The role of motor network reorganization during rehabilitation

There are roughly 282,000 individuals living with spinal cord injury in the United States alone（National Spinal Cord Injury Statistical Center,Birmingham,AL,USA）.Spinal cord injury often results in permanent functional impairments with only a limited capacity for spontaneous recovery.For the return of motor function,such as locomotion or hand and arm dexterity,

RAFting the rapids of axon regeneration signaling

The functional regeneration of damaged axons and severed connections in the mature central nervous sys- tem （CNS） remains a challenging goal of neurological research. Mature CNS neurons are refractory to axon regeneration for two major reasons, one, because the ac- tivity of cell-intrinsic mechanisms that drive axon growth during development is low- and often further suppressed after an injury - and two, because certain molecules that are part of mature extracellular matrix and myelin act as strong inhibitors of axon growth. Genetic removal of growth inhibitory molecules can increase axon sprouting, but is not sufficient to enable long-range axon growth. Since axon growth is robust during early developmental stages, it has long been hypothesized that mature injured neurons may be ＂reprogrammed＂ to the earlier growth state by re-activation of the intracellular growth signaling cascades that drive axon elongation in the developing fetus.

Recent advances in two-photon imaging: technology developments and biomedical applications

In the past two decades, two-photon microscopy （TPM） transforms biomedicalresearch, allowing non- destructive high-resolution fluorescent molecular imaging and label-free imaging in vivo and in real time. Here we review the recent advances of TPM technologyincluding novel laser sources, new image acquisition paradiams, and microendoscopicimaging systems. Then, we survey the capabilities of TPM imagingof biological relevant molecules such as nicotinamideadenine dinucleotide （NADH）, flavin adenine dinucleotide （FAD）,and reactive oxygen species （ROS）. Biomedical applications of TPM in neuroscience and cancer detection are demonstrated.

Nucleotide sequence conservation of novel and established cis-regulatory sites within the tyrosine hydroxylase gene promoter

Tyrosine hydroxylase （TH） is the rate-limiting enzyme in catecholamine biosynthesis and its gene proximal promoter （〈 1 kb upstream from the transcription start site） is essential for regulating transcription in both the developing and adult nervous systems. Several putative regulatory elements within the TH proximal promoter have been reported, but evolutionary conservation of these dements has not been thoroughly investigated. Since many vertebrate species are used to model development, function and disorders of human catecholaminergic neurons, identifying evolutionarily conserved transcription regulatory mechanisms is a high priority. In this study, we align TH proximal promoter nucleotide sequences from several vertebrate species to identify evolutionarUy conserved motifs. This analysis identified three elements （a TATA box, cyclic AMP response element （CRE） and a 5＇-GGTGG-3＇ site） that constitute the core of an ancient vertebrate TH promoter. Focusing on only eutherian mammals, two regions of high conservation within the proximal promoter were identified： a -250 bp region adjacent to the transcription start site and a -85 bp region located approximately 350 bp further upstream. Within both regions, conservation of previously reported cis-regulatory motifs and human single nucleotide variants was evaluated. Transcription reporter assays in a TH-expressing cell line demonstrated the functionality of highly conserved motifs in the proximal promoter regions and electromobility shift assays showed that brain-region specific complexes assemble on these motifs. These studies also identified a non-canonical CRE binding （CREB） protein recognition element in the proximal promoter. Together, these studies provide a detailed analysis of evolutionary conservation within the TH promoter and identify potential cisregulatory motifs that underlie a core set of regulatory mechanisms in mammals.