bluuebunny/crossref_metadata_2025 huggingface dataset:
Zwitterionic States in Gas‐Phase Polypeptide Ions Revealed by 157‐nm Ultra‐Violet Photodissociation
Authors: Kjeldsen Frank , Silivra Oleg A. , Zubarev Roman A.
Published: July 2006

A new method of detecting the presence of deprotonation and determining its position in gas‐phase polypeptide cations is described. The method involves 157‐nm ultra‐violet photodissociation (UVPD) and is based on monitoring the losses of CO2 (44 Da) from electronically excited deprotonated carboxylic groups relative to competing COOH losses (45 Da) from neutral carboxylic groups. Loss of CO2 is a strong indication of the presence of a zwitterionic [(+)⋅⋅⋅(−)⋅⋅⋅(+)] salt bridge in the gas‐phase polypeptide cation. This method provides a tool for studying, for example, the nature of binding within polypeptide clusters. Collision‐activated dissociation (CAD) of decarboxylated cations localizes the position of deprotonation. Fragment abundances can be used for the semiquantitative assessment of the branching ratio of deprotonation among different acidic sites, however, the mechanism of the fragment formation should be taken into account. Cations of Trp‐cage proteins exist preferentially as zwitterions, with the deprotonation position divided between the Asp9 residue and the C terminus in the ratio 3:2. The majority of dications of the same molecule are not zwitterions. Furthermore, 157‐nm UVPD produces abundant radical cations M.+ from protonated molecules through the loss of a hydrogen atom. This method of producing M.+ ions is general and can be applied to any gas‐phase peptide cation. The abundance of the molecular radical cations M.+ produced is sufficient for further tandem mass spectrometry (MS/MS), which, in the cases studied, yielded side‐chain loss of a basic amino acid as the most abundant fragmentation channel together with some backbone cleavages.
Chiral Ytterbium Complex‐Catalyzed Direct Asymmetric Aldol‐Tishchenko Reaction: Synthesis of anti‐1,3‐Diols
Authors: Mlynarski Jacek , Rakiel Bartosz , Stodulski Maciej , Suszczyńska Agata , Frelek Jadwiga
Published: July 2006

The asymmetric aldol‐Tishchenko reaction of aromatic aldehydes with aliphatic and aromatic ketones has been developed as an efficient strategy for the synthesis of anti‐1,3‐diols in good yield with high diastereocontrol and good levels of enantioselectivity. This domino‐type reaction is catalyzed by a chiral ytterbium complex that promotes both the aldol reaction through enolization of the carbonyl compound and the Evans–Tishchenko reduction of the aldol intermediate. The stereochemistry of the resulting diols is also investigated and finally proved by using CD techniques.
Cover Picture: Moving Targets: Recognition of Alkyl Groups (Chem. Eur. J. 23/2006)
Authors: Schramm Michael P. , Rebek Julius
Published: July 2006

Unusual conformations are adopted by alkanes to maximize interaction with natural and synthetic hydrophobic cavities. In their Concept article on page 5924 ff., J. Rebek, Jr. and M. P. Schramm describe how the coiling of alkanes results in an increase in steric strain through the introduction of gauche conformations, but through mutual adaptation, the union of host and guest overcomes these otherwise unfavorable interactions.
Plasticity within striatal direct pathway neurons after neonatal dopamine depletion is mediated through a novel functional coupling of serotonin 5‐HT2 receptors to the ERK 1/2 map kinase pathway
Authors: Brown Pierre , Gerfen Charles R.
Published: July 2006

Dysfunction within the striatal direct and indirect projecting systems arises after 6‐hydroxydopamine (6‐OHDA)‐induced dopamine depletion, highlighting the central regulatory function of dopamine in motor systems. However, the striatal 5‐hydroxytryptamine (5‐HT) innervation remains intact after 6‐OHDA lesions, suggesting that the 5‐HT system may contribute to the lesion‐induced dysfunction, or alternatively, it may adapt and compensate for the dopamine deficit. Neonatal 6‐OHDA lesions actually give rise to a 5‐HT axonal hyperinnervation within the dorsal striatum, further reinforcing the idea that the 5‐HT system plays a central role in striatal function after dopamine depletion. Here we show that neonatal but not adult 6‐OHDA lesions result in a novel coupling of 5‐HT2 receptors to the ERK1/2/MAP Kinase pathway, a signaling cascade known to regulate neuronal plasticity. Chloroamphetamine‐induced 5‐HT release or direct stimulation of striatal 5‐HT2 receptors via the 5‐HT2 agonist DOI, produced robust ERK1/2 phosphorylation throughout the dorsal striatum of neonatal lesioned animals, a response not observed within the intact striatum. Pretreatment with the select 5‐HT2 receptor antagonist Ketanserin blocked DOI‐induced ERK1/2 phosphorylation. This drug‐induced ERK1/2 phosphorylation was subsequently shown to be restricted to direct pathway striatal neurons. Our data show that adaptation of direct pathway neurons after neonatal 6‐OHDA lesions involves coupling of 5‐HT2 receptors to the ERK1/2/MAP Kinase cascade, a pathway not typically active in these neurons. Because dopamine‐mediated signaling is redundant after 6‐OHDA lesions, 5‐HT‐mediated stimulation of the ERK1/2/MAP Kinase pathway may provide an alternative signaling route allowing the regulation of neuronal gene expression and neuronal plasticity in the absence of dopamine. J. Comp. Neurol. 498:415–430, 2006. Published 2006 Wiley‐Liss, Inc.
Contribution of feedforward thalamic afferents and corticogeniculate feedback to the spatial summation area of macaque V1 and LGN
Authors: Angelucci Alessandra , Sainsbury Kesi
Published: July 2006

Neurons in the primary visual cortex (V1) respond best to oriented gratings of optimal size within their receptive field (RF) and are suppressed by larger gratings involving the nonclassical RF surround. A V1 neuron's optimal stimulus size is larger at lower stimulus contrast. A central question in visual neuroscience is what circuits generate the size tuning of V1 cells. We recently demonstrated that V1 horizontal connections integrate signals within a region of the RF center corresponding to the V1 neuron's optimal stimulus size at low contrast; extrastriate feedback connections to V1, instead, are longer range and can integrate signals from the most distant regions of the V1 cell's RF surround. Here, we have determined the contribution of geniculocortical feedforward and corticogeniculate feedback connections to the size‐tuning of macaque V1 and lateral geniculate (LGN) neurons, respectively. Specifically, we have quantitatively compared the visuotopic extent of geniculate feedforward afferents to V1 with the size of the RF center and surround of neurons in the V1 input layers and the visuotopic extent of V1 feedback connections to the LGN with the RF size of cells in V1 layer 6, where these connections originate. We find geniculate feedforward connections to provide visuotopic information to V1 that is spatially coextensive with the V1 neuron's optimal stimulus size measured with high‐contrast gratings. V1 feedback connections restrict their influence to an LGN region visuotopically coextensive with the size of the minimum response field (or classical RF) of V1 layer 6 cells and commensurate with the LGN region from which they receive feedforward connections. J. Comp. Neurol. 498:330–351, 2006. © 2006 Wiley‐Liss, Inc.
Postnatal development and gender‐dependent expression of TIP39 in the rat brain
Authors: Dobolyi Arpád , Wang Jing , Irwin Sarah , Usdin Ted Björn
Published: July 2006

Tuberoinfundibular peptide of 39 residues (TIP39) is a selective agonist of the parathyroid hormone 2 (PTH2) receptor. The topographical distributions of TIP39 and the PTH2 receptor in the brain, described for young male rats, suggested that TIP39 has limbic and endocrine functions. In the present study, we investigated the expression of TIP39 and the PTH2 receptor in male and female rat brain during postnatal development by means of in situ hybridization histochemistry, quantitative RT‐PCR, and immunocytochemistry. TIP39's distribution and expression levels are similar in young female and male brains. TIP39 mRNA levels peak at postnatal day 14 and subsequently decline both in the subparafascicular area and in the medial paralemniscal nucleus, the two major sites where TIP39 is synthesized. A greater developmental decrease in TIP39 expression in males leads to greater levels in older females than older males. The decrease is partially reversed by prepubertal but not postpubertal gonadectomy. TIP39 peptide levels in cell bodies change in parallel with mRNA levels, whereas TIP39 appears and disappears somewhat later in nerve fibers. In addition, TIP39 peptide levels are also sexually dimorphic in older rats. In contrast, PTH2 receptor expression in the brain does not decrease during puberty and is not sexually dimorphic even in old animals. The appearance of TIP39 during early, and decline during late, postnatal development together with the gender‐dependent levels in mature animals suggests that TIP39 may play a role in sexual maturation or gender‐specific functions. J. Comp. Neurol. 498:375–389, 2006. Published 2006 Wiley‐Liss, Inc.
Direct synaptic contacts on the myenteric ganglia of the rat stomach from the dorsal motor nucleus of the vagus
Authors: Hayakawa Tetsu , Kuwahara Sachi , Maeda Seishi , Tanaka Koichi , Seki Makoto
Published: July 2006

The myenteric ganglia regulate not only gastric motility but also secretion, because a submucous plexus is sparsely developed in the rodent stomach. We have examined whether the neurons of the dorsal motor nucleus of the vagus (DMV) have direct synaptic contacts on the myenteric ganglia and the ultrastructure of the vagal efferent terminals by using wheat germ agglutinin conjugated to horseradish peroxidase (WGA‐HRP). The myenteric ganglia of the rat were composed of four types of neurons, i.e., small, medium‐sized, large, and elongated neurons. The average numbers of axosomatic terminals per profile were 2.0 on the small neurons, 3.1 on the medium‐sized neurons, 1.2 on the large neurons, and 4.2 on the elongated neuron. More than half of the axosomatic terminals contained round vesicles and formed asymmetric synaptic contacts on the small, medium‐sized, and large neurons. About 80% of the axosomatic terminals on the elongated neurons contained pleomorphic vesicles and formed asymmetric synaptic contacts. When WGA‐HRP was injected into the DMV, many anterogradely labeled terminals were found around the myenteric neurons. The labeled terminals were large (3.16 ± 0.10 μm) and contacted exclusively the somata. Most of them (about 90%) contained round vesicles and formed asymmetric synaptic contacts. Serial ultrathin sections revealed that almost all neurons in a ganglion received projections from the DMV. The vagal axon terminals generally contacted the medium‐sized or the elongated neurons, whereas a few labeled terminals contacted the small and the large neurons. The present results indicate that the DMV projects to all types of neurons and that their axon terminals contain mostly round synaptic vesicles and form asymmetric synaptic contacts. J. Comp. Neurol. 498:352–362, 2006. © 2006 Wiley‐Liss, Inc.
Synapse loss from chronically elevated glucocorticoids: Relationship to neuropil volume and cell number in hippocampal area CA3
Authors: Tata Despina A. , Marciano Veronica A. , Anderson Brenda J.
Published: July 2006

Individuals with clinical disorders associated with elevated plasma glucocorticoids, such as major depressive disorder and Cushing's syndrome, are reported to have smaller hippocampal volume. To understand how the hippocampus responds at the cellular and subcellular levels to glucocorticoids and how such changes are related to volume measures, we have undertaken a comprehensive study of glucocorticoid effects on hippocampal CA3 volume and identified elements in the neuropil including astrocytic volume and cell and synapse number and size. Male Sprague‐Dawley rats were injected with corticosterone (40 mg/kg), the primary glucocorticoid in rodents, or vehicle for 60 days. The CA3 was further subdivided so that the two‐thirds of CA3 (nearest the dentate gyrus) previously shown to be vulnerable to corticosterone could be analyzed as two separate subfields. Corticosterone had no effect on neuropil volume or glial volume in the proximal subfield but caused a strong tendency for astrocytic processes to make up a larger proportion of the tissue and for volume of tissue made of constituents other than glial cells (primarily neuronal processes) to be smaller in the middle subfield. Within the neuropil, there were no cellular or subcellular profiles that indicated degeneration, suggesting that corticosterone does not cause prolonged damage. Corticosterone did not reduce cell number or cell or nonperforated synapse size but did cause a pronounced loss of synapses. This loss occurred in both subfields and, therefore, was independent of volume loss. Together, the findings suggest that volume measures can underestimate corticosterone effects on neural structure. J. Comp. Neurol. 498:363–374, 2006. © 2006 Wiley‐Liss, Inc.
Anwendung von Spannverfahren nach ETAG 013
Authors: Hartz Uwe
Published: July 2006

Das Vorspannen von Betontragwerken ist ein umfassender und anspruchsvoller Verfahrensablauf, der beginnend mit der Tragwerksplanung und der Auswahl eines geeigneten Spannverfahrens über die Vorfertigung und Lieferung auch die Montage, das Vorspannen und das Herstellen eines dauerhaften Korrosionsschutzes für das Spannglied einschließt. Nur durch das enge Zusammenwirken aller beteiligten Partner kann dieser Ablauf zu einem zufriedenstellenden Ergebnis geführt werden. Die Mitglieder der EOTA‐Working group zur Erarbeitung der Leitlinie für Spannverfahren waren sich darin einig, dass eine sichere und dauerhafte Vorspannung über die gesamte Lebensdauer von Tragwerken nur gew&�uml;hrleistet werden kann, wenn neben den Produkteigenschaften auch an die Anwendung des Spannverfahrens auf der Baustelle hohe Anforderungen gestellt werden, wobei dem Zulassungsinhaber und der ausführenden Spezialfirma aufgrund ihrer Bedeutung und Verantwortlichkeiten die entscheidende Rolle zukommt.
Genetic inducible fate mapping in mouse: Establishing genetic lineages and defining genetic neuroanatomy in the nervous system
Authors: Joyner Alexandra L. , Zervas Mark
Published: July 2006

A fascinating aspect of developmental biology is how organs are assembled in three dimensions over time. Fundamental to understanding organogenesis is the ability to determine when and where specific cell types are generated, the lineage of each cell, and how cells move to reside in their final position. Numerous methods have been developed to mark and follow the fate of cells in various model organisms used by developmental biologists, but most are not readily applicable to mouse embryos in utero because they involve physical marking of cells through injection of tracers. The advent of sophisticated transgenic and gene targeting techniques, combined with the use of site‐specific recombinases, has revolutionized fate mapping studies in mouse. Furthermore, using genetic fate mapping to mark cells has opened up the possibility of addressing fundamental questions that cannot be studied with traditional methods of fate mapping in other organisms. Specifically, genetic fate mapping allows both the relationship between embryonic gene expression and cell fate (genetic lineage) to be determined, as well as the link between gene expression domains and anatomy (genetic anatomy) to be established. In this review, we present the ever‐evolving development of genetic fate mapping techniques in mouse, especially the recent advance of Genetic Inducible Fate Mapping. We then review recent studies in the nervous system (focusing on the anterior hindbrain) as well as in the limb and with adult stem cells to highlight fundamental developmental processes that can be discovered using genetic fate mapping approaches. We end with a look toward the future at a powerful new approach that combines genetic fate mapping with cellular phenotyping alleles to study cell morphology, physiology, and function using examples from the nervous system. Developmental Dynamics 235:2376–2385, 2006. © 2006 Wiley‐Liss, Inc.
A Reagentless Tyrosinase Biosensor Based on 1,6‐Hexanedithiol and Nano‐Au Self‐Assembled Monolayers
Authors: Liu Zhimin , Liu Jia , Shen Guoli , Yu Ruqin
Published: July 2006

An amperometric tyrosinase biosensor was developed via a simple and effective immobilization method using the self‐assembled monolayers (SAMs) technique. The organic monolayer film was first formed by the spontaneous assembly of thiolor sulfur compound (1,6‐hexanedithiol, HDT) from solution onto gold electrode. When these thiol‐rich surfaces were exposed to Au colloid, the sulfurs form strong bonds to gold nanoparticles, anchoring the clusters to the electrode substrate. After the assembly of gold nanoparticles layer, a new nano‐Au surface was obtained. Thus, the tyrosinase could be immobilized onto the electrode. The tyrosinase retained its activity well in such an immobilization matrix. The various experimental variables for the enzyme electrode were optimized. The resulting biosensor can reach 95% of steady‐state current within 10 s, and the trend in the sensitivity of different phenolic compounds was as follows: catechol>phenol>p‐cresol. In addition, the apparent Michaelis–Menten constant (K$\rm{ {_{m}^{app}})}$ and the stability of the enzyme electrode were estimated.
An Aptamer‐Based Protein Biosensor by Detecting the Amplified Impedance Signal
Authors: Xu Ying , Yang Lin , Ye Xiaoyan , He Pingang , Fang Yuzhi
Published: July 2006

A label‐free electrochemical impedance based protein biosensor was introduced by using aptamer as recognition tool. Our sensing protocol utilizes the affinity interaction between the thrombin and the self‐assembled DNA aptamer on gold electrode. This specific interaction increases the electrode interfacial electronic transfer resistance. The resistance signal is then “amplified” by using guanidine hydrochloride to denature the captured thrombin for increasing the hydrated radius of the thrombin, consequently blocking the electron transfer from solution to electrode. The sensor sensitivity is improved using this strategy and as low as 1.0×10−14 mol L−1 thrombin (enzymatic activity 10 U/mg) can be detected out.
Solvent‐Polymeric ISEs Tailored for Measurements in Solutions Containing Tetrabutylammonium, Cesium, and Calcium Ions
Authors: Grekovich Alexander L. , Alekseeva Maria V. , Schulze Klaus‐Dieter , Mikhelson Konstantin N.
Published: July 2006

Ion‐selective electrodes are described, with membranes tailored for measurements of tetrabutylammonium ions in aqueous and formamide solutions, and for measurements of cesium and calcium ions in the presence of tetrabutylammonium. It is shown that reliable measurements of cesium ions are possible when a correction is introduced for interference from tetrabutylammonium, using Nikolsky selectivity coefficient. A novel membrane composition is described which ensures high selectivity to calcium ions over tetrabutylammonium.
The dielectric behavior of outdoor high‐voltage polymeric insulation due to environmental aging
Authors: Ehsani M. , Bakhshandeh G. R. , Morshedian J. , Borsi H. , Gockenbach E. , Shayegani A. A.
Published: July 2006

Most of breakdowns are caused by aging effects of high‐voltage insulation used within these components, and there is still a need of suitable tools to diagnose such systems non‐destructively and reliably in the field. Several methods have been published in the last decade for which reliable diagnostics are claimed. One of these methods is based on changes of the dielectric properties of the insulation. Dielectric spectroscopy provides information on molecular dynamics and free charge carriers and it is sensitive to the insulation morphology, that is crystallinity, oxidation, additives, and impurities (ions and dipolar molecules). The measurement of dielectric constants and dielectric losses in frequency domain help to quantify the chemical and physical changes in the bulk of polymer due to aging. The results of frequency domain measurements in this contribution show that the effects of aging of insulators can be analyzed by this method. This paper demonstrates the use of a dielectric spectroscopy technique for monitoring the effect of different aging on silicone rubber, ethylene–propylene diene monomer (EPDM), and blend of silicone‐EPDM and new polymeric alloy. New polymeric alloy is found to be suitable for humid environment and shows good hydro‐thermal resistance compared to other polymers; also it is cheaper than other materials. Copyright © 2006 John Wiley & Sons, Ltd.
Intracranial pressure monitoring in patients with acute liver failure: A questionable invasive surveillance
Authors: Bernuau Jacques , Durand François
Published: July 2006

Monitoring of intracranial pressure (ICP) in acute liver failure (ALF) is controversial as a result of the reported complication risk (approximately 20%) and limited therapeutic options for intracranial hypertension. Using prospectively collected information from 332 patients with ALF and severe encephalopathy, we evaluated a recent experience with ICP monitoring in the 24 centers constituting the U.S. ALF Study Group. Special attention was given to the rate of complications, changes in management, and outcome after liver transplantation (LT). ICP monitoring was used in 92 patients (28% of the cohort), but the frequency of monitoring differed between centers (P < .001). ICP monitoring was strongly associated with the indication of LT (P < .001). A survey performed in a subset of 58 patients with ICP monitoring revealed intracranial hemorrhage in 10.3% of the cohort, half of the complications being incidental radiological findings. However, intracranial bleeding could have contributed to the demise of 2 patients. In subjects listed for LT, ICP monitoring was associated with a higher proportion of subjects receiving vasopressors and ICP-related medications. The 30-day survival post-LT was similar in both monitored and nonmonitored groups (85% vs. 85%). In conclusion, the risk of intracranial hemorrhage following ICP monitoring may have decreased in the last decade, but major complications are still present. In the absence of ICP monitoring, however, patients listed for LT appear to be treated less aggressively for intracranial hypertension. In view of the high 30-day survival rate after LT, future studies of the impact of intracranial hypertension should also focus on long-term neurological recovery from ALF.
Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy
Authors: van Bömmel Florian , Zöllner Bernhard , Sarrazin Christoph , Spengler Ulrich , Hüppe Dietrich , Möller Bernd , Feucht Heinz-Hubert , Wiedenmann Bertram , Berg Thomas
Published: July 2006

Incomplete virological response to adefovir dipivoxil (ADV) has been observed in patients with lamivudine-resistant hepatitis B virus (HBV) infection and may be associated with developing resistance and disease progression. We therefore investigated whether the efficacy of viral suppression could be improved by replacing ADV with tenofovir disoproxil fumarate (TDF). Twenty patients with chronic HBV infection (18 HBeAg+), viral breakthrough during lamivudine therapy, and persistent viral replication (>104 copies/mL) after 15 months of ADV monotherapy (range 4-28 months) were treated with TDF 300 mg daily and were retrospectively analyzed. A screening for nucleoside/nucleotide analogue resistance mutations within the HBV polymerase gene was performed in all patients by direct sequencing. Within a median of 3.5 months, application of TDF led to undetectable HBV DNA in 19 of 20 patients, as demonstrated by suppression of HBV DNA below the detection limit of 400 copies/mL. Initially elevated ALT levels had normalized in 10 of 14 patients by the end of follow-up (median 12 months, range 3-24 months). Four patients lost HBeAg, after 3, 4, 5, and 16 months, and one patient seroconverted to anti-HBs after 16 months of TDF therapy. Lamivudine-associated mutations (rtV173L, rtL180M, rtM204V/I) could be detected in 6 patients at baseline of TDF, but this obviously did not influence the response. ADV-resistant mutations were not detected. No side effects were reported.

In conclusion

, these preliminary observations strongly suggest that TDF might be a highly effective rescue drug for HBV-infected patients with altered responsiveness to treatment with lamivudine and ADV.
Thrombin generation in patients with cirrhosis: The role of platelets
Authors: Tripodi Armando , Primignani Massimo , Chantarangkul Veena , Clerici Marigrazia , Dell'Era Alessandra , Fabris Federica , Salerno Francesco , Mannucci Pier Mannuccio
Published: July 2006

Coagulation factor defects, thrombocytopenia, and thrombocytopathy are associated with cirrhosis. However, bleeding in patients who have cirrhosis does not entirely correlate with abnormal coagulation tests. Recently, it was shown that because of the concomitant abnormalities of the procoagulant and anticoagulant drives, thrombin generation in plasma patients with cirrhosis is normal when assessed with assays that include thrombomodulin (the main protein C activator). However, thrombin is also generated

in vivo

as a function of platelets, suggesting that thrombocytopenia and thrombocytopathy might affect thrombin generation in patients with cirrhosis. We addressed this issue using an assay that accounts for the contribution of plasma and platelets. The study showed that platelet-rich plasma with platelets adjusted by dilution of autologous platelet-rich into autologous platelet-poor plasma to a standard count (100 × 109/L) generates as much thrombin in patients with cirrhosis as in controls (1,063 nmol/L vs. 1,167 nmol/L;

P

value not significant). When platelets were adjusted to correspond to whole-blood counts, patients with cirrhosis generated significantly less thrombin than controls (949 nmol/L vs. 1,239 nmol/L;

P

< .001). Furthermore, thrombin generation correlated with platelet numbers (ρ = 0.50;

P

< .001). In addition, the amount of thrombin generated as a function of the whole-blood patients' platelet counts increased significantly when the numbers were adjusted to 100 × 109/L (953 nmol/L vs.1,063 nmol/L;

P

< .001).

In conclusion

, severe thrombocytopenia may limit thrombin generation in patients with cirrhosis. These findings might justify platelet transfusion in patients with low platelet counts when they bleed spontaneously or before undergoing surgery or liver biopsy. Controlled clinical trials supporting this indication are warranted.
Aspartyl-asparagyl β hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms
Authors: Cantarini Chiara M. , de la Monte Suzanne M. , Pang Maoyin , Tong Ming , D'Errico Antonia , Trevisani Franco , Wands Jack R.
Published: July 2006

Aspartyl-(Asparagyl)-β-hydroxylase (AAH) is overexpressed in various malignant neoplasms, including hepatocellular carcinomas (HCCs). The upstream regulation of AAH and its functional role in Notch-mediated signaling and motility in HCC cells was accessed. The mRNA transcript levels of AAH, insulin receptor substrate (IRS), insulin and insulin-like growth factor (IGF) receptors and polypeptides, Notch, Jagged, and HES were measured in 15 paired samples of HCC and adjacent HCC-free human liver biopsy specimens using real-time quantitative RT-PCR and Western blot analysis. Overexpression of AAH was detected in 87% of the HCC relative to the paired HCC-free liver tissue. IRS-1, IRS-2, and IRS-4 were each overexpressed in 80% of the HCC samples, and IGF-I and IGF-2 receptors were overexpressed in 40% and 100% of the HCCs, respectively. All HCC samples had relatively increased levels of Notch-1 and HES-1 gene expression. Overexpression of AAH led to increased levels of Notch, and co-immunoprecipitation experiments demonstrated a direct interaction between AAH and Notch as well as its ligand Jagged.

In conclusion,

contributions to the malignant phenotype of HCC is due to activation of IGF-I and IGF-II signaling that results in over-expression of both AAH and Notch. The functional role of AAH in relation to cell motility has been linked to increased activation of the Notch signaling pathway.
HepatoProteomics: Applying proteomic technologies to the study of liver function and disease
Authors: Diamond Deborah L. , Proll Sean C. , Jacobs Jon M. , Chan Eric Y. , Camp David G. , Smith Richard D. , Katze Michael G.
Published: July 2006

The wealth of human genome sequence information now available, coupled with technological advances in robotics, nanotechnology, mass spectrometry, and information systems, has given rise to a method of scientific inquiry known as functional genomics. By using these technologies to survey gene expression and protein production on a near global scale, the goal of functional genomics is to assign biological function to genes with currently unknown roles in physiology. This approach carries particular appeal in disease research, where it can uncover the function of previously unknown genes and molecular pathways that are directly involved in disease progression. With this knowledge may come improved diagnostic techniques, prognostic capabilities, and novel therapeutic approaches. In this regard, the continuing evolution of proteomic technologies has resulted in an increasingly greater impact of proteome studies in many areas of research and hepatology is no exception. Our laboratory has been extremely active in this area, applying both genomic and proteomic technologies to the analysis of virus-host interactions in several systems, including the study of hepatitis C virus (HCV) infection and HCV-associated liver disease. Since proteomic technologies are foreign to many hepatologists (and to almost everyone else), this article will provide an overview of proteomic methods and technologies and describe how they are being used to study liver function and disease.
Structural controls on groundwater flow and groundwater salinity in the Spicers Creek catchment, Central West region, New South Wales
Authors: Morgan Karina , Jankowski Jerzy , Taylor Geoffrey
Published: July 2006

Saline seepage zone development, and hence the onset of dryland salinity, is a major environmental problem occurring within the Spicers Creek catchment. The primary objective of this paper was to identify previously unmapped faults and show the correlation between these faults and groundwater salinization. As identified from this study, there is a close association between geological structural features and the formation of saline seepage zones. The most saline groundwaters in the catchment were encountered where two geological structures join and form a fault intersection. These saline groundwaters are found at various depths within the fractured aquifers, and changes in groundwater chemistry in the aquifers are associated with the presence of fault zones. 18O and δ2H stable isotopes, together with 87Sr/86Sr isotopic ratios, indicate that groundwaters within the fault zones are enriched in 18O and have a strontium signature similar to seawater. This study identifies several geological structures in the Spicers Creek catchment and demonstrates that groundwaters with the highest salinity arise where fault intersections occur. The results of this study may be used to interpret further the mechanisms leading to seepage zone formation in dryland salinity‐affected catchments located throughout the Central West region of New South Wales, Australia. Copyright © 2006 John Wiley & Sons, Ltd.
Biological Indicator Systems in Floodplains – a Review
Authors: Dziock Frank , Henle Klaus , Foeckler Francis , Follner Klaus , Scholz Mathias
Published: July 2006

Based on a literature review, the different approaches to biological indicator systems in floodplains are summarised. Four general categories of bioindication are defined and proposed here: 1. Classification indicators, 2.1 Environmental indicators, 2.2 Biodiversity indicators, 3. Valuation indicators. Furthermore, existing approaches in floodplains are classified according to the four categories. Relevant and widely used approaches in floodplains are explained in more detail. The results of the RIVA project are put into the context of these indication approaches. It is concluded that especially functional assessment approaches using biological traits of the species can be seen as very promising and deserve more attention by conservation biologists and floodplain ecologists. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Life‐History Data in Bioindication Procedures, Using the Example of Hoverflies (Diptera, Syrphidae) in the Elbe Floodplain
Authors: Dziock Frank
Published: July 2006

This is the first study to relate syrphid life history traits to environmental variables with a multi‐trait approach. We aimed to answer two questions: 1. Do syrphid species respond to small scale changes in environmental variables in seasonally flooded grasslands in a Central European floodplain (Elbe)? 2. Can species response to environmental variables be explained by the biological characteristics of the species expressed by their life history traits? Despite their large mobility, syrphids did respond significantly to small scale changes in environmental variables (groundwater (GW) depth, cation exchange capacity, amplitude of variation of the GW‐depth). On the other hand, the biological traits of the syrphids did not sufficiently explain syrphid occurrence at the sites. Possible explanations are discussed and an outlook for further studies is given. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Performance of Plants, Molluscs, and Carabid Beetles as Indicators of Hydrological Conditions in Floodplain Grasslands
Authors: Follner Klaus , Henle Klaus
Published: July 2006

Floodplain systems are among the most complex ecosystems. To assess their ecological condition, several indicator systems have been developed. However, none of them quantifies environmental factors related to the dynamics of water levels, which is a major driver for the occurrence and distribution of species in floodplains. We present a new bioindicator system for the duration of inundation per year and mean depth of groundwater during the vegetation period. The new indicator system is based on carabid beetles, molluscs, and plants. The indicator system generally proved to be precise as well as temporally and spatially transferable within the same river system, the Elbe River in Germany. The indication based on plants was clearly most precise and transferable. The results are discussed in terms of application of the indicator system. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Expression of Th1/Th2 cytokines in human blood after in vitro treatment with chlorpyrifos, and its metabolites, in combination with endotoxin LPS and allergen Der p1
Authors: Duramad Paurene , Tager Ira B. , Leikauf John , Eskenazi Brenda , Holland Nina T.
Published: July 2006

Exposure to organophosphate (OP) pesticides has been associated with respiratory symptoms and may be related to asthma; however, few studies have examined the molecular basis for these associations. Asthma and allergic disorders are characterized by elevated Th2 cytokines (IL‐4, IL‐5, IL‐13), whereas the chronic inflammatory response in asthmatic airways is maintained by Th1 cytokine IFN‐γ. The goal of this in vitro study was to examine the effects of OP chlorpyrifos (CPF), and its metabolites chlorpyrifos‐oxon (CPO) and 3,5,6‐trichloro‐2‐pyridinol (TCP), singly, and in combination with endotoxin lipopolysaccharide (LPS) or house dust mite Dermatophagoides pteronyssinus (Der p1) allergen, on expression of IFN‐γ and IL‐4, Th1 and Th2 signature cytokines, respectively. Cytokine expression was measured by ELISA and flow cytometry. Human blood cultures were treated with CPF/CPO/TCP (1–1000 µg ml−1) and LPS (1.5–2.5 µg ml−1) or Der p1 (200 AU ml−1) and supernatants were collected at 48 h. Pesticides CPF, CPO and TCP did not induce cytokine expression in vitro, while LPS and Der p1 induced IFN‐γ and IL‐4 expression, respectively. Whole blood cultures treated with low doses of CPO (1 and 10 µg ml−1), in combination with LPS, expressed higher levels of IFN‐γ than LPS alone (P < 0.05). While CPO increased LPS‐dependent induction of IFN‐γ, CPO treatment did not alter Der p1 induction of IL‐4. The interaction between CPO and LPS, which results in an increased type 1 immune response, should be investigated further, particularly since the combination of OP pesticides and endotoxin is common in rural, agricultural communities. Copyright © 2006 John Wiley & Sons, Ltd.
Immobilization and characterization of γ‐aminobutyric acid on gold surface
Authors: Wang Tingting , Ehteshami Gholam , Massia Stephen , Muthuswamy Jit
Published: July 2006

γ‐Aminobutyric acid (GABA) is one of two main inhibitory neurotransmitters in the central nervous system that plays an important role in neuronal function and dysfunction. Immobilization of GABA molecules on a rigid surface in an ordered fashion will provide an opportunity to understand some of the fundamental properties related to its structure and function. In this study, we report a novel strategy for immobilization of bioactive GABA on gold substrate. GABA was immobilized in three consecutive steps, namely gold substrate amination, dextran covalent attachment, and GABA immobilization. Surface chemistry was verified at each step using XPS and FTIR. Bioactivity of GABA immobilized on the gold surface was studied using atomic force microscopy to reveal antigen‐antibody binding. Nonspecific protein adsorption on the bioactive surface was analyzed quantitatively using anti‐GABA antibody and an enzyme linked nonspecific anti‐immunoglobulin‐G antibody in an ELISA assay. GABA functionalized surface has high affinity for anti‐GABA, while showing significantly low affinity for nonspecific anti‐IgG antibody. All these data support the presence of a bio‐functional immobilized GABA on the gold surface. In conclusion, we report a novel technique for immobilizing bioactive GABA molecules in an orderly fashion on gold substrates. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Biocompatibility of poly(ether)urethane‐gold nanocomposites
Authors: Hsu Shan‐hui , Tang Cheng‐Ming , Tseng Hsiang‐Jung
Published: July 2006

We have prepared the nanocomposites of a polyether‐type waterborne polyurethane (PU) incorporated with different amounts (17.4–174 ppm) of gold (Au) nanoparticles (∼5 nm). The nanocomposite containing a certain amount (43.5 ppm) of gold was previously demonstrated to possess the optimal thermal and mechanical properties, as well as much reduced foreign body reactions in subcutaneous rats. In this study, the surface morphology, biocompatibility, oxidative degradation, and free radical scavenging ability of the nanocomposites were characterized in vitro. The nanocomposite at 43.5 ppm of gold (“PU‐Au 43.5 ppm”) exhibited different surface morphology confirmed by the atomic force microscope. PU‐Au 43.5 ppm also showed enhanced cellular proliferation, reduced platelet and monocyte activation, and much less bacterial adhesion, relative to PU alone or nanocomposites at the other Au contents, in general. This better biocompatibility was associated with the surface morphological change in the presence of Au. The oxidative degradation in PU‐Au 43.5 ppm was also inhibited. The increased oxidative stability corresponded to the greater free radical scavenging ability of the nanocomposites. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Evaluation of decellularized esophagus as a scaffold for cultured esophageal epithelial cells
Authors: Ozeki Masayasu , Narita Yuji , Kagami Hideaki , Ohmiya Naoki , Itoh Akihiro , Hirooka Yoshiki , Niwa Yasumasa , Ueda Minoru , Goto Hidemi
Published: July 2006

Recently, decellularized tissue has been reported to have the potential to regenerate a variety of tissues. However, the optimal protocol for a decellularized esophagus has not been studied. Here, we investigated the effect of different decellularization protocols on the histology andbiocompatibility of decellularized esophagi in view of future applications to tissue engineering. The esophageal mucosal epithelium (EP) from 4‐week‐old Wistar rats was enzymatically dissociated and cultured with growth‐arrested feeder cells. Two methods for decellularization usingdeoxycholic acid (DEOX) or Triton X‐100 (TRITON) were compared on esophagi from adult Wistar rats. Those treated with DEOX showed superior mechanical properties, maintenance of extracellular matrix, and lower DNA content than those treated with TRITON. To evaluate the biocompatibility of the scaffold, cultured (passage 3) esophageal epithelial cells were seeded inside the decellularized esophagus and cultured for 7 days. The cells seeded onto the decellularized esophagus were examined histologically and immunocytochemically. Esophageal epithelial cells were stratified into three to four cellular layers in vitro inside thedecellularized esophagus, to show polarity. The results from immunocytochemistry indicated that the seeded epithelial cells expressed characteristic marker proteins for native esophageal EP. Decellularized esophagus showed suitable compatibility as a scaffold material for esophageal tissue engineering. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Late Devensian and Holocene relative sea‐level changes on the Isle of Skye, Scotland, UK
Authors: Selby Katherine A. , Smith David E.
Published: July 2006

Detailed litho‐ and biostratigraphical analyses from three coastal sites in contrasting coastal settings on the Isle of Skye, Scotland, UK, reveal evidence for several changes in relative sea level during the Late Devensian and Holocene. At the start of the record, relative sea level in the area was high at ca. 12 500 14C (ca. 14 800 cal.) yr BP but then fell, reaching a low point during the Younger Dryas, at ca. 11 000–10 000 14C (ca. 13 000–11 600 cal.) yr BP, when a rock platform, correlated with the Main Rock Platform, was formed. In the early–middle Holocene, relative sea level was rising by ca. 8000 14C (ca. 8800 cal.) yr BP and in northeast Skye a lagoonal surface, correlated with the Main Postglacial Shoreline, was formed at ca. 6600 14C (ca. 7500 cal.) yr BP. By the late Holocene, relative sea level was again falling, but a rise, registered at at least two sites, began probably before ca. 4000 14C (ca. 4500 cal.) yr BP, and a second lagoonal surface in northeast Skye, correlated with the Blairdrummond Shoreline, was formed, although by ca. 3000 14C (ca. 3200 cal.) yr BP relative sea level in the area had resumed its downward trend. The pattern of relative sea‐level changes disclosed is compared with evidence elsewhere in Scotland. Copyright © 2006 John Wiley & Sons, Ltd.
Development and characteristics of a fire‐resistant grease
Authors: Jones J. A. , Macphail A. C. B.
Published: July 2006

To reduce the incidence of fires in coal‐mines, the British National Coal Board (NCB) has requested a fire‐resistant grease which would be used in conveyor idler bearings and which would give the performance of good mineral oil‐based greases. A candidate grease was produced by the authors' company, based on phosphate ester, which is under field test by the NCB and running satisfactorily after one year. The results are encouraging so that consideration is being given to use of this type of grease in other applications.
Ester base stocks
Authors: Szydywar J.
Published: July 2006

Natural esters contained in animal fats such as sperm oil, lard oil or in vegetable oils like rapeseed and castor oil have been the main lubricants from antiquity until the early 19th century. By 1890, petroleum oils had almost completely displaced natural oils. However, fatty products were still used as ‘oiliness agents’ to reduce friction and wear in bearings and gears lubricated by petroleum products. About 1937, Dr Herman Zorn of IG Farben Industrie in Germany began an intensive search for lubricants having the lubricating properties of natural oils, such as castor oil, while eliminating the tendency of these natural products to gel at low temperatures and to form gums and lacquers when used in engine operation. This paper describes the properties, types and applications of esters, as a main group of synthetic lubricants developed during the last four decades.
COBRA analysis of laboratory degraded synthetic turbine engine lubricants
Authors: Centers Phillip W. , Smith Hoover A.
Published: July 2006

The Complete Oil Breakdown Rate Analyser (COBRA) is an instrument that detects ill‐defined electrochemical changes in synthetic ester‐based lubricants as those fluids are oxidatively degraded. In several Air Force field applications, the COBRA has proven useful in determining lubricant condition or in identifying abnormally operating engines in which excessive lubricant degradation occurred. In laboratory analyses of field samples from programmes involving several engine types, correlation of COBRA with total acid number or viscosity was poor, but consumption of one or more oxidants appeared to be consistently associated with high COBRA values. To determine if such correlation exists, this study was conducted to evaluate laboratory degraded synthetic lubricants. Results of the laboratory study indicate that COBRA increases rapidly after depletion of typical antioxidants, increases with higher total acid numbers and trends with viscosity data. The poor correlation observed between COBRA and total acid number and viscosity for field samples is attributed to differences in for example engine breather designs, and oxidative environments, which can significantly alter the properties of the residual engine lubricant analysed by COBRA. Due to the presumed test apparatus and engine design dependence of COBRA data, COBRA correlation must be established for each application.
The relationships between structure and rheological properties of hydrocarbons and oxygenated compounds used as base stocks
Authors: Denis J.
Published: July 2006

The growing interest shown by industry in synthetic lubricants for severely stressed engines and machines has led the author's organisation to investigate the best hydrocarbon and oxygenated structures which serve to achieve a good compromise between viscosity index and pour point. Several analyses of structure and property relationships have been published. The American Petroleum Institute's project 421 has given the characteristics of many light hydrocarbons from C10 to C35 belonging to different chemical families. During the Second World War, American and German research centres investigated a large number of esters and selected the best diacid and polyol ester structures.

The compromise between the viscosity index and pour point has been studied for hydrocarbons and oxygenated products as to their prospects for use as base stocks. With hydrocarbons having a long main chain which is substituted either by a very branched chain, or by a chain ending with a saturated ring, it is possible to reach a viscosity index of around 160 for a pour point of −20°C. The introduction of ester functions in a hydrocarbon chain improves the compromise between viscosity index and pour point. Diacid esters constituted of linear diacids and branched monoalcohols are very favourable, but the best compromise is achieved by polyalkoxy
‐ether‐esters and polyalkoxy diesters. Unhappily these are miscible to hydrocarbons only if the hydrocarbon chains are sufficiently long. Of course for formulation of lubricants, other properties also linked to chemical structure should be taken into account, such as thermal and oxidative stability, antiwear behaviour, hydrolytic stability, and compatibility with additives.

The data presented here and other data derived from research projects conducted in the author's laboratory, some jointly with Produits Chimiques Ugine Kuhtmann, have been analysed to determine the possibilities for main synthetic lubricant base stocks.