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At least 469 records · Page 26Linked to original sources
PubMed2004

Purification and functional assessment of C3a, C4a and C5a of the common carp (Cyprinus carpio) complement.

Promotion of inflammatory response is an important role of the complement system, but this kind of function is poorly documented for the lower vertebrates. Here we report chemotactic activity of purified anaphylactic fragments derived from the complement components C3, C4 and C5 of the common carp. The purified anaphylatoxins are two C5a-desArg peptides derived from the C5-I isotype, an intact form and a desArg form of C4a from C4-2 isotype, and an intact form and a desArg form of C3a from C3-H1 isoform. These were identified by N-terminal sequencing, mass spectrometry, and peptide mass fingerprinting. In the chemotaxis assay using carp kidney neutrophils, the two C5a-desArg fragments, which are probably allotypic variants, showed a potent chemotactic activity at 0.5-1 nM, whereas C3a or C4a showed no significant activity. The results suggest that C3a, C4a and C5a of bony fish have functionally diverged to the state similar to their mammalian homologs.

Amino Acid Sequence↗
PubMed2026

Identification and differential regulation of proteasome β family genes by viral infection and cytokines in grass carp (Ctenopharyngodon idella).

Proteasome β (PSMB) subunits are essential components of the proteasome complex and play important roles in antigen processing and immune regulation. In this study, we identified 14 Psmb genes in grass carp (Ctenopharyngodon idella), including seven constitutive Psmbs (Psmb1-7), three immunoproteasome genes (Psmb8-10), two thymoproteasome-related paralogs (Psmb11a and Psmb11b), and two telelost-specific members (Psmb12 and Psmb13). Comparative genomic analyses showed that grass carp Psmb genes are highly conserved in genomic organization, gene synteny, and predicted β-subunit-like protein structures, supporting the evolutionary conservation of the proteasome β-subunit family in fish. Phylogenetic and syntenic analyses further revealed lineage-specific expansion of immunoproteasome-related Psmb genes in teleost fish, with Psmb12 and Psmb13 likely derived from duplications of Psmb9 and Psmb10, respectively. Tissue expression analysis suggested functional divergence among duplicated Psmb members, as constitutive Psmbs were relatively enriched in the brain, whereas immunoproteasome-related and teleost-specific Psmbs were highly expressed in immune- and mucosa-associated tissues. Moreover, GCRV-I infection rapidly induced Psmb8-10 and Psmb11b expression in CIK cells. IFN-γ induced a broader set of Psmb genes than IFNa, whereas IL-10 selectively suppressed several Psmbs. Together, these findings highlight the evolutionary conservation, expansion, and immune-related diversification of the Psmb family in teleost fish.

Animals↗
PubMed2005

The Drosophila ortholog of the human Wnt inhibitor factor Shifted controls the diffusion of lipid-modified Hedgehog.

The Hedgehog (Hh) family of morphogenetic proteins has important instructional roles in metazoan development and human diseases. Lipid modified Hh is able to migrate to and program cells far away from its site of production despite being associated with membranes. To investigate the Hh spreading mechanism, we characterized Shifted (Shf) as a component in the Drosophila Hh pathway. We show that Shf is the ortholog of the human Wnt inhibitory factor (WIF), a secreted antagonist of the Wingless pathway. In contrast, Shf is required for Hh stability and for lipid-modified Hh diffusion. Shf colocalizes with Hh in the extracellular matrix and interacts with the heparan sulfate proteoglycans (HSPG), leading us to suggest that Shf could provide HSPG specificity for Hh. We also show that human WIF inhibits Wg signaling in Drosophila without affecting the Hh pathway, indicating that different WIF family members might have divergent functions in each pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Different age distribution patterns of human, nematode, and Arabidopsis duplicate genes.

We studied the age distribution of duplicate genes in each of four eukaryotic genomes: human, Arabidopsis thaliana, Caenorhabditis elegans, and Drosophila melanogaster. The four distributions differ greatly from each other, contrary to the previous proposal of a universal L-shaped distribution in all eukaryotic genomes studied. Indeed, only the distribution in humans is L-shaped. The distribution in Arabidopsis is consistent with the hypothesis of an ancient genome duplication with no recent burst of duplication events, while the distribution in C. elegans is nearly uniform. We also applied a nonparametric method to the human distribution to show that the rate of loss of duplicate genes decreases over time, contrary to the proposal of an exponential decay. One possible explanation of the decreasing rate of loss of duplicate genes over time could be rapid functional divergence between duplicate genes, providing an advantage for the retention of both duplicates.

Algorithms↗
PubMed2005

Rapid expansion of killer cell immunoglobulin-like receptor genes in primates and their coevolution with MHC Class I genes.

The gene family of killer cell immunoglobulin-like receptors (KIRs) in primates provides the first line of defense against virus infection and tumor transformation. Interacting with MHC class I molecules, KIRs can regulate the cytotoxic activity of natural killer (NK) cells and distinguish the tumor and virus infected cells from normal body cells. Phylogenetic analysis and comparison of domain structures identified three major groups of KIR genes (group I, II, and III genes). These groups of KIR genes, generated by a series of gene duplications, have acquired different MHC-binding specificity. Inference of ancestral KIR sequences suggested that the functional divergence of group I genes from group II genes occurred by positive selection at the MHC-binding sites after duplication. Our evolutionary study has shown that group I genes diverged from group II genes about 17 million years ago (Mya) apparently after separation of hominoids from Old World (OW) monkeys. Around the same time, gene duplication generating the class I MHC-C locus appears to have occurred. These findings suggest that KIR and MHC class I genes have coevolved as an interacting system. The KIR gene family has experienced a rapid expansion in primate species. The rate of expansion of this gene family seems to be one of the highest among all hominoid gene families. The KIR gene family is also subject to birth-and-death evolution.

Amino Acid Sequence↗
PubMed2005

Annexin-like alpha giardins: a new cytoskeletal gene family in Giardia lamblia.

Through a genome survey and phylogenetic analysis, we have identified and sequenced 14 new coding regions for alpha-giardins in Giardia lamblia. These proteins are related to annexins and comprise a multi-gene family with 21 members. Many alpha giardins are highly expressed proteins that are very immunogenic during acute giardiasis in humans. However, little is known about the function of these proteins. By using PCR with different combinations of gene-specific primers, we demonstrated that several of the genes localised to the same chromosomal fragment. These data point towards a molecular evolution through gene duplication and subsequent functional divergence. Semi-quantitative reverse transcriptase-PCR analysis of the Giardia life cycle revealed large differences in mRNA expression levels of the alpha giardins. Epitope tagging of the alpha-giardins localised them to different cytoskeletal components, such as the flagella and the adhesive disc, but also to the plasma membrane. These localisation experiments suggest alpha-giardins play a role in cell motility, attachment and membrane stability.

Animals↗
PubMed2004

Genetic dissection of the formation of the forebrain in Medaka, Oryzias latipes.

The forebrain, consisting of the telencephalon and diencephalon, is essential for processing sensory information. To genetically dissect formation of the forebrain in vertebrates, we carried out a systematic screen for mutations affecting morphogenesis of the forebrain in Medaka. Thirty-three mutations defining 25 genes affecting the morphological development of the forebrain were grouped into two classes. Class 1 mutants commonly showing a decrease in forebrain size, were further divided into subclasses 1A to 1D. Class 1A mutation (1 gene) caused an early defect evidenced by the lack of bf1 expression, Class 1B mutations (6 genes) patterning defects revealed by the aberrant expression of regional marker genes, Class 1C mutation (1 gene) a defect in a later stage, and Class 1D (3 genes) a midline defect analogous to the zebrafish one-eyed pinhead mutation. Class 2 mutations caused morphological abnormalities in the forebrain without considerably affecting its size, Class 2A mutations (6 genes) caused abnormalities in the development of the ventricle, Class 2B mutations (2 genes) severely affected the anterior commissure, and Class 2C (6 genes) mutations resulted in a unique forebrain morphology. Many of these mutants showed the compromised sonic hedgehog expression in the zona-limitans-intrathalamica (zli), arguing for the importance of this structure as a secondary signaling center. These mutants should provide important clues to the elucidation of the molecular mechanisms underlying forebrain development, and shed new light on phylogenically conserved and divergent functions in the developmental process.

Animals↗
PubMed2005

Differential localization of MAPK-activated protein kinases RSK1 and MSK1 in mouse brain.

RSK1 and MSK1 are closely related members of the MAP kinase-activated kinase family and are direct substrates and effectors of the well-studied mitogen-activated protein kinases. Although extensively characterized at the biochemical level, little is known about the localization of these protein kinases in the brain. We utilized immunohistochemistry to determine the cellular and subcellular localization of RSK1 and MSK1 in the adult mouse brain. RSK1 is expressed at highest levels in cerebellum, especially in granule neurons and within neuropil of the molecular layer. RSK1 is also expressed in microglia throughout the brain. In a focal trauma model, RSK1 immunoreactivity is increased in activated microglia. RSK1 expression is also prominent in many large pyramidal neurons throughout the brain. At the subcellular level, RSK1 is highly concentrated in the golgi apparatus of both neurons and astroglia. In contrast, MSK1 is expressed at highest levels in striatal and olfactory tubercle neurons and to a lesser degree in cerebellar Purkinje cells. MSK1 is also expressed in a subset of astroglia. At the subcellular level, MSK1 is confined to the nucleus of all expressing cell types. The differential cellular and subcellular localizations of RSK1 and MSK1 suggest divergent functional roles in the brain, with RSK1 poised to regulate membrane trafficking or membrane-localized signaling, and MSK1 involved in modification of nuclear histones and transcription factors.

Animals↗
PubMed2005

Biochemical and structural impact of natural polymorphism in the HLA-A3 superfamily.

Class I alleles of the HLA-A3 superfamily (-A*0301, -A*1101, -A*3101, -A*3301, and -Aw*6801) share largely overlapping peptide repertoires. Cross-reactive T cell responses between HLA-A3-like molecule/peptide complexes have been demonstrated in vitro and during natural diseases. In spite of this immune relatedness, HLA-A3-like molecules exhibit noticeable differences in their antigen-selecting and -presenting properties. Identifying molecular and structural features responsible for these differences is important for understanding how natural polymorphism leads to functional divergence within the HLA-A3 superfamily. Towards this goal, we used an approach that combines thermal stability data on recombinant, soluble HLA-A3-like molecules complexed with a nonamer and decamer HIV-1 peptide, together with a detailed structural analysis of these HLA-A3-like molecule/peptide complexes based on crystal and molecular model structures. Our studies revealed the importance of residues 9 and 67 for modulating peptide selection within the B pocket; of residue 97 for modulating peptide selection within the F pocket interdependently with the presence (or absence) of a middle, secondary anchor residue; and of residues 70, 73, 97, 152, and 156 for modulating peptide presentation in the central region of the groove that leads to altered antigenic surfaces. Overall, our detailed assessment of the biochemical and structural impact of natural polymorphism within the HLA-A3 superfamily has permitted to understand how HLA-A3-like molecules differ at the level of their primary and secondary anchor pockets causing fine differences in their peptide-selecting and -presenting properties. A better understanding of the molecular immunological properties of HLA-A3-like molecules is significantly important for the rationale design of broad peptide-based vaccines.

Alleles↗
PubMed2006

Mechanisms for detecting auditory temporal and spectral deviations operate over similar time windows but are divided differently between the two hemispheres.

In order to keep track of potentially relevant information in the acoustic environment, the human brain processes sounds to a high extent even when they are not attended: it extracts basic features, encodes regularities, and detects deviances. Here, we deliver evidence that the initial 300 ms of a sound contribute more to this preattentive processing than the sound's later parts. We directly compared the influence of the temporal distance relative to sound onset on the processing of the sound's duration and frequency information. The mismatch negativity (MMN), an event-related potential indicator for preattentive feature encoding and deviance detection, was measured for infrequent duration deviants and frequency modulation deviants. The onset of either deviancy was at 100, 200, 300, or 400 ms relative to sound onset. MMN was only elicited for deviations occurring within the first 300 ms after sound onset for both types of deviants. Its neural sources were localized in supra-temporal cortices with source current density analyses (SCD) and variable resolution electromagnetic tomography (VARETA), revealing a right-hemispheric preponderance for frequency modulations but not for duration shortenings. This suggests that preattentive deviance detection is based upon partly diverging functional memory registers for temporal and dynamic spectral information. The influence of temporal distance on MMN in both conditions supports the view that temporal and spectral sound properties are integrated into an auditory object representation prior to preattentive deviance detection. Importantly, the decline of MMN to unattended sounds with larger temporal distance suggests that parts beyond 300 ms are less important for preattentive auditory object representation.

Acoustic Stimulation↗
PubMed2006

Cloning and characterization of chalcone synthase from the moss, Physcomitrella patens.

Since the early evolution of land plants from primitive green algae, flavonoids have played an important role as UV protective pigments in plants. Flavonoids occur in liverworts and mosses, and the first committed step in the flavonoid biosynthesis is catalyzed by chalcone synthase (CHS). Although higher plant CHSs have been extensively studied, little information is available on the enzymes from bryophytes. Here we report the cloning and characterization of CHS from the moss, Physcomitrella patens. Taking advantage of the available P. patens EST sequences, a CHS (PpCHS) was cloned from the gametophores of P. patens, and heterologously expressed in Escherichia coli. PpCHS exhibited similar kinetic properties and substrate preference profile to those of higher plant CHS. p-Coumaroyl-CoA was the most preferred substrate, suggesting that PpCHS is a naringenin chalcone producing CHS. Consistent with the evolutionary position of the moss, phylogenetic analysis placed PpCHS at the base of the plant CHS clade, next to the microorganism CHS-like gene products. Therefore, PpCHS likely represents a modern day version of one of the oldest CHSs that appeared on earth. Further, sequence analysis of the P. patens EST and genome databases revealed the presence of a CHS multigene family in the moss as well as the 3'-end heterogeneity of a CHS gene. Of the 19 putative CHS genes, 10 genes are expressed and have corresponding ESTs in the databases. A possibility of the functional divergence of the multiple CHS genes in the moss is discussed.

Acyltransferases↗
PubMed2026

Contrasting redox-related physiological responses associated with HaGATA23 and HaGATA36 during Orobanche cumana parasitism in sunflower (Helianthus annuus L.).

Helianthus annuus is an economically important Asteraceae species used for seed oil production and ornamental purposes, but its production is seriously affected by the root-parasitic plant Orobanche cumana. GATA transcription factors are zinc-finger DNA-binding regulators involved in plant development and stress adaptation. However, the molecular characteristics of GATA transcription factors in Helianthus annuus and their contribution to Helianthus annuus -Orobanche cumana interaction remain poorly understood. Here, 36 HaGATA members were retrieved from the Helianthus annuus genome and classified into four phylogenetic clades. Chromosomal placement, collinearity, gene structure, motif composition, and promoter elements varied among the 36 HaGATA members, indicating evolutionary conservation coupled with functional diversification. Expression analysis and RT-qPCR analyses revealed differential expression patterns among HaGATA genes under O. cumana stress, with HaGATA23 markedly downregulated and HaGATA36 strongly upregulated. Overexpression of HaGATA23 was associated with increased malondialdehyde (MDA) accumulation and unfavorable changes in antioxidant enzyme activities, whereas its silencing showed the opposite physiological tendency. In contrast, overexpression of HaGATA36 reduced malondialdehyde accumulation, increased peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activities, while its silencing showed the reverse tendency. These results indicate that HaGATA23 and HaGATA36 are candidate genes associated with contrasting redox-related physiological responses during O. cumana stress. This work provides evidence that GATA transcription factors are associated with redox-related physiological responses in sunflower under O. cumana treatment and identifies HaGATA23 and HaGATA36 as functionally divergent candidate genes for further validation.

Helianthus↗
PubMed2006

Bayesian shadows of molecular mechanisms cast in the light of evolution.

A great many carefully designed experiments will be required to fully understand biological mechanisms in atomic detail. A complementary approach is to use powerful statistical procedures to rapidly test numerous scientific hypotheses using vast numbers of protein sequences--the cell's own blueprints for specifying biological mechanisms. Bayesian inference of the evolutionary constraints imposed on functionally divergent proteins can reveal key components of the molecular machinery and thereby suggest likely mechanisms to test experimentally. This approach is demonstrated by considering how DNA polymerase clamp-loader AAA+ ATPases couple DNA recognition to ATP hydrolysis and clamp loading.

Adenosine Triphosphatases↗
PubMed2005

Plant conserved non-coding sequences and paralogue evolution.

Genome duplication is a powerful evolutionary force and is arguably most prominent in plants, where several ancient whole-genome duplication events have been documented. Models of gene evolution predict that functional divergence between duplicates (subfunctionalization) is caused by the loss of regulatory elements. Studies of conserved non-coding sequences (CNSs), which are putative regulatory elements, indicate that plants have far fewer CNSs per gene than mammals, suggesting that plants have less complex regulatory mechanisms. Furthermore, a recent study of a duplicated gene pair in maize suggests that CNSs are lost in a complementary fashion, perhaps driving subfunctionalization. If subfunctionalization is common, one expects duplicate genes to diverge in expression; recent microarray analyses in Arabidopsis thalinia suggest that this is the case. Plant genomes are relatively complex on a genomic level because of the prevalence of whole-genome duplication and, paradoxically, subfunctionalization after duplication can lead to relatively simple regulatory regions on a per gene basis.

Base Sequence↗
PubMed2005

Handling calcium signaling: Arabidopsis CaMs and CMLs.

The Arabidopsis genome harbors seven calmodulin (CAM) and 50 CAM-like (CML) genes that encode potential calcium sensors. The CAMs encode only four protein isoforms. Selective pressure to maintain multiple CAMs indicates nonredundancy. Sequence divergence, even in the EF hand calcium-binding motif, exists among the CMLs and, therefore, divergent functions are likely to have evolved. Expression data recently available from Massively Parallel Signature Sequencing and Genevestigator compilation of microarrays are reviewed. The seven Arabidopsis CAMs are highly and relatively uniformly expressed. Differential expression is evident among the distinct CMLs over developmental stages, in various organs and in response to many different stimuli. In spite of the potential importance in mediating plant calcium signaling, the physiological functions of the Arabidopsis CaMs and CMLs remain largely unknown.

Amino Acid Sequence↗
PubMed2005

HIV-1 infection initiates changes in the expression of a wide array of genes in U937 promonocytes and HUT78 T cells.

Human monocytes/macrophages (M/M) are the major targets for human immunodeficiency virus type 1 (HIV-1) infection. To characterize the global effects of acute HIV-1 infection on gene expression in M/M, the expression levels of 550 host cell RNA transcripts in U937 human promonocytes at 2-3 days after HIV-1 infection were assessed using cDNA microarray analysis and were compared to those in the infected HUT78, a CD4+ T cell line. Confirmed by semiquantitative RT-PCR, our results showed that 12 genes were up-regulated and 26 genes were down-regulated in the infected U937 cells at 2-3 days post-infection, whereas 8 genes were up-regulated and 20 genes were down-regulated in the infected HUT78 cells at 2-3 days post-infection. These genes encode a host of proteins with divergent functions in a variety of cellular processes including apoptosis (FAS, Fas ligand, PIN, HSP90beta, bcl-2, bcl-x), cell signal transduction (Ras, RGS1, IRF-1, STAT3), receptor-mediated signaling transduction (CD71, CD69, CD3delta), cell cycle and growth (c-myc, cytokines, kinase), transcriptional regulation (EWS, CREB-2), and chemotaxis (beta-chemokines, RANTES), supporting the general effects of HIV-1 infection on cells of different origin. Although most identified genes were regulated similarly in both infected cell lines, differences in gene regulation, such as c-myc, CD71, CD69, and beta-chemokines, between the two infected cell lines were also identified in this study. These differences may further our understanding of the pathogenicity of HIV and enable the discovery of novel therapeutic approach for AIDS.

Antigens, CD↗
PubMed2004

Differences in expression pattern and function between zebrafish hoxc13 orthologs: recruitment of Hoxc13b into an early embryonic role.

Vertebrate Hox genes are generally believed to initiate expression at the primitive streak or early neural plate stages. The timing and spatial restrictions of the Hox expression patterns during these stages correlate well with their demonstrated role in axial patterning. Here we demonstrate that one zebrafish hoxc13 ortholog, hoxc13a, has an expression pattern in the developing tail bud that is consistent with the gene playing a role in axial patterning. However, the second hoxc13 ortholog, hoxc13b, is maternally expressed and is detectable in every cell of early cleavage embryos through gastrulae. In addition, both transcript and protein are detectable at these stages. At 19 h post fertilization (hpf), hoxc13b expression is up-regulated in the tail bud, becoming restricted to the tail bud by 24 hpf. Importantly, by 24 hpf, hoxc13b morphants show a specific developmental delay, which can be rescued by co-injecting synthetic capped hoxc13a or hoxc13b message. These data suggest some functional divergence due to altered expression patterns of the two hoxc13 orthologs after duplication. Further characterization of the hoxc13b morphant delay reveals that it is biphasic in nature, with the first phase of the delay occurring before gastrulation, suggesting a new role for vertebrate Hox genes before their conserved role in axial patterning. The extent of the delay does not change through 20 hpf; however, an additional delay emerges at this time. Notably, this second phase of the delay correlates with hoxc13b expression pattern becoming restricted to the tail bud.

Amino Acid Sequence↗
PubMed2007

Molecular characterization and gene expression pattern of two putative molt-inhibiting hormones from Litopenaeus vannamei.

Two cDNA sequences (Liv-MIH1 and Liv-MIH2) were cloned from the eyestalk ganglia of the white shrimp Litopenaeus vannamei. The conceptually translated peptide precursors consist of a mature peptide (77 residues for Liv-MIH1, 75 residues for Liv-MIH2), preceded by a 28-residue signal peptide. Both mature peptides share highest sequence identity with other known MIHs, and contain several conserved residues that have been proposed to be functionally critical for MIH activity. Analysis of genomic sequences reveals that both genes are organized in a 3 exon/2 intron manner, with the same sites of intron insertion. The transcripts of Liv-MIH1 and Liv-MIH2 were detected exclusively in the eyestalk, but not in other neural and non-neural tissues examined. Phylogenetic analysis indicates that Liv-MIH1 and Liv-MIH2 cluster with the type II peptides that are considered as penaeid MIH. In addition, a quantitative real-time polymerase chain reaction (PCR) assay was developed and validated for the quantification of gene expression of Liv-MIH1 and Liv-MIH2. Transcript levels for both genes remained constant through stages A - D(1') (ranges of relative expression levels are 97.9+/-2.9 to 104.5+/-8.9% for Liv-MIH1, and 85.6+/-6.7 to 104.7+/-10.8% for Liv-MIH2), and declined afterwards, reaching a lowest level during stage D(2)D(3) (40.6+/-0.4% for Liv-MIH1, and 48.5+/-3.2% for Liv-MIH2). These significant decreases in the transcript levels correspond to a significant increase in hemolymph ecdysteroid titers at stage D(2)D(3). These results clearly indicate that Liv-MIH1 and Liv-MIH2 are type II peptides of the crustacean hyperglycemic hormone family and most likely function as MIHs in the white shrimp. They are discussed with regard to the presence of multiple MIHs and possible functional divergence of type II peptides in Penaeidae, as well as endocrine regulation of crustacean molting.

Amino Acid Sequence↗