bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glia maturation factor-γ mediates neutrophil chemotaxis
Authors: Aerbajinai Wulin , Liu Lunhua , Chin Kyung , Zhu Jianqiong , Parent Carole A , Rodgers Griffin P 
Published: June 2011

ABSTRACTChemotaxis is fundamental to the directional migration of neutrophils toward endogenous and exogenous chemoattractants. Recent studies have demonstrated that ADF/cofilin superfamily members play important roles in reorganizing the actin cytoskeleton by disassembling actin filaments. GMFG, a novel ADF/cofilin superfamily protein that is expressed in inflammatory cells, has been implicated in regulating actin reorganization in microendothelial cells, but its function in neutrophils remains unclear. Here, we show that GMFG is an important regulator for cell migration and polarity in neutrophils. Knockdown of endogenous GMFG impaired fMLF- and IL-8 (CXCL8)-induced chemotaxis in dHL-60 cells. GMFG knockdown attenuated the formation of lamellipodia at the leading edge of cells exposed to fMLF or CXCL8, as well as the phosphorylation of p38 and PAK1/2 in response to fMLF or CXCL8. Live cell imaging revealed that GMFG was recruited to the leading edge of cells in response to fMLF, as well as CXCL8. Overexpression of GMFG enhanced phosphorylation of p38 but not of PAK1/2 in dHL-60 cells. In addition, we found that GMFG is associated with WAVE2. Taken together, our findings suggest that GMFG is a novel factor in regulating neutrophil chemotaxis by modulating actin cytoskeleton reorganization.
Modulation of regulatory T cell-Th17 balance by plasmacytoid dendritic cells
Authors: Gautreau Laetitia , Chabannes Dominique , Heslan Michèle , Josien Régis 
Published: June 2011

ABSTRACTTregs represent an interesting therapeutic tool to modulate immune responses that could be deleterious in autoimmune diseases and in transplantation. However, phenotype and functions of Tregs do not seem to be stable, and recent data suggest that FoxP3-expressing Tregs can be driven to produce IL-17. In this study, we have analyzed the role of pDCs versus cDCs on Treg responses and underlined that pDCs have an intrinsic, unique capacity to induce IL-17 secretion from T cells. We showed in rats that FoxP3+ Tregs were able to secrete IL-17 only when stimulated by allogeneic, mature pDCs but not cDCs. In addition, in rats and mice, mature pDCs but not cDCs inhibited in vitro Treg-suppressive functions and in the presence of Tregs, supported Th17 differentiation from naive T cells through secretion of high amounts of IL-6. These data suggest an important role for pDCs in modulating or switching Treg function and allowing Th17 differentiation.
Optimal walking speed following changes in limb geometry
Authors: Leurs Françoise , Ivanenko Yuri P. , Bengoetxea Ana , Cebolla Ana-Maria , Dan Bernard , Lacquaniti Francesco , Cheron Guy A. 
Published: June 2011

SUMMARY
The principle of dynamic similarity states that the optimal walking speeds of geometrically similar animals are independent of size when speed is normalized to the dimensionless Froude number (Fr). Furthermore, various studies have shown similar dimensionless optimal speed (Fr ∼0.25) for animals with quite different limb geometries. Here, we wondered whether the optimal walking speed of humans depends solely on total limb length or whether limb segment proportions play an essential role. If optimal walking speed solely depends on the limb length then, when subjects walk on stilts, they should consume less metabolic energy at a faster optimal speed than when they walk without stilts. To test this prediction, we compared kinematics, electromyographic activity and oxygen consumption in adults walking on a treadmill at different speeds with and without articulated stilts that artificially elongated the shank segment by 40 cm. Walking on stilts involved a non-linear reorganization of kinematic and electromyography patterns. In particular, we found a significant increase in the alternating activity of proximal flexors–extensors during the swing phase, despite significantly shorter normalized stride lengths. The minimal metabolic cost per unit distance walked with stilts occurred at roughly the same absolute speed, corresponding to a lower Fr number (Fr ∼0.17) than in normal walking (Fr ∼0.25). These findings are consistent with an important role of limb geometry optimization and kinematic coordination strategies in minimizing the energy expenditure of human walking.
Decreased hydrophobicity of iridescent feathers: a potential cost of shiny plumage
Authors: Eliason Chad M. , Shawkey Matthew D. 
Published: June 2011

SUMMARYHonest advertisement models posit that sexually selected traits are costly to produce, maintain or otherwise bear. Brightly coloured feathers are thought to be classic examples of these models, but evidence for a cost in feathers not coloured by carotenoid pigments is scarce. Unlike pigment-based colours, iridescent feather colours are produced by light scattering in modified feather barbules that are characteristically flattened and twisted towards the feather surface. These modifications increase light reflectance, but also expose more surface area for water adhesion, suggesting a potential trade-off between colour and hydrophobicity. Using light microscopy, spectrometry, contact angle goniometry and self-cleaning experiments, we show that iridescent feathers of mallards, Anas platyrhynchos, are less hydrophobic than adjacent non-iridescent feathers, and that this is primarily caused by differences in barbule microstructure. Furthermore, as a result of this decreased hydrophobicity, iridescent feathers are less efficient at self-cleaning than non-iridescent feathers. Together, these results suggest a previously unforeseen cost of iridescent plumage traits that may help to explain the evolution and distribution of iridescence in birds.
Sweat analysis using indirect ion-selective electrode on the routine chemistry analyser meets UK guidelines
Authors: Hulstein Janine J J , van 't Sant Peter 
Published: June 2011

Background According to consensus documents, sweat testing remains the standard for diagnosing cystic fibrosis. We studied a novel method of sweat analysis on two chemistry platforms: Dimension Vista (Siemens Healthcare Diagnostics) and Aeroset (Abbott). Methods Sweat collected from healthy individuals and aqueous samples in the critical range for sweat analysis were measured using the Orion 290 plus (Thermo Electron Corporation), Chiron 925 chloride analyser (Sherwood Scientific Ltd), flame photometry, sweat-chek analyser and indirect ion-selective electrodes (ISE) of Vista and Aeroset. For measurement on ISE, an addition protocol was designed. Results Within-run and between-run variation coefficients of Aeroset and Vista remained <5% as prescribed by UK guidelines. The correlation between the chloride analyser and chloride concentrations analysed on Vista or Aeroset was, respectively, y = 0.96x + 7.61 ( r2 0.990) and y = 0.97x + 1.10 ( r2 0.930) and between sweat-chek (conductivity) and sodium concentrations analysed on Vista or Aeroset was, respectively, y = 1.08x - 4.0 ( r2 0.967) and y = 1.13x - 1.00 ( r2 0.939). When classified according to medical decision rules (30 mmol/L and 60 mmol/L chloride, combined with sodium concentration), the same classification was found with the ISE-module and conventional methods for all samples. Conclusion We describe a simple procedure for sweat analysis using the ISE-module of two different chemistry platforms. This procedure meets the requirements as described in UK guidelines.
Vancomycin Dosing: Assessment of Time to Therapeutic Concentration and Predictive Accuracy of Pharmacokinetic Modeling Software
Authors: Nunn Maya O , Corallo Carmela E , Aubron Cecile , Poole Susan , Dooley Michael J , Cheng Allen C 
Published: June 2011

BACKGROUND: Therapeutic drug monitoring is usually required for safe and effective administration of vancomycin. However, dosing recommendations from published guidelines are not suitable in achieving therapeutic vancomycin concentrations in a timely manner in patients with normal renal function. OBJECTIVE: To audit vancomycin dosing and concentrations at our institution and evaluate the predictive accuracy of a pharmacokinetic simulation program, with a view to implementing a pharmacy-based pharmacokinetic service for vancomycin monitoring. METHODS: Patients receiving vancomycin were identified prospectively through the therapeutic drug monitoring archives. Patient information was obtained from medication charts and medical records that were located on wards. Data were entered into the MM-USC*Pack program (Jelliffe R, University of Southern California, 2008, version 12.10). This software was used to predict initial and subsequent concentrations of vancomycin based on patient parameters. The predictive accuracy of this software was evaluated by comparing the predicted concentrations to the observed concentrations. RESULTS: During a 6-week period, 204 concentrations were measured in 77 patients. The most common dosing regimen was 1 g every 12 hours. Overall, initial trough concentrations were subtherapeutic (<10 mg/L) in 58% of patients and trough concentrations did not become therapeutic at any stage throughout therapy in 25% of patients. The pharmacokinetic modeling software demonstrated little systematic bias (−3.1%), but the precision (median prediction error) was 23% (interquartile range, 11-45%). Predictions were poorer in obese patients (body mass index >35 kg/m2) and in patients with unstable renal function. CONCLUSIONS: A delay in attaining target trough concentrations was observed in a significant proportion of patients. Pharmacokinetic modeling software is a potential tool to improve the timeliness of achieving adequate dosing by allowing concentrations to be determined prior to steady-state. The program was able to predict vancomycin concentrations across a heterogeneous patient population with little systematic bias, but only moderate precision.
Persistent Hiccups Associated with Epidural Ropivacaine in a Newborn
Authors: Bagdure Dayanand N , Reiter Pamela D , Bhoite Girija R , Dobyns Emily L , Laoprasert Pramote 
Published: June 2011

OBJECTIVE: To report a case of persistent hiccups associated with epidural ropivacaine in a newborn infant. CASE SUMMARY: A term female infant (3.05 kg) received epidural ropivacaine for pain control during and after an operative procedure to correct a tracheoesophageal fistula. Three intermittent doses of ropivacaine were administered during the operative period (total dose 2.29 mg/kg) followed by a continuous epidural (caudal) infusion (0.1% ropivacaine; initial dose 0.23 mg/kg/h plus fentanyl 0.46 μg/kg/h). The infant was extubated in the recovery area and transferred to the intensive care unit. Within hours of transfer, she developed persistent hiccups. The epidural infusion was titrated for pain control, up to 0.32 mg/kg/h (ropivacaine). The hiccup frequency increased to every 10-30 seconds, with the patient appearing hypotonic with lip trembling and intermittent tongue fasciculation. An electroencephalogram did not show any epileptiform activity or focal features consistent with seizure activity. The epidural infusion was reduced to 0.26 mg/kg/h (ropivacaine), with dramatic improvement in hiccups and tone. The infusion was discontinued and complete resolution of hiccups was observed. DISCUSSION: Ropivacaine is commonly used for infiltration anesthesia and peripheral and epidural block anesthesia. Use of the Naranjo probability scale determined that our patient's hiccups were probably caused by ropivacaine. To our knowledge, this is the first report of persistent hiccups associated with epidural ropivacaine. CONCLUSIONS: Clinicians should consider the potential of neurotoxicity, manifested as persistent hiccups, when epidural ropivacaine is administered to young infants.
Pregabalin-Induced Hepatotoxicity
Authors: Sendra Juan Moll , Junyent Teresa Torrecilla , Pellicer Maria José Remigia 
Published: June 2011

OBJECTIVE: To report a case of acute elevation of hepatic enzyme levels as a probable adverse reaction associated with pregabalin. CASE SUMMARY: A 59-year-old man with a history of mantle cell lymphoma developed neuropathic pain and was treated with pregabalin 25 mg daily. Fourteen days after beginning pregabalin therapy, he developed left ankle edema and elevation of liver enzyme levels. Peak values were aspartate transaminase 907 U/L, alanine transaminase 1582 U/L, and γ-glutamyltransferase 510 U/L. Pregabalin was discontinued and hepatic enzyme levels returned gradually (over 4 months) to baseline levels. DISCUSSION: Many medications are commonly associated with liver injury; few cases of pregabalin-associated hepatotoxicity have been documented. A MEDLINE search (1966-November 2010) revealed 2 reports of acute liver injury with the initiation of pregabalin. In our patient, with hemosiderosis after hematopoietic cell transplantation, pregabalin worsened the underlying liver injury. The low pregabalin dosage and the short time to elevation of liver enzyme levels suggest an idiosyncratic reaction. According to the Naranjo probability scale and the Council for International Organizations of Medical Sciences probability scale, this reaction was probably due to pregabalin. CONCLUSIONS: Prescribers should be alert to the possibility of idiosyncratic hepatotoxicity associated with pregabalin use.
Colchicine for the Primary Prevention of the Postpericardiotomy Syndrome
Authors: Mack Diana R , Cahoon William D , Lowe Denise K 
Published: June 2011

OBJECTIVE: To review literature regarding the safety and efficacy of colchicine for the primary prevention of the postpericardiotomy syndrome (PPS). DATA SOURCES: Searches of MEDLINE (1966-April 2011) and Cochrane Database (1993-April 2011) were conducted. Key search terms included postpericardiotomy syndrome, postcardiac injury syndrome, and colchicine. Limits were set for articles written in English with human subjects. Additional data were identified through bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. All primary data were eligible for inclusion if they evaluated the safety and/or efficacy of colchicine for the primary prevention of PPS. Two prospective trials were identified and included for review. DATA SYNTHESIS: PPS occurs in 10-40% of patients who undergo cardiac surgery and is associated with significant morbidity. Effective medications used for the treatment of PPS include nonsteroidal antiinflammatory drugs or corticosteroids. Unfortunately, effective drug therapy for the primary prevention of PPS does not exist. Colchicine, an antiinflammatory agent with possible immunopathic ***antifibroblast properties, has shown benefit in the treatment and secondary prevention of pericarditis; thus, its use for primary prevention of PPS has been investigated. Limited data evaluating colchicine for the primary prevention of PPS have been published. However, results of the largest, well-designed trial showed positive efficacy outcomes for colchicine reducing the incidence of PPS with minimal adverse effects. CONCLUSIONS: At this time, there are not sufficient data to recommend colchicine as routine therapy for the primary prevention of PPS in patients undergoing cardiac surgery. Large clinical trials need to be conducted.
Luminescence properties of uranium(VI) citrate and uranium(VI) oxalate species and their application in the determination of complex formation constants
Authors: Günther A. , Steudtner Robin , Schmeide K. , Bernhard G. 
Published: June 2011

AbstractFor the first time, the interaction of uranium(VI) with citric acid and oxalic acid in aqueous solution was investigated using time-resolved laser-induced fluorescence spectroscopy (TRLFS) between pH 2 and 4. The complex species UO2cit−and (UO2)2(cit)22−formed in citrate medium as well as UO2ox and UO2(ox)22−formed in oxalate medium show no luminescence emissions at room temperature. However, by coupling the fluorescence measurement technique with a low temperature system (−120 ºC, cryo-TRLFS), emission signals of the various complex species could be detected. The emission signals are bathochromic shifted in comparison to the emission maxima of the uncomplexed uranium(VI) cation. Using the spectroscopic data, the corresponding complex formation constants were calculated, which corroborate literature data.
CDC73-related hereditary hyperparathyroidism: five new mutations and the clinical spectrum
Authors: Frank-Raue Karin , Haag Christine , Schulze Egbert , Keuser Roger , Raue Friedhelm , Dralle Henning , Lorenz Kerstin 
Published: June 2011

ObjectiveHyperparathyroidism-jaw tumour (HPT-JT) syndrome is a rare autosomal dominant cause of benign and malignant parathyroid tumours, ossifying jaw tumours, various cystic and neoplastic renal abnormalities and benign and malignant uterine tumours. Disease-causing mutations have been localised in the tumour suppressor gene CDC73. There is limited information available on the mutations, and resulting phenotypes and long-term follow-up data are especially scarce.DesignWe analysed the clinical data from 16 patients (including three families) carrying mutations in the CDC73 gene. We describe five new mutations/gene variants, the corresponding phenotypes of these carriers and the long-term follow-up.MethodsThe 16 patients were evaluated at an endocrine outpatient clinic and at a surgical department. DNA samples were obtained for sequence analysis of the CDC73 gene.ResultsClinical features of HPT-JT syndrome were detected in 13 of the 15 carriers with germline CDC73 mutations. The major features were benign (n=7; 47%) or cancerous (n=3; 20%) HPT-JT was present in eight cases (53%). Most patients had severe hypercalcaemia, and median serum calcium levels were 3.36 mmol/l. A patient with non-secretory parathyroid carcinoma was included. HPT was diagnosed at a median age of 28.5 years. Mutational analysis of the CDC73 gene identified eight sequence changes, three of them have been reported previously, whereas five are novel: c.1346delG, c.88_94delTTCTCCT, the non-coding variants, c.307+5G>T and c.424−5T>C and c.*12C>A of unknown significance.ConclusionsThis study significantly increases the information available on the mutations and phenotypes of HPT-JT syndrome.
On the Fixation Process of a Beneficial Mutation in a Variable Environment
Authors: Uecker Hildegard , Hermisson Joachim 
Published: June 2011

Abstract
A population that adapts to gradual environmental change will typically experience temporal variation in its population size and the selection pressure. On the basis of the mathematical theory of inhomogeneous branching processes, we present a framework to describe the fixation process of a single beneficial allele under these conditions. The approach allows for arbitrary time-dependence of the selection coefficient s(t) and the population size N(t), as may result from an underlying ecological model. We derive compact analytical approximations for the fixation probability and the distribution of passage times for the beneficial allele to reach a given intermediate frequency. We apply the formalism to several biologically relevant scenarios, such as linear or cyclic changes in the selection coefficient, and logistic population growth. Comparison with computer simulations shows that the analytical results are accurate for a large parameter range, as long as selection is not very weak.
The Balance Between Mutators and Nonmutators in Asexual Populations
Authors: Desai Michael M , Fisher Daniel S 
Published: June 2011

Abstract
Mutator alleles, which elevate an individual’s mutation rate from 10 to 10,000-fold, have been found at high frequencies in many natural and experimental populations. Mutators are continually produced from nonmutators, often due to mutations in mismatch-repair genes. These mutators gradually accumulate deleterious mutations, limiting their spread. However, they can occasionally hitchhike to high frequencies with beneficial mutations. We study the interplay between these effects. We first analyze the dynamics of the balance between the production of mutator alleles and their elimination due to deleterious mutations. We find that when deleterious mutation rates are high in mutators, there will often be many “young,” recently produced mutators in the population, and the fact that deleterious mutations only gradually eliminate individuals from a population is important. We then consider how this mutator–nonmutator balance can be disrupted by beneficial mutations and analyze the circumstances in which fixation of mutator alleles is likely. We find that dynamics is crucial: even in situations where selection on average acts against mutators, so they cannot stably invade, the mutators can still occasionally generate beneficial mutations and hence be important to the evolution of the population.
Successive and Targeted DNA Integrations in the Drosophila Genome by Bxb1 and φC31 Integrases
Authors: Huang Juan , Ghosh Pallavi , Hatfull Graham F , Hong Yang 
Published: June 2011

Abstract
At present φC31 is the only phage integrase system available for directionally regulated site-specific DNA integration in the Drosophila genome. Here we report that mycobacteriophage Bxb1 integrase also mediates targeted DNA integration in Drosophila with high specificity and efficiency. By alternately using Bxb1 and φC31, we were able to carry out multiple rounds of successive and targeted DNA integrations in our genomic engineering founder lines for the purpose of generating complex knock-in alleles.
A Role for Histone H4K16 Hypoacetylation in Saccharomyces cerevisiae Kinetochore Function
Authors: Choy John S , Acuña Rachel , Au Wei-Chun , Basrai Munira A 
Published: June 2011

Abstract
Hypoacetylated H4 is present at regional centromeres; however, its role in kinetochore function is poorly understood. We characterized H4 acetylation at point centromeres in Saccharomyces cerevisiae and determined the consequences of altered H4 acetylation on chromosome segregation. We observed low levels of tetra-acetylated and K16 acetylated histone H4 (H4K16Ac) at centromeres. Low levels of H4K16Ac were also observed at noncentromeric regions associated with Cse4p. Inhibition of histone deacetylases (HDAC) using nicotinamide (NAM) caused lethality in cse4 and hhf1-20 kinetochore mutants and increased centromeric H4K16Ac. Overexpression of Sas2-mediated H4K16 acetylation activity in wild-type cells led to increased rates of chromosome loss and synthetic dosage lethality in kinetochore mutants. Consistent with increased H4K16 acetylation as a cause of the phenotypes, deletion of the H4K16 deacetylase SIR2 or a sir2-H364Y catalytic mutant resulted in higher rates of chromosome loss compared to wild-type cells. Moreover, H4K16Q acetylmimic mutants displayed increased rates of chromosome loss compared to H4K16R nonacetylatable mutants and wild-type cells. Our work shows that hypoacetylated centromeric H4 is conserved across eukaryotic centromeres and hypoacetylation of H4K16 at centromeres plays an important role in accurate chromosome segregation.