bluuebunny/crossref_metadata_2025 huggingface dataset:
Assignment of the human fast skeletal muscle troponin C gene (TNNC2) between D20S721 and GCT10F11 on chromosome 20 by somatic cell hybrid analysis
Authors: TOWNSEND P. J. , YACOUB M. H. , BARTON P. J. R.
Published: December 2004

The chromosomal location of the human fast skeletal muscle troponin C (TNNC2) gene was determined using somatic cell hybrids. PCR‐based analysis of a ‘monochromosomal’ hybrid panel identified the presence of the TNNC2 gene on human chromosome 20 and subsequent analysis of the Genebridge4 radiation hybrid panel located the gene between D20S721 and GCT10F11 with a lod score of >3.
Localization of the fast skeletal muscle troponin I gene (TNNI2) to 11p15.5: genes for troponin I and T are organized in pairs
Authors: BARTON P. J. R. , TOWNSEND P. J. , BRAND N. J. , YACOUB M. H.
Published: December 2004

We have localized the gene encoding the fast skeletal muscle isoform of troponin I (TNNI2) to 11p15.5 by PCR‐based analysis of somatic cell hybrid panels: based on the Genebridge4 radiation hybrid panel, TNNI2 is coincident with the marker D11S922. The gene encoding the fast skeletal muscle troponin T gene (TNNT3) has been previously assigned to 11p15.5 suggesting that TNNI2 and TNNT3 may be closely linked. The overall location of genes encoding troponin I and T isoforms now reveals that they are organized at three loci each containing a troponin I/troponin T gene pair. This organization contrasts with all other sarcomeric protein genes and has implications for the evolution of these two gene families, for their regulation and for the analysis of mutations suspected to result in cardiomyopathy.
Natural selection in industrialized countries: a study of three generations of Italian newborns
Authors: ULIZZI L. , ASTOLFI P. , ZONTA L. A.
Published: December 2004

We have studied the impact of natural selection on the Italian population, analysing the relationship between stillbirth and three related variables: birth weight, birth order and maternal age. A progressive relaxation of selection with time has been demonstrated by the reduction of the Haldane index calculated with respect to the three variables.
Population paths implied by the mean number of pairwise nucleotide differences among mitochondrial DNA sequences
Authors: BONNEUIL N.
Published: December 2004

Scenarios, such as populations experiencing a bottleneck or an exponential growth, have been suggested as candidates for explaining the observed differences among mitochondrial DNA sequences in a sample of a given population closed to migrations. Here, population size is considered as capable of varying, and the set of the at least 95% most probable population paths capable of producing the observed mean number of pairwise nucleotide differences is delineated. To do this, the mean and the variance of coalescence times of two genes taken in an n‐genes sample with varying population size are expressed. The observed mean coalescence time already echoed a set of population paths due to the variance associated to the coalescent process, but only specific scenarios have been studied, such as the bottleneck or the exponential function. However, mitochondrial DNA data does not reflect a single scenario, after the effect of the variance. These scenarios implied by pairwise nucleotide differences are described through a set‐valued function, the ‘regulation map’, a convenient way to represent temporal population paths.
Sodium nitroprusside‐induced rat fundus relaxation is ryanodine‐sensitive and involves L‐type Ca2+ channel and small conductance Ca2+‐sensitive K+ channel components
Authors: Geeson J. , Larsson K. , Hourani S. M. O. , Toms N. J.
Published: December 2004

1 The aim of this study was to examine whether sodium nitroprusside (SNP)‐induced relaxation of rat fundus longitudinal smooth muscle involves ryanodine‐sensitive Ca2+ release.

2 SNP (300 nm–30 μm) elicited concentration‐dependent relaxation of precontracted (1 μm carbachol) rat fundus, an effect almost abolished by the selective guanylyl cyclase inhibitor, 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxaline‐1‐one (ODQ, 10 μm).

3 SNP‐mediated relaxations were almost abolished by 10 μm ryanodine.

4 SNP‐mediated relaxations were also reduced by either 1 μm apamin (a selective small conductance Ca2+‐sensitive K+ channel, SKCa, inhibitor) or the selective L‐type Ca2+ channel inhibitor, nicardipine (3 μm).

5 SNP‐induced relaxations were insensitive to 1 mm tetraethylammonium chloride (an inhibitor of large‐conductance Ca2+‐sensitive K+ channels) and 1 μm glibenclamide (an ATP‐sensitive K+ channel inhibitor).

6 These data suggest that SNP‐mediated fundus relaxation occurs via a cGMP‐mediated and ryanodine‐sensitive mechanism which requires, at least in part, SKCa and L‐type Ca2+ channel activity.
The role of α1D‐adrenoceptors in prostatic contraction examined using protection studies
Authors: Chess‐Williams R. , Mason S. , Sellers D. J. , Wyllie M. , Chapple C. R.
Published: December 2004

1 The aim of the study was to investigate the role of the α1D‐adrenoceptor in α1‐adrenoceptor‐induced contraction of human prostate by means of protection experiments.

2 Responses of human prostate strips to noradrenaline were recorded, along with responses of rat aorta and vas deferens, tissues possessing predominantly α1D‐ and α1A‐adrenoceptors respectively, for comparison. α1‐adrenoceptors were then inactivated by incubation with the irreversible antagonist phenoxybenzamine. In some tissues α1A‐ or α1D‐adrenoceptors were ‘protected’ from inactivation by incubation in the presence of the selective α1A‐ or 1D‐adrenoceptor antagonists 5‐methylurapidil and BMY 7378 before recording further responses to noradrenaline.

3 Phenoxybenzamine reduced the maximum noradrenaline‐induced response and the potency of noradrenaline in all tissues. In rat vas deferens and human prostate, 5‐methylurapidil protected α1A‐adrenoceptors in a concentration–dependent manner. In rat aorta, 10 nm BMY 7378 almost fully protected α1D‐adrenoceptors. However, concentrations of BMY 7378 up to 30‐fold higher failed to protect receptors in the human prostate.

4 These results suggest that in human prostate functional α1D‐adrenoceptors do not contribute to noradrenaline‐induced contractile responses.
Comparison of the effect of cyclic AMP on the content and release of dopamine and 1‐methyl‐4‐phenylpyridinium (MPP+) in PC12 cells
Authors: Ribeiro L. , Azevedo I. , Martel F.
Published: December 2004

1 The aim of this work was to investigate the effect of acute and chronic exposure of rat pheochromocytoma (PC12) cells to elevated cAMP, using forskolin, dibutyryl‐cAMP (db‐cAMP) or isobutylmethylxanthine (IBMX), on endogenous dopamine content and release and on [3H]‐1‐methyl‐4‐phenylpyridinium ([3H]‐MPP+) uptake and release, under basal conditions and under KCl‐stimulation.

2 Cultured PC12 cells synthetized and accumulated large amounts of dopamine, but not noradrenaline or adrenaline. The release of dopamine by the cells was markedly increased in response to 50 mm KCl.

3 Acute and chronic treatment of the cells with forskolin (30 μm), but not IBMX (100 μm), slightly increased the spontaneous release of dopamine and significantly decreased the release induced by 50 mm KCl.

4 Chronic treatment of the cells with forskolin (30 μm), but not IBMX (100 μm), markedly decreased the cellular content of dopamine.

5 Cultured PC12 cells removed and accumulated [3H]‐MPP+, which, similarly to dopamine, was released by KCl.

6 Acute treatment of the cells with forskolin (30 μm) or db‐cAMP (2.5 mm), but not IBMX (100 μm), slightly increased the spontaneous release, but did not affect KCl‐induced release of [3H]‐MPP+. On the other hand, chronic treatment of the cells with forskolin produced, on [3H]‐MPP+, similar effects to those obtained for dopamine.

7 Acute and chronic treatment of the cells with reserpine (50 nm) produced similar results to those obtained with forskolin on either dopamine or [3H]‐MPP+ handling.

8 In conclusion, cAMP, similarly to reserpine, increases the spontaneous release and decreases the KCl‐induced release of [3H]‐MPP+ and dopamine. This suggests that cAMP impairs the vesicular monoamine transporter.
The chronological life span of Saccharomyces cerevisiae
Authors: Fabrizio Paola , Longo Valter D.
Published: December 2004

Simple model systems have played an important role in the discovery of fundamental mechanisms of aging. Studies in yeast, worms and fruit flies have resulted in the identification of proteins and signalling pathways that regulate stress resistance and longevity. New findings indicate that these pathways may have evolved to prevent damage and postpone aging during periods of starvation and may be conserved from yeast to mammals. We will review the yeast S. cerevisiae model system with emphasis on the chronological life span as a model system to study aging and the regulation of stress resistance in eukaryotes.
Base excision repair activities required for yeast to attain a full chronological life span
Authors: Maclean Morag J. , Aamodt Randi , Harris Nicholas , Alseth Ingrun , Seeberg Erling , Bjørås Magnar , Piper Peter W.
Published: December 2004

The chronological life span of yeast, the survival of stationary (G0) cells over time, provides a model for investigating certain of the factors that may influence the aging of non‐dividing cells and tissues in higher organisms. This study measured the effects of defined defects in the base excision repair (BER) system for DNA repair on this life span. Stationary yeast survives longer when it is pregrown on respiratory, as compared to fermentative (glucose), media. It is also less susceptible to viability loss as the result of defects in DNA glycosylase/AP lyases (Ogg1p, Ntg1p, Ntg2p), apurinic/apyrimidinic (AP) endonucleases (Apn1p, Apn2p) and monofunctional DNA glycosylase (Mag1p). Whereas single BER glycosylase/AP lyase defects exerted little influence over such optimized G0 survival, this survival was severely shortened with the loss of two or more such enzymes. Equally, the apn1Δ and apn2Δ single gene deletes survived as well as the wild type, whereas a apn1Δapn2Δ double mutant totally lacking in any AP endonuclease activity survived poorly. Both this shortened G0 survival and the enhanced mutagenicity of apn1Δapn2Δ cells were however rescued by the overexpression of either Apn1p or Apn2p. The results highlight the vital importance of BER in the prevention of mutation accumulation and the attainment of the full yeast chronological life span. They also reveal an appreciable overlap in the G0 maintenance functions of the different BER DNA glycosylases and AP endonucleases.
Increased p27, an essential component of cell cycle control, in Alzheimer's disease
Authors: Ogawa Osamu , Lee Hyoung‐gon , Zhu Xiongwei , Raina Arun , Harris Peggy L. R. , Castellani Rudolph J. , Perry George , Smith Mark A.
Published: December 2004

A number of recent findings have demonstrated re‐expression of cell cycle‐related proteins in vulnerable neurones in Alzheimer's disease. We hypothesize that this attempt by neurones to re‐enter mitosis is a response to external growth stimuli that leads to an abortive re‐entry into the cell cycle and, ultimately, neuronal degeneration. In this study, to further delineate the role of mitotic processes in the pathogenesis of Alzheimer's disease, we investigated p27, a cyclin‐dependent kinase inhibitor that plays a negatively regulatory role in cell cycle progression that, once phosphorylated at Thr187, is degraded via an ubiquitin‐proteasome pathway. Here we report that both p27 and phosphorylated p27 (Thr187) show increases in the cytoplasm of vulnerable neuronal populations in Alzheimer's disease vs. age‐matched control subjects. Importantly, phosphorylated p27 (Thr187) shows considerable overlap with tau‐positive neurofibrillary pathology, including neurofibrillary tangles, dystrophic neurites and neuropil threads. The findings presented here suggest that dysregulation of the cell cycle plays a crucial role in the pathogenesis of Alzheimer's disease that may provide a novel mechanistic basis for therapeutic intervention.
Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin‐like signals
Authors: Walker Glenda A. , Lithgow Gordon J.
Published: December 2004

Insulin‐like signalling is a key determinate of lifespan in diverse species including mammals but the mechanism by which this pathway influences the rate of aging is unknown. In the roundworm Caenorhabditis elegans, mutations in the insulin‐like signalling pathway extend adult lifespan and are associated with up‐regulation of stress response genes including those for heat shock proteins (HSPs). We tested the hypothesis that the C. elegans insulin‐like signalling pathway determines longevity through modulating HSP levels. We introduced extra copies of the gene encoding HSP‐16 and this conferred stress resistance and longevity both in a wildtype and a long‐lived mutant strain. The DAF‐16 transcription factor is essential for maximal hsp‐16 expression and for lifespan extension conferred by hsp‐16. This demonstrates that lifespan is determined in part by insulin‐like regulation of molecular chaperones.
Mitochondria: are they the seat of senescence?
Authors: Fridovich Irwin
Published: December 2004

The frequently quoted figure for the fractional univalent reduction of oxygen to superoxide in mitochondria is certainly too high by at least one order of magnitude. This is so because the higher number (2%) was derived from mitochondria whose cytochrome c oxidase was blocked with cyanide. Nevertheless, even the more correct number (0.1%) means that the production of and H2O2 in mitochondria is large and apt to result in damage to macromolecules in spite of such defensive enzymes as superoxide dismutases and glutathione peroxidase. The data available for nematodes and flies provide a compelling case for the view that the accumulation of oxidative damage to specific mitochondrial proteins leads to the progressive dysfunction that we see as senescence. The data available from work with mammals are much weaker and do not yet allow a strong position to be taken.
Transpupillary thermotherapy for idiopathic subfoveal choroidal neovascularization
Authors: Kumar Atul , Prakash Gunjan , Singh Rajindra P.
Published: December 2004

Purpose: To assess the efficacy of transpupillary thermotherapy (TTT) for the management of idiopathic subfoveal choroidal neovascularization (CNV).

Methods: This was a prospective, non‐controlled, clinical case trial involving 21 eyes of 21 patients with a mean age of 36 years. All 21 eyes had idiopathic subfoveal CNV and were subjected to diode laser TTT. Laser beam size ranged from 1.2 mm to 3.0 mm and power settings ranged between 300 mW and 600 mW. The end‐point was an area of no visible colour change. Pre‐ and post‐laser evaluations of ETDRS visual acuity, contrast sensitivity, slit‐lamp biomicroscopy and fluorescein angiography were carried out.

Results: The nine predominantly occult and 12 predominantly classic subfoveal membranes were followed‐up for a mean of 5.1 months after TTT. Overall, 17 eyes (81%) showed improvement or stabilization in ETDRS visual acuity. Contrast sensitivity improved in 17 eyes (81%). Reading speed improved in 15 eyes (71%). Retreatment was needed in three eyes (14%).

Conclusion: Transpupillary thermotherapy treatment is a potential strategy for treating idiopathic subfoveal CNV in both its classic and occult forms.
A prospective longterm study of primary chronic angle closure glaucoma
Authors: Sihota Ramanjit , Sood Aman , Gupta Viney , Gupta Vishal , Dada Tanuj , Agarwal Harish C.
Published: December 2004

Purpose:  To prospectively evaluate the longterm outcome of therapy for chronic primary angle closure glaucoma (PACG) and to assess the efficacy of medical and surgical treatment in terms of intraocular pressure (IOP) and visual field stabilization.

Methods:  Seventy consecutive patients with chronic PACG, whose IOP remained > 21 mmHg despite a patent iridotomy, had their IOP controlled by medications or trabeculectomy performed without antimetabolites. They were followed over a 6‐year period. Best corrected visual acuity, IOP (mean of annual diurnal variation readings), cup : disc ratio and visual fields were recorded. A trabeculectomy was performed if the IOP was not adequately controlled on maximal tolerable medical therapy or if there was a progression of the glaucomatous defect. Data from one eye of each patient were analysed; if both eyes met the inclusion criteria, one was randomly selected for the analysis. The baseline parameters were compared with those at the end of 6 years.

Results:  A total of 46 eyes (65%) were controlled medically throughout the 6‐year follow‐up period, while 24 eyes (35%) required surgery. The mean IOP was 25.4 ± 4.9 mmHg at baseline and 15.6 ± 4.6 mmHg at 6 years follow‐up (p < 0.001). Stereoscopic evaluation of the cup : disc ratio did not show a significant change from a mean of 0.6 ± 0.18 at baseline to a mean of 0.64 ± 0.2 at 6 years (p = 0.12). Progression of visual field defects was seen in seven eyes (10%), which had statistically larger cup : disc ratios (p = 0.04) and more extensive visual field deficits at the initial assessment (p = 0.04), and which also maintained higher levels of IOP (p = 0.03) over the 6 years of follow‐up.

Conclusions:  Stable visual fields and good longterm IOP control were seen in 90% of chronic primary angle closure glaucoma eyes on medical/surgical therapy over 6 years.
Lycanthropy – psychopathological and psychodynamical aspects
Authors: Garlipp P. , Gödecke‐Koch T. , Dietrich D. E. , Haltenhof H.
Published: December 2004

Objective: The imagination of being transformed into an animal or being an animal is called lycanthropy. The phenomenon is presented and psychodynamical aspects are discussed.

Method: A literature review forms the base of this discussion of a psychopathological phenomenon.

Results: The lycanthropic symptomatology represents a spectrum of continuity of developmental and culture‐dependent normal behaviour via partial forms to the complete picture of lycanthropy. It is observed in different mental disorders.

Conclusion: Lycanthropy is interpreted by the authors as a delusion in the sense of the self‐identity disorder defined by Scharfetter. It is mainly found in affective and schizophrenic disorders but can be a symptom of other psychiatric disorders as well. Psychodynamically this kind of delusion can be interpreted as an attempt to project suppressed affects, especially with aggressive or sexual content, into the figure of an animal. Psychotherapy and/or neuroleptic medication can be effective.
Elderly suicide in Hong Kong – a case‐controlled psychological autopsy study
Authors: Chiu H. F. K. , Yip P. S. F. , Chi I. , Chan S. , Tsoh J. , Kwan C. W. , Li S. F. , Conwell Y. , Caine E.
Published: December 2004

Objective:  To examine some of the risk factors for late life suicide in Hong Kong Chinese using a case‐controlled psychological autopsy approach.

Method:  Informants of 70 subjects aged 60 or above who had committed suicide as well as a community sample of 100 elderly controls were interviewed. Subjects and controls were assessed for the presence of mental illness, history of suicide attempt and data on health care utilization.

Results:  Eighty‐six per cent of suicide subjects suffered from a psychiatric problem before committing suicide, compared with 9% of control subjects. Among the psychiatric problems, major depression was the commonest diagnosis. Seventy‐seven per cent of suicide subjects had consulted a doctor within 1 month of suicide. One‐third of suicide subjects had a history of suicide attempt. Rates of current psychiatric diagnosis, rates of medical consultation and history of suicide attempt are all significantly higher in suicide subjects than controls.

Conclusion:  Our findings support the view that depressive disorders and a past history of suicide attempt are risk factors of late‐life suicide in the Chinese population of Hong Kong, similar to findings in western studies.
The predictive effect of episodes on the risk of recurrence in depressive and bipolar disorders – a life‐long perspective
Authors: Kessing L. V. , Hansen M. G. , Andersen P. K. , Angst J.
Published: December 2004

Objective:  It is generally accepted that one of the most important predictors of recurrence in depressive and bipolar disorders is the number of previous episodes. However, very few studies have considered the individual tendency toward recurrence in analyses of the effect of the number of episodes on the risk of subsequent recurrence in affective disorder.

Method:  Frailty models were used to estimate the effect of the number of episodes on the rate of recurrence taking into account the individual frailty toward recurrence. The study base consisted of 406 patients, 186 patients with depressive disorder and 220 patients with bipolar disorder, who were admitted between 1959 and 1963 to the Psychiatric Hospital University of Zurich with an affective episode and followed up to 1997.

Results:  The individual rate of subsequent recurrence was found to increase with the number of episodes even when the effect was adjusted for the individual frailty toward recurrence. The effect of episodes was the same in depressive and bipolar disorders and for men and women.

Conclusion:  It seems increasingly valid that in depressive and bipolar disorders, the risk of subsequent recurrence increases with the number of episodes.
Delineating disability, labour force participation and employment restrictions among persons with psychosis
Authors: Waghorn G. , Chant D. , White P. , Whiteford H.
Published: December 2004

Objective: To delineate at a population level: activity restrictions, labour market participation, educational attainment, employment restrictions and employment characteristics of persons with psychosis compared with healthy non‐disabled persons.

Method: Confidentialized data files were provided by the Australian Bureau of Statistics. The data were collected in a national survey titled ‘Survey of Disability, Ageing and Carers, Australia 1998’. Multi‐stage sampling strategies obtained a probability sample of 42 664 individuals. Trained interviewers using ICD‐10 computer‐assisted interviews identified household residents with psychosis.

Results: Among householders with psychosis aged 15–64 years, 75.2% were non‐participants in the labour market, 21.1% were employed and 3.7% were looking for work. Completing school years 10 and 11, and vocational training, appeared to offer an employment advantage.

Conclusion: Persons with psychotic disorders have low rates of labour force participation and may benefit from greater participation in educational and vocational services. Implications for policy development are discussed.
Digital system for vacuum and gas-filled devices testing
Authors: Pejovic Milic M.
Published: December 2004

This article describes an improved electrical system aimed at measuring and data acquisition of the breakdown voltage of vacuum and gas-filled devices at low pressures using a discretized dynamic method. The previous system [M. M. Pejovic, C. S. Milosavljevic, and M. M. Pejovic, Rev. Sci. Instrum. 74, 3127 (2002)] included a complex analog circuit for breakdown detection, which did not provide the required reliability. The smallest voltage step which this system could provide was 250 mV. In order to increase the reliability of the breakdown detection, the Keithley model 248 high power supply was added to the system. The breakdown is detected from a monitor output at model 248 rear panel. The disadvantage of this system was the fact that the minimal value of the voltage step in this case is 1 V. An additional Keithley model 2400 Source Meter was introduced as a serial connection with the Keithley model 248 with the aim of decreasing the minimal value of the voltage step, which is in this case 1 mV. PC controls both Keithley models using standard IEEE 488 interface bus. This system provides a minimal voltage step value of 1 mV which results in a high precision in breakdown voltage determination. The proposed system controls a large number of parameters, which makes significantly influences the breakdown voltage value. The system was tested with a neon-filled tube at 6.6 mbar, where two parameters were varied, the relaxation time and the voltage step. The experimental results are in accordance with the literature regarding the influence of these two parameters on the breakdown voltage of gas-filled tubes.
Fast thermal-pulse measurements of space-charge distributions in electret polymers
Authors: Mellinger Axel , Singh Rajeev , Gerhard-Multhaupt Reimund
Published: December 2004

Space-charge depth profiles in various electret polymers have been measured in both the time and the frequency domain using thermal pulses and waves, respectively. A comparison of the two techniques on corona-charged polytetrafluoroethylene showed that the thermal-pulse method yielded similar results as the thermal-wave technique, but approximately 20–50 times faster. The article discusses sensitivity limitations as well as possible applications, including the real-time monitoring of space-charge decay under UV irradiation.
Electrostatic ion beam trap for electron collision studies
Authors: Heber O. , Witte P. D. , Diner A. , Bhushan K. G. , Strasser D. , Toker Y. , Rappaport M. L. , Ben-Itzhak I. , Altstein N. , Schwalm D. , Wolf A. , Zajfman D.
Published: December 2004

We describe a system combining an ion beam trap and a low energy electron target in which the interaction between electrons and vibrationally cold molecular ions and clusters can be studied. The entire system uses only electrostatic fields for both trapping and focusing, thus being able to store particles without a mass limit. Preliminary results for the electron impact neutralization of C2− ions and aluminum clusters are presented.
Optimization of momentum imaging systems using electric and magnetic fields
Authors: Gisselbrecht M. , Huetz A. , Lavollée M. , Reddish T. J. , Seccombe D. P.
Published: December 2004

Time-of-flight (TOF) momentum imaging systems utilize the x, y, t information from charged particles striking a position-sensitive detector to infer the x, y, and z components of the particles’ initial momenta. This measurement capability can lead to the complete experimental determination of multi-ionization/fragmentation dynamics. In the case of electron detection, the addition of a magnetic field leads to a significantly increased operational energy range. This study shows that the TOF system has to be carefully designed in order to optimize the magnetic confinement effect. Expressions for the optimal dimensions of a single electric field TOF system are derived and factors contributing to the resolution are discussed, along with their application to an existing imaging system.
Performance of the infrared microspectroscopy beamline at CAMD
Authors: Kizilkaya Orhan , Scott John D. , Morikawa Eizi , Garber James D. , Perkins Richard S.
Published: December 2004

The first infrared (IR) beamline at the Center for Advanced Microstructures and Devices (CAMD) at Louisiana State University has been successfully constructed and commissioned. The beamline features a simple optical design with a minimal number of optical components. A pair of mirrors, planar and toroidal, is utilized for extracting synchrotron radiation (50 and 15 mrad, in horizontal and vertical directions, respectively) from the bending magnet port to a diamond window located outside of the shielding wall. Synchrotron radiation is then collimated by an off-axis parabolic mirror and fed into a Thermo Nicolet Continuum microscope through a Thermo Nicolet Nexus 670 FT-IR spectrometer. The microscope’s performances with synchrotron-radiation and conventional-thermal sources were compared in the mid-IR spectral range (11700–400cm−1). Effective beam spot size at sample position of the microscope was measured to be 35×12μm2 (FWHM). It was also determined that synchrotron radiation has substantial advantages over the conventional thermal source: ∼30 times better intensity and ∼100 times better S/N at aperture size of the microscope smaller than 15×15μm2. This performance allows infrared spectroscopy analysis in a small area with a diffraction-limited spatial resolution.
Widespread sulfenic acid formation in tissues in response to hydrogen peroxide
Authors: Saurin Adrian T. , Neubert Hendrik , Brennan Jonathan P. , Eaton Philip
Published: December 2004

A principal product of the reaction between a protein cysteinyl thiol and hydrogen peroxide is a protein sulfenic acid. Because protein sulfenic acid formation is reversible, it provides a mechanism whereby changes in cellular hydrogen peroxide concentration may directly control protein function. We have developed methods for the detection and purification of proteins oxidized in this way. The methodology is based on the arsenite-specific reduction of protein sulfenic acid under denaturing conditions and their subsequent labeling with biotin–maleimide. Arsenite-dependent signal generation was fully blocked by pretreatment with dimedone, consistent with its reactivity with sulfenic acids to form a covalent adduct that is nonreducible by thiols. The biotin tag facilitates the detection of protein sulfenic acids on Western blots probed with streptavidin–horseradish peroxidase and also their purification by streptavidin–agarose. We have characterized protein sulfenic acid formation in isolated hearts subjected to hydrogen peroxide treatment. We have also purified and identified a number of the proteins that are oxidized in this way by using a proteomic approach. Using Western immunoblotting we demonstrated that a highly significant proportion of some individual proteins (68% of total in one case) form the sulfenic derivative. We conclude that protein sulfenic acids are widespread physiologically relevant posttranslational oxidative modifications that can be detected at basal levels in healthy tissue, and are elevated in response to hydrogen peroxide. These approaches may find widespread utility in the study of oxidative stress, particularly because hydrogen peroxide is used extensively in models of disease or redox signaling.
Emergent trade-offs and selection for outbreak frequency in spatial epidemics
Authors: van Ballegooijen W. Marijn , Boerlijst Maarten C.
Published: December 2004

Nonspatial theory on pathogen evolution generally predicts selection for maximal number of secondary infections, constrained only by supposed physiological trade-offs between pathogen infectiousness and virulence. Spread of diseases in human populations can, however, exhibit large scale patterns, underlining the need for spatially explicit approaches to pathogen evolution. Here, we show, in a spatial model where all pathogen traits are allowed to evolve independently, that evolutionary trajectories follow a single relationship between transmission and clearance. This trade-off relation is an emergent system property, as opposed to being a property of pathogen physiology, and maximizes outbreak frequency instead of the number of secondary infections. We conclude that spatial pattern formation in contact networks can act to link infectiousness and clearance during pathogen evolution in the absence of any physiological trade-off. Selection for outbreak frequency offers an explanation for the evolution of pathogens that cause mild but frequent infections.
Essential role for smooth muscle BK channels in alcohol-induced cerebrovascular constriction
Authors: Liu Pengchong , Xi Qi , Ahmed Abu , Jaggar Jonathan H. , Dopico Alejandro M.
Published: December 2004

Binge drinking is associated with increased risk for cerebrovascular spasm and stroke. Acute exposure to ethanol at concentrations obtained during binge drinking constricts cerebral arteries in several species, including humans, but the mechanisms underlying this action are largely unknown. In a rodent model, we used fluorescence microscopy, patch-clamp electrophysiology, and pharmacological studies in intact cerebral arteries to pinpoint the molecular effectors of ethanol cerebrovascular constriction. Clinically relevant concentrations of ethanol elevated wall intracellular Ca
2+
concentration and caused a reversible constriction of cerebral arteries (EC
50
= 27 mM; E
max
= 100 mM) that depended on voltage-gated Ca
2+
entry into myocytes. However, ethanol did not directly increase voltage-dependent Ca
2+
currents in isolated myocytes. Constriction occurred because of an ethanol reduction in the frequency (–53%) and amplitude (–32%) of transient Ca
2+
-activated K
+
(BK) currents. Ethanol inhibition of BK transients was caused by a reduction in Ca
2+
spark frequency (–49%), a subsarcolemmal Ca
2+
signal that evokes the BK transients, and a direct inhibition of BK channel steady-state activity (–44%). In contrast, ethanol failed to modify Ca
2+
waves, a major vasoconstrictor mechanism. Selective block of BK channels largely prevented ethanol constriction in pressurized arteries. This study pinpoints the Ca
2+
spark/BK channel negative-feedback mechanism as the primary effector of ethanol vasoconstriction.
Genomic dissection of the cell-type-specification circuit in
Saccharomyces cerevisiae
Authors: Galgoczy David J. , Cassidy-Stone Ann , Llinás Manuel , O'Rourke Sean M. , Herskowitz Ira , DeRisi Joseph L. , Johnson Alexander D.
Published: December 2004

The budding yeast
Saccharomyces cerevisiae
has three cell types (a cells, α cells, and a/α cells), each of which is specified by a unique combination of transcriptional regulators. This transcriptional circuit has served as an important model for understanding basic features of the combinatorial control of transcription and the specification of cell type. Here, using genome-wide chromatin immunoprecipitation, transcriptional profiling, and phylogenetic comparisons, we describe the complete cell-type-specification circuit for
S
.
cerevisiae
. We believe this work represents a complete description of cell-type specification in a eukaryote.
Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds
Authors: Radisic Milica , Park Hyoungshin , Shing Helen , Consi Thomas , Schoen Frederick J. , Langer Robert , Freed Lisa E. , Vunjak-Novakovic Gordana
Published: December 2004

The major challenge of tissue engineering is directing the cells to establish the physiological structure and function of the tissue being replaced across different hierarchical scales. To engineer myocardium, biophysical regulation of the cells needs to recapitulate multiple signals present in the native heart. We hypothesized that excitation–contraction coupling, critical for the development and function of a normal heart, determines the development and function of engineered myocardium. To induce synchronous contractions of cultured cardiac constructs, we applied electrical signals designed to mimic those in the native heart. Over only 8 days
in vitro
, electrical field stimulation induced cell alignment and coupling, increased the amplitude of synchronous construct contractions by a factor of 7, and resulted in a remarkable level of ultrastructural organization. Development of conductive and contractile properties of cardiac constructs was concurrent, with strong dependence on the initiation and duration of electrical stimulation.
Structure, initial excited-state relaxation, and energy storage of rhodopsin resolved at the multiconfigurational perturbation theory level
Authors: Andruniów Tadeusz , Ferré Nicolas , Olivucci Massimo
Published: December 2004

We demonstrate that a “brute force” quantum chemical calculation based on an
ab initio
multiconfigurational second order perturbation theory approach implemented in a quantum mechanics/molecular mechanics strategy can be applied to the investigation of the excited state of the visual pigment rhodopsin (Rh) with a computational error <5 kcal·mol
-1
. As a consequence, the simulation of the absorption and fluorescence of Rh and its retinal chromophore in solution allows for a nearly quantitative analysis of the factors determining the properties of the protein environment. More specifically, we demonstrate that the Rh environment is more similar to the “gas phase” than to the solution environment and that the so-called “opsin shift” originates from the inability of the solvent to effectively “shield” the chromophore from its counterion. The same strategy is used to investigate three transient structures involved in the photoisomerization of Rh under the assumption that the protein cavity does not change shape during the reaction. Accordingly, the analysis of the initially relaxed excited-state structure, the conical intersection driving the excited-state decay, and the primary isolable bathorhodopsin intermediate supports a mechanism where the photoisomerization coordinate involves a “motion” reminiscent of the so-called bicycle-pedal reaction coordinate. Most importantly, it is shown that the mechanism of the ∼30 kcal·mol
-1
photon energy storage observed for Rh is not consistent with a model based exclusively on the change of the electrostatic interaction of the chromophore with the protein/counterion environment.
Long-range oxidative damage to cytosines in duplex DNA
Authors: Shao Fangwei , O'Neill Melanie A. , Barton Jacqueline K.
Published: December 2004

Charge transport (CT) through DNA has been found to occur over long molecular distances in a reaction that is sensitive to intervening structure. The process has been described mechanistically as involving diffusive charge-hopping among low-energy guanine sites. Using a kinetically fast electron hole trap,
N
4
-cyclopropylcytosine (
CP
C), here we show that hole migration must involve also the higher-energy pyrimidine bases. In DNA assemblies containing either [Rh(phi)
2
(bpy′)]
3+
or an anthraquinone derivative, two highenergy photooxidants, appreciable oxidative damage at a distant
CP
C is observed. The damage yield is modulated by lower-energy guanine sites on the same or complementary strand. Significantly, the efficiency in trapping at
CP
C is equivalent to that at
N
2
-cyclopropylguanosine (
CP
G). Indeed, even when
CP
G and
CP
C are incorporated as neighboring bases on the same strand, their efficiency of photodecomposition is comparable. Thus, CT is not simply a function of the relative energies of the isolated bases but instead may require orbital mixing among the bases. We propose that charge migration through DNA involves occupation of all of the DNA bases with radical delocalization within transient structure-dependent domains. These delocalized domains may form and break up transiently, facilitating and limiting CT. This dynamic delocalized model for DNA CT accounts for the sensitivity of the process to sequence-dependent DNA structure and provides a basis to reconcile and exploit DNA CT chemistry and physics.
Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis
Authors: Tang Zhanyun , Sun Yuxiao , Harley Sara E. , Zou Hui , Yu Hongtao
Published: December 2004

Sister chromatids in mammalian cells remain attached mostly at their centromeres at metaphase because of the loss of cohesion along chromosome arms in prophase. Here, we report that Bub1 retains centromeric cohesion in mitosis of human cells. Depletion of Bub1 or Shugoshin (Sgo1) in HeLa cells by RNA interference causes massive missegregation of sister chromatids that originates at centromeres. Surprisingly, loss of chromatid cohesion in Bub1 and Sgo1 RNA-interference cells does not appear to require the full activation of separase but, instead, triggers a mitotic arrest that depends on Mad2 and Aurora B. Bub1 maintains the steady-state levels and centromeric localization of Sgo1. Therefore, Bub1 protects centromeric cohesion through Shugoshin in mitosis.
IL‐12 Production Induced by Agaricus blazei Fraction H (ABH) Involves Toll‐like Receptor (TLR)
Authors: Kasai H. , He L. M. , Kawamura M. , Yang P. T. , Deng X. W. , Munkanta M. , Yamashita A. , Terunuma H. , Hirama M. , Horiuchi I. , Natori T. , Koga T. , Amano Y. , Yamaguchi N. , Ito M.
Published: December 2004

Agaricus blazei Murill is an edible fungus used in traditional medicine, which has various well‐documented medicinal properties. In the present study, we investigated the effects of hemicellulase‐derived mycelia extract (Agaricus blazei fraction H: ABH) on the immune system. First, we examined the cytokine‐inducing activity of ABH on human peripheral mononuclear cells (PBMC). The results indicated that ABH induced expression of IL‐12, a cytokine known to be a critical regulator of cellular immune responses. Flow cytometric analysis demonstrated the induction of IL‐12 production by the CD14‐positive cell population, consisting of monocytes/macrophages (Mo/Mφ). Furthermore, the elimination of Mo/Mφ attenuated IL‐12 production in PBMC. ABH‐induced IL‐12 production was inhibited by anti‐CD14 and anti‐TLR4 antibodies but not by anti‐TLR2 antibody. The activity of ABH was not inhibited by polymyxin B, while the activity of lipopolysaccharide used as a reference was inhibited. Oral administration of ABH enhanced natural killer (NK) activity in the spleen. These findings suggest that ABH activated Mo/Mφ in a manner dependent on CD14/TLR4 and NK activity.
‘Economic rationalism’ in Canberra and Canada: Public sector reorganisation, politics, and power
Authors: Schwartz Herman
Published: December 2004

Australian public sector institutions and public sector labour relations experienced intense change during the 1980s and 1990s. Proponents of restructuring sought to insert market‐like pressures into areas formerly governed by bureaucratic mechanisms. This reversed a trend towards continual growth in state provision of non‐market based social protection and social welfare, and continual growth in the public sector's share of the economy. The politics and content of Australian public sector restructuring under Labor and then the Liberals substantially resembled restructuring efforts in two Canadian provinces. In all three examples, political pacts between unions in the exposed and non‐exposed sectors, and between organised labour and capital, determined the direction of change. But the level of institutional robustness of these various actors determined both the pace and effectiveness of change. Weak employer organisations and unions incapable of sustaining pacts in Canada produced wider oscillations in policy content that attained less substantive success than in Australia.
Replacement Cost Asset Valuation and Regulation of Energy Infrastructure Tariffs
Authors: Johnstone D. J.
Published: December 2004

In Australia, access tariffs (rental charges) paid by third party users to the owners of energy transmission assets (e.g., gas pipelines) are determined by regulators on the basis of their depreciated optimized replacement cost (known as DORC). Reliance on the replacement cost, rather than actual cost, of existing assets inflates tariffs and incites the criticism that asset owners earn a return on investments of a scale never made. The economic rationale of the regulators’ model is that it emulates the workings of a contestable market, by setting tariffs at a level just short of that required to motivate a new entrant (system duplication). Properly reconstructed, this model constitutes a dynamic and internally consistent theory of replacement cost valuation and depreciation. Its mathematical consequences, however, especially with regard to the valuation of sunk assets with long times to expiry, are shown to be practically and politically unpalatable. In particular, the implied tariff levels for such assets are very close to those that would apply to new infrastructure assets built today at today's prices. Regulators unwilling to accept this implication of a new‐entrant‐exclusion pricing logic are left with no alternative framework for DORC.
‘Shopping Around’ for Accounting Practices: The Financial Statement Presentation of French Groups
Authors: Ding Yuan , Stolowy Hervé , Tenenhaus Michel
Published: December 2004

This article illustrates the progressive move away from traditional accounting practices through a study of the presentation of financial statements. Based on a sample of one hundred large French industrial and commercial groups over a ten‐year period, and applying a logistic regression method, our survey confirms a trend among French companies, which are increasingly turning their backs on traditional national practices as regards the balance sheet format, the income statement format, the voluntary disclosure of a statement of changes in shareholders’ equity and the cash flow statement format. This move towards ‘alternative’ practices is made possible by the flexibility of French regulation, and can probably be explained by the desire of French firms to attract more investment on international capital markets. However, this trend shows no signs of a clear orientation towards any particular accounting model (IAS, U.S. or U.K.). The behaviour of the French firms observed in our study can be considered as a kind of ‘shopping around’ for accounting practices.
Domestic Practice, Comparative International Analyses and Accounting Discretion—Italian Savings Banks’ Pension Cost Accounting
Authors: Capalbo Francesco
Published: December 2004

In countries where the use of financial statements is minimal and relative accounting debate less intense, domestic practices may gain benefit from being consistently applied. Comparison with foreign experience is crucial. It leads to questioning of the appropriateness of practices that might otherwise never be discussed, particularly where they are developed in such a way as to favour the stakeholders controlling the accounting process. A salient example evidencing the above claims is to be found in the Italian savings banks (hereafter ‘banks’) accounting for the cost of defined benefits pension plans. The Italian financial system is credit‐based. While banks play a predominant role, the financial industry itself enjoys significant autonomy in setting its accounting standards. This is especially so in respect of the accounting for the cost of pensions as savings banks have offered the most significant and almost unique example of employees’ defined benefit pension plans in Italy.

 The present article compares some aspects of the long debated international and Anglo‐Saxon standards’ recommendations with the infrequently questioned Italian domestic practice. The substantial deviations that emerge in the Italian system favour particularly management and proprietorship by allowing a significant degree of discretion regarding the labour cost figure, thereby enhancing the banks’ salary bargaining strength.
Harmony, Statistical Inference with the Herfindahl H Index and C Index
Authors: Taplin Ross H.
Published: December 2004

The Herfindahl H index and C index provide measures of harmony of accounting measurement practices by summarizing the extent to which companies use the same accounting practice. While the values of these indices are compared to obtain some idea concerning the relative harmony of accounting practice, standard errors for these estimates are not generally provided. That is, an index is calculated from a sample but no guidance is provided concerning likely values of the index in the population from which the sample was drawn. The present article fills this gap in the literature by providing formulae to estimate the standard error of the H and C indices calculated from a sample. The formulae are illustrated with several examples from the literature to show how conclusions are either enhanced or modified by the addition of these standard errors. It is shown that while both indices are biased, this bias is generally negligible. It is hoped that in future authors will quote not only the value of the index itself but also the standard error so differences between index values (both within and between studies) can be judged as being either significantly different or explainable by sampling variation alone.
Context and content in New Orleans: AAA 2002
Authors: Peterson Mark Allen
Published: December 2004

Conference reviewed:

Mark Allen Peterson, Context and Content in New Orleans AAA Meeting, New Orleans, 20–24 November 2002
A Supermarket of anthropology: AAA 2002
Authors: Berg Mette Louise
Published: December 2004

Conference reviewed:

Mette Louise Berg, A Supermarket of Anthropology AAA Meeting, New Orleans, 20–24 November 2002