Unique Extensions Research Articles

Dissecting the sequence specific functions of alternative N-terminal isoforms of mouse bullous pemphigoid antigen 1

Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family of proteins that is involved in cross-linking the cytoskeletal elements and attaching them to cell junctions. BPAG1 null mice develop severe degeneration of sensory neurons that was attributed in part due to the absence of a splice variant called BPAG1a that harbors an actin-binding domain at the N-terminus. Additional alternative splicing also results in BPAG1a isoforms with different first exons, leading to three additional types of BPAG1a called isoforms 1, 2 and 3 (or BPAG1a1, BPAG1a2, and BPAG1a3). These unique N-terminal extensions of the BPAG1a isoforms are of variable length. In this study, we characterized these N-terminal isoforms and evaluated the influence of these unique N-terminal sequences to the actin-binding properties. The unique N-terminal region of isoform 1 is very short and was not expected to affect the property of the ABD that followed it. In contrast, transfection studies and mutagenesis analyses signified that the N-terminal sequences of isoform 2 had the ability to bundle actin filaments and the N-terminal region that contained isoform 3 showed cortical localization. Isoforms 1, 2 and 3 also displayed differential tissue expression profiles. Taken together, these data suggested that the unique N-terminal regions of these isoforms have different roles that may be tailored to meet tissue specific functions.

Petaloid-type cms in carrot is not associated with expression of atp8 (orfB)

Two different atp8 reading frames with divergent C-terminal extensions were identified in a sterility-inducing mitochondrial type (mitotype) of carrot; examination of three fertility-inducing mitotypes revealed atp8 reading frames that were either terminated at a position conserved among other plant atp8 genes or continued with unique C-terminal extensions. Similarities between the C-terminal extensions suggest ancient common ancestry, but the level of sequence divergence implies lack of functional conservation. Northern analysis indicated that the C-terminal extensions are transcribed and are present within the primary atp8 transcripts. Western analysis revealed that the products of the two extended atp8 reading frames encoded by the sterility-inducing mitotype are significantly smaller than those predicted by complete translation of their C-terminal extensions, but are slightly larger than the products from unextended reading frames. No alterations were observed in atp8 transcripts or proteins isolated from flowers of the sterility-inducing mitotype that were phenotypically fertile as a result of segregation for nuclear fertility-restoring Ms or Rf alleles, and thus, there is no evidence that expression of atp8 is directly involved in the petaloid cms phenotype in carrot.

The carboxyl‐terminal extension on fungal mitochondrial DNA polymerases: identification of a critical region of the enzyme from Saccharomyces cerevisiae

Fungal mitochondrial DNA (mtDNA) polymerases, in comparison to their metazoan counterparts, harbour unique carboxyl-terminal extensions (CTEs) of varying lengths and unknown function. To determine the essential regions of the 279 residue CTE of the yeast enzyme (Mip1p), several CTE-truncation variants were expressed in Saccharomyces cerevisiae. The respiratory competence of mip1delta175 cells, in which Mip1p lacks the C-terminal 175 residues, is indistinguishable from that of wild-type. In contrast, strains harbouring Mip1pdelta351 and Mip1pdelta279 rapidly lose mtDNA. Approximately one in six mip1delta216 transformants grew on glycerol, albeit poorly. Fluorescence microscopy and Southern blot analysis revealed lower levels of mtDNA in these cells, and the rapid loss of mtDNA during fermentative, but not respiratory, growth. Therefore, only the polymerase-proximal segment of the Mip1p CTE is necessary for mitochondrial function. Comparison of this essential segment with the sequences of other fungal mtDNA polymerases revealed novel features shared among the mtDNA polymerases of the Saccharomycetales.

A 60 kDa COX1 protein in mitochondria of carrot irrespective of the presence of C-terminal extensions in the cox1 reading frames

An inverted repeat in the mitochondrial DNA of carrot mitochondrial type (mitotype) SW3 has been sequenced in the context of its up- and downstream genomic environments. The 3,159 bp repeat encodes rps7 and cox1, but the cox1 reading frame does not encode a stop codon at a position predicted by alignment with other plant cox1 genes; cox1 extends into both of the downstream flanking sequences as unique C-terminal extensions of 224 (cox1-1) or 284 (cox1-2) amino acids. Northern and RT-PCR analyses revealed that rps7 and cox1 are co-transcribed and RNA-edited. In three additional mitotypes of carrot, rps7 and cox1 are co-transcribed, but are present as single copies within the genome. In mitotype FG17, the cox1 gene has a C-terminal extension like cox1-1, but in mitotypes FW2 and FW4, the cox1 genes lack C-terminal extensions and have stop codons and 3' UTRs like those of other plant cox1 genes. The C-terminal extensions are transcribed in SW3 and FG17 and result in longer primary transcripts than those from FW2 and FW4. Western immunoblotting of mitochondrial proteins from all mitotypes detected COX1 products of the predicted unextended size in all mitotypes, irrespective of the presence of a C-terminal extension in the reading frame.

Class II Histone Deacetylases Confer Signal Responsiveness to the Ankyrin-Repeat Proteins ANKRA2 and RFXANK

Class II histone deacetylases (HDACs) contain unique amino-terminal extensions that mediate interactions with members of the myocyte enhancer factor-2 (MEF2) family of transcription factors and responsiveness to kinases, including Ca2+/calmodulin-dependent kinase (CaMK). Despite intense investigation of class II HDACs, little is known of MEF2-independent mechanisms for transcriptional repression by these chromatin-modifying enzymes. Here, we demonstrate that class II HDACs 4 and 5 physically associate with ankyrin-repeat proteins ANKRA2 and RFXANK (RFX-B/Tvl-1/ANKRA1). ANKRA2 is a megalin- and BKCa potassium channel-interacting factor, whereas RFXANK is a positive regulator of major histocompatibility complex II (MHC II) gene expression. HDAC4 and HDAC5 interact with the ankyrin repeats of ANKRA2 and RFXANK and, through association with RFXANK, repress MHC II promoter activation. HDACs 4 and 5 also repress endogenous HLA-DRA gene expression induced by CIITA. Phosphorylation of class II HDACs by CaMK results in CRM1-dependent nuclear export of HDAC/RFXANK complexes. These results define a novel transcriptional pathway under the control of class II HDACs and suggest a role for these transcriptional repressors as signal-responsive regulators of antigen presentation.

On the Borel Complexity of Hahn-Banach Extensions

The classical Hahn-Banach Theorem states that any linear bounded functional defined on a linear subspace of a normed space admits a norm-preserving linear bounded extension to the whole space. The constructive and computational content of this theorem has been studied by Bishop, Bridges, Metakides, Nerode, Shore, Kalantari, Downey, Ishihara and others and it is known that the theorem does not admit a general computable version. We prove a new computable version of this theorem without unrolling the classical proof of the theorem itself. More precisely, we study computability properties of the uniform extension operator which maps each functional and subspace to the set of corresponding extensions. It turns out that this operator is upper semi-computable in a well-defined sense. By applying a computable version of the Banach-Alaoglu Theorem we can show that computing a Hahn-Banach extension cannot be harder than finding a zero on a compact metric space. This allows us to conclude that the Hahn-Banach extension operator is ∑20–computable while it is easy to see that it is not lower semi-computable in general. Moreover, we can derive computable versions of the Hahn-Banach Theorem for those functionals and subspaces which admit unique extensions.

Implementation and evaluation of HPF/SX V2

AbstractWe are developing HPF/SX V2, a High Performance Fortran (HPF) compiler for vector parallel machines. It provides some unique extensions as well as the features of HPF 2.0 and HPF/JA. In particular, this paper describes four of them: (1) the ON directive of HPF 2.0; (2) the REFLECT and LOCAL directives of HPF/JA; (3) vectorization directives; and (4) automatic parallelization. We evaluate these features through some benchmark programs on NEC SX‐5. The results show that each of them achieved a 5–8 times speedup in 8‐CPU parallel execution and the four features are useful for vector parallel execution. We also evaluate the overall performance of HPF/SX V2 by using over 30 well‐known benchmark programs from HPFBench, APR Benchmarks, GENESIS Benchmarks, and NAS Parallel Benchmarks. About half of the programs showed good performance, while the other half suggest weakness of the compiler, especially on its runtimes. It is necessary to improve them to put the compiler to practical use. Copyright © 2002 John Wiley & Sons, Ltd.

Signaling pathways and physiological functions of Drosophila melanogaster FMRFamide-related peptides.

FMRFamide-related peptides (FaRPs) contain a C-terminal RFamide but unique N-terminal extensions. They are expressed throughout the animal kingdom and affect numerous biological activities. Like other animal species, Drosophila melanogaster contains multiple genes that encode different FaRPs. The ease of genetic manipulations, the availability of genomic sequence data, the existence of established bioassays, and its short lifespan make D. melanogaster a versatile experimental organism in which to investigate peptide processing, functions, and signal transduction pathways. Here, the structures, precursor organizations, distributions, and activities of FaRPs encoded by D. melanogaster FMRFamide (dFMRFamide), myosuppressin (Dms), and sulfakinin (Dsk) genes are reviewed, and predictions are made on their signaling pathways and biological functions.

Affine extension of noncrystallographic Coxeter groups and quasicrystals

Unique affine extensions $H^{\aff}_2$, $H^{\aff}_3$ and $H^{\aff}_4$ are determined for the noncrystallographic Coxeter groups $H_2$, $H_3$ and $H_4$. They are used for the construction of new mathematical models for quasicrystal fragments with 10-fold symmetry. The case of $H^{\aff}_2$ corresponding to planar point sets is discussed in detail. In contrast to the cut-and-project scheme we obtain by construction finite point sets, which grow with a model specific growth parameter.

A testbed for configuration management policy programming

Even though the number and variety of available configuration management systems has grown rapidly in the past few years, the need for new configuration management systems still remains. Driving this need are the emergence of situations requiring highly specialized solutions, the demand for management of artifacts other than traditional source code and the exploration of entirely new research questions in configuration management. Complicating the picture is the trend toward organizational structures that involve personnel working at physically separate sites. We have developed a testbed to support the rapid development of configuration management systems. The testbed separates configuration management repositories (i.e., the stores for versions of artifacts) from configuration management policies (i.e., the procedures, according to which the versions are manipulated) by providing a generic model of a distributed repository and an associated programmatic interface. Specific configuration management policies are programmed as unique extensions to the generic interface, while the underlying distributed repository is reused across different policies. The authors describe the repository model and its interface and present their experience in using a prototype of the testbed, called NUCM, to implement a variety of configuration management systems.

AA.AG@Helix.Ends: A:A and A:G base-pairs at the ends of 16 s and 23 s rRNA helices

This study reveals that AA and AG oppositions occur frequently at the ends of helices in RNA crystal and NMR structures in the PDB database and in the 16 S and 23 S rRNA comparative structure models, with the G usually 3′ to the helix for the AG oppositions. In addition, these oppositions are frequently base-paired and usually in the sheared conformation, although other conformations are present in NMR and crystal structures. These A:A and A:G base-pairs are present in a variety of structural environments, including GNRA tetraloops, E and E-like loops, interfaced between two helices that are coaxially stacked, tandem G:A base-pairs, U-turns, and adenosine platforms. Finally, given structural studies that reveal conformational rearrangements occurring in regions of the RNA with AA and AG oppositions at the ends of helices, we suggest that these conformationally unique helix extensions might be associated with functionally important structural rearrangements.

Diffusion Semigroups in Spaces of Continuous Functions with Mixed Topology

We study transition semigroups and Kolmogorov equations corresponding to stochastic semilinear equations on a Hilbert space H. It is shown that the transition semigroup is strongly continuous and locally equicontinuous in the space of polynomially increasing continuous functions on H when endowed with the so-called mixed topology. As a result we characterize cores of certain second order differential operators in such spaces and show that they have unique extensions to generators of strongly continuous semigroups.

Examining the Robustness of Ideological Voting: Evidence from the Confederate House of Representatives

A majority of work on Congressional voting behavior finds that members of Congress establish ideological positions and maintain them throughout the entirety of their careers, regardless of how their career aspirations, political positions, or underlying constituencies change. Based on this evidence, Poole (1998) concludes that members of Congress die in their ideological boots. I examine the robustness of the thesis more closely, using vote-scaling techniques and roll-call voting data from a different American legislative system: the Congress of the Confederate States of America. Initial results run contrary to the ideological-boots thesis, as I uncover low levels of cross-system stability among members who moved from the U.S. House to the Confederate House. Examining further, I argue that high levels of ideological stability follow from a strong party system being in place to structure voting, which has traditionally been the case in the two-party U.S. House but was not the case in the partyless Confederate House. This result aside, I do find a moderate but increasing level of ideological stability among members of the Confederate House in a session-by-session analysis, which is robust to a serious shock (Federal invasion) to the constituency-representative linkage underlying the electoral connection. This latter finding suggests that as long as there are electoral incentives associated with ideological labels, then ideologies will develop regardless of party structure. ecent work in the field of Congressional voting behavior suggests that members of Congress (MCs) die in their ideological boots. That is, according to Poole (1998, 3), based upon the roll-call voting record, once elected to Congress, members adopt an ideological position and maintain that position throughout their careers-once a liberal or a conservative or a moderate, always a liberal or a conservative or a moderate. This finding applies not only to members of the contemporary Congress, but MCs from bygone eras as well, as Poole and Rosenthal (1997) find high levels of individual-level ideological stability across nearly all of United States Congressional history. Moreover, additional evidence suggests that members of Congress remain ideologically consistent even in the face of changing personal or electoral conditions: members' voting records remain essentially the same, regardless of whether they plan to retire (Lott 1987; Van Beek 1991; Lott and Bronars 1993; Poole and Rosenthal 1997), plan to run for a higher office (Hibbing 1986; Poole and Romer 1993), serve in a higher office (Grofman, Griffin, and Berry 1995; Poole and Rosenthal 1997), or have their districts redrawn (Poole and Romer 1993; Poole 1998). This article examines the thesis further to assess whether it is truly a general finding. Rather than examine voting behavior in the U.S. Congress, however, I focus on voting behavior in a heretofore forgotten institution in American history: the Congress of the Confederate States of America. I contend that the Confederate Congress is a suitable forum to explore the robustness of the ideological-boots thesis, because it provides two unique extensions to the study of individual-level ideological stability that cannot be pursued in a study of the U.S. Congress. First, a significant number of individuals who served in the Confederate House had

Poly(ADP-ribose) polymerase interacts with novel Drosophila ribosomal proteins, L22 and l23a, with unique histone-like amino-terminal extensions.

Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that recognizes and binds to the nicks and ends of DNA, and catalyses successive ADP-ribosylation reactions. To clarify the function of PARP at the molecular level, we searched proteins which interact with PARP. In the auto-modification domain of PARP in Drosophila, there is a putative leucine-zipper motif which can interact with other protein molecules. To find interacting proteins we examined the auto-modification domain of Drosophila PARP, using the Far-Western screening method. From six independent cDNA clones isolated, we characterized two clones, PBP-3 and PBP-12. The predicted amino acid sequences from 109 to 269 of PBP-3 and from 184 to 312 of PBP-12 had more than 62% identities to mammalian L23a (rpl23a) and L22 (rpl22), the ribosomal proteins of the large subunit. This indicated that PBP-3 and PBP-12 are Drosophila homologues of L23a and L22, respectively. These Drosophila ribosomal protein L22 and L23a have additional Ala-, Lys- and Pro-rich sequences at the amino terminus, which have a resemblance to the carboxy-terminal portion of histone H1. Thus, Drosophila L22 and L23a might have two functions, namely the role of DNA-binding similar to histone H1 and the role of organizing the ribosome.

Structure and function of ubiquitin conjugating enzyme E2-25K: the tail is a core-dependent activity element.

Individual members of the conserved family of ubiquitin conjugating enzymes (E2s) mediate the ubiquitination and turnover of specific substrates of the ubiquitin-dependent degradation pathway. E2 proteins have a highly conserved core domain of approximately 150 amino acids which contains the active-site Cys. Certain E2s have unique terminal extensions, which are thought to contribute to selective E2 function by interacting either with substrates or with trans-acting factors such as ubiquitin-protein ligases (E3s). We used the mammalian ubiquitin conjugating enzyme E2-25K in a biochemical test of this hypothesis. The properties of two truncated derivatives show that the 47-residue tail of E2-25K is necessary for three of the enzyme's characteristic properties: high activity in the synthesis of unanchored K48-linked polyubiquitin chains; resistance of the active-site Cys residue to alkylation; and an unusual discrimination against noncognate (nonmammalian) ubiquitin activating (E1) enzymes. However, the tail is not sufficient to generate these properties, as shown by the characteristics of a chimeric enzyme in which the tail of E2-25K was fused to the core domain of yeast UBC4. These and other results indicate that the specific biochemical function of the tail is strongly dependent upon unique features of the E2-25K core domain. Thus, divergent regions within the conserved core domains of E2 proteins may be highly significant for function. Expression of truncated E2-25K as a glutathione S-transferase (GST) fusion protein resulted in the apparent recovery of E2-25K-specific properties, including activity in chain synthesis. However, the catalytic mechanism utilized by the truncated fusion protein proved to be distinct from the mechanism utilized by the wild-type enzyme. The unexpected properties of the fusion protein were due to GST-induced dimerization. These results indicate the potential for self-association to modulate the polyubiquitin chain synthesis activities of E2 proteins, and indicate that caution should be applied in interpreting the activities of GST fusion proteins.

Defaults in domain theory

This paper uses ideas from artificial intelligence to show how default notions can be defined over Scott domains. We combine these ideas with ideas arising in domain theory to shed some light on the properties of nonmonotonicity in a general model-theoretic setting. We consider in particular a notion of default nonmonotonic entailment between prime open sets in the Scott topology of a domain. We investigate in what ways this notion obeys the so-called laws of cautious monotony and cautious cut, proposed by Gabbay, Kraus, Lehmann, and Magidor. Our notion of nonmonotonic entailment does not necessarily satisfy cautious monotony, but does satisfy cautious cut. In fact, we show that any reasonable notion of nonmonotonic entailment on prime opens over a Scott domain, satisfying in particular the law of cautious cut, can be concretely represented using our notion of default entailment. We also give a variety of sufficient conditions for defaults to induce cumulative entailments, those satisfying cautious monotony. In particular, we show that defaults with unique extensions are a representation of cumulative nonmonotonic entailment. Furthermore, a simple characterization is given for those default sets which determine unique extensions in coherent domains. Finally, a characterization is given for Scott domains in which default entailment must be cumulative. This is the class of daisy domains; it is shown to be cartesian closed, a purely domain-theoretic result.

Nonmonotonic consequences in default domain theory

Default domain theory is a framework for representing and reasoning about commonsense knowledge. Although this theory is motivated by ideas in Reiter’s work on default logic, it is in some sense a dual framework. We make Reiter’s default extension operator into a constructive method of building models, not theories. Domain theory, which is a well established tool for representing partial information in the semantics of programming languages, is adopted as the basis for constructing partial models. This paper considers some of the laws of nonmonotonic consequence, due to Gabbay and to Kraus, Lehmann, and Magidor, in the light of default domain theory. We remark that in some cases Gabbay’s law of cautious monotony is open to question. We consider an axiomatization of the nonmonotonic consequence relation on prime open sets in the Scott topology – the natural logic – of a domain, which omits this law. We prove a representation theorem showing that such relations are in one to one correspondence with the consequence relations determined by extensions in Scott domains augmented with default sets. This means that defaults are very expressive: they can, in a sense, represent any reasonable nonmonotonic entailment. Results about what kind of defaults determine cautious monotony are also discussed. In particular, we show that the property of unique extensions guarantees cautious monotony, and we give several classes of default structures which determine unique extensions.

The absolute rigidity of the Neveu–Schwarz and Ramond superalgebras

We prove that the second cohomology group with coefficients in the adjoint module of both the infinite-dimensional Lie superalgebras k(1) and k+(1), as well as their unique central extensions, which are known as the Neveu–Schwarz and the Ramond superalgebras, respectively, is equal to zero. This particularly implies that all these Lie superalgebras are rigid, i.e. they can only be deformed in a trivial manner.

Unique minimal rank extensions of triangular operators

The problem to find the minimal rank extensions of the lower triangular part of a finite rank matrix kernel appears in a natural way (see [3]) in the study of minimal representations of semi-separable integral operators or, equivalently, of minimal realizations of boundary value systems. In particular, one is interested in those kernels for which the minimal rank extension is unique. In this paper we give a full description of this class of so-called unique matrix kernels. We also define and characterize lower uniqueness for finite and semi-infinite block operator matrices. To state one of our main results, let k( t, s) be an m x n matrix kernel defined on the square [a, b] x [a, b]. Following [3] we say that k is lower separable if the lower triangular part k, of k, which is defined by kL,(t, 8) = k(t, s), a<s<t<b, admits a finite rank extension, i.e., there exists a finite rank matrix kernel h on [a, b] x [a, b] such that k, is the lower triangular part of h. Recall that for an m x n matrix kernel h on [a, fl] x [y, S] the rank of

On unique extensions of positive additive set functions. II

On unique extensions of positive additive set functions. II