bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Design of Neutral Intramolecular Complexes Bearing Two Silicon Atoms Anchored by a Carbonyl Oxygen Atom:N,N′‐Bis(silylmethyl)propylene Ureas
Authors: Sidorkin Valery F. , Belogolova Elena F. , Pestunovich Vadim A.
Published: December 2005

B3LYP and MP2 computations have been performed on a variety ofSi,Si′‐substitutedN,N′‐bis(silylmethyl)propylene ureas. According to electron‐density atoms‐in‐molecules (AIM) and electron localization function (ELF) quantum‐topological analyses, a transition from the unstable non‐chelate forms of these compounds to mono‐ and bis‐chelate forms results in the successive interaction of one and two tetracoordinate silicon atoms with the carbonyl oxygen and the formation, respectively, of one and two covalent, polar Si⋅⋅⋅O bonds. This previously unknown XSi←O→SiX type of bonding in isomers possessing an anchor structure may be classified as a five‐center, six‐electron (5c‐6e) bond. The factors that favor the existence ofSi,Si′‐substitutedN,N′‐bis(silylmethyl)propylene ureas exclusively in the form of stable, bridged complexes (the size of equatorial ligands and the electronegativity of axial substituents at the silicon atom, change in the donor capability of the carbonyl group, and effect of the polar solvent) are discussed.
Synthesis and Some Properties of Binuclear Ruthenocenes Bridged by Oligoynes: Formation of Bis(cyclopentadienylidene)cumulene Diruthenium Complexes in the Two‐Electron Oxidation
Authors: Sato Masaru , Kubota Yusuke , Kawata Yasushi , Fujihara Takashi , Unoura Kei , Oyama Aiko
Published: December 2005

The monoynes [Rc*CCRc*] and [Rc′CCRc′] were obtained in improved yields using [Mo(CO)6]/2‐FC6H5OH as a catalyst in the alkyne metathesis of [Rc*CCMe] and [Rc′CCMe], respectively (Rc=ruthenocenyl, Rc*=1′′,2′′,3′′,4′′,5′′‐pentamethylruthenocenyl, and Rc′=2′,3′,4′,5′‐tetramethylruthenocenyl groups). The diynes [Rc*(CC)2Rc*] and [Rc′(CC)2Rc′] were synthesized by the oxidative coupling of the corresponding terminal ethynes in good yields. The triyne [Rc*(CC)3Rc*] and the tetrayne [Rc*(CC)4Rc*] were prepared by the hetero‐ and homocoupling of [Rc*CCCCH], which was obtained from the reaction of [Rc*CCCHO] with Li[N2CSiMe3], respectively. Although the oxidation waves did not always exhibit a clear two‐electron oxidation process, the oxidation potentials shifted to a lower potential with an increase in the number of methyl substituents on the ruthenocenyl ring, and shifted to a higher potential with the increase in the number of CC units; this result is in contrast to that found in the [Rc(CHCH)nRc] series. The chemical oxidation of [Rc′CCRc′] yielded a stable two‐electron‐oxidized species, the structure of which was confirmed by X‐ray crystallography to be [Ru2(μ2‐ η6:η6‐C5Me4CCC5Me4)(η‐C5H5)2](BF4)2. Changing the substituents (Rc, Rc*, and Rc′) had no effect on the chemical oxidation, but in the case of the Rc′ series the Me substituent increased the stability of the two‐electron‐oxidized species in solution. The diyne [Rc*(CC)2Rc*] and the triyne [Rc*(CC)3Rc*] also gave a similar but unstable two‐electron‐oxidized species. In acetone or acetonitrile, the two‐electron‐oxidized species of [Rc*CCRc*] and [Rc*(CC)2Rc*] gradually formed the corresponding bis(fulvene)‐type complexes. This implies that the two‐electron‐oxidized species of [Rc*(CC)nRc*] are destabilized with the increasing n.
Polar Self‐Assembly: Steric Effects Leading to Polar Mixed‐Ligand Coordination Cages
Authors: Zhang Jianyong , Miller Philip W. , Nieuwenhuyzen Mark , James Stuart L.
Published: December 2005

We present a highly unusual example of self‐assembly, specifically a polar, mixed‐ligand cage which forms in preference to symmetrical homo‐ligand products, and which suggests that steric effects can be exploited to obtain novel non‐uniform polyhedral cages. In particular, reaction between the bulky tripodal triphosphine 2,4,6‐tris(diphenylphosphino)triazine, L1, the non‐bulky tripodal trinitrile 2,4,6‐tris(cyanomethyl)trimethylbenzene, L2 and silver hexafluoroantimonate, AgSbF6, in a 3:1:4 ratio gives the mixed‐ligand aggregate [Ag4(L1)3(L2)(SbF6)]3+, 1‐SbF6, instantly as the only product in quantitative yield. The X‐ray crystal structure of complex 1‐SbF6 is consistent with the suspected solution‐state structure. The cage derives from trigonal‐pyramidal geometry, the basal vertices of which are defined by three bulky triphosphines, L1, and the apical vertex by the non‐bulky trinitrile, L2. There is apical elongation amounting to 19 % in comparison to the ideal uniform tetrahedron. The cage also encapsulates an SbF6 anion. 19F NMR spectra in solution for the analogous PF6 complex [Ag4(L1)3(L2)(PF6)]3+, 1‐PF6, confirm that one anion is also encapsulated in solution. The synthesis of the analogous CF3SO3− complex, [Ag4(L1)3(L2)(OTf)]3+, 1‐OTf, in solution is also described, although 1‐PF6 and 1‐OTf could not be isolated due to slow decomposition in solution. The selective formation of these mixed‐ligand cages is discussed in terms of ligand–ligand and ligand‐included anion steric repulsions, which we propose prevent the formation of the competing hypothetical homo‐ligand tetrahedral structure [Ag4(L1)4(SbF6)]3+, and thus favour the mixed ligand cage. “Cage cone angles” for L1 and L2 are estimated at 115 ° and 101 °, respectively. Variable‐temperature 31P NMR spectroscopy shows that complex 1‐SbF6 and the related previously reported partial tetrahedral complex [Ag4(L1)3(anion)]3+ undergo dynamic twisting processes in solution between enantiomeric C3‐symmetry conformations.
Associations of demographic and lifestyle characteristics with prostate‐specific antigen (PSA) concentration and rate of PSA increase
Authors: Kristal Alan R. , Chi Chen , Tangen Catherine M. , Goodman Phyllis J. , Etzioni Ruth , Thompson Ian M.
Published: December 2005

BACKGROUND

The objective of this study was to examine whether demographic and lifestyle characteristics are associated with prostate‐specific antigen (PSA) levels and the rate of PSA increase (PSA velocity).

METHODS

Data for this study came from 3341 participants in the placebo arm of the Prostate Cancer Prevention Trial who, based on biopsies at the end of the study, were free of prostate carcinoma. Linear regression was used to assess associations of age, race, smoking, body mass index (BMI), physical activity, diet, and supplement use with PSA concentration during the second year of the trial, and linear mixed models were used to assess associations of these factors with PSA velocity (the percentage increase in PSA per year) during 6 years of the trial.

RESULTS

Between the group of men ages 50–59 years and the group of men age 70 years and older, mean PSA increased by 0.22 ng/mL, and PSA velocity decreased by 1.2 percentage points (both P < 0.001). The PSA level among men who had a BMI ≥ 35 kg/cm2 was 0.20 ng/mL lower than the PSA level among men who had a BMI < 25 kd/cm2 (P < 0.001), but BMI was not associated with PSA velocity. PSA velocity was 1.2 percentage points higher in African‐American men compared with white men (P = 0.043). Low energy intake and the use of high‐dose calcium supplements were associated with significantly lower PSA velocity (both P = 0.05). Weight gain also was associated with lower PSA velocity.

CONCLUSIONS

Differences in PSA concentration associated with demographic and lifestyle characteristics were small and were not likely to bias the interpretation of a single PSA test. Age, race, energy intake, calcium supplement use, and weight change were associated with substantial differences in PSA velocity, and the clinical interpretation of PSA velocity may be biased by these factors. Cancer 2006. © 2005 American Cancer Society.
Predictors of enrollment in lung cancer clinical trials
Authors: Du Wei , Gadgeel Shirish M. , Simon Michael S.
Published: December 2005

BACKGROUND

Clinical trials may offer patients innovative therapeutic options with potentially better outcomes, which are particularly relevant for patients afflicted with lung carcinoma, because current therapies provide only modest survival benefits. Only approximately 5% of patients with newly diagnosed cancer participate in clinical trials nationwide, and African‐American (AA) patients are particularly under‐represented.

METHODS

To determine predictors of clinical trials enrollment, the authors reviewed the medical records of 427 patients with lung carcinoma (175 AA patients and 252 non‐AA patients) who were eligible for clinical trials between 1994 and 1998 at the Karmanos Cancer Institute in Detroit, Michigan. Logistic regression analysis was used to assess the association of patient demographic characteristics and clinical trial enrollment.

RESULTS

Ninety‐one patients (21%) were enrolled onto a lung cancer clinical trial during the period of the current study. Enrollment was associated significantly with race (P < 0.001), gender (P = 0.048), age (P = 0.005), and insurance type (P = 0.024). After multivariable adjustment, only race and gender remained significant predictors of enrollment. AA patients were less likely to enroll than non‐AA patients (odds ratio [OR], 0.485; 95% confidence interval [95% CI], 0.243–0.966), and men were more likely than women to enroll (OR, 1.812; 95% CI, 1.033–3.178).

CONCLUSIONS

The current results suggest disparities by race and gender in the enrollment of patients onto lung cancer clinical trials and support the need to improve educational and outreach endeavors that would make clinical trials available to a wider range of eligible patients. Cancer 2006. © 2005 American Cancer Society.
Atmospheric Plasma Deposition of Coatings Using a Capacitive Discharge Source
Authors: Moravej M. , Hicks R. F.
Published: December 2005

In this paper, a review is provided of the plasma‐enhanced (PE)CVD of thin films using an atmospheric‐pressure (AP) capacitive discharge source. This source is unique in that the organometallic precursors are fed downstream of the plasma, where reactions occur exclusively between neutral molecules, radicals, and the substrate surface. As a result, the properties of the films differ from those obtained in low‐pressure (<1 torr) gas discharges. For example, glass may be deposited on plastic with no carbon contamination and less than 15 mol‐% hydroxyl groups, yielding material with good scratch protection. Silicon nitride and amorphous hydrogenated silicon films have also been prepared by AP‐PECVD. These material processes further illustrate the unique attributes of this new deposition technology.
Aerosol‐Assisted Plasma Deposition of Barrier Coatings using Organic‐Inorganic Sol‐Gel Precursor Systems
Authors: Vangeneugden D. , Paulussen S. , Goossens O. , Rego R. , Rose K.
Published: December 2005

Hybrid organic‐inorganic precursors and sol–gel systems thereof, obtained via wet‐chemical hydrolysis, were atomized and introduced into an atmospheric pressure dielectric barrier discharge (DBD) in nitrogen. The precursors used are tetraethoxysilane (TEOS), glycidoxypropyltrimethoxysilane (GLYMO), methacryloxypropyltrimethoxysilane (MEMO), propyltrimethoxysilane (PTMO), and a new high molecular weight siloxane precursor (Bayrecit). The obtained coatings were analyzed by means of Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and field emission scanning electron microscopy (FESEM). Deposition rates varied between 30 nm min–1 and 175 nm min–1. Injection of hydrolized sol–gel precursor systems resulted in higher deposition rates. Films deposited on PET foil were tested for their oxygen barrier properties. Plasma‐assisted coating deposition of the sol–gel systems proved to be superior to wet‐chemical application and conventional thermal or UV curing. However, the best barrier performance was obtained with a coating from non‐hydrolyzed Bayrecit. The lowest oxygen transmission rate (OTR) on PET obtained so far is 5 cm3 m–2 day–1 bar–1.
Chemical Vapor Deposition Enhanced by Atmospheric Pressure Non‐thermal Non‐equilibrium Plasmas
Authors: Alexandrov S. E. , Hitchman M. L.
Published: December 2005

This review gives an overview of the characteristics of various non‐thermal, non‐equilibrium plasmas and discusses applications of AP‐PECVD with dielectric barrier discharges, corona discharges, RF discharges, and microwave discharges.
Editorial: Atmospheric Pressure Plasma Enhanced CVD
Authors: Hitchman M. L.
Published: December 2005

This is an innovative issue of CVD for it is the first devoted to a single topic: Atmospheric Pressure PECVD (AP‐PECVD). A brief overview is given of the subject of AP‐PECVD, of the papers in this Special Issue, and of the exciting possibilities for commercial developments of the technology. The Editor highlights future Special Issues that have been commissioned and are in preparation.
The involvement of neuropeptides in evolution, signaling, behavioral regulation and psychopathology: focus on vasopressin
Authors: Landgraf Rainer , Holsboer Florian
Published: December 2005

This brief commentary focuses on the involvement of neuropeptides in a variety of brain functions. As exemplified with vasopressin, neuropeptides are released within distinct brain areas to contribute to regionally and temporally varying modes of neuromodulator and neurotransmitter actions, thus providing a theoretically unlimited variability in interneuronal signaling. As primary products of protein biosynthesis, neuropeptides and their receptors are critical substrates for the evolution of behavior, including emotionality. Particularly its capability of responding to stressful stimuli and mediating genetic polymorphisms make the central release of vasopressin a key process for converging (i.e., environmentally and genetically driven) behavioral regulation. This release along a continuum from basal to very high levels in the extracellular fluid of distinct brain areas explains the wide spectrum of vasopressin effects in the brain, including its role in psychopathology. Drug Dev. Res. 65:185–190, 2005. © 2005 Wiley‐Liss, Inc.
Homeostasis within the corticotropin‐releasing factor system via CRF2receptor activation: a novel approach for the treatment of anxiety
Authors: Valdez Glenn R. , Zorrilla Eric P. , Koob George F.
Published: December 2005

Anxiety and depression are highly prevalent forms of mental illness that are often thought of as stress‐related disorders because their symptoms are frequently triggered by stressful life events. Clinical studies provide strong evidence for the involvement of corticotropin‐releasing factor (CRF), a key regulator of the stress response, in anxiety and depression. Recent evidence from studies involving CRF2receptor knockout mice and CRF2receptor‐specific ligands suggests that the two CRF receptor subtypes have a differential role in mediating the stress response, where activation of the CRF1receptor leads to increases in the stress response and the CRF2receptor represents a compensatory coping mechanism to oppose this action. This proposed differential regulation of stress‐related behaviors via the two CRF receptor subtypes suggests that a disruption of homeostasis within the stress system may be a key underlying factor in the regulation of psychiatric disorders associated with chronic stress. Therefore, it appears that restoring the neurochemical balance within the CRF system via CRF2receptor activation may provide a novel approach in the treatment of stress‐related disorders. Drug Dev. Res. 65:205–215, 2005. © 2005 Wiley‐Liss, Inc.
Galanin receptors as novel drug targets for the treatment of depression and anxiety
Authors: Lu Xiaoying , Barr Alasdair M. , Bartfai Tamas
Published: December 2005

The 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

Melanin‐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

The 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

Recent 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

The 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

A 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

Streptococcus 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

Thymic 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

Ginsan, 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

Expression 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

A 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

The 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

Hydrolysis 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

The 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

Molecular 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

CE 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

Fluorophore‐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

Cholinesterases (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.
Proteomic evaluation reveals that olfactory ensheathing cells but not Schwann cells express calponin
Authors: Boyd J. Gordon , Jahed Ali , McDonald Todd G. , Krol Karmen M. , Van Eyk Jennifer E. , Doucette Ronald , Kawaja Michael D.
Published: December 2005

Human clinical trials have begun worldwide that use olfactory ensheathing cells (OECs) to ameliorate the functional deficits following spinal cord injury. These trials have been initiated largely because numerous studies have reported that OECs transform into Schwann Cell (SC)‐like cells that myelinate axons and support new growth in adult rats with spinal injury. This phenomenon is remarkable because OECs do not myelinate olfactory axons in their native environment. Furthermore, these myelinating OECs are morphologically identical to SCs, which can invade the spinal cord after injury. One factor that has contributed to a possible confusion in the identification of these cells is the lack of phenotypic markers to distinguish unequivocally between OECs and SCs. Such markers are required to first assess the degree of SC contamination in OEC cultures before intraspinal implantation, and then to accurately identify grafted OECs and invading SCs in the injured spinal cord. Using two‐dimensional gel electrophoresis, we have identified calponin, an actin binding protein, as the first definitive phenotypic marker that distinguishes between OECs and SCs in vitro and in vivo. We have also provided ultrastructural evidence that calponin‐immunopositive OECs do not transform into myelinating SC‐like cells after intraspinal implantation. Rather, the grafted OECs retain their morphological and neurochemical features. These data yield new insight into the phenotypic characteristics of OECs, which together with invading SCs can enhance regeneration of the injured spinal cord. © 2005 Wiley‐Liss, Inc.
cAMP cascade (PKA, Epac, adenylyl cyclase, Gi, and phosphodiesterases) regulates myelin phagocytosis mediated by complement receptor‐3 and scavenger receptor‐AI/II in microglia and macrophages
Authors: Makranz Chen , Cohen Goni , Reichert Fanny , Kodama Tatsuhiko , Rotshenker Shlomo
Published: December 2005

The removal by phagocytosis of degenerated myelin is central for repair in Wallerian degeneration that follows traumatic injury to axons and in autoimmune demyelinating diseases (e.g., multiple sclerosis). We tested for roles played by the cAMP cascade in the regulation of myelin phagocytosis mediated by complement receptor‐3 (CR3/MAC‐1) and scavenger receptor‐AI/II (SRAI/II) separately and combined in mouse microglia and macrophages. Components of the cAMP cascade tested are cAMP, adenylyl cyclase (AC), Gi, protein kinase A (PKA), exchange protein directly activated by cAMP (Epac), and phosphodiesterases (PDE). PKA inhibitors H‐89 and PKI14‐22 amide inhibited phagocytosis at normal operating cAMP levels (i.e., those occurring in the absence of reagents that alter cAMP levels), suggesting activation of phagocytosis through PKA at normal cAMP levels. Phagocytosis was inhibited by reagents that elevate endogenous cAMP levels to above normal: Gi‐inhibitor Pertussis toxin (PTX), AC activator Forskolin, and PDE inhibitors IBMX and Rolipram. Phagocytosis was inhibited also by cAMP analogues whose addition mimics abnormal elevations in endogenous cAMP levels: nonselective 8‐bromo‐cAMP, PKA‐specific 6‐Benz‐cAMP, and Epac‐specific 8‐CPT‐2′‐O‐Me‐cAMP, suggesting that abnormal high cAMP levels inhibit phagocytosis through PKA and Epac. Altogether, observations suggest a dual role for cAMP and PKA in phagocytosis: activation at normal cAMP levels and inhibition at higher. Furthermore, a balance between Gi‐controlled cAMP production by AC and cAMP degradation by PDE maintains normal operating cAMP levels that enable efficient phagocytosis. ©2005 Wiley‐Liss, Inc.
Survival of neural precursor cells in growth factor‐poor environment: Implications for transplantation in chronic disease
Authors: Einstein Ofira , Ben‐Menachem‐Tzidon Ofra , Mizrachi‐Kol Rachel , Reinhartz Etti , Grigoriadis Nikolaos , Ben‐Hur Tamir
Published: December 2005

A key issue for therapeutic neural stem cell transplantation in chronic diseases is the long‐term survival of transplanted cells in the brain. The normal adult central nervous system does not support the survival of transplanted cells. Presumably, the limited availability of trophic factors maintains the survival of resident cells but is insufficient for supporting the survival of transplanted cells. Specifically, in multiple sclerosis, a chronic relapsing disease, it would be necessary to maintain long‐term survival of transplanted cells through phases of relapses and remissions. It may be beneficial to transplant cells as early as possible, in a form that will keep their survival independent of tissue support and ready for immediate mobilization upon tissue demand during disease relapse. In the present study, we examined whether, in the form of neurospheres, multipotential neural precursor cells (NPCs) survive in a growth factor‐poor environment while maintaining their potential to respond to environmental cues. We found that after removal of growth factors from the culture medium of neurospheres in vitro, NPC proliferation decreased significantly, but most cells survived for a prolonged time and maintained their stem cell characteristics. After re‐exposure to growth factors, neurosphere cells resumed proliferation and could differentiate along neural lineages. Furthermore, neurospheres, but not single NPCs, that were transplanted into the brain ventricles of intact animals survived within the ventricles for at least a month and responded to induction of experimental autoimmune encephalomyelitis and brain inflammation by extensive migration into the brain white matter and differentiated into glial lineage cells. © 2005 Wiley‐Liss, Inc.
Prognostic impact of cytogenetic aberrations in patients with multiple myeloma or monoclonal gammopathy of unknown significance
Authors: Schilling Georgia , Dierlamm Judith , Hossfeld Dieter K
Published: December 2005

Chromosomal aberrations are the most important prognostic factors in haematological malignancies. Detection of certain genetic changes leads to risk adapted strategies in leukaemia therapy. In multiple myeloma the importance of genetic alterations and their prognostic impact is of growing interest. Several therapeutic approaches seem to be uneffective for patients harbouring certain chromosomal abnormalities.

Although the yield of metaphases due to a low proliferation rate is considerably lower in plasma cell dyscrasias, a number of chromosomal changes with prognostic implications have been identified in the past years, particularly due to the introduction of new techniques.

This article gives a short survey of the most important genetic alterations and their prognostic influence on the outcome of patients with plasma cell malignancies known to date. Copyright © 2005 John Wiley & Sons, Ltd.
Evidence of abortive plasma cell differentiation in Hodgkin and Reed‐Sternberg cells of classical Hodgkin lymphoma
Authors: Buettner Maike , Greiner Axel , Avramidou Athanasia , Jäck Hans‐Martin , Niedobitek Gerald
Published: December 2005

Hodgkin and Reed‐Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) show genotypic features of germinal centre‐derived B‐cells in most cases. Nevertheless, these cells typically lack expression of B‐cell antigens. Previous studies have suggested that plasma cell differentiation may occur in HRS cells and that this may account for the down‐regulation of B‐cell antigens. However, these results are controversial. We have addressed this question using immunohistochemistry and a panel of antibodies directed against antigens which are differentially expressed during terminal B‐cell differentiation. Pax‐5, a transcription factor required for B‐lineage commitment, and IRF4/Mum1, which is physiologically expressed in germinal centre cells and plasma cells, were consistently detectable in HRS cells. Bcl‐6, a transcription factor expressed in germinal centre B‐cells, was present in HRS cells of approximately 25% of cHL cases. Expression of the B‐lymphocyte‐induced maturation protein‐1 (Blimp‐1), a key regulator of plasma cell differentiation, was observed in HRS cells of 23% of cHL cases. In these cases, Blimp‐1 expression was restricted to a small proportion of HRS cells. HRS cells were consistently negative for the plasma cell marker CD138. These results suggest that plasma cell differentiation may be initiated in a small subset of HRS cells but remains abortive. Thus, terminal differentiation is unlikely to explain the lack of B‐cell antigen expression in HRS cells. Copyright © 2005 John Wiley & Sons, Ltd.