Myelin is a biologically active membrane receiving and processing signals from axons. Whereas, much is known about its structure and molecular composition, the intracellular signal transduction pathways, active during specific phases of myelinogenesis for regulating myelin formation remain poorly understood. Recent genetic loss-of-function studies have suggested a key role of extracelluar-signal-regulated-kinases-1 and -2 (ERK1/2), downstream mediators of mitogen-activated-protein-kinases (MAPKs), in promoting CNS and PNS myelination. In contrast, other studies, largely in vitro, have suggested that activation of ERK1/2 pathway can be detrimental for glial cell function and myelination. Given these conflicting reports, we investigated the effects of cell-autonomous activation of ERK1/2 in glial cells during developmental myelination in the intact CNS and PNS. Two lines of transgenic mice with sustained activation of ERK1/2 in oligodendrocyte progenitors (OPCs), oligodendrocytes, and Schwann cells were generated. Consistent with our loss-of-function studies, gain of ERK1/2 function in oligodendrocyte-lineage cells significantly increased myelin thickness, independent of oligodendrocyte differentiation or initiation of myelination. Additionally, increased activation of ERK1/2 in OPCs during early development resulted in transient hyper-proliferation and overproduction of OPCs, but generation of normal numbers of myelinating oligodendrocytes. Thus, these in vivo studies suggest a beneficial biphasic requirement of ERK1/2 during developmental myelination in the CNS, deployed first during early stages of the oligodendrocyte lineage for promoting OPC expansion and then redeployed later in myelinating oligodendrocytes for promoting myelin growth. Furthermore, Schwann cells with activated ERK1/2 hypermyelinate PNS axons, suggesting that ERK1/2 signaling is a conserved mechanism that promotes both CNS and PNS developmental myelination.

Wrapping of the myelin sheath around axons by oligodendrocytes is critical for the rapid conduction of electrical signals, required for the normal functioning of the central nervous system (CNS). Myelination is a multistep process where oligodendrocytes progress through a well-coordinated differentiation program regulated by multiple extracellular growth and differentiation signals. The intracellular-transduction of the extracellular signals that regulate myelination is poorly understood. Here we demonstrate a critical role for two important signaling molecules, extracelluar-signal-regulated-kinases-1 and -2 (ERK1/ERK2), downstream mediators of mitogen-activated protein kinases (MAPK), in the control of CNS myelin thickness. We generated and analyzed two lines of mice lacking both ERK1/ERK2 function specifically in oligodendrocyte-lineage cells. In the absence of ERK1/ERK2 signaling oligodendrocyte progenitor cells (OPC) proliferated and differentiated on schedule. Mutant oligodendrocytes also ensheathed axons normally and made a few wraps of compact myelin. However, the subsequent increase in myelination that correlated myelin thickness in proportion to the axon caliber failed to occur. Furthermore, although the numbers of differentiated oligodendrocytes in the adult mutants were unchanged, they showed an inability to upregulate the transcription of major myelin genes that normally occurs during active myelination. Similarly, in vitro ERK1/ERK2 deficient NG2+ oligodendrocytes differentiated normally but failed to form typical myelin-like membrane sheets. None of these effects were observed in single ERK1 or ERK2 mutants. These studies suggest that the predominant role of ERK1/ERK2 signaling in vivo is in promoting rapid myelin growth to increase its thickness, subsequent to oligodendrocyte differentiation and the initiation of myelination.

Luminescence properties of carbon nanotubes are strongly affected by exciton diffusion, which plays an important role in various nonradiative decay processes. Here we perform photoluminescence microscopy on hundreds of individual air-suspended carbon nanotubes to elucidate the interplay between exciton diffusion, end quenching, and exciton-exciton annihilation processes. A model derived from random-walk theory as well as Monte Carlo simulations are utilized to analyze nanotube length dependence and excitation power dependence of emission intensity. We have obtained the values of exciton diffusion length and absorption cross section for different chiralities, and diameterdependent photoluminescence quantum yield have been observed. The simulations have also revealed the nature of a one-dimensional coalescence process, and an analytical expression for the power dependence of emission intensity is given.

Myelination is the culmination of a complex process in which oligodendrocyte (OL) progenitors transition through defined stages in a well-coordinated differentiation program. The signaling mechanisms that regulate this progression are poorly understood. Here we investigate the role of extracellular signal-regulated-kinase-1,-2 (Erk1/2) and the mammalian target of rapamycin (mTOR), downstream effectors of the Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways, at specific stages of OL development in vitro. Using a panel of developmental stage-specific antigenic markers and pharmacological inhibitors, we provide evidence that Erk1/2 signaling regulates transition of early progenitors to the late progenitor stage and, as a consequence, to the immature OL stage, but not the transition of immature OL to the mature OL stage. In contrast, mTOR signaling is not required for early progenitor transition to late progenitor stage. Surprisingly, it is also not required for the transition of late progenitors to terminally differentiated immature OLs, as has been reported previously, but is required for the next sequential transition of immature OLs to the mature OL stage. Furthermore, mTOR signaling regulates OL cytoskeletal organization and major myelin protein expression. These in vitro findings correlate with our in vivo data showing that inhibition of mTOR by rapamycin injection attenuated the onset of myelination in the early postnatal brain. Thus, these studies demonstrate that Erk1/2 and mTOR signaling sequentially regulates distinct stages of OL progenitor differentiation and suggest that cells in the OL-lineage require distinct signaling mechanisms to transition through specific stages of their development.

Fruit bats are suspected to be a natural reservoir of filoviruses, including Ebola and Marburg viruses. Using an enzyme-linked immunosorbent assay based on the viral glycoprotein antigens, we detected filovirus-specific immunoglobulin G antibodies in 71 of 748 serum samples collected from migratory fruit bats (Eidolon helvum) in Zambia during 2006-2013. Although antibodies to African filoviruses (eg, Zaire ebolavirus) were most prevalent, some serum samples showed distinct specificity for Reston ebolavirus, which that has thus far been found only in Asia. Interestingly, the transition of filovirus species causing outbreaks in Central and West Africa during 2005-2014 seemed to be synchronized with the change of the serologically dominant virus species in these bats. These data suggest the introduction of multiple species of filoviruses in the migratory bat population and point to the need for continued surveillance of filovirus infection of wild animals in sub-Saharan Africa, including hitherto nonendemic countries.

Myelin, formed by oligodendrocytes (OLs) in the CNS, is critical for axonal functions, and its damage leads to debilitating neurological disorders such as multiple sclerosis. Understanding the molecular mechanisms of myelination and the pathogenesis of human myelin disease has been limited partly by the relative lack of identification and functional characterization of the repertoire of human myelin proteins. Here, we present a large-scale analysis of the myelin proteome, using the shotgun approach of 1-dimensional PAGE and liquid chromatography/tandem MS. Three hundred eight proteins were commonly identified from human and mouse myelin fractions. Comparative microarray analysis of human white and gray matter showed that transcripts of several of these were elevated in OL-rich white matter compared with gray matter, providing confidence in their detection in myelin. Comparison with other databases showed that 111 of the identified proteins/transcripts also were expressed in OLs, rather than in astrocytes or neurons. Comparison with 4 previous myelin proteomes further confirmed more than 50% of the identified proteins and revealed the presence of 163 additional proteins. A select group of identified proteins also were verified by immunoblotting. We classified the identified proteins into biological subgroups and discussed their relevance in myelin biogenesis and maintenance. Taken together, the study provides insights into the complexity of this metabolically active membrane and creates a valuable resource for future in-depth study of specific proteins in myelin with relevance to human demyelinating diseases.microarray ͉ oligodendrocyte ͉ proteomics ͉ mass spectrometry

The unique emission properties of single-walled carbon nanotubes are attractive for achieving increased functionality in integrated photonics. In addition to being room-temperature telecom-band emitters that can be directly grown on silicon, they are ideal for coupling to nanoscale photonic structures. Here we report on high-efficiency coupling of individual air-suspended carbon nanotubes to silicon photonic crystal nanobeam cavities. Photoluminescence images of dielectric- and air-mode cavities reflect their distinctly different mode profiles and show that fields in the air are important for coupling. We find that the air-mode cavities couple more efficiently, and estimated spontaneous emission coupling factors reach a value as high as 0.85. Our results demonstrate advantages of ultralow mode-volumes in air-mode cavities for coupling to low-dimensional nanoscale emitters.

An anuran amphibian, South African clawed frog (Xenopus laevis), is used to study the immune system, as it possesses a set of acquired immune system represented by T and B lymphocytes and the immunoglobulins. The acquired immune system is impaired throughout the larva and the metamorphosis stage in the amphibians. On the other hand, the role of innate immune system in the tadpole remains unclear. Recently, insect Toll protein homologues, namely, Toll-like receptors (TLRs), have been identified as sensors recognizing microbe-pattern molecules in vertebrates. Whole-genome analysis of Xenopus tropicalis supported the existence of the tlr genes in the frog. In this study, we annotated 20 frog tlr gene nucleotide sequences from the latest genome assembly version 4.1 on the basis of homology and identified cDNAs of the predicted frog TLR proteins. Phylogenetic analysis showed that the repertoire of the frog TLRs consisted of both fish- and mammalian-type TLRs. We showed that the frog TLRs are constitutively expressed in the tadpole as well as in the adult frog. Our results suggest that tadpoles are protected from microbes by the innate system that includes TLRs, despite impaired acquired immune system in tadpoles. This is the first report on the properties of TLRs in the most primitive terrestrial animals like amphibia.