Nucleolar localization of an isoform of the IGF-I precursor

BACKGROUND: Alternative exons encode different isoforms of the human insulin-like growth factor-I (IGF-I) precursor without altering mature IGF-I. We hypothesized that the various IGF-I precursors may traffic IGF-I differently. Chimeric IGF-I precursors were made with green fluorescent protein (GFP) cloned between the signal and mature IGF-I domains. RESULTS: Chimeras containing exons 1 or 2 were located in the cytoplasm, consistent with a secretory pathway, and suggesting that both exons encoded functional signal peptides. Exon 5-containing chimeras localized to the nucleus and strongly to the nucleolus, while chimeras containing exon 6 or the upstream portion of exon 5 did not. Nuclear and nucleolar localization also occurred when the mature IGF-I domain was deleted from the chimeras, or when signal peptides were deleted. CONCLUSIONS: We have identified a nucleolar localization for an isoform of the human IGF-I precursor. The findings are consistent with the presence of a nuclear and nucleolar localization signal situated in the C-terminal part of the exon 5-encoded domain with similarities to signals in several other growth factors

Embolism recovery strategies and nocturnal water loss across species influenced by biogeographic origin

© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd. Drought-induced tree mortality is expected to increase in future climates with the potential for significant consequences to global carbon, water, and energy cycles. Xylem embolism can accumulate to lethal levels during drought, but species that can refill embolized xylem and recover hydraulic function may be able to avoid mortality. Yet the potential controls of embolism recovery, including cross-biome patterns and plant traits such as nonstructural carbohydrates (NSCs), hydraulic traits, and nocturnal stomatal conductance, are unknown. We exposed eight plant species, originating from mesic (tropical and temperate) and semi-arid environments, to drought under ambient and elevated CO 2 levels, and assessed recovery from embolism following rewatering. We found a positive association between xylem recovery and NSCs, and, surprisingly, a positive relationship between xylem recovery and nocturnal stomatal conductance. Arid-zone species exhibited greater embolism recovery than mesic zone species. Our results indicate that nighttime stomatal conductance often assumed to be a wasteful use of water, may in fact be a key part of plant drought responses, and contribute to drought survival. Findings suggested distinct biome-specific responses that partially depended on species climate-of-origin precipitation or aridity index, which allowed some species to recover from xylem embolism. These findings provide improved understanding required to predict the response of diverse plant communities to drought. Our results provide a framework for predicting future vegetation shifts in response to climate change

A multi-scale brain map derived from whole-brain volumetric reconstructions

Animal nervous system organization is crucial for all body functions and its disruption can lead to severe cognitive and behavioural impairment1. This organization relies on features across scales—from the localization of synapses at the nanoscale, through neurons, which possess intricate neuronal morphologies that underpin circuit organization, to stereotyped connections between different regions of the brain2. The sheer complexity of this organ means that the feat of reconstructing and modelling the structure of a complete nervous system that is integrated across all of these scales has yet to be achieved. Here we present a complete structure–function model of the main neuropil in the nematode Caenorhabditis elegans—the nerve ring—which we derive by integrating the volumetric reconstructions from two animals with corresponding3 synaptic and gap-junctional connectomes. Whereas previously the nerve ring was considered to be a densely packed tract of neural processes, we uncover internal organization and show how local neighbourhoods spatially constrain and support the synaptic connectome. We find that the C. elegans connectome is not invariant, but that a precisely wired core circuit is embedded in a background of variable connectivity, and identify a candidate reference connectome for the core circuit. Using this reference, we propose a modular network architecture of the C. elegans brain that supports sensory computation and integration, sensorimotor convergence and brain-wide coordination. These findings reveal scalable and robust features of brain organization that may be universal across phyla

Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in Caenorhabditis elegans through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic, and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate’s body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour

Mass and Angular Momentum in General Relativity

We present an introduction to mass and angular momentum in General Relativity. After briefly reviewing energy-momentum for matter fields, first in the flat Minkowski case (Special Relativity) and then in curved spacetimes with or without symmetries, we focus on the discussion of energy-momentum for the gravitational field. We illustrate the difficulties rooted in the Equivalence Principle for defining a local energy-momentum density for the gravitational field. This leads to the understanding of gravitational energy-momentum and angular momentum as non-local observables that make sense, at best, for extended domains of spacetime. After introducing Komar quantities associated with spacetime symmetries, it is shown how total energy-momentum can be unambiguously defined for isolated systems, providing fundamental tests for the internal consistency of General Relativity as well as setting the conceptual basis for the understanding of energy loss by gravitational radiation. Finally, several attempts to formulate quasi-local notions of mass and angular momentum associated with extended but finite spacetime domains are presented, together with some illustrations of the relations between total and quasi-local quantities in the particular context of black hole spacetimes. This article is not intended to be a rigorous and exhaustive review of the subject, but rather an invitation to the topic for non-experts. In this sense we follow essentially the expositions in Szabados 2004, Gourgoulhon 2007, Poisson 2004 and Wald 84, and refer the reader interested in further developments to the existing literature, in particular to the excellent and comprehensive review by Szabados (2004).Comment: 41 pages. Notes based on the lecture given at the C.N.R.S. "School on Mass" (June 2008) in Orleans, France. To appear as proceedings in the book "Mass and Motion in General Relativity", eds. L. Blanchet, A. Spallicci and B. Whiting. Some comments and references added

Pseudo-acetylation of multiple sites on human Tau proteins alters Tau phosphorylation and microtubule binding, and ameliorates amyloid beta toxicity

Tau is a microtubule-associated protein that is highly soluble and natively unfolded. Its dysfunction is involved in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD), where it aggregates within neurons. Deciphering the physiological and pathogenic roles of human Tau (hTau) is crucial to further understand the mechanisms leading to its dysfunction in vivo. We have used a knock-out/knock-in strategy in Drosophila to generate a strain with hTau inserted into the endogenous fly tau locus and expressed under the control of the endogenous fly tau promoter, thus avoiding potential toxicity due to genetic over-expression. hTau knock-in (KI) proteins were expressed at normal, endogenous levels, bound to fly microtubules and were post-translationally modified, hence displaying physiological properties. We used this new model to investigate the effects of acetylation on hTau toxicity in vivo. The simultaneous pseudo-acetylation of hTau at lysines 163, 280, 281 and 369 drastically decreased hTau phosphorylation and significantly reduced its binding to microtubules in vivo. These molecular alterations were associated with ameliorated amyloid beta toxicity. Our results indicate acetylation of hTau on multiple sites regulates its biology and ameliorates amyloid beta toxicity in vivo

‘Equally unequal or unequally equal’: Adopting a substantive equality approach to gender discrimination in Nigeria

The purpose of this article is to critically assess the approach of Nigerian courts to interpreting section 42 of the Constitution. This article argues that Nigerian courts are yet to develop a substantive equality approach to interpreting section 42 of the Constitution. Rather, the courts have tended to adopt the formal equality approach to interpreting the section. Analysing some decisions of the Court of Appeal and the Supreme Court, the article argues that in order to safeguard women’s rights and address gender inequality in the country, Nigerian courts should lean towards substantive equality approach to the interpretation of section 42 of the Constitution. This is not only consistent with Nigeria’s obligations under international law but also crucial to addressing historical imbalances between men and women in the country

Providing alcohol-related screening and brief interventions to adolescents through health care systems: Obstacles and solutions

Duncan Clark and Howard Moss identify obstacles to alcohol-related screening and treatment for adolescents and propose policy solutions

Regulation of Granulocyte and Macrophage Populations of Murine Bone Marrow Cells by G-CSF and CD137 Protein

BACKGROUND: Granulocytes and monocytes/macrophages differentiate from common myeloid progenitor cells. Granulocyte colony-stimulating factor (G-CSF) and CD137 (4-1BB, TNFRSF9) are growth and differentiation factors that induce granulocyte and macrophage survival and differentiation, respectively. This study describes the influence of G-CSF and recombinant CD137-Fc protein on myelopoiesis. METHODOLOGY/PRINCIPAL FINDINGS: Both, G-CSF and CD137 protein support proliferation and survival of murine bone marrow cells. G-CSF enhances granulocyte numbers while CD137 protein enhances macrophage numbers. Both growth factors together give rise to more cells than each factor alone. Titration of G-CSF and CD137 protein dose-dependently changes the granulocyte/macrophage ratio in bone marrow cells. Both factors individually induce proliferation of hematopoietic progenitor cells (lin-, c-kit+) and differentiation to granulocytes and macrophages, respectively. The combination of G-CSF and CD137 protein further increases proliferation, and results in a higher number of macrophages than CD137 protein alone, and a lower number of granulocytes than G-CSF alone demonstrating that CD137 protein-induced monocytic differentiation is dominant over G-CSF-induced granulocytic differentiation. CD137 protein induces monocytic differentiation even in early hematopoietic progenitor cells, the common myeloid progenitors and the granulocyte macrophage progenitors. CONCLUSIONS/SIGNIFICANCE: This study confirms earlier data on the regulation of myelopoiesis by CD137 receptor - ligand interaction, and extends them by demonstrating the restriction of this growth promoting influence to the monocytic lineage