bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection with Absidia corymbifera in bank voles (Clethrionomys glariolus)
Authors: Corbel M. J. , Redwood D. W. , Eades Susan M.
Published: June 2007

Bank voles, Clethrlonomys glariolus, kept under laboratory conditions were highly susceptible to both naturally-acquired and experimental Infection with the phycomycete Absidia corymbifera. The infection was manifested as an acute lethal disease characterized by fungal invasion of the kidneys, central nervous system and, less frequently, other tissues. Natural infection was probably acquired via the respiratory route.
The response of the caecotrophy rhythm of the rabbit to single light signals
Authors: Jilge Burghart
Published: June 2007

The direction of temporary phase shifts depends on the timing of the light signal in the dark period (1800-0600). Delays predominated following signals between 2100 and 2400, while advances tended, even more uniformly, to follow signals given between 0100 and 0400. In one animal the caecotrophy rhythm split into 2 components after a light signal at 0400, while in another it was so disturbed that the signal was followed by a coprostasis of 10 days. The phase responses to light stimuli of the rabbit caecotrophy rhythm correspond well with those obtained in nocturnal rodents.
The breeding performance of the Pirbright Dunkin-Hartley guineapig after discontinuing the feeding of green food as a supplement, with particular reference to productivity
Authors: Eveleigh J. R.
Published: June 2007

Since discontinuing feeding green food as a supplement and feeding autoclaved meadow hay and extruded diet containing vitamin C, the productivity of the guineapig colony has been maintained, with a reduction in deaths and discards after weaning.
Investigation into the transplacental transmission of Encephalitozoon cuniculi in rabbits
Authors: Owen Dawn G. , Gannon J.
Published: June 2007

An investigation into the transmission of Encephalito-zoon cuniculi was undertaken in both naturally- and experimentally-infected rabbits. Only 2 nurslings were found with rising antibody titres at 8-10 weeks of age, when infection could have been caused by environmental contamination.
Diagnosis of Mycoplasma pulmonis infection of rats by an indirect immunofluorescence test compared with 4 other diagnostic methods
Authors: Kraft V. , Meyer Barbara , Thunert A. , Deerberg F. , Rehm Sabine
Published: June 2007

Efficiency of indirect immunofluorescence microscopy (IFM) for detection of M. pulmonis antibody (IgG) in rats was compared with results of enzyme-linked immunosorbent assay (ELISA), complement fixation (CF), cultural isolation and histopathology. IFM was carried out on M. pulmonis infected BHK-21 cells grown on cover slips or multitest slides. After acetone fixation these antigen carriers could be stored at -20°C for several months so that serological tests could be done at any time and completed within 2 h. The IFM was strain specific and the sensitivity of the test was comparable with that of the ELISA, whereas the CF-test proved to be very insensitive. For routine monitoring, only in cases of fresh infections should time consuming cultural procedures be preferred to serological tests. Chronic disease stages were readily detected by histological examination.
Use of portable filter units to control the animal house environment
Authors: Baskerville Margaret , Seamer J. H.
Published: June 2007

The application of portable recirculating filter units to the control of laboratory animal house environments was investigated. Under practical conditions such a unit effected reductions in the ammonia level and bacterial content of the atmosphere of a room housing rats.
The influence of dietary magnesium on reduction of nephrocalcinosis in rats fed purified diet
Authors: Harwood E. J.
Published: June 2007

The severity of nephrocalcinosis in female Colworth Wistar rats fed on a standard purified diet was reduced by increasing the magnesium content of the diet; both its incidence and severity could be increased in males of the same strain by lowering the dietary magnesium level.
A design for flexible intestinal cannulas
Authors: Buttle H. L. , Clapham C. , Oldham J. D.
Published: June 2007

A design for a cannula made by fixing silicone rubber tubing to rigid internal and external flanges is described. These cannulas have been used to fit simple duodenal, simple ileal and abomasal fistulas in adult lactating cattle for periods up to 1 year and have caused minimal tissue reaction at the site of fistulation.
Chronic intracarotid cannulation of pigeons for administration of behaviorally active peptides
Authors: Wendt D. J. , Normile H. J. , Dawe Elizabeth J. , Trompeter T. , Barraco R. A.
Published: June 2007

Chronic intracarotid cannulation of the common carotid artery was performed in the pigeon. The catheter system of polyethylene tubing consisted of an indwelling component and an injection component. The indwelling component was exteriorized at the occiput so the bird could not reach the catheter with its beak. Following surgery, the pigeons were housed individually and received food and water ad libitum and no special care was necessary. The catheter was flushed daily with heparin in 0·9% NaCl solution to maintain patency. 30 pigeons were continuously or intermittently infused with bioactive peptides for up to 60 days after cannulation.
Compact portable system for continuous central venous infusion in rats
Authors: Shaw J. F. L.
Published: June 2007

A new method of cannula protection is described. This allows the use of a shorter connection between the infusion pump and the mobile rat, and the whole apparatus is easily transportable.
Ultrastructural studies of chronic pneumonia in guineapigs
Authors: Baskerville A. , Dowsett A. B. , Baskerville Margaret
Published: June 2007

Pulmonary interstitial fibrosis commenced as focal proliferation of fibroblasts and accumulation of macrophages in interalveolar septa and was followed by deposition of excess collagen. Epithelium of airways and alveoli remained normal. Perivascular nodules of lymphoid tissue which developed in the lungs of many older animals had a high mitotic rate, but the lymphocytes were morphologically normal. Micro-organisms were not observed in the lungs of any animal.
Response of mice to transtracheal pulmonary inoculation of anaerobic bacteria
Authors: File T. M. , Fass R. J. , Prior R. B.
Published: June 2007

The transtracheal inoculation of a mixture of anaerobic bacteria, with or without hydrochloric acid, into the lungs of mice caused nonlethal pneumonia and abscesses in a minority of challenged animals. All animals cleared organisms and recovered by 30 days. Secondary infection with Escherichia coli was common but did not affect the response to challenge with the anaerobes.
Haematological, coagulation and blood chemistry data in red-bellied tamarins Saguinus labiatus
Authors: Wadsworth Peter F. , Hiddleston William A. , Jones David V. , Fowler John S. L. , Ferguson Robert A.
Published: June 2007

Haematology, coagulation and clinical chemistry data are reported for a group of male and female red-bellied tamarins ( Saguinus labiatus). The tamarins were juvenile and young adults and were bred in captivity. High mean values for activities of alkaline phosphatase, alanine amino-transferase, aspartate aminotransferase and creatine kinase were noted. The findings are compared with data obtained from other members of the family Callitrichidae.
Spontaneous short-term fluctuations in the daily pattern of heart rate, body temperature and locomotor activity in the laboratory rat
Authors: Büttner D. , Wollnik Franziska
Published: June 2007

Heart rate (HR), body temperature (BT) and locomotor activity (LA) were measured continuously over 5 days in freely moving rats. In addition to the well-known circadian rhythms, all variables exhibited considerable fluctuations in amplitude mainly during the dark, but also in the light periods. The values of HR varied from 286 ± 12 to 470 ± 26 b.p.m. and BT from 36·15 ± 0·15°C to 38·45 ± 0·25°C. The large variability of HR, BT and LA within a single day was due more to large short-term fluctuations within periods of about 3-5 hours duration, than to differences between the light and the dark period. Good consistency of daily patterns and similarity of the 3 variables was found within the animals. Usually there were 3 or 4 regular peaks during the dark and often another peak 3-4 hours after the onset of light. Correlation coefficients, calculated on the basis of 5-min mean values, were highly significant ( P<0·001) for LA vs HR (0·61-0·73), LA vs BT (0·40-0·53), and HR vs BT (0·61-0·68). Between-hour correlations were higher than these common correlations of 5-min values. HR vs BT (0·76-0·83) and LA vs BT (0·63-0·79) correlated as well as LA vs HR (0·72-0·83). The short-term fluctuations (within-hours) gave lower correlation coefficients for LA vs BT (0·23-0·32) and HR vs BT (0·29-0·41) than LA vs HR (0·40-0·70). This seems to result from a physiological delay of BT relative to HR and LA.
Noma in Saguinus oedipus: A report of 2 cases
Authors: Brack M.
Published: June 2007

2 cases of noma in cotton topped marmosets ( Saguinus oedipus) are reported. The condition did not respond to antibiotic therapy, but was successfully treated in one animal by local application of ethacridine lactate.
The suitability of immunosuppressed mice kept in a standard animal unit as recipients of human tumour xenografts
Authors: Hay J. H. , Morten J. E. N. , Clarke Barbara , Swinton June
Published: June 2007

CBA/Lac mice were immunosuppressed by thymectomy and whole body irradiation with 250 kVp X-rays following pretreatment with cytosine arabinoside. The optimum radiation dose for immunosuppression with prolonged survival was 7·35 Gy. The animals were kept in a standard animal unit with an overall survival rate of 83%. They were found to be suitable for large scale, long-term, xenotransplantation experiments at 20% of the cost of nude mice.
Vascular access for extracorporeal therapy in the rabbit
Authors: Canaud B. , Charlton B. , Antony Jayne , Schindhelm K. , Moran J. E.
Published: June 2007

A technique allowing short-term blood access for extracorporeal therapy in rabbits is described. The technique utilizes silicone rubber cannulae and teflon vessel tips to construct an externalized carotid-jugular arteriovenous shunt. The insertion procedure takes 1 h and extracorporeal blood flows in excess of 10 ml/min are obtainable for up to 7 days. Blood flow may still be obtained following shunt clotting by insertion of smaller diameter catheters through the arterial cannula. This technique has been successfully used for extracorporeal therapy in rabbit disease models.
Effects of ketamine anaesthesia, stress and repeated bleeding on the haematology of vervet monkeys
Authors: Wall Holly S. , Worthman Carol , Else J. G.
Published: June 2007

Haematology values are presented for the vervet monkey ( Cercopithecus aethiops), and the relative effects of high dose ketamine anaesthesia, stress of capture and repeated bleedings assessed. Anaesthesia resulted in decreased WBC and RBC values, attributed to depression of cardiovascular function. These effects were the reverse of those of alarm and strenuous exercise (leukocytosis and polycythaemia) during capture. Stress resulted in relatively high white and low red blood cell counts. Opposing effects of stress and anaesthesia led to comparable haematological values for trained, non-anaesthetized vervets and stressed, anaesthetized vervets. Effects of repeated bleedings were opposite in anaesthetized and non-anaesthetized animals. These effects, however, along with those of ketamine anaesthesia and stress, were relatively insignificant compared with the wide variation in haematological values found among individuals. The biological importance of these effects thus appeared to be slight. The concept of 'normal values' is discussed.
Salmonella ochiogu: experimental infection of laboratory rats (Rattus rattus)
Authors: Onyekaba C. O.
Published: June 2007

Oral infection of experimental rats with 108 colony forming units of Salmonella ochiogu resulted in clinical salmonellosis in 42 of 98 (43%) rats and a carrier state in 56 of 98 (57%). Infection was characterized by septicaemia, pneumonia and loss of condition. Organisms were shed in faeces on the First day after infection and cultures of most visceral organs revealed good systemic dissemination of the serotype, which was pathogenic to experimental rats.
An isolator system for mice infected with Eimeria spp. and other parasites
Authors: Rawlinson Elaine M. , Nowell F. , Conisbee A.
Published: June 2007

An effective isolator system built to house mice individually and avoid the risk of cross-contamination by parasites is described. Each mouse received a separate supply of filtered air. Waste air passed from the system under positive pressure. A suitable method of operating the system is discussed.
A Decomposition-Based Genetic Algorithm for the Resource-Constrained Project-Scheduling Problem
Authors: Debels Dieter , Vanhoucke Mario
Published: June 2007

In the last few decades, the resource-constrained project-scheduling problem has become a popular problem type in operations research. However, due to its strongly NP-hard status, the effectiveness of exact optimisation procedures is restricted to relatively small instances. In this paper, we present a new genetic algorithm (GA) for this problem that is able to provide near-optimal heuristic solutions. This GA procedure has been extended by a so-called decomposition-based genetic algorithm (DBGA) that iteratively solves subparts of the project. We present computational experiments on two data sets. The first benchmark set is used to illustrate the performance of both the GA and the DBGA. The second set is used to compare the results with current state-of-the-art heuristics and to show that the procedure is capable of producing consistently good results for challenging problem instances. We illustrate that the GA outperforms all state-of-the-art heuristics and that the DBGA further improves the performance of the GA.
A Model Reference Adaptive Search Method for Global Optimization
Authors: Hu Jiaqiao , Fu Michael C. , Marcus Steven I.
Published: June 2007

Model reference adaptive search (MRAS) for solving global optimization problems works with a parameterized probabilistic model on the solution space and generates at each iteration a group of candidate solutions. These candidate solutions are then used to update the parameters associated with the probabilistic model in such a way that the future search will be biased toward the region containing high-quality solutions. The parameter updating procedure in MRAS is guided by a sequence of implicit probabilistic models we call reference models. We provide a particular algorithm instantiation of the MRAS method, where the sequence of reference models can be viewed as the generalized probability distribution models for estimation of distribution algorithms (EDAs) with proportional selection scheme. In addition, we show that the model reference framework can also be used to describe the recently proposed cross-entropy (CE) method for optimization and to study its properties. Hence, this paper can also be seen as a study on the effectiveness of combining CE and EDAs. We prove global convergence of the proposed algorithm in both continuous and combinatorial domains, and we carry out numerical studies to illustrate the performance of the algorithm.
An Exact Algorithm for Higher-Dimensional Orthogonal Packing
Authors: Fekete Sándor P. , Schepers Jörg , van der Veen Jan C.
Published: June 2007

Higher-dimensional orthogonal packing problems have a wide range of practical applications, including packing, cutting, and scheduling. Combining the use of our data structure for characterizing feasible packings with our new classes of lower bounds, and other heuristics, we develop a two-level tree search algorithm for solving higher-dimensional packing problems to optimality. Computational results are reported, including optimal solutions for all two-dimensional test problems from recent literature.

This is the third in a series of articles describing new approaches to higher-dimensional packing.
Traffic Estimation and Capacity Assignment in Multimedia Distribution Networks with Guaranteed Quality of Service
Authors: Kalvenes Joakim , Keon Neil
Published: June 2007

This paper considers the provisioning of transmission line bandwidth on a private network with given traffic routing for the purpose of distribution of video-on-demand service with guaranteed end-to-end quality of service. We present an architecture for video-on-demand service delivery and model the assignment of bandwidth in the distribution network as a constrained, nonlinear optimization problem. To solve this optimization problem, we develop three new auction algorithm-based solution procedures. The optimization problem assumes that there is a functional relationship between the maximum acceptable end-to-end delay and the bandwidth requirement for the links in the distribution network. Absent reliable video traffic data models for MPEG-2 format, we sample a large number of DVD-recorded movies to form a basis for randomly generated aggregate traffic streams. The aggregate traffic streams are used in a simulation experiment to measure the maximum transmission buffer occupancy for each given traffic stream for different transmission rates. Based on this simulation experiment, we derive an empirical transmission line provisioning function that guarantees delivery of all video frames without frame loss within a maximum frame delay tolerance. To illustrate the effectiveness of the proposed solution procedure for the bandwidth assignment problem, we solve to near optimality 570 small problem instances under three demand structures and 100 large problem instances with uniformly distributed demand.
Two-Moment Approximations for Maxima
Authors: Crow Charles S. , Goldberg David , Whitt Ward
Published: June 2007

We introduce and investigate approximations for the probability distribution of the maximum of n independent and identically distributed nonnegative random variables, in terms of the number n and the first few moments of the underlying probability distribution, assuming the distribution is unbounded above but does not have a heavy tail. Because the mean of the underlying distribution can immediately be factored out, we focus on the effect of the squared coefficient of variation (SCV, c2, variance divided by the square of the mean). Our starting point is the classical extreme-value theory for representative distributions with the given SCV—mixtures of exponentials for c2 ⩾ 1, convolutions of exponentials for c2 ⩽ 1, and gamma for all c2. We develop approximations for the asymptotic parameters and evaluate their performance. We show that there is a minimum threshold n*, depending on the underlying distribution, with n ⩾ n* required for the asymptotic extreme-value approximations to be effective. The threshold n* tends to increase as c2 increases above one or decreases below one.
On the Integration of Production and Financial Hedging Decisions in Global Markets
Authors: Ding Qing , Dong Lingxiu , Kouvelis Panos
Published: June 2007

We study the integrated operational and financial hedging decisions faced by a global firm who sells to both home and foreign markets. Production occurs either at a single facility located in one of the markets or at two facilities, one in each market. The company has to invest in capacity before the selling season starts when the demand in both markets and the currency exchange rate are uncertain. The currency exchange rate risk can be hedged by delaying allocation of the capacity to specific markets until both the currency and demand uncertainties are resolved and/or by buying financial option contracts on the currency exchange rate when capacity commitment is made. A mean-variance utility function is used to model the firm’s risk aversion in decision making. We derive the joint optimal capacity and financial option decision, and analyze the impact of the delayed allocation option and the financial options on capacity commitment and the firm’s performance. We show that the firm’s financial hedging strategy ties closely to, and can have both quantitative and qualitative impact on, the firm’s operational strategy. The use, or lack of use of financial hedges, can go beyond affecting the magnitude of capacity levels by altering global supply chain structural choices, such as the desired location and number of production facilities to be employed to meet global demand.
Dynamic Pricing Strategies with Reference Effects
Authors: Popescu Ioana , Wu Yaozhong
Published: June 2007

We consider the dynamic pricing problem of a monopolist firm in a market with repeated interactions, where demand is sensitive to the firm’s pricing history. Consumers have memory and are prone to human decision-making biases and cognitive limitations. As the firm manipulates prices, consumers form a reference price that adjusts as an anchoring standard based on price perceptions. Purchase decisions are made by assessing prices as discounts or surcharges relative to the reference price in the spirit of prospect theory.

We prove that optimal pricing policies induce a perception of monotonic prices, whereby consumers always perceive a discount, respectively surcharge, relative to their expectations. The effect is that of a skimming or penetration strategy. The firm’s optimal pricing path is monotonic on the long run, but not necessarily at the introductory stage. If consumers are loss averse, we show that optimal prices converge to a constant steady-state price, characterized by a simple implicit equation; otherwise, the optimal policy cycles. The range of steady states is wider the more loss averse consumers are. Steady-state prices decrease with the strength of the reference effect and with customers’ memory, all else equal. Offering lower prices to frequent customers may be suboptimal, however, if these are less sensitive to price changes than occasional buyers.

If managers ignore such long-term implications of their pricing strategy, the model indicates that they will systematically price too low and lose revenue. Our results hold under very general reference dependent demand models.
Parents grieving the loss of their child: Interdependence in coping
Authors: Meij Leoniek Wijngaards‐de. , Stroebe Margaret. , Schut Henk. , Stroebe Wolfgang. , van den Bout Jan. , Heijden Peter G. M. , Dijkstra Iris.
Published: June 2007

Objectives

A longitudinal study was conducted among bereaved parents, to examine the relationship between parents' own and their partners' ways of coping in terms of the constructs loss‐orientation and restoration‐orientation (coping strategies based on the bereavement‐specific Dual Process Model (Stroebe & Schut, 1999)), and psychological adjustment following the death of their child.

Method

219 couples participated at 6, 13 and 20 months post‐loss. Use of the Actor Partner Interdependence Model within multi‐level regression analyses enabled assessment of both actor as well as partner effects, and permitted differentiating these effects according to the gender of the parent.

Results

Loss‐orientation was predictive of negative psychological adjustment, while restoration‐orientation was related to better adjustment. Furthermore, high levels of restoration‐oriented coping buffered the negative effect of high levels of loss‐orientation on depression. In the interpersonal context, results indicated that for men, having a female partner high in restoration‐oriented coping was related to positive adjustment.

Conclusion

In coping with the loss of their child, intra‐personal as well as interpersonal processes are relevant for the adjustment process of parents after the loss of their child.
Identity formation in multiparty negotiations
Authors: Swaab Roderick I. , Postmes Tom , Spears Russell
Published: June 2007

Based on the recently proposed Interactive Model of Identity Formation, we examine how top‐down deductive and bottom‐up inductive identity formations influence intentions and behaviour in multiparty negotiations. Results show that a shared identity can be deduced from the social context through recognition of superordinate similarities. However, shared identities can also be induced by intragroup processes in which individuals get acquainted with one another on an interpersonal basis. Both top‐down and bottom‐up processes led to the formation of a sense of shared identity, and this in turn exerted a positive influence on behavioural intentions and actual behaviour in multiparty negotiations.
Self‐evaluative emotions and expectations about self‐evaluative emotions in health‐behaviour change
Authors: Dijkstra Arie , Buunk Abraham P.
Published: June 2007

Engaging in a behaviour that has negative physical consequences is considered to be a threat to the self because it makes the self appear inadequate and non‐adaptive. This self‐threat is experienced as self‐evaluative emotions. The self‐threat can be removed by refraining from the unhealthy behaviour. The experience of self‐threat influences behaviour because it contributes to expectations about the occurrence of self‐evaluative emotions in the case of behaviour change.

The results of Study 1, conducted among 503 smokers, showed that self‐evaluative emotions were the central predictor of quitting activity during a 7‐month period, among measures related to the negative consequences of smoking. The results of Study 2, conducted among 409 smokers, showed that expectations about the self‐evaluative emotions that follow quitting smoking predicted quitting activity during a 9‐month period and that these expectations partly mediated the relation between self‐evaluative emotions and quitting. The results of Study 3, conducted among 255 smokers, showed that information on the negative outcomes of smoking led to quitting activity only when there was room to change self‐evaluative outcome expectations. In addition, increases in these expectations predicted quitting activity during a 6‐month period.

The results suggest that negative self‐evaluative emotions are a central motive to change unhealthy behaviour and that self‐evaluative outcome expectations govern the behaviour change. The results can be understood within Steele's (1999) Self‐affirmation theory.
Perceived control predicting the recovery of individual‐specific walking behaviours following stroke: Testing psychological models and constructs
Authors: Bonetti D. , Johnston M.
Published: June 2007

Objectives Perceived control predicts activity limitations, but there are many control belief concepts and how these are defined and measured has implications for intervention design. This study examined whether individual‐specific activity limitations and recovery were predicted by theoretically derived control conceptualizations, the Theory of Planned Behaviour and an integrated model (Theory of Planned Behaviour with the World Health Organization ICF (International Classification of Functioning, Disability and Health) model).

Design This predictive cohort study used measures of impairment, intention and perceived control (perceived behavioural control, Theory of Planned Behaviour; self‐efficacy, Social Cognitive Theory; locus of control, Social Learning Theory), assessed 2 weeks after hospital discharge, to predict walking limitation (UK SIP: FLP) and recovery after 6 months. Theoretically derived items were individually tailored for patients' baseline walking limitation.

Participants Two hundred and three stroke patients (124 men and 79 women; mean age=68.88, SD = 12.31 years)

Results Walking limitation and walking recovery (respectively) were predicted by perceived behavioural control (r = −.36**, .26**) and self‐efficacy (r = −.30**, .22**), but not locus of control (r = −.07, .02). Both theoretical models accounted for significant variance in walking limitation and recovery – but not beyond that explained by perceived behavioural control. Predictive power was not improved by modifying the control component or by including impairment in regression equations.

Conclusions Results suggest that perceived control predicts individual‐specific disability and recovery and that reductions in activity limitations may be achieved by manipulating control cognitions. In addition, reducing impairments may not have maximal effect on reducing disability unless beliefs about control over performing the behaviour are also influenced.
Exploring the relationships among early maladaptive schemas, psychological mindedness and self‐reported college adjustment
Authors: Cecero John J. , Beitel Mark , Prout Tracy
Published: June 2007

Objectives. The primary aim of this research was to study the statistical effects of psychological mindedness (PM) upon the relationship between early maladaptive schemas (EMS) and self‐reported college adjustment.

Design. A cross‐sectional design was employed to assess correlations among study variables and to assess the role of PM as moderator or mediator in the relationship between EMS and adjustment.

Methods. Into this study, 264 undergraduate students were recruited in partial fulfilment of research requirements in introductory psychology class. Participants completed the Young Schema Questionnaire, the Psychological Mindedness Scale and the Student Adaptation to College Questionnaire.

Results. At the level of bivariate correlations, EMS were inversely associated with college adjustment and with PM, and PM was positively associated with adjustment. In a multiple regression equation with PM and EMS entered separately and then as an interaction term as predictors of adjustment, PM was not a significant moderator. However, in a path analysis, the indirect effect of EMS on adjustment through PM was significant, suggesting that PM is a significant mediator.

Conclusions. These findings suggest that the assessment of EMS and PM may enhance an understanding of problems with college adjustment and that interventions to reduce the negative effects of EMS may indeed benefit from efforts to improve PM and its correlates.
Chemical parameters influencing fine-tuning in the binding of macrolide antibiotics to the ribosomal tunnel
Authors: Pyetan Erez , Baram David , Auerbach-Nevo Tamar , Yonath Ada
Published: June 2007

In comparison to existing structural, biochemical, and therapeutical data, the crystal structures of large ribosomal subunit from the eubacterial pathogen model Deinococcus radiodurans in complex with the 14-membered macrolides erythromycylamine, RU69874, and the 16-membered macrolide josamycin, highlighted the similarities and differences in macrolides binding to the ribosomal tunnel. The three compounds occupy the macrolide binding pocket with their desosamine or mycaminose aminosugar, the C4-C7 edge of the macrolactone ring and the cladinose sugar sharing similar positions and orientations, although the latter, known to be unnecessary for antibiotic activity, displays fewer contacts. The macrolactone ring displays altogether few contacts with the ribosome and can, therefore, tilt in order to optimize its interaction with the 23S rRNA. In addition to their contacts with nucleotides of domain V of the 23S RNA, erythromycylamine and RU69874 interact with domain II nucleotide U790, and RU69874 also reaches van der Waals distance from A752, in a fashion similar to that observed for the ketolides telithromycin and cethromycin. The variability in the sequences and consequently the diversity of the conformations of macrolide binding pockets in various bacterial species can explain the drug's altered level of effectiveness on different organisms and is thus an important factor in structure-based drug design.
Physical origin of chemical phenomena: Interpretation of acidity, basicity, and hydride affinity by trichotomy paradigm
Authors: Maksić Zvonimir B. , Vianello Robert
Published: June 2007

Some of the most important aspects of modeling in chemistry are discussed in detail. It is argued that the interpretive side of (quantum) chemistry is indispensable, since it gives sense to a myriad of experimental and computational results. The usefulness of some physical modeling is illustrated by the trichotomy approach in rationalizing acidity, basicity, and hydride affinities of neutral organic compounds. According to trichotomy paradigm, the simple chemical reaction of protonation and H-attachment can be decomposed into three separate sequential steps, which in turn mirror the initial-, intermediate-, and final-state effects. Ample evidence is given, which convincingly shows that the trichotomy approach has some distinct advantages in interpreting aforementioned properties that belong to the most important ones in chemistry and biochemistry.
Addition reactions of E-E and E-H bonds to triple bond of alkynes catalyzed by Pd, Pt, and Ni complexes (E=S, Se)
Authors: Beletskaya Irina P. , Ananikov Valentine P.
Published: June 2007

The synthetic application and mechanistic aspects of transition-metal (Ni, Pd, Pt) catalyzed addition of E-E and E-H (E=S, Se) bonds to alkynes were investigated in detail. This study revealed major factors controlling the selectivity of such addition reactions. A new Ni-based catalytic system with a self-organized nanostructured catalyst has been designed to perform chemical transformation in high yield, under mild conditions.
De novo design approach based on nanorecognition toward development of functional molecules/materials and nanosensors/nanodevices
Authors: Singh N. Jiten , Lee Han Myoung , Suh Seung Bum , Kim Kwang S.
Published: June 2007

For the design of functional molecules and nanodevices, it is very useful to utilize nanorecognition (which is governed mainly by interaction forces such as hydrogen bonding, ionic interaction, π-H/π-π interactions, and metallic interactions) and nanodynamics (involving capture, transport, and release of electrons, photons, or protons). The manifestation of these interaction forces has led us to the design and realization of diverse ionophores/receptors, organic nanotubes, nanowires, molecular mechanical devices, molecular switches, enzyme mimetics, protein folding/unfolding, etc. In this review, we begin with a brief discussion of the interaction forces, followed by some of our representative applications. We discuss ionophores with chemo-sensing capability for biologically important cations and anions and explain how the understanding of hydrogen bonding and π-interactions has led to the design of self-assembled nanotubes from calix[4]hydroquinone (CHQ). The binding study of neutral and cationic transition metals with the redox system of hydroquinone (HQ) and quinone (Q) predicts what kind of nanostructures would form. Finally, we look into the conformational changes between stacked and edge-to-face conformers in π-benzoquinone-benzene complexes controlled by alternating electrochemical potential. The resulting flapping motion illustrates a promising pathway toward the design of mobile nanomechanical devices.
Synthesis, structure, and complexing properties of macrocyclic receptors for anions
Authors: Chmielewski Michał J. , Zieliński Tomasz , Jurczak Janusz
Published: June 2007

Understanding of structure-affinity relationships is crucial for rational receptor design, however, such studies for anion receptors are still limited. Therefore, we investigated this issue in the case of amide-based macrocyclic receptors derived from aromatic diacids (i.e., isophthalic and dipicolinic). Using these model compounds, we examined the macrocyclic effect, the influence of intramolecular hydrogen bonds, and the correlation between the ring size and anion affinity. We found that in contrast to what was known for acyclic diamides, macrocyclic isophthalamide receptors bind anions more weakly than their dipicolinic analogs. Comprehensive structural studies revealed that such behavior is due to intramolecular hydrogen bonds present in isophthalamide receptors. Furthermore, we demonstrated how this obstacle can be overcome by the preparation of a hybrid macrocycle based on both building blocks.
Microemulsions as microreactors in physical organic chemistry
Authors: García-Río Luis , Leis J. Ramon , Mejuto Juan Carlos , Pérez-Lorenzo Moisés
Published: June 2007

Microemulsions are very versatile reaction media which nowadays find many applications, ranging from nanoparticle templating to preparative organic chemistry. The thermodynamically stable and microheterogeneous nature of microemulsions, used as reaction media, induces drastic changes in the reagent concentrations, and this can be specifically used for tuning the reaction rates. In particular, amphiphilic organic molecules can accumulate and orient at the oil-water interface, inducing regiospecificity in organic reactions. In this review, we will show the recent tendencies of the use of microemulsions as organic reaction media.
Silicon rehybridization and molecular rearrangements in hypercoordinate silicon dichelates
Authors: Kost Daniel , Gostevskii Boris , Kalikhman Inna
Published: June 2007

Hydrazide-based hypercoordinate silicon dichelates are remarkably flexible in terms of geometry and reactivity: this paper demonstrates how rather subtle constitutional changes result in dramatic geometrical and reactivity changes. A change of ligand-donor group from NMe2to N=CMe2changes the solid-state geometry from bicapped tetrahedral to octahedral. These two geometries are shown to coexist in solution in dynamic equilibrium. Hexacoordinate complexes are shown to dissociate to pentacoordinate compounds in two distinct ways: ionic or neutral, depending on substitution. Hexacoordinate dichelates with imino-donor groups undergo a skeletal rearrangement (intramolecular aldol-type condensation of imines), catalyzed by their dissociated halide counterions. However, even in the absence of counterions, silacyclobutane dichelates undergo a similar rearrangement.
Lipoprotein-Associated Phospholipase A2 Predicts 5-Year Cardiac Mortality Independently of Established Risk Factors and Adds Prognostic Information in Patients with Low and Medium High-Sensitivity C-Reactive Protein (The Ludwigshafen Risk and Cardiovascular Health Study)
Authors: Winkler Karl , Hoffmann Michael M , Winkelmann Bernhard R , Friedrich Isolde , Schäfer Günther , Seelhorst Ursula , Wellnitz Britta , Wieland Heinrich , Boehm Bernhard O , März Winfried
Published: June 2007

Background: Lipoprotein-associated phospholipase A2 (LpPLA2), also denoted as platelet-activating factor acetylhydrolase, is a lipoprotein-bound enzyme involved in inflammation and atherosclerosis. In this cohort study we investigated LpPLA2 activity to predict cardiac mortality in patients scheduled for coronary angiography.

Methods: LpPLA2 activity was determined in 2513 patients with and in 719 patients without angiographically confirmed coronary artery disease (CAD).

Results: During the median observation period of 5.5 years, 501 patients died. In patients with tertiles of LpPLA2 activity of 420–509 U/L or ≥510 U/L, unadjusted hazard ratios (HRs) for cardiac death were 1.7 (95% CI 1.3–2.4; P = 0.001), and 1.9 (95% CI 1.4–2.5; P <0.001), respectively, compared with patients with LpPLA2 activity ≤419 U/L. After we accounted for established risk factors and included angiographic CAD status, high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide, the 3rd tertile of LpPLA2 activity predicted cardiac 5-year mortality with an HR of 2.0 (95% CI 1.4–3.1; P = 0.001). LpPLA2 activity increased the adjusted risk for cardiac death by 2-fold in patients with hsCRP <3 mg/L in the 2nd (HR 2.4, 95% CI 1.4–4.2; P = 0.002) and 3rd (HR 2.1, 95% CI 1.1–4.0; P = 0.02) tertiles of LpPLA2 activity and in patients with hsCRP of 3–10 mg/L in the 3rd tertile (HR 1.9, 95% CI 1.0–3.6; P = 0.03) of LpPLA2 activity.

Conclusions: LpPLA2 activity predicts risk for 5-year cardiac mortality independently from established risk factors and indicates risk for cardiac death in patients with low and medium-high hsCRP concentrations. Therefore, LpPLA2 activity may provide information for the identification and management of patients at risk beyond established risk stratification strategies.
Distribution of 15 Human Kallikreins in Tissues and Biological Fluids
Authors: Shaw Julie LV , Diamandis Eleftherios P
Published: June 2007

Background: Kallikreins (KLKs) are a group of 15 secreted serine proteases. Some KLKs are established or candidate cancer biomarkers, but for most the physiological function is unknown. We characterized the protein and mRNA abundance patterns of all 15 KLKs in multiple panels of human tissues and biological fluids.

Methods: We used sensitive and specific sandwich-type ELISAs for each KLK. Reverse transcription PCR was used for transcript amplification. Multiple panels of human tissue extracts (adult and fetal) were tested, along with various biological fluids.

Results: Quantitative protein expression data on 7 sets of adult and 3 sets of fetal tissues were collected for all 15 KLKs. KLKs were also quantified in the following biological fluids: seminal plasma, breast milk, follicular fluid, breast cyst fluid, breast cancer cytosol, amniotic fluid, ovarian cancer ascites, cerebrospinal fluid, cervicovaginal fluid, and urine. The data were used to generate heat maps of KLK concentrations in tissues and fluids and categorize KLK abundance as highly restricted (KLK2 and KLK3 in prostate), restricted (KLK5 in skin, salivary gland, breast, and esophagus; KLK6 in brain and central nervous system; KLK7 in esophagus, heart, liver, and skin; KLK8 in breast, esophagus, skin, and tonsil; KLK13 in esophagus and tonsil), or wide (KLKs 1, 4, 9, 10, 11, 12, 14, and 15).

Conclusions: Quantitative KLK concentrations in tissues and fluids aid in the elucidation of KLK function, and coexpression patterns provide clues for KLK participation in proteolytic cascades.
Apparent Loss of Urinary Albumin during Long-term Frozen Storage: HPLC vs Immunonephelometry
Authors: Brinkman Jacoline W , de Zeeuw Dick , Lambers Heerspink Hiddo J , Gansevoort Ronald T , Kema Ido P , de Jong Paul E , Bakker Stephan JL
Published: June 2007

Background: Urinary albumin detection by immunonephelometry is decreased by ∼30% in samples that have been frozen at −20 °C. An HPLC method for assessment of urinary albumin that detects immunoreactive and immunochemically nonreactive albumin has been introduced as an alternative to immunonephelometry. We investigated whether this technique is affected by sample temperature, particularly freezing.

Methods: Urine samples (n = 295) were collected from the general population (Prevention of Renal and Vascular End-Stage Disease Study). Samples were assessed by both immunonephelometry and HPLC when fresh and after storage at −20 °C for 4, 8, and 12 months and at −80 °C for 12 months.

Results: With immunonephelometry, storage for 4, 8, and 12 months at −20 °C resulted in mean (SD) urine albumin changes of −21% (29%), −28% (29%), and −34% (31) (P <0.001 for trend). Storage at −80 °C resulted in a 5% (19%) change after 12 months of storage (not significant). With HPLC, storage for 4, 8, and 12 months at −20 °C resulted in urine albumin changes of −33% (28%), −43% (24%), and −55% (21%; P <0.001 vs immunonephelometry). Storage at −80 °C resulted in a −29% (29%) change (P <0.001 vs immunonephelometry).

Conclusion: Loss of albumin after freezing urine depends not only on freezing temperature but also on detection method. Detection of albumin by immunonephelometry appears to be significantly less influenced by freezing than detection by HPLC. Storage at −80 °C appears to prevent loss when using immunonephelometry, whereas HPLC still shows considerable loss even when urine is frozen at −80 °C. We propose that for reliable measurement of urine albumin, fresh samples should be used.
Importance of tRNA interactions with 23S rRNA for peptide bond formation on the ribosome: studies with substrate analogs
Authors: Beringer Malte , Rodnina Marina V.
Published: June 2007

The major enzymatic activity of the ribosome is the catalysis of peptide bond formation. The active site – the peptidyl transferase center – is composed of ribosomal RNA (rRNA), and interactions between rRNA and the reactants, peptidyl-tRNA and aminoacyl-tRNA, are crucial for the reaction to proceed rapidly and efficiently. Here, we describe the influence of rRNA interactions with cytidine residues in A-site substrate analogs (C-puromycin or CC-puromycin), mimicking C74 and C75 of tRNA on the reaction. Base-pairing of C75 with G2553 of 23S rRNA accelerates peptide bond formation, presumably by stabilizing the peptidyl transferase center in its productive conformation. When C74 is also present in the substrate analog, the reaction is slowed down considerably, indicating a slow step in substrate binding to the active site, which limits the reaction rate. The tRNA-rRNA interactions lead to a robust reaction that is insensitive to pH changes or base substitutions in 23S rRNA at the active site of the ribosome.
Morphing the minimal and full-length hammerhead ribozymes: implications for the cleavage mechanism
Authors: Scott William G.
Published: June 2007

The hammerhead ribozyme is a small, intensively studied catalytic RNA, and has been used as a prototype for understanding how RNA catalysis works. In 2003, the importance of a set of tertiary contacts that appear in natural sequences of the hammerhead RNA was finally understood. The presence of these contact regions in stems I and II in ‘full-length hammerhead ribozymes’ is accompanied by an up to 1000-fold catalytic rate enhancement, indicating a profound structural effect upon the active site. Although the new structure resolved most of what appeared to be irreconcilable differences with mechanistic studies in solution, it did so in a way that is simultaneously reconcilable with earlier crystallographic mechanistic studies, within the limits imposed by the truncated sequence of the minimal hammerhead. Here we present an analysis of the correspondence between the full-length and minimal hammerhead crystal structures, using adiabatic morphing calculations that for the first time test the hypothesis that the minimal hammerhead structure occasionally visits the active conformation, both in solution and in the crystalline state in a sterically allowed manner, and argue that this is the simplest hypothesis that consistently explains all of the experimental observations.
Long-range impact of peripheral joining elements on structure and function of the hepatitis delta virus ribozyme
Authors: Tinsley Rebecca A. , Walter Nils G.
Published: June 2007

The HDV ribozyme is an RNA enzyme from the human pathogenic hepatitis delta virus (HDV) that has recently also been identified in the human genome. It folds into a compact, nested double-pseudoknot. We examined here the functional relevance of the capping loop L4 and the helical crossover J1/2, which tightly interlace the two helical stacks of the ribozyme. Peripheral structural elements such as these are present in cis-acting, but not trans-acting ribozymes, which may explain the order-of-magnitude decrease in cleavage activity observed in trans-acting ribozymes with promise in gene therapy applications. Comparison of a systematic set of cis- and trans-acting HDV ribozymes shows that the absence of either L4 or J1/2 significantly and independently impacts catalytic activity. Using terbium(III) footprinting and affinity studies, as well as distance measurements based on time-resolved fluorescence resonance energy transfer, we find that J1/2 is most important for conferring structural properties similar to those of the cis-acting ribozyme. Our results are consistent with a model in which removal of either a helical crossover or surprisingly a capping loop induces greater dynamics and expansion of the catalytic core at long range, impacting local and global folding, as well as catalytic function.