bluuebunny/crossref_metadata_2025 huggingface dataset:
A Nonselenoprotein from Amphioxus Deiodinates Triac But Not T3: Is Triac the Primordial Bioactive Thyroid Hormone?
Authors: Klootwijk Wim , Friesema Edith C. H. , Visser Theo J.
Published: June 2011

Thyroid hormone (TH) is important for metamorphosis in many species, including the cephalochordate Branchiostoma floridae, a marine invertebrate (amphioxus) living in warmer coastal areas. Branchiostoma expresses a TH receptor, which is activated by 3,3′,5-triiodothyroacetic acid (TA3) but not by T3. The Branchiostoma genome also contains multiple genes coding for proteins homologous to iodothyronine deiodinases in vertebrates, selenoproteins catalyzing the activation or inactivation of TH. Three Branchiostoma deiodinases have been cloned: two have a catalytic Sec, and one, bfDy, has a Cys residue. We have studied the catalytic properties of bfDy in transfected COS1 cells by HPLC analysis of reactions with 125I-labeled substrates and dithiothreitol as cofactor. We could not detect deiodination of T4, T3, or rT3 by bfDy but observed rapid and selective inner ring deiodination (inactivation) of TA3 and 3,3′,5,5′-tetraiodothyroacetic acid (TA4). Deiodination of TA3 by bfDy was optimal at 25 C and 10 mm dithiothreitol. bfDy was extremely labile at 37 C, showing a half-life of less than 2 min, in contrast with a half-life of more than 60 min at 25 C. Deiodination of labeled TA3 was inhibited dose dependently by unlabeled TA3≈TA4>T4≈T3. Michaelis-Menten analysis yielded Michaelis-Menten constant values of 6.8 and 68 nm and maximum velocity values of 1.4 and 5.4 pmol/min·mg protein for TA3 and TA4, respectively. bfDy was not inhibited by propylthiouracil and iodoacetate and only weakly by goldthioglucose and iopanoic acid. In conclusion, we demonstrate rapid inactivation of TA3 and TA4 but not of T3 and T4 by the first reported natural nonselenodeiodinase. Our findings support the hypothesis that TA3 is a primordial bioactive TH.
Differential altered stability and transcriptional activity of ΔNp63 mutants in distinct ectodermal dysplasias
Authors: Browne Gareth , Cipollone Rita , Lena Anna Maria , Serra Valeria , Zhou Huiqing , van Bokhoven Hans , Dötsch Volker , Merico Daniele , Mantovani Roberto , Terrinoni Alessandro , Knight Richard A. , Candi Eleonora , Melino Gerry
Published: June 2011

Heterozygous mutations of p63, a key transcription factor in epithelial development, are causative in a variety of human ectodermal dysplasia disorders. Although the mutation spectrum of these disorders displays a striking genotype–phenotype association, the molecular basis for this association is only superficially known. Here, we characterize the transcriptional activity and protein stability of ΔNp63 mutants (that is, mutants of a p63 isoform that lacks the N-terminal transactivation domain) that are found in ectrodactyly–ectodermal dysplasia–cleft syndrome (EEC), ankyloblepharon–ectodermal dysplasia–clefting syndrome (AEC) and nonsyndromic split-hand/split-foot malformation (SHFM). DNA-binding and sterile alpha motif (SAM) domain mutants accumulate in the skin of EEC and AEC syndrome patients, respectively, and show extended half lives in vitro. By contrast, C-terminal mutations found in SHFM patients have half-lives similar to that of the wild-type protein. The increased half-life of EEC and AEC mutant proteins was reverted by overexpression of wild-type ΔNp63. Interestingly, the mutant proteins exhibit normal binding to and degradation by the E3 ubiquitin ligase Itch. Finally, EEC and AEC mutant proteins have reduced transcriptional activity on several skin-specific gene promoters, whereas SHFM mutant proteins are transcriptionally active. Our results, therefore, provide evidence for a regulatory feedback mechanism for p63 that links transcriptional activity to regulation of protein homeostasis by an unknown mechanism. Disruption of this regulatory mechanism might contribute to the pathology of p63-related developmental disorders.
Knockdown of Fbxo7 reveals its regulatory role in proliferation and differentiation of haematopoietic precursor cells
Authors: Meziane El Kahina , Randle Suzanne J. , Nelson David E. , Lomonosov Mikhail , Laman Heike
Published: June 2011

Fbxo7 is an unusual F-box protein because most of its interacting proteins are not substrates for ubiquitin-mediated degradation. Fbxo7 directly binds p27 and Cdk6, enhances the level of cyclin D–Cdk6 complexes, and its overexpression causes Cdk6-dependent transformation of immortalised fibroblasts. Here, we test the ability of Fbxo7 to transform haematopoietic pro-B (Ba/F3) cells which, unexpectedly, it was unable to do despite high levels of Cdk6. Instead, reduction of Fbxo7 expression increased proliferation, decreased cell size and shortened G1 phase. Analysis of cell cycle regulators showed that cells had decreased levels of p27, and increased levels of S phase cyclins and Cdk2 activity. Also, Fbxo7 protein levels correlated inversely with those of CD43, suggesting direct regulation of its expression and, therefore, of B cell maturation. Alterations to Cdk6 protein levels did not affect the cell cycle, indicating that Cdk6 is neither rate-limiting nor essential in Ba/F3 cells; however, decreased expression of Cdk6 also enhanced levels of CD43, indicating that expression of CD43 is independent of cell cycle regulation. The physiological effect of reduced levels of Fbxo7 was assessed by creating a transgenic mouse with a LacZ insertion into the Fbxo7 locus. Homozygous Fbxo7LacZ mice showed significantly increased pro-B cell and pro-erythroblast populations, consistent with Fbxo7 having an anti-proliferative function and/or a role in promoting maturation of precursor cells.
Interaction between LIS1 and PDE4, and its role in cytoplasmic dynein function
Authors: Murdoch Hannah , Vadrevu Suryakiran , Prinz Anke , Dunlop Allan J. , Klussmann Enno , Bolger Graeme B. , Norman James C. , Houslay Miles D.
Published: June 2011

LIS1, a WD40 repeat scaffold protein, interacts with components of the cytoplasmic dynein motor complex to regulate dynein-dependent cell motility. Here, we reveal that cAMP-specific phosphodiesterases (PDE4s) directly bind PAFAH1B1 (also known as LIS1). Dissociation of LIS1–dynein complexes is coupled with loss of dynein function, as determined in assays of both microtubule transport and directed cell migration in wounded monolayers. Such loss in dynein functioning can be achieved by upregulation of PDE4, which sequesters LIS1 away from dynein, thereby uncovering PDE4 as a regulator of dynein functioning. This process is facilitated by increased intracellular cAMP levels, which selectively augment the interaction of long PDE4 isoforms with LIS1 when they become phosphorylated within their regulatory UCR1 domain by protein kinase A (PKA). We propose that PDE4 and dynein have overlapping interaction sites for LIS1, which allows PDE4 to compete with dynein for LIS1 association in a process enhanced by the PKA phosphorylation of PDE4 long isoforms. This provides a further example to the growing notion that PDE4 itself may provide a signalling role independent of its catalytic activity, exemplified here by its modulation of dynein motor function.
Arabidopsis RHD3 mediates the generation of the tubular ER network and is required for Golgi distribution and motility in plant cells
Authors: Chen Jun , Stefano Giovanni , Brandizzi Federica , Zheng Huanquan
Published: June 2011

In plant cells, the endoplasmic reticulum (ER) and Golgi apparatus form a unique system in which single Golgi stacks are motile and in close association with the underlying ER tubules. Arabidopsis has three RHD3 (ROOT HAIR DEFECTIVE 3) isoforms that are analogous to the mammalian atlastin GTPases involved in shaping ER tubules. We used live-cell imaging, genetic complementation, split ubiquitin assays and western blot analyses in Arabidopsis and tobacco to show that RHD3 mediates the generation of the tubular ER network and is required for the distribution and motility of Golgi stacks in root and leaf epidermal cells. We established that RHD3 forms homotypic interactions at ER punctae. In addition, the activity of RHD3 on the tubular ER is specifically correlated with the cellular distribution and motility of Golgi stacks because ER to Golgi as well as Golgi to plasma membrane transport was not affected by RHD3 mutations in the conserved GDP/GTP motifs. We found a possible partial redundancy within the RHD3 isoforms in Arabidopsis. However, yeast Sey1p, a functional atlastin homologue, and RHD3 are not interchangeable in complementing the respective loss-of-function mutants, suggesting that the molecular mechanisms controlling ER tubular morphology might not be entirely conserved among eukaryotic lineages.
Von Hippel-Lindau gene product directs cytokinesis: a new tumor suppressor function
Authors: Sinha Sutapa , Mondal Gourish , Hwang Eun Ju , Han Da Woon , Dutta Shamit K. , Iyer Seethalakshmi , Karumanchi S. Ananth , Kim Keun Il , Couch Fergus J. , Mukhopadhyay Debabrata
Published: June 2011

One of the mechanisms of tumorigenesis is that the failure of cell division results in genetically unstable, multinucleated cells. Here we show that pVHL, a tumor suppressor protein that has been implicated in the pathogenesis of renal cell carcinoma (RCC), plays an important role in regulation of cytokinesis. We found that pVHL-deficient RCC 786-O cells were multinucleated and polyploid. Reintroduction of wild-type pVHL into these cells rescued the diploid cell population, whereas the mutant pVHL-K171G failed to do so. We demonstrate that lysine 171 of pVHL is important for the final step of cytokinesis: the midbody abscission. The pVHL-K171G caused failure to localize the ESCRT-1 interacting protein Alix and the v-SNARE complex component Endobrevin to the midbody in 786-O cells, leading to defective cytokinesis. Moreover, SUMOylation of pVHL at lysine 171 might modulate its function as a cytokinesis regulator. pVHL tumor suppressor function was also disrupted by the K171G mutation, as evidenced by the xenograft tumor formation when 786-O clones expressing pVHL-K171G were injected into mice. Most RCC cell lines show a polyploid chromosome complement and consistent heterogeneity in chromosome number. Thus, this study offers a way to explain the chromosome instability in RCC and reveals a new direction for the tumor suppressor function of pVHL, which is independent of its E3 ubiquitin ligase activity.
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

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

Honest 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.
Teaching Note—Fitting a Theoretical Model to a Real Queue
Authors: McNickle Don
Published: June 2011

A carefully structured practical queue-modelling assignment improves the understanding of queueing theory and teaches modelling and data-analysis skills. The assignment also demonstrates that it may be better to use models to estimate operating characteristics such as mean waiting times, even in circumstances where the system in question and the characteristics can be directly observed.
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

For 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

Objective

Hyperparathyroidism-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.

Design

We 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.

Methods

The 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.

Results

Clinical 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.

Conclusions

This 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

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

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

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

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.
Current results on the neuroscience of intelligence
Authors: Németh Kornél
Published: June 2011

Az intelligenciakutatás az elmúlt két évtizedben, felhasználva a modern technika kínálta lehetőségeket, próbálja integrálni a napról napra növekvő mennyiségű idegtudományi eredményeket. A 21. század elején az intelligencia neurális hátterének kutatása a strukturális és funkcionális képalkotók, az EEG elterjedésének és széles körű hozzáférhetőségének köszönhetően új fejezethez érkezett. A felhalmozódott idegtudományi eredmények rendszerezése és egymáshoz való viszonyának tisztázása komoly kihívás, de elengedhetetlen az érdemi továbblépéshez. Az intelligencia neurális reprezentációját vizsgáló összefoglalómban egészséges, beteg, gyerek és felnőtt mintán végzett strukturális és funkcionális képalkotó technikákkal, EEG-vel gyűjtött legújabb idegtudományi eredményeket tekintem át. Az adatok szerint az intelligencia agyi alapja egy megosztott integrált hálózat.
Genotoxicity of Endosseous Implants Using Two Cellular Lineages In Vitro
Authors: Matsumoto Mariza , Filho Hugo Nary , Ferrari Raquel , Fernandes Kristianne , Renno Ana Claudia , Ribeiro Daniel
Published: June 2011

The genotoxic potential of corrosion eluates obtained from a single dental implant using murine fibroblasts or osteoblasts cells in vitro by the single-cell gel (comet) assay was examined. A single commercially available dental implant (Biotechnology) was eluted in a solution consisting of equal amounts of acetic acid and sodium chloride (0.1 M) for 1, 3, 7, 14, and 21 days. Murine fibroblast or osteoblast cultures were then exposed to all corrosion eluates obtained from endosseous dental implants for 30 minutes at 37°C. The results suggest that none of the eluates produced genotoxic changes in murine fibroblasts regardless of the length of exposure to the eluate. Similarly, no genotoxicity was found in osteoblasts. The results suggest that the dental implant eluates tested in this study did not induce genetic damage as depicted by the single-cell gel (comet) assay. Because DNA damage is an important event during oncogenesis, this study represents a relevant contribution to estimate the real risks to the cellular system induced by the corrosion products of a dental implant.
Early and Middle Triassic trends in diversity, evenness, and size of foraminifers on a carbonate platform in south China: implications for tempo and mode of biotic recovery from the end-Permian mass extinction
Authors: Payne Jonathan L. , Summers Mindi , Rego Brianna L. , Altiner Demir , Wei Jiayong , Yu Meiyi , Lehrmann Daniel J.
Published: June 2011

Delayed biotic recovery from the end-Permian mass extinction has long been interpreted to result from environmental inhibition. Recently, evidence of more rapid recovery has begun to emerge, suggesting the role of environmental inhibition was previously overestimated. However, there have been few high-resolution taxonomic and ecological studies spanning the full Early and Middle Triassic recovery interval, leaving the precise pattern of recovery and underlying mechanisms poorly constrained. In this study, we document Early and Middle Triassic trends in taxonomic diversity, assemblage evenness, and size distribution of benthic foraminifers on an exceptionally exposed carbonate platform in south China. We observe gradual increases in all metrics through Early Triassic and earliest Middle Triassic time, with stable values reached early in the Anisian. There is little support in our data set for a substantial Early Triassic lag interval during the recovery of foraminifers or for a stepwise recovery pattern. The recovery pattern of foraminifers on the GBG corresponds well with available global data for this taxon and appears to parallel that of many benthic invertebrate clades. Early Triassic diversity increase in foraminifers was more gradual than in ammonoids and conodonts. However, foraminifers continued to increase in diversity, size, and evenness into Middle Triassic time, whereas diversity of ammonoids and conodonts declined. These contrasts suggest decoupling of recovery between benthic and pelagic environments; it is unclear whether these discrepancies reflect inherent contrasts in their evolutionary dynamics or the differential impact of Early Triassic ocean anoxia or associated environmental parameters on benthic ecosystems.
Paleolongitudinal estimates for paleocontinents derived from interplate distances based on Late Ordovician bivalves
Authors: Schmachtenberg William F.
Published: June 2011

The geographic distribution of 293 Modern bivalve genera has been analyzed and found to be statistically correlated with distance. In particular, a least-squares regression analysis of the data indicates that the distance between faunal realms (D) in kilometers can be estimated using the equation D = (ln(d) + 0.4233)/−0.00013, where d is the Dice coefficient of faunal similarity. Analysis of 59 genera of Late Ordovician bivalves indicates that the above equation also describes their biogeographic distribution.

Using this formula, the distance between Laurentia and Scotland/Northwest Ireland was estimated to be 5500 kilometers. This is consistent with the reconstruction of a connection among these areas during the Late Ordovician based on brachiopod and graptolite biogeographic data.

Paleomagnetic and paleoclimatic data also suggest that Avalonia, Baltica, and Laurentia were at tropical latitudes. Distances between these paleocontinents can therefore be used to estimate paleolongitudes. If the location of England on the eastern side of Avalonia is used as zero degrees paleolongitude for the Late Ordovician as it is today, the paleolongitude for South America, Laurentia, Scotland and northwest Ireland, and Baltica would be 125°W, 45°W, 10°W, and 15°E, respectively. Because of drifting of the Avalonia plate, these paleolongitudes probably do not coincide with the longitudinal grid used today. The paleolongitudes indicate only the relative spacing between continents in the past. The methodology in this study should be useful for improving the accuracy of paleogeographic reconstructions for the Late Ordovician throughout the Cenozoic, and especially the Paleozoic periods for which magnetic seafloor anomaly data are not available.
A ubiquitous ∼62-Myr periodic fluctuation superimposed on general trends in fossil biodiversity. II. Evolutionary dynamics associated with periodic fluctuation in marine diversity
Authors: Melott Adrian L. , Bambach Richard K.
Published: June 2011

We use Fourier analysis to investigate evolutionary dynamics related to periodicities in marine fossil biodiversity. Coherent periodic fluctuation in both origination and extinction of “short-lived” genera (those that survive <45 Myr) is the source of an observed ∼62 million year periodicity (which we confirmed in an earlier paper and also found to be ubiquitous in global compilations of marine diversity). We also show that the evolutionary dynamics of “long-lived” genera (those that survive >45 Myr) do not participate in the periodic fluctuation in diversity and differ from those of “short-lived” genera. The difference between the evolutionary dynamics of long- and short-lived genera indicates that the periodic pattern is not simply an artifact of variation in quality of the geologic record. Also, the interplay of these two previously undifferentiated systems, together with the secular increase in abundance of “long-lived” genera, is probably the source of observed but heretofore unexplained differences in evolutionary dynamics between the Paleozoic and post-Paleozoic as reported by others. Testing for cycles similar to the 62-Myr cycle in fossil biodiversity superimposed on the long-term trends of the Phanerozoic as described in Paper I, we find a significant (but weaker) signal in sedimentary rock packages, particularly carbonates, which suggests a connection. The presence of a periodic pattern in evolutionary dynamics of the more vulnerable “short-lived” component of the marine fauna demonstrates that a long-term periodic fluctuation in environmental conditions capable of affecting evolution in the marine realm characterizes our planet's history. Coincidence in timing is more consistent with a common cause than with sampling bias. A previously identified set of mass extinctions preferentially occur during the declining phase of the 62-Myr periodicity, supporting the idea that the periodicity relates to variation in biotically important stresses. Further work should focus on finding links to physical phenomena that might reveal the causal system or systems.
Do convergent ecomorphs evolve through convergent morphological pathways? Cranial shape evolution in fossil hyaenids and borophagine canids (Carnivora, Mammalia)
Authors: Tseng Zhijie Jack , Wang Xiaoming
Published: June 2011

Cases of convergent evolution, particularly within ecomorphological contexts, are instructive in identifying universally adaptive morphological features across clades. Tracing of evolutionary pathways by which ecomorphological convergence takes place can further reveal mechanisms of adaptation, which may be strongly influenced by phylogeny. Ecomorphologies of carnivorous mammals represent some of the most outstanding cases of convergent evolution in the Cenozoic radiation of mammals. This study examined patterns of cranial shape change in the dog (Canidae) and hyena (Hyaenidae) families, in order to compare the evolutionary pathways that led to the independent specialization of bone-cracking hypercarnivores within each clade. Geometric morphometrics analyses of cranial shape in fossil hyaenids and borophagine canids provided evidence for deep-time convergence in morphological pathways toward the independent evolution of derived bone-crackers. Both clades contained stem members with plesiomorphic generalist/omnivore cranial shapes, which evolved into doglike species along parallel pathways of shape change. The evolution of specialized bone-crackers from these doglike forms, however, continued under the constraint of a full cheek dentition and restriction on rostrum length reduction in canids, but not hyaenids. Functionally, phylogenetic constraint may have limited borophagine canids to crack bones principally with their carnassial instead of the third premolar as in hyaenids, but other cranial shape changes associated with durophagy nevertheless evolved in parallel in the two lineages. Size allometry was not a major factor in cranial shape evolution in either lineage, supporting the interpretation of functional demands as drivers for the observed convergence. The comparison between borophagines and hyaenids showed that differential effects of alternative functional “solutions” that arise during morphological evolution may be multiplied with processes of the “macroevolutionary ratchet” already in place to further limit the evolutionary pathways available to specialized lineages.
Community Health Nursing Practice Education: Preparing the Next Generation
Authors: Pijl-Zieber Em M , Grant Kalischuk Ruth
Published: June 2011

Undergraduate nursing practice rotations today are quite different from what many practicing nurses experienced during their own education. This is especially true of community health practice rotations. Increasingly, non-traditional community health sites are being used as practice sites—sites such as schools, homeless shelters, non-profit agencies, and even churches. Increasingly, non-traditional practice experiences are eclipsing traditional practice experiences involving home care and public health. Why has this shift occurred, and what do these experiences offer students? Do these experiences actually prepare nursing students for clinical practice once they graduate? What does preparing the next generation of community health nurses entail?
CAM in Canadian Hospitals: The New Frontier?
Authors: Hollenberg Daniel B , Tsasis Peter , Kelley Nancy
Published: June 2011

The provision in hospitals of traditional, complementary and alternative medicine (TCAM), as recognized by the World Health Organization, is now widespread in many of the worlds healthcare systems. As a significant part of integrative medicine (IM) or healthcare (IHC), research has now begun to focus on the varied parameters of hospital-based TCAM, however, little research has been conducted on the topic in the Canadian context.Drawing on a multi-site case study of four Canadian hospitals, qualitative observation was conducted at hospital sites, and interviews were conducted with senior hospital leaders and biomedical and TCAM hospital practitioners. The main focus of inquiry was to obtain the views of hospital leaders on the topic of incorporating TCAM, and to examine the motivations for TCAM inclusion, economic dimensions and level of integration between TCAM and biomedicine.Hospital leaders were both highly critical of TCAM and cautiously supportive. Inclusion of TCAM was directly related to hospital leadership and institutional relationships, while TCAM practitioners remained marginalized due to economic, geographical, political and epistemological barriers.Although signs of integration were apparent, significant challenges remained that prevented TCAM practitioners from operating as fully-fledged hospital providers. An integrated change strategy is needed that engages the TCAM professions in mainstream interprofessional education and training opportunities, and that also addresses wider structural and political barriers.
The Wage Impact of Immigration in Germany - New Evidence for Skill Groups and Occupations
Authors: Steinhardt Max Friedrich
Published: June 2011

This paper contributes to the ongoing debate regarding the appropriate approach to use in identifying the impact of immigration on native workers’ labor market outcomes. The initial regression analysis makes use of German administrative data and is based on the variation of foreign workers’ shares within education-experience cells over time. It confirms previous findings suggesting that immigration in Germany had no adverse impact on native wages. However, the paper highlights that in Germany immigrants and natives with similar education and experience are likely to work in different occupations. The subsequent analysis based on occupational clustering uses the same data and finds significant adverse wage effects for natives, particularly for those in basic service occupations. The paper argues, therefore, that an identification strategy based on formal education characteristics might lead to biased estimates if a country’s labor market is characterized by occupational segmentation of immigrants.
Impact on force decrease at the end of actuator plunger motion
Authors: Zagirnyak Mykhaylo , Branspiz Yurii , Pshenychnyi Andrii , Miljavec Damijan
Published: June 2011

Impact on force decrease at the end of actuator plunger motion

It is shown that decrease and damping of the traction force at the end of the plunger move is possible not only due to application of a special keeper design, but also due to change of the plunger shank geometric form. The computer modeling with the use of finite element method is used to analyze the influence of system geometry on force distribution along plunger movement. The damping effect is confirmed when special shape plunger shanks are used.
Steady-state modelling method for matrix-reactance frequency converter with boost topology
Authors: Korotyeyev Igor , Zięba Beata
Published: June 2011

Steady-state modelling method for matrix-reactance frequency converter with boost topology

This paper presents a method intended for calculation of steady-state processes in AC/AC three-phase converters that are described by nonstationary periodical differential equations. The method is based on the extension of nonstationary differential equations and the use of Galerkin's method. The results of calculations are presented in the form of a double Fourier series. As an example, a three-phase matrix-reactance frequency converter (MRFC) with boost topology is considered and the results of computation are compared with a numerical method.
Application of optimal current driver for the torque control of BLDC motor
Authors: Bernat Jakub , Stępień Sławomir
Published: June 2011

Application of optimal current driver for the torque control of BLDC motor

This research presents the novel control strategy of the brushless DC motor. The optimal current driver is designed using Linear Quadratic Regulator and feedback linearization. Additionally, the current reshaping strategy is applied to control the motor torque. Thus, the torque controller is built based on the optimal current driver. The motor is simulated using the FEM analysis.