bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis
Authors: Lips Esther H , van Eijk Ronald , de Graaf Eelco JR , Oosting Jan , de Miranda Noel FCC , Karsten Tom , van de Velde Cornelis J , Eilers Paul HC , Tollenaar Rob AEM , van Wezel Tom , Morreau Hans
Published: October 2008

Background

Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes.

Methods

We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry.

Results

Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of EFNA1 in cases with 1q gain, and EFNA1 expression was correlated with the expression of a target gene (VEGF). The BOP1 gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. SMAD2 was the most down-regulated gene on 18q, and on 20q, STMN3 and TGIF2 were highly up-regulated. Immunohistochemistry for SMAD4 correlated with SMAD2 gene expression and 18q loss.

Conclusion

On basis of integrative analysis this study identified one well known CRC gene (SMAD2) and several other genes (EFNA1, BOP1, TGIF2 and STMN3) that possibly could be used for rectal cancer characterization.
No effect of an oleoylethanolamide-related phospholipid on satiety and energy intake: a randomised controlled trial of phosphatidylethanolamine
Authors: Lithander FE , Strik CM , McGill A-T , MacGibbon AK , McArdle BH , Poppitt SD
Published: October 2008

Background

Phosphatidylethanolamine (PE) is a phospholipid which is biosynthesized into long chain N-acylethanolamines (NAEs) including oleoylethanolamide (OEA), a known inhibitor of food intake. The aim of this study was to investigate whether PE-containing lipids can also inhibit intake. This was a 4 treatment intervention where 18 male participants were given a high-fat test breakfast (2.5MJ, 53 en% fat) containing (i) high-phospholipid, high-PE lipid (ii) high-phospholipid, medium-PE lipid (iii) no-phospholipid, no-PE control lipid or (iv) water control, in a randomised cross-over. Visual analogue scales (VAS) were used to assess post-ingestive hunger and satiety, and energy intake (EI) was measured at an ad libitum lunch meal after 3.5hours.

Results

When compared with the water control, the 3 lipid treatments resulted in lower levels of hunger and thoughts of food, greater fullness and satisfaction (all, treatment*time interaction, P<0.001), and a lower EI (P<0.05). However, there was no difference in any of the VAS measures when the 2 PE lipid treatments were compared with no-PE control lipid, nor when medium-PE was compared with high-PE. Unexpectedly participants ate significantly more energy at the lunch meal when the 2 PE lipid treatments (medium-PE:5406 kJ, 334 sem; high-PE:5288 kJ, 244 sem) were compared with the no-PE control lipid (5072 kJ, 262 sem, P<0.05), although there was no dose effect between the medium- and high-PE treatments.

Conclusion

Despite the close relationship of PE with OEA, there was no evidence from this acute study that dietary phospholipids containing PE can favourably modify eating behaviour.
Human activated protein C variants in a rat model of arterial thrombosis
Authors: Malm Karl , Arnljots Björn , Dahlbäck Björn
Published: October 2008

Background

Activated protein C (APC) inhibits coagulation by degrading activated factor V (FVa) and factor VIII (FVIIIa), protein S (PS) functioning as a cofactor to APC.

Methods

By mutagenesis of the vitamin K-dependent Gla domain of APC, we have recently created an APC variant having enhanced anticoagulant activity due to increased affinity for negatively charged phospholipid membranes. In the present study, the potential antithrombotic effects of this APC variant, and of a variant APC that is additionally mutated in the serine protease domain, have been evaluated in a blind randomized study in a rat model of arterial thrombosis. In this model, we have previously found the combination of bovine APC and PS to be highly antithrombotic. Four treatment groups each containing 10 rats were, in a blind random fashion, given intravenous bolus injections of wild-type or mutant variants of APC (0.8 mg/kg) together with human PS (0.6 mg/kg) or human PS (0.6 mg/kg) alone. A control group with 20 animals where given vehicle only.

Results

A trend to increased patency rates was noted in a group receiving one of the APC variants, but it did not reach statistical significance.

Conclusion

In conclusion, administration of human APC variants having enhanced anticoagulant efficacy together with human PS in a rat model of arterial thrombosis did not give an efficient antithrombotic effect. The lack of effect may be due to species-specific differences between the human protein C system and the rat hemostatic system.
Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations
Authors: Shi Hong , Zhong Hua , Peng Yi , Dong Yong-Li , Qi Xue-Bin , Zhang Feng , Liu Lu-Fang , Tan Si-Jie , Ma Runlin Z , Xiao Chun-Jie , Wells R Spencer , Jin Li , Su Bing
Published: October 2008

Background

The phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000–30,000 years ago, migrated northward, spreading throughout East Asia. However, the fragmented distribution of one East Asian specific Y chromosome lineage (D-M174), which is found at high frequencies only in Tibet, Japan and the Andaman Islands, is inconsistent with this scenario.

Results

In this study, we collected more than 5,000 male samples from 73 East Asian populations and reconstructed the phylogeography of the D-M174 lineage. Our results suggest that D-M174 represents an extremely ancient lineage of modern humans in East Asia, and a deep divergence was observed between northern and southern populations.

Conclusion

We proposed that D-M174 has a southern origin and its northward expansion occurred about 60,000 years ago, predating the northward migration of other major East Asian lineages. The Neolithic expansion of Han culture and the last glacial maximum are likely the key factors leading to the current relic distribution of D-M174 in East Asia. The Tibetan and Japanese populations are the admixture of two ancient populations represented by two major East Asian specific Y chromosome lineages, the O and D haplogroups.
The Comparative Toxicogenomics Database facilitates identification and understanding of chemical-gene-disease associations: arsenic as a case study
Authors: Davis Allan P , Murphy Cynthia G , Rosenstein Michael C , Wiegers Thomas C , Mattingly Carolyn J
Published: October 2008

Background

The etiology of many chronic diseases involves interactions between environmental factors and genes that modulate physiological processes. Understanding interactions between environmental chemicals and genes/proteins may provide insights into the mechanisms of chemical actions, disease susceptibility, toxicity, and therapeutic drug interactions. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) provides these insights by curating and integrating data describing relationships between chemicals, genes/proteins, and human diseases. To illustrate the scope and application of CTD, we present an analysis of curated data for the chemical arsenic. Arsenic represents a major global environmental health threat and is associated with many diseases. The mechanisms by which arsenic modulates these diseases are not well understood.

Methods

Curated interactions between arsenic compounds and genes were downloaded using export and batch query tools at CTD. The list of genes was analyzed for molecular interactions, Gene Ontology (GO) terms, KEGG pathway annotations, and inferred disease relationships.

Results

CTD contains curated data from the published literature describing 2,738 molecular interactions between 21 different arsenic compounds and 1,456 genes and proteins. Analysis of these genes and proteins provide insight into the biological functions and molecular networks that are affected by exposure to arsenic, including stress response, apoptosis, cell cycle, and specific protein signaling pathways. Integrating arsenic-gene data with gene-disease data yields a list of diseases that may be associated with arsenic exposure and genes that may explain this association.

Conclusion

CTD data integration and curation strategies yield insight into the actions of environmental chemicals and provide a basis for developing hypotheses about the molecular mechanisms underlying the etiology of environmental diseases. While many reports describe the molecular response to arsenic, CTD integrates these data with additional curated data sets that facilitate construction of chemical-gene-disease networks and provide the groundwork for investigating the molecular basis of arsenic-associated diseases or toxicity. The analysis reported here is extensible to any environmental chemical or therapeutic drug.
Computed Tomography Colonography in Acromegaly
Authors: Resmini Eugenia , Tagliafico Alberto , Bacigalupo Lorenzo , Giordano Giorgia , Melani Enrico , Rebora Alberto , Minuto Francesco , Rollandi Gian Andrea , Ferone Diego
Published: October 2008

Introduction and Aim: Acromegalic patients have an increased risk for the development of colorectal cancer. For this reason, since 1996, screening colonoscopy has been recommended in all patients with acromegaly. The aim of our study was to assess the feasibility and to evaluate the results of computed tomography (CT)-colonography in acromegaly.

Patients and Methods: We examined 23 acromegalic patients with no history of colorectal cancer (11 females and 12 males; age range 18–79 yr; disease duration range 1–15 yr) with CT-colonography. Twenty of them underwent traditional colonoscopy after the CT-colonography.

Results: CT-colonography examination results were adequate in 17 of 23 cases (73%). CT-colonography found 12 polyps in eight patients, 95% confirmed by traditional colonoscopy. One polyp was a sigmoid cancer, and the diagnosis was confirmed at surgery. There were no polyps found by traditional colonoscopy that CT-colonography was not able to identify. The lesions were located in right colon (two), transversum (three), left colon (five), and sigmoid colon (two). Patient acceptance of the technique was good in 65%, medium in 20%, and poor in 15%.

Conclusion: For the first time we have demonstrated that CT-colonography has the potential ability to replace traditional colonoscopy in acromegalic patients. CT-colonography could be used as a screening modality for colon cancer in acromegaly.
Effect of Glucagon-Like Peptide-1 on β- and α-Cell Function in Isolated Islet and Whole Pancreas Transplant Recipients
Authors: Rickels Michael R. , Mueller Rebecca , Markmann James F. , Naji Ali
Published: October 2008

Context: Glucose-dependent insulin secretion is often impaired after islet transplantation where reduced β-cell secretory capacity indicates a low functional β-cell mass.

Objective: We sought to determine whether glucagon-like peptide-1 (GLP-1) enhanced glucose-dependent insulin secretion and glucagon suppression in islet recipients, and whether GLP-1 effects were dependent on functional β-cell mass by simultaneously studying recipients of whole pancreas transplants.

Setting: The study was performed in a clinical and translational research center.

Participants: Five intraportal islet and six portally drained pancreas transplant recipients participated in the study.

Intervention: Subjects underwent glucose-potentiated arginine testing with GLP-1 (1.5 pmol · kg−1 · min−1) or placebo infused on alternate randomized occasions, with 5 g arginine injected under basal and hyperglycemic clamp conditions.

Results: Basal glucose was lower with increases in insulin and decreases in glucagon during GLP-1 vs. placebo in both groups. During the hyperglycemic clamp, a significantly greater glucose infusion rate was required with GLP-1 vs. placebo in both groups (P < 0.05), an effect more pronounced in the pancreas vs. islet group (P < 0.01). The increased glucose infusion rate was associated with significant increases in second-phase insulin secretion in both groups (P < 0.05) that also tended to be greater in the pancreas vs. islet group (P = 0.08), whereas glucagon was equivalently suppressed by the hyperglycemic clamp during GLP-1 and placebo infusions in both groups. The GLP-1-induced increase in second-phase insulin correlated with the β-cell secretory capacity (P < 0.001). The proinsulin secretory ratio (PISR) during glucose-potentiated arginine was significantly greater with GLP-1 vs. placebo infusion in both groups (P < 0.05).

Conclusions: GLP-1 induced enhancement of glucose-dependent insulin secretion, but not glucagon suppression, in islet and pancreas transplant recipients, an effect dependent on the functional β-cell mass that may be associated with depletion of mature β-cell secretory granules.
Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating
Authors: Engler Adam J. , Carag-Krieger Christine , Johnson Colin P. , Raab Matthew , Tang Hsin-Yao , Speicher David W. , Sanger Joseph W. , Sanger Jean M. , Discher Dennis E.
Published: October 2008

Fibrotic rigidification following a myocardial infarct is known to impair cardiac output, and it is also known that cardiomyocytes on rigid culture substrates show a progressive loss of rhythmic beating. Here, isolated embryonic cardiomyocytes cultured on a series of flexible substrates show that matrices that mimic the elasticity of the developing myocardial microenvironment are optimal for transmitting contractile work to the matrix and for promoting actomyosin striation and 1-Hz beating. On hard matrices that mechanically mimic a post-infarct fibrotic scar, cells overstrain themselves, lack striated myofibrils and stop beating; on very soft matrices, cells preserve contractile beating for days in culture but do very little work. Optimal matrix leads to a strain match between cell and matrix, and suggests dynamic differences in intracellular protein structures. A `cysteine shotgun' method of labeling the in situ proteome reveals differences in assembly or conformation of several abundant cytoskeletal proteins, including vimentin, filamin and myosin. Combined with recent results, which show that stem cell differentiation is also highly sensitive to matrix elasticity, the methods and analyses might be useful in the culture and assessment of cardiogenesis of both embryonic stem cells and induced pluripotent stem cells. The results described here also highlight the need for greater attention to fibrosis and mechanical microenvironments in cell therapy and development.
Double Ordered Layers within Microphase-separated Lamellar Structure of Double Liquid Crystalline Side-chain Type Block Copolymer
Authors: Maeda Rina , Hayakawa Teruaki , Tokita Masatoshi , Kakimoto Masa-aki , Urushibata Hiroaki
Published: October 2008

A new hierarchical nanostructure was created by self-assembly of a double liquid crystalline side-chain type block copolymer. The block copolymer was successfully prepared via a nitroxide-mediated living free radical polymerization and formed double ordered layers within a phase-separated lamellar structure of the cast film.
Y-Cell Receptive Field and Collicular Projection of Parasol Ganglion Cells in Macaque Monkey Retina
Authors: Crook Joanna D. , Peterson Beth B. , Packer Orin S. , Robinson Farrel R. , Troy John B. , Dacey Dennis M.
Published: October 2008

The distinctive parasol ganglion cell of the primate retina transmits a transient, spectrally nonopponent signal to the magnocellular layers of the lateral geniculate nucleus. Parasol cells show well-recognized parallels with the α-Y cell of other mammals, yet two key α-Y cell properties, a collateral projection to the superior colliculus and nonlinear spatial summation, have not been clearly established for parasol cells. Here, we show by retrograde photodynamic staining that parasol cells project to the superior colliculus. Photostained dendritic trees formed characteristic spatial mosaics and afforded unequivocal identification of the parasol cells among diverse collicular-projecting cell types. Loose-patch recordings were used to demonstrate for all parasol cells a distinct Y-cell receptive field “signature” marked by a nonlinear mechanism that responded to contrast-reversing gratings at twice the stimulus temporal frequency [second Fourier harmonic (F2)] independent of stimulus spatial phase. The F2 component showed high contrast gain and temporal sensitivity and appeared to originate from a region coextensive with that of the linear receptive field center. The F2 spatial frequency response peaked well beyond the resolution limit of the linear receptive field center, showing a Gaussian center radius of ∼15 μm. Blocking inner retinal inhibition elevated the F2 response, suggesting that amacrine circuitry does not generate this nonlinearity. Our data are consistent with a pooled-subunit model of the parasol Y-cell receptive field in which summation from an array of transient, partially rectifying cone bipolar cells accounts for both linear and nonlinear components of the receptive field.
The Role of MAP1A Light Chain 2 in Synaptic Surface Retention of CaV2.2 Channels in Hippocampal Neurons
Authors: Leenders A. G. Miriam , Lin Lin , Huang Li-Dong , Gerwin Claudia , Lu Pei-Hua , Sheng Zu-Hang
Published: October 2008

Cav2.2 channels are localized at nerve terminals where they play a critical role in neurotransmission. However, the determinant that controls surface retention of these channels has not been identified. Here, we report that presynaptic surface localization of Cav2.2 is mediated through its interaction with light chain 2 (LC2) of microtubule-associated protein MAP1A. Deletion of a 23-residue binding domain within the Cav2.2 C terminus resulted in reduced synaptic distribution of the mutant channels. Using an antibody generated against an extracellular epitope of Cav2.2, we demonstrate that interfering the interaction with LC2 reduced surface expression of endogenous Cav2.2 at presynaptic boutons. In addition, the disruption of LC2–Cav2.2 coupling reduced Ca2+-influx into nerve terminals through Cav2.2 and impaired activity-dependent FM4-64 uptake. The treatments of neurons with Latrunculin A to disrupt actin filaments resulted in reduced density of surface Cav2.2-positive boutons. Furthermore, LC2NT, a LC2 truncated mutant lacking the actin-binding domain, could not rescue Cav2.2 surface expression after suppressing LC2 expression with RNAi. Because actin filaments are major cytomatric components at the presynaptic boutons, these observations suggest a mechanism by which LC2 provides anchoring of surface Cav2.2 to the actin cytoskeleton, thus contributing to presynaptic function.
Executed and Observed Movements Have Different Distributed Representations in Human aIPS
Authors: Dinstein Ilan , Gardner Justin L. , Jazayeri Mehrdad , Heeger David J.
Published: October 2008

How similar are the representations of executed and observed hand movements in the human brain? We used functional magnetic resonance imaging (fMRI) and multivariate pattern classification analysis to compare spatial distributions of cortical activity in response to several observed and executed movements. Subjects played the rock–paper–scissors game against a videotaped opponent, freely choosing their movement on each trial and observing the opponent's hand movement after a short delay. The identities of executed movements were correctly classified from fMRI responses in several areas of motor cortex, observed movements were classified from responses in visual cortex, and both observed and executed movements were classified from responses in either left or right anterior intraparietal sulcus (aIPS). We interpret above chance classification as evidence for reproducible, distributed patterns of cortical activity that were unique for execution and/or observation of each movement. Responses in aIPS enabled accurate classification of movement identity within each modality (visual or motor), but did not enable accurate classification across modalities (i.e., decoding observed movements from a classifier trained on executed movements and vice versa). These results support theories regarding the central role of aIPS in the perception and execution of movements. However, the spatial pattern of activity for a particular observed movement was distinctly different from that for the same movement when executed, suggesting that observed and executed movements are mostly represented by distinctly different subpopulations of neurons in aIPS.
A cAMP Pathway Underlying Reward Prediction in Associative Learning
Authors: Kheirbek Mazen A. , Beeler Jeff A. , Ishikawa Yoshihiro , Zhuang Xiaoxi
Published: October 2008

In associative learning, animals learn to associate external cues or their own actions with appetitive or aversive outcomes. Although the dopamine (DA) system and the striatum/nucleus accumbens have been implicated in both the pavlovian and instrumental form of associative learning, whether specific neuronal signaling mechanisms underlie one form or the other is unknown. Here, we report that the striatum-enriched isoform of adenylyl cyclase (AC), AC5, is selectively required for appetitive pavlovian learning. Mice with genetic deletion of AC5 (AC5KO) acquired instrumental responding yet were unable to use cues that predicted reward delivery. The specificity of this deficit was confirmed by an inability of AC5KO mice to learn a simple appetitive pavlovian conditioning task. Conversely, AC5KO mice showed intact aversive pavlovian learning, suggesting the deficit was specific for learning about appetitive outcomes. Our results suggest that AC5 is a critical component of DA-dependent strengthening of stimulus–reward contingencies.
Cancer and Evolution
Authors: Bodmer Walter. F.
Published: October 2008

Cancer mostly is a disease of old age. Evolutionary pressures have pushed the somatic "error rate", especially the mutation rate, down to a level where for most organisms cancer is no longer of any selective significance. This appears to be a by-product of the selection that gives rise to senescence, following the arguments of Medawar, Holliday, and Kirkwood.

The development of a cancer is discussed from an evolutionary viewpoint, emphasising the role of selection versus mutation and the fact that each cancer is an independent evolutionary process. The nature of the selective advantages associated with the somatic genetic changes during a cancer's evolution can sometimes be inferred by reference to the known types of mutations found in cancers. Examples are given using colorectal cancer as a model. The major selective forces involve the balance between selection for increased growth rate and against apoptosis. There are strong arguments against the much discussed role of genomic instability as a requirement for cancer. Current evidence suggests that instability is a byproduct of selection against apoptosis. There is an important contrast between germ line and somatic changes, the former being the basis for inherited susceptibilities to cancer, while the latter are the fundamental changes that turn a normal cell into a cancer cell.

Tissue stem cells, as in the colonic crypt, provide the source, through division and differentiation, of the differentiated cells in a crypt. Mathematical models can provide an explanation for how the balance in a crypt between stem cells, intermediate proliferating cells, and non-proliferating differentiated cells is maintained. Perturbations of the renewal parameters in the model can explain the evolution of benign tumors, namely polyps or adenomas, and the eventually exponential growth of cells resulting in a fully developed carcinoma. It seems probable that the origin of most carcinomas is in the intermediate proliferating cells, and that these are therefore the likely source of cancer stem cells.
On Ribosome Conservation and Evolution
Authors: Agmon Ilana , Bashan Anat , Yonath Ada
Published: October 2008

The ribosome is a ribozyme whose active site, the peptidyl transferase center (PTC), is situated within a highly conserved universal symmetrical region that connects all ribosomal functional centers involved in amino acid polymerization. The linkage between this elaborate architecture and A-site tRNA position revealed that the A-> P-site passage of the tRNA terminus in the peptidyl transferase center is performed by a rotatory motion, synchronized with the overall tRNA/mRNA sideways movement. Guided by the PTC, the rotatory motion leads to stereochemistry suitable for peptide bond formation, as well as for substrate-mediated catalysis, consistent with quantum mechanical calculations elucidating the transition state mechanism for peptide bond formation and indicating that the peptide bond is being formed during the rotatory motion.

Analysis of substrate binding modes to inactive and active ribosomes illuminated the significant PTC mobility and supported the hypothesis that the ancient ribosome produced single peptide bonds and non-coded chains, utilizing free amino acids. Genetic control of the reaction evolved after poly-peptides capable of enzymatic function were created, and an ancient stable RNA fold was converted into tRNA molecules. As the symmetry relates only the backbone fold and nucleotide orientations, but not nucleotide sequence, it emphasizes the superiority of functional requirement over sequence conservation, and indicates that the PTC has evolved by gene fusion, presumably by taking advantage of similar RNA fold structures.
Do Energetic Costs Underlie Variability and Evolutionary Potential Across Variably Stressful Environments?
Authors: Parsons Peter A.
Published: October 2008

Stress can be viewed as an environmental probe that targets energy carriers, and hence can determine the energetic efficiency or fitness to survive. Thus, variability and evolutionary potential are interpreted in terms of the ecological scenario of predominantly stressful environments in the wild that restrict energy availability. This can explain how the observed variability of direct fitness traits is high at extremes of abiotic stresses, giving U-shaped curves for variability that incorporate more benign regions between the extremes. Some consistency with interpretations based upon conventional quantitative genetic techniques occurs, incorporating this ecological/energetic approach. However, investigations into the quantification of stress levels are required for more comprehensive assessments. Even so, evolutionary potential can in principle be investigated in terms of energetic consequences of the functional biology of organisms in their challenging habitats. This approach appears predictive for variability patterns of direct fitness traits as well as for developmentally more complex morphometric traits and for relationships among fitness traits in natural populations. That is, energetic costs are basic in determining evolutionary potential across variably stressful environments.
Enigmatic Flies: Is Drosophila in the "Evolution Canyon" A Model for Incipient Sympatric speciation?
Authors: Korol Abraham , Rashkovetsky Eugenia , Nevo Eviatar
Published: October 2008

Extensive studies of biota at "Evolution Canyon" (EC) on Mount Carmel (Nahal Oren Canyon, Israel) includeDrosophilaas one of the main model organisms. The microtopography of the EC permits interslope mixing by easy migration of the flies. Nevertheless, we found strong interslope differentiation inDrosophilapopulations derived from the opposite slopes involving habitat choice, as well as various aspects of induced changes in viability and longevity caused by short-term and lifetime high-temperature treatments. The most exciting findings were related to sexual behavior: interslope differences in mating propensity, sexual discrimination, reproductive activity, peculiarities in courtship song patterns, and significant positive assortative mating. Some of the foregoing effects were also confirmed inD. simulans.The evidence suggests that these populations are examples of ongoing divergence taking place regardless of gene flow. However, tests for interslope genetic differentiation inDrosophila, carried out in a number of laboratories, gave somewhat conflicting results. A possible explanation could be that adaptive differentiation can withstand destructive effects of interslope migration, but it should not necessarily be accompanied by differentiation for selectively neutral markers, unless the latter will be in linkage disequilibrium with selected loci. The last condition can also be maintained despite migration, but only under tight linkage and strong selection. For someDrosophilagenes, linkage disequilibrium is known to decay within just a few kilobases. Thus, differentiation for adaptive trait complexes and relevant candidate genes seems to be much better evidence for interslope divergent selection than that displayed by genetic distances estimated using molecular markers.
Risk of Adverse Gastrointestinal Events from Inhaled Corticosteroids
Authors: Hansen Richard A. , Tu Wanzhu , Wang Jane , Ambuehl Roberta , McDonald Clement J. , Murray Michael D.
Published: October 2008

Study Objective. To determine whether patients prescribed inhaled corticosteroids are at risk for adverse gastrointestinal effects.

Design. Retrospective cohort study

Setting. Urban health center with an academic affiliation.

Patients. A total of 19,443 adults (mean age 31.8 yrs) with airways disease, defined as a diagnosis of asthma or chronic obstructive pulmonary disease, and who were prescribed both an inhaled corticosteroid and albuterol (7156 patients) or inhaled albuterol alone (12,287 patients) between 1977 and February 2002.

Measurements and Main Results. The frequency of adverse gastrointestinal events in the patients who used inhaled corticosteroids and albuterol was compared with that in the patients who used albuterol alone. Adverse gastrointestinal outcomes included events such as gastritis, ulcers, and bleeding. Cox proportional hazards models were used to determine the risk of adverse events, controlling for possible confounders such as alcohol use or nonsteroidal antiinflammatory drug use. Adverse gastrointestinal events were observed in 461 (6.4%) patients using inhaled corticosteroids and albuterol and in 302 (2.5%) patients using only albuterol. After controlling for potential confounders, patients who used inhaled corticosteroids and albuterol had an increased risk for adverse gastrointestinal events compared with patients who used only inhaled albuterol (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.02‐1.56). A prescription for a spacer device reduced this risk among patients using an inhaled corticosteroid (HR 0.26, 95% CI 0.20‐0.34).

Conclusion. Patients using inhaled corticosteroids appear to have a slight risk for adverse gastrointestinal events that is mitigated in patients who used a spacer device.
Use of Recombinant Human Erythropoietin and Risk of Severe Retinopathy in Extremely Low‐Birth‐Weight Infants
Authors: Schneider Jacqueline K. , Gardner Debra K. , Cordero Leandro
Published: October 2008

Study Objectives. To evaluate the frequency and severity of retinopathy of prematurity in extremely low‐birth‐weight (ELBW) infants who received recombinant human erythropoietin (rHuEPO), and to compare the frequency of blood cell transfusions these infants required with a matched control group who did not receive rHuEPO.

Design. Retrospective cohort analysis.

Setting. Level III neonatal intensive care unit in a large academic medical center.

Patients. One hundred thirty‐eight ELBW infants who received rHuEPO and 138 ELBW infants who did not (control group) but who were matched by birth weight, gestational age, sex, and year of birth and who survived to the first ophthalmologic examination.

Measurements and Main Results. The rHuEPO was started before the 8th day of life in 115 (83%) of the 138 infants. Stages III‐V retinopathy of prematurity occurred with similar frequency in both groups of infants (rHuEPO group 19% [26 infants] vs control group 20% [27 infants], p>0.05). Infants in the rHuEPO group received fewer transfusions on average during their hospitalization compared with those in the control group (4.2 vs 6.1 transfusions, p<0.01).

Conclusion. Use of rHuEPO for prevention or treatment of anemia of prematurity in ELBW infants does not increase the frequency of severe retinopathy of prematurity and reduces the number of transfusions.
Antibiotic Allergies in the Medical Record: Effect on Drug Selection and Assessment of Validity
Authors: Lutomski Dave M. , LaFollette Jennifer A. , Biaglow Michael A. , Haglund Lisa A.
Published: October 2008

Study Objectives. To determine the frequency with which reported antibiotic allergies alter drug selection and to assess the validity of these allergies.

Design. Retrospective medical record review, with concurrent interviews conducted in a selected subgroup of patients.

Setting. Tertiary care academic medical center.

Patients. Three hundred patients with at least one documented antibiotic allergy and who received an antibiotic while hospitalized.

Measurements and Main Results. Data were collected to determine the patients' allergies documented in the medical record. The first antibiotic regimen that each patient received while hospitalized was evaluated for deviation from the standard of care as determined from institutional protocols, recommendations in the literature, and expert opinion. A total of 416 allergies to antibiotics were reported. Penicillins were the agents most commonly reported (198 reports), followed by sulfonamides, cephalosporins, macrolides, and fluoroquinolones. The reported allergies altered antibiotic therapy in 91 (30.3%) patients. Report of a penicillin or cephalosporin allergy and use of antibiotics for prophylaxis were strong predictors of altered therapy. The subgroup consisted of 100 patients who were interviewed to determine the specific details of their reported allergic reactions. For 22 of the 100 patients, major discrepancies were found between their verbal reports and medical record documentation. The Naranjo adverse drug reaction probability scale was used to determine the validity of their reactions. Among these 100 patients, 109 (78.4%) of 139 reported reactions to antibiotics were deemed to be allergic in nature. For 55 (50.5%) of the 109 allergic reactions, the Naranjo score was 5 or greater, which correlates with probable to definite validity.

Conclusion. Discrepancies between the medical record and in‐depth allergy histories are common, and the validity of reported allergic reactions is frequently questionable. Because documentation of an antibiotic allergy frequently alters therapy, increased effort to verify these reactions may be beneficial.
Using Resource Selection Functions to Improve Estimation of Elk Population Numbers
Authors: ALLEN JAMES R. , MCINENLY LESLIE E. , MERRILL EVELYN H. , BOYCE MARK S.
Published: October 2008

Abstract:Stratification is commonly used to improve sampling efficiency of aerial surveys of ungulate populations with strata typically based on a priori information, such as preflight animal observations or vegetation attributes as surrogates for animal densities. We evaluated the usefulness of stratifying survey units for elk (Cervus elaphus) in the Rocky Mountain foothills of Alberta, Canada, using a resource selection function (RSF). We compared precision and design efficiency (DEFF) of population estimates from stratification approaches based on an RSF model to the past approach using amount of forest cover. We used a sample of telemetry relocations taken over a 3‐year period from 165 elk, rarified to times of the day and months of the year when aerial surveys are conducted, to develop the RSF. We then used the top RSF model, based on Akaike's Information Criterion, to derive the average RSF value for an 8‐km2survey unit. Using survey data from the first year, we evaluated binning schemes to define RSF‐oriented strata based on poststratification and showed that Jenks natural breaks in the RSF values provided the greatest improvement in DEFF and increased precision, compared to 2 other stratification schemes. We then used this approach with data from 2 additional surveys to find that stratification by RSF consistently improves relative precision and design efficiency of elk population estimates, whether we employ pre‐ or poststratification. Where a RSF is available it could be used as a surrogate for animal densities when conducting stratified sampling for population surveys.
Effects of Point Pattern Shape on Home‐Range Estimates
Authors: DOWNS JONI A. , HORNER MARK W.
Published: October 2008

Abstract: Home‐range estimators are commonly tested with simulated animal locational data in the laboratory before the estimators are used in practice. Although kernel density estimation (KDE) has performed well as a home‐range estimator for simulated data, several recent studies have reported its poor performance when used with data collected in the field. This difference may be because KDE and other home‐range estimators are generally tested with simulated point locations that follow known statistical distributions, such as bivariate normal mixtures, which may not represent well the space‐use patterns of all wildlife species. We used simulated animal locational data of 5 point pattern shapes that represent a range of wildlife utilization distributions to test 4 methods of home‐range estimation: 1) KDE with reference bandwidths, 2) KDE with least‐squares cross‐validation, 3) KDE with plug‐in bandwidths, and 4) minimum convex polygon (MCP). For the point patterns we simulated, MCP tended to produce more accurate area estimates than KDE methods. However, MCP estimates were markedly unstable, with bias varying widely with both sample size and point pattern shape. The KDE methods performed best for concave distributions, which are similar to bivariate normal mixtures, but still overestimated home ranges by about 40–50% even in the best cases. For convex, linear, perforated, and disjoint point patterns, KDE methods overestimated home‐range sizes by 50–300%, depending on sample size and method of bandwidth selection. These results indicate that KDE does not produce home‐range estimates that are as accurate as the literature suggests, and we recommend exploring other techniques of home‐range estimation.
Registered Pesticides and Citrus Terpenes as Blackbird Repellents for Rice
Authors: WERNER SCOTT J. , CUMMINGS JOHN L. , PIPAS PATRICIA A. , TUPPER SHELAGH K. , BYRD ROBERT W.
Published: October 2008

Abstract: Nonlethal management alternatives are needed to minimize bird depredation of agricultural crops. We conducted 8 caged feeding tests and 2 field studies to evaluate 2 registered fungicides (GWN‐4770, Gowan Company, Yuma, AZ; Quadris®, Syngenta Crop Protection, Greensboro, NC), a neem oil insecticide (Aza‐Direct®, Gowan Company), and a novel terpene formulation (Gander Gone, Natural Earth Products, Winter Springs, FL) as avian repellents. For all candidate repellents, red‐winged blackbirds (Agelaius phoeniceus) discriminated between untreated and treated rice during preference‐testing in captivity. We observed a positive concentration‐response relationship among birds offered rice treated with 2,500 ppm, 5,000 ppm, 7,500 ppm, 11,000 ppm, or 22,000 ppm GWN‐4770. Relative to pretreatment, blackbirds consumed 34% and 77% less rice treated with 11,000 ppm and 22,000 ppm GWN‐4770, respectively, during the concentration‐response test. Maximum repellency among other tested compounds was <40% during the concentration‐response test. Blackbirds consumed 28% of rice seeds treated with 20,000 ppm GWN‐4770 and 68% of untreated seeds broadcast within rice fields in southwestern Louisiana, USA. We observed 50% fewer unprotected seedlings than those treated with 10,000 ppm GWN‐4770 within a drill‐seeded rice field in southeastern Missouri, USA. The manufacturer subsequently applied for a United States patent for the active ingredient of GWN‐4770 as an avian repellent. Although additional registration criteria and formulation optimization must be satisfied to enable the commercial availability of GWN‐4770 as an avian repellent, additional efficacy studies of GWN‐4770 and other promising repellents under extended field conditions are warranted for protection of newly planted and ripening rice.
Validation of a New Video and Telemetry System for Remotely Monitoring Wildlife
Authors: MACNULTY DANIEL R. , PLUMB GLENN E. , SMITH DOUGLAS W.
Published: October 2008

Abstract: Current techniques for remotely monitoring wildlife lack the capability to survey a wide area or to transmit data in real time. We addressed these technology gaps by developing and testing a new video and telemetry system for remotely sampling wildlife abundance, distribution, and behavior across large open areas. The system consisted of 2 pan‐tilt‐zoom video cameras equipped with 20–200× lens, and an automated telemetry scanner and data logger. All components were charged by wind and solar power and located on a hilltop overlooking an open valley (23 km2) in Yellowstone National Park, USA. A satellite up‐link to the internet transmitted data in real time to the University of Minnesota‐St. Paul and relayed commands from undergraduate students who controlled the cameras and systematically scanned the area at 2‐hour intervals 6 times/day (0800–2000 hr) 7 days/week for about 20 consecutive weeks (Dec‐Jun). During each scan, students recorded presence, activity, and location of bison (Bison bison), coyote (Canis latrans), grizzly bear (Ursus arctos), red fox (Vulpes vulpes), and wolf (Canis lupus). The telemetry system continuously scanned frequencies of 100 tagged wolves, including 4 members of the one resident pack. We determined wolf presence in real time by viewing the incoming data stream, or we assessed presence later after off‐loading the data logger. Matched pairs of simultaneous observations taken by remote and on‐site observers during a 13‐day double‐sampling period were highly correlated (r = 0.71–0.94), but remote observations were biased toward larger, more visible mammals (e.g., bison) and tended to underestimate their abundance. Nevertheless, the system was deployed longer than was practical for on‐site observers and was, therefore, useful for detecting long‐term, fine‐scale trends such as daily changes in bison numbers as a function of snow depth. (JOURNAL OF WILDLIFE MANAGEMENT 72(8):1834–1844; 2008)
Objectives and Metrics for Wildlife Monitoring
Authors: SAUER JOHN R. , KNUTSON MELINDA G.
Published: October 2008

Abstract: Monitoring surveys allow managers to document system status and provide the quantitative basis for management decision‐making, and large amounts of effort and funding are devoted to monitoring. Still, monitoring surveys often fall short of providing required information; inadequacies exist in survey designs, analyses procedures, or in the ability to integrate the information into an appropriate evaluation of management actions. We describe current uses of monitoring data, provide our perspective on the value and limitations of current approaches to monitoring, and set the stage for 3 papers that discuss current goals and implementation of monitoring programs. These papers were derived from presentations at a symposium at The Wildlife Society's 13th Annual Conference in Anchorage, Alaska, USA.
Formulation and Fuzzy Modeling of Viscosity of an Orange-Flavored Carboxymethylcellulose-Whey Protein Isolate Beverage
Authors: Abughoush Mahmoud , Al-Mahasneh Majdi , Samhouri Murad , Al-Holy Murad , Herald Thomas
Published: October 2008

The aim of this study was to employ whey proteins isolate (WPI) and carboxymethylcelulose (CMC) as stabilizers in beverage production and to evaluate viscosity of the products. Three beverages were formulated using 6% WPI combined with three different concentrations of CMC (0.1, 0.5, and 1%). The combination of 6% WPI/1.0% CMC was selected and added to three different ratios of pure orange juice (50:50 "T1," 40:60 "T2," and 15:85 "T3"). The apparent viscosity decreased as shear rate and temperature increased. Additionally, the apparent viscosity for the same treatment at certain shear rate/same temperature increased after storage. In addition, an adaptive neuro-fuzzy inference system (ANFIS) was used to model and identify the viscosity of the resulted beverages. Experimental validation runs were conducted to compare the measured values and the predicted ones. ANFIS models achieved an average prediction error of viscosity of only 9%. It is believed that this approach can be applied to predict many other parameters and properties in beverage industry.
Plasma apelin levels in diabetic patients with and without neuropathy
Authors: Şenol Mehmet , Terekeci Hakan , İpçioğlu Osman , Çağıltay Eylem , Toğrol Erdem , Özdağ Fatih , Şahan Burak , Öktenli Çağatay , Saraçoğlu Mehmet
Published: October 2008

The aim of this study was to investigate the plasma apelin levels in diabetic patients with and without neuropathy. All consecutive diabetic patients who presented for routine follow-up at our outpatient clinic were invited to participate in this clinical study. Forty diabetic patients (20 female and 20 male) and twenty-two non-diabetic control subjects (9 female and 13 male) were included in the study. Neurological evaluations in diabetic subjects were done by nerve conduction studies and evaluated with the Neuropathy Symptom Score. Fasting plasma glucose, HbA1c, lipid and apelin levels were measured in each subject. The mean plasma apelin level was significantly higher in the diabetic patients than in the control subjects (p = 0.026). Apelin levels were statistically similar between diabetic patients with and without neuropathy (p = 0.43). Further, plasma apelin levels were found to be higher in diabetic patients with neuropathy when compared with those of healthy control subjects (p = 0.02). In diabetic patients with neuropathy, plasma apelin levels correlated significantly with diabetes duration (r = 0.5, p = 0.02). We propose that apelin levels in diabetic patients are higher in the presence of neuropathy and longer disease duration, although this might not solely suffice as an indicator for the presence of neuropathy in diabetic patients. Drawing attention to the possible association between the apelinergic system and diabetes mellitus, we believe that further studies with larger samples should be carried out also to investigate the presence of retinopathy and nephropathy.