bluuebunny/crossref_metadata_2025 huggingface dataset:
Shugoshin: a centromeric guardian senses tension
Authors: Goulding Sarah E. , Earnshaw William C.
Published: May 2005

To ensure accurate chromosome segregation during mitosis, the spindle checkpoint monitors chromosome alignment on the mitotic spindle. Indjeian and colleagues have investigated the precise role of the shugoshin 1 protein (Sgo1p) in this process in budding yeast.1 The Sgo proteins were originally identified as highly conserved proteins that protect cohesion at centromeres during the first meiotic division. Together with other recent findings,2 the study highlighted here has identified Sgo1 as a component that informs the mitotic spindle checkpoint when spindle tension is perturbed. This discovery has provided a molecular link between sister chromatid cohesion and tension‐sensing at the kinetochore–microtubule interface. BioEssays 27:588–591, 2005. © 2005 Wiley Periodicals, Inc.
Phase equilibrium in poly(rA) · poly(rU) complexes with Cd2+ and Mg2+ ions, studied by ultraviolet, infrared, and vibrational circular dichroism spectroscopy
Authors: Blagoi Yurii , Gladchenko Galina , Nafie Laurence A. , Freedman Teresa B. , Sorokin Victor , Valeev Vladimir , He Yanan
Published: May 2005

Ultraviolet (UV) and infrared (IR) absorption and vibrational circular dichroism (VCD) spectroscopy were used to study conformational transitions in the double‐stranded poly(rA)· poly(rU) and its components—single‐stranded poly(rA) and poly(rU) in buffer solution (pH 6.5) with 0.1M Na+ and different Mg2+ and Cd2+ (10−6 to 10−2M) concentrations. Transitions were induced by elevated temperature that changed from 10 up to 96°C. IR absorption and VCD spectra in the base‐stretching region were obtained for duplex, triplex, and single‐stranded forms of poly(rA) · poly(rU) at [Mg2+],[Cd2+]/[P] = 0.3. For single‐stranded polynucleotides, the kind of conformational transition (ordering → disordering → compaction, aggregation) is conditioned by the dominating type of Me2+–polymer complex that in turn depends on the ion concentration range. The phase diagram obtained for poly(rA) · poly(rU) has a triple point ([Cd2+] ∼ 10−4M) at which the helix–coil (2 → 1) transition is replaced with a disproportion transition 2AU → A2U + poly(rA) (2 → 3) and the subsequent destruction of the triple helix (3 → 1). The 2 → 1 transitions occur in the narrow temperature interval of 2°–5°. Unlike 2 → 1 and 3 → 1 melting, the disproportion 2 → 3 transition is a slightly cooperative one and observed over a wide temperature range. At [Me2+] ∼ 10−3M, the temperature interval of A2U stability is not less than 20°C. In the case of Cd2+, it increases with the rise of ion concentration due to the decrease of T. The T value is practically unchanged up to [Cd2+] ∼10−3M. Differences between diagrams for Mg2+ and Cd2+ result from the various kinds of ion binding to poly(rA) · poly‐(rU) and poly(rA). © 2005 Wiley Periodicals, Inc. Biopolymers 78: 275–286, 2005
Unzipping DNA from the condensed globule state—Effects of unraveling
Authors: Lam Pui‐Man , Levy J. C.
Published: May 2005

We have studied theoretically the unzipping of a double‐stranded DNA from a condensed globule state by an external force. At constant force, we found that the double‐stranded DNA unzips an at critical force Fc and the number of unzipped monomers M goes as M ∼ (Fc − F)−3, for both the homogeneous and heterogeneous double‐stranded DNA sequence. This is different from the case of unzipping from an extended coil state in which the number of unzipped monomers M goes as M ∼ (Fc − F)−χ, where the exponent χ is either 1 or 2 depending on whether the double‐stranded DNA sequence is homogeneous or heterogeneous, respectively. In the case of unzipping at constant extension, we found that for a double‐stranded DNA with a very large number N of base pairs, the force remains almost constant as a function of the extension, before the unraveling transition, at which the force drops abruptly to zero. Right at the unraveling transition, the number of base pairs remaining in the condensed globule state is still very large and goes as N3/4, in agreement with theoretical predictions of the unraveling transition of polymers stretched by an external force. © 2005 Wiley Periodicals, Inc. Biopolymers 79: 287–291, 2005

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Minimally invasive transthoracotomy–transphrenotomy for concurrent hepatic and pulmonary hydatid disease
Authors: Lone G N , Bhat M A , Ali N , Ahangar A G , Dar A M , Sana I
Published: May 2005

Background

Combined liver and lung hydatid cysts are rare, but pose a challenge in terms of accessibility. The objective of the study was to find an alternative approach to conventional two-stage posterolateral thoracotomy and laparotomy or single-stage extensive thoracolaparotomy.

Methods

Twenty-five patients with right lung and liver hydatid disease underwent single-stage anterior minithoracotomy and phrenotomy. Primary diagnostic tools were chest radiography, ultrasonography and serology. The preferred mode of management of hydatid cysts was enucleation and partial or total capitonnage.

Results

Thirty-six (13·5 per cent) of 267 patients had concurrent hepatic and pulmonary hydatid cysts. Among the 25 patients who had anterior minithoracotomy and phrenotomy the male : female ratio was 2 : 1. Mean operating time was 75 min. Morbidity was negligible and postoperative recovery was prompt. All of the patients survived. The mean hospital stay was 5·2 days. Overall observations were encouraging.

Conclusion

This minimally invasive approach is associated with less morbidity and better cosmesis than conventional procedures. It represents an excellent alternative to other procedures in selected patients.
Surgical outcome of solitary colorectal metastasis to the hepatic caudate lobe
Authors: Tanaka K , Shimada H , Matsuo K , Nagano Y , Togo S
Published: May 2005

Increased risk of early recurrence
Population-based study of short- and long-term survival from colorectal cancer in Denmark, 1977–1999
Authors: Iversen L H , Pedersen L , Riis A , Friis S , Laurberg S , Sørensen H T
Published: May 2005

Background

Survival rates for patients with colorectal cancer have been lower in Denmark than in other European countries. The aim of this study was to examine temporal trends in relative survival from colorectal cancer between 1977 and 1999.

Methods

All patients diagnosed with colorectal cancer between 1977 and 1999 were identified using the nationwide population-based Danish Cancer Registry. Patients were linked with the Danish Central Population Registry to obtain data on survival to December 2002, and to select ten population controls per patient.

Results

A total of 69 562 patients with colorectal cancer were identified, of whom 49·2 per cent were men. Six-month relative survival after diagnosis increased from 69·7 per cent in 1977–1982 to 77·7 per cent in 1995–1999. Five-year relative survival rates increased from 37·8 to 46·8 per cent respectively. Women had slightly higher 5-year relative survival than men throughout the study period. Rectal tumours were associated with better survival than colonic tumours until 2 years after diagnosis, after which tumour location had no impact on survival.

Conclusion

Relative survival of patients with colorectal cancer has improved in Denmark between 1977 and 1999, most probably reflecting better management of the disease.
Cardiac troponin I predicts outcome after ruptured abdominal aortic aneurysm repair
Authors: Tambyraja A L , Dawson A R W , Murie J A , Chalmers R T A
Published: May 2005

Background

Cardiac troponin I (cTnI) is a highly sensitive and specific marker for myocardial injury that predicts mortality in patients with acute coronary syndromes. This study examined the relationship between perioperative cTnI levels and clinical outcome in patients with ruptured abdominal aortic aneurysm (AAA).

Methods

Consecutive patients who underwent operative repair of a ruptured AAA over a 22-month interval and survived for more than 24 h were entered into a prospective observational cohort study. Levels of cTnI were measured immediately before, and at 24 and 48 h after surgery, and related to clinical outcome.

Results

Of 62 patients who underwent attempted operative repair of ruptured AAA, 50 (81 per cent) survived for more than 24 h and were included in this study. Twenty-three (46 per cent) of the 50 had a detectable cTnI level at one or more time points during the first 48 h. Of these, 11 patients had clinical or electrocardiographic evidence of an acute cardiac event and 12 did not; five patients in each of these two groups died. Of 27 patients with no increase in cTnI in the first 48 h, only three died (P = 0·031 and P = 0·043 respectively, relative to the groups with detectable cTnI).

Conclusion

Approximately half of patients who survived repair of ruptured AAA for more than 24 h sustained a detectable myocardial injury within the first 48 h. A perioperative increase in the level of cTnI, with or without clinically apparent cardiac dysfunction, was associated with postoperative death.
Durability of botulinum toxin injection for axillary hyperhidrosis
Authors: James R , Phillips D , Collin J
Published: May 2005

Injections last about 6 months
Diatom/Copepod Interactions in Plankton: The Indirect Chemical Defense of Unicellular Algae
Authors: Pohnert Georg
Published: May 2005

Numerous coexisting species can be observed in the open oceans. This includes the complex community of the plankton, which comprises all free floating organisms in the sea. Traditionally, nutrient limitation, competition, predation, and abiotic factors have been assumed to shape the community structure in this environment. Only in recent years has the idea arisen that chemical signals and chemical defense can influence species interactions in the plankton as well. Key players at the base of the marine food web are diatoms (unicellular algae with silicified cell walls) and their main predators, the herbivorous copepods. It was assumed that diatoms represent a generally good food source for the grazers but recent work indicates that some species use chemical defenses. Secondary metabolites, released by these algae immediately after wounding, are targeted not against the predators themselves but rather at interfering with their reproductive success. This strategy allows diatoms to reduce the grazer population, thereby influencing the marine food web. This review addresses the chemical ecology of the defensive oxylipins formed by diatoms and the question of how these metabolites can act in such a dilute environment. Aspects of biosynthesis, bioassays, and the possible implications of such a chemical defense for the plankton community structure are also discussed.
PIGA (N,N‐Di‐n‐butyl‐5‐chloro‐2‐(4‐chlorophenyl)indol‐3‐ylglyoxylamide), a New Mitochondrial Benzodiazepine‐Receptor Ligand, Induces Apoptosis in C6 glioma Cells
Authors: Chelli Beatrice , Rossi Leonardo , Da Pozzo Eleonora , Costa Barbara , Spinetti Francesca , Rechichi Mariarosa , Salvetti Alessandra , Lena Annalisa , Simorini Francesca , Vanacore Renato , Scatena Fabrizio , Da Settimo Federico , Gremigni Vittorio , Martini Claudia
Published: May 2005

Mitochondrial benzodiazepine‐receptor (mBzR) ligands constitute a heterogeneous class of compounds that show a pleiotropic spectrum of effects within the cells, including the modulation of apoptosis. In this paper, a novel synthetic 2‐phenylindol‐3‐ylglyoxylamide derivative, N,N‐di‐n‐butyl‐5‐chloro‐2‐(4‐chlorophenyl)indol‐3‐ylglyoxylamide (PIGA), which shows high affinity and selectivity for the mBzR, is demonstrated to induce apoptosis in rat C6 glioma cells. PIGA was able to dissipate mitochondrial transmembrane potential (ΔΨm) and to cause a significant cytosolic accumulation of cytochrome c. Moreover, typical features of apoptotic cell death, such as caspase‐3 activation and DNA fragmentation, were also detected in PIGA‐treated cells. Our data expand the knowledge on mBzR ligand‐mediated apoptosis and suggest PIGA as a novel proapoptotic compound with therapeutic potential against glial tumours, in which apoptosis resistance has been reported to be involved in carcinogenesis.
New Inhibitors of the Tat–TAR RNA Interaction Found with a “Fuzzy” Pharmacophore Model
Authors: Renner Steffen , Ludwig Verena , Boden Oliver , Scheffer Ute , Göbel Michael , Schneider Gisbert
Published: May 2005

TAR RNA is a potential target for AIDS therapy. Ligand‐based virtual screening was performed to retrieve novel scaffolds for RNA‐binding molecules capable of inhibiting the Tat–TAR interaction, which is essential for HIV replication. We used a “fuzzy” pharmacophore approach (SQUID) and an alignment‐free pharmacophore method (CATS3D) to carry out virtual screening of a vendor database of small molecules and to perform “scaffold‐hopping”. A small subset of 19 candidate molecules were experimentally tested for TAR RNA binding in a fluorescence resonance energy transfer (FRET) assay. Both methods retrieved molecules that exhibited activities comparable to those of the reference molecules acetylpromazine and chlorpromazine, with the best molecule showing ten times better binding behavior (IC50=46 μM). The hits had molecular scaffolds different from those of the reference molecules.
Examples of Peptide–Peptoid Hybrid Serine Protease Inhibitors Based on the Trypsin Inhibitor SFTI‐1 with Complete Protease Resistance at the P1P1′ Reactive Site
Authors: Stawikowski Maciej , Stawikowska Roma , Jaśkiewicz Anna , Zabłotna Ewa , Rolka Krzysztof
Published: May 2005

Research in the field of protease inhibitors is focused on obtaining potent, specific and protease‐resistant inhibitors. To our knowledge, there are no reports in the literature that consider the application of N‐substituted glycine residues (peptoid monomers) for the design of peptidomimetic protease inhibitors. We hereby present the chemical synthesis and kinetic properties of two new analogues of the trypsin inhibitor SFTI‐1 modified at the P1 position. Substitution of Lys5 in SFTI‐1 by N‐(4‐aminobutyl)‐glycine and N‐benzylglycine, which mimic Lys and Phe, respectively, made these analogues completely protease‐resistant at their P1P1′ reactive sites. The analogues synthesised appeared to be potent inhibitors of bovine β‐trypsin and α‐chymotrypsin. These noncovalent, competitive and selective peptide–peptoid hybrid (peptomeric) inhibitors might open the way to targeting unwanted proteolysis.
Lewis Acidity/Basicity of π‐Electron Systems: Theoretical Study of a Molecular Interaction between a π System and a Lewis Acid/Base
Authors: Kawahara Shun‐ichi , Tsuzuki Seiji , Uchimaru Tadafumi
Published: May 2005

Molecular interactions between π systems having different π‐electron character (benzene, hexafluorobenzene, and borazine), and a Lewis acid/base (borane and ammonia) were theoretically studied. An attractive interaction between benzene, the electron‐rich π system, and borane was observed. On the other hand, repulsive interactions between benzene and ammonia was observed when the lone pair of nitrogen points toward the benzene ring. In contrast, an attractive interaction between hexafluorobenzene, an electron‐deficient π system, and ammonia was observed. Unexpectedly, a weak attractive interaction between hexafluorobenzene and borane was also observed. Borazine shows an interaction both to borane and ammonia. The attraction between the nitrogen atom of borazine and borane was larger than that between the boron atom of borazine and ammonia.
Highly Hydrated Cations: Deficiency, Mobility, and Coordination of Water in Crystalline Nonahydrated Scandium(III), Yttrium(III), and Lanthanoid(III) Trifluoromethanesulfonates
Authors: Abbasi Alireza , Lindqvist‐Reis Patric , Eriksson Lars , Sandström Dick , Lidin Sven , Persson Ingmar , Sandström Magnus
Published: May 2005

Trivalent lanthanide‐like metal ions coordinate nine water oxygen atoms, which form a tricapped trigonal prism in a large number of crystalline hydrates. Water deficiency, randomly distributed over the capping positions, was found for the smallest metal ions in the isomorphous nonahydrated trifluoromethanesulfonates, [M(H2O)n](CF3SO3)3, in which M=ScIII, LuIII, YbIII, TmIII or ErIII. The hydration number n increases (n=8.0(1), 8.4(1), 8.7(1), 8.8(1) and 8.96(5), respectively) with increasing ionic size. Deuterium (2H) solid‐state NMR spectroscopy revealed fast positional exchange between the coordinated capping and prism water molecules; this exchange started at temperatures higher than about 280 K for lutetium(III) and below 268 K for scandium(III). Similar positional exchange for the fully nonahydrated yttrium(III) and lanthanum(III) compounds started at higher temperatures, over about 330 and 360 K, respectively. An exchange mechanism is proposed that can exchange equatorial and capping water molecules within the restrictions of the crystal lattice, even for fully hydrated lanthanoid(III) ions. Phase transitions occurred for all the water‐deficient compounds at ≈185 K. The hydrated scandium(III) trifluoromethanesulfonate transforms reversibly (ΔH°=−0.80(1) kJ mol−1 on cooling) to a trigonal unit cell that is almost nine times larger, with the scandium ion surrounded by seven fully occupied and two partly occupied oxygen atom positions in a distorted capped trigonal prism. The hydrogen bonding to the trifluoromethanesulfonate anions stabilises the trigonal prism of water ligands, even for the crowded hydration sphere of the smallest metal ions in the series. Implications for the Lewis acid catalytic activity of the hydrated scandium(III) and lanthanoid(III) trifluoromethanesulfonates for organic syntheses performed in aqueous media are discussed.
Visibility, Immobility and Stigma: Young People's Use of Sexual Health Services in Rural Areas†
Authors: Craig Gary , Stanley Nicky
Published: May 2005

Teenage pregnancy has become a major policy issue, for which young people are often publicly held solely responsible. However, a combination of factors substantially increases the risks of conception faced by young people engaging in early sexual activity. This article reports the main findings of a study of teenage pregnancy in linked seaside and rural areas, focusing on the experiences and perceptions of young people living in rural localities. They identify the issues of immobility, visibility and attitudes of stigma as affecting their ability to access sexual health services. The young people highlighted issues for service and policy development and the behaviour of professionals, both within schools and from sexual health services. Education, social and health services and the voluntary sector have important roles to play in responding to their needs.
Squamous cell carcinoma antigen‐immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma
Authors: Beneduce Luca , Castaldi Francesco , Marino Maria , Quarta Santina , Ruvoletto Mariagrazia , Benvegnù Luisa , Calabrese Fiorella , Gatta Angelo , Pontisso Patrizia , Fassina Giorgio
Published: May 2005

BACKGROUND

Early detection of hepatocellular carcinoma (HCC), one of the most common and deadly tumors worldwide, still is difficult due to the lack of adequate biomarkers that show high sensitivity and specificity. The authors recently demonstrated that squamous cell carcinoma antigen (SCCA) variants were overexpressed remarkably in all surgically resected HCCs.

METHODS

For the current study, the authors assessed the presence of SCCA, as a free form and complexed with immunoglobulins, in serum from patients with HCC, cirrhosis, and chronic hepatitis and from healthy control participants and compared SCCA measurement with the measurement of α‐fetoprotein (AFP) levels.

RESULTS

Circulating immune complexes (ICs) composed by SCCA and immunoglobulin M (IgM) IC (SCCA‐IgM IC) were undetectable (< 120 arbitrary units [AU]/mL) in serum from a healthy control population (0 of 73 controls); however, 35 of 50 patients with HCC (70%) were reactive for SCCA‐IgM IC independent of etiology (mean ± standard deviation [SD], 2568.5 ± 6797.3 AU/mL). No correlation was found with AFP levels, which were elevated significantly in only 21 of 50 patients with HCC (42%). By using an AFP cut‐off value of 20 ng/mL, 96% of patients with HCC were positive for at least 1 marker. Among cirrhotic patients, the presence of circulating SCCA‐IgM IC was displayed in 13 of 50 patients (26%), but at lower levels compared with the patients who had HCC (mean ± SD, 147.5 ± 348.3 AU/mL; P < 0.01; Student t test), whereas 9 of 50 patients with chronic hepatitis (18%) were reactive (mean ± SD, 39.5 ± 89.7 AU/mL). No significant presence of free SCCA, free anti‐SCCA variants IgG or IgM, or SCCA‐IgG IC was found.

CONCLUSIONS

The study results indicated that SCCA‐IgM ICs represent novel serologic biomarkers, which, alone or in combination with AFP, can increase the sensitivity for diagnosing HCC significantly. Cancer 2005. © 2005 American Cancer Society.
A phase II study of bortezomib in the treatment of metastatic malignant melanoma
Authors: Markovic Svetomir N. , Geyer Susan M. , Dawkins Fitzroy , Sharfman William , Albertini Mark , Maples William , Fracasso Paula M. , Fitch Tom , LoRusso Patricia , Adjei Alex A. , Erlichman Charles
Published: May 2005

BACKGROUND

Bortezomib is a proteasome inhibitor with manageable clinical toxicity and laboratory evidence of anti‐melanoma activity. Therefore, it was considered for clinical testing in patients with metastatic melanoma.

METHODS

Patients with metastatic melanoma and adequate hematologic, renal, and hepatic function were treated with bortezomib (a 1.5‐mg/m2 intravenous bolus twice weekly for 2 of every 3 weeks). Eligible patients were age ≥ 18 years with an Eastern Cooperative Oncology Group performance status of 0–1. The primary goal of the current study was to evaluate the 18‐week disease progression‐free survival rate and tolerability of bortezomib in these patients.

RESULTS

The current study was intended to treat 45 patients. It was closed at the planned interim analysis due to early evidence of insufficient clinical efficacy. Twenty‐seven patients with a median age of 56 years (range, 32–77 years)were accrued. There were no major clinical responses to treatment. Only 6 patients (22%) achieved stable disease. Of these 6 patients, 4 were still stable after 4 cycles of treatment, but were removed from the study due to toxicity. The median time to disease progression was 1.5 months (95% confidence interval [95% CI], 1.4–1.6) with a median overall survival of 14.5 months (95% CI, 9–22). Having failed bortezomib, most patients proceeded to other clinical trials. Twenty‐six patients were evaluable for toxicity. One patient was removed from the study for other reasons and could not return for the cycle evaluation and thus was never evaluated. Of the 26 patients, no Grade 4/5 treatment‐related toxicities (using the National Cancer Institute Common Toxicity Criteria [version 2.0]) were reported. Eleven patients (42%) had Grade 3 toxicities (believed to be at least possibly related to treatment), including sensory neuropathy, thrombocytopenia, constipation, fatigue, ileus, abdominal pain, and infection without neutropenia. The median number of treatment cycles patients received was two (range, one to six treatment cycles). Two patients (7%) had 1 dose delay and 6 patients (22%) had dose reductions during 1 treatment cycle due to adverse events.

CONCLUSIONS

Single‐agent bortezomib, administered twice weekly × 2 weeks, every 3 weeks at a dose of 1.5 mg/m2, was not found to be effective in the treatment of patients with metastatic melanoma. Cancer 2005. © 2005 American Cancer Society.
Topographic activation of the medial entorhinal cortex by presubicular commissural projections
Authors: Bartesaghi Renata , Di Maio Vito , Gessi Tiziana
Published: May 2005

Previous investigations have shown that presubicular commissural fibers traveling in the caudal part of the dorsal hippocampal commissure (PSD) selectively activated the dorsalmost portion of the entorhinal cortex (EC), where they discharged perforant path neurons to the dorsal dentate gyrus. The dentate activation was followed by that of the dorsal hippocampus. The aim of the present study was to ascertain whether presubiculum commissural projections traveling in the PSD can also activate ventral levels of the EC and, if so, whether this activation is followed by that of the dentate gyrus‐hippocampal system in the ventral hippocampus. The experiments were carried out in adult, anesthetized guinea pigs by field potential analysis. The results showed that presubicular fibers traveling at different PSD loci selectively activated specific EC portions, with caudal fibers activating only the dorsal EC and more rostral fibers activating ventral EC points. The region activated by PSD projections corresponded to the medial EC. Current source‐density (CSD) analysis revealed that at both dorsal and ventral EC levels excitatory synaptic potentials followed by neuron discharge were generated in layer II, site of origin of the perforant path to the dentate gyrus. Activation of either dorsal or ventral levels of the EC was followed by activation of the dentate gyrus‐hippocampal system in corresponding hippocampal segments. The results provide physiological evidence that the commissural presubicular projections activate the EC in a topographic manner. The massive activation of perforant path neurons at all EC levels suggests that presubicular signals may strongly influence the functions played by the EC‐dentate‐hippocampal system. J. Comp. Neurol. 487:283–299, 2005. © 2005 Wiley‐Liss, Inc.
Anatomical abnormalities in dopaminoceptive regions of the cerebral cortex of dopamine D1 receptor mutant mice
Authors: Stanwood Gregg D. , Parlaman Joshua P. , Levitt Pat
Published: May 2005

Alteration of dopamine neurotransmission during development can induce specific changes in neuronal structure and function. Here, we report specific morphological and neurochemical changes of projection neurons and interneurons of the medial frontal cortex of the dopamine D1 receptor null mouse. Using immunostaining of cytoskeletal proteins and a crossbred D1 receptor null:YFP transgenic reporter line, we demonstrate that the apical dendrites of pyramidal cells are abnormally organized in the prefrontal and anterior cingulate cortices of mice lacking the D1 receptor. Neuronal processes exhibit a decrease in bundling and an increase in irregular, tortuous patterning as they weave a course towards the pial surface. In addition, there is increased parvalbumin staining of the dendrites of cortical interneurons in D1 receptor null mice. Both pyramidal and interneuron alterations are evident by the early postnatal period and persist into adulthood. The alterations show regional specificity, in that dendritic profiles of projection neurons and interneurons in somatosensory and visual cortices develop normally. The abnormalities are reminiscent of those induced by prenatal exposure to cocaine in rabbits, an insult which has been shown to produce an attenuation of D1 receptor‐mediated responses through Gsα. These results suggest that loss of D1 receptor‐mediated signaling during development produces permanent alterations in the cellular organization of specific cortical areas involved in attention, cognition, and emotion. Pharmacological and behavioral studies in the D1 null mouse should be interpreted in the context of possible altered circuitry, given the presence of these developmental defects in the organization of dopaminoceptive regions of the cerebral cortex. J. Comp. Neurol. 487:270–282, 2005. © 2005 Wiley‐Liss, Inc.
Expression profiles of EphA3 at both the RNA and protein level in the developing mammalian forebrain
Authors: Kudo Chikako , Ajioka Itsuki , Hirata Yukio , Nakajima Kazunori
Published: May 2005

The ephrin/Eph system is well known to regulate various aspects of brain development. In this study, we analyzed the expression profiles of EphA3 at both the RNA and protein level in developing mouse forebrains. Although the EphA3 gene is known to encode two isoforms of the receptors, a full‐length transmembrane form, and a short, secretory form, only the full‐length isoform was detected in the developing forebrain. We found that, in the early developmental stages, while EphA3 mRNA was expressed in the dorsal thalamus and the cortical intermediate zone (IMZ), the EphA3 protein was detected in the IMZ and the internal capsule, but not in the dorsal thalamus. In the later stages the mRNA was expressed in the most superficial region of the cortical plate, while the protein was expressed in the IMZ. This discrepancy between the mRNA and protein expression patterns might be attributed to the possibility of the protein being transported to the axons to regulate the thalamocortical and corticofugal projection. The results of double‐immunostaining for L1 and EphA3 or TAG‐1 and EphA3 suggested that EphA3 protein was produced mainly in the thalamocortical axons and only partially in the corticofugal axons. In addition, the EphA3 protein was also detected in various other structures, such as the lateral olfactory tract, anterior commissure, and corpus callosum, suggesting the possibility that EphA3 might regulate the formation of various neuronal networks in the developing brain, including the TC projection and the commissural fibers. J. Comp. Neurol. 487:255–269, 2005. © 2005 Wiley‐Liss, Inc.
Energy Flow in Push–Pull Chromophores: Vibrational Dynamics in para‐Nitroaniline
Authors: Gunaratne Tissa , Challa J. Reddy , Simpson M. Cather
Published: May 2005

para‐Nitroaniline (PNA) plays an essential role as the prototype model of push–pull chromophores. The nature and degree of participation of vibrational degrees of freedom in the charge‐transfer and internal‐conversion processes are current issues of great theoretical and practical importance. Ultrafast time‐resolved anti‐Stokes resonance Raman spectroscopy (TRARRS) experiments on PNA in dimethyl sulfoxide with three different excitation wavelengths were performed to probe these dynamical influences. The vibrational dynamics associated with S0 were independent of incident wavelength, and this supports the picture that the S1 dynamics are fast relative to the rate of intersystem crossing. The phenyl breathing mode ν19 (860 cm−1) and the symmetric NO2 stretch ν29 (1310 cm−1) exhibited vibrational lifetimes in S0 of 8.1 and 5.2 ps, respectively. No evidence for inhomogeneous broadening of the charge‐transfer band in the UV/Vis absorption spectrum was found.
Barbituric Acid Sensor Based on Molecularly Imprinted Polymer‐ Modified Hanging Mercury Drop Electrode
Authors: Prasad Bhim Bali , Lakshmi Dhana
Published: May 2005

A barbituric acid sensor based on molecularly imprinted polymer‐modified hanging mercury drop electrode is reported for sensitive and selective analysis in aqueous and blood plasma samples. It was developed by coating directly the barbituric acid‐ imprinted polymer, which is prepared from melamine and chloranil, onto the surface of a hanging mercury drop electrode under charge‐transfer interaction at +0.3 V (vs. Ag/AgCl) in Model 303A electrode system connected with a polarographic analyzer/stripping voltammeter (PAR Model 264A). The binding event of barbituric acid was detected in the imprinted polymer layer through differential pulse, cathodic stripping voltammetric (DPCSV) signal at optimized operational conditions [accumulation potential +0.3 V (vs. Ag/AgCl), accumulation time 120 s, pH 7.0 (without supporting electrolyte), scan rate 10 mV s−1, pulse amplitude 25 mV]. The limit of detection for barbituric acid was found to be 0.54 ppm (RSD=3.7%, S/N=3). The detection was feasible without any problem of matrix effect or cross reactivity in the linearity range of concentration varying from 0.50 to 125.00 ppm of barbituric acid.
Use of the Comet test and micronucleus assay on human white blood cells for in vitro assessment of genotoxicity induced by different drinking water disinfection protocols
Authors: Maffei Francesca , Buschini Annamaria , Rossi Carlo , Poli Paola , Forti Giorgio Cantelli , Hrelia Patrizia
Published: May 2005

Surface water disinfection can lead to the formation of mutagenic/carcinogenic by‐products derived from reactions with naturally occurring inorganic compounds. We investigated the feasibility and potential usefulness of an integrated approach to genotoxicity analysis of drinking water. The approach employed the Comet and micronucleus (MN) assays to evaluate the DNA and chromosomal damage produced by water extracts in human blood cells. Surface water samples from Lago Trasimeno (Italy) were collected in different seasons (July 2000, October 2000, February 2001, and June 2001), and samples were disinfected with sodium hypochloride (NaClO), chlorine dioxide (ClO2), or peracetic acid (PAA). Extracts of untreated and treated water were incubated with primary human leukocytes. The Comet assay revealed both strong seasonal variations and differences between samples processed by the three disinfection protocols. The three disinfectants increased the genotoxicity of the water collected in July 2000 and October 2000, with PAA producing the greatest amount of DNA damage. Extracts of raw water collected in February 2001 produced so much DNA damage that the relative genotoxic potentials of the three disinfectants could not be evaluated. No increase in MN frequency was detected in any of the samples. The multi‐endpoint MN assay indicated, however, that our study samples (especially the sample collected in the February 2001) were cytotoxic. We conclude that this integrated approach to genotoxicity assessment may be useful both for the quality control of raw drinking water and to help compare the potential health risks associated with alternative disinfection processes. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.
Cellular modelling in fluvial geomorphology
Authors: Nicholas Andrew P.
Published: May 2005

This paper outlines the principles of cellular modelling in fluvial geomorphology and addresses issues of model formulation and validation in the context of numerical modelling more generally. In doing so it seeks to highlight the prospects for using cellular approaches to develop an improved understanding of both rivers and models. Copyright © 2005 John Wiley & Sons, Ltd.
High‐resolution detection and mapping of genomic DNA alterations in neuroblastoma
Authors: Mosse Yael P. , Greshock Joel , Margolin Adam , Naylor Tara , Cole Kristina , Khazi Deepa , Hii George , Winter Cynthia , Shahzad Syed , Asziz Muhammad Usman , Biegel Jaclyn A. , Weber Barbara L. , Maris John M.
Published: May 2005

We used array‐based comparative genomic hybridization (aCGH) to measure genomic copy number alterations (CNAs) in 42 neuroblastoma cell lines with known 1p36.3, 2p24 (MYCN), 11q23, and 17q23 allelic status. All cell lines showed CNAs, with an average of 22.0% of the genome of each sample showing evidence of gain (11.6%) or loss (10.4%). MYCN amplification was detected in 81% of cell lines, but other regions with high‐level genomic amplification were observed only rarely. Gain of 17q material was present in 75% of the samples, and four discrete genomic regions at 17q23.2–17q25.3 were defined. Novel regions of gain were identified, including a 2.6‐Mb subtelomeric region at 5p that includes the telomerase reverse transcriptase gene (TERT), which was found in 45% of the cell lines. Hemizygous deletions were noted at 1p36.23–1p36.32 and 11q23.3–11q25 in 60% and 36%, respectively, of the samples, with other frequent (>25%) regions of deletion localized to 1p32.1, 3p21.31–3p22.1, 5q35.2–5q35.3, 7q31.2, 7q34, 9q22.3–9q24.1, 10q26.11–10q26.12, 16q23.1–16q24.3, 18q21.32–18q23, and 20p11.21–20p11.23. A smallest region of overlap (SRO) for CNAs was mapped across all experiments and in each case was consistent with or refined the published data. A single cell line showed a homozygous deletion at 3p22.3, which was verified, and this location was refined by FISH and PCR. There was outstanding concordance of aCGH with PCR‐based CNA detection methods. Several potential cooperating loci were identified, including deletion of 11q23–25, which was highly associated with both regional gain and loss at multiple chromosomal loci but was inversely correlated with the deletion of 1p36. Taking all of this together indicates that aCGH can accurately measure CNAs in the neuroblastoma genome and facilitate gene discovery efforts by high‐throughput refinement of candidate loci. Supplementary material for this article can be found on the Genes, Chromosomes and Cancer website at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat/index.html. © 2005 Wiley‐Liss, Inc.
Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer
Authors: Wu Chew‐Wun , Yin Pen‐Hui , Hung Wen‐Yi , Li Anna Fen‐Yau , Li Shu‐Hui , Chi Chin‐Wen , Wei Yau‐Huei , Lee Hsin‐Chen
Published: May 2005

Gastric carcinoma is one of the most common types of cancer in Taiwan. Somatic mitochondrial DNA (mtDNA) alteration in gastric carcinoma and its association with clinicopathologic features remain unclear. When we used polymerase chain reaction (PCR) and direct sequencing, 15 of the 31 (48%) gastric carcinomas displayed somatic mutations in the D‐loop region, a hot spot for mutations in mtDNA of human cancers. Ten (67%) cancers with the somatic mutations in the D‐loop had insertion or deletion mutations in nucleotide position (np) 303–309 in the mononucleotide repeat region. One carcinoma carried tandem duplication and triplication flanked by mononucleotide repeats starting at np 311 and 568, respectively, in the D‐loop. We also detected the common 4,977‐bp deletion in 17 (55%) of the noncancerous tissue samples, but only in three (9%) carcinomas. Moreover, we quantified the mtDNA content using a competitive PCR technique and found that mtDNA depletion occurred in 17 (55%) of the gastric carcinomas. Although no significant association was found between clinicopathologic features and the mtDNA mutations in the D‐loop, mtDNA depletion was observed significantly in the ulcerated, infiltrating (Borrmann's type III) and diffusely thick (Borrmann's type IV) types of gastric carcinomas (P = 0.018). Our results suggest that somatic mtDNA mutations and mtDNA depletion occur in gastric cancer and that mtDNA depletion is involved in carcinogenesis and/or cancer progression of gastric carcinoma. © 2005 Wiley‐Liss, Inc.
Disruption of the hyaluronan‐based extracellular matrix in spinal cord promotes astrocyte proliferation
Authors: Struve Jaime , Maher P. Colby , Li Ya‐qin , Kinney Shawn , Fehlings Michael G. , Kuntz Charles , Sherman Larry S.
Published: May 2005

Astrocyte proliferation is tightly controlled during development and in the adult nervous system. In the present study, we find that a high‐molecular‐weight (MW) form of the glycosaminoglycan hyaluronan (HA) is found in rat spinal cord tissue and becomes degraded soon after traumatic spinal cord injury. Newly synthesized HA accumulates in injured spinal cord as gliosis proceeds, such that high‐MW HA becomes overabundant in the extracellular matrix surrounding glial scars after 1 month. Injection of hyaluronidase, which degrades HA, into normal spinal cord tissue results in increased numbers of glial fibrillary acidic protein (GFAP)‐positive cells that also express the nuclear proliferation marker Ki‐67, suggesting that HA degradation promotes astrocyte proliferation. In agreement with this observation, adding high‐ but not low‐MW HA to proliferating astrocytes in vitro inhibits cell growth, while treating confluent, quiescent astrocyte cultures with hyaluronidase induces astrocyte proliferation. Collectively, these data indicate that high‐MW HA maintains astrocytes in a state of quiescence, and that degradation of HA following CNS injury relieves growth inhibition, resulting in increased astrocyte proliferation. © 2005 Wiley‐Liss, Inc.
Nucleoside transporter expression and function in cultured mouse astrocytes
Authors: Peng Liang , Huang Rong , Yu Albert C.H. , Fung King Y. , Rathbone Michel P. , Hertz Leif
Published: May 2005

Uptake of purine and pyrimidine nucleosides in astrocytes is important for several reasons: (1) uptake of nucleosides contributes to nucleic acid synthesis; (2) astrocytes synthesize AMP, ADP, and ATP from adenosine and GTP from guanosine; and (3) adenosine and guanosine function as neuromodulators, whose effects are partly terminated by cellular uptake. It has previously been shown that adenosine is rapidly accumulated by active uptake in astrocytes (Hertz and Matz, Neurochem Res 14:755–760, 1989), but the ratio between active uptake and metabolism‐driven uptake of adenosine is unknown, as are uptake characteristics for guanosine. The present study therefore aims at providing detailed information of nucleoside transport and transporters in primary cultures of mouse astrocytes. Reverse transcription‐polymerase chain reaction identified the two equilibrative nucleoside transporters, ENT1 and ENT2, together with the concentrative nucleoside transporter CNT2, whereas CNT3 was absent, and CNT1 expression could not be investigated. Uptake studies of tritiated thymidine, formycin B, guanosine, and adenosine (3‐s uptakes at 1–4°C to study diffusional uptake and 1–60‐min uptakes at 37°C to study concentrative uptake) demonstrated a fast diffusional uptake of all four nucleosides, a small, Na+‐independent and probably metabolism‐driven uptake of thymidine (consistent with DNA synthesis), larger metabolism‐driven uptakes of guanosine (consistent with synthesis of DNA, RNA, and GTP) and especially of adenosine (consistent with rapid nucleotide synthesis), and Na+‐dependent uptakes of adenosine (consistent with its concentrative uptake) and guanosine, rendering neuromodulator uptake independent of nucleoside metabolism. Astrocytes are accordingly well suited for both intense nucleoside metabolism and metabolism‐independent uptake to terminate neuromodulator effects of adenosine and guanosine. © 2005 Wiley‐Liss, Inc.
Glial immunoreactivity for metallothionein in the rat brain
Authors: Young John K. , Garvey Justine S. , Huang P. C.
Published: May 2005

A series of frozen and vibratome coronal sections of the rat brain were examined by immunocytochemistry for the presence of a cysteine‐rich metal binding protein, metallothionein (MT). Astrocytes throughout the brain and brainstem stained positively for MT; neurons and oligodendroglia were unstained. Ependymal cells and tanycyte processes in the hypothalamus were also immunoreactive, along with a narrow zone of immunopositivity along the margins of the area postrema. Gomori‐positive astrocytes in the hypothalamus, identifiable by toluidine blue staining, metal‐containing cytoplasmic granules, represented a subset of MT‐positive astrocytes that may be involved in reactions to blood‐borne metal compounds that penetrate into circumventricular organs of the brain.
Schwann cells and cells in the oligodendrocyte lineage proliferate in response to a 50,000 dalton membrane‐associated mitogen present in developing brain
Authors: Nordlund Michael , Hong Dingming , Fei Xun , Ratner Nancy
Published: May 2005

The neuronal cell surface is believed to carry a mitogenic signal for peripheral glial cells. We have purified a mitogen from fetal bovine brain membranes that, in common with the PNS neuronal mitogen, stimulates the proliferation of Schwann cells in vitro and binds heparin. The purified mitogen has an apparent molecular weight of 50,000 daltons as estimated by elution of activity from non‐reducing polyacrylamide gels. Since the developing central nervous system is a rich source of mitogen, we tested whether the protein is mitogenic for one or more cell types isolated from the developing brain. Purified mitogen was added to enriched cultures of astrocytes or developing oligodendrocytes, or to microglial cells. The analyses demonstrated that the protein is mitogenic for developing oligodendrocytes but not astrocytes or microglial cells. These results suggest that during development a membrane‐associated mitogen present in the brain might regulate the proliferation of developing oligodendrocytes, and consequently, the population size of oligodendrocytes in the brain.
Agonist‐evoked Ca2+ transients in primary astroglial cultures–modulatory effects of valproic acid
Authors: Nilsson Michael , Hansson Elisabeth , Rounnbäuck Lars
Published: May 2005

Cytosolic Ca2+ ([Ca2+]i) activity was measured in individual type 1 astroglial cells in primary culture after exposure to glutamate (Glu), quisqualate (QA), γ‐aminobutyric acid (GABA), 5‐hydroxytryptamine (5HT), and noradrenaline (NA) by using the Ca2+ indicator dye fura‐2/AM in a computerized microspectrofluorimetric system. Various patterns of Ca2+ transients were observed, but the most common was biphasic, having an initial sharp peak, rising immediately after stimulation, and then declining to a lower but sustained Ca2+ level. The only substance that diverged from this pattern was GABA, which induced a Ca2+ response with longer latency and a single‐phase curve. The effects of the anticonvulsive drug Na+‐valproate (VPA) were also investigated. After both acute and chronic (5–7 days) exposure to 10−4 M VPA, the GABA‐evoked rises in [Ca2+]i were completely inhibited. VPA also had acute effects on the 5HT‐ and Glu‐evoked Ca2+ spikes. The Ca2+ responses after 5HT stimulation were greatly reduced after exposure to 10‐4 M VPA. The responses after glutamate stimulation were, on the contrary, increased after a similar exposure. No VPA effects were seen on the curve patterns of QA and NA stimulations. The most frequent agonist‐evoked responses were seen after stimulation with 5HT and NA, where over 80% of the tested cells responded. For QA and Glu, the response frequencies were about 40% each, while for GABA it was 20%. The responses after 5HT and NA stimulation were blocked to baseline levels after exposure to ketanserin (5HT2 receptor antagonist) and a combination of prazosin, yohimbine, and propranolol (α1, α2, and β adrenoceptor antagonists, respectively). The rises in [Ca2+]i after stimulation with QA, Glu, and GABA were partly antagonized by 6‐nitro‐7‐cyano‐quinoxaline‐2,3‐dione (CNQX; a QA receptor antagonist, also tested on the glutamate responses) and bicuculline (GABA receptor antagonists). The biphasic curve forms, after stimulation with Glu, QA, 5HT, and NA, were reduced to single‐phase curves with unaffected or slightly reduced initial peaks when the stimulations were performed in Ca2+‐free medium. Interestingly, in some cells Glu induced a curve form that, different from the other Glu‐evoked responses, consisted of an immediate rise in [Ca2+]i, which persisted at the level of maximal response. Furthermore, this response was completely inhibited in Ca2+‐free buffer. The GABA response was also totally inhibited in Ca2+ ‐free buffer.

The results suggest that astrocytes in primary culture respond differently to various receptor agonists, with regard to both the intracellular Ca2+ spiking behavior and the response frequency. Furthermore, the data also show that certain agonist‐evoked rises in [Ca2+]i can be significantly modulated by the neuroactive agent VPA.