Morphogen gradient reconstitution reveals Hedgehog pathway design principles

In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning

Synthetic Biology of Multicellular Systems: New Platforms and Applications for Animal Cells and Organisms

Like life itself, synthetic biology began with unicellular organisms. Early synthetic biologists built genetic circuits in model prokaryotes and yeast because of their relative biological simplicity and ease of genetic manipulation. With superior genetic tools, faster generation times, and betterunderstood endogenous gene expression machinery, prokaryotes and yeast were (and remain) appealing hosts for the engineering of synthetic systems. Now in its second decade, synthetic biology in unicellular organisms has produced myriad synthetic genetic circuits, a number of industrial applications, and fundamental new biological insights unlikely to have emerged from nonsynthetic approaches

In-Vitro Effect of some Commonly Found Botanicals on the Growth and Sporulation of Choanephora Cucurbitarum (Berkeley and Ravenel)

A soft rot infection of Abelmoschus esculentus, Amaranthus hybridus and Vigna unguiculata was observed in home gardens and Government farms in the 2010 cropping season. This disease caused remarkable yield loss in these crops. Due to residual effects of synthetic chemical control, it became necessary to test the potency of some botanicals on the growth and  sporulation of the fungus as a control measure.  The  procedures involved isolation and identification of the fungus and potency trials of aqueous and ethanolic extracts of the  botanicals on the assay fungus. The isolated fungus was confirmed  as Choanephora cucurbitarum. The extracts were obtained from Zingiber officinale Roscoe, Gmelina arborea Roxb, Chromolaena odorata Linnaeus and Azadirachta indica A. Juss. Different concentrations of the extracts (0%, 10%, 20%, 30%, 40% and 50%) were used. With ethanol extract, there was complete inhibition of growth by all plant extracts and at all concentrations;  and a little growth in aqueous extracts with Azadirachta indica showing the highest inhibitory effect, while C. odorata showed the lowest inhibitory effect on the first day, (A. indica, 0.1 ± 0.0 ≥ G. arborea, 0.1 ± 0.0 ˃ Z. officinale, 0.2 ± 0.0 ˃ C. odorata, 0.3 ± 0.0). On the last day, the level of inhibition was as follows A. indica, 0.4 ± 0.0 ˃ G. arborea, 0.6 ± 0.0 ˃ Z. officinale, 0.7 ± 0.0 ≥ C. odorata 0.7 ± 0.0. The inhibitory effect increased with increase in the percentage concentration of the extracts. The  potency  was also due in part to the phytochemical constituents of the plant extracts which was observed from the screening test that Saponins, Tannins, Alkaloids, Cardiac glycosides, Flavonoids, Reducing Compounds, Polyphenol, Phlobatannins, Anthraquinones and Hydroxymethyl anthraquinones were either present or absent. Ke words: Botanicals, Cross-River, Phytochemicals, Extract, Susceptibility.

Testing a word is not a test of word learning

Although vocabulary acquisition requires children learn names for multiple things, many investigations of word learning mechanisms teach children the name for only one of the objects presented. This is problematic because it is unclear whether children's performance reflects recall of the correct name-object association or simply selection of the only object that was singled out by being the only object named. Children introduced to one novel name may perform at ceiling as they are not required to discriminate on the basis of the name per se, and appear to rapidly learn words following minimal exposure to a single word. We introduced children to four novel objects. For half the children, only one of the objects was named and for the other children, all four objects were named. Only children introduced to one word reliably selected the target object at test. This demonstration highlights the over-simplicity of one-word learning paradigms and the need for a shift in word learning paradigms where more than one word is taught to ensure children disambiguate objects on the basis of their names rather than their degree of salience

Morphogen gradient reconstitution reveals Hedgehog pathway design principles

In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning

The global atmospheric electrical circuit and climate

Evidence is emerging for physical links among clouds, global temperatures, the global atmospheric electrical circuit and cosmic ray ionisation. The global circuit extends throughout the atmosphere from the planetary surface to the lower layers of the ionosphere. Cosmic rays are the principal source of atmospheric ions away from the continental boundary layer: the ions formed permit a vertical conduction current to flow in the fair weather part of the global circuit. Through the (inverse) solar modulation of cosmic rays, the resulting columnar ionisation changes may allow the global circuit to convey a solar influence to meteorological phenomena of the lower atmosphere. Electrical effects on non-thunderstorm clouds have been proposed to occur via the ion-assisted formation of ultra-fine aerosol, which can grow to sizes able to act as cloud condensation nuclei, or through the increased ice nucleation capability of charged aerosols. Even small atmospheric electrical modulations on the aerosol size distribution can affect cloud properties and modify the radiative balance of the atmosphere, through changes communicated globally by the atmospheric electrical circuit. Despite a long history of work in related areas of geophysics, the direct and inverse relationships between the global circuit and global climate remain largely quantitatively unexplored. From reviewing atmospheric electrical measurements made over two centuries and possible paleoclimate proxies, global atmospheric electrical circuit variability should be expected on many timescale

Learning and Long-Term Retention of Large-Scale Artificial Languages

Recovering discrete words from continuous speech is one of the first challenges facing language learners. Infants and adults can make use of the statistical structure of utterances to learn the forms of words from unsegmented input, suggesting that this ability may be useful for bootstrapping language-specific cues to segmentation. It is unknown, however, whether performance shown in small-scale laboratory demonstrations of “statistical learning” can scale up to allow learning of the lexicons of natural languages, which are orders of magnitude larger. Artificial language experiments with adults can be used to test whether the mechanisms of statistical learning are in principle scalable to larger lexicons. We report data from a large-scale learning experiment that demonstrates that adults can learn words from unsegmented input in much larger languages than previously documented and that they retain the words they learn for years. These results suggest that statistical word segmentation could be scalable to the challenges of lexical acquisition in natural language learning.National Science Foundation (U.S.) (NSF DDRIG #0746251

Lightning as a space-weather hazard: UK thunderstorm activity modulated by the passage of the heliospheric current sheet

Lightning flash rates, RL, are modulated by corotating interaction regions (CIRs) and the polarity of the heliospheric magnetic field (HMF) in near-Earth space. As the HMF polarity reverses at the heliospheric current sheet (HCS), typically within a CIR, these phenomena are likely related. In this study, RL is found to be significantly enhanced at the HCS and at 27 days prior/after. The strength of the enhancement depends on the polarity of the HMF reversal at the HCS. Near-Earth solar and galactic energetic particle fluxes are also ordered by HMF polarity, though the variations qualitatively differ from RL, with the main increase occurring prior to the HCS crossing. Thus, the CIR effect on lightning is either the result of compression/amplification of the HMF (and its subsequent interaction with the terrestrial system) or that energetic particle preconditioning of the Earth system prior to the HMF polarity change is central to solar wind lightning coupling mechanism