Both embryonic and adult neurogenesis involves the self-renewal/proliferation, survival, migration and lineage differentiation of neural stem/progenitor cells. Such dynamic process is tightly regulated by intrinsic and extrinsic factors and complex signaling pathways. Misregulated neurogenesis contributes much to a large range of neurodevelopmental defects and neurodegenerative diseases. The signaling of NFκB regulates many genes important in inflammation, immunity, cell survival and neural plasticity. During neurogenesis, NFκB signaling mediates the effect of numerous niche factors such as cytokines, chemokines, growth factors, extracellular matrix molecules, but also cross-talks with other signaling pathways such as Notch, Shh, Wnt/β-catenin. This review summarizes current progress on the NFκB signaling in all aspects of neurogenesis, focusing on the novel role of NFκB signaling in initiating early neural differentiation of neural stem cells and embryonic stem cells.

Neurons are the basic units of connectivity in the nervous system. As a signature feature, neurons form polarized structures: dendrites and axons, which integrate either sensory stimuli or inputs from upstream neurons and send outputs to target cells, respectively. The separation of dendritic and axonal compartments is achieved in two steps during development: 1) dendrite and axon specification: how neurites are initially specified as dendrites and axons; and 2) dendrite and axon commitment: how dendrites and axons are committed to distinct compartmental fates and architectures. To understand neural circuit assembly and to correct erroneous dendrite or axon growth in a compartment-specific manner, it is essential to understand the regulatory mechanisms underlying dendrite and axon commitment. Compared to extensive studies on dendrite and axon specification, little is known about the molecular mechanisms exclusively dedicated to dendrite or axon commitment. Recent studies have uncovered the requirement of transcriptional regulation in this process. Here, we review the studies on transcriptional regulators: Dar1, p300-SnoN, NeuroD, which have been shown to separate dendrite- and axon-specific growth of the same neuron type after compartmental fates are specified.

The development of the mammalian neocortex involves rounds of symmetric and asymmetric cell division of neural progenitors to fulfill needs of both self-renewal of progenitors and production of differentiated progenies such as neurons and glia. The machinery for asymmetric cell division is evolutionarily conserved and extensively used in organogenesis and homeostasis of adult tissues. Here we summarize recent progress regarding cellular characteristics of different types of neural progenitors in mammals, highlighting how asymmetric cell division is utilized during cortical development.

The initial diagnosis of Parkinson’s disease (PD) is currently based on a clinical assessment. Many patients who receive an initial diagnosis of PD have parkinsonian features related to other diseases such as essential tremor, vascular parkinsonism and atypical parkinsonian disorder. It has been challenging to differentiate PD from those disorders, especially in the early disease stages, due to an overlap of clinical signs and symptoms. Therefore, there is a great need for development of noninvasive, highly sensitive, and widely available imaging methods that can potentially be used to assistant physicians to make more accurate diagnosis of the disease; and to longitudinally monitor treatment of PD. Recent advance of pharmacological MRI (phMRI) technology allows non-invasively mapping functional stages for nigrostriatal dopamine (DA) system. This article aims to review research findings primarily from our group in nonhuman primates modeling the neurodegenerative disease on the value of phMRI techniques in the diagnosis of PD.

The scientific community has shown great interest in the field of mass spectrometry-based proteomics and peptidomics for its applications in biology. Proteomics technologies have evolved to produce large data sets of proteins or peptides involved in various biologic and disease progression processes generating testable hypothesis for complex biologic questions. This review provides an introduction to relevant topics in proteomics and peptidomics including biologic material selection, sample preparation, separation techniques, peptide fragmentation, post-translational modifications, quantification, bioinformatics, and biomarker discovery and validation. In addition, current literature, remaining challenges, and emerging technologies for proteomics and peptidomics are presented.

Functional protein microarray is an important tool for high-throughput and large-scale systems biology studies. Besides the progresses that have been made for protein microarray fabrication, significant advancements have also been achieved for applying protein microarrays on determining a variety of protein biochemical activities. Among these applications, detection of protein binding properties, such as protein-protein interactions (PPIs), protein-DNA interactions (PDIs), protein-RNA interactions, and antigen-antibody interactions, are straightforward and have substantial impacts on many research fields. In this review, we will focus on the recent progresses in protein-protein, protein-DNA, protein-RNA, protein-small molecule, protein-lipid, protein-glycan, and antigen-antibody interactions. We will also discuss the challenges and future directions of protein microarray technologies. We strongly believe that protein microarrays will soon become an indispensible tool for both basic research and clinical applications.

Artemia embryos can endure extreme temperature, long-term anoxia, desiccation and other wide variety of stressful conditions. How the embryos survive these stresses is a very interesting and unsolved subject. To solve this question we analyzed the nucleotide and deduced protein sequence for Hsp26, a molecular chaperone specific to Artemia embryo development. cDNAs of Hsp26 were sequenced from eight Artemia species and deduced Hsp26 amino acid sequences were analyzed. Computer-assisted analysis indicated that the 5′-untranslated region and all the 3 introns contain many putative cis-acting elements for Hsp26 gene expression during development, including heat shock elements (HSEs), Dfd, dl, CF2-II, Hb and AP-1 binding sites. Secondary structure of the Hsp26 3′-untranslated terminator contains the basic structure basis for transcriptional termination. Hsp26 shares sequence similarity with sHSPs (small heat shock protein) from other organisms. The physico-chemical properties of the deduced protein, such as theoretical molecular weight, protein extinction coefficient, isoelectric point and antigenic sites were also obtained. One seven-peptide nuclear localization signals (NLS) “PFRRRMM” was found, which suggested that the Hsp26 protein was hypothesized to be located inside the nucleus. The numbers of phosphorylation sites of serine, threonine and tyrosine and kinase specific phosphorylation sites are also located in Hsp26 protein sequence. These studies will help us achieve a better understanding of Hsp26 and broad implications for sHSPs function in crustacean embryo development.

Tumor-associated macrophages (TAMs) play a critical role in melanoma growth and metastasis. Infiltration of TAMs correlates with the poor prognosis of melanoma. TAMs are differentiated from monocytes in response to the tumor microenvironment cue. However, the mechanism how TAMs adapt to the tumor microenvironment after differentiation from monocytes is not fully understood. In addition, specific identification of TAMs in melanoma is difficult because the expression of the most commonly used macrophage marker, CD68, is also expressed in melanoma cells. In an earlier study, we found by gene microarray analysis that seven members of the metallothionein (MTs) family were upregulated in melanoma-conditioned medium induced macrophages (MCIM-Mф). MTs have been implicated in zinc metabolism and inflammation. In the present study, we confirmed that expression of metallothionein is induced in M-CSF differentiated macrophages (M-CSF/Mф) and MCIM-Mф at both the mRNA and protein levels using real-time PCR, immunofluorescence, and western blot analysis. Furthermore, we demonstrated the presence of metallothionein in melanoma tissues in vivo and that metallothionein was co-localized with TAMs markers, CD68 and CD163. Finally, we demonstrated the induction of the zinc importer gene Zip8 both in M-CSF/Mф and MCIM-Mф. Our study identifies metallothionein as a novel marker for TAMs and suggests that metallothionein might play important roles in macrophage adaptation and function in the tumor microenvironment.

Thyroid hormone receptors (TR), ligand-mediated transcription factors, regulate cell growth, differentiation, and apoptosis. In humans, two different genes encode TR-α and TR-β and they are often co-expressed in various tissues at different levels. To explore the role of TR in esophageal cancer, we analyzed expression of TR-β1 mRNA (most abundantly expressed in the majority of normal cells) in normal and malignant esophageal tissue specimens using in situ hybridization. The TR-β1 mRNA was detected in 92.3% (96 of 104) of normal esophageal mucosa, whereas TR-β1 mRNA was only detected in 55.8% (58 of 104 cases) of esophageal squamous cell carcinoma specimens (P<0.00001). Expression of TR-β1 mRNA was associated with well-differentiated cancers (P<0.001). Furthermore, we determined whether the loss of heterozygosity (LOH) in TR-β gene locus would be responsible for the lost TR-β1 expression. Analysis of 73 esophageal tissue specimens generated 39 informative cases, 17 of which showed LOH (43.6%) but only 9 of these 17 cases were correlated with lost TR-β1 expression. This study demonstrated that expression of TR-β1 mRNA was lost in esophageal cancer tissues, which may be due to multiple mechanisms.

Cryosection in plants is usually challenging because of the larger amounts of water contained in plant cell than animal cell. The formation of ice crystals within the plant cells easily destroys subcellular detail during freeze processing. And cell walls make freezing plant tissues hardly sliced and preserve the cell structure in subtle ways. In this study, the technique was improved on infusion, embedding and flatting sections with the winter wheat Variety Aikang58 as raw material.