bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annotation of novel neuropeptide precursors in the migratory locust based on transcript screening of a public EST database and mass spectrometry
Authors: Clynen Elke , Huybrechts Jurgen , Verleyen Peter , De Loof Arnold , Schoofs Liliane 
Published: August 2006

Abstract

Background
For holometabolous insects there has been an explosion of proteomic and peptidomic information thanks to large genome sequencing projects. Heterometabolous insects, although comprising many important species, have been far less studied. The migratory locust Locusta migratoria, a heterometabolous insect, is one of the most infamous agricultural pests. They undergo a well-known and profound phase transition from the relatively harmless solitary form to a ferocious gregarious form. The underlying regulatory mechanisms of this phase transition are not fully understood, but it is undoubtedly that neuropeptides are involved. However, neuropeptide research in locusts is hampered by the absence of genomic information.

Results
Recently, EST (Expressed Sequence Tag) databases from Locusta migratoria were constructed. Using bioinformatical tools, we searched these EST databases specifically for neuropeptide precursors. Based on known locust neuropeptide sequences, we confirmed the sequence of several previously identified neuropeptide precursors (i.e. pacifastin-related peptides), which consolidated our method. In addition, we found two novel neuroparsin precursors and annotated the hitherto unknown tachykinin precursor. Besides one of the known tachykinin peptides, this EST contained an additional tachykinin-like sequence. Using neuropeptide precursors from Drosophila melanogaster as a query, we succeeded in annotating the Locusta neuropeptide F, allatostatin-C and ecdysis-triggering hormone precursor, which until now had not been identified in locusts or in any other heterometabolous insect. For the tachykinin precursor, the ecdysis-triggering hormone precursor and the allatostatin-C precursor, translation of the predicted neuropeptides in neural tissues was confirmed with mass spectrometric techniques.

Conclusion
In this study we describe the annotation of 6 novel neuropeptide precursors and the neuropeptides they encode from the migratory locust, Locusta migratoria. By combining the manual annotation of neuropeptides with experimental evidence provided by mass spectrometry, we demonstrate that the genes are not only transcribed but also translated into precursor proteins. In addition, we show which neuropeptides are cleaved from these precursor proteins and how they are post-translationally modified.
Comparison of different methods in analyzing short-term air pollution effects in a cohort study of susceptible individuals
Authors: Peters Annette , von Klot Stephanie , Berglind Niklas , Hörmann Allmut , Löwel Hannelore , Nyberg Fredrik , Pekkanen Juha , Perucci Carlo A , Stafoggia Massimo , Sunyer Jordi , Tiittanen Pekka , Forastiere Francesco 
Published: August 2006

Abstract
Background
Short-term fluctuations of ambient air pollution have been associated with exacerbation of cardiovascular disease. A multi-city study was designed to assess the probability of recurrent hospitalization in a cohort of incident myocardial infarction survivors in five European cities. The objective of this paper is to discuss the methods for analyzing short-term health effects in a cohort study based on a case-series.

Methods
Three methods were considered for the analyses of the cohort data: Poisson regression approach, case-crossover analyses and extended Cox regression analyses. The major challenge of these analyses is to appropriately consider changes within the cohort over time due to changes in the underlying risk following a myocardial infarction, slow time trends in risk factors within the population, dynamic cohort size and seasonal variation.

Results
Poisson regression analyses, case-crossover analyses and Extended Cox regression analyses gave similar results. Application of smoothing methods showed the capability to adequately model the complex time trends.

Conclusion
From a practical point of view, Poisson regression analyses are less time-consuming, and therefore might be used for confounder selection and most of the analyses. However, replication of the results with Cox models is desirable to assure that the results are independent of the analytical approach used. In addition, extended Cox regression analyses would allow a joint estimation of long-term and short-term health effects of time-varying exposures.
HLA-DR expression on monocytes and systemic inflammation in patients with ruptured abdominal aortic aneurysms
Authors: Haveman Jan Willem , van den Berg Aad P , Verhoeven Eric LG , Nijsten Maarten WN , van den Dungen Jan JAM , The Hauw T , Zwaveling Jan Harm 
Published: August 2006

Abstract
Introduction
Mortality from ruptured abdominal aortic aneurysms (RAAA) remains high. Severe systemic inflammation, leading to multi-organ failure, often occurs in these patients. In this study we describe the level of HLA-DR expression in a consecutive group of patients following surgery for RAAA and compare results between survivors and non-survivors. A similar comparison is made for IL-6 and IL-10 levels and Sequential Organ Failure Assessment (SOFA) scores.

Methods
This is a prospective observational study. Patients with RAAA were prospectively analysed. Blood samples were collected on days 1, 3, 5, 7, 10 and 14. The fraction of CD-14 positive monocytes expressing HLA-DR was measured by flow-cytometry. IL-6 and IL-10 levels were measured by ELISA.

Results
The study included 30 patients with a median age of 70 years, of which 27 (90%) were men. Six patients died from multiple organ failure, all other patients survived. The SOFA scores were significantly higher in non-survivors on days 1 through 14. HLA-DR expression on monocytes was significantly lower on days 3, 5, 7, 10 and 14 in non-survivors. IL-6 and IL-10 levels were significantly higher in non-survivors on day 1 and days 1 and 3, respectively.

Conclusion
HLA-DR expression on monocytes was decreased, especially in non-survivors. All patients with RAAA displayed a severe inflammatory and anti-inflammatory response with an increased production of IL-6 and IL-10. Poor outcome is associated with high levels of IL-6 and IL-10 and a high SOFA score in the first three days after surgery, while low levels of HLA-DR expression are observed from day three after RAAA repair.
Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer
Authors: Hess Kenneth R. , Anderson Keith , Symmans W. Fraser , Valero Vicente , Ibrahim Nuhad , Mejia Jaime A. , Booser Daniel , Theriault Richard L. , Buzdar Aman U. , Dempsey Peter J. , Rouzier Roman , Sneige Nour , Ross Jeffrey S. , Vidaurre Tatiana , Gómez Henry L. , Hortobagyi Gabriel N. , Pusztai Lajos 
Published: August 2006

Purpose We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases. Patients and Methods One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with oligonecleotide microarrays on fine-needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases. Results Overall pCR rate was 26% in both cohorts. In the training set, 56 probes were identified as differentially expressed between pCR versus residual disease, at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes + prediction algorithm) in full cross-validation. Many predictors performed equally well. A nominally best 30-probe set Diagonal Linear Discriminant Analysis classifier was selected for independent validation. It showed significantly higher sensitivity (92% v 61%) than a clinical predictor including age, grade, and estrogen receptor status. The negative predictive value (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but not statistically significant. The combination of genomic and clinical information yielded a predictor not significantly different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant. Conclusion A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).
Lactate Dehydrogenase 5 Expression in Operable Colorectal Cancer: Strong Association With Survival and Activated Vascular Endothelial Growth Factor Pathway—A Report of the Tumour Angiogenesis Research Group
Authors: Koukourakis Michael I. , Giatromanolaki Alexandra , Sivridis Efthimios , Gatter Kevin C. , Harris Adrian L. 
Published: August 2006

Purpose Lactate dehydrogenase 5 (LDH-5) regulates, under hypoxic conditions, the anaerobic transformation of pyruvate to lactate for energy acquisition. Several studies have shown that serum LDH may be an ominous prognostic marker in malignant tumors. The clinical significance of tissue LDH-5, however, remains largely unexplored. Patients and Methods We investigated the immunohistochemical expression of LDH-5 in a series of 128 stage II/III colorectal adenocarcinomas treated with surgery alone. In addition, markers of tumor hypoxia (hypoxia-inducible factor 1 alpha [HIF1α]), angiogenesis (vascular endothelial growth factor [VEGF] and phosporylated kinase domain receptor [pKDR]/flk-1 receptor) and the tumor vascular density (CD31 positive standard vascular density [sVD] and pKDR positive activated vascular density [aVD]) were assessed. Results The expression of LDH-5, together with that of HIF1α and pKDR, was both nuclear and cytoplasmic. Assessment, with minimal interobserver variability, was achieved using a previously described scoring system. LDH-5 was significantly associated with HIF1α (P = .01), aVD (P = .001) and, particularly, with pKDR expression in cancer cells (P = .0001). Tissue LDH-5 expression was linked with elevated serum LDH levels, but serum levels failed to reflect tissue expression in 71% of LDH-5 positive cases. In univariate analysis tissue LDH-5 was associated with poor survival (P = .0003, HR 15.1), whereas in multivariate analysis this isoenzyme was the strongest independent prognostic factor (P = .0009). VEGF, pKDR, aVD, sVD and vascular invasion were all significantly related to unfavorable prognosis. Conclusion The immunohistochemical assessment of tissue LDH-5 and pKDR provides important prognostic information in operable colorectal cancer. The strong association between LDH-5 and pKDR expression would justify their use as surrogate markers to screen patients for tyrosin kinase inhibitor therapy.
The Impact of Glucocorticoid Replacement Regimens on Metabolic Outcome and Comorbidity in Hypopituitary Patients
Authors: Filipsson Helena , Monson John P. , Koltowska-Häggström Maria , Mattsson Anders , Johannsson Gudmundur 
Published: August 2006

Abstract
Background: Hypopituitary patients with untreated GH deficiency and patients on inappropriately high doses of glucocorticoid (GC) share certain clinical features.
Objective: The aim of the study was to examine the influence of GC substitution on clinical characteristics in hypopituitary patients before and after GH replacement therapy.
Method: A total of 2424 hypopituitary patients within the KIMS (Pfizer International Metabolic Database) were grouped according to ACTH status. Comparisons were performed between subjects on hydrocortisone (HC) (n = 1186), cortisone acetate (CA) (n = 487), and prednisolone/dexamethasone (n = 52), and ACTH-sufficient patients (AS) (n = 717) before and after 1 yr of GH treatment in terms of body mass index, waist and hip circumference, blood pressure, glucose, glycosylated hemoglobin (HbA1c), serum lipids, IGF-I, and comorbidity. Hydrocortisone equivalent (HCeq) doses were calculated, and measurements were adjusted for sex and age.
Results: At baseline, the HC group had increased total cholesterol, triglycerides, waist circumference, and HbA1c, and the prednisolone/dexamethasone group had increased waist/hip ratio as compared with AS. After HCeq dose adjustment, the HC group retained higher HbA1c than the CA group. GC-treated patients showed a dose-related increase in serum IGF-I, body mass index, triglycerides, low-density lipoprotein cholesterol and total cholesterol levels. Subjects with HCeq doses less than 20 mg/d (n = 328) at baseline did not differ from AS in metabolic endpoints. The 1-yr metabolic response to GH was similar in all GC groups and dose categories. All new cases of diabetes (n = 12), stroke (n = 8), and myocardial infarction (n = 3) during GH treatment occurred in GC-treated subjects.
Conclusion: HCeq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile. CA replacement may have metabolic advantages compared with other GCs.
Vascular Endothelial and Smooth Muscle Function Relates to Body Mass Index and Glucose in Obese and Nonobese Children
Authors: Peña Alexia Sophie , Wiltshire Esko , MacKenzie Karen , Gent Roger , Piotto Lino , Hirte Craig , Couper Jennifer 
Published: August 2006

Abstract
Context: Endothelial and smooth muscle dysfunction are critical precursors of atherosclerosis. These can be detected in children at risk of cardiovascular disease.
Objective: The objective of this study is to evaluate endothelial and smooth muscle function and their determinants using flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN) in obese, nonobese, and type 1 diabetes mellitus (T1DM) children.
Design: This is a cross-sectional study.
Subjects: The study subjects were 270 children [140 males, mean age 13.7 (2.8) yr] including 58 obese, 53 nonobese, and 159 T1DM children.
Measurements: Vascular function (FMD and GTN), body mass index (BMI) z-score, blood pressure, glucose, glycosylated hemoglobin, lipids, folate, homocysteine, and high sensitive C-reactive protein were measured.
Results: FMD and GTN were significantly lower in obese and T1DM compared with nonobese subjects (P &lt; 0.001, P &lt; 0.001). FMD and GTN were similarly reduced in obese and T1DM subjects (P = 0.22, P = 0.28). In all nondiabetic subjects (n = 111), both FMD and GTN were significantly and independently related to BMI z-score (r = −0.28, P = 0.003, β = −0.36, P &lt; 0.001) and weight z-score (β = −0.31, P = 0.002; r = −0.52, P &lt; 0.001). FMD related independently to total cholesterol (β = −0.22, P = 0.02). GTN related independently to vessel diameter (β = −0.49, P &lt; 0.001). GTN related to glucose within the normal range (r = −0.34, P = 0.001).
Conclusions: Children with obesity and T1DM have a similar degree of vascular dysfunction. BMI and weight adjusted for age and sex relate to endothelial and smooth muscle function in nonobese and obese children. Glucose relates to smooth muscle function in nonobese nondiabetic children. This suggests a continuum effect of BMI and glucose within the normal range on vascular function in childhood.
The Relative Roles of Follicle-Stimulating Hormone and Luteinizing Hormone in Maintaining Spermatogonial Maturation and Spermiation in Normal Men
Authors: Matthiesson Kati L. , McLachlan Robert I. , O’Donnell Liza , Frydenberg Mark , Robertson David M. , Stanton Peter G. , Meachem Sarah J. 
Published: August 2006

AbstractContext:. Male hormonal contraception via gonadotropin and intratesticular androgen withdrawal disrupts spermatogenesis at two principal sites: 1) spermatogonial maturation, and 2) spermiation.Objective: The objective of this study was to explore the relative dependence of each stage of germ cell development on FSH and LH/intratesticular androgen action.Design, Setting, and Participants: Eighteen men enrolled in this prospective, randomized 14-wk study at Prince Henrys Institute.Interventions: Subjects (n = 6/group) were assigned to 6 wk of 1) testosterone (T) implant (4 × 200 mg sc once)+depot medroxy progesterone acetate (DMPA; 150 mg im once); 2) T implant+DMPA+FSH (300 IU sc twice weekly); and 3) T implant+DMPA+human chorionic gonadotropin (hCG; 1000 IU sc twice weekly as an LH substitute). Men then underwent a vasectomy and testicular biopsy with previously reported control data used for comparison.Main Outcome Measures: Germ cell number (assessed by the optical disector stereological approach) and intratesticular androgen levels were determined.Results: T+DMPA alone significantly suppressed type B spermatogonia, preleptotene through to pachytene spermatocytes, and round spermatids from control (P &lt; 0.05). All germ cell subtypes were maintained at control levels by either FSH or LH activity, except pachytene spermatocytes, which were found to be lower in the hCG vs. FSH (P &lt; 0.01) and control groups (P &lt; 0.05).Conclusions: FSH and LH maintained spermatogenesis independently in this gonadotropin-suppressed model. Compared with LH, FSH showed better maintenance of pachytene spermatocyte number, whereas improved conversion to round spermatids was suggested with hCG treatment. Future contraceptive treatment strategies must consider independent regulation of spermatogenesis by both FSH and LH/intratesticular androgens for maximum efficacy.
Differential Effects of a Perioperative Hyperinsulinemic Normoglycemic Clamp on the Neurohumoral Stress Response during Coronary Artery Surgery
Authors: van Wezel H. B. , Zuurbier C. J. , de Jonge E. , van Dam E. W. C. M. , van Dijk J. , Endert E. , de Mol B. A. , Fliers E. 
Published: August 2006

Abstract
Background: Hyperglycemia in patients undergoing coronary artery bypass grafting (CABG) is associated with adverse outcome. Although insulin infusion strategies are increasingly used to improve outcome, a pathophysiological rationale is currently lacking. The present study was designed to quantify the effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during CABG.
Methods: Forty-four nondiabetic patients, scheduled for elective CABG, were randomized to either a control group (n = 22) receiving standard care or to a clamp group (n = 22) receiving additionally a perioperative hyperinsulinemic (regular insulin at a fixed rate of 0.1 IU·kg−1·h−1) normoglycemic (plasma glucose between 3.0 and 6.0 mmol·liter−1) clamp during 26 h. We measured the endocrine response of the hypothalamus-pituitary-adrenal (HPA) axis, the sympathoadrenal axis, and glucagon, as well as plasma glucose and insulin at regular intervals from the induction of anesthesia at baseline through the end of the second postoperative day (POD).
Results: There were no differences in clinical outcome between the groups. In the control group, hyperglycemia developed at the end of surgery and remained present until the final measurement point on POD2, whereas plasma insulin levels remained unchanged until the morning of POD1. In the intervention group, normoglycemia was well maintained during the clamp, whereas insulin levels ranged between 600 and 800 pmol·liter−1. In both groups, plasma ACTH and cortisol increased from 6 h after discontinuation of cardiopulmonary bypass onward. However, during the clamp period, a marked reduction in the HPA axis response was found in the intervention group, as reflected by a 47% smaller increase in area under the curve in plasma ACTH (P = 0.035) and a 27% smaller increase in plasma cortisol (P = 0.002) compared with the control group. Compared with baseline, epinephrine and norepinephrine increased by the end of the clamp interval until POD2 in both groups. Surprisingly, the area under the curve of epinephrine levels was 47% higher (P = 0.026) after the clamp interval in the intervention group as compared with the control group.
Conclusion: A hyperinsulinemic normoglycemic clamp during CABG delays and attenuates the HPA axis response during the first 18 h of the myocardial reperfusion period, whereas after the clamp, plasma epinephrine is higher. The impact of delaying cortisol responses on clinical outcome of CABG remains to be elucidated.
Competition and cooperation between tenascin-R, lecticans and contactin 1 regulate neurite growth and morphology
Authors: Zacharias Ute , Rauch Uwe 
Published: August 2006

The extracellular matrix molecule tenascin-R (TN-R) and the proteoglycans of the lectican family show an overlapping distribution in the developing brain, have been implicated in similar cellular processes and form a complex network of interactions. Previously, we have demonstrated that TN-R induces microprocesses along neurites and enlarged growth cones of tectal cells by interacting with the cell adhesion molecule contactin 1.Here, we describe competition and cooperation between TN-R, lecticans and contactin 1, and their functional consequences for tectal cells. Aggrecan, brevican and neurocan inhibit the effects of TN-R on microprocess formation and growth cone size. This blocking effect is due to competition of lecticans with binding of TN-R to its neuronal receptor contactin 1, as shown by a sandwich-binding assay. Interaction of aggrecan with TN-R fibronectin type III domains 4-A is necessary for its inhibitory effect on both microprocess formation and TN-R binding to contactin 1. However, the chondroitin sulfate chains are not involved. Time-lapse video microscopy showed that aggrecan has no acute effect on motility and morphology of microprocesses and growth cones but induces long-term neurite retraction after pre-treatment with TN-R.In contrast to the competition described above, TN-R cooperates with brevican and neurocan to induce attachment of tectal cells and neurite outgrowth, probably by forming a bridge between the lectican substrate and contactin 1 as the neuronal receptor.Our findings suggest that a complex network of protein-protein interactions within the brain extracellular matrix, as shown here for TN-R and lecticans, is important for the fine-regulation of developmental processes such as microprocess formation along the neurite and neurite outgrowth.
A MO Theoretical Study of Organic Dyes I. Effect of Chemical Softness on the Electronic Spectra
Authors: Nishimoto Kichisuke 
Published: August 2006

Abstract
In order to obtain reasonable results for the π-electronic spectra of organic dyes with simple semi-empirical MO methods, a new approximation for the two-center electron repulsion integral (new gamma) is proposed which takes the chemical softness of the π-conjugated system into account. New gamma was successfully applied to PPP calculations of the electronic spectra of linear polyenes, simple cyanines, and simple merocyanines. The calculated results agree satisfactorily with the experimental data. On the contrary, a calculation based on the conventional PPP parameters gives shorter wavelengths for the absorption maxima of the electronic spectra of charge-resonance systems, such as cyanines and merocyanines. Furthermore, they give very strange electronic spectral shifts for merocyanines (see text), due to an inbalance between the one- and two-electron parts of the electronic transition energy.