素mRNA的区域性表达

目的　观察尾壳核 (CP)头部背内侧区、背外侧区、腹内侧区和腹外侧区生长抑素 (SOM )mRNA阳性神经元分布特点。方法　采用原位杂交组织化学方法。结果　CP头部不同区域SOMmRNA阳性神经元的密度存在差异 ,腹内侧区SOMmRNA阳性神经元的密度明显高于其他区 (P <0 0 1)。结论　CP头部不同区域的SOMmRNA阳性神经元密度存在差异 ,这可能是CP头部不同区域机能差异的形态学基础之一。     

大鼠隔区接受海马一氧化氮合酶(NOS)阳性神经元的投射

目的逆行追踪大鼠海马NOS阳性神经元向隔区的投射。方法用HRP逆行追踪与NADPH-d组化方法相结合进行研究。结果背、腹、后海马均有NOS阳性神经元投射至隔区各亚细胞群,后海马NOS阳性神经元向隔外侧核(sl)、隔三角核和隔伞核(ts,sf)的投射量,占后海马至隔外侧核、隔三角核和隔伞核投射量的80％左右。结论大鼠隔区接受海马NOS神经元的投射。     

Role of Tim50 in the Transfer of Precursor Proteins from the Outer to the Inner Membrane of Mitochondria

Transport of essentially all matrix and a number of inner membrane proteins is governed, entirely or in part, by N-terminal presequences and requires a coordinated action of the translocases of outer and inner mitochondrial membranes (TOM and TIM23 complexes). Here, we have analyzed Tim50, a subunit of the TIM23 complex that is implicated in transfer of precursors from TOM to TIM23. Tim50 is recruited to the TIM23 complex via Tim23 in an interaction that is essentially independent of the rest of the translocase. We find Tim50 in close proximity to the intermembrane space side of the TOM complex where it recognizes both types of TIM23 substrates, those that are to be transported into the matrix and those destined to the inner membrane, suggesting that Tim50 recognizes presequences. This function of Tim50 depends on its association with TIM23. We conclude that the efficient transfer of precursors between TOM and TIM23 complexes requires the concerted action of Tim50 with Tim23.     

Structure-Function Analysis of Nucleolin and ErbB Receptors Interactions

Background

The ErbB receptor tyrosine kinases and nucleolin are major contributors to malignant transformation. Recently we have found that cell-surface ErbB receptors interact with nucleolin via their cytoplasmic tail. Overexpression of ErbB1 and nucleolin leads to receptor phosphorylation, dimerization and anchorage independent growth.

Methodology/Principal Findings

In the present study we explored the regions of nucleolin and ErbB responsible for their interaction. Using mutational analyses, we addressed the structure–function relationship of the interaction between ErbB1 and nucleolin. We identified the ErbB1 nuclear localization domain as nucleolin interacting region. This region is important for nucleolin-associated receptor activation. Notably, though the tyrosine kinase domain is important for nucleolin-associated receptor activation, it is not involved in nucleolin/ErbB interactions. In addition, we demonstrated that the 212 c-terminal portion of nucleolin is imperative for the interaction with ErbB1 and ErbB4. This region of nucleolin is sufficient to induce ErbB1 dimerization, phosphorylation and growth in soft agar.

Conclusions/Significance

The oncogenic potential of ErbB depends on receptor levels and activation. Nucleolin affects ErbB dimerization and activation leading to enhanced cell growth. The C-terminal region of nucleolin and the ErbB1 NLS-domain mediate this interaction. Moreover, when the C-terminal 212 amino acids region of nucleolin is expressed with ErbB1, it can enhance anchorage independent cell growth. Taken together these results offer new insight into the role of ErbB1 and nucleolin interaction in malignant cells.