bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic treatment with glucocorticoids alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels
Authors: Zhu Meng‐Yang , Wang Wei‐Ping , Huang Jingjing , Regunathan Soundar 
Published: September 2007

AbstractIn the present study, we examined the possible effect of chronic treatment with glucocorticoids on the morphology of the rat brain and levels of endogenous agmatine and arginine decarboxylase (ADC) protein, the enzyme essential for agmatine synthesis. Seven‐day treatment with dexamethasone, at a dose (10 and 50 μg/kg/day) associated to stress effects contributed by glucocorticoids, did not result in obvious morphologic changes in the medial prefrontal cortex and hippocampus, as measured by immunocytochemical staining with β‐tubulin III. However, 21‐day treatment (50 μg/kg/day) produced noticeable structural changes such as the diminution and disarrangement of dendrites and neurons in these areas. Simultaneous treatment with agmatine (50 mg/kg/day) prevented these morphological changes. Further measurement with HPLC showed that endogenous agmatine levels in the prefrontal cortex and hippocampus were significantly increased after 7‐day treatments with dexamethasone in a dose‐dependent manner. On the contrary, 21‐day treatment with glucocorticoids robustly reduced agmatine levels in these regions. The treatment‐caused biphasic alterations of endogenous agmatine levels were also seen in the striatum and hypothalamus. Interestingly, treatment with glucocorticoids resulted in a similar change of ADC protein levels in most brain areas to endogenous agmatine levels: an increase after 7‐day treatment versus a reduction after 21‐day treatment. These results demonstrated that agmatine has neuroprotective effects against structural alterations caused by glucocorticoids in vivo. The parallel alterations in the endogenous agmatine levels and ADC expression in the brain after treatment with glucocorticoids indicate the possible regulatory effect of these stress hormones on the synthesis and metabolism of agmatine in vivo.
Calcium channel subtypes differentially regulate fusion pore stability and expansion
Authors: Ardiles Alvaro O. , González‐Jamett Arlek M , Maripillán Jaime , Naranjo David , Caviedes Pablo , Cárdenas Ana María 
Published: September 2007

AbstractVarious studies have focused in the relative contribution of different voltage‐activated Ca2+ channels (VACC) to total transmitter release. However, how Ca2+ entry through a given VACC subtype defines the pattern of individual exocytotic events remains unknown. To address this question, we have used amperometry in bovine chromaffin cells. L, N, and P/Q channels were individually or jointly blocked with furnidipine, ω‐conotoxin GVIA, ω‐agatoxin IVA, or ω‐conotoxin MVIIC. The three channel types contributed similarly to cytosolic Ca2+ signals induced by 70 mmol/L K+. However, they exhibited different contributions to the frequency of exocytotic events and they were shown to differently regulate the final steps of the exocytosis. When compared with the other VACC subtypes, Ca2+ entry through P/Q channels effectively induced exocytosis, it decreased fusion pore stability and accelerated its expansion. Conversely, Ca2+ entry through N channels was less efficient in inducing exocytotic events, also slowing fusion pore expansion. Finally, Ca2+ entry through L channels inefficiently induced exocytosis, and the individual blockade of this channel significantly modified fusion pore dynamics. The distance between a given VACC subtype and the release sites could account for the differential effects of the distinct VACC on the fusion pore dynamics.
Prolyl hydroxylase inhibitors delay neuronal cell death caused by trophic factor deprivation
Authors: Lomb David J. , Straub Jennifer A. , Freeman Robert S. 
Published: September 2007

AbstractNerve growth factor (NGF) serves a critical survival‐promoting function for developing sympathetic neurons. Following removal of NGF, sympathetic neurons undergo apoptosis characterized by the activation of c‐Jun N‐terminal kinases (JNKs), up‐regulation of BH3‐only proteins including BcL‐2‐interacting mediator of cell death (BIM)EL, release of cytochromecfrom mitochondria, and activation of caspases. Here we show that two small‐molecule prolyl hydroxylase inhibitors frequently used to activate hypoxia‐inducible factor (HIF) – ethyl 3,4‐dihydroxybenzoic acid (DHB) and dimethyloxalylglycine (DMOG) – can inhibit apoptosis caused by trophic factor deprivation. Both DHB and DMOG blocked the release of cytochromecfrom mitochondria after NGF withdrawal, whereas only DHB blocked c‐Jun up‐regulation and phosphorylation. DHB, but not DMOG, also attenuated the induction of BIMELin NGF‐deprived neurons, suggesting a possible mechanism whereby DHB could inhibit cytochromecrelease. DMOG, on the other hand, was substantially more effective at stabilizing HIF‐2α and inducing expression of the HIF target genehexokinase 2than was DHB. Thus, while HIF prolyl hydroxylase inhibitors can delay cell death in NGF‐deprived neurons, they do so through distinct mechanisms that, at least in the case of DHB, are partly independent of HIF stabilization.
Developmental mercury exposure elicits acute hippocampal cell death, reductions in neurogenesis, and severe learning deficits during puberty
Authors: Falluel‐Morel Anthony , Sokolowski Katie , Sisti Helene M. , Zhou Xiaofeng , Shors Tracey J. , DiCicco‐Bloom Emanuel 
Published: September 2007

AbstractNormal brain development requires coordinated regulation of several processes including proliferation, differentiation, and cell death. Multiple factors from endogenous and exogenous sources interact to elicit positive as well as negative regulation of these processes. In particular, the perinatal rat brain is highly vulnerable to specific developmental insults that produce later cognitive abnormalities. We used this model to examine the developmental effects of an exogenous factor of great concern, methylmercury (MeHg). Seven‐day‐old rats received a single injection of MeHg (5 μg/gbw). MeHg inhibited DNA synthesis by 44% and reduced levels of cyclins D1, D3, and E at 24 h in the hippocampus, but not the cerebellum. Toxicity was associated acutely with caspase‐dependent programmed cell death. MeHg exposure led to reductions in hippocampal size (21%) and cell numbers 2 weeks later, especially in the granule cell layer (16%) and hilus (50%) of the dentate gyrus defined stereologically, suggesting that neurons might be particularly vulnerable. Consistent with this, perinatal exposure led to profound deficits in juvenile hippocampal‐dependent learning during training on a spatial navigation task. In aggregate, these studies indicate that exposure to one dose of MeHg during the perinatal period acutely induces apoptotic cell death, which results in later deficits in hippocampal structure and function.
Necrostatin‐1 protects against glutamate‐induced glutathione depletion and caspase‐independent cell death in HT‐22 cells
Authors: Xu Xingshun , Chua Chu C. , Kong Jiming , Kostrzewa Richard M. , Kumaraguru Udayasankar , Hamdy Ronald C. , Chua Balvin H. L. 
Published: September 2007

AbstractGlutamate, a major excitatory neurotransmitter in the CNS, plays a critical role in neurological disorders such as stroke and Parkinson’s disease. Recent studies have suggested that glutamate excess can result in a form of cell death called glutamate‐induced oxytosis. In this study, we explore the protective effects of necrostatin‐1 (Nec‐1), an inhibitor of necroptosis, on glutamate‐induced oxytosis. We show that Nec‐1 inhibits glutamate‐induced oxytosis in HT‐22 cells through a mechanism that involves an increase in cellular glutathione (GSH) levels as well as a reduction in reactive oxygen species production. However, Nec‐1 had no protective effect on free radical‐induced cell death caused by hydrogen peroxide or menadione, which suggests that Nec‐1 has no antioxidant effects. Interestingly, the protective effect of Nec‐1 was still observed when cellular GSH was depleted by buthionine sulfoximine, a specific and irreversible inhibitor of glutamylcysteine synthetase. Our study further demonstrates that Nec‐1 significantly blocks the nuclear translocation of apoptosis‐inducing factor (a marker of caspase‐independent programmed cell death)and inhibits the integration of Bcl‐2/adenovirus E1B 19 kDa‐interacting protein 3 (a pro‐death member of the Bcl‐2 family) into the mitochondrial membrane. Taken together, these results demonstrate for the first time that Nec‐1 prevents glutamate‐induced oxytosis in HT‐22 cells through GSH related as well as apoptosis‐inducing factor and Bcl‐2/adenovirus E1B 19 kDa‐interacting protein 3‐related pathways.
PERMANENT GENETIC RESOURCES: Isolation and characterization of microsatellite loci in the Mediterranean shore crab Carcinus aestuarii (Decapoda, Portunidae)
Authors: MARINO ILARIA A. M. , BARBISAN FEDERICA , GENNARI MICOL , BISOL PAOLO MARIA , ZANE LORENZO 
Published: September 2007

AbstractWe characterized nine polymorphic microsatellites in the Mediterranean shore crab Carcinus aestuarii (Decapoda: Portunidae). Microsatellites were isolated from a partial genomic library enriched for multiple motifs. All loci were polymorphic, with number of alleles ranging from two to 16 and a mean observed heterozygosity of 0.75. Seven loci were in Hardy–Weinberg equilibrium, and two showed weak heterozygote deficiency. No linkage disequilibrium was found between loci. In addition, we tested Hardy–Weinberg and linkage equilibrium of three Carcinus maenas loci, already reported to cross‐amplify in C. aestuarii. These molecular markers will be potentially useful to investigate genetic structure of this species.
Respiratory modulation of cardiovascular rhythms before and after short‐duration human spaceflight
Authors: Verheyden B. , Beckers F. , Couckuyt K. , Liu J. , Aubert A. E. 
Published: September 2007

AbstractAim:  Astronauts commonly return from space with altered short‐term cardiovascular dynamics and blunted baroreflex sensitivity. Although many studies have addressed this issue, post‐flight effects on the dynamic circulatory control remain incompletely understood. It is not clear how long the cardiovascular system needs to recover from spaceflight as most post‐flight investigations only extended between a few days and 2 weeks.Methods:  In this study, we examined the effect of short‐duration spaceflight (1–2 weeks) on respiratory‐mediated cardiovascular rhythms in five cosmonauts. Two paced‐breathing protocols at 6 and 12 breaths min−1 were performed in the standing and supine positions before spaceflight, and after 1 and 25 days upon return. Dynamic baroreflex function was evaluated by transfer function analysis between systolic pressure and the RR intervals.Results:  Post‐flight orthostatic blood pressure control was preserved in all cosmonauts. In the standing position after spaceflight there was an increase in heart rate (HR) of approx. 20 beats min−1 or more. Averaged for all five cosmonauts, respiratory sinus dysrhythmia and transfer gain reduced to 40% the day after landing, and had returned to pre‐flight levels after 25 days. Low‐frequency gain decreased from 6.6 (3.4) [mean (SD)] pre‐flight to 3.9 (1.6) post‐flight and returned to 5.7 (1.3) ms mmHg−1 after 25 days upon return to Earth. Unlike alterations in the modulation of HR, blood pressure dynamics were not significantly different between pre‐ and post‐flight sessions.Conclusion:  Our results indicate that short‐duration spaceflight reduces respiratory modulation of HR and decreases cardiac baroreflex gain without affecting post‐flight arterial blood pressure dynamics. Altered respiratory modulation of human autonomic rhythms does not persist until 25 days upon return to Earth.
PROTEIN COMPLEX PREDICTION USING AN INTEGRATIVE BIOINFORMATICS APPROACH
Authors: VAN BERLO ROGIER J. P. , WESSELS LODEWYK F. A. , DE RIDDER DICK , REINDERS MARCEL J. T. 
Published: September 2007

Since protein complexes play a crucial role in biological cells, one of the major goals in bioinformatics is the elucidation of protein complexes. A general approach is to build a prediction rule based on multiple data sources, e.g. gene expression data and protein interaction data, to assess the likelihood of two proteins having complex association.a We critically revisit the step of predictor construction, i.e. the determination of a proper training set, an optimal classifier, and, most importantly, an optimal feature set. We use an exhaustive set of features, which includes the 2hop-feature as introduced by Wong et al.23 for predicting synthetic sick or lethal interactions. Post-processing of the likelihoods of protein interaction is then required to extract protein complexes. We propose a new protocol for combining these likelihood estimates. The protocol interprets the probabilities of complex association as output by the prediction rule as distances and employs hierarchical clustering to find groups of interacting proteins. In contrast to the computationally expensive search-and-score approach of Sharan et al.,19 this protocol is very fast and can be applied to fully connected graphs. The protocol identifies trusted protein complexes with high confidence. We show that the 2hop-feature is relevant for predicting protein complexes. Furthermore, several interesting hypotheses about new protein complexes have been generated. For example, our approach linked the protein FYV4 to the mitochondrial ribosomal subunit. Interestingly, it is known that this protein is located in the mitochondrion, but its biological role is unknown. Vid22 and YGR071C were also linked, which corresponds to the new TAP data of Krogan et al.14
Using T3, an Improved Decision Tree Classifier, for Mining Stroke-related Medical Data
Authors: Saraee M. , Theodoulidis B. , Keane J. A. , Tjortjis C. 
Published: September 2007

Summary

Objectives:
Medical data are a valuable resource from which novel and potentially useful knowledge can be discovered by using data mining. Data mining can assist and support medical decision making and enhance clinical managementand investigative research. The objective of this work is to propose a method for building accurate descriptive and predictive models based on classification of past medical data. We also aim to compare this method with other well established data mining methods and identify strengths and weaknesses.

Method:
We propose T3, a decision tree classifier which builds predictive models based on known classes, by allowing for a certain amount of misclassification error in training in order to achieve better descriptive and predictive accuracy. We then experiment with a real medical data set on stroke, and various subsets, in order to identify strengths and weaknesses. We also compare performance with a very successful and well established decision tree classifier.

Results:
T3 demonstrated impressive performance when predicting unseen cases of stroke resulting in as little as 0.4% classification error while the state of the art decision tree classifier resulted in 33.6% classification error respectively.

Conclusions:
This paper presents and evaluates T3, a classification algorithm that builds decision trees of depth at most three, and results in high accuracy whilst keeping the tree size reasonably small. T3 demonstrates strong descriptive and predictive power without compromising simplicity and clarity. We evaluate T3 based on real stroke register data and compare it with C4.5, a well-known classification algorithm, showing that T3 produces significantly more accurate and readable classifiers.
Comparing Properties of Audit Data and Routinely Collected Register Data in Case of Performance Assessment of Hip Fracture Treatment in Finland
Authors: Nurmi-Lüthje I. , Lüthje P. , Tanninen S. , Narinen A. , Keskimäki I. , Sund R. 
Published: September 2007

Summary

Objectives:
To compare prospective audit data and secondary administrative register data in the production of performance assessment information in the case of hip fracture treatment, and to cross-validate the quality of information.

Methods:
First, a conceptual model for the performance assessment of hip fracture treatment was defined. This model was then utilized in comparisons between the prospective audit data concerning 106 consecutive hip fracture patients from the Kuusankoski Regional Hospital and corresponding register data from the Finnish Health Care Register and the Causes of Death Register. We examined the completeness of registration of patients and also the accuracy and degree of completeness of the registered data. Observed differences were checked against the medical records.

Results:
Register data lack clinical detail, but outperform prospective data in the recording of inpatient care history. Completeness of the register data is very good. The accuracy of easily measurable variables in the register is at least 95%. The agreement between register and audit data was 86.3% for detailed hip fracture diagnosis. Polyserial correlation between the functional dependency variables was 0.68.

Conclusions:
Register and audit data have certain limitations and problems, but both seem to be suitable for the performance assessment of hip fracture treatment. To improve the feasibilityof the administrative register data, the voluntary input of additional hip fracture event data to the register should be made possible. Standardized instructions that guide the use of available register classifications in a sensible way would improvethe quality of data.
A Study of Trained Clinicians’ Blood Glucose Predictions Based on Diaries of People with Type 1 Diabetes
Authors: Randløv J. , Poulsen J. U. , Hejlesen O. , Kildegaard J. 
Published: September 2007

Summary

Objectives:
How accurate can trained clinicians predict blood glucose concentrations? Good clinical treatment is, among other things, related to understanding the factors influencing blood glucose level. We analyze trained clinician’s prediction accuracy in comparison with selected computer-implemented prediction algorithms and models.

Methods:
We have in this study included diaries of 12 people with type 1 diabetes. This test group consists of seven males and five females, ages 24 to 60, HbA1c 6.0 to 8.9 and a BMI between 20 and 28 kg/m2. Eight experienced clinicians tried to predict the blood glucose measurements based on minimum three days of diary history. Selected prediction algorithms and models were used for comparison. The reason we focus on type 1 diabetes is that it has the most critical insulin requirement, so accurate prediction can be more critical than for type 2.

Results:
An accuracy of 28.5% and an error of 26.7% were found from predictions made by the clinicians. A physiological model and an artificial intelligence model showed higher accuracy of 32.2% and 34.2% in comparison with the clinicians (p < 0.05). A simple predictor algorithm based on the mean blood glucose history showed significant (p < 0.05) lower total root mean square error compared to predictions made by the clinicians.

Conclusion:
To predict blood glucose level from diaries has shown to be profoundly difficult even for experienced clinicians in comparison with predictions from computer algorithms and models. This suggests that computer-based systems incorporating predicting algorithms and models are likely to contribute positively to the day-to-day treatment of people with diabetes.
Analysis of Differences in Proportions from Clustered Data with Multiple Measurements in Diagnostic Studies
Authors: Busse R. , Schwenke C. 
Published: September 2007

Summary

Objectives:
In diagnostic studies, proportions such as sensitivities are often to be calculated and to be compared between different diagnostic procedures. As statistical unit of analysis, multiple observational units may be assessed within each patient, i.e., multiple lesions in an organ. As a requirement, these are to be assessed by multiple blinded readers. In this paper we propose a method to cover correlations between units within patients, correlations between procedures and correlations between different raters assessing each observational unit.

Methods:
The proposed approach is a two-step method to analyze clustered data with multiple measurements to compare diagnostic procedures in a paired modality design and the correlation between the readers in a paired reader design. The performance of the approach was compared to a generalized estimation equations model (GEEs) by power simulations.

Results:
Power simulations suggest, that the two-step approach is not inferior to GEEs with regard to the single readers as well as with regard to the average reader.

Conclusions:
An intuitive approach was developed next to established methods to analyze “paired modality, paired reader” and “unpaired modality, paired reader” studies with binary endpoints when estimating proportions and differences in proportions for clustered data with multiple measurements. This two-step approach is an alternative method to cover routine designs of diagnostic studies where the difference of proportions is to be estimated directly along with confidence intervals.
Right Ventricular Assistance by Continuous Flow Device
Authors: Ferrari G. , Lazzari C. De 
Published: September 2007

Summary

Objectives·.
This work is another step in the development of the circulatory model CARDIOSIM® and of its model library. Continuous flow assistance is often used to support the right ventricular failure. Computer simulation is one of the methods to study the effect of this assistance on the failing ventricle. The purpose of this study was to evaluate the effect of this support on some hemodynamic variables, when different right ventricular end-systolic elastance and pump speed values were applied.

Methods:
The rotary blood pump model was included into the software package CARDIOSIM®, which reproduces the cardiovascular system. Lumped parameters models were used to reproduce the circulatory phenomena. Variable elastance models reproduced the Starling’s law of the heartfor both ventricles. In the study right ventricular end-systolic elastance (EmaxraT) and the rotational speed of the pumptookthree different values. All the other parameters of the model were constants.

Results:
The rotational speed of the pump had a significant influence on right ventricular end-diastolic and end-systolic volumes, right atrial pressure (Pra), right ventricular (Qro) and pump flows. The effects on pulmonary arterial pressure (Pap) were more evident when the right ventricular end-systolic elastance was low. When the speed of the device increased the mean value of Pra decreased for each value of EmaxMT. The total flow (Qro + pump flow) increased when the speed of the pump increased.

Conclusions:
Our simulation (in good agreement with the results presented in literature) showed that Hemo-pump produces a rise in total flow, a drop in blood flow pumped out by the right ventricle and a drop in right atrial pressure.