Churchill regulates cell movement and mesoderm specification by repressing Nodal signaling

<p>Abstract</p> <p>Background</p> <p>Cell movements are essential to the determination of cell fates during development. The zinc-finger transcription factor, Churchill (ChCh) has been proposed to regulate cell fate by regulating cell movements during gastrulation in the chick. However, the mechanism of action of ChCh is not understood.</p> <p>Results</p> <p>We demonstrate that ChCh acts to repress the response to Nodal-related signals in zebrafish. When ChCh function is abrogated the expression of mesodermal markers is enhanced while ectodermal markers are expressed at decreased levels. In cell transplant assays, we observed that ChCh-deficient cells are more motile than wild-type cells. When placed in wild-type hosts, ChCh-deficient cells often leave the epiblast, migrate to the germ ring and are later found in mesodermal structures. We demonstrate that both movement of ChCh-compromised cells to the germ ring and acquisition of mesodermal character depend on the ability of the donor cells to respond to Nodal signals. Blocking Nodal signaling in the donor cells at the levels of Oep, Alk receptors or Fast1 inhibited migration to the germ ring and mesodermal fate change in the donor cells. We also detect additional unusual movements of transplanted ChCh-deficient cells which suggests that movement and acquisition of mesodermal character can be uncoupled. Finally, we demonstrate that ChCh is required to limit the transcriptional response to Nodal.</p> <p>Conclusion</p> <p>These data establish a broad role for ChCh in regulating both cell movement and Nodal signaling during early zebrafish development. We show that <it>chch </it>is required to limit mesodermal gene expression, inhibit Nodal-dependant movement of presumptive ectodermal cells and repress the transcriptional response to Nodal signaling. These findings reveal a dynamic role for <it>chch </it>in regulating cell movement and fate during early development.</p

Selective Oxygen Atom Insertion into an Aryl-Palladium Bond

The chemistry of a palladium(II) complex containing both an alkyl- and an aryl-palladium bond is reported. The reaction of [Pd(CH2CMe2C6H4)(MesN=CHCH=NMes)] with bromine or iodine leads to reductive elimination of 1,1-dimethylcyclobutabenzene with formation of [PdX2(MesN=CHCH=NMes)] (X = Br, I). However, the reaction with hydrogen peroxide gives [Pd(CH2CMe2C6H4O)(MesN=CHCH=NMes)] by overall oxygen atom insertion into the aryl-palladium rather than the alkyl-palladium bond. This complex [Pd(CH2CMe2C6H4O)(MesN=CHCH=NMes)] reacts with bromine, iodine, or hydrogen peroxide to give 3,3-dimethyl-2,3-dihydrobenzofuran and the corresponding complex [PdX2(MesN=CHCH=NMes)]. The mechanisms of reaction and basis for selectivity are discussed. The results support the view that oxygen atom insertion is a mechanistically viable pathway for selective catalytic oxidation of hydrocarbons by the green oxidant hydrogen peroxide

Competing, Coverage-Dependent Decomposition Pathways for C_2H_y Species on Nickel (111)

Competing, coverage-dependent pathways for ethane (CH_3CH_3) decomposition on Ni(111) are proposed on the basis of quantum mechanics (QM) calculations, performed by using the PBE flavor of density functional theory (DFT), for all C_2H_y species adsorbed to a periodically infinite Ni(111) surface. For CH_2CH_3, CHCH_3, and CCH_3, we find that the surface C is tetrahedral in each case, with the surface C forming bonds to one, two, or three Ni atoms with bond energies scaling nearly linearly (E_(bond) = 32.5, 82.7, and 130.8 kcal/mol, respectively). In each of the remaining six C_2H_y species, both C atoms are able to form bonds to the surface. Three of these (CH_2CH_2, CHCH_2, and CCH_2) adsorb most favorably at a fcc-top site with the methylene C located at an on-top site and the other C at an adjacent fcc site. The bond energies for these species are E_(bond) = 19.7, 63.2, and 93.6 kcal/mol, respectively. The remaining species (CHCH, CCH, and C_2) all prefer binding at fcc-hcp sites, where the C atoms sit in a pair of adjacent fcc and hcp sites, with binding energies of E_(bond) = 57.7, 120.4, and 162.8 kcal/mol, respectively. We find that CHCH_(ad) is the most stable surface species (ΔH_(eth) = −18.6), and an important intermediate along the lowest-energy decomposition pathway for ethane on Ni(111). The second most stable species, CCH_3, is a close competitor (ΔH_(eth) = −18.2 kcal/mol), lying along an alternative decomposition pathway that is preferred for high-surface-coverage conditions. The existence of these competing, low- and high-coverage decomposition pathways is consistent with the experiments. The QM results reported here were used as training data in the development of the ReaxFF reactive force field describing hydrocarbon reactions on nickel surfaces [Mueller, J. E.; van Duin, A: C. T.; Goddard, W. A. J. Phys. Chem. C 2010, 114, 4939−4949]. This has enabled Reactive dynamics studying the chemisorption and decomposition of systems far too complex for quantum mechanics. Thus we reported recently, the chemisorption and decomposition of six different hydrocarbon species on a Ni_(468) nanoparticle catalysts using this ReaxFF description [Mueller, J. E.; van Duin, A: C. T.; Goddard, W. A. J. Phys. Chem. C 2010, 114, 5675−5685]

New Lewis Structures through the application of the Hypertorus Electron Model

The hypertorus electron model is applied to the chemical bond. As a consequence, the bond topology can be determined. A linear correlation is found between the normalized bond area and the bond energy. The normalization number is a whole number. This number is interpreted as the Lewis&#x27;s electron pair. A new electron distribution in the molecule follows. This discovery prompts to review the chemical bond, as it is understood in chemistry and physics

Kinetics of the photolysis of benzenetricarbonylchromium(0) in chloroform

In contrast to the photolysis of Cr(CO)3(C6H6) in nonhalogenated solvents, in which the products are CrL(CO)2(C6H6) in the presence of a donor L, or Cr(CO)6 and C6H6 if no donor is present, the photo-reaction in chloroform yields CrCl3. No significant portion of the reaction occurs through absorption of 254nm light by CHCl3• The quantum yield is 1.4, consistent with a mechanism in which several radicals are formed upon chlorination of the chromium, which then cause further decomposition of the reactant. In 24% CCl4, the reaction still occurs primarily through the excited state metal complex, but there is a solvent-initiated contribution, which is more significant the lower the reactant concentration. The quantum yield for the solvent-initiated pathway is 0.3 in 24% CCL4

Studies of CH Activation in Unsaturated Amides and Esters by Trinuclear Metal Carbonyl Clusters of Osmium

The chemistry of the reaction of Os3(CO)10(NCCH3)2 with representatives of unsaturated amides and esters, RCOCHCH2 (R=(CH3)2N, CH3O) has been investigated. In these reactions, it has been observed that a CH bond on the β-carbon atom is readily activated by triosmium carbonyl clusters. The activation of β-carbon C-H bond in unsaturated amides and esters provides a robust platform for studying multicenter C-H bond transformations and for C-C bond formation via hydrogen shift and CO insertion processes. In this work, proposed mechanistic approaches have been taken in order to better understand and study the relationship between the characterized species. In addition, a few non-identified species have been predicted to exist. Furthermore, recommendations on how this work can be further studied and improved have been made. A series of activated unsaturated amides and esters: Os2(CO)6(µ-H)(µ O=C(N(CH3)2)CHCH), 1, Os4(CO)12(µ- O=C(N(CH3)2)CHCH)2, 2, Os3(CO)9(µ-O=C(N(CH3)2)CH2CHCCHC(N(CH3)2)=O), 3, Os3(CO)8(µ-O=C(N(CH3)2)CHCH)2, 4, Os6(CO)20(µ-H)(µ-O=C(N(CH3)2) CHCH), 5, HOs3(CO)10(µ-O=C(N(CH3)2)CHCH), 6, Os5(CO)15(µ-O=C(N(CH3)2)CHCH)2, 7, and Os3(CO)9(µ-H)(µ-O=C(OCH3)CHCH), 8, were synthesized and isolated. They are described in Chapter 1. Each of the new compounds has been characterized by FT-IR, NMR (1H), mass-spectra and single crystal X-ray diffraction analysis

The Ariadne's Clew Algorithm

We present a new approach to path planning, called the ``Ariadne's clew algorithm''. It is designed to find paths in high-dimensional continuous spaces and applies to robots with many degrees of freedom in static, as well as dynamic environments --- ones where obstacles may move. The Ariadne's clew algorithm comprises two sub-algorithms, called SEARCH and EXPLORE, applied in an interleaved manner. EXPLORE builds a representation of the accessible space while SEARCH looks for the target. Both are posed as optimization problems. We describe a real implementation of the algorithm to plan paths for a six degrees of freedom arm in a dynamic environment where another six degrees of freedom arm is used as a moving obstacle. Experimental results show that a path is found in about one second without any pre-processing

Aziridine-Metathesis based Approaches to Alkaloid Synthesis

The aim of the project is to synthesise (-)-morphine utilising aziridine and metathesischemistry. The thesis is divided into three chapters.Chapter 1 provides brief reviews on the subjects of total synthesis of morphine; ringrearrangementmetathesis (RRM) and regioselective ring-opening of aziridines.Chapter 2 focuses on the research findings in the past three years. Two routes, A and B,were investigated in attempts to synthesise morphine (Scheme 1). In route A, sulfonylcyclopentene II was prepared from ring-closing metathesis of a diene precursor, whichwas synthesised from lithiated cinnamylsulfone and butadiene monoxide. Subsequently,RRM reactions of several [alpha]-SO2Ph allyl derivatives of II were investigated and someinteresting results were obtained. The synthesis of 2,3-trans vinylaziridine III wasachieved in seven steps beginning with a Grignard reaction of (4-methoxyphenyl)magnesium bromide with butadiene monoxide. Subsequently, somehighly regioselective ring-opening reactions of III with sulfur-stabilised anionicnucleophiles were achieved. However, in an attempt to synthesise compound I from IIand III, no reaction was observed. This led to the investigation of route B, in which fivemethods for the synthesis of compound IV were investigated. The practical approachdeployed a novel Al-mediated substitution of the 4-tosyl group of the tosyltetrahydropyridine counterpart of IV, prepared from V and III, with a phenylthio group.Chapter 3 provides the experimental details and characterisation data.Imperial Users onl

GINI DP 3: New Dataset of Educational Inequality

This paper describes a new dataset collecting measures of educational level and inequality for 31 countries over several birth cohorts. Drawing on four representative international datasets (ESS, EIJSILC, IALS and ISSP), we collect measures of individual educational attainment and aggregate them to generate synthetic indices of education level and dispersion by countries and birth cohorts. The paper provides a detailed description of the procedures and methodologies adopted to build the new dataset, analyses the validity and consistency of the measures across surveys and discusses the relevance of these data for future research. The .csv, .dta, .xml dataset is readily available to GINI members (see website data portal); other scholars may put in a request to the authors YEL Classification: I21, D30, Y1