bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant deviations from Hardy–Weinberg equilibrium caused by low levels of microsatellite genotyping errors
Authors: MORIN PHILLIP A. , LEDUC RICHARD G. , ARCHER FREDERICK I. , MARTIEN KAREN K. , HUEBINGER RYAN , BICKHAM JOHN W. , TAYLOR BARBARA L. 
Published: January 2009

AbstractMicrosatellite genotyping from samples with varying quality can result in an uneven distribution of errors. Previous studies reporting error rates have focused on estimating the effects of both randomly distributed and locus‐specific errors. Sample‐specific errors, however, can also significantly affect results in population studies despite a large sample size. From two studies including six microsatellite markers genotyped from 272 sperm whale DNA samples, and 33 microsatellites genotyped from 213 bowhead whales, we investigated the effects of sample‐ and locus‐specific errors on calculations of Hardy–Weinberg equilibrium. The results of a jackknife analysis in these two studies identified seven individuals that were highly influential on estimates of Hardy–Weinberg equilibrium for six different markers. In each case, the influential individual was homozygous for a rare allele. Our results demonstrate that Hardy–Weinberg P values are very sensitive to homozygosity in rare alleles for single individuals, and that > 50% of these cases involved genotype errors likely due to low sample quality. This raises the possibility that even small, normal levels of laboratory errors can result in an overestimate of the degree to which markers are out of Hardy–Weinberg equilibrium and hence overestimate population structure. To avoid such bias, we recommend routine identification of influential individuals and multiple replications of those samples.
Asymptomatic pericardial effusion in patients with systemic lupus erythematosus
Authors: Sugiura T , Kumon Y , Kataoka H , Matsumura Y , Takeuchi H , Doi YL 
Published: January 2009

To determine the frequency and clinical correlates of asymptomatic pericardial effusion (PE) in patients with systemic lupus erythematosus (SLE), echocardiography and electrocardiography were performed in 50 consecutive patients with SLE. Among 50 patients with SLE, 12 patients (24%) had PE and 17 patients (34%) had hypoalbuminaemia. Patients with PE had a significantly lower serum albumin ( P < 0.001), higher incidence of proteinuria ( P = 0.003), higher C-reactive protein ( P = 0.036) and pulmonary artery systolic pressure ( P = 0.011) and tended to have a higher incidence of PR-segment depression ( P = 0.082) compared with those without PE. When four variables (PR-segment depression, C-reactive protein, serum albumin and pulmonary artery systolic pressure) were used in the multivariate analysis, serum albumin ( P = 0.005, odds ratio = 0.016) and pulmonary artery systolic pressure ( P = 0.010, odds ratio = 1.106) emerged as significant variables related to the occurrence of asymptomatic PE. Thus, an increase in hydrostatic pressure of the right heart cavities and a decrease in colloid osmotic pressure were important factors associated with the presence of asymptomatic PE in patients with SLE.
Wound healing defect of Vav3−/− mice due to impaired β2-integrin–dependent macrophage phagocytosis of apoptotic neutrophils
Authors: Sindrilaru Anca , Peters Thorsten , Schymeinsky Jürgen , Oreshkova Tsvetelina , Wang Honglin , Gompf Anne , Mannella Francesca , Wlaschek Meinhard , Sunderkötter Cord , Rudolph Karl Lenhard , Walzog Barbara , Bustelo Xosé R. , Fischer Klaus D. , Scharffetter-Kochanek Karin 
Published: January 2009

AbstractVav proteins are guanine-nucleotide exchange factors implicated in leukocyte functions by relaying signals from immune response receptors and integrins to Rho-GTPases. We here provide first evidence for a role of Vav3 for β2-integrins–mediated macrophage functions during wound healing. Vav3−/− and Vav1−/−/Vav3−/− mice revealed significantly delayed healing of full-thickness excisional wounds. Furthermore, Vav3−/− bone marrow chimeras showed an identical healing defect, suggesting that Vav3 deficiency in leukocytes, but not in other cells, is causal for the impaired wound healing. Vav3 was required for the phagocytotic cup formation preceding macrophage phagocytosis of apoptotic neutrophils. Immunoprecipitation and confocal microscopy revealed Vav3 activation and colocalization with β2-integrins at the macrophage membrane upon adhesion to ICAM-1. Moreover, local injection of Vav3−/−or β2-integrin(CD18)−/− macrophages into wound margins failed to restore the healing defect of Vav3−/− mice, suggesting Vav3 to control the β2-integrin–dependent formation of a functional phagocytic synapse. Impaired phagocytosis of apoptotic neutrophils by Vav3−/− macrophages was causal for their reduced release of active transforming growth factor (TGF)-β1, for decreased myofibroblasts differentiation and myofibroblast-driven wound contraction. TGF-β1 deficiency in Vav3−/− macrophages was causally responsible for the healing defect, as local injection of either Vav3-competent macrophages or recombinant TGF-β1 into wounds of Vav3−/− mice fully rescued the delayed wound healing.
Detecting intergene correlation changes in microarray analysis: a new approach to gene selection
Authors: Hu Rui , Qiu Xing , Glazko Galina , Klebanov Lev , Yakovlev Andrei 
Published: January 2009

Abstract

Background
Microarray technology is commonly used as a simple screening tool with a focus on selecting genes that exhibit extremely large differential expressions between different phenotypes. It lacks the ability to select genes that change their relationships with other genes in different biological conditions (differentially correlated genes). We intend to enrich the above procedure by proposing a nonparametric selection procedure that selects differentially correlated genes.

Results
Using both simulations and resampling techniques, we found that our procedure correctly detected genes that were not differentially expressed but differentially correlated. We also applied our procedure to a set of biological data and found some potentially important genes that were not selected by the traditional method.

Discussion and Conclusion
Microarray technology yields multidimensional information on the function of the whole genome. Rather than treating intergene correlation as a nuisance to the traditional gene selection procedures which are essentially univariate, our method utilizes the rich information contained in the correlation as a new selection criterion. It can provide additional useful candidate genes for the biologists.
Anti-Helicobacter pylori activity and immunostimulatory effect of extracts from Byrsonima crassa Nied. (Malpighiaceae)
Authors: Bonacorsi Cibele , Raddi Maria Stella G , Carlos Iracilda Z , Sannomiya Miriam , Vilegas Wagner 
Published: January 2009

Abstract

Background
Several in vitro studies have looked at the effect of medicinal plant extracts against Helicobacter pylori (H. pylori). Regardless of the popular use of Byrsonima crassa (B. crassa) as antiemetic, diuretic, febrifuge, to treat diarrhea, gastritis and ulcers, there is no data on its effects against H. pylori. In this study, we evaluated the anti-H. pylori of B. crassa leaves extracts and its effects on reactive oxygen/nitrogen intermediates induction by murine peritoneal macrophages.

Methods
The minimal inhibitory concentration (MIC) was determined by broth microdilution method and the production of hydrogen peroxide (H2O2) and nitric oxide (NO) by the horseradish peroxidase-dependent oxidation of phenol red and Griess reaction, respectively.

Results
The methanolic (MeOH) and chloroformic (CHCl3) extracts inhibit, in vitro, the growth of H. pylori with MIC value of 1024 μg/ml. The MeOH extract induced the production H2O2 and NO, but CHCl3 extract only NO.

Conclusion
Based in our results, B. crassa can be considered a source of compounds with anti-H. pylori activity, but its use should be done with caution in treatment of the gastritis and peptic ulcers, since the reactive oxygen/nitrogen intermediates are involved in the pathogenesis of gastric mucosal injury induced by ulcerogenic agents and H. pylori infections.
Characterization and comparative profiling of the small RNA transcriptomes in two phases of locust
Authors: Wei Yuanyuan , Chen Shuang , Yang Pengcheng , Ma Zongyuan , Kang Le 
Published: January 2009

Abstract
Background
All the reports on insect small RNAs come from holometabolous insects whose genome sequence data are available. Therefore, study of hemimetabolous insect small RNAs could provide more insights into evolution and function of small RNAs in insects. The locust is an important, economically harmful hemimetabolous insect. Its phase changes, as a phenotypic plasticity, result from differential gene expression potentially regulated at both the post-transcriptional level, mediated by small RNAs, and the transcriptional level.

Results
Here, using high-throughput sequencing, we characterize the small RNA transcriptome in the locust. We identified 50 conserved microRNA families by similarity searching against miRBase, and a maximum of 185 potential locust-specific microRNA family candidates were identified using our newly developed method independent of locust genome sequence. We also demonstrate conservation of microRNA*, and evolutionary analysis of locust microRNAs indicates that the generation of miRNAs in locusts is concentrated along three phylogenetic tree branches: bilaterians, coelomates, and insects. Our study identified thousands of endogenous small interfering RNAs, some of which were of transposon origin, and also detected many Piwi-interacting RNA-like small RNAs. Comparison of small RNA expression patterns of the two phases showed that longer small RNAs were expressed more abundantly in the solitary phase and that each category of small RNAs exhibited different expression profiles between the two phases.

Conclusions
The abundance of small RNAs in the locust might indicate a long evolutionary history of post-transcriptional gene expression regulation, and differential expression of small RNAs between the two phases might further disclose the molecular mechanism of phase changes.
Watching, Sight, and the Temporal Shape of Perceptual Activity
Authors: Crowther Thomas 
Published: January 2009

There has been relatively little discussion, in contemporary philosophy of mind, of the active aspects of perceptual processes. This essay presents and offers some preliminary development of a view about what it is for an agent to watch a particular material object throughout a period of time. On this view, watching is a kind of perceptual activity distinguished by a distinctive epistemic role.The essay presents a puzzle about watching an object that arises through elementary reflection on the consequences of two apparent truths about watching an object throughout a period of time. It proposes that the puzzle can be resolved by a view according to which for an agent to watch an object throughout a period of time is for that agent to maintain visual awareness of that object with the aim of perceptually knowing what that object is doing.The essay goes on to make some further suggestions about how the apparatus developed in connection with the notion of watching may enable us to offer related explanations of other kinds of perceptual activity. It proposes that a useful distinction can be drawn between perceptual activities like watching which have as their aim knowledge of what an object is doing and activities like looking or visually scrutinizing which have as their aims knowledge of the states or conditions of the objects of perceptual awareness.
Water homeostasis in bees, with the emphasis on sociality
Authors: Nicolson Susan W. 
Published: January 2009

SUMMARYAvenues of water gain and loss in bees are examined here at two levels of organisation: the individual and the colony. Compared with the majority of terrestrial insects, bees have a high water turnover. This is due to their nectar diet and, in larger species, substantial metabolic water production during flight, counteracted by high evaporative and excretory losses. Water fluxes at the colony level can also be very high. When incoming nectar is dilute, honeybees need to remove large volumes of water by evaporation. On the other hand, water is not stored in the nest and must be collected for evaporative cooling and for feeding the brood. Water regulation has many similarities at individual and colony levels. In particular, manipulation of nectar or water on the tongue is extensively used by bees to increase evaporation for either food-concentrating or cooling purposes.
Too much of a good thing: how insects cope with excess ions or toxins in the diet
Authors: O'Donnell M. J. 
Published: January 2009

SUMMARYMuch of our understanding of the ionoregulatory and excretory physiology of blood-feeding insects can be traced to a series of papers by Simon Maddrell and colleagues in the 1970s and 1980s. These studies of the Malpighian (renal)tubules of Rhodnius prolixus revealed a number of physiological adaptations to the short-term and long-term stresses associated with blood feeding. More recent electrophysiological studies using voltage- and ion-selective microelectrodes have extended our understanding of the mechanisms and control of ion transport by the secretory and reabsorptive segments of the Rhodnius Malpighian tubule. The discovery that the rates of transport of organic anions, urates and Ca2+ are synchronized to coincide with the appearance of the products of blood meal digestion in the haemolymph of Rhodnius has stimulated parallel studies in Drosophila. This recent research has examined how excretory mechanisms for organic cations and organic anions are altered by exposure to such compounds in the diet. These studies also show that the Drosophila Malpighian tubule provides a useful model for analysis of the roles of transporters such as P-glycoproteins and multidrug resistance-associated proteins in the excretion of toxins.
Neuroendocrine control of ionic homeostasis in blood-sucking insects
Authors: Coast Geoffrey M. 
Published: January 2009

SUMMARYThe pioneering work of Simon Maddrell established that the rapid postprandial diuresis of the haematophagous insect Rhodnius prolixusis controlled by a diuretic hormone and demonstrated the role of the Malpighian tubules in meeting the volumic, osmotic and ionic challenges posed by an enormous blood meal. A number of diuretic and antidiuretic hormones that control secretion of primary urine by Malpighian tubules have now been identified, but little is known of the interplay between these hormones and those that regulate transport processes in the hindgut. This review therefore focuses on the control of ionic homeostasis in Rhodnius and mosquitoes, because primary urine is voided virtually unchanged during the rapid diuresis that follows a blood meal. At such times, the hindgut has a negligible impact on the volume and composition of the final urine, and neurohormones acting on the Malpighian tubules have a dominant role in the control of ionic homeostasis.
Signaling to the apical membrane and to the paracellular pathway: changes in the cytosolic proteome ofAedesMalpighian tubules
Authors: Beyenbach Klaus W. , Baumgart Sabine , Lau Kenneth , Piermarini Peter M. , Zhang Sheng 
Published: January 2009

SUMMARYUsing a proteomics approach, we examined the post-translational changes in cytosolic proteins when isolated Malpighian tubules of Aedes aegyptiwere stimulated for 1 min with the diuretic peptide aedeskinin-III (AK-III,10–7 mol l–1). The cytosols of control (C)and aedeskinin-treated (T) tubules were extracted from several thousand Malpighian tubules, subjected to 2-D electrophoresis and stained for total proteins and phosphoproteins. The comparison of C and T gels was performed by gel image analysis for the change of normalized spot volumes. Spots with volumes equal to or exceeding C/T ratios of ±1.5 were robotically picked for in-gel digestion with trypsin and submitted for protein identification by nanoLC/MS/MS analysis. Identified proteins covered a wide range of biological activity. As kinin peptides are known to rapidly stimulate transepithelial secretion of electrolytes and water by Malpighian tubules, we focused on those proteins that might mediate the increase in transepithelial secretion. We found that AK-III reduces the cytosolic presence of subunits A and B of the V-type H+ ATPase, endoplasmin, calreticulin, annexin,type II regulatory subunit of protein kinase A (PKA) and rab GDP dissociation inhibitor and increases the cytosolic presence of adducin, actin,Ca2+-binding protein regucalcin/SMP30 and actin-depolymerizing factor. Supporting the putative role of PKA in the AK-III-induced activation of the V-type H+ ATPase is the effect of H89, an inhibitor of PKA,on fluid secretion. H89 reverses the stimulatory effect of AK-III on transepithelial fluid secretion in isolated Malpighian tubules. However,AK-III does not raise intracellular levels of cAMP, the usual activator of PKA, suggesting a cAMP-independent activation of PKA that removes subunits A and B from the cytoplasm in the assembly and activation of the V-type H+ ATPase. Alternatively, protein kinase C could also mediate the activation of the proton pump. Ca2+ remains the primary intracellular messenger of the aedeskinins that signals the remodeling of the paracellular complex apparently through protein kinase C, thereby increasing transepithelial anion secretion. The effects of AK-III on active transcellular and passive paracellular transport are additive, if not synergistic, to bring about the rapid diuresis.
Long-term treatment of acromegalic patients resistant to somatostatin analogues with the GH receptor antagonist pegvisomant: its efficacy in relation to gender and previous radiotherapy
Authors: Marazuela Mónica , Lucas Tomás , Alvarez-Escolá Cristina , Puig-Domingo Manel , de la Torre Nuria Garcia , de Miguel-Novoa Paz , Duran-Hervada Alejandra , Manzanares Rafael , Luque-Ramírez Manuel , Halperin Irene , Casanueva Felipe F , Bernabeu Ignacio 
Published: January 2009

ContextPegvisomant is an effective treatment for somatostatin analogue-resistant acromegaly, but the determinants defining the response to this treatment are largely unknown.ObjectiveTo investigate the efficacy of pegvisomant treatment in resistant acromegalic patients (e.g. serum IGF1 at least 1.25×upper normal limit) in a clinical setting and the factors conditioning this response.Design and settingA retrospective cross-sectional study performed in six Spanish University hospitals from 2004 to 2007.PatientsForty-four acromegalic patients (61.4% female, mean age: 49±14), 95% of whom had undergone pituitary surgery and 61% having received pituitary radiotherapy. The mean follow-up was 22.7±11.2 months.Main outcome measuresIGF1 levels reflected treatment efficacy, and the influence of gender, age, weight, previous radiotherapy and duration of treatment was assessed.ResultsIGF1 normalisation was achieved in 84% of the patients. Male gender (P<0.05), previous irradiation (P<0.05) and the treatment duration (r=0.364, P<0.02) were associated with a better response to pegvisomant therapy. There was a significant decrease in HbA1c (P<0.001) and in the mean insulin dose (P<0.01) in acromegalic diabetic patients. Although 25% of patients experienced mild adverse events, pegvisomant was only withdrawn in four patients due to side effects (two cases of tumour growth, one liver dysfunction and one headache).ConclusionsLong-term pegvisomant is a very effective therapy in resistant acromegaly. Male gender and prior radiotherapy influence the therapeutic response rate.
Cytoreductive Nephrectomy in Metastatic Clear-Cell Renal Cell Carcinoma: Perspectives in the Tyrosine Kinase Inhibitor Era
Authors: Biswas Swethajit , Kelly John , Eisen Tim 
Published: January 2009

Learning Objectives
Summarize the relationship of data on nephrectomy in metastatic RCC to immunotherapy. Apply to your practice available prognostic predictive scoring systems. Compare and contrast the potential benefits and costs of cytoreductive nephrectomy in the TKI era.
This article is available for continuing medical education credit at CME.TheOncologist.com.
The National Cancer Institute and Its Director: Worthy of Our Full Support
Authors: Chabner Bruce A. 
Published: January 2009

Abstract
Editor-in-Chief of The Oncologist, Bruce A. Chabner, M.D., calls for full support of the National Cancer Institute and its Director, John E. Niederhuber, in the institute’s five priorities outlined in the article in this issue by Dr. Niederhuber and colleagues.
A quantitative structure-activity relationship for predicting metabolic biotransformation rates for organic chemicals in fish
Authors: Arnot Jon A. , Meylan William , Tunkel Jay , Howard Phil H. , Mackay Don , Bonnell Mark , Boethling Robert S. 
Published: January 2009

AbstractAn evaluated database of whole body in vivo biotransformation rate estimates in fish was used to develop a model for predicting the primary biotransformation half-lives of organic chemicals. The estimated biotransformation rates were converted to half-lives and divided into a model development set (n = 421) and an external validation set (n = 211) to test the model. The model uses molecular substructures similar to those of other biodegradation models. The biotransformation half-life predictions were calculated based on multiple linear regressions of development set data against counts of 57 molecular substructures, the octanol-water partition coefficient, and molar mass. The coefficient of determination (r2) for the development set was 0.82, the cross-validation (leave-one-out coefficient of determination, q2) was 0.75, and the mean absolute error (MAE) was 0.38 log units (factor of 2.4). Results for the external validation of the model using an independent test set were r2 = 0.73 and MAE = 0.45 log units (factor of 2.8). For the development set, 68 and 95% of the predicted values were within a factor of 3 and a factor of 10 of the expected values, respectively. For the test (or validation) set, 63 and 90% of the predicted values were within a factor of 3 and a factor of 10 of the expected values, respectively. Reasons for discrepancies between model predictions and expected values are discussed and recommendations are made for improving the model. This model can predict biotransformation rate constants from chemical structure for screening level bioaccumulation hazard assessments, exposure and risk assessments, comparisons with other in vivo and in vitro estimates, and as a contribution to testing strategies that reduce animal usage.
The Modifying Effect of Social Class on the Relationship Between Body Mass Index and Breast Cancer Incidence
Authors: Torio Celeste Marie , Klassen Ann C. , Curriero Frank C. , Caballero Benjamin , Helzlsouer Kathy 
Published: January 2009

Objectives. We sought to determine whether social class modifies the effect of BMI on breast cancer incidence. Methods. Participants included 5642 postmenopausal White women recruited in 1989 to CLUE II, a prospective cohort study in Washington County, Maryland. We obtained exposure data from CLUE II and the 1990 US Census. We used survival and random-effects Cox proportional hazards analyses to determine the association of social class and BMI with breast cancer incidence. Results. Education was independently associated with increased risk of breast cancer incidence (hazard ratio [HR] = 1.06; 95% confidence interval [CI] = 1.01, 1.11; P < .05); contextual measures of social class were not. Education modified the effect of BMI at age 21 years (HR = 0.98; 95% CI = 0.97, 0.99); area-level social class modified the effect of BMI at baseline (HR = 0.97; 95% CI = 0.94, 0.99) and BMI change (HR = 0.98; 95% CI = 0.95, 1.00). Subpopulation analyses that were adjusted for hormone use, parity, and breast-feeding found similar effects. Conclusions. Social class moderates the influence of body size on breast cancer incidence. Public health efforts, therefore, should advocate for policies that improve social conditions to decrease the burden of breast cancer.