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PubMed1990

Adjustments of photosystem stoichiometry in chloroplasts improve the quantum efficiency of photosynthesis.

The efficiency of photosynthetic electron transport depends on the coordinated interaction of photosystem II (PSII) and photosystem I (PSI) in the electron-transport chain. Each photosystem contains distinct pigment-protein complexes that harvest light from different regions of the visible spectrum. The light energy is utilized in an endergonic electron-transport reaction at each photosystem. Recent evidence has shown a large variability in the PSII/PSI stoichiometry in plants grown under different environmental irradiance conditions. Results in this work are consistent with the notion of a dynamic, rather than static, thylakoid membrane in which the stoichiometry of the two photosystems is adjusted and optimized in response to different light quality conditions. Direct evidence is provided that photosystem stoichiometry adjustments in chloroplasts are a compensation strategy designed to correct unbalanced absorption of light by the two photosystems. Such adjustments allow the plant to maintain a high quantum efficiency of photosynthesis under diverse light quality conditions and constitute acclimation that confers to plants a significant evolutionary advantage over that of a fixed photosystem stoichiometry in thylakoid membranes.

Journal Article↗
PubMed2004

Natural hybridization between a deciduous (Nothofagus antarctica, Nothofagaceae) and an evergreen (N. dombeyi) forest tree species: evidence from morphological and isoenzymatic traits.

BACKGROUND AND AIMS: Trees with a partial leaf-shedding pattern and other morphological features a priori considered intermediate between those of the deciduous Nothofagus antarctica (G. Forster) Oersted and the evergreen N. dombeyi (Mirb.) Oersted (Nothofagaceae) were found in natural stands. The hybridization between a deciduous and an evergreen species of Nothofagus has not been reported so far in natural communities. METHODS: The putative hybrids and the two presumed parental species were compared using 14 enzyme systems as well as shoot, leaf and reproductive morphology. KEY RESULTS: Six enzyme systems showed good resolution (MDH-B, IDH, SKDH, 6-PGDH, GOT and PGI) and in four of them (PGI, MDH-B, SKDH and 6-PGDH) the putative hybrids showed intermediate zymogram patterns between N. antarctica and N. dombeyi. Both principal coordinates analysis on isozyme data and principal components analysis (PCA) on quantitative morphological traits of shoots and leaves separated both parental species and located the putative hybrids closer to N. antarctica than to N. dombeyi. In the PCA, the number of basal cataphylls and the length : width ratio of leaves were the variables most discriminating among shoots of the three entities. The putative hybrids were intermediate between both species regarding leaf vernation, outline and venation, variation in leaf shape (length/width) with position on the parent shoot and in staminate inflorescence and cupule morphology. For other morphological traits, the putative hybrids resembled one of the parental species or differed from both species (e.g. valve morphology). CONCLUSIONS: Isoenzymatic and morphological data sets support the idea of the hybrid nature (probably F1 generation) of the semi-deciduous trees found. Nothofagus antarctica and N. dombeyi are probably more closely related than previously assumed. The relevance of pollen type in revealing evolutionary relationships between Nothofagus species is supported, and that of leaf-shedding pattern is rejected.

Crosses, Genetic↗
PubMed2002

Evolution of a protein-rich mitochondrial ribosome: implications for human genetic disease.

Mitochondrial ribosomes comprise the most diverse group of ribosomes known. The mammalian mitochondrial ribosomes (55S) differ unexpectedly from bacterial (70S) and cytoplasmic ribosomes (80S), as well as other kinds of mitochondrial ribosomes. The bovine mitochondrial ribosome has been developed as a model system for the study of human mitochondrial ribosomes to address several questions related to the structure, function, biosynthesis and evolution of these interesting ribosomes. Bovine mitochondrial ribosomal proteins (MRPs) from each subunit have been identified and characterized with respect to individuality and electrophoretic properties, amino acid sequence, topographic disposition, RNA binding properties, evolutionary relationships and reaction with affinity probes of ribosomal functional domains. Several distinctive properties of these ribosomes are being elucidated, including their antibiotic susceptibility and composition. Mammalian mitochondrial ribosomes lack several of the major RNA stem structures of bacterial ribosomes but they contain a correspondingly higher protein content (as many as 80 proteins), suggesting a model where proteins have replaced RNA structural elements during the evolution of these ribosomes. Despite their lower RNA content they are physically larger than bacterial ribosomes, because of the 'extra' proteins they contain. The extra proteins in mitochondrial ribosomes are 'new' in the sense that they are not homologous to proteins in bacterial or cytoplasmic ribosomes. Some of the new proteins appear to be bifunctional. All of the mammalian MRPs are encoded in nuclear genes (a separate set from those encoding cytoplasmic ribosomal proteins) which are evolving more rapidly than those encoding cytoplasmic ribosomal proteins. The MRPs are imported into mitochondria where they assemble coordinately with mitochondrially transcribed rRNAs into ribosomes that are responsible for translating the 13 mRNAs for essential proteins of the oxidative phosphorylation system. Interest is growing in the structure, organization, chromosomal location and expression of genes for human MRPs. Proteins which are essential for mitoribosome function are candidates for involvement in human genetic disease.

Animals↗
PubMed2003

Properties of human mitochondrial ribosomes.

Mammalian mitochondrial ribosomes (55S) differ unexpectedly from bacterial (70S) and cytoplasmic ribosomes (80S), as well as other kinds of mitochondrial ribosomes. Typical of mammalian mitochondrial ribosomes, the bovine mitochondrial ribosome has been developed as a model system for the study of human mitochondrial ribosomes, to address several questions related to the structure, function, biosynthesis and evolution of these interesting ribosomes. Bovine mitochondrial ribosomal proteins (MRPs) from each subunit have been identified and characterized with respect to individuality and electrophoretic properties, amino acid sequence, topographic disposition, RNA binding properties, evolutionary relationships and reaction with affinity probes of ribosomal functional domains. Several distinctive properties of these ribosomes are being elucidated, including their antibiotic susceptibility and composition. Human mitochondrial ribosomes lack several of the major RNA stem structures of bacterial ribosomes but they contain a correspondingly higher protein content (as many as 80 proteins), suggesting a model where proteins have replaced RNA structural elements during the evolution of these ribosomes. Despite their lower RNA content they are physically larger than bacterial ribosomes, because of the 'extra' proteins they contain. The extra proteins in mitochondrial ribosomes are 'new' in the sense that they are not homologous to proteins in bacterial or cytoplasmic ribosomes. Some of the new proteins appear to be bifunctional. All of the mammalian MRPs are encoded in nuclear genes (a separate set from those encoding cytoplasmic ribosomal proteins) which are evolving more rapidly than those encoding cytoplasmic ribosomal proteins. The MRPs are imported into mitochondria where they assemble coordinately with mitochondrially transcribed rRNAs into ribosomes that are responsible for translating the 13 mRNAs for essential proteins of the oxidative phosphorylation system.

Escherichia coli↗
PubMed2001

Prediction of contact maps with neural networks and correlated mutations.

Contact maps of proteins are predicted with neural network-based methods, using as input codings of increasing complexity including evolutionary information, sequence conservation, correlated mutations and predicted secondary structures. Neural networks are trained on a data set comprising the contact maps of 173 non-homologous proteins as computed from their well resolved three-dimensional structures. Proteins are selected from the Protein Data Bank database provided that they align with at least 15 similar sequences in the corresponding families. The predictors are trained to learn the association rules between the covalent structure of each protein and its contact map with a standard back propagation algorithm and tested on the same protein set with a cross-validation procedure. Our results indicate that the method can assign protein contacts with an average accuracy of 0.21 and with an improvement over a random predictor of a factor >6, which is higher than that previously obtained with methods only based either on neural networks or on correlated mutations. Furthermore, filtering the network outputs with a procedure based on the residue coordination numbers, the accuracy of predictions increases up to 0.25 for all the proteins, with an 8-fold deviation from a random predictor. These scores are the highest reported so far for predicting protein contact maps.

Algorithms↗
PubMed2003

The mechanism of action of the tumour suppressor gene PTEN.

Intracellular levels of phosphorylation are regulated by the coordinated action of protein kinases and phosphatases. Disregulation of this balance can lead to cellular transformation. Here we review knowledge of the mechanisms of one protein phosphatase, the tumour suppressor PTEN/MMAC/TEP 1 apropos its role in tumorigenesis and signal transduction. PTEN plays an important role in the phosphatidyl-inositol-3-kinase (PI3-K) pathway by catalyzing degradation of phosphatidylinositol-(3,4,5)-triphosphate generated by PI3-K. This inhibits downstream targets mainly protein kinase B (PKB/Akt), cell survival and proliferation. PTEN contributes to cell cycle regulation by blockade of cells entering the S phase of the cell cycle, and by upregulation of p27(Kip1) which is recruited into the cyclin E/cdk2 complex. PTEN also modulates cell migration and motility by regulation of the extracellular signal-related kinase - mitogen activated protein kinase (ERK-MAPK) pathway and by dephosphorylation of focal adhesion kinase (FAK). We also emphasize the increasingly important role that PTEN has from an evolutionary point of view. A number of PTEN functions have been elucidated but more information is needed for utilization in clinical application and potential cancer therapy.

Animals↗
PubMed2006

Modelling epistatic effects of embryo and endosperm QTL on seed quality traits.

Coordinated expression of embryo and endosperm tissues is required for proper seed development. The coordination among these two tissues is controlled by the interaction between multiple genes expressed in the embryo and endosperm genomes. In this article, we present a statistical model for testing whether quantitative trait loci (QTL) active in different genomes, diploid embryo and triploid endosperm, epistatically affect a trait expressed on the endosperm tissue. The maximum likelihood approach, implemented with the EM algorithm, was derived to provide the maximum likelihood estimates of the locations of embryo- and endosperm-specific QTL and their main effects and epistatic effects. This model was used in a real example for rice in which two QTL, one from the embryo genome and the other from the endosperm genome, exert a significant interaction effect on gel consistency on the endosperm. Our model has successfully detected Waxy, a candidate gene in the embryo genome known to regulate one of the major steps of amylose biosynthesis in the endosperm. This model will have great implications for agricultural and evolutionary genetic research.

Algorithms↗
PubMed2026

Genome-wide identification, structural characterization, and evolutionary analysis of growth-related gene families in African catfish (Clarias gariepinus).

The somatotropic axis encompassing growth hormone (GH), insulin-like growth factor (IGF), myostatin (MSTN), and prolactin (PRL) signalling cascades is the master regulator of somatic growth, metabolism, and development in vertebrates. African catfish (Clarias gariepinus), a commercially pivotal aquaculture species, now possesses a chromosome-level reference genome (CGAR_prim_01v2); however, a systematic, genome-wide characterization spanning all five interconnected growth-related gene families has not previously been undertaken in this species. Here, we identified and characterized 15 growth-related genes spanning gh1, ghra, ghrb, Igf1, Igf2a, Igf2b, igf1ra, Igf1rb, Igf2r, Mstna, Mstnb, prl, prlra, prlrb, and smtlb distributed across 13 chromosomes. Complete one-to-one orthology with zebrafish confirmed strong dosage-balance conservation across >120 million years of teleost divergence. Physicochemical analysis resolved a clear biochemical dichotomy between compact, basic secreted ligands (19.88-45.81 kDa; pI up to 10.02) and large, acidic, heavily glycosylated membrane receptors (56.82-270.80 kDa; pI 4.85-5.97). Phylogenetic analysis confirmed 3R whole-genome duplication origins for all paralog pairs, while synteny analysis revealed a disruption of the ancestral gh1-prl chromosomal block in C. gariepinus, a finding that warrants further comparative and functional investigation. This genomic atlas provides the sequence and structural information including exon-intron boundaries, domain architecture, and chromosomal coordinates needed as a prerequisite for future marker-assisted selection and CRISPR-based myostatin-editing efforts in African catfish aquaculture, though translation into applied breeding outcomes will require subsequent functional and expression studies.

Animals↗
PubMed1990

A set of human putative lymphocyte G0/G1 switch genes includes genes homologous to rodent cytokine and zinc finger protein-encoding genes.

Lymphocyte G0/G1 switch genes (G0S genes) are potential oncogenes and may regulate, be regulated by, or be coordinately regulated with, latent lymphotropic viruses. To identify these genes, a cDNA library was prepared from blood mononuclear cells that had been cultured for 2 hr with a T-cell mitogen (lectin) and cycloheximide. Eight differentially hybridizing recombinants were characterized by RNA and DNA blotting and sequencing. One cDNA (G0S7) corresponded to the oncogene c-fos. Another cDNA (G0S19) was homologous (70%) to a cDNA encoding a murine inhibitor of stem cell proliferation (the cytokine MIP1 alpha) and, less closely, to other members of the "small inducible" secreted protein-encoding gene family. Whereas cDNA hybridization to genomic DNA blots indicated a small subfamily of G0S19 genes, simple patterns of bands indicated that most cDNAs, including G0S30 cDNA, corresponded to single-copy genes. The 3' noncoding sequence of G0S30 cDNA was homologous (87-89%) to the 3' noncoding sequences of certain rodent genes (NGFI-A, Krox24, EGR1) that encode zinc finger proteins (putative transcriptional regulators). This degree of evolutionary conservation suggests an important function for the 3' noncoding region. The 3' noncoding regions of some cDNAs contained the TTATTTAT (mRNA destabilization) element. The corresponding RNAs each formed doublets in agarose gels. Previous studies of c-fos RNA from HeLa cells indicate that this is due to cycloheximide-dependent stabilization of poly(A) tails. Our results reveal the power of cycloheximide enrichment in isolating what would appear to be significant low-abundance mRNAs.

Base Sequence↗
PubMed2001

The Sambungmacan 3 Homo erectus calvaria: a comparative morphometric and morphological analysis.

The Sambungmacan (Sm) 3 calvaria, discovered on Java in 1977, was illegally removed from Indonesia in 1998 and appeared in New York City in early 1999 at the Maxilla & Mandible, Ltd. natural history shop. Here we undertake an analysis of its phylogenetic and systematic position using geometric morphometrics and comparative morphology. The coordinates of points in the sagittal plane from glabella to opisthion were resampled to yield "lines" of 50 semi-landmarks. Coordinates of glabella, bregma, lambda, inion, and opisthion were also collected and analyzed separately. Casts of Homo erectus fossils from Indonesia, China, and Kenya and of "archaic H. sapiens" from Kabwe and Petralona, as well as 10 modern human crania, were used as the primary comparative sample. The modern humans were well separated from the fossils in a graphical superimposition of Procrustes-aligned semi-landmarks as well as in principal component and canonical discriminant analyses. In all of these, Sm 3 falls intermediate between the fossil and modern groups. Morphological comparisons of Sm 3 with a selection of Homo erectus fossils revealed its greatest similarity to specimens from Ngandong and the Sm 1 calvaria. Compared to all other H. erectus, Sm 3 was distinctive in its more vertical supratoral plane, less anteriorly projecting glabella and less sharply angled occiput. In these features it was somewhat similar to modern humans. It is not yet possible to determine if this similarity implies an evolutionary relationship or (more likely) individual or local populational variation. Several features of Sm 3 (small size, gracile supraorbital torus and lack of angular torus, and position in principal component analysis) suggest that it was a female. The use of geometric morphometrics provides a means to statistically test the shapes of such fossils in a manner not easily duplicated by other methods. The intermediate position of Sm 3 between fossil and modern samples in several different subanalyses exemplifies the value of this approach.

Animals↗
PubMed1996

Divergent evolution in the mechanisms controlling major histocompatibility complex class II gene transcription in mouse and human.

The expression of the major histocompatibility complex (MHC) class II gene family is developmentally regulated and, in general, in a coordinate manner. In this study, we show that the expression of the entire repertoire of human class II genes, otherwise transcriptionally silent in the bare lymphocyte syndrome-derived BLS1 cell line, can be rescued by somatic cell hybridization with normal mouse spleen cells. The analysis of the interspecies cell hybrids revealed a particularly important and unprecedented aspect. A return to the BLS1-like, human MHC class II-negative phenotype due to segregation of mouse chromosomes was accompanied in certain hybrids by loss of IE, but not IA cell surface antigen expression. At the molecular level, this was the result of lack of E alpha-specific mRNA in the presence of E beta-, A alpha- and A beta-specific mRNA. Thus, the mouse trans-acting function operating across species barriers and able to complement the defect of human BLS1 cells diverged in mice to control Ea, but not Eb, Aa and Ab gene expression. These findings suggest that evolutionary pressure has maintained the expression of the MHC class II multigene family under the control of quite distinct species-specific transcriptional mechanisms.

Animals↗
PubMed2005

Sexual dimorphism in the Japanese cranial base: a Fourier-wavelet representation.

An approach, computational shape analysis (CSA), is presented here which utilizes a Fourier-wavelet representation to numerically describe shape features of biological forms. Two elements are involved: 1) elliptical Fourier functions (EFFs), to provide estimates of global aspects, and 2) continuous wavelet transforms (CWTs) to generate an objective estimate of localized features. EFFs are computed, using a set of pseudohomologous points, to create a precise analog of the boundary. This computed contour is then normalized by scaling and rotated in two-dimensional space to insure a representation that is invariant with respect to starting point, size, and orientation. The predicted point coordinates derived from the EFFs are submitted to CWT for further processing. Wavelet coefficients are then computed to identify localized features, localization being a subjective process with EFFs. The advantage of wavelets is that they eliminate the inevitable subjectivity inherent in the choice of measurements. To test the usefulness of CSA, a sample of cranial base (CB) lateral radiographic outlines was available. Five archaeological periods, Yayoi, Kofun, Kamakura, Edo, and Modern, were utilized (n = 297). Statistically significant differences in sex and archaeological age were found. Although archaeological age differences were present, they were small and random in character, suggesting stability in the CB structures. In contrast, sexually dimorphic differences were present in every group from the Yayoi to the Modern period. This presence of sexually dimorphic differences in shape was consistent with earlier studies of M. nemestrina, G. gorilla, and P. troglodytes. Consequently, it is suggested that the pattern of sexual dimorphism documented in the Japanese CB is a primate pattern with an ancient evolutionary history. The results demonstrate, both visually and numerically, that CSA is a powerful approach for describing both global and localized features of craniofacial structures such as the CB.

Anthropology, Physical↗
PubMed2006

Paired-end sequence mapping detects extensive genomic rearrangement and translocation during divergence of Francisella tularensis subsp. tularensis and Francisella tularensis subsp. holarctica populations.

Comparative genome hybridization of the Francisella tularensis subsp. tularensis and F. tularensis subsp. holarctica populations have shown that genome content is highly conserved, with relatively few genes in the F. tularensis subsp. tularensis genome being absent in other F. tularensis subspecies. To determine if organization of the genome differs between global populations of F. tularensis subsp. tularensis and F. tularensis subsp. holarctica, we have used paired-end sequence mapping (PESM) to identify regions of the genome where synteny is broken. The PESM approach compares the physical distances between paired-end sequencing reads of a library of a wild-type reference F. tularensis subsp. holarctica strain to the predicted lengths between the reads based on map coordinates of two different F. tularensis genome sequences. A total of 17 different continuous regions were identified in the F. tularensis subsp. holarctica genome (CR(holar)(c)(tica)) which are noncontiguous in the F. tularensis subsp. tularensis genome. Six of the 17 different CR(holarctica) are positioned as adjacent pairs in the F. tularensis subsp. tularensis genome sequence but are translocated in F. tularensis subsp. holarctica, implying that their arrangements are ancestral in F. tularensis subsp. tularensis and derived in F. tularensis subsp. holarctica. PCR analysis of the CR(holarctica) in 88 additional F. tularensis subsp. tularensis and F. tularensis subsp. holarctica isolates showed that the arrangements of the CR(holarctica) are highly conserved, particularly in F. tularensis subsp. holarctica, consistent with the hypothesis that global populations of F. tularensis subsp. holarctica have recently experienced a periodic selection event or they have emerged from a recent clonal expansion. Two unique F. tularensis subsp. tularensis-like strains were also observed which likely are derived from evolutionary intermediates and may represent a new taxonomic unit.

Biological Evolution↗
PubMed2006

Identification and characterization of L-arabonate dehydratase, L-2-keto-3-deoxyarabonate dehydratase, and L-arabinolactonase involved in an alternative pathway of L-arabinose metabolism. Novel evolutionary insight into sugar metabolism.

Azospirillum brasiliense possesses an alternative pathway of L-arabinose metabolism, different from the known bacterial and fungal pathways. In the preceding articles, we identified and characterized L-arabinose-1-dehydrogenase and alpha-ketoglutaric semialdehyde dehydrogenase, which catalyzes the first and final reaction steps in this pathway, respectively (Watanabe, S., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 2612-2623 and Watanabe, S., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 28876-28888). We here report the remaining three enzymes, L-arabonate dehydratase, L-2-keto-3-deoxyarabonate (L-KDA) dehydratase, and L-arabinolactonase. N-terminal amino acid sequences of L-arabonate dehydratase and L-KDA dehydratase purified from A. brasiliense cells corresponded to those of AraC and AraD genes, which form a single transcriptional unit together with the L-arabinose-1-dehydrogenase gene. Furthermore, the L-arabinolactonase gene (AraB) was also identified as a component of the gene cluster. Genetic characterization of the alternative L-arabinose pathway suggested a significant evolutional relationship with the known sugar metabolic pathways, including the Entner-Doudoroff (ED) pathway and the several modified versions. L-arabonate dehydratase belongs to the ILVD/EDD family and spectrophotometric and electron paramagnetic resonance analysis revealed it to contain a [4Fe-4S](2+) cluster. Site-directed mutagenesis identified three cysteine ligands essential for cluster coordination. L-KDA dehydratase was sequentially similar to DHDPS/NAL family proteins. D-2-Keto-3-deoxygluconate aldolase, a member of the DHDPS/NAL family, catalyzes the equivalent reaction to L-KDA aldolase involved in another alternative L-arabinose pathway, probably associating a unique evolutional event between the two alternative L-arabinose pathways by mutation(s) of a common ancestral enzyme. Site-directed mutagenesis revealed a unique catalytic amino acid residue in L-KDA dehydratase, which may be a candidate for such a natural mutation.

Amino Acid Sequence↗
PubMed2003

Epigenetic phenomena and the evolution of plant allopolyploids.

Allopolyploid speciation is widespread in plants, yet the molecular requirements for successful orchestration of coordinated gene expression for two divergent and reunited genomes are poorly understood. Recent studies in several plant systems have revealed that allopolyploid genesis under both synthetic and natural conditions often is accompanied by rapid and sometimes evolutionarily conserved epigenetic changes, including alteration in cytosine methylation patterns, rapid silencing in ribosomal RNA and protein-coding genes, and de-repression of dormant transposable elements. These changes are inter-related and likely arise from chromatin remodeling and its effects on epigenetic codes during and subsequent to allopolyploid formation. Epigenetic modifications could produce adaptive epimutations and novel phenotypes, some of which may be evolutionarily stable for millions of years, thereby representing a vast reservoir of latent variation that may be episodically released and made visible to selection. This epigenetic variation may contribute to several important attributes of allopolyploidy, including functional diversification or subfunctionalization of duplicated genes, genetic and cytological diploidization, and quenching of incompatible inter-genomic interactions that are characteristic of allopolyploids. It is likely that the evolutionary success of allopolyploidy is in part attributable to epigenetic phenomena that we are only just beginning to understand.

Biological Evolution↗
PubMed2004

The molecular genetics of lung morphogenesis and injury repair.

Lung development, as well as epithelial injury repair, is tightly coordinated by a fine balance between stimulatory versus inhibitory genes that appear to co-regulate the function of stem/progenitor cells in the lung. Recently, it has been noted that many of the same genes direct development of the respiratory organs (tracheae) in the fruit fly Drosophila as in mice and men. For example, FGF receptor tyrosine kinase signaling is essential for respiratory organogenesis in both fly and mouse and is negatively regulated by the sprouty genes, a family of inducible FGF pathway inhibitors. Additionally, FGF signaling is required for formation of new alveoli, protection of alveolar epithelial cells from injury, as well as migration and proliferation of putative alveolar stem/progenitor cells during lung repair. Conversely, TGFbeta receptor serine-threonine kinase signaling via Smads 2, 3 and 4 inhibits lung morphogenesis and can inhibit postnatal alveolar development, while excessive TGFbeta signaling via Smad3 causes interstitial fibrosis. On the other hand, BMP4 stimulates morphogenesis of intact embryonic lung, while inhibiting proliferation of isolated epithelium. We speculate that evolutionary-developmental, functional conservation of the FGF- FGFR-SPROUTY stimulatory pathway as well as of the TGFbeta/BMP-SMAD modulatory pathways identifies them as potential therapeutic targets for rational therapy. Novel therapy to activate lung stem/progenitor cells, ameliorate lung injury, augment lung repair and/or induce lung regeneration could be highly beneficial in both children and adults with intractable pulmonary insufficiency.

Animals↗
PubMed2006

Free radical biology and medicine: it's a gas, man!

We review gases that can affect oxidative stress and that themselves may be radicals. We discuss O(2) toxicity, invoking superoxide, hydrogen peroxide, and the hydroxyl radical. We also discuss superoxide dismutase (SOD) and both ground-state, triplet oxygen ((3)O(2)), and the more energetic, reactive singlet oxygen ((1)O(2)). Nitric oxide ((*)NO) is a free radical with cell signaling functions. Besides its role as a vasorelaxant, (*)NO and related species have other functions. Other endogenously produced gases include carbon monoxide (CO), carbon dioxide (CO(2)), and hydrogen sulfide (H(2)S). Like (*)NO, these species impact free radical biochemistry. The coordinated regulation of these species suggests that they all are used in cell signaling. Nitric oxide, nitrogen dioxide, and the carbonate radical (CO(3)(*-)) react selectively at moderate rates with nonradicals, but react fast with a second radical. These reactions establish "cross talk" between reactive oxygen (ROS) and reactive nitrogen species (RNS). Some of these species can react to produce nitrated proteins and nitrolipids. It has been suggested that ozone is formed in vivo. However, the biomarkers that were used to probe for ozone reactions may be formed by non-ozone-dependent reactions. We discuss this fascinating problem in the section on ozone. Very low levels of ROS or RNS may be mitogenic, but very high levels cause an oxidative stress that can result in growth arrest (transient or permanent), apoptosis, or necrosis. Between these extremes, many of the gasses discussed in this review will induce transient adaptive responses in gene expression that enable cells and tissues to survive. Such adaptive mechanisms are thought to be of evolutionary importance.

Free Radicals↗
PubMed2002

Identification of a lycopene beta-cyclase required for bacteriorhodopsin biogenesis in the archaeon Halobacterium salinarum.

Biogenesis of the light-driven proton pump bacteriorhodopsin in the archaeon Halobacterium salinarum requires coordinate synthesis of the bacterioopsin apoprotein and carotenoid precursors of retinal, which serves as a covalently bound cofactor. As a step towards elucidating the mechanism and regulation of carotenoid metabolism during bacteriorhodopsin biogenesis, we have identified an H. salinarum gene required for conversion of lycopene to beta-carotene, a retinal precursor. The gene, designated crtY, is predicted to encode an integral membrane protein homologous to lycopene beta-cyclases identified in bacteria and fungi. To test crtY function, we constructed H. salinarum strains with in-frame deletions in the gene. In the deletion strains, bacteriorhodopsin, retinal, and beta-carotene were undetectable, whereas lycopene accumulated to high levels ( approximately 1.3 nmol/mg of total cell protein). Heterologous expression of H. salinarum crtY in a lycopene-producing Escherichia coli strain resulted in beta-carotene production. These results indicate that H. salinarum crtY encodes a functional lycopene beta-cyclase required for bacteriorhodopsin biogenesis. Comparative sequence analysis yields a topological model of the protein and provides a plausible evolutionary connection between heterodimeric lycopene cyclases in bacteria and bifunctional lycopene cyclase-phytoene synthases in fungi.

Amino Acid Sequence↗