Myosin II has distinct functions in PNS and CNS myelin sheath formation

The myelin sheath forms by the spiral wrapping of a glial membrane around the axon. The mechanisms responsible for this process are unknown but are likely to involve coordinated changes in the glial cell cytoskeleton. We have found that inhibition of myosin II, a key regulator of actin cytoskeleton dynamics, has remarkably opposite effects on myelin formation by Schwann cells (SC) and oligodendrocytes (OL). Myosin II is necessary for initial interactions between SC and axons, and its inhibition or down-regulation impairs their ability to segregate axons and elongate along them, preventing the formation of a 1:1 relationship, which is critical for peripheral nervous system myelination. In contrast, OL branching, differentiation, and myelin formation are potentiated by inhibition of myosin II. Thus, by controlling the spatial and localized activation of actin polymerization, myosin II regulates SC polarization and OL branching, and by extension their ability to form myelin. Our data indicate that the mechanisms regulating myelination in the peripheral and central nervous systems are distinct

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier

Mitochondria and other membranous organelles are frequently enriched in the nodes and paranodes of peripheral myelinated axons, particularly those of large caliber. The physiologic role(s) of this organelle enrichment and the rheologic factors that regulate it are not well understood. Previous studies suggest that axonal transport of organelles across the nodal/paranodal region is locally regulated. In this study, we have examined the ultrastructure of myelinated axons in the sciatic nerves of mice deficient in the contactin-associated protein (Caspr), an integral junctional component. These mice, which lack the normal septate-like junctions that promote attachment of the glial (paranodal) loops to the axon, contain aberrant mitochondria in their nodal/paranodal regions. These mitochondria are typically large and swollen and occupy prominent varicosities of the nodal axolemma. In contrast, mitochondria located outside the nodal/paranodal regions of the myelinated axons appear normal. These findings suggest that paranodal junctions regulate mitochondrial transport and function in the axoplasm of the nodal/paranodal region of myelinated axons of peripheral nerves. They further implicate the paranodal junctions in playing a role, either directly or indirectly, in the local regulation of energy metabolism in the nodal region

Nectin-like proteins mediate axon–Schwann cell interactions along the internode and are essential for myelination

Axon–glial interactions are critical for the induction of myelination and the domain organization of myelinated fibers. Although molecular complexes that mediate these interactions in the nodal region are known, their counterparts along the internode are poorly defined. We report that neurons and Schwann cells express distinct sets of nectin-like (Necl) proteins: axons highly express Necl-1 and -2, whereas Schwann cells express Necl-4 and lower amounts of Necl-2. These proteins are strikingly localized to the internode, where Necl-1 and -2 on the axon are directly apposed by Necl-4 on the Schwann cell; all three proteins are also enriched at Schmidt-Lanterman incisures. Binding experiments demonstrate that the Necl proteins preferentially mediate heterophilic rather than homophilic interactions. In particular, Necl-1 on axons binds specifically to Necl-4 on Schwann cells. Knockdown of Necl-4 by short hairpin RNA inhibits Schwann cell differentiation and subsequent myelination in cocultures. These results demonstrate a key role for Necl-4 in initiating peripheral nervous system myelination and implicate the Necl proteins as mediators of axo–glial interactions along the internode

A 500 kpc HI Extension of the Virgo Pair NGC4532/DDO137 Detected by the Arecibo Legacy Fast ALFA (ALFALFA) Survey

We report the discovery of a ~500 kpc H I extension southwest of the Virgo Cluster H I-rich pair NGC 4532/DDO 137, detected as part of the Arecibo Legacy Fast ALFA (ALFALFA) Survey. The feature is the longest and most massive H I tail structure so far found in the Virgo Cluster and, at 1.8 Mpc from M87, the most distant from the main concentration of the intracluster medium. The structure is spatially and spectrally separated into two ridges and is defined by diffuse emission and discrete clumps of mass (2.5–6.8) × 107 M☉. All emission is blueshifted with respect to the NGC 4532/DDO 137 pair emission. Including diffuse emission, the structure has a total mass of up to 7 × 108 M☉, equivalent to ~10% of the system\u27s H I mass. Optical R-band imaging finds no counterparts to a level of 26.5 mag arcsec−2. The characteristics of the structure appear most consistent with a tidal origin

Functionally distinct PI 3-kinase pathways regulate myelination in the peripheral nervous system

Functionally and spatially distinct PI 3-K pathways act either early to promote myelination downstream of axonal Neuregulin1 or late to inhibit myelination downstream of α6β4 integrin and Sgk1

Luminosity-Metallicity Relation for dIrr Galaxies in the Near-Infrared

(abridged) The present work is a first step to collect homogeneous abundances and near-infrared (NIR) luminosities for a sample of dwarf irregular (dIrr) galaxies, located in nearby groups. The use of NIR luminosities is intended to provide a better proxy to mass than the blue luminosities commonly used in the literature; in addition, selecting group members reduces the impact of uncertain distances. Accurate abundances are derived to assess the galaxy metallicity. Optical spectra are collected for Hii regions in the dIrrs, allowing the determination of oxygen abundances by means of the temperature-sensitive method. For each dIrr galaxy H-band imaging is performed and the total magnitudes are measured via surface photometry. This high-quality database allows us to build a well-defined luminosity-metallicity relation in the range -13 >= M(H) >= -20. The scatter around its linear fit is reduced to 0.11 dex, the lowest of all relations currently available. There might exist a difference between the relation for dIrrs and the relation for giant galaxies, although a firm conclusion should await direct abundance determinations for a significant sample of massive galaxies. This new dataset provides an improved luminosity-metallicity relation, based on a standard NIR band, for dwarf star-forming galaxies. The relation can now be compared with some confidence to the predictions of models of galaxy evolution. Exciting follow-ups of this work are (a) exploring groups with higher densities, (b) exploring nearby galaxy clusters to probe environmental effects on the luminosity-metallicity relation, and (c) deriving direct oxygen abundances in the central regions of star-forming giant galaxies, to settle the question of a possible dichotomy between the chemical evolution of dwarfs and that of massive galaxies.Comment: 23 pages, 10 figures, accepted by A&

Star forming dwarf galaxies

Star forming dwarf galaxies (SFDGs) have a high gas content and low metallicities, reminiscent of the basic entities in hierarchical galaxy formation scenarios. In the young universe they probably also played a major role in the cosmic reionization. Their abundant presence in the local volume and their youthful character make them ideal objects for detailed studies of the initial stellar mass function (IMF), fundamental star formation processes and its feedback to the interstellar medium. Occasionally we witness SFDGs involved in extreme starbursts, giving rise to strongly elevated production of super star clusters and global superwinds, mechanisms yet to be explored in more detail. SFDGs is the initial state of all dwarf galaxies and the relation to the environment provides us with a key to how different types of dwarf galaxies are emerging. In this review we will put the emphasis on the exotic starburst phase, as it seems less important for present day galaxy evolution but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres

A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling

A BAFF receptor mutation associated with non-Hodgkin lymphoma provides new insight into the proximal players of normal BAFF-R signaling