P1 Elements Research Articles

RECONSTRUCTION OF AN APPARATUS OF NEOSTRACHANOGNATHUS TAHOENSIS FROM ORITATE, JAPAN AND SPECIES OF NEOSTRACHANOGNATHUS FROM OMAN

Abstract: The apparatus of an Early Triassic conodont Neostrachanognathus tahoensisKoike, 1998 from Oritate, Kumamoto Prefecture, Japan, and a species of Neostrachanognathus from Oman were reconstructed. On the basis of five natural assemblages from the Oritate area, the three‐dimensional apparatus model of N. tahoensis is interpreted as bilaterally symmetrical and composed of 14 elements consisting of pairs of P1, P2, P3, S1, S2, S3, and S4 elements. The P1 and P2 elements are coniform elements, the P3 elements are digyrate forms, and the S elements are bipennate ramiforms. The S elements are arranged rostrally in the apparatus and the pairs of the P1, P2, and P3 elements are subvertically arranged caudally and ventrally to the S array. One of the natural assemblages was formed by rostrocaudal collapse of the apparatus on the sea floor, whereas the other assemblages indicate that conodont animals came to rest nearly parallel with the substrate prior to burial. A collection of isolated elements from Jabal Safra, Oman, includes a second species of Neostrachanognathus with a comparable apparatus.

Size variation of conodont elements of the Hindeodus–Isarcicella clade during the Permian–Triassic transition in South China and its implication for mass extinction

Based on the analysis of thousands of conodont specimens from the Permian –Triassic (P–T) transition at Meishan (the GSSP of P–T Boundary) and Shangsi sections in South China, this study investigates the size variation of Hindeodus and Isarcicella P1 elements during the mass extinction interval. The results demonstrate that Hindeodus– Isarcicella underwent 4 episodes of distinct size reduction during the P–T transition at the Meishan Section and 2 episodes of size reduction in the earliest Triassic at Shangsi. The size reductions at Meishan took place at the junctions of beds 24d/24e, 25/26, 27b/27c and 28/29, and at the junctions of beds 28/29c and 30d/31a at Shangsi. The two earliest Triassic size reduction episodes were correlative between the two sections. These changes coincide with some important geological events such as eustatic sea-level changes, anoxic events, carbon isotope oscillations, miniaturization of brachiopods and microbial changes. Through detailed investigation of the palaeoenvironment and the palaeoecology of Hindeodus– Isarcicella, the authors propose that the main causes of the size reduction was a sharp decline of food availability because of the mass extinction and the anoxic event during the P/T transition. The pattern of size reduction supports suggestions that the end-Permian mass extinction was multi-episodal, consisting of 3 extinction events rather than a single catastrophic event.

Revision of the conodont Idiognathodus simulator (Ellison 1941), the marker species for the base of the Late Pennsylvanian global Gzhelian Stage

Idiognathodus simulator (Ellison 1941) and Idiognathodus eudoraensis n. sp. constitute twomembers of a distinct group of Late Pennsylvanian species that are characterized by an eccentric groove on the P1 element and Type IIIb symmetry,where dextral and sinistral P1 elements show different morphological features. The oldest species, Idiognathodus eudoraensis n. sp., probably developed from a species of Idiognathodus during the late middle Kasimovian. The simulator group is not closely related to Streptognathodus, which is characterized by a deep medial trough. The distinctive morphology of I. simulator [s.s.], redescribed here, in conjunction with itswidespread distribution inNorthAmerica and Eurasia, has led its first appearance to be selected as the event marker for the base of the global Gzhelian Stage. The simulator group includes other species that have been named in Eurasia, and will require additional work to adequately resolve species ranges and interpret its evolutionary history.

The Pennsylvanian conodont genus <i>Gondolella</i> Stauffer & Plummer, 1932: reinterpretation of the original type specimens and concepts

Abstract. In order to ensure stability of nomenclature among species of Gondolella, lectotypes are selected from among the cotypes (syntypes in modern usage) proposed by Stauffer & Plummer (1932) for species that it is concluded were parts of the apparatuses of two species of that genus. It is recognized that many of their specimens actually represent growth stages of individual species, and many of the names used by Stauffer & Plummer are placed in synonymy. Interpreted synonyms include not only gondolelli-form P1 elements, but other parts of the apparatus, especially P2 elements assigned to Euprioniodina by Stauffer & Plummer. Thus, Gondolella bella has synonyms as P1 elements: G. curvata, G. magna, G. minuta, probably G. sp. A, S1 element Euprioniodina coronata and P2 elements: E. exserta, E. eximia and E. intertexta. In a similar manner, the type species of the genus, Gondolella elegantula, has synonyms G. insolita, G. lanceolata (P1 elements), and probably Euprioniodina sp. B (P2 element?).

Sephardiellinae, a new Middle Triassic conodont subfamily

Sephardiellinae (nov. subfam.) encompasses a Middle Triassic Gondolleloid lineage that originated in the Sephardic realm, westernmost shallow Neotethys, from where, in the course of the Ladinian and earliest Carnian, some of its species spread to the world oceans, before extinction as a result of the Carnian salinity crisis. It is composed of two genera, Sephardiella and Pseudofurnishius. Differential criteria in its septimembrate apparatus are the basal cavity structure of P1 element and morphological variations in the P2 and S3 elements.

Mixed Discontinuous Finite Element Methods for Multiphase Flow in Porous Media

In this paper we present an application of mixed discontinuous finite element methods to the simulation of two phase immiscible flow in porous media. The partial differential system describing this flow is written in terms of an elliptic equation for a global pressure and a parabolic equation for a saturation. Both of these two equations are solved using the mixed discontinuous finite element methods. Numerical results are presented for P0, P1, and P2 discontinuous elements. The P0 results are very close to thoseb generated by the standard finite difference method, while the P1 and P2 results seem more accurate.

A natural assemblage of Ellisonia sp. cf. E. triassica Müller (Vertebrata: Conodonta) from the uppermost Permian in the Suzuka Mountains, central Japan

A natural assemblage of Ellisonia sp. cf. E. triassica Müller was recovered from the uppermost Permian close to the Permian-Triassic boundary in the Nabejiriyama section in the Mt. Ryozen area, Suzuka Mountains, central Japan. This natural assemblage and collections of similar ellisonids from the Taho Formation of Ehime Prefecture, southwestern Japan, demonstrate that the Ellisonia apparatus is composed of eight kinds of elements: breviform digyrate M, symmetrical S0, extensiform digyrate S1 and S2, bipennate S3 and S4, and angulate P1 and P2 elements. The apparatus structure of Ellisonia is comparable to the standard 15-element plan of Carboniferous ozarkodinids and prioniodinids. The apparatus structure of the present natural assemblage is important in discussing the phylogenetic affinity of the genus Ellisonia.

Early Triassic Neospathodus (Conodonta) apparatuses from the Taho Formation, southwest Japan

Two conodont apparatuses, Neospathodus symmetricus Orchard, 1995 and N. chionensis (Bender, 1967) are reconstructed on the basis of the material from the Spathian (Lower Triassic) limestone in the Taho Formation of Ehime Prefecture, southwest Japan. The Neospathodus apparatuses are composed of eight types of elements: digyrate (cypridodelliform) M, alate S0, digyrate (enantiognathiform) S1, digyrate (grodelliform) S2, bipennate S3/4, angulate P2, and segminate P1 elements. This apparatus structure is the same as that for Neogondolella and is comparable to the standard 15-element plan of the Carboniferous ozarkodinids.

Neuron Cell Type-specific SNAP-25 Expression Driven by Multiple Regulatory Elements in the Nematode Caenorhabditis elegans

In order to characterize the mechanisms regulating neuronal expression of the nematode SNAP-25 gene, we identified the SNAP-25 genes of Caenorhabditis elegans and Caenorhabditis briggsae. Comparative sequence analysis and reporter assays revealed two putative 5′ regulatory elements, P1 and P2, and four elements, I1h, I1m, I2h, and I2m, in the first intron. Nuclear extracts contained activities that bound the P2 and I1h elements. Different elements were required for SNAP-25 expression in different neuronal subsets; P1 was required in DA and DD motor neurons, and I1m and I2m were required in DB and DA neurons, respectively. P2 was active in amphid and phasmid neurons, I1h in pharyngeal neurons, and I2h in touch receptor neurons. The I2h element contained a putative binding site for transcription factor UNC-86. Both UNC-86 and MEC-3 were required for I2h activity in the mechanosensory neurons: in these neurons, GFP expression driven by I2h was abolished in animals bearing either an unc- 86 null or a mec- 3 null mutation, or an unc- 86 mutation that leads to defective interaction with MEC-3. Deletion of the MEC-3 binding site also abolished the GFP expression. Gel mobility-shift assay results suggest that transcriptional regulation of SNAP-25 may involve multiple transcription factors.

3,4‐Disubstituted Azetidinones as Selective Inhibitors of the Cysteine Protease Cathepsin K. Exploring P2 Elements for Selectivity.

AbstractFor Abstract see ChemInform Abstract in Full Text.

3,4-disubstituted azetidinones as selective inhibitors of the cysteine protease cathepsin K. Exploring P2 elements for selectivity.

A novel series of 3,4-disubstituted azetidinones based inhibitors of the cysteine protease cathepsin K (Cat K) has been identified. Although not optimized, some of these compounds show at least 100-fold selectivity against other cathepsins. The use of cyclic moieties as P2 elements has proven to be crucial to achieve a high degree of selectivity.

Pitx Factors Are Involved in Basal and Hormone-regulated Activity of the Human Prolactin Promoter

The pituitary-specific POU homeodomain factor Pit-1 likely interacts with other factors for cell-specific expression of prolactin. Here we identify the paired-like homeobox transcription factors Pitx1 and Pitx2 as factors functionally activating the proximal human prolactin promoter (hPRL-164luc). Using in vitro binding assays and a series of site-specific mutations of the proximal hPRL promoter, we mapped the B1 and B2 bicoid sites involved in Pitx-mediated transactivation of the hPRL-164luc construct. In somatolactotroph GH4C1 cells, basal proximal hPRL promoter activity was inhibited by a Pitx2 dominant-negative form in a dose-dependent manner, whereas binding disruptive mutations in the Pitx sites significantly reduced basal activity of the promoter. We also show that synergistic activation of hPRL-164luc by Pitx2 and Pit-1 requires the integrity of the B2 Pitx binding site, and at least one of the P1 and P2 Pit-1 response elements. In addition, mutation in the B2 Pitx site results in attenuation of the promoter's responsiveness to forskolin, thyrotropin-releasing hormone, and epidermal growth factor. Conversely, Pitx1 or Pitx2 overexpression in GH4C1 cells leads to an enhancement of the drugs stimulatory effects. Altogether, these results suggest that full responsiveness to several signaling pathways regulating the hPRL promoter requires the B2 Pitx binding site and that Pitx factors may be part of the proteic complex involved in these regulations. Finally, in situ hybridization analysis showing coexpression of the PRL and Pitx2 genes in rat and human lactotroph cells corroborates the physiological relevance of these results.

Design, synthesis, and SAR of substituted acrylamides as factor Xa inhibitors

Substituted acrylamides were used as templates that bridge P1 and P4 binding elements, resulting in a series of potent (sub-nanomolar) and selective factor Xa inhibitors. In this template, cis-geometry of P1 and P4 ligands is highly preferred. SAR on the substituting groups, as well as on modification of P1 and P4 moieties is described. Compounds in this series show good in vivo efficacy in animal models.

The Quadratic Residues —1 and —3

Let p be an odd prime. Then -1 is a quadratic residue (mod p) if and only if p 1 (mod 4), and 3 is a quadratic residue (mod p) if and only if p = 1 (mod 6). These results are well known. The first follows immediately from Euler's criterion and it appears as a theorem in just about every book in which quadratic residues are discussed. The proof of the result about -3 usually requires a little more effort and the law of quadratic reciprocity. The purpose of this note is to show that the if' part of both results follows from Lagrange's theorem in group theory and the theory of algebraic field extensions. Let Zp be the field of integers (mod p). Assume that -1 is not a square (quadratic residue) in Zp. The quadratic extension Zp( -1) has p2 elements. Thus its group of nonzero elements Zp( -)* has p2_ 1 elements and the subgroup Zp* (the group of nonzero elements in Zp) has p 1 elements. The group we want to examine is the factor group Zp( -1)*/Zp*, with p + 1 elements. A direct calculation shows that the coset represented by 1 + has order 4. Thus 4 divides p + 1, which means that p -1 (mod 4). To prove the result about -3, extend Zp to Zp( -3). The order of the coset represented by 3 + -3 in the factor group Zp(-30)*/Zp* is 6. So, again by Lagrange's theorem, p -1 (mod 6).

Polynomials Solving Dirichlet Boundary Value Problems

Let p be an odd prime. Then -1 is a quadratic residue (mod p) if and only if p 1 (mod 4), and 3 is a quadratic residue (mod p) if and only if p = 1 (mod 6). These results are well known. The first follows immediately from Euler's criterion and it appears as a theorem in just about every book in which quadratic residues are discussed. The proof of the result about -3 usually requires a little more effort and the law of quadratic reciprocity. The purpose of this note is to show that the if' part of both results follows from Lagrange's theorem in group theory and the theory of algebraic field extensions. Let Zp be the field of integers (mod p). Assume that -1 is not a square (quadratic residue) in Zp. The quadratic extension Zp( -1) has p2 elements. Thus its group of nonzero elements Zp( -)* has p2_ 1 elements and the subgroup Zp* (the group of nonzero elements in Zp) has p 1 elements. The group we want to examine is the factor group Zp( -1)*/Zp*, with p + 1 elements. A direct calculation shows that the coset represented by 1 + has order 4. Thus 4 divides p + 1, which means that p -1 (mod 4). To prove the result about -3, extend Zp to Zp( -3). The order of the coset represented by 3 + -3 in the factor group Zp(-30)*/Zp* is 6. So, again by Lagrange's theorem, p -1 (mod 6).

Regulation of interleukin 4 gene transcription: alterations in atopic disease?

Induction of interleukin 4 (IL-4) transcription in helper T (Th) cells under physiological conditions follows from engagement of the T cell receptor by antigenic peptides presented by antigen-presenting cells in association with MHC class II molecules (1). This trigger will activate two intracellular signaling pathways crucial to IL-4 expression, that is, a protein kinase C (PKC)-dependent pathway leading to the synthesis of activator protein 1 (AP-1) family proteins and a calcium (Ca 2 1 )dependent pathway resulting in calcineurin-mediated dephosphorylation and nuclear translocation of preexisting cytosolic nuclear factor of activated T cells (NFAT). The PKC pathway is potentiated by CD28-mediated costimulation (2), whereas the Ca 2 1 pathway can be fully blocked by cyclosporin A and FK506 (3). Both the mouse and human IL-4 promoters contain five binding elements (designated P0 to P4) for the NFAT family of transcription factors, with only minimal interspecies variation with respect to their sequence, orientation, and location within the proximal 250 base pairs (bp) of the promoter region (4–6). The P0 element is located just upstream of the transcription start site and P4 is located at about 2 250 bp in the 5 9 -flanking region (Figure 1). Although all P elements to some extent contribute to IL-4 gene control, the major positive regulatory P elements seem to be P1 (4, 7) and P4 (reviewed in Reference 1). As are P2 and P3, both P1 and P4 are immediately flanked by sequences with affinity for AP-1 family proteins (8–10), allowing for cooperative binding with NFAT proteins. The strong reduction of IL-4 promoter activity as observed, for example, after mutation of either the P1NFATor the adjacent AP-1-binding motif (9) emphasizes the importance of collaborative NFAT/AP-1 binding at such composite elements. The proximal part of the IL-4 promoter region, containing the transcription start site (indicated as 1 1 in Figure 1) and the P0 and P1 elements, can function as a minimal promoter in reporter gene assays, conferring inducible expression and a certain degree of Th2-specific regulation (11, 12). Initial studies gave no indication of Th1or Th2-specific recruitment of particular NFAT or AP-1 family proteins to these sites (9, 13). Instead, the mechanism underlying the Th2 specificity of IL-4 expression may be based on quantitative differences in the availability of NFAT and/or AP-1 family proteins. Furthermore, because the cooperative DNA binding of NFAT and AP-1 proteins has an auxiliary function for the binding of other transcription factors (5, 14–16), these additional transcription factors are likely to be involved in tissue-specific IL-4 expression. Th2-SPECIFIC IL-4 GENE CONTROL

Vav synergizes with protein kinase C theta to mediate IL-4 gene expression in response to CD28 costimulation in T cells.

The secretion of IL-4, which displays many important immunoregulatory functions, is restricted to cells of the Th2 subtype. In this study, we investigated the early signaling events leading to the activation of IL-4 transcription. Vav, the protein kinase C (PKC) isoform theta, and the adaptor protein SLP76 (SH2-domain-containing leukocyte protein of 76 kDa), induced transcription from the IL-4 promoter. Vav and PKC theta synergistically activated human IL-4 promoter transcription and IL-4 mRNA production and were found to be constitutively associated in vivo. CD3/CD28-induced IL-4 transcription was inhibited upon coexpression of dominant negative forms of Vav, the adaptor proteins LAT (linker for activation of T cells) and SLP76, PKC theta, and components of the pathways leading to the activation of c-Jun N-terminal kinase (mitogen-activated protein kinase kinase 7 (MKK7), mixed lineage kinase 3 (MLK3)) and NF-kappa B (I kappa B kinase alpha and I kappa B kinase beta). The Vav/PKC theta-mediated synergistic activation of IL-4 transcription was not inhibited by cyclosporin A. Three independent experimental approaches revealed that Vav/PKC theta-derived signals selectively target the P1 and positive regulatory element (PRE)-I elements contained within the human IL-4 promoter. Vav/PKC theta strongly activated a luciferase reporter construct controlled by trimerized P1 or PRE-I elements and furthermore stimulated DNA binding of nuclear proteins to the P1 and PRE-I elements. Vav/PKC theta-induced transcription from the IL-4 promoter was almost completely abrogated by mutation of either the P1 or the PRE-I element within the entire IL-4 promoter.

Stat6 Inhibits Human Interleukin-4 Promoter Activity in T Cells

The differentiation of naive T-helper (Th) cells into cytokine-secreting effector Th cells requires exposure to multiple signals, including exogenous cytokines. Interleukin-4 (IL-4) plays a major role in this process by promoting the differentiation of IL-4-secreting Th2 cells. In Th2 cells, IL-4 gene expression is tightly controlled at the level of transcription by the coordinated binding of multiple transcription factors to regulatory elements in the proximal promoter region. Nuclear factor of activated T cell (NFAT) family members play a critical role in regulating IL-4 transcription and interact with up to five sequences (termed P0 through P4) in the IL-4 promoter. The molecular mechanisms by which IL-4 induces expression of the IL-4 gene are not known, although the IL-4-activated transcription factor signal transducer and activator of transcription 6 (Stat6) is required for this effect. We report here that Stat6 interacts with three binding sites in the human IL-4 promoter by electrophoretic mobility shift assays. These sites overlap the P1, P2, and P4 NFAT elements. To investigate the role of Stat6 in regulating IL-4 transcription, we used Stat6-deficient Jurkat T cells with different intact IL-4 promoter constructs in cotransfection assays. We show that, whereas a multimerized response element from the germline IgE promoter was highly induced by IL-4 in Stat6-expressing Jurkat cells, the intact human IL-4 promoter was repressed under similar conditions. We conclude that the function of Stat6 is highly dependent on promoter context and that this factor promotes IL-4 gene expression in an indirect manner.

Rings which are nearly principal ideal domains

We study a class of rings which are closely related to principal ideal domains, and prove in particular that finitely-generated projective modules over such rings are free. Examples include the ring of Lipschitz quaternions; Z[a½] with d = —3 or d = —7; and any subring R of M2(Z) such that R ⊇ M2(pZ) for some prime number/? and R/M2(pZ) is a field with p2 elements.

Nodule-specific expression of Rhizobium meliloti symbiotic promoters P1 and P2 in chickpea-Rhizobium sp. symbiosis

Developmentally specific expression of Rhizobium spp. genes involved in symbiotic N2 fixation is known to operate through cascade regulation of various nif and fix operons. Fusion constructs of lacZ under symbiotic promoters P1 (for nifHDK operon) and P2 (for fixABCX operon) of Rhizobium meliloti were mobilized into Rhizobium spp. (Cicer) strains Rcd301 and RCR13. The assays for β-galactosidase activity to monitor the expression of lacZ under these promoters was performed in host backgrounds of Escherichia coli, R. meliloti, and Rhizobium spp. (Cicer). The enzyme assays indicated significant levels of expression from P1 and P2 promoters in chickpea rhizobia, specifically in symbiotic cells from nodules. However, as in R. meliloti, these promoters did not induce strong expression in free-living cells of Rhizobium spp. (Cicer). This indicates functional homology of R. meliloti promoters in rhizobium spp. (Cicer). Functional cross-reactivity of trans regulatory factors like NtrA, NtrC, and NifA between these rhizobia seems evident from the nodule-specific expression of P1 and P2 cis elements.