Synthesis and evaluation of a bifunctional chelate for development of Bi(III)-labeled radioimmunoconjugates

A new bifunctional ligand C-DEPA was designed and synthesized as a component for antibody-targeted radiation therapy (radioimmunotherapy, RIT) of cancer. C-DEPA was conjugated to a tumor targeting antibody, trastuzumab, and the corresponding C-DEPA-trastuzumab conjugate was evaluated for radiolabeling kinetics with ^205/6Bi. C-DEPA-trastuzumab conjugate rapidly bound ^205/6Bi, and ^205/6Bi-C-DEPA-trastuzumab conjugate was stable in human serum for 72 h. The in vitro radiolabeling kinetics and serum stability data suggest that C-DEPA is a potential chelate for preclinical RIT applications using ²¹²Bi and ²¹³Bi.     

Investigations into the relationship between feedback loops and functional importance of a signal transduction network based on Boolean network modeling

Background  

A number of studies on biological networks have been carried out to unravel the topological characteristics that can explain the functional importance of network nodes. For instance, connectivity, clustering coefficient, and shortest path length were previously proposed for this purpose. However, there is still a pressing need to investigate another topological measure that can better describe the functional importance of network nodes. In this respect, we considered a feedback loop which is ubiquitously found in various biological networks.     

日粮水平对鲇鱼日总代谢,特殊动力作用和活动代谢的影响

在２５℃不同日粮水平（饥饿─４％体重／ｄ）条件下,采用封闭式呼吸仪测定了３１尾鲇鱼（体重７２．９─１３３．３ｇ）的日总代谢率,然后,将鱼限制在呼吸室中的限动笼内测定了其中２０尾鲇鱼的静止日总代谢率,并计算出了鲇鱼的特殊动力作用（ＳＤＡ）和活动代谢率。日总代谢率和活动代谢率都随日粮水平的升高呈“Ｖ”形变化,分别在约１％和２％体重／ｄ的日粮水平时最低,ＳＤＡ的能量支出占摄入能量的２２．１４％。     

Sema6B,Sema6C,and Sema6D Expression and Function during Mammalian Retinal Development

In the vertebrate retina, the formation of neural circuits within discrete laminae is critical for the establishment of retinal visual function. Precise formation of retinal circuits requires the coordinated actions of adhesive and repulsive molecules, including repulsive transmembrane semaphorins (Sema6A, Sema5A, and Sema5B). These semaphorins signal through different Plexin A (PlexA) receptors, thereby regulating distinct aspects of retinal circuit assembly. Here, we investigate the physiological roles of three Class 6 transmembrane semaphorins (Sema6B, Sema6C, and Sema6D), previously identified as PlexA receptor ligands in non-retinal tissues, in mammalian retinal development. We performed expression analysis and also phenotypic analyses of mice that carry null mutations in each of genes encoding these proteins using a broad range of inner and outer retinal markers. We find that these Class 6 semaphorins are uniquely expressed throughout postnatal retinal development in specific domains and cell types of the developing retina. However, we do not observe defects in stereotypical lamina-specific neurite stratification of retinal neuron subtypes in Sema6B^−/− or Sema6C^−/−; Sema6D^−/− retinas. These findings indicate these Class 6 transmembrane semaphorins are unlikely to serve as major PlexA receptor ligands for the assembly of murine retinal circuit laminar organization.     

Non-coding RNAs regulate tumor cell plasticity

Tumor metastasis is one of the most serious challenges for human cancers as the majority of deaths caused by cancer are associated with metastasis, rather than the primary tumor. Recent studies have demonstrated that tumor cell plasticity plays a critical role in tumor metastasis by giving rise to various cell types which is necessary for tumor to invade adjacent tissues and form distant metastasis. These include differentiation of cancer stem cells (CSCs), or epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET). A growing body of evidence has demonstrated that the biology of tumor cell plasticity is tightly linked to functions of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Therefore, understanding the mechanisms how non-coding RNAs regulate tumor cell plasticity is essential for discovery of new diagnostic markers and therapeutic targets to overcome metastasis.