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Unique Functions (unique + function)
Selected AbstractsNon-enzymatic developmental functions of acetylcholinesterase , the question of redundancyFEBS JOURNAL, Issue 20 2008Glynis Johnson Despite in vitro demonstrations of non-enzymatic morphogenetic functions in acetylcholinesterase (AChE), the AChE knockout phenotype is milder than might be expected, casting doubt upon the relevance of such functions in vivo. Functional redundancy is a possible explanation. Using in vitro findings that AChE is able to bind to laminin-111, together with detailed information about the interaction sites, as well as an epitope analysis of adhesion-inhibiting anti-AChE mAbs, we have used molecular docking and bioinformatics techniques to explore this idea, investigating structurally similar molecules that have a comparable spatiotemporal expression pattern in the embryonic nervous system. On this basis, molecules with which AChE could be redundant are the syndecans, glypicans, perlecan, the receptor tyrosine kinase Mer, and the low-density lipoprotein receptor. It is also highly likely that AChE may be redundant with the homologous neuroligins, although there is no evidence that the latter are expressed before synaptogenesis. AChE was observed to dock with Gas6, the ligand for Mer, as well as with apolipoprotein E3 (but not apolipoprotein E4), both at the same site as the laminin interaction. These findings suggest that AChE may show direct functional redundancy with one or more of these molecules; it is also possible that it may itself have a unique function in the stabilization of the basement membrane. As basement membrane molecules are characterized by multiple molecular interactions, each contributing cumulatively to the construction and stability of the network, this may account for AChE's apparently promiscuous interactions, and also for the survival of the knockout. [source] Timing and tuning of CD27,CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathologyIMMUNOLOGICAL REVIEWS, Issue 1 2009Martijn A. Nolte Summary:, After binding its natural ligand cluster of differentiation 70 (CD70), CD27, a tumor necrosis factor receptor (TNFR)-associated factor-binding member of the TNFR family, regulates cellular activity in subsets of T, B, and natural killer cells as well as hematopoietic progenitor cells. In normal immune responses, CD27 signaling appears to be limited predominantly by the restricted expression of CD70, which is only transiently expressed by cells of the immune system upon activation. Studies performed in CD27-deficient and CD70-transgenic mice have defined a non-redundant role of this receptor,ligand pair in shaping adaptive T-cell responses. Moreover, adjuvant properties of CD70 have been exploited for the design of anti-cancer vaccines. However, continuous CD27,CD70 interactions may cause immune dysregulation and immunopathology in conditions of chronic immune activation such as during persistent virus infection and autoimmune disease. We conclude that optimal tuning of CD27,CD70 interaction is crucial for the regulation of the cellular immune response. We provide a detailed comparison of costimulation through CD27 with its closely related family members 4-1BB (CD137), CD30, herpes virus entry mediator, OX40 (CD134), and glucocorticoid-induced TNFR family-related gene, and we argue that these receptors do not have a unique function per se but that rather the timing, context, and intensity of these costimulatory signals determine the functional consequence of their activity. [source] Novel Triaromatic Ester Mesogenic Liquid Crystalline Epoxy Resin Containing Both Methyl Substituent and Ethoxy Flexible Spacer: Synthesis and CuringMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 11 2008Guo-dong Liu Abstract A novel triaromatic ester liquid crystalline epoxy resin (LCER) that contains both a methyl substituent and an ethoxy flexible spacer, p -methylphenylene di{4-[(2,3-epoxypropoxy)ethoxy]benzoate} (MPEPEB), has been synthesized. The mesotropic property has been investigated by differential scanning calorimetry (DSC) and polarized light optical microscopy (POM). MPEPEB shows a lower melting temperature at 78.7,°C and a broad nematic mesophase temperature range of about 55,°C. Meanwhile MPEPEB shows a mesophase to ,50,°C upon cooling. The curing behavior of MPEPEB with 2,6-diamino-3,5-diethyltoluene (DAE) has been investigated by means of DSC and POM during isothermal and dynamic processes. Although there is little difference between the activation energies obtained from the kinetic data, a marked difference is found between the isothermal and dynamic investigation. The curing reaction in the isothermal investigation roughly obeys n- th order kinetics, while two exothermal peaks appear in the dynamic DSC curves of MPEPEB/DAE. A comparison of the isothermal and dynamic data shows that the curing rate is not a unique function of temperature and curing degree. The cured networks have lower glass temperatures and show a mesophase at room temperature which disappears at about 86,88,°C. [source] Convective Available Potential Energy (CAPE) in mixed phase cloud conditionsTHE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue 624 2007B. Früh Abstract An approximate but pragmatic approach is presented to define Convective Available Potential Energy (CAPE) in mixed phase cloud conditions. The underlying process calls for mixed (i.e. liquid and ice) phase parcels and assumes the liquid fraction to be a unique function of temperature. The approach is meant to represent average conditions. Differences between this and more traditional approaches are quantified and discussed for mean tropical conditions. Generally freezing increases parcel temperature and, hence, buoyancy. If freezing occurs isobarically (as was often assumed in the past), all water changes phase at a single level resulting in a discontinuity in buoyancy at that level. By contrast, the mixed phase parcel process implies a continuous phase transition in a finite range of temperatures Tfs , T , Tfe, leading to a gradual change of buoyancy with altitude and preventing any temperature inversion. The details of this gradual change depend on the choice of the specified temperature range [Tfs, Tfe]. High in the troposphere, where all water is frozen irrespective of the details, the differences between the buoyancy profiles are small (but finite). CAPE is very sensitive to the treatment of the freezing process. Isobaric freezing at a relatively high temperature (e.g. , 5 °C) in a reversible process may increase CAPE by a factor of 2 to 3, and this increase is similar in magnitude to the difference between the pseudo-adiabatic and the reversible processes for pure water parcels. Both of these processes are considered less realistic than the reversible mixed phase process with continuous freezing over a broad temperature range [Tfs, Tfe] = [,5 °C, , 40 °C]; the corresponding CAPE lies about half way between the reversible and irreversible pure water processes. For clouds with finite precipitation efficiency the effect of freezing is less pronounced than for reversible conditions. Copyright © 2007 Royal Meteorological Society [source] Modelling tropical atmospheric convection in the context of the weak temperature gradient approximationTHE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue 608 2005David J. Raymond Abstract A cumulus ensemble model is used to simulate the interaction between tropical atmospheric convection and the large-scale tropical environment in the context of Sobel and Bretherton's (2000) weak temperature gradient approximation. In this approximation, gravity waves are assumed to redistribute buoyancy anomalies over a broad area of the tropics, thus maintaining the local virtual-temperature profile close to the large-scale mean. This result is implemented in the model by imposing the advective effects of a hypothetical mean vertical velocity which is just sufficient to counteract the local heating induced by convection and radiation. The implied vertical advection in the moisture equation and entrainment of air from the surrounding environment have major effects on the evolution of convection in the model. The precipitation produced by the model mimics the results of a very simple model of tropical precipitation introduced by Raymond (2000), in that the mean rainfall rate predicted by the cumulus ensemble model is, to a good approximation, a function only of the mean column precipitable water. The evolution of the precipitable water, and hence the precipitation rate, is a result of the imbalance between the surface flux of moist entropy into the domain and the radiative loss of entropy out of the top of the domain. This evolution leads to a statistically steady solution in which the resulting precipitation rate is a unique function of the entropy flux imbalance. These results support the hypothesis that tropical precipitation averaged over distance scales of a few hundred kilometres and time scales of a day is a consequence only of local thermodynamic factors. Copyright © 2005 Royal Meteorological Society [source] The porphobilinogen synthase family of metalloenzymesACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2000Eileen K. Jaffe The porphobilinogen synthase (PBGS) family of enzymes catalyzes the first common step in the biosynthesis of the essential tetrapyrroles such as chlorophyll and porphyrin. Although PBGSs are highly conserved at all four levels of protein structure, there is considerable diversity in the use of divalent cations for the catalytically essential and allosteric roles. Assumptions regarding commonalities among the PBGS proteins coupled with the diversity of usage of metal ions has led to a confused literature. The recent publication of crystal structures for three PBGS proteins coupled with more than 50 individual PBGS sequences allows an evaluation of these assumptions. This topical review focuses on the usage of metals by the PBGS family of proteins. It raises doubt concerning a dogma that there has been an evolutionary shift between ZnII and MgII at one or more of the divalent metal-binding sites. It also raises the possibility that there may be up to four specific divalent metal ion-binding sites, each serving a unique function that can be alternatively filled by amino acids in some of the PBGSs. [source] Cloning the bacterial bphC gene into Nicotiana tabacum to improve the efficiency of PCB phytoremediationBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2009M. Novakova Abstract The aim of this work is to increase the efficiency of the biodegradation of polychlorinated biphenyls (PCBs) by the introduction of bacterial genes into the plant genome. For this purpose, we selected the bphC gene encoding 2,3-dihydroxybiphenyl-1,2-dioxygenase from Pseudomonas testosteroni B-356 to be cloned into tobacco plants. The dihydroxybiphenyldioxygenase enzyme is the third enzyme in the biphenyl degradation pathway, and its unique function is the cleavage of biphenyl. Three different constructs were designed and prepared in E. coli: the bphC gene being fused with the ,-glucuronidase (GUS) gene, with the luciferase (LUC) gene, and with histidine tail in three separate plant cloning vectors. The GUS and LUC genes were chosen because they can be used as markers for the easy detection of transgenic plants, while histidine tail better enables the isolation of protein expressed in plant tissue. The prepared vectors were then introduced into cells of Agrobacterium tumefaciens. The transient expression of the prepared genes was first studied in cells of Nicotiana tabacum. Once this ability had been established, model tobacco plants were transformed by agrobacterial infection with the bphC/GUS, bphC/LUC, and bphC/His genes. The transformed regenerants were selected on media using a selective antibiotic, and the presence of transgenes and mRNA was determined by PCR and RT-PCR. The expression of the fused proteins BphC/GUS and BphC/LUC was confirmed histochemically by analysis of the expression of their detection markers. Western blot analysis was performed to detect the presence of the BphC/His protein immunochemically using a mouse anti-His antibody. Growth and viability of transgenic plants in the presence of PCBs was compared with control plants. Biotechnol. Bioeng. 2009;102: 29,37. © 2008 Wiley Periodicals, Inc. [source] Fly Six-type homeodomain proteins Sine oculis and Optix partner with different cofactors during eye developmentDEVELOPMENTAL DYNAMICS, Issue 3 2005Kristy L. Kenyon Abstract Two members from the Six class of homeobox transcription factors, Sine oculis (SO) and Optix, function during development of the fly visual system. Differences in gain-of-function phenotypes and gene expression suggest that these related factors play distinct roles in the formation of the fly eye. However, the molecular nature of their functional differences remains unclear. In this study, we report the identification of two novel factors that participate in specific partnerships with Sine oculis and Optix during photoreceptor neurons formation and in eye progenitor cells. This work shows that different cofactors likely mediate unique functions of Sine oculis and Optix during the development of the fly eye and that the repeated requirement for SO function at multiple stages of eye development reflects the activity of different SO,cofactor complexes. Developmental Dynamics 234:497,504, 2005. © 2005 Wiley-Liss, Inc. [source] Cx31 and Cx43 double-deficient mice reveal independent functions in murine placental and skin developmentDEVELOPMENTAL DYNAMICS, Issue 3 2005Mark Kibschull Abstract The overlapping expression of gap junctional connexins in tissues has indicated that the channels may compensate for each other. During development, Cx31 and Cx43 are coexpressed in preimplantation embryos, in the spongiotrophoblast of the placenta and in the epidermis. This study shows that Cx31/Cx43 double-deficient mice exhibit the known phenotypes of the single-knockout strains but no combined effects. Thus, Cx43, coexpressed with Cx31 at midgestation in the spongiotrophoblast of the placenta, cannot be responsible for a partial rescue of the lethal Cx31 knockout phenotype, as assumed before (Plum et al. [ 2001] Dev Biol 231:334,337). It follows that both connexins have unique functions in placental development. Despite an altered expression of other epidermal connexin mRNAs, epidermal differentiation and physiology was unaltered by the absence of Cx31 and Cx43. Therefore, in epidermal and preimplantation development, gap junctional communication can probably be compensated by other isoforms coexpressed with Cx31 and Cx43. Developmental Dynamics 233:853,863, 2005. © 2005 Wiley-Liss, Inc. [source] Foxo1 regulates marginal zone B-cell developmentEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2010Jing Chen Abstract A fundamental component of signaling initiated by the BCR and CD19 is the activation of phosphoinositide 3-kinase. Downstream of phosphoinositide 3-kinase, the protein kinase AKT phosphorylates several substrates, including members of the forkhead box subgroup O (Foxo) transcription factor family. Among the Foxo proteins, Foxo1 has unique functions in bone marrow B-cell development and peripheral B-cell function. Here, we report a previously unrecognized role for Foxo1 in controlling the ratio of mature B-cell subsets in the spleen. Conditional deletion of Foxo1 in B cells resulted in an increased percentage of marginal zone B cells and a decrease in follicular (FO) B cells. In addition, Foxo1 deficiency corrected the absence of marginal zone B cells that occurs in CD19-deficient mice. These findings show that Foxo1 regulates the balance of mature B-cell subsets and is required for the marginal zone B-cell deficiency phenotype of mice lacking CD19. [source] The ABCA1 cholesterol transporter associates with one of two distinct dystrophin-based scaffolds in Schwann cellsGLIA, Issue 6 2008Douglas E. Albrecht Abstract Cytoskeletal scaffolding complexes help organize specialized membrane domains with unique functions on the surface of cells. In this study, we define the scaffolding potential of the Schwann cell dystrophin glycoprotein complex (DGC) by establishing the presence of four syntrophin isoforms, (,1, ,1, ,2, and ,2), and one dystrobrevin isoform, (,-dystrobrevin-1), in the abaxonal membrane. Furthermore, we demonstrate the existence of two separate DGCs in Schwann cells that divide the abaxonal membrane into spatially distinct domains, the DRP2/periaxin rich plaques and the Cajal bands that contain Dp116, utrophin, ,-dystrobrevin-1 and four syntrophin isoforms. Finally, we show that the two different DGCs can scaffold unique accessory molecules in distinct areas of the Schwann cell membrane. Specifically, the cholesterol transporter ABCA1, associates with the Dp116/syntrophin complex in Cajal bands and is excluded from the DRP2/periaxin rich plaques. © 2008 Wiley-Liss, Inc. [source] Heparin and Heparan Sulfate BiosynthesisIUBMB LIFE, Issue 4 2002Kazuyuki Sugahara Abstract Heparan sulfate is one of the most informationally rich biopolymers in Nature. Its simple sugar backbone is variously modified to different degrees depending on the cellular conditions. Thus, it matures to have an enormously complicated structure, which most likely exhibits a considerable number of unique overlapping sequences with peculiar sulfation profiles. Such sequences are recognized by specific complementary proteins, which form a huge group of "heparin-binding proteins," and the sugar sequences in turn support unique functions of the respective proteins through specific interactions. The heparan sulfate sequences are not directly encoded by genes, but are created by elaborate biosynthetic mechanisms, which ensure the generation of these indispensable sequences. In heparan sulfate biosynthesis, the tetrasaccharide sequence (GlcA-Gal-Gal-Xyl-), designated the protein linkage region, is first assembled on a specific Ser residue at the glycosaminoglycan attachment site of a core protein. A heparan sulfate chain is then polymerized on this fragment by alternate additions of GlcNAc and GlcA through the actions of glycosyltransferases with overlapping specificities encoded by the tumor suppressor EXT family genes. Then follow various modifications by N -deacetylation and N -sulfation of glucosamine, C5-epimerization of GlcA and multiple O -sulfations of the component sugars. Recent studies have achieved purification of several, and molecular cloning of most, of the enzymes responsible for these reactions. Some of these enzymes are bifunctional. The availability of cDNA probes has facilitated elucidation of the crystal structures for two of the biosynthetic enzymes, demonstration of their intracellular location, and their occurrence in complexes to achieve rapid and efficient synthesis of complex sugar sequences. Genomic structure and transcript analysis have shown the existence of multiple isoforms for most of the sulfotransferases. Many aspects of the heparan sulfate biosynthetic scheme are shared by the structural analog heparin, which is synthesized in mast cells and some other mammalian cells and is several-fold higher degree of polymerization and more extensive modification than heparan sulfate. [source] The psychologist's role in the collaborative process of psychopharmacologyJOURNAL OF CLINICAL PSYCHOLOGY, Issue 6 2002Kenneth A. Weene This is a discussion of a collaborative approach between psychologists, physicians, patients, and others in the administration of psychotropic medication. It is based on a systems point of view. In that perspective, not only are the people indicated above a system, but also the patient is considered from a holistic-systems point of view. It requires that the psychologist not only be a member of the system, and a well-versed in medication member at that; (s)he must also be an observer of the system, be able to take a meta perspective, in order to be able to exercise some unique functions,functions for which psychologists are well-trained. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 617,621, 2002. [source] Minimum sequence requirements for selective RNA-ligand binding: A molecular mechanics algorithm using molecular dynamics and free-energy techniquesJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 14 2006Peter C. Anderson Abstract In vitro evolution techniques allow RNA molecules with unique functions to be developed. However, these techniques do not necessarily identify the simplest RNA structures for performing their functions. Determining the simplest RNA that binds to a particular ligand is currently limited to experimental protocols. Here, we introduce a molecular-mechanics based algorithm employing molecular dynamics simulations and free-energy methods to predict the minimum sequence requirements for selective ligand binding to RNA. The algorithm involves iteratively deleting nucleotides from an experimentally determined structure of an RNA-ligand complex, performing energy minimizations and molecular dynamics on each truncated structure, and assessing which truncations do not prohibit RNA binding to the ligand. The algorithm allows prediction of the effects of sequence modifications on RNA structural stability and ligand-binding energy. We have implemented the algorithm in the AMBER suite of programs, but it could be implemented in any molecular mechanics force field parameterized for nucleic acids. Test cases are presented to show the utility and accuracy of the methodology. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006 [source] Analysis of clogging behaviors of diatomaceous ceramic membranes during membrane filtration based upon specific depositAICHE JOURNAL, Issue 7 2010Eiji Iritani Abstract Fouling behaviors in membrane filtration of dilute suspension of polystyrene latex (PSL) were examined under constant-pressure conditions using diatomaceous ceramic membranes which are semi-permeable to the PSL. Flux decline behaviors were evaluated in consideration of the effect of the solid permeation through the membrane. The conventional characteristic filtration equation was modified by applying the Kozeny-Carman equation to the filtrate flow through the membrane pores. In the model, the porosity and specific surface area of the membrane were represented by unique functions of the solid deposit retained in the membrane pores. The variations of the filtration rate and filtrate volume with the filtration time were accurately described based upon the modified characteristic filtration equation. It was revealed that the extent of the membrane blocking per unit deposit load increased with the decrease in the pore size of the membrane and with decreasing pressure, but was little influenced by the suspension concentration. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Alcohol Biomarkers in Applied Settings: Recent Advances and Future Research OpportunitiesALCOHOLISM, Issue 6 2010Raye Z. Litten During the past decade, advances have been made in the identification, development, and application of alcohol biomarkers. This is important because of the unique functions that alcohol biomarkers can serve in various applied settings. To carry out these functions, biomarkers must display several features including validity, reliability, adequacy of temporal window of assessment, reasonable cost, and transportability. During the past two decades, several traditional alcohol biomarkers have been studied in multiple human studies. Meanwhile, several new, promising biomarkers, including various alcohol metabolites and alcohol biosensors, are being explored in human studies. In addition, researchers have explored using biomarkers in combination and using biomarkers in combination with self-reports, resulting in increased sensitivity with little sacrifice in specificity. Despite these advances, more research is needed to validate biomarkers, especially the new ones, in humans. Moreover, recent advances in high-throughput technologies for genomics, proteomics, and metabolomics offer unique opportunities to discover novel biomarkers, while additional research is needed to perfect newly developed alcohol sensors. Development of more accurate biomarkers will help practicing clinicians to more effectively screen and monitor individuals who suffer from alcohol use disorders. [source] Prostate-Specific genes and their regulation by dihydrotestosteroneTHE PROSTATE, Issue 3 2008Ma Ci Abstract BACKGROUND Prostate is a well-known androgen-dependent tissue. METHODS By sequencing 4,294,186 serial analysis of gene expression (SAGE) tags, we have investigated the transcriptomes of normal mouse prostate, liver, testis, lung, brain, femur, skin, adipose tissue, skeletal muscle, vagina, ovary, mammary gland, and uterus in order to identify the most abundant and tissue-specific transcripts in the prostate, as well as to target the androgen responsive transcripts specifically regulated in the prostate. Small interference RNA (siRNA) in LNCaP cells was applied to validate the roles of prostate-specific/enriched ARGs in the growth of human prostate cancer cells. RESULTS The most abundant transcripts were involved in prostatic secretion, energy metabolism and immunity. Previously well-known prostate-specific transcripts, including many transcripts involved in prostatic secretion, polyamine biosynthesis and transport, and immunity were specific/enriched in the prostate. Only 22 transcripts among 114 androgen-regulated genes (ARGs) in the mouse prostate were modulated by dihydrotestosterone (DHT) in two or more tissues. The siRNA results showed that inhibition of HSPA5 and MAT2A gene expression repressed growth of human cancer LNCaP cells. Conclusions The current study globally assessed the transcriptome of the prostate and revealed the most abundant and tissue-specific transcripts which are responsible for the unique functions of this organ. These prostate-specific ARGs might be used as targets to develop safe and effective gene-based therapy for the prevention and treatment of prostate cancer. Prostate 68: 241,254, 2008. © 2007 Wiley-Liss, Inc. [source] Thermally Responsive Supramolecular Nanomeshes for On/Off Switching of the Rotary Motion of F1 -ATPase at the Single-Molecule LevelCHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2008Satoshi Yamaguchi Dr. Abstract The artificial regulation of protein functions is essential for the realization of protein-based soft devices, because of their unique functions conducted within a nano-sized molecular space. We report that self-assembled nanomeshes comprising heat-responsive supramolecular hydrogel fibers can control the rotary motion of an enzyme-based biomotor (F1 -ATPase) in an on/off manner at the single-molecule level. Direct observation of the interaction of the supramolecular fibers with a microbead unit tethered to the F1 -ATPase and the clear threshold in the size of the bead required to stop ATPase rotation indicates that the bead was physically blocked so as to stop the rotary motion of ATPase. The temperature-induced formation and collapse of the supramolecular nanomesh can produce or destroy, respectively, the physical obstacle for ATPase so as to control the ATPase motion in an off/on manner. Furthermore, this switching of the F1 -ATPase motion could be spatially restricted by using a microheating device. The integration of biomolecules and hard materials, interfaced with intelligent soft materials such as supramolecular hydrogels, is promising for the development of novel semi-synthetic nano-biodevices. [source] | ||||||||||||||||