Deficiency of Huntingtin Has Pleiotropic Effects in the Social Amoeba Dictyostelium discoideum

Huntingtin is a large HEAT repeat protein first identified in humans, where a polyglutamine tract expansion near the amino terminus causes a gain-of-function mechanism that leads to selective neuronal loss in Huntington's disease (HD). Genetic evidence in humans and knock-in mouse models suggests that this gain-of-function involves an increase or deregulation of some aspect of huntingtin's normal function(s), which remains poorly understood. As huntingtin shows evolutionary conservation, a powerful approach to discovering its normal biochemical role(s) is to study the effects caused by its deficiency in a model organism with a short life-cycle that comprises both cellular and multicellular developmental stages. To facilitate studies aimed at detailed knowledge of huntingtin's normal function(s), we generated a null mutant of hd, the HD ortholog in Dictyostelium discoideum. Dictyostelium cells lacking endogenous huntingtin were viable but during development did not exhibit the typical polarized morphology of Dictyostelium cells, streamed poorly to form aggregates by accretion rather than chemotaxis, showed disorganized F-actin staining, exhibited extreme sensitivity to hypoosmotic stress, and failed to form EDTA-resistant cell–cell contacts. Surprisingly, chemotactic streaming could be rescued in the presence of the bivalent cations Ca2+ or Mg2+ but not pulses of cAMP. Although hd− cells completed development, it was delayed and proceeded asynchronously, producing small fruiting bodies with round, defective spores that germinated spontaneously within a glassy sorus. When developed as chimeras with wild-type cells, hd− cells failed to populate the pre-spore region of the slug. In Dictyostelium, huntingtin deficiency is compatible with survival of the organism but renders cells sensitive to low osmolarity, which produces pleiotropic cell autonomous defects that affect cAMP signaling and as a consequence development. Thus, Dictyostelium provides a novel haploid organism model for genetic, cell biological, and biochemical studies to delineate the functions of the HD protein

Oviposition Site Selection by the Dengue Vector Aedes aegypti and Its Implications for Dengue Control

Controlling the mosquito Aedes aegypti is of public health importance because, at present, it is the only means to stop dengue virus transmission. Implementing successful mosquito control programs requires understanding what factors regulate population abundance, as well as anticipating how mosquitoes may adapt to control measures. In some species of mosquitoes, females choose egg-laying sites to improve the survival and growth of their offspring, a behavior that ultimately influences population distribution and abundance. In the current study, we tested whether Ae. aegypti actively choose the containers in which they lay their eggs and determined what cues are most relevant to that process. We also explored whether females select containers that provide the most food for their larval progeny. Surprisingly, egg-laying females were most attracted to sites containing other immature Ae. aegypti, rather than to sites containing the most food. We propose that this behavior may contribute to density-dependent competition for food among larvae and play a larger role than previously thought in regulating Ae. aegypti populations. We recommend that accounting for, and even taking advantage of, this natural behavior will lead to more effective strategies for dengue prevention

Large Colloids in Cholesteric Liquid Crystals

International audienceno abstrac

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Systems approach to tamper protection

Tamper-protection is a fundamental requirement of effective containment and surveillance systems. Cost effective designs require that the tamper protection requirements be considered early in the design phase and at the system level. A discussion of tamper protection alternatives as well as an illustrative example system is presented

Monitoring Atmospheric, Soil, and Dissolved CO2 Using a Low-Cost, Arduino Monitoring Platform (CO2-LAMP): Theory, Fabrication, and Operation

Variability of CO2 concentrations within the Earth system occurs over a wide range of time and spatial scales. Resolving this variability and its drivers in terrestrial and aquatic environments ultimately requires high-resolution spatial and temporal monitoring; however, relatively high-cost gas analyzers and data loggers can present barriers in terms of cost and functionality. To overcome these barriers, we developed a low-cost Arduino monitoring platform (CO2-LAMP) for recording CO2 variability in electronically harsh conditions: humid air, soil, and aquatic environments. A relatively inexpensive CO2 gas analyzer was waterproofed using a semi-permeable, expanded polytetrafluoroethylene membrane. Using first principles, we derived a formulation of the theoretical operation and measurement of PCO2(aq) by infrared gas analyzers submerged in aquatic environments. This analysis revealed that an IRGA should be able to measure PCO2(aq) independent of corrections for hydrostatic pressure. CO2-LAMP theoretical operation and measurement were also verified by accompanying laboratory assessment measuring PCO2(aq) at multiple water depths. The monitoring platform was also deployed at two sites within the Springfield Plateau province in northwest Arkansas, USA: Blowing Springs Cave and the Savoy Experimental Watershed. At Blowing Springs Cave, the CO2-LAMP operated alongside a relatively greater-cost CO2 monitoring platform. Over the monitoring period, measured values between the two systems covaried linearly (r2 = 0.97 and 0.99 for cave air and cave stream dissolved CO2, respectively). At the Savoy Experimental Watershed, measured soil CO2 variability capturing sub-daily variation was consistent with previously documented studies in humid, temperate soils. Daily median values varied linearly with soil moisture content (r2 = 0.84). Overall, the CO2-LAMP captured sub-daily variability of CO2 in humid air, soil, and aquatic environments that, while out of the scope of the study, highlight both cyclical and complex CO2 behavior. At present, long-term assessment of platform design is ongoing. Considering cost-savings, CO2-LAMP presents a working base design for continuous, accurate, low-power, and low-cost CO2 monitoring for remote locations

Steady state, erosional continuity, and the topography of landscapes developed in layered rocks

The concept of topographic steady state has substantially informed our understanding of the relationships between landscapes, tectonics, climate, and lithology. In topographic steady state, erosion rates are equal everywhere, and steepness adjusts to enable equal erosion rates in rocks of different strengths. This conceptual model makes an implicit assumption of vertical contacts between different rock types. Here we hypothesize that landscapes in layered rocks will be driven toward a state of erosional continuity, where retreat rates on either side of a contact are equal in a direction parallel to the contact rather than in the vertical direction. For vertical contacts, erosional continuity is the same as topographic steady state, whereas for horizontal contacts it is equivalent to equal rates of horizontal retreat on either side of a rock contact. Using analytical solutions and numerical simulations, we show that erosional continuity predicts the form of flux steady-state landscapes that develop in simulations with horizontally layered rocks. For stream power erosion, the nature of continuity steady state depends on the exponent, n, in the erosion model. For n = 1, the landscape cannot maintain continuity. For cases where n ≠ 1, continuity is maintained, and steepness is a function of erodibility that is predicted by the theory. The landscape in continuity steady state can be quite different from that predicted by topographic steady state. For n < 1 continuity predicts that channels incising subhorizontal layers will be steeper in the weaker rock layers. For subhorizontal layered rocks with different erodibilities, continuity also predicts larger slope contrasts than in topographic steady state. Therefore, the relationship between steepness and erodibility within a sequence of layered rocks is a function of contact dip. For the subhorizontal limit, the history of layers exposed at base level also influences the steepness–erodibility relationship. If uplift rate is constant, continuity steady state is perturbed near base level, but these perturbations decay rapidly if there is a substantial contrast in erodibility. Though examples explored here utilize the stream power erosion model, continuity steady state provides a general mathematical tool that may also be useful to understand landscapes that develop by other erosion processes

Using TNT-NN to unlock the fast full spatial inversion of large magnetic microscopy data sets

Modern magnetic microscopy (MM) provides high-resolution, ultra-high-sensitivity moment magnetometry, with the ability to measure at spatial resolutions better than 10⁻⁴ m and to detect magnetic moments weaker than 10⁻¹⁵ Am². These characteristics make modern MM devices capable of particularly high-resolution analysis of the magnetic properties of materials, but generate extremely large data sets. Many studies utilizing MM attempt to solve an inverse problem to determine the magnitude of the magnetic moments that produce the measured component of the magnetic field. Fast Fourier techniques in the frequency domain and non-negative least-squares (NNLS) methods in the spatial domain are the two most frequently used methods to solve this inverse problem. Although extremely fast, Fourier techniques can produce solutions that violate the non-negativity of moments constraint. Inversions in the spatial domain do not violate non-negativity constraints, but the execution times of standard NNLS solvers (the Lawson and Hanson method and Matlab’s lsqlin) prohibit spatial domain inversions from operating at the full spatial resolution of an MM. In this paper, we present the applicability of the TNT-NN algorithm, a newly developed NNLS active set method, as a means to directly address the NNLS routine hindering existing spatial domain inversion methods. The TNT-NN algorithm enhances the performance of spatial domain inversions by accelerating the core NNLS routine. Using a conventional computing system, we show that the TNT-NN algorithm produces solutions with residuals comparable to conventional methods while reducing execution time of spatial domain inversions from months to hours or less. Using isothermal remanent magnetization measurements of multiple synthetic and natural samples, we show that the capabilities of the TNT-NN algorithm allow scans with sizes that made them previously inaccesible to NNLS techniques to be inverted. Ultimately, the TNT-NN algorithm enables spatial domain inversions of MM data on an accelerated timescale that renders spatial domain analyses for modern MM studies practical. In particular, this new technique enables MM experiments that would have required an impractical amount of inversion time such as high-resolution stepwise magnetization and demagnetization and 3-dimensional inversions. Keywords: Magnetic microscopy; Rock magnetism; Non-negative least-square