bluuebunny/crossref_metadata_2025 huggingface dataset:
GM3 synthase gene is a novel biomarker for histological classification and drug sensitivity against epidermal growth factor receptor tyrosine kinase inhibitors in non‐small cell lung cancer
Authors: Noguchi Mariko , Suzuki Tomoko , Kabayama Kazuya , Takahashi Hiroki , Chiba Hirofumi , Shiratori Masanori , Abe Shosaku , Watanabe Atsushi , Satoh Masaaki , Hasegawa Tadashi , Tagami Seiichi , Ishii Atsushi , Saitoh Masaki , Kaneko Masanori , Iseki Ken , Igarashi Yasuyuki , Inokuchi Jin‐ichi
Published: August 2007

Expression of gangliosides and alterations in their composition have been observed during cell proliferation and differentiation and in certain cell cycle phases, brain development and cancer malignancy. To investigate the characteristics of GM3 synthase, SAT‐I mRNA and ganglioside GM3 expression levels in lung cancer, we examined the expression levels of SAT‐I mRNA as well as GM3 in 40 tumor tissues surgically removed from non‐small cell lung cancer patients. Adenocarcinoma tissues expressed SAT‐I mRNA levels that were significantly higher than those of squamous and other carcinomas (P < 0.0001). Moreover, the SAT‐I mRNA levels were high in the bronchioalveolar carcinoma subtype and low in the solid and mucin subtypes of adenocarcinomas (P = 0.049, 0.049 and 0.013, respectively). To clarify the relationship between SAT‐I mRNA and epidermal growth factor receptor (EGFR)‐tyrosine kinase (TK) inhibitor sensitivity, we carried out drug sensitivity tests for the EGFR‐TK inhibitors gefitinib and AG1478 using eight adenocarcinoma cell lines expressing no EGFR mutations. The IC50 values for gefitinib and AG1478 decreased dramatically with increasing SAT‐I mRNA levels (R2 = 0.81 and 0.59, respectively), representing a wide range of drug sensitivities among adenocarcinoma cell lines. To explore a possible mechanism of how GM3 could enhance the sensitivity to EGFR‐TK inhibitors, the SAT‐I gene was introduced stably into a GM3‐negative clone of murine 3LL lung cancer cells to produce GM3‐reconstituted clones. We found an increase in EGFR protein levels and gefitinib sensitivity in GM3‐reconstituted cells, suggesting the involvement of GM3 in the turnover of EGFR protein. Therefore, it is highly expected that, by measuring the expression levels of SAT‐I mRNA in lung biopsy samples from non‐small cell lung cancer patients, enhanced pathological identification and individualized chemotherapeutic strategies can be established for the appropriate use of EGFR‐TK inhibitors. (Cancer Sci 2007; 98: 1625–1632)
Cellular localization and functional characterization of the equilibrative nucleoside transporters of antitumor nucleosides
Authors: Endo Yoshio , Obata Tohru , Murata Daigo , Ito Mariho , Sakamoto Kazuki , Fukushima Masakazu , Yamasaki Yasundo , Yamada Yuji , Natsume Nagato , Sasaki Takuma
Published: August 2007

Nucleoside transporters play an important role in the disposition of nucleosides and their analogs. To elucidate the relationship between chemosensitivity to antitumor nucleosides and the functional expression of equilibrative nucleoside transporters (ENT), we established stable cell lines of human fibrosarcoma HT‐1080 and gastric carcinoma TMK‐1 that constitutively overexpressed green fluorescent protein‐tagged hENT1, hENT2, hENT3 and hENT4. Both hENT1 and hENT2 were predictably localized to the plasma membrane, whereas hENT3 and hENT4 were localized to the intracellular organelles. The chemosensitivity of TMK‐1 cells expressing hENT1 and hENT2 to cytarabine and 1‐(3‐C‐ethynyl‐β‐d‐ribopentofuranosyl) cytosine increased markedly in comparison to that of mock cells. However, no remarkable changes in sensitivity to antitumor nucleosides were observed in cell lines that expressed both hENT3 and hENT4. These data suggest that hENT3 and hENT4, which are mainly located in the intracellular organelles, are not prominent nucleoside transporters like hENT1 and hENT2, which are responsible for antitumor nucleoside uptake. (Cancer Sci 2007; 98: 1633–1637)
What I Would Most Like to Know ‐ How can Addiction Occur with other than Drug Involvements?
Authors: Peele Stanton
Published: August 2007

An increasing recognition of the possibility of addiction with regard to activities other than drug use seems to call for a re‐evaluation of key strands of thought about the nature of addiction, namely its relationship to the biological substratum and the relevance of cultural and individual interpretation of experience in addiction.
The Severity of Alcohol Dependence Questionnaire (SADQ) in a Sample of Irish Problem Drinkers
Authors: Meehan John P. , Webb Marcus G. T. , Unwin Antony R.
Published: August 2007

Validation of the Severity of Alcohol Dependence Questionnaire (SADQ) was attempted in a sample of 102 Irish problem drinkers. Analysis of questionnaire responses showed reasonable accord with the findings of the designers of the SADQ, suggesting that the questionnaire is a useful and valid instrument for the investigation of alcoholics. The findings gave qualified support for the concept of the alcohol dependence syndrome. Maximum agreement with a findings gave qualified support for the concept of the alcohol dependence syndrome. Maximum agreement with a clinician's rating of moderate and severe dependence was achieved at a cut‐off score of 30 on the SADQ. Results also suggested it might be possible to use the SADQ to distinguish between minimal and mild to moderate dependence.
Some Observations on the Wernicke Korsakoff Syndrome in Australia
Authors: Price John , Kerr Ray
Published: August 2007

The high incidence of the Wernicke‐Korsakoff syndrome in Australia is described. Examination of patients with this syndrome in a Queensland mental hospital reveals an excess of those who had undergone partial gastrectomy and excesses of single males and widowers. There was a relative deficit of females within this diagnostic category. Although there are reasons for relating the high incidence of the Wernicke‐Korsakoff syndrome to high rates of beer consumption, it is concluded that these do not explain the situtation adequately and that life‐stly factors are likely to be of greater importance.
The Haemolysis Resistance Test (HRT) in Chronic Excessive Drinkers: A Pilot Study
Authors: Negrete J. C. , Hosein E. A. , Lee H. , Goehlert U.
Published: August 2007

A detailed description is given of an assay to test osmotic fragility of erythrocytes in the absence and presence of ethanol (HRT). Samples from alcohol treated rats, and from alcoholic human subjects, showed fragility curves which responded to ethanol in vitro significantly differently when compared to their respective controls. The results with human samples appear to be independent of age, sex, recent abstinence from ethanol, degree of liver dysfunction, and serum cholesterol levels. At this pilot study, the HRT shows a positive predictive accuracy of 76.2 per cent and a negative one of 73 per cent.
The Collectivity of Drinking Cultures: A Theory of the Distribution of Alcohol Consumption.*
Authors: Skog Ole‐Jørgen
Published: August 2007

In this paper it is argued that Ledermann's so‐called single‐distribution theory is not based on substantial hypotheses about human drinking behaviour, and that it therefore fails to explain anything. An alternative theory of the distribution of alcohol consumption is outlined. The theory is founded on two basic hypotheses about human drinking behaviour. The theory is tested against survey data from different countries, and it is concluded that a strong collective components exists in human drinking habits. As a main rule, the population tends to move in concert up and down the scale of consumption.
Inter‐expert agreement of seven criteria in causality assessment of adverse drug reactions
Authors: Arimone Yannick , Miremont‐Salamé Ghada , Haramburu Françoise , Molimard Mathieu , Moore Nicholas , Fourrier‐Réglat Annie , Bégaud Bernard
Published: August 2007

What is already known about this subject

• In pharmacovigilance, many methods have been proposed for causality assessment of adverse drug reactions.

• Expert judgement is commonly used to evaluate the causal relationship between a drug treatment and the occurrence of an adverse event. This form of judgement relies either explicitly or implicitly on causality criteria.

What this study adds

• Our study compares the judgements of five senior experts using global introspection about drug causation and seven causality criteria on a random set of putative adverse drug reactions.

• Even if previous publications have shown poor agreement between experts using global introspection, few have compared judgements of well trained pharmacologists, familiar with using a standardized causality assessment method.

Aims

To evaluate agreement between five senior experts when assessing seven causality criteria and the probability of drug causation.

Methods

A sample of 31 adverse event‐drug pairs was constituted. For each pair, five experts separately assessed (i) the probability of drug causation, which was secondarily divided into seven causality levels: ruled out (0–0.05), unlikely (0.06–0.25), doubtful (0.26–0.45), indeterminate (0.46–0.55), plausible (0.56–0.75), likely (0.76–0.95), and certain (0.96–1); and (ii) seven causality criteria. To test discrepancies between experts, the kappa index was used.

Results

The agreement of the five experts was very poor (kappa = 0.05) for the probability of drug causation. Among the seven levels of causality, only ‘doubtful’ showed a significant rate of agreement (kappa = 0.32, P < 0.001). For all criteria, the kappa index was significant except for the item ‘risk(s) factor(s)’ (kappa = 0.09). Agreement between experts was good (0.64, P < 0.001) only for the criterion ‘reaction at site of application or toxic plasma concentration of the drug or validated test’. However, the rate of agreement with kappa indices of the causality criteria ranged from 0.12 to 0.38.

Conclusions

This study confirms that in the absence of an operational procedure, agreement between experts is low. This should be considered when designing a causality assessment method. In particular, criteria inducing a low level of agreement should have their weight reduced.
Overview of model‐building strategies in population PK/PD analyses: 2002–2004 literature survey
Authors: Dartois C. , Brendel K. , Comets E. , Laffont C. M. , Laveille C. , Tranchand B. , Mentré F. , Lemenuel‐Diot A. , Girard P.
Published: August 2007

What is already known about this subject

• The reviews already published on population pharmacokinetic/pharmacodynamic (PK/PD) analyses have focused on theory and have presented some clinical applications, evaluated validation practices in limited circumstances, defined the interest and sometimes the complexity of this approach in drug development or proposed a list of relevant articles.

• None of them has exhaustively evaluated published analyses and more precisely the model‐building steps.

• In view of the statistical complexity of population PK/PD methodology, more attention is required to how models are built and how they are reported in the literature.

What this study adds

• With a strict methodology and by establishing a standardized tool, this survey provides an exhaustive, objective and up‐to‐date review of model‐building practices.

• It reveals deficiencies in information reporting in most articles and the genuine need for guidance in publishing.

• An initial, minimal list of items is suggested, which can be used by authors and reviewers in pharmacology journals.

• The value of published peer‐reviewed papers could be greatly improved if authors were to address the suggested list of items systematically.

Aims

A descriptive survey of published population pharmacokinetic and/or pharmacodynamic (PK/PD) analyses from 2002 to 2004 was conducted and an evaluation made of how model building was performed and reported.

Methods

We selected 324 articles in Pubmed using defined keywords. A data abstraction form (DAF) was then built comprising two parts: general characteristics including article identification, context of the analysis, description of clinical studies from which the data arose, and model building, including description of the processes of modelling. The papers were examined by two readers, who extracted the relevant information and transmitted it directly to a MySQL database, from which descriptive statistical analysis was performed.

Results

Most published papers concerned patients with severe pathology and therapeutic classes suffering from narrow therapeutic index and/or high PK/PD variability. Most of the time, modelling was performed for descriptive purposes, with rich rather than sparse data and using NONMEM software. PK and PD models were rarely complex (one or two compartments for PK; Emax for PD models). Covariate testing was frequently performed and essentially based on the likelihood ratio test. Based on a minimal list of items that should systematically be found in a population PK–PD analysis, it was found that only 39% and 8.5% of the PK and PD analyses, respectively, published from 2002 to 2004 provided sufficient detail to support the model‐building methodology.

Conclusions

This survey allowed an efficient description of recent published population analyses, but also revealed deficiencies in reporting information on model building.
Exposure–response analysis reveals that clinically important toxicity difference can exist between bioequivalent carbamazepine tablets
Authors: Tothfalusi Laszlo , Speidl Szilvia , Endrenyi Laszlo
Published: August 2007

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The occurrence of central nervous system‐related adverse effects has been apparently related to the absorption rate of carbamazepine (CBZ).

• However, the differing absorption rate metrics of four carbamazepine formulations in a bioequivalence study were unclearly associated with the incidence of adverse effects.

WHAT THIS STUDY ADDS

• The relationship between the incidence of most neurological adverse effects and the absorption rate of CBZ was quantitatively established.

• A mixed‐effect PK–PD model demonstrated the rapid development of acute tolerance to these effects.

• Characterization of PD and PK–PD sensitivities showed that clinically significant differences in toxicity can exist between bioequivalent CBZ formulations.

AIMS

To assess whether, using the current regulatory criteria, therapeutically important differences can exist between bioequivalent carbamazepine (CBZ) tablets. A secondary goal was to demonstrate quantitatively the relationship between the risk of neurological adverse effects to orally ingested CBZ and the rate of absorption.

METHODS

Results of a bioequivalence study by Olling et al. (Biopharm Drug Dispos 1999; 20: 19–28) were reanalysed. Following an exploratory data analysis step, a mixed‐effect pharmacokinetic–pharmacodynamic (PK–PD) model was built to describe the dependence of adverse events on the CBZ concentration.

RESULTS

Rapid development of tolerance was demonstrated for most neurological adverse effects, with a characteristic half‐life of 02.29 h and an initial EC50 of 2.33 mg l−1. The resulting tolerance PK–PD model was characterized further using the tools and terminology of sensitivity analysis. It was demonstrated that the maximum concentration (Cmax) exhibits poor PK and PD sensitivities, and that clinically significant differences can exist between formulations which otherwise comply with the bioequivalence requirements. In contrast, another PK metric, the partial AUC, was a much better marker of the early neurological adverse events observable during the absorption phase of the drug.

CONCLUSIONS

In clinical and regulatory considerations, the development of acute tolerance for adverse effects of CBZ must be taken into account. Partial AUC reflects more sensitively the risk of adverse events than Cmax. Instead of the current trend of tightening of the bioequivalence criteria for narrow therapeutic index drugs, the use of alternative, more sensitive PK metrics is proposed.
Communication skills in child protection: how do social workers talk to parents?
Authors: Forrester Donald , Kershaw Sophie , Moss Helen , Hughes Laura
Published: August 2007

Communication skills are fundamental to social work practice, yet there is little research on the skills that workers have or how they use them. This study analyses 24 taped interviews between social workers and an actor playing a parent (a ‘simulated client’). Two child protection scenarios with different levels of seriousness were used. On average, social workers asked many closed questions and often raised concerns. They used few reflections and rarely identified positives. In all but one interview, social workers were rated as achieving clarity over issues of concern; however, they tended to demonstrate low levels of empathy. The responses of the simulated client were rated for resistance and information disclosure. The factor that most strongly influenced simulated client responses was empathy. Empathic social workers created less resistance and increased the amount of information disclosed by clients. This was not associated with failure to identify and discuss concerns. Empathy, therefore, appears to be central to good social work communication in child protection situations. Given the comparatively low level of empathy expressed by most participants, development of skills in maintaining empathic communication while raising child protection concerns appears a priority. Practical, theoretical and training implications are discussed.
SORL1 adds another piece to the complex puzzle of Alzheimer disease genetics
Authors: Katzov H
Published: August 2007

The neuronal sortilin‐related receptor SORL1 is genetically associated with Alzheimer disease Rogaeva et al. (2007) Nature Genetics 39: 168–177
The importance of grana stacking for xanthophyll cycle‐dependent NPQ in the thylakoid membranes of higher plants
Authors: Goss Reimund , Oroszi Steffen , Wilhelm Christian
Published: August 2007

In the present study we have examined the effects of grana stacking on the rate of violaxanthin (Vx) de‐epoxidation and the extent of non‐photochemical quenching of chlorophyll a fluorescence (NPQ) in isolated thylakoid membranes of spinach. Our results show that partial and complete unstacking of thylakoids in reaction media devoid of sorbitol and MgCl2 did not significantly affect the efficiency of Vx de‐epoxidation. Under high light (HL) illumination we found slightly higher values of Vx conversion in stacked membranes, whereas in thylakoids incubated at pH 5.2 in the dark, representing the pH‐optimum of Vx de‐epoxidase, de‐epoxidation was slightly increased in the unstacked membranes. Partial and complete unstacking of grana membranes, however, had a dramatic effect on the HL‐induced NPQ. High NPQ values could only be achieved in stacked thylakoid membranes in the presence of MgCl2 and sorbitol. In unstacked membranes NPQ was drastically decreased. The effects of grana stacking on the xanthophyll cycle‐dependent component of NPQ were even more pronounced, and complete unstacking of thylakoid membranes led to a total loss of this quenching component. Our data imply that grana stacking in the thylakoid membranes of higher plants is of high importance for the process of overall NPQ. For the xanthophyll cycle‐dependent component of NPQ it may even be essential. Possible effects of grana stacking on the mechanism of zeaxanthin‐dependent quenching are discussed.
Evaluation of pre‐hospital trauma triage criteria: a prospective study at a Danish level I trauma centre
Authors: Kann S. H. , Hougaard K. , Christensen E. F.
Published: August 2007

Background:  The aim of the present study was to evaluate the precision of our trauma triage protocol [based on the American College of Surgeons, Committee on Trauma (ACS COT)] in identifying severely injured defined as an injury severity score (ISS) > 15. Our hypothesis was that isolated mechanism‐of‐injury criteria were responsible for a significant over‐triage leading to over‐use of our trauma team.

Methods:  Design: A prospective cohort study. Setting: A level I trauma centre, Aarhus, Denmark. Patients and participants: Among all injured patients admitted during a 6‐month period in 2003 we identified severely injured. During the study period, trauma team activations were consecutively registered and triage criteria were prospectively collected. Sensitivity, specificity, positive predictive value, over‐triage and under‐triage were calculated.

Results:  Out of 15,162 patients in the emergency department, 848 injured patients were included and 59 (7%) were severely injured. We had 242 trauma team activations with 54 (22%) severely injured. Sensitivity was 92%, specificity 76%, giving an over‐triage of 24% and an under‐triage of 8%. The positive predictive value was 22%. Among 60 patients with mechanism‐of‐injury as the only criterion, five were severely injured in contrast to 12 out of 20 patients with mechanism‐of‐injury combined with physiological and/or anatomical criteria.

Conclusion:  The positive predictive value of our triage protocol was low, only 22%. This was mainly as a result of a significant over‐triage from isolated mechanism‐of‐injury criteria. We recommend revision of the triage protocol and reallocation of our trauma team resources.
A study of blood glucose in paediatric laparoscopy
Authors: Dave N. , Khan M. A. H. , Halbe A. R. , Kadam P. P. , Oak S. N. , Parelkar S. V.
Published: August 2007

Background:  There are few studies on stress responses to laparoscopic surgery in children. This study was conducted to assess the blood glucose levels in children undergoing laparoscopy. We also studied the effect of two different intravenous (i.v.) solutions on blood glucose in open and laparoscopic procedures.

Methods:  One hundred and twenty healthy children, aged 2–12 years, undergoing either open or laparoscopic surgery, were randomized to receive either dextrose normal saline (DS) or Ringer’s lactate peri‐operatively (RL). All patients had blood glucose measurements performed immediately after induction but prior to the i.v. infusion of any fluid. Blood glucose was again measured 1 h after induction in the open cases and 1 h after insufflation in the laparoscopy cases.

Results:  In the groups, baseline blood glucose values were comparable. In all groups, blood glucose concentrations increased from the immediate post‐induction (baseline) values. When RL was infused, the 1‐h blood glucose was higher in the laparoscopy group as compared with the open group. However, when DS was infused the difference between the 1‐h blood glucose in the open and laparoscopic procedures was not statistically significant. In the laparoscopy group, the 1‐h blood glucose value was significantly higher in the patients receiving dextrose solution.

Conclusion:  Laparoscopic procedures in children are associated with a rise in blood glucose levels similar to open surgery. The hyperglycaemic response was more pronounced when dextrose‐containing solutions were infused peri‐operatively.
Effect of 3 g of intravenous paracetamol on post‐operative analgesia, platelet function and liver enzymes in patients undergoing tonsillectomy under local anaesthesia
Authors: Silvanto M. , Munsterhjelm E. , Savolainen S. , Tiainen P. , Niemi T. , Ylikorkala O. , Scheinin H. , Olkkola K. T.
Published: August 2007

Background:  Paracetamol is often given as an adjunctive analgesic to reduce opioid‐related adverse effects but its optimal dose is unknown. We studied the analgesic effect and safety of a single 3‐g intravenous (i.v.) dose of paracetamol in adults.

Methods:  One hundred and seven patients undergoing tonsillectomy under local anaesthesia were randomly allocated to receive i.v. 3 g of paracetamol, 75 mg of diclofenac or placebo prior to surgery. The consumption of post‐operative morphine using a patient‐controlled analgesia‐device was quantified for 6 h. Platelet aggregation and the concentrations of paracetamol, liver aminotransferases, glutathione transferase alpha 1‐1 (GSTA1‐1) and thromboxane B2 were measured.

Results:  During the first hours after surgery, both paracetamol and diclofenac reduced (P < 0.05) the consumption of morphine but had no effect thereafter. The values for the 6‐h cumulative consumption of morphine in patients given paracetamol (18.7 ± 13.8 mg), diclofenac (16.1 ± 9.9 mg) and placebo (22.0 ± 12.1 mg) did not differ. Paracetamol had no effect on platelet aggregation, which was impaired only by diclofenac in response to arachidonic acid (P < 0.005). Both paracetamol (P < 0.01) and diclofenac (P < 0.005) inhibited the release of thromboxane B2 at 1 h but they did not affect serum aminotransferase and GSTA1‐1 levels. One patient given paracetamol displayed a transient increase in GSTA1‐1 and liver aminotransferases.

Conclusion:  During the initial hours after tonsillectomy, the administration of 3 g of i.v. paracetamol and 75 mg of diclofenac reduced the consumption of morphine. Both drugs also reduced the release of thromboxane B2 from activated platelets but only diclofenac had a negative effect on platelet aggregation. In sensitive individuals, large doses of paracetamol may disturb the hepatocellular integrity. We do not recommend the use of i.v. doses of paracetamol higher than 1 g.
Recombination diversifies chloroplast trnF pseudogenes in Arabidopsis lyrata
Authors: ANSELL S. W. , SCHNEIDER H. , PEDERSEN N. , GRUNDMANN M. , RUSSELL S. J. , VOGEL J. C.
Published: August 2007

Extensive intraspecific variation in the chloroplast trnL(UAA)–trnF(GAA) spacer of model plant Arabidopsis lyrata is caused by multiple copies of a tandemly repeated trnF pseudogene undergoing parallel independent changes in copy number. Linkage disequilibrium and secondary structure analyses indicate that the diversification of pseudogene copies is driven by complex processes of structurally mediated illegitimate recombination. Disperse repeats sharing similar secondary structures interact, facilitating reciprocal exchange of structural motifs between copies via intramolecular and intermolecular recombinations, forming chimeric sequences and iterative expansion and contraction in pseudogene copy numbers. Widely held assumptions that chloroplast sequence evolution is simple and structural changes are informative are violated. Our findings have important implications for the use of this highly variable region in Brassicaceae studies. The reticulate evolution and nonindependent nucleotide substitution render the pseudogene inappropriate for standard phylogenetic reconstruction, but over short evolutionary timescales they may be useful for assessing gene flow, hybridization and introgression.
Gene Expression of Secretory Carbonic Anhydrase Isozymes in Striated Ducts of Canine Salivary Glands Using Laser Microdissection System
Authors: Ichihara N. , Tsukamoto A. , Kasuya T. , Shibata S. , Nishita T. , Murakami M. , Amasaki H. , Asari M.
Published: August 2007

To clarify whether striated duct cells in canine salivary glands synthesize secretory carbonic anhydrase (CA‐VI), as is the case with serous acinar cells, the present study utilized laser microdissection to harvest striated duct cells from canine parotid and submandibular glands, and total RNA extracted from these cells was then amplified by reverse transcription‐polymerase chain reaction to assess CA‐VI gene expression. The results confirmed the local expression of CA‐VI mRNA in striated duct cells. This clarified that, in canine salivary glands, CA‐VI is synthesized in not only serous acinar cells, but also striated duct cells.
The Distribution of Taste Buds in Garra rufa
Authors: ÇInar K. , ŞEnol N. , Kuru N.
Published: August 2007

The distribution and relative frequency of external taste buds (TB) of Garra rufa were studied. TB of Garra rufa were observed on different body location (lips, lateral and ventral areas, forehead, operculum and dorsal–pelvic–pectoral–anal fins). TB are at the highest frequency in lips, forehead, pectoral and anal fins. These structures are moderate as a number in operculum, La2 (between pelvic and anal fins) areas, and then decreased a few in other areas.
Intended Receivers and Functional Significance of Grunt and Girney Vocalizations in Free‐Ranging Female Rhesus Macaques
Authors: Whitham Jessica C. , Gerald Melissa S. , Maestripieri Dario
Published: August 2007

We investigated the intended receivers and contexts of occurrence of grunt and girney vocalizations in rhesus macaques (Macaca mulatta) to assess whether these calls are best interpreted as signals of benign intent or as calls that may function to attract the attention of other individuals or induce arousal. We focally observed 19 free‐ranging adult female rhesus macaques. Female calls increased dramatically after infants were born, and most were directed toward mother–infant dyads. When infants were physically separated from their mothers, callers visually oriented toward infants in over 90% of the cases, suggesting that infants were the intended receivers of grunts and girneys. Approaches followed by vocalizations were more likely to lead to the caller grooming the mother, less likely to elicit a submissive response, and more likely to result in infant handling than approaches without calls. Infant handling, however, was not necessarily benign. Vocalizations were often emitted from a distance >1 m and were rarely followed by approaches or social interactions. Our results suggest that grunts and girneys are unlikely to have evolved as signals that encode information about the caller's intention or subsequent behavior. Whereas girneys may be acoustically designed to attract infants’ attention and elicit arousal, grunts may have no adaptive communicative function. Mothers, however, may have learned that other females’ grunts and girneys are unlikely to be associated with significant risk and, therefore, are generally tolerant of the caller's proximity and behavior.
Parental Effort in Relation to Structural Plumage Coloration in the Mountain Bluebird (Sialia currucoides)
Authors: Balenger Susan L. , Scott Johnson L. , Brubaker Jessica L. , Ostlind Emilene
Published: August 2007

Indicator models of sexual selection suggest that costly ornaments signal reliable information regarding an individual's quality to potential mates. In species that produce altricial offspring, the amount of parental care provided by both males and females can impact reproductive success. The Good Parent Hypothesis proposes that ornamentation in biparental species can act as an honest signal of parental ability to potential mates. We tested this hypothesis using the mountain bluebird (Sialia currucoides), a sexually dichromatic, socially monogamous species in which both sexes have structurally based ornamental plumage coloration. A male's plumage color predicted neither the rate at which it provisioned nestlings nor brood growth rate. The same was true for females. We also found no indication of assortative mating by color or body condition. Feeding rates within pairs were positively correlated, which we suggest may be due to pairs responding similarly to the perceived needs of nestlings or to local area prey availability. In sum, our results do not support the Good Parent Hypothesis as an explanation for the evolution of ornamental plumage color in mountain bluebirds. We suggest alternative hypotheses for the evolution of ornamental plumage color in this species.
Social Monitoring Reflects Dominance Relationships in a Small Captive Group of Brown Capuchin Monkeys (Cebus apella)
Authors: Pannozzo Pamela L. , Phillips Kimberley A. , Haas Meghan E. , Mintz Eric M.
Published: August 2007

In several studies of social monitoring in primates, subordinate animals directed more visual attention toward dominant animals than vice versa. This behavior is thought to enable subordinate animals to avoid conflict. We sought to clarify whether visual attention behavior functions in this manner in a small captive group of brown capuchin monkeys, Cebus apella. We tested the hypothesis that social monitoring is related to dominance status. Dominance status was determined based on the directionality of aggressive behavior, and visual attention was quantified by using focal animal sampling. Subordinate animals directed significantly more visual attention toward others than dominant animals. Subordinate animals also looked more frequently at the animals that attacked them and others the most. The results indicate that social monitoring behavior in this captive group was driven by conflict‐avoidance.
Male and Female Mate‐Choice Decisions byEvarcha culicivora, An East African Jumping Spider
Authors: Cross Fiona R. , Jackson Robert R. , Pollard Simon D.
Published: August 2007

There has been a considerable recent interest in the criteria by which animals choose mates and in the extent to which mating systems tend to be based on mutual mate choice. In this study, we considerEvarcha culicivora, a salticid spider from East Africa. This species has some unusual characteristics, including active display by females as well as males, males that kill females more frequently than females kill males and wide intrasexual variation in body size. For females, larger males are especially dangerous. Here, we demonstrate, using two experimental designs (live‐mate choice and mount choice), that virgin males, virgin females and previously mated males prefer larger opposite‐sex individuals as potential mates, but mated females prefer smaller, safer males as potential mates.
Geographic Variation in Male Sexual Signals in Strawberry Poison Frogs (Dendrobates pumilio)
Authors: Pröhl Heike , Hagemann Sabine , Karsch Jan , Höbel Gerlinde
Published: August 2007

In this paper, we compare the advertisement calls of 207 neotropical strawberry poison frogs (Dendrobates pumilio) collected in 21 localities along a transect from northern Costa Rica to western Panama. Populations varied most in call duration and call rate, while pulse rate and duty cycle were less variable. Multivariate analyses showed that call variation followed a cline with higher call rates, shorter calls, lower duty cycles and higher pulse rates in the southeast. Body size decreased towards the southeast and explained most variation in dominant frequency, as well as some residual variation in call rate. We conclude that a combination of geography and morphology is largely responsible for call variation within this species. Two inferred bio‐acoustic groups were roughly in accordance with two genetic groups, geographically separated in central Costa Rica. However, genetic distances among populations did not co‐vary with call dissimilarity after correction for geographic distances. Thus, differences in calls between genetic groups are probably mainly a result of clinal variation. These findings agree with the general observation that bio‐acoustic variation is often not (highly) associated with genetic divergence. Moreover, colour polymorphism observed among Panamanian populations was not reflected in a higher variability in call parameters relative to the monomorphic Costa Rican populations.
CHRONIC SUPPLEMENTATION OF CREATINE AND VITAMINS C AND E INCREASES SURVIVAL AND IMPROVES BIOCHEMICAL PARAMETERS AFTER DOXORUBICIN TREATMENT IN RATS
Authors: Santos Ronaldo VT , Batista Miguel L , Caperuto Érico C , Costa Rosa Luis FBP
Published: August 2007

Doxorubicin is an anti‐cancer drug with well‐described effects against a wide range of tumours. However, doxorubicin also exhibits dose‐dependent cytotoxicity. The purpose of the present study was to determine whether chronic supplementation of creatine or a mix of vitamins C and E could increase survival and improve plasma parameters 48 h after doxorubicin treatment.

Rats were divided into four groups: (i) saline (control); (ii) doxorubicin treated; (iii) a creatine (0.2 g/kg per day)‐supplemented group; and (iv) a vitamin C (250 mg/kg per day) and E (400 IU/kg per day)‐supplemented group. After 30 days supplementation of rats with either creatine or the vitamins, one dose of doxorubicin (15 mg/kg, i.p.) was administered.

There was no difference in weight loss among the groups until the 3rd day after doxorubicin treatment, but the creatine‐ and vitamin‐supplemented groups lived longer compared with the doxorubicin only treated group (6, 7 and 3 days, respectively). The doxorubicin‐treated group lost 13.4% bodyweight over 3 days, whereas the creatine‐ and vitamin‐supplemented groups lost approximately 35% 3 days after the administration of doxorubicin. Doxorubicin treatment resulted in an increase in alanine aminotransferase (ALT; P < 0.05), lactate dehydrogenase (LDH; P < 0.05), urea (P < 0.05) and creatinine (P < 0.05) compared with levels observed in the control group. Conversely, creatine supplementation promoted a partial return to control values for LDH (P < 0.05) and creatinine (P < 0.05), whereas the vitamin mix reversed the changes in ALT (P < 0.05), LDH (P < 0.05), urea (P < 0.05) and creatinine (P < 0.05).

In conclusion, the results of the present study indicate that the two supplementation protocols decreased the cytotoxic effects of doxorubicin and that a protective effect was more noticeable in animals supplemented with the mixture of vitamins C and E.
EFFECT OF THE HEME OXYGENASE INDUCER HEMIN ON BLOOD HAEMOSTASIS MEASURED BY HIGH‐FREQUENCY ULTRASOUND
Authors: Rochefort Gaël Y , Libgot Rachel , Desbuards Nicolas , Schlecht Deborah , Halimi Jean‐Michel , Ossant Frederic , Eder Veronique , Antier Daniel
Published: August 2007

Heme compounds, like hemin, a heme oxygenase‐1 inducer, are used in the treatment of acute porphyria treatment. The side‐effects of hemin on haemostasis have been reported. To address those effects, in the present study we used a sensitive, high‐frequency ultrasound technique to record acoustic velocity and to investigate whole blood clotting in Wistar rats treated chronically with hemin (50 mg/kg per day).

The hemin‐induced disturbances in haemostasis measured were comparable to the heparin reference treatment, with a significant decrease in clotting velocity in both groups compared with controls (e.g. the time to clot was 40 ± 5, 53 ± 13 and 10 ± 2 min, respectively; P < 0.05). Precautions must be taken when using high doses of hemin or in the treatment of bleeding diseases.

Further investigations are required to explore the effects of hemin in thrombosis models, because it could be a promising ‘old drug’ for the treatment of venous thrombosis in patients.
GLUTAMATE RECEPTOR PLASTICITY AT EXCITATORY SYNAPSES IN THE BRAIN
Authors: Genoux David , Montgomery Johanna M
Published: August 2007

Synapse plasticity, defined as an activity dependent change in the strength of synapses, was first described in 1973 and, since those seminal experiments were reported, the field of synapse plasticity has expanded into one of the most widely studied areas in neuroscience.

Significant effort has been focused on determining the expression mechanisms of the changes in synapse strength. The present review will focus on the changes in the post‐synaptic expression of glutamate receptors that have been shown to occur during the expression of synapse plasticity.

Biochemical studies of excitatory synapses in the central nervous system have revealed a high density of proteins concentrated at dendritic spines. These proteins appear to play critical roles in synaptic structure, plasticity and in trafficking receptors to synapses.

There is growing evidence that synapse plasticity could be the cellular basis of certain forms of learning and memory. Determining the behavioural correlates of this fundamental synaptic process will continue to be addressed in current and future research.
DOES SPIKE TIMING‐DEPENDENT SYNAPTIC PLASTICITY UNDERLIE MEMORY FORMATION?
Authors: Letzkus Johannes J , Kampa Björn M , Stuart Greg J
Published: August 2007

Synaptic plasticity is thought to underlie learning and memory formation in the brain. However, how synaptic plasticity is induced during these processes remains controversial. An attractive candidate mechanism for learning at the neuronal level is spike timing‐dependent synaptic plasticity (STDP), which depends on the precise (msec) timing of the synaptic input and the post‐synaptic action potential. This temporal relationship resembles typical features of associative learning. Here, we review recent evidence suggesting that STDP is likely to underlie certain forms of learning.

First, we discuss the cellular mechanisms of STDP elucidated by in vitro experiments. A special focus is put onto aspects known to differ between in vitro preparations and the in vivo situation.

Second, we review the experimental induction of STDP in vivo, in various systems ranging from Xenopus tectum to human motor cortex.

The last part of the review addresses the question whether STDP can be induced by activity patterns occurring during normal behaviour.

We conclude that STDP is a robust phenomenon in vivo and a likely mechanism underlying sensory map plasticity in the neocortex. Further experimental evidence is required to determine whether STDP also has a role in more complex forms of learning.
INTRACELLULAR CALCIUM IN THE FERTILIZATION AND DEVELOPMENT OF MAMMALIAN EGGS
Authors: Jones Keith T
Published: August 2007

Mammalian eggs are arrested at metaphase of their second meiotic division when ovulated and remain arrested until fertilized. The sperm delivers into the egg phospholipase C (PLC) ζ, which triggers a series of Ca2+ spikes lasting several hours. The Ca2+ spikes provide the necessary and sufficient trigger for all the events of fertilization, including exit from metaphase II arrest and extrusion of cortical granules that block the entry of other sperm.

The oscillatory Ca2+ signal switches on calmodulin‐dependent protein kinase II (CaMKII), which phosphorylates the egg‐specific protein Emi2, earmarking it for degradation. To remain metaphase II arrested, eggs must maintain high levels of maturation‐promoting factor (MPF) activity, a heterodimer of CDK1 and cyclin B1. Emi2 prevents loss of MPF by blocking cyclin B1 degradation, a process that is achieved by inhibiting the activity of the anaphase‐promoting complex/cyclosome. However, CaMKII is not the primary initiator in the extrusion of cortical granules.

Ca2+ spiking is also observed in mitosis of one‐cell embryos, probably because PLCζ contains a nuclear localization signal and so is released into the cytoplasm following nuclear envelope breakdown. The function of these mitotic Ca2+ spikes remains obscure, although they are not absolutely required for passage through mitosis.

Intriguingly, the pattern of Ca2+ spikes observed at fertilization has an effect on both pre‐ and postimplantation development in a manner that is independent of their ability to activate eggs. This suggests that the Ca2+ spikes set in train at fertilization are having effects on processes initiated in the newly fertilized egg but whose influences are only observed several cell divisions later. The nature of the signals remains little explored, but their importance is clear and so warrants further investigation.
COMBUSTION‐DERIVED NANOPARTICLES: MECHANISMS OF PULMONARY TOXICITY
Authors: BéruBé Kelly , Balharry Dominique , Sexton Keith , Koshy Lata , Jones Tim
Published: August 2007

The general term ‘nanoparticle’ (NP) is used to define any particle less than 100 nm in at least one dimension and NPs are generally classified as natural, anthropogenic or engineered in origin. Anthropogenic, also referred to as ‘ultrafine’ particles (UFPs), are predominately combustion derived and are characterized by having an equivalent spherical diameter less than 100 nm.

These particles, considered to be ‘combustion‐derived nanoparticles’ (CDNPs), are of toxicological interest given their nanosized dimensions, with properties not displayed by their macroscopic counterparts.

The pulmonary deposition efficiency of inhaled UFPs, along with their large surface areas and bound transition metals, is considered important in driving the emerging health effects linked to respiratory toxicity.

The toxicology of CDNPs is currently used to predict the health outcomes in humans following exposure to manufactured NPs. Their similar physicochemistry would suggest similar adverse health effects (i.e. pulmonary (and perhaps cardiac) toxicity). As such, it is essential to fully understand CDNP nanotoxicology in order to minimize occupational and environmental exposure.
POTENTIATION OF 3,4‐METHYLENEDIOXYMETHAMPHETAMINE‐INDUCED 5‐HT RELEASE IN THE RAT SUBSTANTIA NIGRA BY CLORGYLINE, A MONOAMINE OXIDASE A INHIBITOR
Authors: Hewton Ryan , Salem Abdallah , Irvine Rodney J
Published: August 2007

It is well established that the commonly used recreational drugs 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) and para‐methoxyamphetamine (PMA) facilitate the release and prevent the reuptake of 5‐hydroxytryptamine (5‐HT, serotonin). Although these drugs have similar potencies for their abilities to increase the release and inhibit the re‐uptake of 5‐HT, PMA has greater potency as an inhibitor of monoamine oxidase (MAO)‐A.

The present study compared the abilities of PMA and MDMA to increase extracellular 5‐HT concentrations in animals with functional MAO‐A and when MAO‐A activity was inhibited by clorgyline.

Samples of extracellular fluid from rat substantia nigra were collected using microdialysis and then analysed for 5‐HT and 5‐hydroxyindol acetic acid (5‐HIAA) by high‐performance liquid chromatography coupled with electrochemical detection. The 5‐HT‐mediated effects on body temperature and behaviour were also recorded. Rats were pretreated with saline or 10 mg/kg, i.p., clorgyline and, 24 h later, injected with 10 mg/kg MDMA, PMA or saline.

Both MDMA and PMA produced significant increases in extracellular 5‐HT concentrations (482 ± 83 and 726 ± 287%, respectively; P < 0.05). Rats treated with PMA and MDMA displayed significantly increased 5‐HT‐related behavours (P < 0.05). Furthermore, only MDMA was capable of producing additional significant increases in 5‐HT concentrations (1033 ± 131%; P < 0.01) when coadministered with clorgyline.

The results of the present study suggest that PMA and MDMA are similar in their abilities to increase extracellular 5‐HT levels in animals with functional MAO‐A activity. However, coadministration of these substituted amphetamines with an MAO‐A inhibitor causes significant potentiation in the ability to increase extracellular levels of 5‐HT for MDMA, but not PMA.