236 research outputs found
A Common Origin for Neutrino Anarchy and Charged Hierarchies
The generation of exponential flavor hierarchies from extra-dimensional
wavefunction overlaps is re-examined. We find, surprisingly, that coexistence
of anarchic fermion mass matrices with such hierarchies is intrinsic and
natural to this setting. The salient features of charged fermion and neutrino
masses and mixings can thereby be captured within a single framework. Both
Dirac and Majorana neutrinos can be realized. The minimal phenomenological
consequences are discussed, including the need for a fundamental scale far
above the weak scale to adequately suppress flavor-changing neutral currents.
Two broad scenarios for stabilizing this electroweak hierarchy are studied,
warped compactification and supersymmetry. In warped compactifications and
"Flavorful Supersymmetry," where non-trivial flavor structure appears in the
new TeV physics, Dirac neutrinos are strongly favored over Majorana by lepton
flavor violation tests. We argue that this is part of a more general result for
flavor-sensitive TeV-scale physics. Our scenario strongly suggests that the
supersymmetric flavor problem is not solved locally in the extra dimension, but
rather at or below the compactification scale. In the supersymmetric Dirac
case, we discuss how the appearance of light right-handed sneutrinos
considerably alters the physics of dark matter.Comment: Comparison with the Froggatt-Nielsen mechanism omitted. Some
clarifications added. This is the version accepted by PRL with a longer
abstract
microRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states.
© 2014 Macmillan Publishers LimitedThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.Progenitor maintenance, timed differentiation and the potential to enter quiescence are three fundamental processes that underlie the development of any organ system. In the nervous system, progenitor cells show short-period oscillations in the expression of the transcriptional repressor Hes1, while neurons and quiescent progenitors show stable low and high levels of Hes1, respectively. Here we use experimental data to develop a mathematical model of the double-negative interaction between Hes1 and a microRNA, miR-9, with the aim of understanding how cells transition from one state to another. We show that the input of miR-9 into the Hes1 oscillator tunes its oscillatory dynamics, and endows the system with bistability and the ability to measure time to differentiation. Our results suggest that a relatively simple and widespread network of cross-repressive interactions provides a unifying framework for progenitor maintenance, the timing of differentiation and the emergence of alternative cell states.Wellcome Trus
Dry and Humid Periods Reconstructed from Tree Rings in the Former Territory of Sogdiana (Central Asia) and Their Socio-economic Consequences over the Last Millennium
One of the richest societies along the Silk Road developed in Sogdiana,
located in present-day Tajikistan, Uzbekistan, and Kyrgyzstan. This urban civilisation
reached its greatest prosperity during the golden age of the Silk Road (sixth to
ninth century ce). Rapid political and economic changes, accelerated by climatic
variations, were observed during last millennium in this region. The newly developed
tree-ring-based reconstruction of precipitation for the pastmillennium revealed
a series of dry and wet stages. During the Medieval Climate Anomaly (MCA), two
dry periods occurred (900–1000 and 1200–1250), interrupted by a phase of wetter
conditions. Distinct dry periods occurred around 1510–1650, 1750–1850, and
1920–1970, respectively. The juniper tree-ring record of moisture changes revealed
that major dry and pluvial episodes were consistent with those indicated by hydroclimatic
proxy data from adjacent areas. These climate fluctuations have had longand
short term consequences for human history in the territory of former Sogdiana
In Vivo Fate Analysis Reveals the Multipotent and Self-Renewal Features of Embryonic AspM Expressing Cells
Radial Glia (RG) cells constitute the major population of neural progenitors of the mouse developing brain. These cells are located in the ventricular zone (VZ) of the cerebral cortex and during neurogenesis they support the generation of cortical neurons. Later on, during brain maturation, RG cells give raise to glial cells and supply the adult mouse brain of Neural Stem Cells (NSC). Here we used a novel transgenic mouse line expressing the CreERT2 under the control of AspM promoter to monitor the progeny of an early cohort of RG cells during neurogenesis and in the post natal brain. Long term fate mapping experiments demonstrated that AspM-expressing RG cells are multi-potent, as they can generate neurons, astrocytes and oligodendrocytes of the adult mouse brain. Furthermore, AspM descendants give also rise to proliferating progenitors in germinal niches of both developing and post natal brains. In the latter –i.e. the Sub Ventricular Zone- AspM descendants acquired several feature of neural stem cells, including the capability to generate neurospheres in vitro. We also performed the selective killing of these early progenitors by using a Nestin-GFPflox-TK allele. The forebrain specific loss of early AspM expressing cells caused the elimination of most of the proliferating cells of brain, a severe derangement of the ventricular zone architecture, and the impairment of the cortical lamination. We further demonstrated that AspM is expressed by proliferating cells of the adult mouse SVZ that can generate neuroblasts fated to become olfactory bulb neurons
Functional Dicer Is Necessary for Appropriate Specification of Radial Glia during Early Development of Mouse Telencephalon
Early telencephalic development involves transformation of neuroepithelial stem cells into radial glia, which are themselves neuronal progenitors, around the time when the tissue begins to generate postmitotic neurons. To achieve this transformation, radial precursors express a specific combination of proteins. We investigate the hypothesis that micro RNAs regulate the ability of the early telencephalic progenitors to establish radial glia. We ablate functional Dicer, which is required for the generation of mature micro RNAs, by conditionally mutating the Dicer1 gene in the early embryonic telencephalon and analyse the molecular specification of radial glia as well as their progeny, namely postmitotic neurons and basal progenitors. Conditional mutation of Dicer1 from the telencephalon at around embryonic day 8 does not prevent morphological development of radial glia, but their expression of Nestin, Sox9, and ErbB2 is abnormally low. The population of basal progenitors, which are generated by the radial glia, is disorganised and expanded in Dicer1-/- dorsal telencephalon. While the proportion of cells expressing markers of postmitotic neurons is unchanged, their laminar organisation in the telencephalic wall is disrupted suggesting a defect in radial glial guided migration. We found that the laminar disruption could not be accounted for by a reduction of the population of Cajal Retzius neurons. Together, our data suggest novel roles for micro RNAs during early development of progenitor cells in the embryonic telencephalon
Study of pallial neurogenesis in shark embryos and the evolutionary origin of the subventricular zone
The dorsal part of the developing telencephalon is one of the brain areas that has suffered most drastic changes throughout vertebrate evolution. Its evolutionary increase in complexity was thought to be partly achieved by the appearance of a new neurogenic niche in the embryonic subventricular zone (SVZ). Here, a new kind of amplifying progenitors (basal progenitors) expressing Tbr2, undergo a second round of divisions, which is believed to have contributed to the expansion of the neocortex. Accordingly, the existence of a pallial SVZ has been classically considered exclusive of mammals. However, the lack of studies in ancient vertebrates precludes any clear conclusion about the evolutionary origin of the SVZ and the neurogenic mechanisms that rule pallial development. In this work, we explore pallial neurogenesis in a basal vertebrate, the shark Scyliorhinus canicula, through the study of the expression patterns of several neurogenic markers. We found that apical progenitors and radial migration are present in sharks, and therefore, their presence must be highly conserved throughout evolution. Surprisingly, we detected a subventricular band of ScTbr2-expressing cells, some of which also expressed mitotic markers, indicating that the existence of basal progenitors should be considered an ancestral condition rather than a novelty of mammals or amniotes. Finally, we report that the transcriptional program for the specification of glutamatergic pallial cells (Pax6, Tbr2, NeuroD, Tbr1) is also present in sharks. However, the segregation of these markers into different cell types is not clear yet, which may be linked to the lack of layering in anamniotesThis work was supported by the Spanish Ministerio de Economía y Competitividad-FEDER (BFU2014-5863-1P)S
Astrocytes: biology and pathology
Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions
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