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Several Molecules (several + molecule)
Selected AbstractsSynthesis and Anticonvulsant Properties of New Mannich Bases Derived from 3-Aryl-pyrrolidine-2,5-diones.ARCHIV DER PHARMAZIE, Issue 6 2010Part Abstract A series of new Mannich bases of N -[(4-arylpiperazin-1-yl)-methyl]-3-(chlorophenyl)-pyrrolidine-2,5-diones 10,23 have been synthesized and evaluated for their anticonvulsant activity in maximum electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. Their neurotoxicity was determined using a rotorod screen. Several molecules showed a promising anticonvulsant profile especially in the MES-test. In this model of seizures, the most active were N -[{4-(4-chlorophenyl)-piperazin-1-yl}-methyl]-3-(3-chlorophenyl)-pyrrolidine-2,5-dione 16 and N -[{4-(3-trifluoromethylphenyl)-piperazin-1-yl}-methyl]-3-(3-chlorophenyl)-pyrrolidine-2,5-dione 17 with ED50 values of 21.4 mg/kg and 28.83 mg/kg, respectively. Selected derivatives 10, 14, and 16 were tested in the psychomotor seizure 6-Hz test from which N -[{4-(2-chlorophenyl)-piperazin-1-yl}-methyl]-3-(2-chlorophenyl)-pyrrolidine-2,5-dione 10 revealed the highest protection with an ED50 of 78 mg/kg. Compounds 10, 12, and 17 were also tested in the pilocarpine-induced status PIPS test. Furthermore, 17 was examined in the hippocampal kindling screen after i. p. administration to rats. [source] In search for correlation among markers for limbal stem cells nicheACTA OPHTHALMOLOGICA, Issue 2009C CURCIO Purpose The corneoscleral limbus is known to be the site of corneal epithelial stem cells (SC). Several molecules have been proposed as SC markers but none of them is able to univocally identify them. The aim of this study was to evaluate co-expression of different SC markers in human limbus. Methods In this work five corneoscleral specimens from normal human donor eye-bank eyes (age 52-73 years) were fixed in formalin, divided in 8 segments, embedded in paraffin and examined by immunohistochemistry and immunofluorescence for p63, vimentin (vim), laminin 5, integrin (Int) ,6, Int ,1, Int ,4, connexin 43, ki67 and N-cadherin positivity. We firstly analyzed the distribution and the anatomical structure of limbal crypts in each of the segments. Then we evaluated the percentage of positive areas in the niches. Finally we looked for colocalizations and possible correlations among markers. Results We confirmed a different number of niches among the segments of the same corneoscleral rim. Moreover we observed high variability of niches number among patients which interestingly correlates with the percentage of p63 positivity of niche cells. Confocal microscopy double staining for p63 and vim did not show evident colocalization and vim + cells were seen in the superficial layers rather than in the deep layer of crypts. Int ,1 staining directly correlated with p63 positivity while the remaining proteins appeared variably and widely distributed Conclusion Colocalization was evident at least for two SC markers (Int ,1/p63) within the basal layers, while vim, expressed mainly in the superficial layers could act as late progenitor cell marker. [source] The adaptive responses in several mediators linked with hypertrophy and atrophy of skeletal muscle after lower limb unloading in humansACTA PHYSIOLOGICA, Issue 2 2009K. Sakuma Abstract Aim:, To determine the adaptive changes in several molecules regulating muscle hypertrophy and atrophy after unloading, we examined whether unilateral lower limb suspension changes the mRNA and protein levels of SRF-linked (RhoA, RhoGDI, STARS and SRF), myostatin-linked (myostatin, Smad2, Smad3 and FLRG) and Foxo-linked (P-Akt, Foxo1, Foxo3a and Atrogin-1) mediators. Methods:, A single lower limb of each of eight healthy men was suspended for 20 days. Biopsy specimens were obtained from the vastus lateralis muscle pre- and post-suspension. Results:, The volume of the vastus lateralis muscle was significantly decreased after unloading. The amount of RhoA, RhoGDI or SRF protein in the muscle was not significantly changed post-suspension. An RT-PCR semiquantitative analysis showed increased levels of myostatin mRNA but not Smad2, Smad3 or FLRG mRNA. Unloading did not elicit significant changes in the amount of p-Smad3 or myostatin protein in the muscle. The amount of p-Akt protein was markedly reduced in the unloaded muscle. Lower limb suspension did not influence the expression pattern of Foxo1, Foxo3a or Atrogin-1. Conclusion:, Unloading inducing a mild degree of muscle atrophy may decrease p-Akt and increase myostatin but not SRF-linked mediators. [source] The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticityDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2010Eero Castrén Abstract Recent evidence suggests that neuronal plasticity plays an important role in the recovery from depression. Antidepressant drugs and electroconvulsive shock treatment increase the expression of several molecules, which are associated with neuronal plasticity, in particular the neurotrophin BDNF and its receptor TrkB. Furthermore, these treatments increase neurogenesis and synaptic numbers in several brain areas. Conversely, depression, at least in its severe form, is associated with reduced volumes of the hippocampus and prefrontal cortex and in at least some cases these neurodegenerative signs can be attenuated by successful treatment. Such observations suggest a central role for neuronal plasticity in depression and the antidepressant effect, and also implicate BDNF signaling as a mediator of this plasticity. The antidepressant fluoxetine can reactivate developmental-like neuronal plasticity in the adult visual cortex, which, under appropriate environmental guidance, leads to the rewiring of a developmentally dysfunctional neural network. These observations suggest that the simple form of the neurotrophic hypothesis of depression, namely, that deficient levels of neurotrophic support underlies mood disorders and increases in these neurotrophic factors to normal levels brings about mood recovery, may not sufficiently explain the complex process of recovery from depression. This review discusses recent data on the role of BDNF and its receptors in depression and the antidepressant response and suggests a model whereby the effects of antidepressant treatments could be explained by a reactivation of activity-dependent and BDNF-mediated cortical plasticity, which in turn leads to the adjustment of neuronal networks to better adapt to environmental challenges. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 2010 [source] Alkanethiols Modified Gold Electrodes for Selective Detection of Molecules with Different Polarity and Molecular Size.ELECTROANALYSIS, Issue 3-5 2009Application to Vitamin B2 Analysis Abstract The cyclic voltammetry behavior of several molecules with different polarity and molecular size on gold electrodes modified with nonfunctionalized alkanethiols of different chain length, usually employed as chromatographic stationary phases, are studied. The redox systems hexacyanoferrate(II/III), ferrocene/ferrocine and hydroquinone/quinone are chosen as template molecules. As modifiers, ethanethiol, 1-octanethiol and di- n -octadecyldisulfide are selected. We can conclude that polar molecules can reach the electrode surface through channels created by the modifiers. However, when nonpolar compounds are analyzed, the nonpolar interactions between the analyte and the terminal group of the modifier lead to retention of the compound, retarding its arrival to the electrode surface. A molecule with polar and nonpolar part was used for the application of this conclusion. If the gold electrode is modified with di- n -octadecyldisulfide, the electrochemical behavior of vitamin B2 becomes simpler than that observed on a bare one. This result allows a sensitive and selective procedure to be developed for direct determination of vitamin B2 in pharmaceutical formulations. [source] Is my antibody-staining specific?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008How to deal with pitfalls of immunohistochemistry Abstract Immunohistochemistry is a sensitive and versatile method widely used to investigate the cyto- and chemoarchitecture of the brain. It is based on the high affinity and selectivity of antibodies for a single epitope. However, it is now recognized that the specificity of antibodies needs to be tested in control experiments to avoid false-positive results due to non-specific binding to tissue components or recognition of epitopes shared by several molecules. This ,Technical Spotlight' discusses other pitfalls, which are often overlooked, although they can strongly influence the outcome of immunohistochemical experiments. It also recapitulates the minimal set of information that should be provided in scientific publications to allow proper evaluation and replication of immunohistochemical experiments. In particular, tissue fixation and processing can have a strong impact on antigenicity by producing conformational changes to the epitopes, limiting their accessibility (epitope masking) or generating high non-specific background. These effects are illustrated for an immunoperoxidase staining experiment with three antibodies differing in susceptibility to fixation, using tissue from mice processed under identical conditions, except for slight variations in tissue fixation. In these examples, specific immunostaining can be abolished depending on fixation strength, or detected only after prolonged postfixation. As a consequence, antibody characterization in immunohistochemistry should include their susceptibility towards fixation and determination of the optimal conditions for their use. [source] Neutralization of the membrane protein Nogo-A enhances growth and reactive sprouting in established organotypic hippocampal slice culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2008Luis M. Craveiro Abstract The reduced ability of central axons to regenerate after injury is significantly influenced by the presence of several molecules that inhibit axonal growth. Nogo-A is one of the most studied and most potent of the myelin-associated growth inhibitory molecules. Its neutralization, as well as interference with its signalling, allows for enhanced axonal sprouting and growth following injury. Using differentiated rat organotypic hippocampal slice cultures treated for 5 days with either of two different function-blocking anti-Nogo-A antibodies, we show an increase in CA3 fibre regeneration after lesion. In intact slices, 5 days of anti-Nogo-A antibody treatment led to increased sprouting of intact CA3 fibres that are positive for neurofilament 68. A transcriptomic approach confirmed the occurrence of a growth response on the molecular level upon Nogo-A neutralization in intact cultures. Our results demonstrate that Nogo-A neutralization for 5 days is sufficient for the induction of growth in mature CNS tissue without the prerequisite of an injury. Nogo-A may therefore act as a tonic growth suppressor/stabilizer in the adult intact hippocampus. [source] Ternary complex formation of EphA4, FGFR and FRS2, plays an important role in the proliferation of embryonic neural stem/progenitor cellsGENES TO CELLS, Issue 3 2010Takahiro Sawada EphA4 belongs to a superfamily of receptor tyrosine kinases and interacts with several molecules including fibroblast growth factor receptors (FGFRs) as we reported earlier. Several receptor tyrosine kinases, FGFRs, Trks, Alk and Ret, are currently known to transduce a signal through a docking protein, fibroblast growth factor receptor substrate 2, (FRS2,). However, nothing has been reported about the interaction of FRS2, with EphA4. Using the yeast two-hybrid system and the in vitro binding and kinase assays, we found that the mid-kinase region of EphA4 directly interacts with the FRS2, PTB domain upon tyrosine phosphorylation of the EphA4 juxtamembrane (JM) domain and EphA4 directly phosphorylates FRS2,. We also found that the FRS2, PTB domain and the amino-terminal region of EphA4 bind to the amino- and carboxy-terminal regions of the FGFR JM domain, respectively, suggesting that FRS2, and EphA4 interact with FGFR simultaneously. Furthermore, a kinase-dead EphA4 mutant that constitutively binds to FGFR functions as a dominant-negative molecule for signaling through both EphA4 and FGFR, and so does the truncated FRS2, lacking multiple tyrosine phosphorylation sites. These dominant-negative mutants similarly inhibit the ligand-dependent proliferation of the mouse embryonic neural stem/progenitor cells. These results suggest the formation of a ternary complex comprising EphA4, FGFR and FRS2,. The signaling complex appears to integrate the input from FGFR and EphA4, and release the output signal through FRS2,. [source] Elucidation of the molecular mechanism of platelet activation: Dense granule secretion is regulated by small guanosine triphosphate-binding protein Rab27 and its effector Munc13-4GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2006Hisanori Horiuchi Cardiovascular diseases such as myocardial and cerebral infarction are common critical diseases occurring more frequently in the elderly. The trigger of the diseases is platelet activation following plaque rupture or erosion. Investigation of the molecular mechanism in platelet activation has been exclusively performed pharmacologically. We have succeeded in establishing the granule secretion and aggregation assays using permeabilized platelets. These systems enabled us to examine the molecular mechanism in platelet activation with molecular biological and biochemical methods. Using these assay systems, we have been investigating the molecular mechanism of platelet activation. With a support grant from the Novartis Foundation for Gerontological Research, we found several molecules involved in the regulation. In this report, I present the progress in the research of the granule secretion mechanism in activated platelets, which was reported in the Japanese Geriatric Society Meeting in 2005. [source] One-particle density matrix functional for correlation in molecular systemsINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 6 2003Mario Piris Abstract Based on the analysis of the general properties for the one- and two-particle reduced density matrices, a new natural orbital functional is obtained. It is shown that by partitioning the two-particle reduced density matrix in an antisymmeterized product of one-particle reduced density matrices and a correction ,c we can derive a corrected Hartree,Fock theory. The spin structure of the correction term from the improved Bardeen,Cooper,Schrieffer theory is considered to take into account the correlation between pairs of electrons with antiparallel spins. The analysis affords a nonidempotent condition for the one-particle reduced density matrix. Test calculations of the correlation energy and the dipole moment of several molecules in the ground state demonstrate the reliability of the formalism. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 317,323, 2003 [source] The VMFCI method: A flexible tool for solving the molecular vibration problemJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 5 2006P. Cassam-Chenaï Abstract The present article introduces a general variational scheme to find approximate solutions of the spectral problem for the molecular vibration Hamiltonian. It is called the "vibrational mean field configuration interaction" (VMFCI) method, and consists in performing vibrational configuration interactions (VCI) for selected modes in the mean field of the others. The same partition of modes can be iterated until self-consistency, generalizing the vibrational self-consistent field (VSCF) method. As in contracted-mode methods, a hierarchy of partitions can be built to ultimately contract all the modes together. So, the VMFCI method extends the traditional variational approaches and can be included in existing vibrational codes based on the latter approaches. The flexibility and efficiency of this new method are demonstrated on several molecules of atmospheric interest. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 627,640, 2006 [source] Myogenesis and molecules, insights from zebrafish Danio rerioJOURNAL OF FISH BIOLOGY, Issue 8 2009S.-W. Chong Myogenesis is a fundamental process governing the formation of muscle in multicellular organisms. Recent studies in zebrafish Danio rerio have described the molecular events occurring during embryonic morphogenesis and have thus greatly clarified this process, helping to distinguish between the events that give rise to fast v. slow muscle. Coupled with the well-known Hedgehog signalling cascade and a wide variety of cellular processes during early development, the continual research on D. rerio slow muscle precursors has provided novel insights into their cellular behaviours in this organism. Similarly, analyses on fast muscle precursors have provided knowledge of the behaviour of a sub-set of epitheloid cells residing in the anterior domain of somites. Additionally, the findings by various groups on the roles of several molecules in somitic myogenesis have been clarified in the past year. In this study, the authors briefly review the current trends in the field of research of D. rerio trunk myogenesis. [source] Differential regulation of blood vessel formation between standard and delayed bone healingJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2009Jasmin Lienau Abstract Blood vessel formation is a prerequisite for bone healing. In this study, we tested the hypothesis that a delay in bone healing is associated with an altered regulation of blood vessel formation. A tibial osteotomy was performed in two groups of sheep and stabilized with either a rigid external fixator leading to standard healing or with a highly rotationally unstable one leading to delayed healing. At days 4, 7, 9, 11, 14, 21, and 42 after surgery, total RNA was extracted from the callus. Gene expressions of vWF, an endothelial cell marker, and of several molecules related to blood vessel formation were studied by qPCR. Furthermore, histology was performed on fracture hematoma and callus sections. Histologically, the first blood vessels were detected at day 7 in both groups. mRNA expression levels of vWF, Ang1, Ang2, VEGF, CYR61, FGF2, MMP2, and TIMP1 were distinctly lower in the delayed compared to the standard healing group at several time points. Based on differential expression patterns, days 7 and 21 postoperatively were revealed to be essential time points for vascularization of the ovine fracture callus. This work demonstrates for the first time a differential regulation of blood vessel formation between standard and mechanically induced delayed healing in a sheep osteotomy model. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Cooperative interaction of n -butylammonium ion with 1,3-alternate tetrapropoxycalix [4]arene: NMR and theoretical studyMAGNETIC RESONANCE IN CHEMISTRY, Issue 5 2008Jaroslav K Abstract The interaction of 1,3-alternate tetrapropoxycalix[4]arene (1) with n -butylammonium ion (2) in CD2Cl2 was examined using 1H, 13C and 14N NMR spectroscopy and DFT (density functional theory) calculations. NMR shows that 1 forms with 2 an equimolecular hydrogen-bonded complex with the equilibrium constant 5.91 × 103 l/mol at 296 K. The structure of the complex can be shown to be asymmetric at 203 K, with 2 interacting by hydrogen bonds with the two ethereal oxygen atoms of one half of 1 and with the , system of the other half, but is rapidly averaged to an apparent C4h symmetry by chemical exchange at higher temperatures. Using two related but independent techniques based on transverse and rotating-frame proton relaxation, it is shown that only an intermolecular exchange of 2 between the bound and free states takes place, in contrast to previously studied interaction of 1 with H3O+. Its correlation time is 0.169 ms. It is shown by DFT calculations that such swift exchange is not possible without a cooperative interaction of both 2 and 1 with several molecules of water present. Similarities and contrasts between the exchange processes of 2 and H3O+ bound to 1 are discussed, in particular with respect to the apparent quantum tunneling of the latter inside the molecule of the complex. Copyright © 2008 John Wiley & Sons, Ltd. [source] Polymers with benzofuro-benzofuran structures,POLYMER INTERNATIONAL, Issue 10 2002Behzad Pourabas Abstract Several kinds of molecules and also polymers are going to be discussed in the present article. Common feature in these molecules and polymers is the possessing of a specific structural part, namely benzofuro,benzofuran. This structure will appear in several molecules and kinds of polymers in the text. A condensation reaction between glyoxal and phenols is the reaction needed to produce the mentioned structural part, ie benzofuro,benzofuran. Because of the importance of this reaction, a brief historical background in the initial section of the article, and some discussion on the structural assignment of the reaction product and the reaction mechanism is also given in sections later on. Types of polymers, which are discussed in this article, are mainly heat stable polymers including polyamide, poly(ether ketone sulfone), polybenzimidazole, poly(amide-benzimidazole) and polyarylates. Polyester, polyhaydrezide and polymers with NLO property are the other kinds of the discussed polymers in the text with the benzofuro,benzofuran structure in their main chain. There is not any detailed procedure provided in the text about the synthesis of the molecules or even the polymers and the general procedures provided follow only the methodological purposes of the authors. Thermal properties of the polymers are discussed in the final section of the article with an attempt to provide a comparative argument in order to reach a relationship between structure and thermal properties. © 2001 Society of Chemical Industry. [source] Trafficking of macromolecules and organelles in cultured Dystonia musculorum sensory neurons is normalTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2006Madeline Pool Abstract Dystonia musculorum (dt) mice suffer from a recessive neuropathy characterized by the progressive loss of sensory axons. The gene responsible for this disorder, dystonin/Bpag1, encodes several alternatively spliced forms of a cytoskeletal linker protein. Neural isoforms of dystonin/Bpag1 are predicted to link actin filaments to microtubules. Consistent with this, previous observations have demonstrated that the cytoskeleton within sensory neurites of dt mice is perturbed. Also, recent results have indicated that a neural isoform of dystonin/Bpag1 interacts with the dynein motor complex. Because microtubule organization and dynein motor function are essential for trafficking, we hypothesized that this process would be perturbed in dt sensory neurons. Here, we demonstrate that cultured primary dorsal root ganglion (DRG) neurons express dystonin/Bpag1 and that loss of this expression causes an increase in apoptosis and a decrease in average neurite length. In contrast, detailed examination showed that the organization of microtubules is indistinguishable in DRG neuronal cultures from neonatal dt and wild-type mice. In addition, the steady-state distribution of several molecules and organelles is unchanged in these cultures. Furthermore, the speeds of mitochondrial movement in both anterograde and retrograde directions were comparable in dt and wild-type sensory neurons cultured from neonatal mice. Thus, dystonin/Bpag1 is not essential for microtubule network assembly since the microtubule network is intact in short-term cultures of sensory neurons from neonatal mice lacking this protein. In addition, dystonin/Bpag1 is not an essential part of the dynein motor complex for mitochondrial transport since mitochondrial trafficking is normal in cultured sensory neurons from dt mice. J. Comp. Neurol. 494:549,558, 2006. © 2005 Wiley-Liss, Inc. [source] Secondary Apoptosis of Spiral Ganglion Cells Induced by Aminoglycoside: Fas,Fas Ligand Signaling Pathway,THE LARYNGOSCOPE, Issue 9 2008Woo Yong Bae MD Abstract Objectives/Hypothesis: Hair cell loss results in the secondary loss of spiral ganglion neurons (SGNs), over a period of several weeks. The death of the SGNs themselves results from apoptosis. Previous studies have shown that several molecules are involved in the apoptosis of SGNs that occurred secondary to hair cell loss. However, the precise mechanism of apoptosis of the SGNs remains unclear. The aim of this study was to ascertain the secondary apoptosis of spiral ganglion cells induced by aminoglycoside and to investigate the role of the Fas,FasL signaling pathway using guinea pigs as an experimental animal model. Study Design: Laboratory study using experimental animals. Methods: Guinea pigs weighing 250 to 300 g (n = 21) from 3 to 4 weeks of age were used. Gentamicin (60 ,L) was injected through a cochleostomy site on their left side. At 1 (n = 7), 2 (n = 7), and 3 (n = 7) weeks after gentamicin treatment, their cochleas were obtained from their temporal bone. Hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining were performed to observe apoptosis. To investigate the involvement of the Fas,FasL signaling pathway in the secondary apoptosis of SGNs, we performed reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunohistochemistry. Results: A progressive loss of spiral ganglion cells with increasing time after gentamicin treatment was observed on light microscopic examination. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining demonstrated induction of apoptotic cell death in SGNs after gentamicin treatment. Expression of FasL increased over time after gentamicin treatment as determined by RT-PCR and western blotting. On immunohistochemical staining, we observed the localization of FasL in the SGNs. The proapoptotic molecules Bax and Bad were increased, but levels of the antiapoptotic molecule Bcl-2 were decreased at increasing survival times after gentamicin treatment on RT-PCR. The gentamicin-treated group displayed initial activation of caspase-8 and increased the cleavage of caspase-3, caspase-8, and PARP protein in a time-dependent manner. Conclusions: The secondary apoptosis of SGNs could be a result of the apoptotic Fas,FasL signaling pathway. Blocking the Fas,FasL signaling pathway could be considered as a method for preventing secondary degeneration of SGNs, and further studies are needed to confirm this. [source] Angiogenesis: now and then,APMIS, Issue 7-8 2004CARLA COSTA Angiogenesis or new blood vessel formation plays an essential role during embryogenesis, adult vascular remodeling and in several pathological disorders, as in tumor development. Although sprouting of blood vessels is the principal angiogenic mechanism, additional ones, such as the recruitment of bone marrow-derived cells, have recently been described. These processes are controlled by several molecules, although members of the VEGF family of angiogenic factors and its receptors seem to be the main mediators. Initially, VEGF receptors were described as endothelial specific; however, further studies have reported their presence in several types of cells of non-endothelial origin, such as tumor cells. This VEGF receptor altered expression has suggested an angiogenesis-independent growth advantage mechanism on certain types of cancers by the generation of autocrine loops. A possible role in tumorigenesis and a potential novel target in cancer therapy have been hypothesized. Detection of other receptors and molecules considered to be angiogenic players has also been observed on tumor cells. Currently, their clinical significance as well as their potential as therapeutic targets for the treatment of certain cancers is being evaluated, having in mind the future development of promising mechanism-based therapies. The aspects mentioned above are the main focus of this review, which aims to throw light on recent findings respecting angiogenesis and novel therapeutic approaches. [source] Tyrosine and phenylalanine supplementation on Diplodus sargus larvae: effect on growth and qualityAQUACULTURE RESEARCH, Issue 10 2010Margarida Saavedra Abstract Phenylalanine is the precursor of tyrosine, which is involved in the synthesis of several molecules with key roles in the regulation of metabolism and growth, stress response and pigmentation. In this study, three experimental diets were tested: an amino acid (AA) balanced diet supplemented with phenylalanine, another supplemented with phenylalanine and tyrosine and a non-supplemented AA balanced diet. Rotifers were enriched with liposomes encapsulating free AA in order to obtain a balanced AA profile. The experimental diets resulted in similar larval survival, growth, enzyme activities of AA catabolism and nitrogen excretion in all treatments. High levels of skeletal deformities were registered and significant differences were found between the control and the phenylalanine treatment for the percentage of vertebral compressions in the trunk region of the vertebral column (30% in the control and 5% in the phenylalanine group). A significantly higher survival to a temperature stress test was found for larvae fed the diet supplemented with phenylalanine and tyrosine. The results suggest that supplementation of phenylalanine/tyrosine in fish diets may be useful in order to reduce skeletal deformities and mortalities caused by stress. The present study confirms that AA requirements may be sufficient for covering growth and survival but insufficient to cover other metabolic processes. [source] U1A RNA-binding domain at 1.8,Å resolutionACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2003Peter B. Rupert The human U1A RNA-binding domain (RBD1) adopts one of the most common protein folds, the RNA-recognition motif, and is a paradigm for understanding RNA,protein interactions. A 2.8,Å resolution structure of the unbound RBD1 has previously been determined [Nagai et al. (1990). Nature (London), 348, 515,520] and revealed a well defined ,/, core with disordered termini. Using a longer construct, a 1.8,Å resolution structure of the unbound domain was determined that reveals an ordered C-terminal helix. The presence of this helix is consistent with a solution structure of the free domain [Avis et al. (1996). J. Mol. Biol.257, 398,411]; however, in the solution structure the helix occludes the RNA-binding surface. In the present structure, the helix occupies a position similar to that seen in a 1.9,Å resolution RNA,RBD1 complex structure [Oubridge et al. (1994). Nature (London), 372, 432,438]. The crystals in this study were grown from 2.2,M sodium malonate. It is possible that the high salt concentration helps to orient the C-terminal helix in the RNA-bound conformation by strengthening hydrophobic interactions between the buried face of the helix and the ,/, core of the protein. Alternatively, the malonate (several molecules of which are bound in the vicinity of the RNA-binding surface) may mimic RNA. [source] Structural studies of the catalytic core of the primate foamy virus (PFV-1) integraseACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 8 2010Stéphane Réty Retroviral integrases are vital enzymes in the viral life cycle and thus are important targets for antiretroviral drugs. The structure of the catalytic core domain of the integrase from human foamy virus, which is related to HIV-1, has been solved. The structure of the protein is presented in two different crystal forms, each containing several molecules in the asymmetric unit, with and without the essential manganese or magnesium ion, and the structures are compared in detail. This allows regions of high structural variability to be pinpointed, as well as the effect of divalent cations on the conformation of the catalytic site. [source] Evidence for Yeast Autophagy during Simulation of Sparkling Wine Aging: A Reappraisal of the Mechanism of Yeast Autolysis in WineBIOTECHNOLOGY PROGRESS, Issue 2 2005Eduardo Cebollero Yeast autolysis is the source of several molecules responsible for the quality of wines aged in contact with yeast cells. However, the mechanisms of yeast autolysis during wine aging are not completely understood. All descriptions of yeast autolysis in enological conditions emphasize the disturbance of cell organization as the starting event in the internal digestion of the cell, while no reference to autophagy is found in wine-related literature. By using yeast mutants defective in the autophagic or the Cvt pathways we have demonstrated that autophagy does take place in wine production conditions. This finding has implications for the genetic improvement of yeasts for accelerated autolysis. [source] Wnt signaling in caudal dysgenesis and diabetic embryopathyBIRTH DEFECTS RESEARCH, Issue 10 2008Gabriela Pavlinkova Abstract BACKGROUND: Congenital defects are a major complication of diabetic pregnancy, and the leading cause of infant death in the first year of life. Caudal dysgenesis, occurring up to 200-fold more frequently in children born to diabetic mothers, is a hallmark of diabetic pregnancy. Given that there is also an at least threefold higher risk for heart defects and NTDs, it is important to identify the underlying molecular mechanisms for aberrant embryonic development. METHODS: We have investigated gene expression in a transgenic mouse model of caudal dysgenesis, and in a pharmacological model using situ hybridization and quantitative real-time PCR. RESULTS: We identified altered expression of several molecules that control developmental processes and embryonic growth. CONCLUSIONS: The results from our models point towards major implication of altered Wnt signaling in the pathogenesis of developmental anomalies associated with embryonic exposure to maternal diabetes. Birth Defects Research (Part A) 82:710,719, 2008. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||||||||