bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galanin receptors as novel drug targets for the treatment of depression and anxiety
Authors: Lu Xiaoying , Barr Alasdair M. , Bartfai Tamas 
Published: December 2005

AbstractThe neuropeptide galanin and its three receptors are widely distributed throughout the mammalian brain, with highest levels in limbic brain nuclei. Galanin is co‐localized with classical neurotransmitters, including acetylcholine and the monoamines serotonin and noradrenaline. Behaviorally, the galaninergic system regulates numerous cognitive and affective behaviors that are essential for normal homeostasis. Recently, a large body of preclinical evidence suggests that galanin and its receptors represent putative targets for the development of novel anxiolytic and antidepressant drugs, which we describe in detail in the current review. Studies of galanin receptor knockout mice indicate a role for both the galanin receptor type 1 (GalR1) and GalR2 in mouse models of anxiety. We have previously demonstrated that levels of galanin mRNA are increased in limbic brain nuclei after different modalities of antidepressant treatment in rats, whereas the behavioral effects of a subchronic selective serotonin reuptake inhibitor can be reversed by the galanin receptor antagonist M40. Furthermore, the systemically active GalR1/GalR2 agonists, galnon and galmic, display antidepressant‐like effects in the rat forced swim test. Initial results with a selective GalR3 antagonist indicate similar antidepressant‐like effects in both rat and mouse preclinical screens. These promising results warrant further study of the galaninergic system as a novel substrate for the development of both anxiolytic and antidepressant drugs. Drug Dev. Res. 65:227–236, 2005. © 2005 Wiley‐Liss, Inc.
Melanin‐concentrating hormone receptor 1 antagonists for the treatment of depression and anxiety
Authors: Chaki Shigeyuki , Yamaguchi Jun‐ichi , Yamada Hisaharu , Kanuma Kosuke , Sekiguchi Yoshinori 
Published: December 2005

AbstractMelanin‐concentrating hormone (MCH) is a cyclic, 19‐amino‐acid neuropeptide produced in the lateral hypothalamus. MCH is implicated in a number of physiological processes including feeding behavior, energy balance, reproductive function, memory, sleep‐wake regulation, and emotional states. Since the discoveries in the mid‐1990 s that MCH is an appetite stimulant in rodents and that KO mice lacking MCH become lean, together with the findings that MCH receptor 1 (MCH1R) is responsible for these functions, most research has been focused on the roles of the MCH system in feeding and energy homeostasis. It is now established that MCH plays a key role in controlling feeding and energy homeostasis via MCH1R, and some pharmaceutical companies have reported nonpeptidic MCH1R antagonists with diverse structural features in the treatment of obesity. Recently, emerging lines of evidence have indicated that MCH1R plays important roles not only in feeding and energy balance but also in regulation of emotion. Indeed, MCH1R is widely distributed in the regions associated with emotion, and MCH1R antagonists have been demonstrated to exhibit antidepressant and anxiolytic effects in various rodent models. This review describes recent advances in research to clarify the involvement of MCH in depression and anxiety. The paper will also discuss the potential value of MCH1R antagonists in the treatment of depressive and anxiety disorders. Drug Dev. Res. 65:278–290, 2005. © 2005 Wiley‐Liss, Inc.
Small molecule melanin‐concentrating hormone receptor 1 (MCH1R) antagonists as anxiolytic and antidepressive agents
Authors: Dyck Brian 
Published: December 2005

AbstractThe search for new anxiolytics and antidepressants with a more rapid onset of action has led researchers to pursue neuropeptide receptors as molecular targets for these indications. Among these peptide targets, melanin‐concentrating hormone (MCH) has shown promising, albeit inconsistent, data supporting a role for this peptide in human emotional disorders. Neurochemical and neuroanatomical studies have revealed that MCH plays a key role in animal feeding and other behavior; however, alteration of MCH signaling by transgenesis or treatment with endogenous and synthetic MCH1R ligands has produced confounding results in animal models of human emotional disorders. This review describes recent contributions to the understanding of the role of MCH in animal stress response. Drug Dev. Res. 65:291–300, 2005. © 2005 Wiley‐Liss, Inc.
Preclinical approaches to examine novel concepts of the pathophysiology of depressive disorders: lessons learned from tree shrews
Authors: Fuchs Eberhard , Czéh Boldizsár , Flügge Gabriele 
Published: December 2005

AbstractRecent studies have provided evidence that mood disorders such as major depression not only have a neurochemical basis but are also associated with alterations in neuronal and glial structures. Antidepressants may act by restoring structure as well as function of neural networks meaning that they may, as a fundamental principle, affect neural plasticity underlying normal brain functioning. To examine this novel concept of the pathophysiology of depression and antidepressant medication, we have carried out a series of experiments using the social stress paradigm in tree shrews, an animal model with a high validity for the pathophysiology of major depression. We found that 1 month of stress reduced the proliferation rate of newly born neurons in the dentate gyrus and decreased hippocampal volume. Notably, the suppressive effects of social conflict stress on hippocampal structure could be counteracted by treatments with different antidepressants such as clomipramine, tianeptine, and the selective NK1 receptor antagonists L‐760735. In addition, the stress‐induced decrease in number of parvalbumin‐containing cells in the hippocampal formation, presumably GABAergic interneurons, was prevented by concomitant treatment with fluoxetine. These studies show that different classes of antidepressants can reverse the structural alterations of the hippocampal formation induced by stress. Drug Dev. Res. 65:309–317, 2005. © 2005 Wiley‐Liss, Inc.
Remission and recovery in depression treatment
Authors: Trivedi Madhukar H. , Kleiber Beverly , Greer Tracy L. 
Published: December 2005

AbstractThe array of drugs available for the treatment of Major Depressive Disorder (MDD) continues to increase. Treatment emphasis has shifted away from an “adequate” response to an antidepressant medication, moving toward the goal of full symptomatic remission and return to normal function. This has been aided by the advent of treatment algorithms or guidelines. These algorithms provide a comprehensive plan for addressing MDD, starting with the simplest, safest treatment and methodically progressing towards more complicated treatment if the patient proves to be treatment‐refractory. Clinicians may choose to switch medications if a patient shows no response, and partial responders may continue a given treatment, adding an augmenting agent. Remission rates may be higher for those drugs that act on both serotonin and norepinephrine receptors. Whether a dual action medication or a combination of drugs with differing mechanisms of action, the resultant synergistic effects are often beneficial. Difficulties remain in treating patients with MDD, including inadequate treatment and poor patient adherence. Not all patients are helped with the currently available medications. Exciting work is being done on brain‐derived neurotrophic factor (BDNF) and peptide neurotransmitters known as neurokinins. Other current research efforts include monoaminergic modulators such as beta agonists, second messenger systems, 5‐HT1A agonists, partial agonists and antagonists, dual reuptake blocks of serotonin and dopamine, serotonin 1D antagonists (possibly producing a rapid‐onset antidepressant), neurokinin antagonists, and other novel neurotransmitter mechanisms. Ideally, new treatments for MDD should be effective for most people and be quick acting, allowing more patients to reach full, sustained remission and functional recovery. Drug Dev. Res. 65:335–343, 2005. © 2005 Wiley‐Liss, Inc.
Stability of IQ measures in teenagers and young adults with developmental dyslexia
Authors: Gunnel Ingesson S. 
Published: December 2005

AbstractA follow‐up study was performed to investigate the stability of IQ measures in a group of dyslexic teenagers and young adults. Earlier research had shown contradictory results. The 65 subjects, 12 years old on the average at first test, were retested after a mean interval of six and a half years. There was a significant relative decrease in verbal IQ (VIQ), which was interpreted as either an effect of low reliability of tests used, or an effect of the dyslexic individuals' less experience with reading and writing, and as a consequence, a lag in verbal ability, the second interpretation being in line with earlier findings in groups of children with learning disabilities. Performance IQ improved significantly and the tentative interpretation was that of a compensatory process, in the sense that the dyslexic children might develop a more visual, intuitive and creative way to process information and solve problems. The conclusion was that caution should be taken, before making important decisions on the basis of a single intelligence test, and that dyslexic children might be at risk to lag behind their peers in terms of VIQ, especially if they are not provided with suitable special education. Copyright © 2005 John Wiley & Sons, Ltd.
Serum and mucosal antibody responses to pneumococcal protein antigens in children:relationships with carriage status
Authors: Zhang Qibo , Bernatoniene Jolanta , Bagrade Linda , Pollard Andrew J. , Mitchell Timothy J. , Paton James C. , Finn Adam 
Published: December 2005

AbstractStreptococcus pneumoniae causes significant morbidity and mortality especially in children. Some pneumococcal protein antigens can protect mice against infection. Little information is available concerning the nature of naturally acquired protective immunity to pneumococci in humans induced by these antigens. This study investigates the relationships between systemic and local antibody production and carriage in children. Children undergoing adenoidectomy (n=112, ages 2–12 years) were studied. Nasopharyngeal swabs were collected for pneumococcal culture. Serum and saliva were assayed for antibodies to several pneumococcal proteins: choline binding protein A (CbpA), pneumolysin (Ply), pneumococcal surface adhesin A (PsaA) and pneumococcal surface protein A (PspA). Adenoidal mononuclear cells (MNC) were cultured with pneumococcal culture supernatants or recombinant proteins. Cell culture supernatants were analyzed for antigen‐specific antibodies. Carriage rates fell with age and serum levels of anti‐CbpA, Ply and PspA rose. Anti‐CbpA and ‐Ply serum and salivary IgG antibody levels were higher in children who were culture negative than those who were colonized. Antigen stimulation increased respective antigen‐specific IgG production by adenoidal MNC and these responses were greater in those who were colonized than in culture‐negative children. Antibodies to CbpA and Ply may protect children aged 2 years and older against pneumococcal colonization. Adenoids may be important local induction and effector sites for both mucosal and systemic antibody production to pneumococcal proteins in children.
CD69 down‐modulation and inhibition of thymic egress by short‐ and long‐term selective chemical agonism of sphingosine 1‐phosphate receptors
Authors: Alfonso Christopher , McHeyzer‐Williams Michael G. , Rosen Hugh 
Published: December 2005

AbstractThymic development requires proliferation, selection, maturation and release of mature single‐positive CD4 and CD8 T cells into the periphery. In mice, non‐selective sphingosine‐1 phosphate (S1P) receptor agonists, active on four of the five known S1P receptors, alter thymocyte phenotype and egress. Here, we show that down‐modulation of CD69 occurs acutely and transiently at a discrete and late stage of medullary development after a single‐dose administration of S1P1 receptor‐selective agonist, which induces long‐term tonic receptor activation in the absence of receptor degradation. In addition, agonist acutely inhibited egress of mature thymocytes into peripheral lymphoid organs, suggesting that both the phenotype and migration of medullary thymocytes are regulated simultaneously and coordinately by agonism of S1P1 alone. Long‐term dosing shifted the early/late medullary thymocyte ratio with an expansion of the late medullary compartment, as mature CD69– thymocytes were retained within the thymus. Therefore, chemical agonism of S1P1 accelerates medullary phenotypic maturation and inhibits egress, leading to the expansion and accumulation of the recent thymocyte emigrant population in the medulla. However, chemical agonism fails to replicate the S1P1‐null CD69hi late medullary phenotype, suggesting that agonism and gene deletion operate by distinct mechanisms, and that functional receptor antagonism may not be required for lymphocyte sequestration.
The immunomodulator ginsan induces resistance to experimental sepsis by inhibiting Toll‐like receptor‐mediated inflammatory signals
Authors: Ahn Ji‐Yeon , Choi In‐Soo , Shim Ji‐Young , Yun Eun‐Kyung , Yun Yeon‐Sook , Jeong Gajin , Song Jie‐Young 
Published: December 2005

AbstractGinsan, a polysaccharide extracted from Panax ginseng, has multiple immunomodulatory effects. In this study, we show that pretreatment of ginsan (25 μg/kg) protected mice from lethality induced by Staphylococcus aureus challenge. This survival benefit was associated with enhanced bacterial clearance from circulation, spleen and kidney. The phagocytic activity of macrophages treated with ginsan was significantly enhanced against S. aureus. However, the production of proinflammatory cytokines, such as TNF‐α, IL‐1β, IL‐6, IFN‐γ, IL‐12, and IL‐18, was markedly down‐regulated in ginsan‐treated mice compared with those of control‐infected mice. The expression of Toll‐like receptor (TLR) 2 and the adaptor molecule MyD88, which was greatly increased in septic macrophages, was significantly reduced by ginsan treatment in vitro. Similarly, the expression of phospho‐JNK1/2, phospho‐p38 MAPK, and NF‐κB was decreased in the same culture system. These results illustrate that the antiseptic activity of ginsan can be attributed to enhanced bacterial clearance, and reduced proinflammatory cytokines via the TLR signaling pathway.
The chicken Ig light chain 3′‐enhancer is essential for gene expression and regulates gene conversion via the transcription factor E2A
Authors: Conlon Thomas M. , Meyer Kerstin B. 
Published: December 2005

AbstractExpression of the rearranged chicken immunoglobulin light chain (IgL) gene is regulated by a V gene promoter, a matrix attachment region (MAR) in the J‐C intron and an enhancer downstream of the Ig constant region. Using knockout analysis, we demonstrate that the 3′‐enhancer is not only required for gene activation but is also essential for the maintenance of gene expression. Deletion of the MAR on the other hand increases IgL transcription, indicating that the MAR acts as negative regulator. We demonstrate that Id1 and Id3, dominant‐negative regulators of basic‐region helix‐loop‐helix (bHLH) transcription factors, are able to reduce chicken IgL 3′‐enhancer activity in transient assays and strongly reduce the rate of gene conversion (GC) in DT40 clone 18 cells. Conversely, overexpression of avian E47, a bHLH transcription factor, leads to a dramatic increase in GC rates independent of IgL or activation‐induced cytidine deaminase RNA levels. Thus, E47 is the first transcription factor to activate GC without an apparent increase in transcription.
Asymmetric Synthesis of the Polyol Subunit of the Polyene Macrolide Antibiotic RK‐397
Authors: Gerber‐Lemaire Sandrine , Carmona Ana T. , Meilert Kai T. , Vogel Pierre 
Published: December 2005

AbstractA total asymmetric synthesis of the polyol subunit of the polyene macrolide antibiotic RK‐397 has been developed by the stereoselective functionalization of (1R,1′S,6S,6′R)‐3,3′‐methylenebis(cyclohept‐3‐ene‐1,6‐diol). The pathway generates a large variety of stereoisomeric intermediates and thus can be applied to the preparation of analogues of this natural antibiotic. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Defunctionalization of γ‐Alkylidene‐α‐hydroxybutenolides by Palladium(0)‐Catalyzed Reaction of Enol Triflates with Hexylboronic Acid
Authors: Ahmed Zafar , Langer Peter 
Published: December 2005

AbstractThe Suzuki reaction of hexylboronic acid with enol triflates derived from γ‐alkylidene‐α‐hydroxybutenolides resulted in reductive formation of α‐unsubstituted γ‐alkylidenebutenolides. The formation of the products can be explained based on an “oxidative addition/transmetalation/β‐hydride elimination/reductive elimination” mechanism. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Acceleration of Thiol Ester Hydrolysis by Cyclodextrins: Evidence from Rate and Computational Studies
Authors: Annalakshmi Subramanian , Pitchumani Kasi 
Published: December 2005

AbstractHydrolysis of diaryl thiol esters with different substituents is studied in the presence of cyclodextrins under alkaline conditions. The presence of cyclodextrin enhances the rate of hydrolysis significantly and covalent catalysis by secondary hydroxy groups of cyclodextrin is proposed. The observed results and the proposed model find support in molecular dynamics simulations and free energy calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Orsellides A–E: An Example for 6‐Deoxyhexose Derivatives Produced by Fungi
Authors: Schlörke Oliver , Zeeck Axel 
Published: December 2005

AbstractThe antibacterial orsellides A–E (1–5), novel esters consisting of orsellinic acid (6) and a 6‐deoxyhexose, were isolated from Chaetomium sp. (strain Gö 100/9) together with the known metabolites globosumones A (7) and B (8). The structures of the new compounds were elucidated by detailed spectroscopic analysis. The biosynthesis of these metabolites was studied by feeding 13C‐labelled precursors to growing cultures of strain Gö 100/9. The sugar moieties of the orsellides A–E (1–5) as well as the side chains of globosumones A (7) and B (8) originate from carbohydrate intermediates. Thus, the orsellides are rare examples for fungal metabolites containing deoxyhexose building blocks that are normally characteristic for bacterial secondary metabolites. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
A novel diagnostic strategy for trisomy 21 using short tandem repeats
Authors: Yan Jing , Wu Jin , Li Yingbi , Wang He , Huang Zhongying , Zhou Xueping , Zhang Weijuan , Hou Yiping 
Published: December 2005

AbstractMolecular technique with STRs can rapidly diagnose aneuploidy. In order to improve its fidelity, we developed a novel STR‐based strategy for fast diagnosis of trisomy 21 and constructed a multimarker diagnostic system according to it. The system is based on nine STRs, of which two were previously known and seven were newly identified from the genomic sequence of the long arm of chromosome 21. They were confirmed to be highly polymorphic in the Chinese population by PCR amplification and gel electrophoresis. The combination of nine STR markers, when applied to DNA from 102 Chinese individuals with normal karyotype, did not yield any false‐positives, and clearly revealed three different alleles in DNA from 15 out of 18 trisomy 21 patients. The results show that our new strategy can provide an alternative molecular technique for the rapid detection of aneuploidy.
Development of a capillary electrophoresis method for the determination of soybean proteins in soybean–rice gluten‐free dietary products
Authors: García‐Ruiz Carmen , García María Angeles , García María Concepcion , Marina María Luisa 
Published: December 2005

AbstractCE has been applied for the first time to the simultaneous separation of soybean and rice proteins. Treated and untreated capillaries with different effective lengths as well as separation media at different pHs were tested. For that purpose, samples and standard solutions were prepared in 25:75 ACN–water media containing 0.3% v/v acetic acid. The use of an untreated capillary of 50 cm effective length together with an 80 mM borate buffer (pH 8.5) modified with 20% v/v ACN and UV detection at 254 nm were the conditions working the best. These conditions enabled the determination of soybean proteins in gluten‐free dietary commercial products elaborated with soybean protein and/or soybean flour and rice flour using the standard additions calibration method. The method was linear up to 26 mg/mL of soybean proteins, the precision (expressed as RSD) was always better than 6%, and recoveries obtained for soybean proteins when spiking commercial products were very close to 100%.
Effect of monosaccharide composition, glycosidic linkage position and anomericity on the electrophoretic mobility of labeled oligosaccharides
Authors: Masuoka James , Hazen Kevin C. 
Published: December 2005

AbstractFluorophore‐assisted carbohydrate electrophoresis (FACE) is useful for separation and characterization of oligosaccharides from various sources and for comparing several samples at once. While characterizing fungal surface glycans by FACE we observed that samples and standards of the same mass did not comigrate as expected. Subsequent experiments showed that the samples did not contain contaminating sugars. Therefore, our observation suggested that glycan electrophoretic mobility is affected by factors in addition to molecular mass. This work assesses the contribution of monosaccharide composition, linkage position, and linkage anomericity to glycan mobility. Commercially available (and synthesized when available) bioses of known composition were derivatized with a charged fluorophore, and electrophoretic mobilities compared in a slab gel format. The results indicate that all three parameters mentioned above affect observed migration. Further, no migration patterns emerged to suggest a set of rules for assigning band identity based on mobility alone. These results emphasize the importance of including known, matched, standards to facilitate interpretation of FACE data.
Capillary electrophoresis versus differential scanning calorimetry for the analysis of free enzyme versus enzyme‐ligand complexes: In the search of the ligand‐free status of cholinesterases
Authors: Rochu Daniel , Cléry‐Barraud Cécile , Renault Frédérique , Chevalier Aurélie , Bon Cassian , Masson Patrick 
Published: December 2005

AbstractCholinesterases (ChEs) are highly efficient biocatalysts whose active site is buried in a deep, narrow gorge. The talent of CE to discover inhibitors in the gorge of highly purified preparations has fairly altered the meaning of a ChE ligand‐free status. To attempt at a description of this one, we investigated the stability of Bungarus fasciatus acetylcholinesterase (AChE), alone or complexed with different inhibitors. Determination of midtransition temperature for thermal denaturation, using differential scanning calorimetry (DSC) and CE, provided conflicting results. Discrepancies strongly question the reality of a ligand‐free AChE state. DSC allowed estimation of the stability of AChE‐ligands complexes, and to rank the stabilizing effect of different inhibitors. CE acted as a detector of hidden ligands, provided that they were charged, reversibly bound, and thus dissociable upon action of electric fields. Then, CE allowed quantification of the stability of ligand‐free AChE. CE and DSC providing each fractional and nonredundant information, cautious attention must be paid for actual estimation of the conformational stability of ChEs. Because inhibitors used in purification of ChEs by affinity chromatography are charged, CE remains a leading method to estimate enzyme stability and detect the presence of bound hidden ligands.