Identification of Positionally Distinct Astrocyte Subtypes whose Identities Are Specified by a Homeodomain Code

Astrocytes constitute the most abundant cell type in the central nervous system (CNS) and play diverse functional roles, but the ontogenetic origins of this phenotypic diversity are poorly understood. We have investigated whether positional identity, a fundamental organizing principle governing the generation of neuronal subtype diversity, is also relevant to astrocyte diversification. We identified three positionally distinct subtypes of white-matter astrocytes (WMA) in the spinal cord, which can be distinguished by the combinatorial expression of Reelin and Slit1. These astrocyte subtypes derive from progenitor domains expressing the homeodomain transcription factors Pax6 and Nkx6.1, respectively. Loss- and gain-of-function experiments indicate that the positional identity of these astrocyte subtypes is controlled by Pax6 and Nkx6.1 in a combinatorial manner. Thus, positional identity is an organizing principle underlying astrocyte, as well as neuronal, subtype diversification and is controlled by a homeodomain transcriptional code whose elements are reutilized following the specification of neuronal identity earlier in development

Modification of classical electron transport due to collisions between electrons and fast ions

A Fokker-Planck model for the interaction of fast ions with the thermal electrons in a quasi-neutral plasma is developed. When the fast ion population has a net flux (i.e. the distribution of the fast ions is anisotropic in velocity space) the electron distribution function is significantly perturbed from Maxwellian by collisions with the fast ions, even if the fast ion density is orders of magnitude smaller than the electron density. The Fokker-Planck model is used to derive classical electron transport equations (a generalized Ohm's law and a heat flow equation) that include the effects of the electron-fast ion collisions. It is found that these collisions result in a current term in the transport equations which can be significant even when total current is zero. The new transport equations are analyzed in the context of a number of scenarios including $\alpha$ particle heating in ICF and MIF plasmas and ion beam heating of dense plasmas

The Transcription Factor NFIA Controls the Onset of Gliogenesis in the Developing Spinal Cord

The mechanisms controlling the transition from neurogenesis to gliogenesis in the vertebrate CNS are incompletely understood. We identified a family of transcription factors, called NFI genes, which are induced throughout the spinal cord ventricular zone (VZ) concomitantly with the induction of GLAST, an early marker of gliogenesis. NFIA is both necessary and sufficient for GLAST induction in the VZ. Unexpectedly, NFIA is also essential for the continued inhibition of neurogenesis in VZ progenitors. This function is mediated by the requirement of NFIA for the expression of HES5, a Notch effector. However, Notch effectors are unable to promote glial-fate specification in the absence of NFIA. Thus, NFIA links the abrogation of neurogenesis to a generic program of gliogenesis, in both astrocyte and oligodendrocyte VZ progenitors. At later stages, NFIA promotes migration and differentiation of astrocyte precursors, a function that is antagonized in oligodendrocyte precursors by Olig2

Telephone and face to face methods of assessment of veteran's community reintegration yield equivalent results

<p>Abstract</p> <p>Background</p> <p>The Community Reintegration of Service Members (CRIS) is a new measure of community reintegration developed to measure veteran's participation in life roles. It consists of three sub-scales: Extent of Participation (Extent), Perceived Limitations with Participation (Perceived), and Satisfaction with Participation (Satisfaction). Testing of the CRIS measure to date has utilized in-person administration. Administration of the CRIS measure by telephone, if equivalent to in-person administration, would be desirable to lower cost and decrease administrative burden. The purpose of this study was to test the equivalence of telephone and in-person mode of CRIS administration.</p> <p>Methods</p> <p>A convenience sample of 102 subjects (76% male, 24% female, age mean = 49 years, standard deviation = 8.3) were randomly assigned to received either telephone interview at Visit 1 and in-person interview at Visit 2, or in-person interview at Visit 1 and telephone interview a Visit 2. Both Visits were conducted within one week. Intraclass correlation coefficients, ICC (2,1), were used to evaluate correspondence between modes for both item scores and summary scores. ANOVAs with mode order as a covariate were used to test for presence of an ordering effect.</p> <p>Results</p> <p>ICCs (95%CI) for the subscales were 0.92 (0.88-0.94) for Extent, 0.85 (0.80-0.90) for Perceived, and 0.89 (0.84-0.93) for Satisfaction. No ordering effect was observed.</p> <p>Conclusion</p> <p>Telephone administration of the CRIS measure yielded equivalent results to in-person administration. Telephone administration of the CRIS may enable lower costs of administration and greater adoption.</p

Organic Geochemical Studies. I. Molecular Criteria for Hydrocarbon Genesis

In recent years the search for life-forms at the earliest periods of geological time has been continued not only at the morphological level but also at the molecular level. This has been possible as a result of the increase in the biochemical knowledge and with the advent of analytical techniques that are capable of describing the intimate molecular architecture of individual molecules in acute detail. The fundamental premises upon which this organic geochemical approach rest are the following: that certain molecules, possessing a characteristic structural skeleton, show a reasonable stability to degradation over long periods of geological time; that their structural specificity can be understood in terms of known biosynthetic sequences; and that their formation by any non-biological means is of negligible probability. In this manuscript it is proposed to critically re-examine these premises and to establish criteria whereby one can differentiate molecules derived from biological systems from those that have their origin in non-biological processes. The importance of establishing such criteria lies in the significance these criteria have in determining whether life exists, or has existed, on other planets. Within the very near future it may be possible to provide an initial answer to this question when the first lunar samples are returned to the earth for analysis

Directing Astroglia from the Cerebral Cortex into Subtype Specific Functional Neurons

Forced expression of single defined transcription factors can selectively and stably convert cultured astroglia into synapse-forming excitatory and inhibitory neurons

The neurogenic potential of astrocytes is regulated by inflammatory signals

Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, adult parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, these 'reactive' astrocytes offer an alternative source of cells for central nervous system (CNS) repair following injury or disease. At present, the mechanisms that regulate the potential of different types of astrocytes are poorly understood. We used in vitro and ex vivo astrocytes to identify candidate pathways important for regulation of astrocyte potential. Using in vitro neural progenitor cell (NPC)-derived astrocytes, we found that exposure of more lineage-restricted astrocytes to either tumor necrosis factor alpha (TNF-α) (via nuclear factor-κB (NFκB)) or the bone morphogenetic protein (BMP) inhibitor, noggin, led to re-acquisition of NPC properties accompanied by transcriptomic and epigenetic changes consistent with a more neurogenic, NPC-like state. Comparative analyses of microarray data from in vitro-derived and ex vivo postnatal parenchymal astrocytes identified several common pathways and upstream regulators associated with inflammation (including transforming growth factor (TGF)-β1 and peroxisome proliferator-activated receptor gamma (PPARγ)) and cell cycle control (including TP53) as candidate regulators of astrocyte phenotype and potential. We propose that inflammatory signalling may control the normal, progressive restriction in potential of differentiating astrocytes as well as under reactive conditions and represent future targets for therapies to harness the latent neurogenic capacity of parenchymal astrocytes

Roles of glial cells in synapse development

Brain function relies on communication among neurons via highly specialized contacts, the synapses, and synaptic dysfunction lies at the heart of age-, disease-, and injury-induced defects of the nervous system. For these reasons, the formation—and repair—of synaptic connections is a major focus of neuroscience research. In this review, I summarize recent evidence that synapse development is not a cell-autonomous process and that its distinct phases depend on assistance from the so-called glial cells. The results supporting this view concern synapses in the central nervous system as well as neuromuscular junctions and originate from experimental models ranging from cell cultures to living flies, worms, and mice. Peeking at the future, I will highlight recent technical advances that are likely to revolutionize our views on synapse–glia interactions in the developing, adult and diseased brain