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Pathways of ubiquitin conjugation.

The covalent attachment of the polypeptide ubiquitin to proteins marks them for degradation by the ubiquitin/26S proteasome-dependent degradation pathway. This pathway functions in regulating many fundamental processes required for cell viability. Phylogenetic analysis of ubiquitin sequences reveals greater variability among lower eukaryotes and defines essential residues, many of which are conserved among the three ubiquitin-like proteins known to undergo parallel ligation pathways. The hierarchical design of the ubiquitin conjugation mechanism provides great flexibility for the divergent evolution of new functions mediated by this posttranslational modification. Within this hierarchy, a single ubiquitin-activating enzyme provides charged intermediates to multiple targeting pathways defined by cognate ubiquitin carrier protein (E2)/ligase (E3) pairs. Sequence analysis of E2 isozymes shows that the E2 superfamily is composed of distinct function-specific families. The apparent lack of E2/E3 specificity suggested in the literature results from the presence of multiple isozymes within many E2 families and erroneous family assignments based on incomplete data sets. Other apparent inconsistencies are explained by interfamily sequence relationships among some E2 isoforms.

Amino Acid Sequence↗

Lanthanum carbonate: a new phosphate binder.

PURPOSE OF REVIEW: Hyperphosphatemia remains an important aspect in the management of end-stage renal disease patients. Consequently, there is a need for new, efficient and well-tolerated phosphate binders. In this review, a new phosphate-binding drug, lanthanum carbonate, with an attractive preclinical efficacy profile compared with existing binders, is discussed. Although the available human efficacy and safety data over 3 years are encouraging, the consequences of low-level tissue deposition continue to be evaluated in longer-term clinical studies. RECENT FINDINGS: Lanthanum carbonate has been shown in clinical studies of up to 3 years to be an effective, well-tolerated phosphate binder. Reported adverse effects are mainly gastrointestinal, and do not differ from those of calcium carbonate. The gastrointestinal absorption of lanthanum is very low. Whereas the element is mainly excreted by the liver, renal excretion of the absorbed fraction is less than 2%. Bone lanthanum levels seen after long-term treatment (up to 4 years) seem not to affect the physicochemical process of mineralization, or osteoblast number/function. Preliminary data on the localization of lanthanum in bone have shown the element to be present at both active and quiescent sites of bone mineralization, independent of the type of renal osteodystrophy, a profile distinct from aluminum, as well as diffusely distributed throughout the mineralized bone matrix especially in rats/humans with an increased bone turnover. A randomized, comparator-controlled, parallel group, open-label study comparing lanthanum carbonate with calcium carbonate in dialysis patients showed no evolution towards low bone turnover in the lanthanum group, and no aluminum-like effect on bone. SUMMARY: Lanthanum carbonate seems to be a potent phosphate-binding drug, minimally absorbed from the gut, with an encouraging safety profile, and no deleterious effects on bone.

Bone and Bones↗

Cellular automaton models of driven diffusive Frenkel-Kontorova-type systems.

Three cellular automaton models of increasing complexity are introduced to model driven diffusive systems related to the generalized Frenkel-Kontorova (FK) models recently proposed by Braun et al. [Phys. Rev. E 58, 1311 (1998)]. The models are defined in terms of parallel updating rules. Simulation results are presented for these models. The features are qualitatively similar to those models defined previously in terms of sequentially updating rules. Essential features of the FK model such as phase transitions, jamming due to atoms in the immobile state, and hysteresis in the relationship between the fraction of atoms in the running state and the bias field are captured. Formulating in terms of parallel updating rules has the advantage that the models can be treated analytically by following the time evolution of the occupation on every site of the lattice. Results of this analytical approach are given for the two simpler models. The steady state properties are found by studying the stable fixed points of a closed set of dynamical equations obtained within the approximation of retaining spatial correlations only up to two nearest-neighboring sites. Results are found to be in good agreement with numerical data.

Journal Article↗

Inter-genomic displacement via lateral gene transfer of bacterial trp operons in an overall context of vertical genealogy.

BACKGROUND: The growing conviction that lateral gene transfer plays a significant role in prokaryote genealogy opens up a need for comprehensive evaluations of gene-enzyme systems on a case-by-case basis. Genes of tryptophan biosynthesis are frequently organized as whole-pathway operons, an attribute that is expected to facilitate multi-gene transfer in a single step. We have asked whether events of lateral gene transfer are sufficient to have obscured our ability to track the vertical genealogy that underpins tryptophan biosynthesis. RESULTS: In 47 complete-genome Bacteria, the genes encoding the seven catalytic domains that participate in primary tryptophan biosynthesis were distinguished from any paralogs or xenologs engaged in other specialized functions. A reliable list of orthologs with carefully ascertained functional roles has thus been assembled and should be valuable as an annotation resource. The protein domains associated with primary tryptophan biosynthesis were then concatenated, yielding single amino-acid sequence strings that represent the entire tryptophan pathway. Lateral gene transfer of several whole-pathway trp operons was demonstrated by use of phylogenetic analysis. Lateral gene transfer of partial-pathway trp operons was also shown, with newly recruited genes functioning either in primary biosynthesis (rarely) or specialized metabolism (more frequently). CONCLUSIONS: (i) Concatenated tryptophan protein trees are congruent with 16S rRNA subtrees provided that the genomes represented are of sufficiently close phylogenetic spacing. There are currently seven tryptophan congruency groups in the Bacteria. Recognition of a succession of others can be expected in the near future, but ultimately these should coalesce to a single grouping that parallels the 16S rRNA tree (except for cases of lateral gene transfer). (ii) The vertical trace of evolution for tryptophan biosynthesis can be deduced. The daunting complexities engendered by paralogy, xenology, and idiosyncrasies of nomenclature at this point in time have necessitated an expert-assisted manual effort to achieve a correct analysis. Once recognized and sorted out, paralogy and xenology can be viewed as features that enrich evolutionary histories.

Bacteria↗

[Crohn's disease and ascites].

Crohn's disease is not usually included among the causes of ascites. Although cases of Crohn's disease presenting as ascites have occasionally been described, the appearance of ascites during follow-up, with no relationship with other complications of the disease, such as thrombosis of the suprahepatic veins, has not been previously described. We present the case of a 36-year-old female patient with Crohn's disease who presented ascites during evolution. Evacuative paracenteses were required. No causes apart from Crohn's disease were found. Ascites followed a parallel course to acute episodes of this disease.

Adult↗

[Breast cancer treatment in 2004: towards a tailored approach].

Breast cancer remains one of the most frequent malignancies that general practitioners are confronted with. Given their key-counselling role for the affected families, they need regular updates on the multi-disciplinary management of the disease. This has been characterized by an evolution towards less aggressive surgery, sparing many women the morbidity of a full axillary node dissection; in parallel, there is increasing hope for "individualized" adjuvant medical treatment, given the development of new technologies that provide an "identity card" of the genes expressed by each tumour. These technologies should improve our ability to identify which women truly need adjuvant chemotherapy and to select the best medical treatment on an individual basis. While providing these messages of hope, this chapter also reviews the major classes of drugs used for the treatment of advanced breast cancer.

Breast Neoplasms↗

Microalbuminuria, as predictor of late diabetic complications. A prospective study.

To assess the predictive value of microalbuminuria (M) for diabetic macro- and microangiopathy, neuropathy and some related risk factors studies were carried out in 105 diabetic subjects. All examinations were repeated after one year. Microalbuminuria was found to parallel all late diabetic complications, at the beginning of investigations and also after a one-year evolution. It also positively correlated with some risk factors for angiopathy, such as plasma lipid parameters, blood pressure, body mass index and duration of disease.

Adolescent↗

Prognostic significance of antithrombin III, plasminogen and proactivator of plasminogen activity in viral hepatitis.

Antithrombin III/AT III/, plasminogen (Plg) and proactivator of plasminogen [PPlg] activity were studied in 663 patients with various liver diseases and 547 healthy subjects. Parallel analysis of AT III, Plg and PPlg gives a very valuable prognostic information concerning the forthcoming evolution of viral hepatitis [v.h] and acute liver failure. The prognosis of v.h. in the cases with normal Plg activity is independent from the AT III activity in 98% of the cases it is associated with clinical improvement. The combination with low Plg and elevated AT III activity suggested clinical improvement in 65-90% of the patients. Most critical is the combination between low Plg and low AT III activity. This combination suggests clinical aggravation and danger of hepatic coma. The existence of 4 patterns of AT III activity is shown: elevated, normal in physiological condition, normal in pathological condition and decreased activity.

Antithrombin III↗

Intrapsychic outcome in projective identification.

Four possible outcomes of projective identification (Klein, 1946) are identified. First is a parallel sending, receiving, and giving back between both parties. Second, there is an inability to access the receiver, leading to annihilation anxieties. Third is an experience of the receiver not being able to process the message, leading to the sender's fantasy of hurting or destroying the object. Finally, there is the experience of the object becoming outraged at being asked to receive a message and subsequently attacking the sender. These are all fantasy states that come about in the context of the most basic of human communications, the process of projective identification. Projective identification is a fantasy-dominated experience and a dialectical process within both interpersonal and intrapsychic forums. These four potential states are separated for theoretical purposes but are always cross-influencing and creating each other in the unconscious. The situations described between mother and infant are paralleled in the analytic situation, the difference being the chronological and developmental passage of time and the evolution of the original fantasy material.

Adult↗

Protein stability and the evolution of the cell membrane.

Cholesterol has been shown to regulate the activity of several membrane proteins. Although this phenomenon represents an important factor in the regulation of ion homeostasis, insights are needed to fully understand the role of this lipid in cell function in order to better comprehend the effect of bilayer components upon membrane function. Since evolution has shaped the composition of the membrane bilayer, it becomes of interest to study these changes in parallel with the many functions of membranes such as ion transport. The present study employing a plasma membrane preparation obtained from calf ventricular muscle demonstrates that cholesterol partially inhibits the Ca(2+),Mg(2+)-ATPase as the catalytic function of the calcium pump, when incubation reaction temperatures are below 42 degrees C. In contrast, when incubation reaction temperatures are above 42 degrees C, cholesterol apparently promotes enzyme stabilization reflected in higher activity. Although the activation energy values for the enzyme are almost the same at ranges between 15 and 40 degrees C, the use of elevated temperatures promote higher enzyme inactivation rates in control than in cholesterol enriched membranes. Cholesterol apparently is promoting stabilization that in turn protects the enzyme against thermal inactivation. This protective effect is reflected in a decrease of inactivation rate values and energy released during enzyme catalysis. The modification of many membrane properties throughout million of years made it possible for new evolutionary driving forces to show themselves as new characteristics in eukaryotes such as the one discussed in this study, dealing with the presence of cholesterol in the cell membrane directly associated to the promotion of protein thermostability.

Animals↗

Evolution of subgroup A respiratory syncytial virus: evidence for progressive accumulation of amino acid changes in the attachment protein.

The variability of the attachment (G) proteins of 48 subgroup A isolates of respiratory syncytial virus (RSV) isolated over 38 years has been examined. Nucleotide sequences of two variable regions of the G protein genes were determined following amplification by PCR. The isolates showed temporal rather than geographical clustering, and there was evidence for progressive accumulation of amino acid changes at an average rate of approximately 0.25% per year estimated over the entire protein. The cocirculation of lineages of RSV at present appears to be the result of a process of evolution and survival of particular genotypes and the extinction of others. Analysis of reactivity of the isolates with monoclonal antibodies showed that their antigenic profiles closely paralleled their relatedness by nucleotide sequence, suggesting that antigenic drift due to immune selection may be occurring.

Amino Acid Sequence↗

Ion-Pair Charge-Transfer Complexes Based on (o-Phenylenebis(oxamato))cuprate(II) and Cyclic Diquaternary Cations of 1,10-Phenanthroline and 2,2'-Bipyridine: Synthesis, Crystal Structure, and Physical Properties.

The ion pair charge-transfer (IPCT) complexes (C(14)H(12)N(2))[Cu(opba)].3H(2)O (1) and Na(2)(C(12)H(12)N(2))[Cu(opba)](2).4H(2)O (2), opba = o-phenylenebis(oxamate), have been isolated. Both compounds crystallize in the triclinic space group P&onemacr;. Crystal data for the compounds 1, a = 7.3216(13) Å, b = 10.1756(9) Å, c = 16.4890(16) Å, alpha = 107.786(8) degrees, beta = 94.79(1) degrees, gamma = 104.16(1) degrees, V = 1117.4(3) Å(3), Z = 2, R = 0.033 for 5332 observed reflections with I > 3sigma(I); 2, a = 6.732(3) Å, b = 11.169(3) Å, c = 12.126(2) Å, alpha = 111.01(2) degrees, beta = 102.71(3) degrees, gamma = 93.57(3) degrees, V = 820.1(5) Å(3), Z = 2, R = 0.065 for 3354 observed reflections with I > 3sigma(I). The crystal structures consist of alternated anion complex and diquaternary cation layers pi-pi interacting through the corresponding aromatic rings. The metallic layers contain the [Cu(opba)](2)(4)(-) dimeric group where the copper(II) ions are in square-pyramidal environment. For both compounds an ion-pair charge-transfer (IPCT) band is observed at 517 nm. Their thermal behavior has also been explained on the basis of the different crystal arrangements. The dimeric nature of compound 1 is clearly confirmed by the observation of temperature-dependent ESR transitions between its singlet and triplet states. The |J| value, determined from the positions of these transitions, is 0.085 cm(-)(1) at room temperature and increases notably with decreasing temperature being 0.14 cm(-)(1) at 4.2 K. Comparison of these exchange constants with those observed for other carboxylate-bridged copper compounds allow us to deduce that the temperature dependence of J is due to lattice shrinkage leading to appreciable change of the Cu-O(ap) distance. The ESR spectrum of compound 2 is characteristic of an axial g-tensor with g( parallel) = 2.178 and g( perpendicular) = 2.049, showing a weak half-field DeltaM(s) = 2 transition in agreement with the dimeric nature of the complex. The thermal evolution of the magnetic susceptibility corresponds to a compound with weak antiferromagnetic interactions. The best fit of the magnetic data to a dimer S = (1)/(2) model gives J = -0.8 cm(-)(1), in good agreement with the topology of the bridging unit with the magnetic orbitals in parallel planes and a Cu-O-Cu angle of 95.4 degrees.

Journal Article↗

Additive Effects on the Microstructure Evolution in Hexadecyltrimethylammonium Bromide Solution and Its Rheological Properties

The effects of various additives on the microstructure evolution in hexadecyltrimethylammonium bromide micellar solution and its rheological properties are investigated. The additives considered in the present study are primary, secondary, and tertiary heptanols and sodium salicylate (NaSal). The microstructure is developed via the two-step shape transitions in the micellar solution; first, the initial spherical micelles undergo shape transition to rod-like or disc-like micelles as the micelles tend to be packed compactly with increase in the surfactant concentration; then further increment in the surfactant concentration makes the anisotropic rod-like micelles overlap each other. Solutions in these states exhibit typical non-Newtonian behaviors such as shear thinning at high shear rates. In the present study, the additive effects on the microstructure evolution are investigated by employing various techniques including a phase modulated flow birefringence, a dynamic light scattering and a dynamic oscillatory rheometry. The results show that addition of the solubilized additives enhances the microstructure transitions, which are affected by the additive concentration and its chemical structure. Presence of the cosurfactants such as heptanols with hydrophobic alkyl chains reduces the repulsion by forming surfactant-alcohol mixed micelles. The primary heptanol can penetrate easily into the micelles and aligned parallel to the surfactant molecules compared with the secondary and tertiary heptanols. Thus, the primary heptanol enhances the two-step shape evolutions more effectively than the other types. In the presence of NaSal, on the other hand, the micellar solution exhibits the viscoelastic properties and the yield stress owing to the formation of networked or worm-like micelles. Copyright 1997 Academic Press. Copyright 1997Academic Press

Journal Article↗

Evolution of leaf developmental mechanisms.

Leaves are determinate organs produced by the shoot apical meristem. Land plants demonstrate a large range of variation in leaf form. Here we discuss evolution of leaf form in the context of our current understanding of leaf development, as this has emerged from molecular genetic studies in model organisms. We also discuss specific examples where parallel studies of development in different species have helped understanding how diversification of leaf form may occur in nature.

Biological Evolution↗

Phylogenetic position of Mediterranean Astereae and character evolution of daisies (Bellis, Asteraceae) inferred from nrDNA ITS sequences.

Phylogenetic analyses of nrITS sequences of Asteraceae revealed that the Bellis group is a natural assemblage comprising all the species of Bellis and Bellium, but not Rhynchospermum. In contrast, we propose to include the genera Bellis, Bellium, and Bellidastrum in the subtribe Bellidinae in the interest of circumscribing natural groups. Our results also suggest an early diversification in the western Mediterranean Basin of two monophyletic lineages, Bellis and Bellium. Three major groups can be distinguished within BELLIS: (1) the B. perennis group, containing five annual and perennial species with three ploidy levels (diploid, octoploid, and decaploid), which are distributed throughout the Mediterranean Basin despite lack of pappus; (2) the Bellis sylvestris group, with five annual and perennial species primarily from the western Mediterranean, in which there are five ploidy levels (diploid, tetraploid, hexaploid, octoploid, and decaploid); and (3) a basal grade consisting of three diploid, perennial species which displays remarkable diversification of morphologies. Striking characteristics, such as an annual life form, polyploidy, and loss of pappus, seem to have occurred in parallel several times and in different geographical areas during the early diversification of Bellis species in the western Mediterranean. Character evolution reconstructions allow us to describe a putative ancestor of the genus Bellis (proto-Bellis).

Asteraceae↗

Molecular phylogeny and evolution of morphology in the social amoebas.

The social amoebas (Dictyostelia) display conditional multicellularity in a wide variety of forms. Despite widespread interest in Dictyostelium discoideum as a model system, almost no molecular data exist from the rest of the group. We constructed the first molecular phylogeny of the Dictyostelia with parallel small subunit ribosomal RNA and a-tubulin data sets, and we found that dictyostelid taxonomy requires complete revision. A mapping of characters onto the phylogeny shows that the dominant trend in dictyostelid evolution is increased size and cell type specialization of fruiting structures, with some complex morphologies evolving several times independently. Thus, the latter may be controlled by only a few genes, making their underlying mechanisms relatively easy to unravel.

Animals↗

Simulation of progressive deformities in adolescent idiopathic scoliosis using a biomechanical model integrating vertebral growth modulation.

While the etiology and pathogenesis of adolescent idiopathic scoliosis are still not well understood, it is generally recognized that it progresses within a biomechanical process involving asymmetrical loading of the spine and vertebral growth modulation. This study intends to develop a finite element model incorporating vertebral growth and growth modulation in order to represent the progression of scoliotic deformities. The biomechanical model was based on experimental and clinical observations, and was formulated with variables integrating a biomechanical stimulus of growth modulation along directions perpendicular (x) and parallel (y, z) to the growth plates, a sensitivity factor beta to that stimulus and time. It was integrated into a finite element model of the thoracic and lumbar spine, which was personalized to the geometry of a female subject without spinal deformity. An imbalance of 2 mm in the right direction at the 8th thoracic vertebra was imposed and two simulations were performed: one with only growth modulation perpendicular to growth plates (Sim1), and the other one with additional components in the transverse plane (Sim2). Semi-quantitative characterization of the scoliotic deformities at each growth cycle was made using regional scoliotic descriptors (thoracic Cobb angle and kyphosis) and local scoliotic descriptors (wedging angle and axial rotation of the thoracic apical vertebra). In all simulations, spinal profiles corresponded to clinically observable configurations. The Cobb angle increased non-linearly from 0.3 degree to 34 degrees (Sim1) and 20 degrees (Sim2) from the first to last growth cycle, adequately reproducing the amplifying thoracic scoliotic curve. The sagittal thoracic profile (kyphosis) remained quite constant. Similarly to clinical and experimental observations, vertebral wedging angle of the thoracic apex progressed from 2.6 degrees to 10.7 degrees (Sim1) and 7.8 degrees (Sim2) with curve progression. Concomitantly, vertebral rotation of the thoracic apex increased of 10 degrees (Sim1) and 6 degrees (Sim2) clockwise, adequately reproducing the evolution of axial rotation reported in several studies. Similar trends but of lesser magnitude (Sim2) suggests that growth modulation parallel to growth plates tend to counteract the growth modulation effects in longitudinal direction. Overall, the developed model adequately represents the self-sustaining progression of vertebral and spinal scoliotic deformities. This study demonstrates the feasibility of the modeling approach, and compared to other biomechanical studies of scoliosis it achieves a more complete representation of the scoliotic spine.

Adolescent↗

Inhibition of oxygen evolution in chloroplasts by ferricyanide.

Preincubation of chloroplasts from pea leaves (Pisum sativum L. cv. Kelvedon) with 0.5 millimolar ferricyanide in the dark, caused a parallel inhibition of the rate of rise of the variable fluorescence and the rate of electron transport. Both reactions were inhibited to a similar extent by varying the time of preincubation, the concentration of ferricyanide during preincubation, and by raising the concentration of salts in the preincubation medium. Ferricyanide treatment of Tris-washed chloroplasts did not inhibit electron transport from the Photosystem II (PSII) electron donor 1,5-diphenylcarbazide to methylviologen. The inhibition of the variable fluorescence rise and of NADP reduction (caused by ferricyanide pretreatment) was bypassed by addition of the PSII electron donor couple hydroquinone/ascorbate. It was concluded that preincubation of chloroplasts with ferricyanide in the dark inhibited electron transport between water and PSII.

Journal Article↗