bluuebunny/crossref_metadata_2025 huggingface dataset:
Cultural transmission of tool use in bottlenose dolphins
Authors: Krützen Michael , Mann Janet , Heithaus Michael R. , Connor Richard C. , Bejder Lars , Sherwin William B.
Published: June 2005

In Shark Bay, wild bottlenose dolphins (Tursiopssp.) apparently use marine sponges as foraging tools. We demonstrate that genetic and ecological explanations for this behavior are inadequate; thus, “sponging” classifies as the first case of an existing material culture in a marine mammal species. Using mitochondrial DNA analyses, we show that sponging shows an almost exclusive vertical social transmission within a single matriline from mother to female offspring. Moreover, significant genetic relatedness among all adult spongers at the nuclear level indicates very recent coancestry, suggesting that all spongers are descendents of one recent “Sponging Eve.” Unlike in apes, tool use in this population is almost exclusively limited to a single matriline that is part of a large albeit open social network of frequently interacting individuals, adding a new dimension to charting cultural phenomena among animals.
A requirement for memory retrieval during and after long-term extinction learning
Authors: Ouyang Ming , Thomas Steven A.
Published: June 2005

Current learning theories are based on the idea that learning is driven by the difference between expectations and experience (the delta rule). In extinction, one learns that certain expectations no longer apply. Here, we test the potential validity of the delta rule by manipulating memory retrieval (and thus expectations) during extinction learning. Adrenergic signaling is critical for the time-limited retrieval (but not acquisition or consolidation) of contextual fear. Using genetic and pharmacologic approaches to manipulate adrenergic signaling, we find that long-term extinction requires memory retrieval but not conditioned responding. Identical manipulations of the adrenergic system that do not affect memory retrieval do not alter extinction. The results provide substantial support for the delta rule of learning theory. In addition, the timing over which extinction is sensitive to adrenergic manipulation suggests a model whereby memory retrieval occurs during, and several hours after, extinction learning to consolidate long-term extinction memory.
A generalized demodulation approach to time-frequency projections for multicomponent signals
Authors: Olhede S , Walden A.T
Published: June 2005

In this paper, we introduce a flexible approach for the time-frequency analysis of multicomponent signals involving the use of analytic vectors and demodulation. The demodulated analytic signal is projected onto the time-frequency plane so that, as closely as possible, each component contributes exclusively to a different ‘tile’ in a wavelet packet tiling of the time-frequency plane, and at each time instant, the contribution to each tile definitely comes from no more than one component. A single reverse demodulation is then applied to all projected components. The resulting instantaneous frequency of each component in each tile is not constrained to a set polynomial form in time, and is readily calculated, as is the corresponding Hilbert energy spectrum. Two examples illustrate the method. In order better to understand the effect of additive noise, the approximate variance of the estimated instantaneous frequency in any tile has been formulated by starting with pure noise and studying its evolving covariance structure through each step of the algorithm. The validity and practical utility of the resulting expression for the variance of the estimated instantaneous frequency is demonstrated via a simulation experiment.
Dynamics of a neural system with a multiscale architecture
Authors: Breakspear Michael , Stam Cornelis J
Published: June 2005

The architecture of the brain is characterized by a modular organization repeated across a hierarchy of spatial scales—neurons, minicolumns, cortical columns, functional brain regions, and so on. It is important to consider that the processes governing neural dynamics at any given scale are not only determined by the behaviour of other neural structures at that scale, but also by the emergent behaviour of smaller scales, and the constraining influence of activity at larger scales. In this paper, we introduce a theoretical framework for neural systems in which the dynamics are nested within a multiscale architecture. In essence, the dynamics at each scale are determined by a coupled ensemble of nonlinear oscillators, which embody the principle scale-specific neurobiological processes. The dynamics at larger scales are ‘slaved’ to the emergent behaviour of smaller scales through a coupling function that depends on a multiscale wavelet decomposition. The approach is first explicated mathematically. Numerical examples are then given to illustrate phenomena such as between-scale bifurcations, and how synchronization in small-scale structures influences the dynamics in larger structures in an intuitive manner that cannot be captured by existing modelling approaches. A framework for relating the dynamical behaviour of the system to measured observables is presented and further extensions to capture wave phenomena and mode coupling are suggested.
Undirected graphs of frequency-dependent functional connectivity in whole brain networks
Authors: Salvador Raymond , Suckling John , Schwarzbauer Christian , Bullmore Ed
Published: June 2005

We explored properties of whole brain networks based on multivariate spectral analysis of human functional magnetic resonance imaging (fMRI) time-series measured in 90 cortical and subcortical subregions in each of five healthy volunteers studied in the (no-task) resting state. We note that undirected graphs representing conditional independence between multivariate time-series can be more readily approached in the frequency domain than the time domain. Estimators of partial coherency and normalized partial mutual informationϕ, an integrated measure of partial coherence over an arbitrary frequency band, are applied. Using these tools, we replicate the prior observations that bilaterally homologous brain regions tend to be strongly connected and functional connectivity is generally greater at low frequencies [0.0004, 0.1518 Hz]. We also show that long-distance intrahemispheric connections between regions of prefrontal and parietal cortex were more salient at low frequencies than at frequencies greater than 0.3 Hz, whereas many local or short-distance connections, such as those comprising segregated dorsal and ventral paths in posterior cortex, were also represented in the graph of high-frequency connectivity. We conclude that the partial coherency spectrum between a pair of human brain regional fMRI time-series depends on the anatomical distance between regions: long-distance (greater than 7 cm) edges represent conditional dependence between bilaterally symmetric neocortical regions, and between regions of prefrontal and parietal association cortex in the same hemisphere, are predominantly subtended by low-frequency components.
Condition-dependent functional connectivity: syntax networks in bilinguals
Authors: Dodel Silke , Golestani Narly , Pallier Christophe , ElKouby Vincent , Le Bihan Denis , Poline Jean-Baptiste
Published: June 2005

This paper introduces a method to study the variation of brain functional connectivity networks with respect to experimental conditions in fMRI data. It is related to the psychophysiological interaction technique introduced by Friston
et al
. and extends to networks of correlation modulation (CM networks). Extended networks containing several dozens of nodes are determined in which the links correspond to consistent correlation modulation across subjects. In addition, we assess inter-subject variability and determine networks in which the condition-dependent functional interactions can be explained by a subject-dependent variable. We applied the technique to data from a study on syntactical production in bilinguals and analysed functional interactions differentially across tasks (word reading or sentence production) and across languages. We find an extended network of consistent functional interaction modulation across tasks, whereas the network comparing languages shows fewer links. Interestingly, there is evidence for a specific network in which the differences in functional interaction across subjects can be explained by differences in the subjects' syntactical proficiency. Specifically, we find that regions, including ones that have previously been shown to be involved in syntax and in language production, such as the left inferior frontal gyrus, putamen, insula, precentral gyrus, as well as the supplementary motor area, are more functionally linked during sentence production in the second, compared with the first, language in syntactically more proficient bilinguals than in syntactically less proficient ones. Our approach extends conventional activation analyses to the notion of networks, emphasizing functional interactions between regions independently of whether or not they are activated. On the one hand, it gives rise to testable hypotheses and allows an interpretation of the results in terms of the previous literature, and on the other hand, it provides a basis for studying the structure of functional interactions as a whole, and hence represents a further step towards the notion of large-scale networks in functional imaging.
The Medawar Lecture 1998 Is science dangerous?
Authors: Wolpert Lewis
Published: June 2005

The idea that science is dangerous is deeply embedded in our culture, particularly in literature, yet science provides the best way of understanding the world. Science is not the same as technology. In contrast to technology, reliable scientific knowledge is value-free and has no moral or ethical value. Scientists are not responsible for the technological applications of science; the very nature of science is that it is not possible to predict what will be discovered or how these discoveries could be applied. The obligation of scientists is to make public both any social implications of their work and its technological applications. A rare case of immoral science was eugenics. The image of Frankenstein has been turned by the media into genetic pornography, but neither cloning nor stem cells or gene therapy raise new ethical issues. There are no areas of research that are so socially sensitive that research into them should be proscribed. We have to rely on the many institutions of a democratic society: parliament, a free and vigorous press, affected groups and the scientists themselves. That is why programmes for the public understanding of science are so important. Alas, we still do not know how best to do this.
Getting Hired: Sex and Race
Authors: PETERSEN TROND , SAPORTA ISHAK , SEIDEL MARC‐DAVID L.
Published: June 2005

The hiring process is currently probably the least understood aspect of the employment relationship. It may very well be the most important for understanding the broad processes of stratification with allocation by sex and race to jobs and firms. A central reason for the lack of knowledge is that it is very difficult to assemble extensive data on the processes that occur at the point of hiring. We analyzed data on all applicants to a large service organization in the U.S. in a 16‐month period in 1993–1994. We investigated the rating at the time of application, the probability of getting hired, and the ratings achieved one, three, and six months after hire. Overall differences between men and women were (a) negligible in rating received at the time of application, (b) small but slightly in favor of women in probability of getting hired, and (c) clearly in favor of women for ratings after hire. The evidence points unambiguously in one direction: Women do not come out worse than men in the hiring process in this organization. To the extent there is a difference, it is to the advantage of women. However, if the posthire performance ratings are free of sex bias, then women should have been hired at an even higher rate. When analyses were done separately by occupation, there are few differences between men and women in getting hired in the three occupations accounting for 94 percent of hires. In the other two, only 8 and 15 hires were made, making statistical analysis less meaningful. However, there is evidence that blacks face a disadvantage in getting hired, and also receive lower ratings after hire. Hispanic men are especially disadvantaged in getting hired.
Mass Layoffs and CEO Turnover
Authors: BILLGER SHERRILYN M. , HALLOCK KEVIN F.
Published: June 2005

We investigate the relationship between layoff announcements and CEO turnover over a 31‐year period. We find that layoffs significantly increase CEO turnover in the following year, and, in some time periods, CEO changes are strongly positively associated with layoff announcements two years earlier. We proceed to show how this relationship has changed over time, and offer several possible explanations. Finally, we find strong evidence that layoffs that are associated with negative stock price reactions are much more likely to lead to CEO turnover than those associated with positive stock price reactions, especially in the earlier years in our sample.
Ratcheting Up: Linked Technology Adoption in Supply Chains
Authors: SMITH MARGARET HWANG , WEIL DAVID
Published: June 2005

It is generally assumed that a firm will adopt complementary technologies simultaneously. Apparel industry data indicate that, because of the close links between suppliers and retailers, there was a ratchet‐up adoption of complementary information technologies. The consequence was that a rapid regime shift occurred without explicit coordination or planning. One implication is that the study of technology adoption may need to be more widely conceptualized to incorporate the relationships between upstream manufacturers and downstream retailers.
The Effects of Employer Matching in 401(k) Plans
Authors: EVEN WILLIAM E. , MACPHERSON DAVID A.
Published: June 2005

This paper uses data from the April 1993 pension supplements to the Current Population Survey (CPS) to investigate the impact of employer matching and employee tenure on participation levels in 401(k) plans. While earlier studies examine similar issues, this study makes several advances. First, consistent with the theory that employers may use matching contributions to satisfy nondiscrimination rules, the study shows that correcting for the endogeneity of employer matching substantially increases the estimated effect of matching on participation levels. Second, the study provides evidence that the large positive association between employee tenure and 401(k) participation is because “stayers” tend to be “savers.”
Viewing Spatial Consequences of Budgetary Policy Changes
Authors: Greenbaum Robert T. , Desai Anand
Published: June 2005

While the research community is often very concerned with the distributional effect of public policy decisions, the geographic distribution of the affected populations is often overlooked. This paper argues that seemingly geographically neutral policies have spatial consequences and that the choice of how to measure them is important. We suggest that maps provide a powerful tool for communicating these ideas to policy makers and that geographical information systems supplemented by spatial statistics yield information that assist policy debates. We develop metrics to illustrate how geographic information provides insights into the spatial consequences of Medicaid expenditure changes in Ohio.
Full Disclosure: Unanticipated Improvements in Property Tax Uniformity
Authors: Cornia Gary C. , Walters Lawrence C.
Published: June 2005

This paper contributes to two strands in the property tax literature. One thread considers the effects of full disclosure requirements or “truth in taxation” on the rate of property tax growth. The second studies the determinants of assessment uniformity. This article focuses on the role of full disclosure in changing administrative incentives and improving the uniformity of the property tax. A panel of 29 Utah counties over a 32‐year period is used in a TSCS analysis. Findings suggest there is substantial evidence that full disclosure improved uniformity in Utah, but limited evidence that it restrained property tax growth.
Molecular characterization of mlo mutants in North American two‐ and six‐rowed malting barley cultivars
Authors: PANSTRUGA RALPH , MOLINA‐CANO JOSÉ LUIS , REINSTÄDLER ANJA , MÜLLER JUDITH
Published: June 2005

Barley lines PRU1, URS1 and URS2 represent three candidate mlo mutants induced in either the two‐rowed cultivar Prudentia or the six‐rowed cultivar Ursula. Both Prudentia and Ursula are North American malting barley varieties with specific malting properties. Here, we analysed the three candidate mutants at the molecular level. We identified lesions in the Mlo gene of all three lines, causing either a premature stop codon (PRU1), a shift in the reading frame (URS1) or a single amino acid replacement (URS2). In a transient gene expression assay, the URS2 mlo allele fails to complement a barley null mutant genotype, indicating that URS2 is a genuine mlo mutant (here designated as mlo‐33). The MLO‐33 mutant variant accumulates to similar levels as the wild‐type MLO protein in Arabidopsis protoplasts, suggesting that MLO‐33 is stable in planta. We show that the mlo‐33 allele can be readily detected in barley genomic DNA by a cleaved amplified polymorphic sequence marker, rendering this allele particularly suited for marker‐assisted breeding.
Non‐host resistance in plants: new insights into an old phenomenon
Authors: NÜRNBERGER THORSTEN , LIPKA VOLKER
Published: June 2005

Resistance of an entire plant species to all isolates of a microbial species is referred to as non‐host or species resistance. An interplay of both constitutive barriers and inducible reactions comprises the basis for this most durable form of plant disease resistance. Activation of inducible plant defence responses is probably brought about by the recognition of invariant pathogen‐associated molecular patterns (PAMP) that are characteristic of whole classes of microbial organisms. PAMP perception systems and PAMP‐induced signalling cascades partially resemble those known to mediate activation of innate immune responses in animals, suggesting an evolutionarily ancient molecular concept of non‐self recognition and immunity in eukaryotes. Genetic dissection has recently provided clues for SNARE‐complex‐mediated exocytosis and directed vesicle trafficking in executing plant non‐host resistance. Recent functional analysis of bacterial effector proteins indicates that establishment of infection in susceptible plants is associated with suppression of plant species resistance.
Molecular and functional characterization of a secreted lipase from Botrytis cinerea
Authors: REIS HOLGER , PFIFFI STEFANIE , HAHN MATTHIAS
Published: June 2005

A previous study has indicated that a cutinolytic lipase from Botrytis cinerea was required for penetration of an intact plant host cuticle and infection (Comménil et al., 1998, Physiol. Mol. Plant Pathol. 52, 1–14). In order to clarify the role of this lipase, the corresponding gene (lip1) was cloned. In vitro, the lip1‐encoded lipase was inducibly expressed and subject to catabolite repression. On the leaf surface, the cuticle served as an inducer. lip1 knock‐out mutants lacked lipase activity; however, no reduction of virulence was observed. To further eliminate cutinolytic activity, the gene encoding cutinase A was also disrupted. In lip1cutA double mutants, extracellular esterases were largely eliminated in vitro and greatly reduced on the leaf surface; yet these mutants also retained full pathogenicity in various host systems. Our data indicate that cutinase and esterase activities are secreted by germinating B. cinerea spores on the surface of host leaves, but they do not seem to be required for host cuticle penetration.
A plant EPF‐type zinc‐finger protein,CaPIF1, involved in defence against pathogens
Authors: OH SANG‐KEUN , PARK JEONG MEE , JOUNG YOUNG HEE , LEE SANGHYEOB , CHUNG EUNSOOK , KIM SOO‐YONG , YU SEUNG HUN , CHOI DOIL
Published: June 2005

To understand better the defence responses of plants to pathogen attack, we challenged hot pepper plants with bacterial pathogens and identified transcription factor‐encoding genes whose expression patterns were altered during the subsequent hypersensitive response. One of these genes,CaPIF1(Capsicum annuum Pathogen‐Induced Factor 1), was characterized further. This gene encodes a plant‐specific EPF‐type protein that contains two Cys2/His2zinc fingers.CaPIF1expression was rapidly and specifically induced when pepper plants were challenged with bacterial pathogens to which they are resistant. In contrast, challenge with a pathogen to which the plants are susceptible only generated weakCaPIF1expression.CaPIF1expression was also strongly induced in pepper leaves by the exogenous application of ethephon, an ethylene‐releasing compound, and salicylic acid, whereas methyl jasmonate had only moderate effects. CaPIF1 localized to the nuclei of onion epidermis when expressed as a CaPIF1–smGFP fusion protein. Transgenic tobacco plants over‐expressingCaPIF1driven by the CaMV 35S promoter showed increased resistance to challenge with a tobacco‐specific pathogen or non‐host bacterial pathogens. These plants also showed constitutive up‐regulation of multiple defence‐related genes. Moreover, virus‐induced silencing of theCaPIF1orthologue inNicotiana benthamianaenhanced susceptibility to the same host or non‐host bacterial pathogens. These observations provide evidence that an EPF‐type Cys2/His2zinc‐finger protein plays a crucial role in the activation of the pathogen defence response in plants.
Pulse pressure is independently associated with sensorimotor peripheral neuropathy in patients with type 2 diabetes
Authors: JARMUZEWSKA E. A. , MANGONI A. A.
Published: June 2005

Objectives.  The mechanisms responsible for the onset and progression of sensorimotor peripheral neuropathy (SMPN) in type 2 diabetes remain largely unknown. Although a link between hypertension and SMPN has been observed, it is not clear which blood pressure (BP) component (i.e. systolic, SBP; diastolic, DBP; or pulse pressure, PP) is primarily involved. We sought to determine the relationship between BP components and parameters of nerve function in type 2 diabetes.

Design.  Cross‐sectional study.

Setting.  Academic medical centre.

Subjects.  A total of 55 consecutive ambulatory patients with type 2 diabetes (age 62.6 ±8.0 years, mean ± SD).

Interventions.  Measurement of clinic BP and 10 neurophysiological parameters: motor nerve conduction velocity (NCV; median, ulnar, posterior tibial and peroneal nerve), sensory amplitude (AMP) and latency (LAT; median, ulnar and sural nerve).

Results.  Univariate analysis showed that age, diabetes duration, SBP and PP were negatively correlated with nerve function. Regression analysis showed that, after correcting for age, duration of diabetes, glycated haemoglobin, body mass index, microalbuminuria and SBP, PP was independently and negatively associated with NCV (median, P =0.011; ulnar, P = 0.001; peroneal, P = 0.006 and posterior tibial, P = 0.005) and signal AMP (ulnar, P = 0.027; sural, P = 0.055), and positively associated with signal LAT (median, P = 0.083; sural, P = 0.021). SBP was negatively associated with signal AMP (median, P = 0.012) and positively associated with LAT (ulnar, P = 0.018). By contrast, DBP failed to show any significant correlation with nerve function.

Conclusions.  The PP is strongly associated with neurophysiological parameters of nerve function in patients with type 2 diabetes. This relationship is independent of traditional risk factors and other BP components.
The use of B‐type natriuretic peptide in the management of elderly patients with acute dyspnoea
Authors: MUELLER C. , LAULE‐KILIAN K. , FRANA B. , RODRIGUEZ D. , RUDEZ J. , SCHOLER A. , BUSER P. , PFISTERER M. , PERRUCHOUD A. P.
Published: June 2005

Objectives.  The aim of this study was to define the impact of B‐type natriuretic peptide (BNP) levels on the management of elderly patients presenting with acute dyspnoea.

Design.  We performed a prospective randomized controlled study in 269 elderly patients at least 70 years of age included in the B‐type natriuretic peptide for Acute Shortness of breath Evaluation (BASEL) study. Patients were randomly assigned to a diagnostic strategy with (n = 136, BNP group) or without (n = 133, control group) the use of BNP levels provided by a rapid bedside assay. The time to discharge and the total cost of treatment were the primary end‐points.

Results.  Amongst elderly patients, baseline characteristics were well matched between both groups. The use of BNP levels significantly reduced the time to discharge (median 9.0 in the BNP group versus 11.0 days in the control group; P = 0.029). Total treatment cost was $5381 (95% CI, 4482–6280) in the BNP group when compared with $7411 (95% CI, 6180–8642; P = 0.009) in the control group. In addition, a significant reduction in 30‐day mortality was observed (9% in the BNP group versus 17% in the control group; P = 0.039).

Conclusions.  Used in conjunction with other clinical information, rapid measurement of BNP in the emergency department improved the management of elderly patients presenting with acute dyspnoea and thereby reduced the time to discharge and the total treatment cost. In addition, BNP testing seemed to reduce 30‐day mortality.
Long‐term outcome of a large series of patients surgically treated for pheochromocytoma
Authors: KHORRAM‐MANESH A. , AHLMAN H. , NILSSON O. , FRIBERG P. , ODÉN A. , STENSTRÖM G. , HANSSON G. , STENQUIST O. , WÄNGBERG B. , TISELL L.‐E. , JANSSON S.
Published: June 2005

Objective.  To analyse the morbidity, mortality and long‐term outcome in a consecutive series of surgically treated patients with pheochromocytoma (PC), or paraganglioma (PG), from the western region of Sweden between 1950 and 1997.

Patients.  All patients (n = 121) who had been hospitalized and treated for PC/PG over 47 years.

Design.  Retrospective review of patients with PC/PG regarding presenting symptoms, tumour characteristics, clinical management and long‐term outcome after treatment.

Setting.  One referral centre for all patients from the western region of Sweden.

Results.  During an observation of 15 ± 6 years, 42 patients died vs. 23.6 expected in the general population (P < 0.001). There was no intra‐ or post‐operative mortality. Four patients with sporadic disease died of malignant PC and six with hereditary disease of associated neuroectodermal tumours. Five patients died of other malignancies, 20 of cardiovascular disease and seven of other causes. Besides older age at primary surgery, elevated urinary excretion of methoxy‐catecholamines was the only observed risk factor for death (P = 0.02). At diagnosis 85% of the patients were hypertensive; one year after surgery more than half were still hypertensive. However, pre‐ and post‐operative hypertension did not influence the risk for death versus controls.

Conclusion.  Pheochromocytoma/PG can be safely treated by surgery. Death of malignant PC/PG was unusual, but the patients as a group had an increased risk of death. We recommend life‐long follow‐up of patients treated for PC/PG with screening for recurrent tumour in sporadic cases and for associated tumours in hereditary cases. This strategy would also be helpful in diagnosing cardiovascular disease at an early stage.
Surviving extreme hypercalcaemia – a case report and review of the literature
Authors: MARIENHAGEN K. , DUE J. , HANSSEN T.‐A. , SVARTBERG J.
Published: June 2005

We report a case of extreme hypercalcaemia associated with a parathyroid adenoma in a young man. The patient presented with classical symptoms of a hypercalcaemic syndrome, and serum calcium and parathyroid hormone levels were 6.92 mmol L−1 and 70.2 pmol L−1 respectively. After stabilizing the patient and reducing the calcium level, a parathyroidectomy was performed. The postoperative course was uneventful with rapidly resolving clinical symptoms. Hypercalcaemic crisis is a rare but life‐threatening complication of primary hyperparathyroidism. It should be suspected in acutely ill patients complaining of muscular weakness, gastrointestinal and cerebral symptoms. To reduce mortality, it is essential to correctly diagnose the condition without delay and provide appropriate emergency management correcting hypercalcaemia and dehydration. Successful parathyroidectomy quickly relieves symptoms and prevents recurrence.
Low level of tissue plasminogen activator activity in non‐diabetic patients with a first myocardial infarction
Authors: LUNDBLAD D. , DINESEN B. , RAUTIO A. , RØDER M. E. , ELIASSON M.
Published: June 2005

Objective.  To explore the role of tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI‐1) in survivors of a first myocardial infarction (MI). Insulin and proinsulin were analysed as potential risk factors.

Design.  Case–control study in northern Sweden.

Subjects.  A total of 115 patients under 65 years of age with a first MI were enrolled and recalled for further examination 3 months later. Twenty‐seven patients were excluded, 17 with known diabetes and 10 who did not come to the follow‐up, giving a final number of 88 patients, 73 men and 15 women. Patients were age‐ and sex matched with control subjects drawn from the local cohort in the MONICA population survey 1994.

Main outcome measures.  We compared MI patients and controls using univariate and multiple regression analyses including odds ratios (OR).

Results.  PAI‐1 activity, fibrinogen, postload insulin and ‐proinsulin were significantly higher and tPA activity significantly lower in MI patients in the univariate analysis. In a multiple regression analysis, including also age, sex and cardiovascular risk factors, these parameters were divided in quartiles. The lowest quartile of tPA activity was significantly associated with MI (OR = 19.1; CI 3.0–123) together with the highest quartiles of fibrinogen (OR = 25; CI 5.2–120) but other variables were not.

Conclusion.  Low tPA activity, i.e. low fibrinolytic activity, characterized nondiabetic subjects after a first MI which is not explained by concomitant disturbances in metabolic and anthropometric variables.
Impact of parathyroidectomy on neutrophil cytosolic calcium in chronic kidney disease patients: a prospective parallel group trial
Authors: DEICHER R. , KIRSCH B. , MÜLLNER M. , KACZIREK K. , NIEDERLE B. , HÖRL W. H.
Published: June 2005

Objectives.  Polymorphonuclear leucocytes (PMNs) of chronic kidney disease (CKD) patients display elevated basal cytosolic calcium concentrations (iCa2+). As parathyroid hormone is considered to substantially contribute to the inappropriate cellular entry of calcium in uraemia, we hypothesized that parathyroidectomy lowers PMN iCa2+.

Design and setting.  Prospective parallel group trial at a tertiary care centre.

Subjects, intervention and main outcome measures.  Two patient cohorts (cohort 1: 14 CKD patients; cohort 2: 14 renal transplant recipients) underwent parathyroidectomy for uncontrolled secondary hyperparathyroidism. We assessed PMN iCa2+ (primary objective) spectrofluorimetrically 1 day before and 20 days after intervention (secondary objective: PMN glucose uptake). Data were compared with those of 16 matched maintenance haemodialysis patients (cohort 3), and to 15 healthy subjects (cohort 4), by generalized estimating equations.

Results.  PMN iCa2+ of cohort 1 decreased over time and was significantly higher than that of cohort 3 before but not after parathyroidectomy [mean difference before/after parathyroidectomy: 19.1nmol L−1 (95% confidence interval: 9.4–22.4), P =0.0003/−3.2 (−20.9–14.5), P = 0.71]. PMN iCa2+ of cohort 2 decreased over time, but we found no significant difference in comparison with cohort 3 [mean difference before/after parathyroidectomy: 6.5 nmol L−1 (−9.4–22.4), P = 0.4/−15.8 (−43.6–12.0), P = 0.25]. PMN iCa2+ of all CKD patients was substantially higher in comparison with that of healthy subjects [cohort 4 vs. 3: −35.3 (−48.9–21.6), P < 0.001]. PMN glucose uptake increased significantly in both interventional cohorts in comparison with cohort 3.

Conclusions.  Parathyroidectomy lowers, but does not normalize PMN iCa2+ of CKD patients. Further variables, possibly uraemic retention solutes, control both PMN iCa2+ and functional responses.
Effect of the Toll‐like receptor 4 (TLR‐4) variants on intima‐media thickness and monocyte‐derived macrophage response to LPS
Authors: NORATA G. D. , GARLASCHELLI K. , ONGARI M. , RASELLI S. , GRIGORE L. , BENVENUTO F. , MAGGI F. M. , CATAPANO A. L.
Published: June 2005

Objectives.  Toll‐like receptor 4 (TLR‐4) is believed to contribute to the initiation and progression of atherosclerosis. The association of the D299G polymorphism of the TLR‐4 gene with the progression of coronary and carotid atherosclerosis, risk of cardiovascular events and myocardial infarction is controversial. We have investigated whether the presence of the D299G polymorphism and the co‐segregated T399I polymorphism affects the intima‐media thickness (IMT) in the general population.

Subjects.  The PLIC study population (n = 1256) was genotyped for the D299G and the T399I polymorphisms.

Results.  The presence of both the D299G and T399I alleles was observed in the 13.0% of the population, carriers of the T399I alone were 1.8% and of the D299G alone were 0.9%. No difference in IMT was detected within the carriers of the D299G and T399I alleles and the wild‐type subjects in the PLIC population. Furthermore, we investigated whether monocyte from D299G to T399I subjects present a defective response to CD40, interleukin (IL)‐6, monocyte chemotactic protein (MCP)‐1, cyclo‐oxygenase (COX)‐2 and PTX3 expression induced by lipopolysaccharide (LPS). When the monocyte‐derived macrophages of these subjects were challenged with LPS (1 μg mL−1), no impact of the polymorphisms on the induction of CD40, MCP‐1 and PTX3 was observed. Only IL‐6 and COX‐2 induction by LPS resulted reduced in the D299G/T399I carriers.

Conclusion.  The presence of the D299G and T399I polymorphisms of the TLR‐4 gene does not play a major role on the progression of carotid atherosclerosis. Macrophages from the subjects carrying the polymorphisms show an impaired response to LPS limited only to a IL‐6 and COX‐2.
End‐stage renal disease – not an equal opportunity disease: the role of genetic polymorphisms
Authors: NORDFORS L. , LINDHOLM B. , STENVINKEL P.
Published: June 2005

Despite several decades of development in renal replacement therapy, end‐stage renal disease (ESRD) patients continue to have markedly increased morbidity and mortality especially caused by cardiovascular disease (CVD). This shows that current strategies, e.g. the focus on dialysis adequacy, to improve the clinical outcome in ESRD patients have to be complemented by novel approaches. Although traditional risk factors are common in dialysis patients they cannot alone explain the unacceptably high prevalence of CVD in this patient group. Much recent interest has therefore focused on the role of various nontraditional cardiovascular risk factors, such as inflammation, vascular calcification and oxidative stress. Recent studies show that genetic factors, such as DNA single nucleotide polymorphisms, may significantly influence the immune response, the levels of inflammatory markers, as well as the prevalence of atherosclerosis in this patient group. To elucidate the respective roles of DNA polymorphisms in genes that encode inflammatory markers (such as IL‐10, IL‐6 and TNF‐α) and other factors that may affect the development of atherosclerosis (such as apolipoprotein E, transforming growth factor and fetuin‐A), sufficiently powered studies are needed in which genotype, the protein product and the specific phenotype all are analysed in relation to outcome. The recent developments in the field of genetics have opened up entirely new possibilities to understand the impact of genotype on disease development and progress and thus offer new options and strategies for treatment. It seems conceivable that in the near future, prognostic or predictive multigene DNA assays will provide the nephrological community with a more precise approach for the identification of ‘high‐risk’ ESRD patients and the development of accurate individual treatment strategies. For this purpose, integrative studies on genotype–phenotype associations and impact on clinical outcome are needed.
Genetic and physiological responses of Bacillus subtilis to metal ion stress
Authors: Moore Charles M. , Gaballa Ahmed , Hui Monica , Ye Rick W. , Helmann John D.
Published: June 2005

Metal ion homeostasis is regulated principally by metalloregulatory proteins that control metal ion uptake, storage and efflux genes. We have used transcriptional profiling to survey Bacillus subtilis for genes that are rapidly induced by exposure to high levels of metal ions including Ag(I), Cd(II), Cu(II), Ni(II) and Zn(II) and the metalloid As(V). Many of the genes affected by metal stress were controlled by known metalloregulatory proteins (Fur, MntR, PerR, ArsR and CueR). Additional metal‐induced genes are regulated by two newly defined metal‐sensing ArsR/SmtB family repressors: CzrA and AseR. CzrA represses the CadA efflux ATPase and the cation diffusion facilitator CzcD and this repression is alleviated by Zn(II), Cd(II), Co(II), Ni(II) and Cu. CadA is the major determinant for Cd(II) resistance, while CzcD protects the cell against elevated levels of Zn(II), Cu, Co(II) and Ni(II). AseR negatively regulates itself and AseA, an As(III) efflux pump which contributes to arsenite resistance in cells lacking a functional ars operon. Our results extend the range of identified effectors for the As(III)‐sensor ArsR to include Cd(II) and Ag(I) and for the Cu‐sensor CueR to include Ag(I) and, weakly, Cd(II) and Zn(II). In addition to systems dedicated to metal homeostasis, specific metal stresses also strongly induced pathways related to cysteine, histidine and arginine metabolism.
Maintaining a healthy SPANC balance through regulatory and mutational adaptation
Authors: Ferenci Thomas
Published: June 2005

Stress protection is an important but costly contributor to bacterial survival. Two distinct forms of environmental protection share a common cost and a significant species‐wide variability. Porin‐mediated outer membrane permeability and the RpoS‐controlled general stress response both involve a trade‐off between self‐preservation and nutritional competence, called the SPANC balance. Interestingly, different Escherichia coli strains exhibit distinct settings of the SPANC balance. It is tilted towards high stress resistance and a restricted diet in some isolates whereas others have broader nutritional capability and better nutrient affinity but lower levels of resistance. Growth‐ or stress‐related selective pressures working in opposite directions (antagonistic pleiotropy) result in polymorphisms affecting porins and RpoS. Consequently, these important cellular components are present at distinct concentrations in different isolates. A generalized hypothesis to explain bacterial adaptation, based on the SPANC investigations, is offered. A holistic approach to bacterial adaptation, involving a gamut of regulation and mutation, is likely to be the norm in broadening the capabilities of a species. Indeed, there is unlikely to be a standard regulatory setting typical for all members of a species. Gene regulation provides a limited fine control for maintaining the right level of adaptation in a particular niche but mutational changes provide the coarse control for adaptation between the species‐wide environments of free‐living bacteria.
Spatial arrangement and macrodomain organization of bacterial chromosomes
Authors: Boccard Frédéric , Esnault Emilie , Valens Michèle
Published: June 2005

Recent developments in fluorescence microscopy have shown that bacterial chromosomes have a defined spatial arrangement that preserves the linear order of genes on the genetic map. These approaches also revealed that large portions of the chromosome in Escherichia coli or Bacillus subtilis are concentrated in the same cellular space, suggesting an organization as large regions defined as macrodomains. In E. coli, two macrodomains of 1 Mb containing the replication origin (Ori) and the replication terminus (Ter) have been shown to relocalize at specific steps of the cell cycle. A genetic analysis of the collision probability between distant DNA sites in E. coli has confirmed the presence of macrodomains by revealing the existence of large regions that do not collide with each other. Two macrodomains defined by the genetic approach coincide with the Ori and Ter macrodomains, and two new macrodomains flanking the Ter macrodomain have been identified. Altogether, these results indicate that the E. coli chromosome has a ring organization with four structured and two less‐structured regions. Implications for chromosome dynamics during the cell cycle and future prospects for the characterization and understanding of macrodomain organization are discussed.
PpsR: a multifaceted regulator of photosynthesis gene expression in purple bacteria
Authors: Elsen Sylvie , Jaubert Marianne , Pignol David , Giraud Eric
Published: June 2005

Purple bacteria control the level of expression and the composition of their photosystem according to light and redox conditions. This control involves several regulatory systems that have been now well characterized. Among them, the PpsR regulator plays a central role, because it directly or indirectly controls the synthesis of all of the different components of the photosystem. In this review, we report our knowledge of the PpsR protein, highlighting the diversity of its mode of action and focusing on the proteins identified in four model purple bacteria (Rhodobacter capsulatus, Rhodobacter sphaeroides, Rubrivivax gelatinosus, Bradyrhizobium ORS278). This regulator exhibits unique regulatory features in each bacterium: it can activate and/or repress the expression of photosynthesis genes, its activity can be modulated or not by the redox conditions, it can interact with other specific regulators and therefore be involved differently in light and/or redox regulatory circuits.
Transcriptional regulation of the one‐carbon metabolism regulon in Saccharomyces cerevisiae by Bas1p
Authors: Subramanian Mohan , Qiao Wen‐ben , Khanam Nurussaba , Wilkins Olivia , Der Sandy D. , Lalich Jonathan D. , Bognar Andrew L.
Published: June 2005

The mechanisms mediating responses to glycine withdrawal in budding yeast were studied using a genome‐wide profiling approach. A striking pattern of repressed expression of genes with an enrichment for those involved in one‐carbon metabolism and AMP biosynthesis was revealed. Sequence analysis of the promoters for the most severely repressed genes identified a conserved sequence, TGACTC, a known binding site for the transcription factors Gcn4p and Bas1p. Loss of BAS1 abolished or significantly reduced the repression of these genes in response to glycine removal but this phenotype was much less apparent in the absence of BAS2 or GCN4. Addition of a Bas1p‐LexA fusion protein to a strain with a LexAop‐LacZ fusion showed a strong glycine effect both in a BAS2 and a bas2 background. A Bas1p‐VP16 fusion protein activated expression in a bas1bas2 strain but no glycine effect was observed while a Bas1p‐Bas2p fusion protein activated expression to a lesser extent with a slight stimulation by glycine. These results suggest that glycine affects Bas1p activation of transcription rather than DNA binding and that Bas2p is not required for this affect. Glycine withdrawal repressed many of the same genes as addition of adenine, a process known to be dependent on Bas1p. However, the glycine response is independent of adenine repression, because glycine regulation occurs normally in ade strains. We did not see any difference in the degree of stimulation by glycine in the presence or absence of adenine even in Ade+ strains. Glycine regulation was also found to be dependent on an intact SHM2 gene, which encodes cytoplasmic serine hydroxymethyltransferase. A reporter plasmid containing a DNA sequence from the GCV2 promoter which confers glycine regulation on heterologous genes was introduced into the yeast deletion set to screen for genes required for glycine regulation. A number of genes, including BAS1 were required for activation by glycine but only the SHM2 gene was required for repression in the absence of glycine. We also showed that regulation of the SHM2 promoter by glycine requires Bas1p but not Bas2p or Gcn4p using a β‐galactosidase reporter. The response of the promoter to glycine required an intact SHM2 gene but was restored in a shm2 strain by addition of formate to the medium.
Novel relationships among DNA methylation, histone modifications and gene expression in Ascobolus
Authors: Barra José L. , Holmes Allyson M. , Grégoire Annie , Rossignol Jean‐Luc , Faugeron Godeleine
Published: June 2005

By studying Ascobolus strains methylated in various portions of the native met2 gene or of the hph transgene, we generalized our previous observation that methylation of the downstream portion of a gene promotes its stable silencing and triggers the production of truncated transcripts which rarely extend through the methylated region. In contrast, methylation of the promoter region does not promote efficient gene silencing. The chromatin state of met2 methylated strains was investigated after partial micrococcal nuclease (MNase) digestion. We show that MNase sensitive sites present along the unmethylated regions are no longer observed along the methylated ones. These chromatin changes are not resulting from the absence of transcription. They are associated, in both met2 and hph, with modifications of core histones corresponding, on the N terminus of histone H3, to an increase of dimethylation of lysine 9 and a decrease of dimethylation of lysine 4. Contrary to other organisms, these changes are independent of the transcriptional state of the genes, and furthermore, no decrease in acetylation of histone H4 is observed in silenced genes.
Salmonella entericaserotype Typhimurium MisL is an intestinal colonization factor that binds fibronectin
Authors: Dorsey Caleb W. , Laarakker Marijke C. , Humphries Andrea D. , Weening Eric H. , Bäumler Andreas J.
Published: June 2005

MisL is an autotransporter protein encoded bySalmonellapathogenicity island 3 (SPI3). To investigate the role of MisL inSalmonella entericaserotype Typhimurium (S.Typhimurium) pathogenesis, we characterized its function during infection of mice and identified a host receptor for this adhesin. In a mouse model ofS.Typhimurium intestinal persistence, amisLmutant was shed with the faeces in significantly lower numbers than the wild type and was impaired in its ability to colonize the cecum. Previous studies have implicated binding of extracellular matrix proteins as a possible mechanism forS.Typhimurium intestinal persistence. A gluthathione‐S‐transferase (GST) fusion protein to the MisL passenger domain (GST–MisL29‐281) was constructed to investigate binding to extracellular matrix proteins. In a solid‐phase binding assay the purified GST–MisL29‐281fusion protein bound to fibronectin and collagen IV, but not to collagen I. MisL expression was not detected by Western blot inS.Typhimurium grown under standard laboratory conditions. However, when expression of the clonedmisLgene was driven by theEscherichia coliarabinose promoter, MisL could be detected in theS.Typhimurium outer membrane by Western blot and on the bacterial cell surface by flow cytometry. Expression of MisL enabledS.Typhimurium to bind fibronectin to its cell surface, resulting in attachment to fibronectin‐coated glass slides and in increased invasiveness for human epithelial cells derived from colonic carcinoma (T84 cells). These data identify MisL as an extracellular matrix adhesin involved in intestinal colonization.