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The anion binding features of diphenylpyrrole‐strapped calix[4]pyrrole 1 have been investigated by means of 1H NMR spectroscopy and ITC (isothermal titration calorimetry), as well as single crystal X‐ray diffraction analyses. Receptor 1 bearing an auxiliary pyrrolic NH donor and solubilizing phenyl groups on the strap was found to bind F−, Cl−, and Br− as their tetrabutylammonium salts with high affinity in DMSO‐d6. In addition, receptor 1 was found to extract the fluoride anion (as both its tetraethylammonium (TEA+) and tetrabutylammonium (TBA+) salts), as well as the chloride anion into chloroform‐d from an aqueous source phase. Cation metathesis using TBAI or the use of a dual host approach involving crown ethers enabled receptor 1 to extract simple alkali metal fluoride or chloride salts from water. Quantitative binding of NaF by receptor 1 was observed in 20 % D2O‐DMSO‐d6 allowing for the direct determination of the NaF concentration in an unknown sample. [ABSTRACT FROM AUTHOR]

Embryo implantation in humans is interstitial, meaning the entire conceptus embeds in the endometrium before the placental trophoblast invades beyond the uterine mucosa into the underlying inner myometrium. Once implanted, embryo survival pivots on the transformation of the endometrium into an anti-inflammatory placental bed, termed decidua, under homeostatic control of uterine natural killer cells. Here, we examine the evolutionary context of embryo implantation and elaborate on uterine remodelling before and after conception in humans. We also discuss the interactions between the embryo and the decidualising endometrium that regulate interstitial implantation and determine embryo fitness. Together, this Review highlights the precarious but adaptable nature of the implantation process. [ABSTRACT FROM AUTHOR]

Gene expression evolution underlies the origin, divergence, and conservation of biological characters including cell-types, tissues, and organ systems. Previously we showed that large-scale gene expression changes in decidual stromal cells (DSCs) contributed to the origins of pregnancy in eutherians and the divergence of pregnancy traits in primates and that transposable elements likely contributed to these gene expression changes. Here we show that two large waves of TEs remodeled the transcriptome and regulatory landscape of DSCs, including a major wave in primates. Genes nearby TE-derived regulatory elements are among the most progesterone responsive in the genome and play essential roles in orchestrating progesterone responsiveness and the core function of decidual cells by donating progesterone receptor binding sites to the genome. We tested the regulatory abilities of 89 TE consensus sequences and found that nearly all of them acted as repressors in mammalian cells, but treatment with a histone deacetylase inhibitor unmasked latent enhancer functions. These data indicate that TEs have played an important role in the development, evolution, and function of primate DSCs and suggest a two-step model in which latent enhancer functions of TEs are unmasked after they lose primary repressor functions. [ABSTRACT FROM AUTHOR]

The risk of developing cancer is correlated with body size and lifespan within species. Between species, however, there is no correlation between cancer and either body size or lifespan, indicating that large, long-lived species have evolved enhanced cancer protection mechanisms. Elephants and their relatives (Proboscideans) are a particularly interesting lineage for the exploration of mechanisms underlying the evolution of augmented cancer resistance because they evolved large bodies recently within a clade of smaller-bodied species (Afrotherians). Here, we explore the contribution of gene duplication to body size and cancer risk in Afrotherians. Unexpectedly, we found that tumor suppressor duplication was pervasive in Afrotherian genomes, rather than restricted to Proboscideans. Proboscideans, however, have duplicates in unique pathways that may underlie some aspects of their remarkable anti-cancer cell biology. These data suggest that duplication of tumor suppressor genes facilitated the evolution of increased body size by compensating for decreasing intrinsic cancer risk. [ABSTRACT FROM AUTHOR]

How new characters originate is a major question in evolution. Ricefish have evolved a novel tissue enabling females to brood eggs externally. A new study finds that genes involved in formation of this novelty also play a role in inflammation, suggesting stress can trigger the origin of novelty. How new characters originate is a major question in evolution. Ricefish have evolved a novel tissue enabling females to brood eggs externally. A new study finds that genes involved in formation of this novelty also play a role in inflammation, suggesting that stress can trigger the origin of novelty. [ABSTRACT FROM AUTHOR]

The steroid hormone progesterone, acting through the progesterone receptor (PR), a ligand-activated DNA-binding transcription factor, plays an essential role in regulating nearly every aspect of female reproductive biology. While many reproductive traits regulated by PR are conserved in mammals, Catarrhine primates evolved several derived traits including spontaneous decidualization, menstruation, and a divergent (and unknown) parturition signal, suggesting that PR may also have evolved divergent functions in Catarrhines. There is conflicting evidence, however, whether the progesterone receptor gene (PGR) was positively selected in the human lineage. Here we show that PGR evolved rapidly in the human stem-lineage (as well as other Catarrhine primates), which likely reflects an episode of relaxed selection intensity rather than positive selection. Coincident with the episode of relaxed selection intensity, ancestral sequence resurrection and functional tests indicate that the major human PR isoforms (PR-A and PR-B) evolved divergent functions in the human stem-lineage. These results suggest that the regulation of progesterone signaling by PR-A and PR-B may also have diverged in the human lineage and that non-human animal models of progesterone signaling may not faithfully recapitulate human biology. Author summary: The hormone progesterone regulates nearly every aspect of female reproductive biology, including when implantation will occur, the timing of the reproductive cycle, as well as the maintenance and cessation of pregnancy at term. These actions are mediated by the progesterone receptor, a transcription factor that binds progesterone and controls the expression of thousands of genes related to reproductive biology. Remarkably, previous studies have suggested that the progesterone receptor evolved rapidly in humans, with signatures of positive selection. However, using a large dataset of mammalian progesterone receptor genes, we found that selection on the progesterone receptor has actually been weakened in humans, with no evidence for positive selection. To explore if this human-specific episode of relaxed selection is associated with functional changes, we resurrected ancestral forms of the progesterone receptor and tested their ability to regulate a target gene. We found that the human progesterone receptor forms have changed in function, suggesting the actions regulated by progesterone may also be different in humans. Our results suggest caution in attempting to apply findings from animal models to progesterone biology of humans. [ABSTRACT FROM AUTHOR]

New Rh (1) and Ir (2) complexes of an N-heterocyclic carbene (NHC) featuring a terthiophene backbone were synthesized. Single crystal X-ray diffraction studies of 1 and 2 at 100 K and 298 K respectively, revealed two enantiotropic polymorphic phases with similar lattice parameters for each compound. The transition temperature between two crystalline forms for each compound was determined by measuring the percentage of reflections with a different space group ranging from 100 K to 298 K. Both 1 and 2 were also found to catalyze the hydrogen transfer reaction. The conducting metallopolymers poly-1 and poly-2 were synthesized from oxidative electropolymerization of 1 and 2, respectively, in CH2Cl2 electrolyte solution on indium tin oxide-(ITO) coated glass. The electrochromic properties of synthesized conducting metallopolymers were studied by UV-vis-NIR spectroelectrochemistry. [ABSTRACT FROM AUTHOR]

Osmoregulation in birds is complicated, with different organs acting concurrently to regulate this physiological process. Of particular interest is how the urinary excretions of birds can remove excess nitrogen while minimizing the need for dietary water and balancing the physiological demands of oviparity. It has long been concluded from chemical analyses, and more recently from genetic studies, that uric acid is the principal constituent of urine in Aves. However, research has also demonstrated that waste material may be modified in the ceca immediately prior to it being expelled. Here, we quantify the chemical composition of the urine component of excreta of six avian species using X-ray diffraction techniques to test the hypothesis that it is principally composed of uric acid, as commonly reported. None of the analyzed samples were found to contain uric acid. Instead, a variety of compounds including ammonium urate, struvite (magnesium ammonium phosphate), and two unknown compounds, were found. Our results show that the uric acid pathway is indeed the system by which nitrogen is removed in these birds, but that additional modification occurs in the urine prior to excretion. These results raise questions for future research on the urinary excretions of birds, including identification of the unknown compounds found in the present study. [ABSTRACT FROM AUTHOR]

The binding properties of the pyrrole-strapped calix[4]pyrrole 2 for cesium halide ion pairs were studied via 1H NMR spectroscopic and single crystal X-ray diffraction analyses. Receptor 2 was found to bind CsF, CsCl, and CsBr in the solid state and in chloroform/methanol (4/1, v/v) solution with relatively high affinity as compared with the parent calix[4]pyrrole 1. It was also revealed by solid-liquid extraction experiments that receptor 2 was capable of solubilizing CsF in CDCl3, a medium in which this salt is otherwise insoluble. Single crystal X-ray diffraction analyses and 1H NMR spectroscopic data recorded in 20% CD3OD in CDCl3 provide support for the suggestion that the strap pyrrolic NH proton of 2, as well as those of the calix[4]pyrrole framework, contribute to anion recognition, thus increasing affinity for cesium halide salts relative to the parent system 1. [ABSTRACT FROM AUTHOR]

The remediation of phosphate-contaminated water bodies and the effective treatment of hyperphosphatemia are two big challenges in which phosphate recognition could play a useful role. Here, we summarise briefly the state of the art in phosphate removal. Next, we present findings from synthetic and phosphate extraction studies that involve polymeric materials with pendent Schiffbase macrocycles designed to function as phosphate anion receptors. [ABSTRACT FROM AUTHOR]

Variation in female reproductive traits, such as fertility, fecundity, and fecundability, is heritable in humans, but identifying and functionally characterizing genetic variants associated with these traits has been challenging. Here, we explore the functional significance and evolutionary history of a T/C polymorphism of SNP rs2071473, which we have previously shown is an eQTL for TAP2 and significantly associated with fecundability (time to pregnancy). We replicated the association between the rs2071473 genotype and TAP2 expression by using GTEx data and demonstrated that TAP2 is expressed by decidual stromal cells at the maternal-fetal interface. Next, we showed that rs2071473 is located within a progesterone-responsive cis -regulatory element that functions as a repressor with the T allele and an enhancer with the C allele. Remarkably, we found that this polymorphism arose before the divergence of modern and archaic humans, segregates at intermediate to high frequencies across human populations, and has genetic signatures of long-term balancing selection. This variant has also previously been identified in genome-wide association studies of immune-related disease, suggesting that both alleles are maintained as a result of antagonistic pleiotropy. [ABSTRACT FROM AUTHOR]

Three new tris(2-pyridylmethyl)amine-based ligands possessing phenylethynyl units have been prepared using Sonogashira couplings and substitution reactions. Copper(ii) complexes of those tetradentate ligands have also been synthesized. Solid-state structures of the six new compounds have been determined by single-crystal X-ray diffraction analyses. Examination of the molecular structures of the ligands revealed the expected triangular geometries with virtually undeformed carbon–carbon triple bonds. While the tertiary nitrogen of the free ligands seem to be prevented from participation in supramolecular non-covalent interactions by the pyridyl hydrogen at the 3-position, the pyridyl nitrogens play a crucial role in the packing mode of the crystal structure. The nitrogens form weak hydrogen bonds, varied in length between 2.32 and 2.66 Å, with the pyridyl hydrogen of its neighbouring molecule. The [N…H–C] contacts enforce one-dimensional columnar assemblies on ligands that organize into wall-like structures, which in turn assemble into three-dimensional structures through CH–π interactions. Structural analyses of Cu(ii) complexes of the ligands revealed propeller-like structures caused by steric crowding of three pyridine ligands. The copper complexes of the ligands having three phenylethynyl substituents showed a remarkably deformed carbon–carbon triple bond enforced by a steric effect of the three phenyl groups. Most significantly, a total of seventy non-covalent interactions, classified into twelve types of hydrogen-involving short contacts, were identified in this study. The phenylethynyl substituent participated in forty-two interactions as a hydrogen bond acceptor, and its role was more distinctive in the crystal structures of the Cu(ii) complexes. [ABSTRACT FROM AUTHOR]

A calix[4]pyrrolestrapped by a bulky calix[4]arene diester lockedin its cone conformation has been prepared. On the basis of 1H NMR spectroscopic analyses carried out in CDCl3, itis concluded that this hybrid system, receptor 2, bindsonly the fluoride anion and does so with remarkably high affinityeven in the presence of an excess of various potentially competingenvironmentally and biologically ubiquitous anions (studied as thetetrabutylammonium, cesium, or lithium salts). Solid statestructural analyses provide support for the notion that receptor 2interacts well with the fluoride anion in the solid state. [ABSTRACT FROM AUTHOR]

A series of tetrakis(1H-pyrrole-2-carbaldehyde) receptors (2, 4, and 6) were synthesized in two steps from commercially available starting materials. The anion binding properties of these receptors can be tuned through electronic switching to stabilize a conformation displaying high affinity for the dihydrogenphosphate and pyrophosphate anions (as the tetrabutylammonium salts) in chloroform. [ABSTRACT FROM AUTHOR]

During the past several decades, considerable effort has focused on self-assembled systems. However, most work has been directed toward understanding the equilibrium between two major chemical entities, namely the dissociated components and the corresponding associated complex. While there are quite a few examples of ‘multiresponsive’ materials, control over ‘multistate’ materials has proved difficult to achieve. Here, we report the formation and the interplay of a selfassembled calix[4]pyrrole array that exhibits three limiting forms, namely a 1:1 self-assembled oligomer, a 2:1 capsule, and the corresponding monomers. Interconversion between these states may be controlled by using the tetraethylammonium cation (TEA+) and/or iodide anion (I−) as chemical inputs. The combination of self-assembly and ion-based control may be used to create systems that display NAND logic behavior. The system outputs have been confirmed by a variety of analytic methods, including UV−vis and 2D 1H DOSY, NOESY NMR spectroscopy, scanning electron microscopy, and single crystal X-ray diffraction analyses. [ABSTRACT FROM AUTHOR]

A novel Ru(II) complex containing 4‐(2‐hydroxybenzyl)‐3‐methyl‐5‐oxo‐2,5‐dihydropyrazole‐1‐carbothioic acid methylamide has been applied as a catalyst for directly aminating alcohols. Preliminary investigation on the reaction mechanism has been done with the help of NMR spectroscopy recorded for regenerated catalysts and an NMR reaction. In addition, a plausible mechanism for the formation of the coupled product has been proposed. [ABSTRACT FROM AUTHOR]

On the basis of ¹H NMR spectroscopic analyses and single crystal X-ray crystal structural data, the ion-pair receptor 1, bearing a calix[4]pyrrole for anion binding and calix[4]arene crown-5 for cation recognition, was found to act as a receptor for both CsF and KF ion-pairs. Both substrates are bound strongly but via different binding modes and with different complexation dynamics. Specifically, exposure to KF in 10% CD3OD in CDCl3 leads first to complexation of the K+ cation by the calix[4]arene crown-5 moiety. As the relative concentration of KF increases, then the calix[4]pyrrole subunit binds the F- anion. Once bound, the K+ cation and the F- anion give rise to a stable 1:1 ion-pair complex that generally precipitates from solution. In contrast to what is seen with KF, the CsF ion-pair interacts with receptor 1 in two different modes in 10% CD3OD in CDCl3. In the first of these, the Cs+ cation interacts with the calix[4]arene crown-5 ring weakly. In the second interaction mode, which is thermodynamically more stable, the Cs+ cation and the counteranion, F-, are simultaneously bound to the receptor framework. Further proof that system 1 acts as a viable ion-pair receptor came from the finding that receptor 1 could extract KF from an aqueous phase into nitrobenzene, overcoming the high hydration energies of the K+ and F- ions. It was more effective in this regard than a 1:1 mixture of the constituent cation and anion receptors (4 and 5). [ABSTRACT FROM AUTHOR]

Regenerated cellulose films containing different nano-particles were produced under the same processing condition using the ionic liquid l-butyl-3-methyliinidazolium chloride (BMIMCI) as a solvent. Four ionic liquid solutions were prepared with 6 (wt%) wood cellulose and nano-particles of silver and zinc oxide (ZnO). Regenerated cellulose films were extruded with a dry-jet and wet-spun method. Water was used as a coagulation bath and a draw was applied during the extrusion. A scanning electron microscope (SEM) was used to evaluate the distribution of the nano-particles in the regenerated films. Film tensile strength was evaluated using a tensile tester. Wide angle X-ray diffraction (WAXD) patterns were measured and analysed to calculate the degree of crystallinity and degree of orientation for those experimental films. A thermogravimetric analyser (TGA) was used to assess the improvement of flame retardant property of the regenerated films by the addition of nano silver and nano zinc oxide. The instrumental analysis results indicated that the performance of flame retardants, degrees of crystallinity and crystal orientation, and mechanical properties of the nanoparticle-enhanced cellulose films were improved. [ABSTRACT FROM AUTHOR]

There is an emerging consensus that gene regulation evolves through changes in cis-regulatory elements and transcription factors. Although it is clear how nucleotide substitutions in cis-regulatory elements affect gene expression, it is not clear how amino-acid substitutions in transcription factors influence gene regulation. Here we show that amino-acid changes in the transcription factor CCAAT/enhancer binding protein-? (CEBPB, also known as C/EBP-?) in the stem-lineage of placental mammals changed the way it responds to cyclic AMP/protein kinase A (cAMP/PKA) signalling. By functionally analysing resurrected ancestral proteins, we identify three amino-acid substitutions in an internal regulatory domain of CEBPB that are responsible for the novel function. These amino-acid substitutions reorganize the location of key phosphorylation sites, introducing a new site and removing two ancestral sites, reversing the response of CEBPB to GSK-3?-mediated phosphorylation from repression to activation. We conclude that changing the response of transcription factors to signalling pathways can be an important mechanism of gene regulatory evolution. [ABSTRACT FROM AUTHOR]

The thermodynamics of binding between several homoallylic alcohols and simple olefinic Rh-(I) compounds was examined with 1H NMR spectroscopy and isothermal titration calorimetry (ITC). 1H NMR titrations revealed moderate binding of these alcohols with [Rh-(COD)2]+ (1) and [Rh-(COD)-(CH3CN)2]+ (3), but weaker binding with [Rh-(NBD)2]+ (2). ITC indicated that the complexation with [Rh-(COD)2]+ is mainly governed by enthalpy, whereas binding with [Rh-(COD)-(CH3CN)2]+ is entirely driven by entropy. The thermodynamic parameters for the homoallylic alcohol binding of Rh-(I) complexes 1–3 are consistent with crystallographic data. [ABSTRACT FROM AUTHOR]

A fundamental challenge in biology is explaining the origin of novel phenotypic characters such as new cell types; the molecular mechanisms that give rise to novelties are unclear. We explored the gene regulatory landscape of mammalian endometrial cells using comparative RNA-Seq and found that 1,532 genes were recruited into endometrial expression in placental mammals, indicating that the evolution of pregnancy was associated with a large-scale rewiring of the gene regulatory network. About 13% of recruited genes are within 200 kb of a Eutherian-specific transposable element (MER20). These transposons have the epigenetic signatures of enhancers, insulators and repressors, directly bind transcription factors essential for pregnancy and coordinately regulate gene expression in response to progesterone and cAMP. We conclude that the transposable element, MER20, contributed to the origin of a novel gene regulatory network dedicated to pregnancy in placental mammals, particularly by recruiting the cAMP signaling pathway into endometrial stromal cells. [ABSTRACT FROM AUTHOR]

Galis and collaborators (2010) claim that our recent paper ( Kohlsdorf and Wagner 2006 ), presenting statistical evidence for the reevolution of digits in the genus Bachia, may be flawed. Their reanalysis of the data does not support the possibility of a reevolution of digits and the authors also argue that such a reevolution would be implausible on functional and developmental grounds. In response, we reanalyzed our data with additional outgroup species. Our results differ from the one published in 2006, but this incongruence is not statistically significant. In contrast, the hypothesis presented by Galis et al. is significantly worse. An analysis of digit number evolution, using novel techniques to test for irreversibility of character loss ( Goldberg and Igic 2008 ), confirmed our original conclusion that there is strong evidence for reevolution of digits in Bachia. We also point out that this result is not in conflict with the hypothesis by Galis and Metz (2001) that mutations affecting the initial digit patterning are associated with strong negative pleiotropic effects and thus unlikely to be fixed in evolution. An important avenue of future research will be to directly test whether reevolved digits develop from conserved digit condensations retained after digit loss. [ABSTRACT FROM AUTHOR]

Optimized syntheses for 1 ,3-dimesitylnaphthoquinimidazolium chloride [1 H}[Cl] and the corresponding silver-NHC complex [AgCI(1)] (2) were developed, enabling access to this versatile reagent in near-quantitative yield. Transmetalation from 2 to [NiCl2(PPh3)2], trans-[PdCl2(PhCN)2], or trans[PtCI2(PhCN)2] afforded the Group 10 complexes trans-[MCI2(1)2] (3a-c, M = Ni, Pd, and Pt, respectively) in excellent overall yield (>95%) after three steps from commercially available starting materials. Electrochemical measurements indicated that the E1/2 and AE1/2 values for the quinone reduction couples were independent of the identity of the bridging transition metal in these complexes. Whereas attempts to isolate the reduced complexes were unsuccessful, UV/vis spectroelectrochemical analysis confirmed that electrochemical reduction of 3a-c in situ afforded optical difference spectra consistent with the formation of the expected reduced species. Complex 3a was found to catalyze the Kumada cross-coupling reaction between PhMgCI and a range of bromoarenes at room temperature. Addition of 2 equiv of cobaltocene (with respect to 3a) to the coupling reaction with bromotoluene caused a decrease in catalytic activity (from 4.7 x 10-5 to 2.7 x 106 s-1), which was attributed to the conversion of 3a to an arrested state. Subsequent introduction of ferrocenium tetrafluoroborate (2 equiv with respect to 3a) restored a significant degree of catalytic activity (kobs = 1.2 x 10-5 s-1). Redox-switching experiments performed over different time scales revealed that the catalyst was stable in the reduced/inactive state and that extended durations in this state did not impede catalytic reactivation upon subsequent oxidation. [ABSTRACT FROM AUTHOR]

Re-evolution of lost complex morphological characters has been proposed for several characters, including insect wings, limbs, eyes in snakes, and digits in lizards, among others. There has also been much interest in whether the transition from oviparity to viviparity is reversible, particularly in squamate reptiles where the transition to viviparity has occurred more times than in any other lineage. Here, we present a phylogenetic analysis of boid snakes based on a concatenated multigene study of all genera of erycines, New and Old World boines, plus other groups thought to be closely related with boines such as monotypic species Calabaria and Casarea. We reconstruct ancestral parity mode on this phylogeny and present statistical evidence that oviparity reevolved in a species of Old World sand boa in the genus Eryx nearly 60 million years after the initial boid transition to viviparity. Remarkably, like other viviparous boas hatchlings of oviparous Eryx lack an egg-tooth providing independent evidence that oviparity is a derived state in these species. [ABSTRACT FROM AUTHOR]

A new receptor, the bisTTF-calix[2]thiophene[2]pyrrole derivative 3, has been prepared from the Lewis acid-catalyzed condensation of 2,5-bis(1-hydroxymethylethyl)thiopheno-TTF and pyrrole. This new system is found to form complexes with the electron-deficient guests, trinitrobenzene (TNB) and picric acid (PA), which serve as models for nitroaromatic explosives. The binding phenomenon, which has been studied in organic solution using proton nuclear magnetic resonance and absorption spectroscopies, results in an easy-to-visualize color change in chloroform that is independent of the presence of chloride anion, a known interferant for an earlier tetrakisTTF-calix[4]pyrrole TNB chemosensor. Support for the proposed binding mode comes from a preliminary solid state structure of the complex formed from TNB, namely TNB⊂ 3. A color change is also observed when dichloromethane solutions of chemosensor 3 are added to solvent-free samples of TNB, PA, and 2,4,6-trinitrotoluene supported on silica gel. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The identification of adaptations and key innovations has long interested biologists because they confer on organisms the ability to exploit previously unavailable ecological resources and respond to novel selective pressures. Although it can be extremely difficult to test for the effects of a character on the rate of lineage diversification, the convergent evolution of a character in multiple lineages provides an excellent opportunity to test for the effect of that character on lineage diversification. Here, I examine the effect of parity mode on the diversification of vipers, which have independently evolved viviparity in at least 13 lineages. I find strong statistical evidence that viviparous species diversify at a greater rate than oviparous species and correlate major decreases in the diversification rate of oviparous species with periods of global cooling, such as the Oligocene. These results suggest that the evolution of viviparity buffered live-bearing species against the negative effects of global climate change during the Cenozoic, and was a key innovation in the evolution and diversification of live-bearing vipers. [ABSTRACT FROM AUTHOR]

Background: During the menstrual cycle, the ovarian steroid hormones estrogen and progesterone control a dramatic transcriptional reprogramming of endometrial stromal cells (ESCs) leading to a receptive state for blastocyst implantation and the establishment of pregnancy. A key marker gene of this decidualization process is the prolactin gene. Several transcriptional regulators have been identified that are essential for decidualization of ESCs, including the Hox genes HoxA- 10 and HoxA-11, and the forkhead box gene FOXO1A. While previous studies have identified downstream target genes for HoxA-10 and FOXO1A, the role of HoxA-11 in decidualization has not been investigated. Here, we show that HoxA-11 is required for prolactin expression in decidualized ESC. While HoxA-11 alone is a repressor on the decidual prolactin promoter, it turns into an activator when combined with FOXO1A. Conversely, HoxA-10, which has been previously shown to associate with FOXO1A to upregulate decidual IGFBP-1 expression, is unable to upregulate PRL expression when coexpressed with FOXO1A. By co-immunoprecipitation and chromatin immunoprecipitation, we demonstrate physical association of HoxA-11 and FOXO1A, and binding of both factors to an enhancer region (-395 to -148 relative to the PRL transcriptional start site) of the decidual prolactin promoter. Because FOXO1A is induced upon decidualization, it serves to assemble a decidual-specific transcriptional complex including HoxA-11. These data highlight cooperativity between numerous transcription factors to upregulate PRL in differentiating ESC, and suggest that this core set of transcription factors physically and functionally interact to drive the expression of a gene battery upregulated in differentiated ESC. In addition, the functional non-equivalence of HoxA-11 and HoxA-10 with respect to PRL regulation suggests that these transcription factors regulate distinct sets of target genes during decidualization. [ABSTRACT FROM AUTHOR]

While the proposal that large-scale genome expansions occurred early in vertebrate evolution is widely accepted, the exact mechanisms of the expansion-such as a single or multiple rounds of whole genome duplication, bloc chromosome duplications, large-scale individual gene duplications, or some combination of these-is unclear. Gene families with a single invertebrate member but four vertebrate members, such as the Hox clusters, provided early support for Ohno's hypothesis that two rounds of genome duplication (the 2R-model) occurred in the stem lineage of extant vertebrates. However, despite extensive study, the duplication history of the Hox clusters has remained unclear, calling into question its usefulness in resolving the role of large-scale gene or genome duplications in early vertebrates. Here, we present a phylogenetic analysis of the vertebrate Hox clusters and several linked genes (the Hox ''paralogon'') and show that different phylogenies are obtained for Dlx and Col genes than for Hox and ErbB genes. We show that these results are robust to errors in phylogenetic inference and suggest that these competing phylogenies can be resolved if two chromosomal crossover events occurred in the ancestral vertebrate. These results resolve conflicting data on the order of Hox gene duplications and the role of genome duplication in vertebrate evolution and suggest that a period of genome reorganization occurred after genome duplications in early vertebrates. [ABSTRACT FROM AUTHOR]

Evolutionary change in gene regulation can result from changes in cis-regulatory elements, leading to differences in the temporal and spatial expression of genes or in the coding region of transcription factors leading to novel functions or both. Although there is a growing body of evidence supporting the importance of cisregulatory evolution, examples of protein-mediated evolution of novel developmental pathways have not been demonstrated. Here, we investigate the evolution of prolactin (PRL) expression in endometrial cells, which is essential for placentation/pregnancy in eutherian mammals and is a direct regulatory target of the transcription factor HoxA-11. Here, we show that (I) endometrial PRL expression is a derived feature of placental mammals, (ii) the PRL regulatory gene HoxA-11 experienced a period of strong positive selection in the stem-lineage of eutherian mammals, and (iii) only HoxA-11 proteins from placental mammals, including the reconstructed ancestral eutherian gene, are able to up-regulate PRL from the promoter used in endometrial cells. In contrast, HoxA-11 from the reconstructed therian ancestor, opossum, platypus, and chicken are unable to up-regulate PRL expression. These results demonstrate that the evolution of novel gene expression domains is not only mediated by the evolution of cis-regulatory elements but can also require evolutionary changes of transcription factor proteins themselves. [ABSTRACT FROM AUTHOR]

A long-standing question in evolutionary and developmental biology concerns the relative contribution of cis-regulatory and protein changes to developmental evolution. Central to this argument is which mutations generate evolutionarily relevant phenotypic variation? A review of the growing body of evolutionary and developmental literature supports the notion that many developmentally relevant differences occur in the cis-regulatory regions of protein-coding genes, generally to the exclusion of changes in the protein-coding region of genes. However, accumulating experimental evidence demonstrates that many of the arguments against a role for proteins in the evolution of gene regulation, and the developmental evolution in general, are no longer supported and there is an increasing number of cases in which transcription factor protein changes have been demonstrated in evolution. Here, we review the evidence that cis-regulatory evolution is an important driver of phenotypic evolution and provide examples of protein-mediated developmental evolution. Finally, we present an argument that the evolution of proteins may play a more substantial, but thus far underestimated, role in developmental evolution. [ABSTRACT FROM AUTHOR]

Abstract: The compounds Bi6+ xT 1− x P2O15+ y , T=Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn and Pb display five polymorphic forms. Polymorph A is formed by the Ti, Mn, Fe and Ni phases. Polymorph B is exhibited by Co and Cu compounds. The Cr phase crystallizes as polymorphic form C and the Zn phase crystallizes as polymorph D. The Pb compound crystallizes in a new structure type designated as polymorph E. The transition metal crystal structures demonstrate a similar motive. OBi4 tetrahedra share edges to form two-dimensional Bi2O2 layers that are spanned by PO4 tetrahedra and TO6− y octahedra, pyramids and a trigonal bipyramid to form a three-dimensional network. Polymorph A crystallizes in space group C2; polymorph B is centrosymmetric with space group C2/c, the unit cell parameters differ and the unit cell volume is about double. Polymorph C crystallizes in space group and polymorph D exhibits space group C2. Bi6.4Pb0.6P2O15.2 can be considered as polymorph E, space group C2, with a new crystal structure but related stoichiometry. [Copyright &y& Elsevier]

A growing debate in evolutionary and developmental biology concerns the relative contribution of cis-regulatory and protein (particularly transcription factor) changes to developmental evolution. Central to this argument are the perceived conservation of transcription factor functions and the modular architecture of cis-regulatory elements. In this paper, we review recent studies on transcription factor proteins that show that transcription factor genes undergo adaptive evolution and evolve novel functions that contribute to the evolution of development. Furthermore, we review experimental work that shows that transcription factor proteins are modular and can evolve with minimal pleiotropic effects. We conclude that changes in the function of proteins are likely directly contributing to developmental evolution. [Copyright &y& Elsevier]

Background: Gene duplication followed by functional divergence has long been hypothesized to be the main source of molecular novelty. Convincing examples of neofunctionalization, however, remain rare. Snake venom phospholipase A2 genes are members of large multigene families with many diverse functions, thus they are excellent models to study the emergence of novel functions after gene duplications. Results: Here, I show that positive Darwinian selection and neofunctionalization is common in snake venom phospholipase A2 genes. The pattern of gene duplication and positive selection indicates that adaptive molecular evolution occurs immediately after duplication events as novel functions emerge and continues as gene families diversify and are refined. Surprisingly, adaptive evolution of group-I phospholipases in elapids is also associated with speciation events, suggesting adaptation of the phospholipase arsenal to novel prey species after niche shifts. Mapping the location of sites under positive selection onto the crystal structure of phospholipase A2 identified regions evolving under diversifying selection are located on the molecular surface and are likely protein-protein interactions sites essential for toxin functions. Conclusion: These data show that increases in genomic complexity (through gene duplications) can lead to phenotypic complexity (venom composition) and that positive Darwinian selection is a common evolutionary force in snake venoms. Finally, regions identified under selection on the surface of phospholipase A2 enzymes are potential candidate sites for structure based antivenin design. [ABSTRACT FROM AUTHOR]

Abstract: Threading polyintercalation has been demonstrated as a unique DNA binding mode in which a polyintercalating moiety threads back and forth through the DNA double helix. This binding topology necessitates linkers residing in both the minor and major grooves in an alternating fashion. In the present work, two novel, rigid, cis and trans oriented spiro-cyclic linkers were synthesized as potential groove binding elements in the context of threading bis-intercalation. Analysis of dissociation kinetics indicated that the cis oriented dimer has dramatically slower dissociation from poly(dGdC) and calf thymus (CT) DNA compared to the trans oriented dimer and a linear dimer control. [Copyright &y& Elsevier]

Background: Hox genes code for homeodomain-containing transcription factors that function in cell fate determination and embryonic development. Hox genes are arranged in clusters with up to 14 genes. This archetypical chordate cluster has duplicated several times in vertebrates, once at the origin of vertebrates and once at the origin of gnathostoms, an additional duplication event is associated with the origin of teleosts and the agnanths, suggesting that duplicated Hox cluster genes are involved in the genetic mechanisms behind the diversification of vertebrate body plans, and the origin of morphological novelties. Preservation of duplicate genes is promoted by functional divergence of paralogs, either by subfunction partitioning among paralogs or the acquisition of a novel function by one paralog. But for Hox genes the mechanisms of paralog divergence is unknown, leaving open the role of Hox gene duplication in morphological evolution. Results: Here, we use several complementary methods, including branch-specific dN/dS ratio tests, branch-site dN/dS ratio tests, clade level amino acid conservation/variation patterns, and relative rate ratio tests, to show that the homeodomain of Hox genes was under positive Darwinian selection after cluster duplications. Conclusion: Our results suggest that positive selection acted on the homeodomain immediately after Hox clusters duplications. The location of sites under positive selection in the homeodomain suggests that they are involved in protein-protein interactions. These results further suggest that adaptive evolution actively contributed to Hox-gene homeodomain functions. [ABSTRACT FROM AUTHOR]

The synthesis and anion binding properties of a new class of calixpyrrole analogue, containing two carbazole subunits in lieu of two of the four acetone bridging elements normally found in calix[4]pyrrole, is described. The compound exists in a winglike structure in the solid state, as judged from single-crystal X-ray diffraction analyses of both the free system and the corresponding benzoate anion complex. Evidence for anion binding in dichloromethane solution was obtained from static fluorescent quenching experiments; these latter revealed a slight preference for acetate relative to other carboxylate anions (e.g., benzoate, oxalate, succinate), as well as various other anionic substrates (i.e., chloride and dihydrogen phosphate). No evidence of binding was observed in the case of bromide, nitrate, and hydrogen sulfate. [ABSTRACT FROM AUTHOR]

The synthesis and X-ray structural characterization of a new terpyrrolic analog of dipyrrolylquinoxaline (DPQ) is described that contains two pyrrole anion recognition groups bridged by a central 1,2-linked pyrrole. Relative to the ‘parent’ DPQ system, this new terpyrrolic scaffold acts as an improved colorimetric and fluorescent sensor for halide and dihydrogen phosphate anions in organic media. This enhancement is particularly dramatic in the case of H2PO4- (studied as its tetrabutylammonium salt); in CH2Cl2 it is bound with an affinity constant, K, of 17,500M-1 by the terpyrrole of this report vs. 80M-1 in the case of DPQ. The present findings thus support the emerging notion that a range of pyrrole-based anion recognition and sensing systems may be produced by replacing the central quinoxaline spacer in DPQs by other bridging subunits and that these new receptors may have properties that differ dramatically from their DPQ ‘parents’. [Copyright &y& Elsevier]

A Cu(I) catalyzed Huisgen cycloaddition was engineered to afford products featuring intramolecular excimer formation (exciplex, ) or intramolecular Förster resonance energy transfer (FRET, , ). It was further demonstrated that this reaction could be silenced by ethylenediaminetetraacetic acid (EDTA), which prohibited the reduction of copper(II) sulfate to the catalytically active Cu(I) species by sodium ascorbate. Exogenous transition metal ions such as Zn2+ and Pb2+ were shown to competitively coordinate with EDTA thus releasing free Cu2+ for the subsequent reduction, and consequently restoring the reaction. The modulated catalysis showed metal ion concentration dependence and could be monitored by both HPLC and fluorescence. This study is a demonstration of a new sensing paradigm, where a catalytic organometallic reaction can be used as the signal amplifying module of a sensing application by engineering a regulatory element into the reaction process, analogous to an allosteric enzyme or an allosteric ribozyme system. [Copyright &y& Elsevier]

A single-crystal was selected from the reaction product of a stoichiometric mixture of Bi3PO7 to which was added 10% TiO2 and its crystal structure determined from three-dimensional X-ray diffraction data. The structure is monoclinic, a=11.233(2) A˚, b=5.410(1) A˚, c=11.233(2) A˚, β=95.13(3)°, space group I2, Z=2; least squares refinement was on F2 and converged to R1=0.0514, wR2=0.146 for 833 unique reflections. The crystal was twinned by a 180° rotoinversion about the [1¯01] direction of the direct lattice, resulting in the interchange of the a and c axes. The structure consists of chains formed by edge sharing of OBi4 tetrahedra. The stacking along [100] consists of these chains bridged by layers formed by TiO6 octahedra and PO4 tetrahedra. The three crystallographically independent Bi ions are surrounded by eight oxygen ions that form two bicapped trigonal prisms and one distorted cubic environment, respectively. The Bi–O distances vary from 2.20(4) to 3.16(4) A˚. Ti is in octahedral environment in which the equatorial distances are 1.82(3) and 2.00(5) A˚ and the apical distances are 2.14(4) A˚. The PO4 tetrahedron is nearly regular. [Copyright &y& Elsevier]

New chiral spiro[2.4]hepta-4,6-dienes were prepared and used in an efficient synthesis of cyclopentadienyl ruthenium complexes with pendant phosphine donors. Solid state structures reveal a conformation trend among three structurally homologous complexes that involves subtle twisting about the tether with increasing substitution at the alpha carbon. These results suggest architectural requirements for future ligand designs. [Copyright &y& Elsevier]

A strategy for the enantioselective catalysis of photomediated reactions in solution is described, involving the use of chiral molecular receptors possessing appendant triplet-sensitizing moieties. Energy transfer is selectively directed to bound substrate as a consequence of the distance dependence of triplet-triplet energy transfer. This effect, which is equivalent to a binding-induced rate enhancement, enables substoichiometric chirality transfer from the receptor template to the substrate, as observed in the intramolecular enone-olefin photo[2 + 2]cycloaddition of a quinolone substrate. [ABSTRACT FROM AUTHOR]

Discusses the preparation of the first-row transition-metal complexes of texaphyrin, a porphyrin-like, monoanionic penta-aza macrocyclic ligand. Results of the single-crystal X-ray diffraction analysis; Determination of solution magnetic moment; Results of the ultraviolet-vis spectroscopic study of metallotexaphyrin solutions; Effect of the transition metal cation binding on the photophysics of the ligand chromophore.

One pot reaction for epoxidation and Suzuki Miyaura coupling of a number of quinolinyl α,β‐unsaturated ketones has been developed by using a predefined palladium(II) catalyst fabricated with 7‐diethylamino‐2‐oxo‐2H‐chromene Schiff bases. Representative epoxide intermediates were isolated and their structures were established by X‐ray crystallography. [ABSTRACT FROM AUTHOR]

A new biomimetic model complex of the active site of acireductone dioxygenase (ARD) was synthesized and crystallographically characterized ([Ni(II)(N-(ethyl-N′Me 2)(Py)(2-t-ButPhOH))(OTf)]- 1). 1 displays carbon–carbon oxidative cleavage activity in the presence of O2 towards the substrate 2-hydroxyacetophenone. This reactivity was monitored via UV-Visible and NMR spectroscopy. We postulate that the reactivity of 1 with O2 leads to the formation of a putative Ni(III)-superoxo transient species resulting from the direct activation of O2via the nickel center during the oxidative reaction. This proposed intermediate and reaction mechanism were studied in detail using DFT calculations. 1 and its substrate bound derivatives display reactivity toward mild outer sphere oxidants, suggesting ease of access to high valent Ni coordination complexes, consistent with our calculations. If confirmed, the direct activation of O2 at a nickel center could have implications for the mechanism of action of ARD and other nickel-based dioxygenases and their respective non-traditional, enzymatic moonlighting functions, as well as contribute to a general understanding of direct oxidation of nickel(II) coordination complexes by O2. [ABSTRACT FROM AUTHOR]

Investigates the ratio between endocyclic and exocyclic cleavage of pyranoside acetals. Effect of the anomer; Importance of temperature; Significance of the aglycon group.

Characterizes the self-assembled monolayers of 7-(10-thiodecoxy)coumarin on gold. Indications of photodimerization of coumarin and its derivatives; Synthesis of the self-assembled monolayers of coumarin and it derivatives; Comparison of the photodimer generated by irradiation on polycrystalline gold-2 with that on polycrystalline gold-1.

Reports on the spin delocalozation in the copper(I) complexes of bis(verdazyl) (BVD) diradicals with copper(II) halides and acetonitrile. Reaction of copper halides with BVD; Electron paramagnetic resonance spectra of organic triplets; Focus on the intraligand electronic exchange.

Examines the interplay between the complementarity and basicity of active methylene compounds and the ability of the traditional hydrogen bond (THB) to increase substrate acidity. Induction of substrate deprotonation in the presence of amide-like nitrogen-hydrogen groups; Molecular mechanics and X-ray analysis.