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Functional Implications (functional + implication)
Kinds of Functional Implications Selected AbstractsTHE MORPHOLOGY OF HYOLITHIDS AND ITS FUNCTIONAL IMPLICATIONSPALAEONTOLOGY, Issue 6 2005MÓNICA MARTÍ MUS Abstract:, The exceptionally preserved hyolithids Gompholites striatulus, Maxilites robustus, Maxilites snajdri and Maxilites sp. are described with particular emphasis on helen and muscle scar morphology. These two aspects of hyolithid morphology have remained controversial. In life position, each helen curved ventrally. When the operculum closed the aperture of the conch, each helen was locked at the commissure slit with its dorsal edge tilted forward. Inside the conch, it was held in the dorsal apertural plane and clear of the inner surface of the operculum. Previously unidentified muscle scars are described from both the operculum and the conch. Dorsal scars on the conch aperture held muscles directed to the operculum. Comparative study of the muscle insertion pattern indicates that hyolithids did not have serially arranged muscles and that all hyolithids may have had a common skeleto-muscular system. The arrangement of the muscle scars with respect to the helens suggests that the latter were capable of relatively complex movements and could have been used to propel the organism over the substrate. The general morphology and orientation of the helens suggests that in addition they functioned to stabilize the organism on the sea-floor. [source] REFLEXLY EVOKED COACTIVATION OF CARDIAC VAGAL AND SYMPATHETIC MOTOR OUTFLOWS: OBSERVATIONS AND FUNCTIONAL IMPLICATIONSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2006Julian FR Paton SUMMARY 1The purpose of the present review is to highlight the pattern of activity in the parasympathetic and sympathetic nerves innervating the heart during their reflex activation. 2We describe the well-known reciprocal control of cardiac vagal and sympathetic activity during the baroreceptor reflex, but point out that this appears to be the exception rather than the rule and that many other reflexes reviewed herein (e.g. peripheral chemoreceptor, nociceptor, diving response and oculocardiac) involve simultaneous coactivation of both autonomic limbs. 3The heart rate response during simultaneous activation of cardiac autonomic outflows is unpredictable because it does not simply reflect the summation of opposing influences. Indeed, it can result in bradycardia (peripheral chemoreceptor, diving and corneal), tachycardia (nociceptor) and, in some circumstances, can predispose to malignant arrhythmias. 4We propose that this cardiac autonomic coactivation may allow greater cardiac output during bradycardia (increased ventricular filling time and stronger contraction) than activation of the sympathetic limb alone. This may be important when pumping blood into a constricted vascular tree, such as is the case during the peripheral chemoreceptor reflex and the diving response. [source] Functional implications of pigments bound to a cyanobacterial cytochrome b6f complexFEBS JOURNAL, Issue 2 2005Stephan-Olav Wenk A highly purified cytochrome b6f complex from the cyanobacterium Synechocystis sp. PCC 6803 selectively binds one chlorophyll a and one carotenoid in analogy to the recent published structure from two other b6f complexes. The unknown function of these pigments was elucidated by spectroscopy and site-directed mutagenesis. Low-temperature redox difference spectroscopy showed red shifts in the chlorophyll and carotenoid spectra upon reduction of cytochrome b6, which indicates coupling of these pigments with the heme groups and thereby with the electron transport. This is supported by the correlated kinetics of these redox reactions and also by the distinct orientation of the chlorophyll molecule with respect to the heme cofactors as shown by linear dichroism spectroscopy. The specific role of the carotenoid echinenone for the cytochrome b6f complex of Synechocystis 6803 was elucidated by a mutant lacking the last step of echinenone biosynthesis. The isolated mutant complex preferentially contained a carotenoid with 0, 1 or 2 hydroxyl groups (most likely 9- cis isomers of ,-carotene, a monohydroxy carotenoid and zeaxanthin, respectively) instead. This indicates a substantial role of the carotenoid , possibly for strucure and assembly , and a specificity of its binding site which is different from those in most other oxygenic photosynthetic organisms. In summary, both pigments are probably involved in the structure, but may also contribute to the dynamics of the cytochrome b6f complex. [source] Ontogeny of escape swimming performance in the spotted salamanderFUNCTIONAL ECOLOGY, Issue 3 2010Tobias Landberg Summary 1.,The life stage suffering the highest predation rate is expected to have the highest escape performance unless developmental or functional constraints interfere. Peak aquatic escape performance in ephemeral pond-breeding amphibians is expected to develop early in the larval period, and metamorphosis is expected to reduce or completely disrupt aquatic escape performance. In anurans, exceptionally low escape performance during metamorphosis creates selection favouring rapid metamorphosis , which minimizes the time individuals spend in the vulnerable transition between tadpole and frog. 2.,We investigated the development of aquatic escape performance in the spotted salamander, Ambystoma maculatum (Shaw, 1802), from embryonic development through metamorphosis. We expected performance to peak early in the larval period as hatchlings face high rates of predation but embryos must first develop escape behaviours. We also tested whether escape performance during metamorphosis was intermediate, as predicted by tail fin resorption, or lower than larvae and adults indicating a major physiological disruption. 3.,Escape performance shows a complex ontogeny that is first positively influenced by embryonic and early larval development and then negatively correlated with tail resorption and body size. Escape distance was the only performance metric not affected by life stage. In contrast, both escape velocity and duration showed ontogenetic peaks early in the larval period with the lowest performance found in early embryos and adults and intermediate performance during metamorphosis. 4.,This pattern suggests that metamorphosis does not impose a major physiological disruption on escape performance. Because spotted salamanders do not pass through a frog-like ,ontogenetic performance valley' during metamorphosis, they may be less subject than anurans to selection favouring rapid metamorphosis. 5.,Functional implications of phenotypic variation should be considered in an ontogenetic framework because the relationship between body size and escape performance can be reversed on either side of an ontogenetic performance peak. The assumption that metamorphosis radically disrupts basic functions such as predator evasion does not seem universally warranted and suggests examination of ontogenetic performance trajectories in a diversity of animals with complex life cycles. [source] GFAP: Functional implications gleaned from studies of genetically engineered miceGLIA, Issue 1 2003Albee Messing Abstract GFAP is the major intermediate filament of mature astrocytes, and its relatively specific expression in these cells suggests an important function. To study the role of the GFAP gene, mice have been created carrying null alleles (no protein), modified alleles (altered protein), or added wild type alleles (elevated protein). Surprisingly, absence of GFAP has relatively subtle effects on development. On the other hand, over-expression can be lethal, and led to the discovery that GFAP coding mutations are responsible for most cases of Alexander disease, a devastating neurodegenerative disorder. Here we review what the various GFAP mouse models reveal about GFAP and astrocyte function. GLIA 43:87,90, 2003. © 2003 Wiley-Liss, Inc. [source] Sulfation of nitrotyrosine: Biochemistry and functional implicationsIUBMB LIFE, Issue 10 2007Ming-Cheh Liu Abstract Nitration of tyrosine, in both protein-bound form and free amino acid form, can readily occur in cells under oxidative/nitrative stress. In addition to serving as a biomarker of oxidative/nitrative stress, elevated levels of nitrotyrosine have been shown to cause DNA damage or trigger apoptosis. An important issue is whether the human body is equipped with mechanisms to counteract the potentially harmful effects of nitrotyrosine. Sulfate conjugation, as mediated by the cytosolic sulfotransferases (SULTs), is widely used for the biotransformation and disposal of a variety of drugs and other xenobiotics, as well as endogenous thyroid/steroid hormones and catecholamine neurotransmitters. Recent studies have revealed that the sulfation of nitrotyrosine occurs in cells under oxidative/nitrative stress, and have pinpointed the SULT1A3 as the responsible SULT enzyme. In this review, we summarized the available information concerning the biochemistry of nitrotyrosine sulfation and the effects of genetic polymorphisms on the nitrotyrosine sulfating activity of SULT1A3. Functional implications of the sulfation of nitrotyrosine are discussed. IUBMB Life, 622-627, 2007 [source] Interspecific variation in sternohyoideus muscle morphology in clariid catfishes: Functional implications for suction feeding,JOURNAL OF MORPHOLOGY, Issue 3 2007Sam Van Wassenbergh Abstract Depression of the hyoid apparatus plays a crucial role in generating suction, especially in fishes with a dorso-ventrally flattened head shape. It is generally assumed that shortening of the sternohyoideus muscle, which connects the hyoid to the pectoral girdle, contributes to hyoid depression. However, a recent study on the clariid catfish Clarias gariepinus has shown that this muscle does not shorten but elongates during this phase through retraction of the pectoral girdle. Here, we test whether this pattern is general among clariid catfish, or if variation in the morphology of the sternohyoideus may result in a different sternohyoideus behavior during hyoid depression. First, sternohyoideus mass, effective cross-sectional area, fiber length and fiber diameter were measured and compared for four clariid species. Next, velocity and magnitude of hyoid depression during prey capture (from high-speed videos), as well as patterns of sternohyoideus strain were analyzed (from high-speed X-ray videos) in these species. While morphology and hyoid depression performance varied considerably among these species, only the species with the most massive sternohyoideus, Gymnallabes typus, showed shortening of the sternohyoideus muscle during the initial part of the expansive phase. The data for Channallabes apus demonstrate that increasing the magnitude of hyoid depression does not necessarily require a shortening of the m. sternohyoideus, as it shows elongation of this muscle during hyoid depression. J. Morphol., 2007. © 2007 Wiley-Liss, Inc. [source] Functional implications for Kir4.1 channels in glial biology: from K+ buffering to cell differentiationJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Michelle L. Olsen Abstract Astrocytes and oligodendrocytes are characterized by a very negative resting potential and a high resting permeability for K+ ions. Early pharmacological and biophysical studies suggested that the resting potential is established by the activity of inwardly rectifying, Ba2+ sensitive, weakly rectifying Kir channels. Molecular cloning has identified 16 Kir channels genes of which several mRNA transcripts and protein products have been identified in glial cells. However, genetic deletion and siRNA knock-down studies suggest that the resting conductance of astrocytes and oligodendrocytes is largely due to Kir4.1. Loss of Kir4.1 causes membrane depolarization, and a break-down of K+ and glutamate homeostasis which results in seizures and wide-spread white matter pathology. Kir channels have also been shown to act as critical regulators of cell division whereby Kir function is correlated with an exit from the cell cycle. Conversely, loss of functional Kir channels is associated with re-entry of cells into the cell cycle and gliosis. A loss of functional Kir channels has been shown in a number of neurological diseases including temporal lobe epilepsy, amyotrophic lateral sclerosis, retinal degeneration and malignant gliomas. In the latter, expression of Kir4.1 is sufficient to arrest the aberrant growth of these glial derived tumor cells. Kir4.1 therefore represents a potential therapeutic target in a wide variety of neurological conditions. [source] Functional implications of radial diaphyseal curvatureAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2009Ignasi Galtés Abstract A recent study (Galtés et al.: Am J Phys Anthropol 135 (2008) 293-300) demonstrated that during pronation, pronator teres exerts a favorable force for radial lateral bending. On the basis of this finding, we hypothesized that the pattern of muscular loading exerted on the radius by this muscle might play a role as a mechanical stimulus involved in radial bowing. The current work relates the hypertrophy of the forearm muscles to the degree of lateral curvature of the radial diaphysis. The analysis is based on an original osteometrical index to estimate radial curvature, and it applies a visual reference method to grade the osteological appearance of 10 entheses of 104 radii from archaeological and contemporary samples. Using these morphological data as an indirect method to measure the association between muscular hypertrophy and bone curvature, this study reveals that the pattern of muscular loading exerted on the apex of the radial shaft by the pronator teres muscle may play an important role as a mechanical stimulus involved in diaphyseal bowing. Am J Phys Anthropol, 2009. © 2008 Wiley-Liss, Inc. [source] Disulfide bond formation through Cys186 facilitates functionally relevant dimerization of trimeric hyaluronan-binding protein 1 (HABP1)/p32/gC1qRFEBS JOURNAL, Issue 1 2002Babal Kant Jha Hyaluronan-binding protein 1 (HABP1), a ubiquitous multifunctional protein, interacts with hyaluronan, globular head of complement component 1q (gC1q), and clustered mannose and has been shown to be involved in cell signalling. In vitro, this recombinant protein isolated from human fibroblast exists in different oligomeric forms, as is evident from the results of various independent techniques in near-physiological conditions. As shown by size-exclusion chromatography under various conditions and glutaraldehyde cross-linking, HABP1 exists as a noncovalently associated trimer in equilibrium with a small fraction of a covalently linked dimer of trimers, i.e. a hexamer. The formation of a covalently-linked hexamer of HABP1 through Cys186 as a dimer of trimers is achieved by thiol group oxidation, which can be blocked by modification of Cys186. The gradual structural transition caused by cysteine-mediated disulfide linkage is evident as the fluorescence intensity increases with increasing Hg2+ concentration until all the HABP1 trimer is converted into hexamer. In order to understand the functional implication of these transitions, we examined the affinity of the hexamer for different ligands. The hexamer shows enhanced affinity for hyaluronan, gC1q, and mannosylated BSA compared with the trimeric form. Our data, analyzed with reference to the HABP1/p32 crystal structure, suggest that the oligomerization state and the compactness of its structure are factors that regulate its function. [source] Distribution of peroxisome proliferator,activated receptor,gamma polymorphisms in Chinese and Dutch patients with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2010Umid Kumar Shrestha Abstract Background: As peroxisome proliferator,activated receptor,gamma (PPAR-,) is frequently expressed in colon, its genetic polymorphism may play a role in the etiology of inflammatory bowel disease (IBD). The aims of the present study were to determine the distribution of PPAR-, polymorphisms Pro12Ala and C161T and to explore the association between the PPAR-, genotypes and phenotypes of IBD patients. Methods: A total of 244 IBD patients [212 ulcerative colitis (UC) and 32 Crohn's disease (CD)] and 220 controls in the Chinese population and 603 IBD patients (302 UC and 301 CD) and 180 controls in the white Dutch population were enrolled in the study. The phenotypes of Chinese IBD patients were grouped according to disease location. The PPAR-, polymorphisms Pro12Ala and C161T were genotyped by PCR-based methods. Results: In the Chinese population, T carriers of the PPAR-, C161T polymorphism were more common in UC patients than in the controls [37.7% vs. 25.5%, odds ratio 1.77, 95% confidence interval 1.18,2.68, P = 0.007], whereas Ala carriers of the Pro12Ala polymorphism showed no significant association in UC patients, but there was a significant association of Ala carriers with more extensive disease among the UC patients (P = 0.002); Pro12Ala and C161T genotypes did not show any associations with CD patients. No associations were found for the PPAR-, C161T SNP studied in the Dutch IBD population. Conclusions: Our study showed the potential association between the PPAR-, C161T polymorphism and UC patients in the central Chinese population. This finding was not replicated in the Dutch population. Further studies are necessary to explore the functional implication of the PPAR-, C161T polymorphism in Chinese UC patients. (Inflamm Bowel Dis 2009;) [source] Propagation of spreading depression inversely correlates with cortical myelin content,ANNALS OF NEUROLOGY, Issue 3 2009Doron Merkler MD Objective Cortical myelin can be severely affected in patients with demyelinating disorders of the central nervous system. However, the functional implication of cortical demyelination remains elusive. In this study, we investigated whether cortical myelin influences cortical spreading depression (CSD). Methods CSD measurements were performed in rodent models of toxic and autoimmune induced cortical demyelination, in neuregulin-1 type I transgenic mice displaying cortical hypermyelination, and in glial fibrillary acidic protein,transgenic mice exhibiting pronounced astrogliosis. Results Cortical demyelination, but not astrogliosis or inflammation per se, was associated with accelerated CSD. In contrast, hypermyelinated neuregulin-1 type I transgenic mice displayed a decelerated CSD propagation. Interpretation Cortical myelin may be crucially involved in the stabilization and buffering of extracellular ion content that is decisive for CSD propagation velocity and cortical excitability, respectively. Our data thus indicate that cortical involvement in human demyelinating diseases may lead to relevant alterations of cortical function. Ann Neurol 2009;66:355,365 [source] Transnatal olfactory continuity in the rabbit: Behavioral evidence and short-term consequence of its disruptionDEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2002Gérard Coureaud Abstract This study investigates the role of prenatal odor learning on postnatal adaptive orientation responses in the newborn rabbit. Preference tests revealed that pups are equally attracted to the odors of placentae and colostrum (Experiments 1,4), suggesting that an odor continuity may exist between the fetal and neonatal environments. To test some predictions derived from this hypothesis, we manipulated the odor of the diet of pregnant-lactating does to control the chemical niches of their perinates. Fetuses exposed in this way to the odor of cumin (C) were selectively attracted as neonates to the odor of pure C (Experiment 6). Prenatal exposure to C also was followed, to a certain extent, by enhanced attraction to C odor in the placenta or colostrum from females which had consumed it (Experiments 5 & 7). Finally, the functional implications of perinatal odor continuity were tested by disrupting it. The odor component of the feto,neonatal transitional environment revealed indeed to affect the ability of certain pups to gain colostrum and milk at the very first sucking opportunities (Experiment 8). © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 372,390, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10038 [source] Differential loss and preservation of glutamate receptor function in bipolar cells in the rd10 mouse model of retinitis pigmentosaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009Theresa Puthussery Abstract Photoreceptor degenerations can trigger morphological alterations in second-order neurons, however, the functional implications of such changes are not well known. We conducted a longitudinal study, using whole-cell patch-clamp, immunohistochemistry and electron microscopy to correlate physiological with anatomical changes in bipolar cells of the rd10 mouse , a model of autosomal recessive retinitis pigmentosa. Rod bipolar cells (RBCs) showed progressive changes in mGluR6-induced currents with advancing rod photoreceptor degeneration. Significant changes in response amplitude and kinetics were observed as early as postnatal day (P)20, and by P45 the response amplitudes were reduced by 91%, and then remained relatively stable until 6 months. These functional changes correlated with the loss of rod photoreceptors and mGluR6 receptor expression. Moreover, we showed that RBCs make transient ectopic connections with cones during progression of the disease. At P45, ON-cone bipolar cells (ON-CBCs) retain mGluR6 responses for longer periods than the RBCs, but by about 6 months these cells also strongly downregulate mGluR6 expression. We propose that the relative longevity of mGluR6 responses in CBCs is due to the slower loss of the cones. In contrast, ionotropic glutamate receptor expression and function in OFF-CBCs remains normal at 6 months despite the loss of synaptic input from cones. Thus, glutamate receptor expression is differentially regulated in bipolar cells, with the metabotropic receptors being absolutely dependent on synaptic input. These findings define the temporal window over which bipolar cells may be receptive to photoreceptor repair or replacement. [source] In vivo neurogenesis in the adult brain: regulation and functional implicationsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2000Eberhard Fuchs First page of article [source] Life-history strategies in freshwater macroinvertebratesFRESHWATER BIOLOGY, Issue 9 2008WILCO C. E. P. VERBERK Summary 1Explaining spatial and temporal differences in species assemblages is a central aim of ecology. It requires a sound understanding of the causal mechanisms underlying the relationship of species with their environment. A species trait is widely acknowledged to be the key that links pattern and process, although the enormous variety of traits hampers generalization about which combination of traits are adaptive in a particular environment. 2In three steps, we used species traits to match species and environment, and chose lentic freshwater ecosystems to illustrate our approach. We first identified key environmental factors and selected the species traits that enable the organism to deal with them. Secondly, we investigated how investments in these traits are related (e.g. through trade-offs). Thirdly, we outlined 13 life-history strategies, based on biological species traits, their interrelations known from life-history theory and their functional implications. 3Species traits and environmental conditions are connected through life-history strategies, with different strategies representing different solutions to particular ecological problems. In addition, strategies may present an integrated response to the environment as they are based on many different traits and their interrelationships. The presence and abundance of (species exhibiting) different life-history strategies in a location may therefore give direct information about how a particular environment is experienced by the species present. 4Life-history strategies can be used to (i) explain differences in species assemblages either between locations or in different periods; (ii) compare waterbodies separated by large geographical distances, which may comprise different regional species pools or span species distribution areas and (iii) reduce often very complex, biodiverse assemblages into a few meaningful, easily interpretable relationships. [source] The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8GENES TO CELLS, Issue 7 2004Kenji Sugawara Microtubule-associated protein light chain 3 (LC3), a mammalian homologue of yeast Atg8, plays an essential role in autophagy, which is involved in the bulk degradation of cytoplasmic components by the lysosomal system. Here, we report the crystal structure of LC3 at 2.05 Ĺ resolution with an R-factor of 21.8% and a free R-factor of 24.9%. The structure of LC3, which is similar to those of Golgi-associated ATPase enhancer of 16 kDa (GATE-16) and GABAA receptor-associated protein (GABARAP), contains a ubiquitin core with two , helices, ,1 and ,2, attached at its N-terminus. Some common and distinct features are observed among these proteins, including the conservation of residues required to form an interaction among ,1, ,2 and the ubiquitin core. However, the electrostatic potential surfaces of these helices differ, implicating particular roles to select specific binding partners. Hydrophobic patches on the ubiquitin core of LC3, GABARAP and GATE-16 are well conserved and are similar to the E1 binding surface of ubiquitin and NEDD8. Therefore, we propose that the hydrophobic patch is a binding surface for mammalian Atg7 similar to a ubiquitin-like conjugation system. We also propose the functional implications of the ubiquitin fold as a recognition module of target proteins. [source] Combined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and functionHAEMOPHILIA, Issue 4 2009A. MARKOFF Summary., Most small lesions in the factor VIII (FVIII) gene that cause haemophilia A (HA) are single nucleotide substitutions resulting in amino acid replacing (missense) mutations and leading to various phenotypes, ranging from mild to severe. We took a combined approach of homology modelling and quantitative evaluation of evolutionary significance of amino acid replacing alterations using the Grantham Matrix Score (GMS) to assess their structural effects and significance of pathological expression. Comparative homology models of all amino acid substitutions summarized in the FVIII mutations database plus these identified and reported lately by us or by our collaborators were evaluated. Altogether 640 amino acid replacing mutations were scored for potential distant or local conformation changes, influence on the molecular stability and predicted contact residues, using available FVIII domain models. The average propensity to substitute amino acid residues by mutation was found comparable to the overall probability of de novo mutations. Missense changes reported with various HA phenotypes were all confirmed significant using GMS. The fraction of these, comprising residues apparently involved in intermolecular interactions, exceeds the average proportion of such residues for FVIII. Predicted contact residues changed through mutation were visualized on the surface of FVIII domains and their possible functional implications were verified from the literature and are discussed considering available structural information. Our predictive modelling adds on the current view of domain interface molecular contacts. This structural insight could aid in part to the design of engineered FVIII constructs for therapy, to possibly enhance their stability and prolong circulating lifetime. [source] Polymorphism of LMP2, TAP1, LMP7 and TAP2 in Brazilian Amerindians and Caucasoids: implications for the evolution of allelic and haplotypic diversityINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2000F. Rueda Faucz In the class II region of the major histocompatibility complex (MHC), four genes implicated in processing of MHC class I-presented antigens have been described. Two of these (TAP1 and TAP2) code for endoplasmic reticulum membrane transporter proteins and the other two (LMP2 and LMP7) for proteasome subunits. These genes are polymorphic, although much less so than classical MHC class I and II genes. There is controversy concerning the possible functional implications of this variation. Population genetics is one of the means of investigating the evolutionary and functional significance of genetic polymorphisms; however, few populations have been analysed with respect to TAP and LMP diversity. We present here the polymorphism of TAP1, TAP2, LMP2 and LMP7 genes in the Kaingang and Guarani Amerindian tribes, and in the Caucasoid population of the Brazilian State of Paraná. Allele frequencies found in the Caucasoids were close to those described for similar populations. Amerindians had a somewhat more restricted polymorphism, and allele and haplotype frequencies differed greatly between the two tribes. Overall linkage disequilibrium (LD) between the four genes was low in the Caucasoids, but high in the Amerindians, for which significant LD was seen for all informative pairs of loci. Comparing results of this and previous studies we observed that, whenever significant LD occurs in non-Amerindians, it tends to be similar in the different ethnic groups. While this might be interpreted as evidence of co-evolution of genes in the TAP-LMP region, the high haplotypic diversity in all populations and low LD in non-Amerindians indicate absence of co-evolution of the different genes. Distributions of allele and genotype frequencies are consistent with the hypothesis of selective neutrality. We conclude that genetic polymorphism of the human TAP and LMP genes and haplotypes is of little, if any, functional significance. [source] Sulfation of nitrotyrosine: Biochemistry and functional implicationsIUBMB LIFE, Issue 10 2007Ming-Cheh Liu Abstract Nitration of tyrosine, in both protein-bound form and free amino acid form, can readily occur in cells under oxidative/nitrative stress. In addition to serving as a biomarker of oxidative/nitrative stress, elevated levels of nitrotyrosine have been shown to cause DNA damage or trigger apoptosis. An important issue is whether the human body is equipped with mechanisms to counteract the potentially harmful effects of nitrotyrosine. Sulfate conjugation, as mediated by the cytosolic sulfotransferases (SULTs), is widely used for the biotransformation and disposal of a variety of drugs and other xenobiotics, as well as endogenous thyroid/steroid hormones and catecholamine neurotransmitters. Recent studies have revealed that the sulfation of nitrotyrosine occurs in cells under oxidative/nitrative stress, and have pinpointed the SULT1A3 as the responsible SULT enzyme. In this review, we summarized the available information concerning the biochemistry of nitrotyrosine sulfation and the effects of genetic polymorphisms on the nitrotyrosine sulfating activity of SULT1A3. Functional implications of the sulfation of nitrotyrosine are discussed. IUBMB Life, 622-627, 2007 [source] Yao C, Stern P, Zhang L. Elevated expression of CaMKII, during osteoclastogenesis and its functional implications.JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2009J Cell Biochem 2006; DOI 10.1002/jcb.2115 The original article to which this Retraction refers was published in J Cell Biochem 2006; DOI 10.1002/jcb.21155. © 2006 Wiley-Liss, Inc.. [source] Simultaneous inhibition of anti-coagulation and inflammation: crystal structure of phospholipase A2 complexed with indomethacin at 1.4,Ĺ resolution reveals the presence of the new common ligand-binding siteJOURNAL OF MOLECULAR RECOGNITION, Issue 6 2009Nagendra Singh Abstract A novel ligand-binding site with functional implications has been identified in phospholipase A2 (PLA2). The binding of non-steroidal anti-inflammatory agent indomethacin at this site blocks both catalytic and anti-coagulant actions of PLA2. A group IIA PLA2 has been isolated from Daboia russelli pulchella (Russell's viper) which is enzymatically active as well as induces a strong anti-coagulant action. The binding studies have shown that indomethacin reduces the effects of both anti-coagulant and pro-inflammatory actions of PLA2. A group IIA PLA2 was co-crystallized with indomethacin and the structure of the complex has been determined at 1.4,Ĺ resolution. The structure determination has revealed the presence of an indomethacin molecule in the structure of PLA2 at a site which is distinct from the conventional substrate-binding site. One of the carboxylic group oxygen atoms of indomethacin interacts with Asp 49 and His 48 through the catalytically important water molecule OW 18 while the second carboxylic oxygen atom forms an ionic interaction with the side chain of Lys 69. It is well known that the residues, His 48 and Asp 49 are essential for catalysis while Lys 69 is a part of the anti-coagulant loop (residues, 54,77). Indomethacin binds in such a manner that it blocks the access to both, it works as a dual inhibitor for catalytic and anti-coagulant actions of PLA2. This new binding site in PLA2 has been observed for the first time and indomethacin is the first compound that has been shown to bind at this novel site resulting in the prevention of anti-coagulation and inflammation. Copyright © 2009 John Wiley & Sons, Ltd. [source] Differential phosphorylation of myosin light chain (Thr)18 and (Ser)19 and functional implications in plateletsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2010T. M. GETZ Summary. Background:, Myosin IIA is an essential platelet contractile protein that is regulated by phosphorylation of its regulatory light chain (MLC) on residues (Thr)18 and (Ser)19 via the myosin light chain kinase (MLCK). Objective:, The present study was carried out to elucidate the mechanisms regulating MLC (Ser)19 and (Thr)18 phosphorylation and the functional consequence of each phosphorylation event in platelets. Results:, Induction of 2MeSADP-induced shape change occurs within 5 s along with robust phosphorylation of MLC (Ser)19 with minimal phosphorylation of MLC (Thr)18. Selective activation of G12/13 produces both slow shape change and comparably slow MLC (Thr)18 and (Ser)19 phosphorylation. Stimulation with agonists that trigger ATP secretion caused rapid MLC (Ser)19 phosphorylation while MLC (Thr)18 phosphorylation was coincident with secretion. Platelets treated with p160ROCK inhibitor Y-27632 exhibited a partial inhibition in secretion and had a substantial inhibition in MLC (Thr)18 phosphorylation without effecting MLC (Ser)19 phosphorylation. These data suggest that phosphorylation of MLC (Ser)19 is downstream of Gq/Ca2+ -dependent mechanisms and sufficient for shape change, whereas MLC (Thr)18 phosphorylation is substantially downstream of G12/13 -regulated Rho kinase pathways and necessary, probably in concert with MLC (Ser)19 phosphorylation, for full contractile activity leading to dense granule secretion. Overall, we suggest that the amplitude of the platelet contractile response is differentially regulated by a least two different signaling pathways, which lead to different phosphorylation patterns of the myosin light chain, and this mechanism results in a graded response rather than a simple on/off switch. [source] Differential expression of cardiac mitochondrial proteinsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 3 2008Julia R. Smith Abstract Mitochondria were isolated from whole hearts of Dahl salt sensitive (SS) and chromosome 13 consomic control (SS.13BN/Mcwi) rats using a mechanical homogenization process followed by density centrifugation. The proteins present in the two mitochondria preparations were quantified; equal amounts of protein from each sample were taken and trypsinized in the presence of either 16O or 18O before pooling. Incorporation of one or two 18O atoms at the C-terminus of the peptide cleaved by trypsin allows the distinction between the two samples. The proteins were identified by automated MS/MS sequencing and relative amounts of each protein assessed by comparison of the intensities of the constituent peptides. Relative quantification was performed using the ZoomQuant (v1.24) software. Nine proteins were found to be differentially expressed. Electron transfer flavoprotein alpha (P13803, ETFA) protein expression was two-fold lower in the SS compared to the SS.13BN. This was confirmed by Western blot and 2-DE gel quantification. Potential functional implications of this differential expression include an impaired capacity of the heart to oxidize fatty acids in the SS strain compared to the control. Mathematical modeling of mitochondrial electron transport predicted that the observed change in ETFA expression may result in decreased activity of the electron transport chain. [source] Middle phalanx skeletal morphology in the hand: Can it predict flexor tendon size and attachments?AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2007Mary W. Marzke Abstract Specific sites on the palmar diaphysis of the manual middle phalanges provide attachment for the flexor digitorum superficialis (FDS) tendon. It has been assumed in the literature that lateral palmar fossae on these bones reflect locations for these attachments and offer evidence for relative size of the flexor tendon. This assumption has led to predictions about relative FDS muscle force potential from sizes of fossae on fossil hominin middle phalanges. Inferences about locomotor capabilities of fossil hominins in turn have been drawn from the predicted force potential of the flexor muscle. The study reported here provides a critical first step in evaluating hypotheses about behavioral implications of middle phalangeal morphology in fossil hominins, by testing the hypothesis that the lateral fossae reflect the size of the FDS tendon and the location of the terminal FDS tendon attachments on the middle phalanx. The middle phalangeal region was dissected in 43 individuals from 16 primate genera, including humans. Qualitative observations were made of tendon attachment locations relative to the lateral fossae. Length measurements of the fossae were tested as predictors of FDS tendon cross-sectional area and of FDS attachment tendon lengths. Our results lead to the conclusion that the hypothesis must be rejected, and that future attention should focus on functional implications of the palmar median bar associated with the lateral fossae. Am J Phys Anthropol, 2007. © 2007 Wiley-Liss, Inc. [source] Effect of the Photoperiod and Administration of Melatonin on the Pars Tuberalis of Viscacha (Lagostomus maximus maximus): An Ultrastructural StudyTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2010Edith Perez Romera Abstract The pituitary pars tuberalis (PT) is a glandular zone exhibiting well-defined structural characteristics. Morphologically, it is formed by specific secretory cells, folliculostellate cells, and migratory cells coming from the pars distalis. The purpose of this work was to investigate differences in specific cellular characteristics in the PT of viscachas captured in summer (long photoperiod) and winter (short photoperiod), as well as the effects of chronic melatonin administration in viscachas captured in summer and kept under long photoperiod. In summer, the PT-specific cells exhibited cell-like characteristics with an important secretory activity and a moderate amount of glycogen. In winter, the PT-specific granulated cells showed ultrastructural variations with signs of a reduced synthesis activity. Also, PT showed a high amount of glycogen and a great number of cells in degeneration. After melatonin administration, the ultrastructural characteristics were similar to those observed in winter, but the amount of glycogen was higher. These results suggest possible functional implications as a result of morphological differences between long and short photoperiods, and are in agreement with the variations of the pituitary-gonadal axis, probably in response to the natural photoperiod changes through the pineal melatonin. The ultrastructural differences observed in PT, after melatonin administration, were similar to those observed in the short photoperiod, thus supporting the hypothesis that these cytological changes are induced by melatonin. Anat Rec, 293:871,878, 2010. © 2010 Wiley-Liss, Inc. [source] Distribution of Lectin-Bindings in the Testis of the Lesser Mouse Deer, Tragulus javanicusANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2009S. Agungpriyono Summary The distribution of lectin bindings in the testis of the smallest ruminant, lesser mouse deer (Tragulus javanicus), was studied using 12 biotinylated lectins specific for d -galactose (peanut agglutinin PNA, Ricinus communis agglutinin RCA I), N -acetyl- d -galactosamine (Dolichos biflorus agglutinin DBA, Vicia villosa agglutinin VVA, Soybean agglutinin SBA), N -acetyl- d -glucosamine and sialic acid (wheat germ agglutinin WGA, s-WGA), d -mannose and d -glucose (Lens culinaris agglutinin LCA, Pisum sativum agglutinin PSA, Concanavalin A Con A), l -fucose (Ulex europaeus agglutinin UEA I), and oligosaccharide (Phaseolus vulgaris agglutinin PHA-E) sugar residues. In Golgi-, cap-, and acrosome-phase spermatids, lectin-bindings were found in the acrosome (PNA, RCA I, VVA, SBA, WGA and s-WGA), and in the cytoplasm (PNA, RCA I, VVA, SBA, WGA, LCA, PSA, Con A and PHA-E). s-WGA binding was confined to the spermatid acrosome, but other lectins were also observed in spermatocytes. In spermatogonia, VVA, WGA, Con A, and PHA-E bindings were observed. Sertoli cells were intensely stained with DBA and Con A, and weakly with PHA-E. In interstitial Leydig cells, RCA I, DBA, VVA, Con A, PSA, LCA, WGA and PHA-E were positive. UEA I was negative in all cell types including spermatogenic cells. Unusual distribution of lectin-bindings noted in the testis of lesser mouse deer included the limited distribution of s-WGA only in the spermatid acrosome, the distribution of DBA in Sertoli cells, Leydig cells and lamina propria, and the absence of UEA I in all type cells. The present results were discussed in comparison with those of other animals and their possible functional implications. [source] Variation in neighbouring genes of the dopaminergic and serotonergic systems affects feather pecking behaviour of laying hensANIMAL GENETICS, Issue 2 2009K. Flisikowski Summary Feather pecking is a behavioural disorder of laying hens and has serious animal welfare and economic implications. One of the several aetiological hypotheses proposes that the disorder results from redirected exploratory behaviour. Variation in the gene encoding the dopamine D4 receptor (DRD4) has been shown to be associated with exploratory behaviour in several species, including in a passerine bird species. We therefore considered DRD4 as a candidate gene for feather pecking. We have annotated DRD4 in the chicken genome and have re-sequenced it in 140 animals belonging to: experimental layer lines divergently selected for high and low propensity to feather pecking; the unselected founder population; and two commercial lines with low and high propensity to feather pecking. We have identified two sub-haplotypes of DRD4 that are highly significantly associated with feather pecking behaviour in the experimental (P = 7.30 × 10,7) as well as in the commercial lines (P = 2.78 × 10,6). Linkage disequilibrium (LD) extends into a neighbouring gene encoding deformed epidermal autoregulatory factor 1 (DEAF1). The product of DEAF1 regulates the transcription of the gene encoding the serotonin (5-hydroxytryptamine) 1A receptor. Thus, DEAF1 represents another candidate gene for feather pecking. Re-sequencing of five animals homozygous for the ,low-pecking' sub-haplotype and of six animals homozygous for the ,high-pecking' sub-haplotype delineated an LD block of 14 833 bases spanning the two genes. None of the variants in the LD block is obviously functional. However, the haplotype information will be useful to select against the propensity to feather pecking in chicken and to elucidate the functional implications of the variants. [source] Defining the glycophenotype of squamous epithelia using plant and mammalian lectins.APMIS, Issue 12 20023-linked N-acetylneuraminic acid in squamous epithelia, Differentiation-dependent expression of, carcinomas, its differential effect on binding of the endogenous lectins galectins- A thorough characterization of the properties of squamous epithelial cells is necessary in order to improve our understanding of the functional aspects of normal development and malignant aberrations. Up to now, studies have focused almost exclusively on monitoring distinct protein markers. With our growing awareness of the coding function of glycan chains of cellular glycoconjugates and their interaction with receptors (lectins) in situ, defining the glycophenotype of these cells has become an important issue. Whereas the commonly applied plant lectins are tools used to map the presence and localization of biochemically defined saccharide epitopes, the introduction of endogenous (mammalian) lectins to this analysis enables us to take the step from monitoring the presence of glycan to understanding the functional implications by revealing ligand properties of the detected epitope for tissue lectin. Thus, in this study we investigated a distinct aspect of glycosylation using plant and mammalian lectins, i.e. the linkage type of sialylation. We first mapped the expression profile of the type of sialylation (,2,3- or ,2,6-linked) by plant lectins. Based on the hypothesis that this factor regulates accessibility of ligands for endogenous lectins we introduced two labeled galectins to this study. Galectin-3 (but not galectin-1) binding was related to cell differentiation in normal adult and developing epithelia, cultured epidermal cells, and carcinomas derived from these epithelia. The presented data suggest that ,2,6-linked N-acetyl- D -neuraminic acid moieties could serve to mask galectin-3-reactive glycoepitopes. As a consequence, monitoring of the linkage type of sialic acid in glycans by plant lectins therefore has implications for the extent of glycan reactivity with endogenous lectins, pointing to a potential function of changes in sialylation type beyond these cell and lectin systems. [source] Carbohydrate-binding properties of goat secretory glycoprotein (SPG-40) and its functional implications: structures of the native glycoprotein and its four complexes with chitin-like oligosaccharidesACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2007Punit Kaur A 40,kDa glycoprotein (SPG-40) secreted during involution works as a protective signalling factor through its binding to viable cells. The crystal structure of the native protein has been determined at 2.3,Ĺ resolution. This is the first report on the carbohydrate-binding properties of SPG-40; the structure determinations of the complexes of SPG-40 with four oligosaccharides of different lengths at resolutions ranging from 2.2 to 2.8,Ĺ are described. Carbohydrate-binding studies with N -acetylglucosamines (GlcNAcn, n = 3,6) using fluorescence spectroscopy revealed poor binding effects with GlcNAc3 and GlcNAc4, while GlcNAc5 and GlcNAc6 bound to SPG-40 with considerable strength; the dissociation constants (Kd) were estimated to be 260 ± 3 and 18 ± 4,µM, respectively. SPG-40 was cocrystallized with GlcNAc3, GlcNAc4, GlcNAc5 and GlcNAc6. The overall structure of native SPG-40 was essentially similar to that reported previously at low resolution. The structures of its complexes with GlcNAc3, GlcNAc4, GlcNAc5 and GlcNAc6 revealed the positions of these oligosaccharides in the carbohydrate-binding groove and provided insights into the mechanism of binding of oligosaccharides to SPG-40, indicating that the preferred subsites in the carbohydrate-binding groove of SPG-40 were from ,4 to ,2. The structure of the protein remained unperturbed upon binding of GlcNAc3 and GlcNAc4, but the structure changed significantly upon binding of GlcNAc5 and GlcNAc6. Significant conformational variations were observed in the sugar-binding groove: Trp78 partially flipped out of the barrel in GlcNAc5, while in the GlcNAc6 complex a completely flipped-out Trp78 was observed along with several other conformational changes, including those of Asp186 and Arg242. Such changes upon binding to carbohydrates have not previously been observed in chitin-hydrolyzing chitinases and reflect less favourable binding of carbohydrates to SPG-40. As this appears to essentially be a binding protein, this loss of binding affinity might be compensated by other intermolecular interactions such as protein,protein interactions and also by the binding of its own glycan chain. [source] | ||||||||||||||||||||||||||||||||||