bluuebunny/crossref_metadata_2025 huggingface dataset:
Locating binding poses in protein-ligand systems using reconnaissance metadynamics
Authors: Söderhjelm Pär , Tribello Gareth A. , Parrinello Michele
Published: March 2012

A molecular dynamics-based protocol is proposed for finding and scoring protein-ligand binding poses. This protocol uses the recently developed reconnaissance metadynamics method, which employs a self-learning algorithm to construct a bias that pushes the system away from the kinetic traps where it would otherwise remain. The exploration of phase space with this algorithm is shown to be roughly six to eight times faster than unbiased molecular dynamics and is only limited by the time taken to diffuse about the surface of the protein. We apply this method to the well-studied trypsin–benzamidine system and show that we are able to refind all the poses obtained from a reference EADock blind docking calculation. These poses can be scored based on the length of time the system remains trapped in the pose. Alternatively, one can perform dimensionality reduction on the output trajectory and obtain a map of phase space that can be used in more expensive free-energy calculations.
Recent changes in pampean agriculture: possible new avenues in coping with global change challenges.
Authors: Satorre E. H.
Published: March 2012

This chapter tries to address three general objectives: (i) to present the main ecological and extensive agriculture characteristics of the pampean region; (ii) to analyse recent technological and productive transformations; and (iii) to discuss the influence of future possible transformation factors. The extensive agriculture of the pampas has experienced huge transformations since the 1990s. The support of scientific and technological knowledge has been relevant in this process; moreover, the concept of sustainability has been central as a condition for change and growth. Overall, in the pampas there exists a possibly well-founded feeling that the ecological impact of agriculture to date has been low. Modern technologies have contributed to simultaneously increased productivity and sustainability in the cropping systems of some ecological regions. However, the adoption of better management practices is still needed in some areas to fully sustain the functioning and structure of the pampas agroecosystems.
Can student teachers acquire core skills for teaching from part‐time employment?
Authors: Wylie Ken , Cummins Brian
Published: March 2012

Part‐time employment among university students has become commonplace internationally. Research has largely focused on the impact of part‐time employment on academic performance. This research takes an original approach in that it poses the question whether students can acquire core skills relevant to teaching from their part‐time employment. The research was conducted in a university college of education. A case study approach was adopted using an opportunistic sample of 285 students drawn from twoBEd programmes. The project is based on an interpretive paradigm, focusing on students’ perceptions of their part‐time employment. The research methodology included a questionnaire containing both closed and open questions, a follow‐up focus group discussion and two case histories. The results showed that the majority of students believed that they had acquired core skills from their part‐time employment. The findings of this research raise important issues about how university courses can effectively build on such learning experiences.
Adhesive behaviour of gecko-inspired nanofibrillar arrays: combination of experiments and finite element modelling
Authors: Wang Zheng-zhi , Xu Yun , Gu Ping
Published: March 2012

A polypropylene nanofibrillar array was successfully fabricated by template-assisted nanofabrication strategy. Adhesion properties of this gecko-inspired structure were studied through two parallel and independent approaches: experiments and finite element simulations. Experimental results show relatively good normal adhesion, but accompanied by high preloads. The interfacial adhesion was modelled by effective spring elements with piecewise-linear constitution. The effective elasticity of the fibre-array system was originally calculated from our measured elasticity of single nanowire. Comparisons of the experimental and simulative results reveal quantitative agreement except for some explainable deviations, which suggests the potential applicability of the present models and applied theories.
Fast flexible electronics using transferrable silicon nanomembranes
Authors: Zhang Kan , Seo Jung-Hun , Zhou Weidong , Ma Zhenqiang
Published: March 2012

A systematic review, covering the aspects of material preparation, device fabrication and process integration, is provided for flexible electronics operating in high-frequency domain based on transferrable monocrystalline silicon (Si) nanomembranes (NM). Previously demonstrated methods of releasing Si NM from silicon-on-insulator source substrates and transferring it to flexible substrates are briefly described. Due to the processing temperature limitation of most flexible substrates, a pre-release NM selective doping scheme is used for Si NMs. With proper selections of ion implantation energy and dose, fully doped Si NMs across their entire thickness with very low sheet resistivity can be obtained, allowing flip transfer of the NMs for backside and even double side processing. A general conclusion of preferred low implantation energy for shallower depth ion implantation is identified. The evolvement of radio frequency (RF) flexible Si thin-film transistor (TFT) structures is described in detail. The continuous performance enhancement of TFTs owing to process and TFT structure innovations is analysed. Demonstrations of flexible Si RF switches and RF inductors and capacitors are also briefly reviewed as valuable components of the general flexible device family, some of which also benefit from the pre-release NM doping technique. With the proved feasibility of these basic RF elements and related processing techniques, more complicated flexible RF circuits can be expected. Future research directions are also discussed, including further enhancement of device performance, building more types of semiconductor devices on flexible substrates, and process integration for flexible circuits and systems.
Gcn5p-dependent acetylation induces degradation of the meiotic transcriptional repressor Ume6p
Authors: Mallory Michael J. , Law Michael J. , Sterner David E. , Berger Shelley L. , Strich Randy
Published: March 2012

Ume6p represses early meiotic gene transcription in Saccharomyces cerevisiae by recruiting the Rpd3p histone deacetylase and chromatin-remodeling proteins. Ume6p repression is relieved in a two-step destruction process mediated by the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. The first step induces partial Ume6p degradation when vegetative cells shift from glucose- to acetate-based medium. Complete proteolysis happens only upon meiotic entry. Here we demonstrate that the first step in Ume6p destruction is controlled by its acetylation and deacetylation by the Gcn5p acetyltransferase and Rpd3p, respectively. Ume6p acetylation occurs in medium lacking dextrose and results in a partial destruction of the repressor. Preventing acetylation delays Ume6p meiotic destruction and retards both the transient transcription program and execution of the meiotic nuclear divisions. Conversely, mimicking acetylation induces partial destruction of Ume6p in dextrose medium and accelerates meiotic degradation by the APC/C. These studies reveal a new mechanism by which acetyltransferase activity induces gene expression through targeted destruction of a transcriptional repressor. These findings also demonstrate an important role for nonhistone acetylation in the transition between mitotic and meiotic cell division.
Vesicular trafficking through cortical actin during exocytosis is regulated by the Rab27a effector JFC1/Slp1 and the RhoA-GTPase–activating protein Gem-interacting protein
Authors: Johnson Jennifer L. , Monfregola Jlenia , Napolitano Gennaro , Kiosses William B. , Catz Sergio D.
Published: March 2012

Cytoskeleton remodeling is important for the regulation of vesicular transport associated with exocytosis, but a direct association between granular secretory proteins and actin-remodeling molecules has not been shown, and this mechanism remains obscure. Using a proteomic approach, we identified the RhoA-GTPase–activating protein Gem-interacting protein (GMIP) as a factor that associates with the Rab27a effector JFC1 and modulates vesicular transport and exocytosis. GMIP down-regulation induced RhoA activation and actin polymerization. Importantly, GMIP-down-regulated cells showed impaired vesicular transport and exocytosis, while inhibition of the RhoA-signaling pathway induced actin depolymerization and facilitated exocytosis. We show that RhoA activity polarizes around JFC1-containing secretory granules, suggesting that it may control directionality of granule movement. Using quantitative live-cell microscopy, we show that JFC1-containing secretory organelles move in areas near the plasma membrane deprived of polymerized actin and that dynamic vesicles maintain an actin-free environment in their surroundings. Supporting a role for JFC1 in RhoA inactivation and actin remodeling during exocytosis, JFC1 knockout neutrophils showed increased RhoA activity, and azurophilic granules were unable to traverse cortical actin in cells lacking JFC1. We propose that during exocytosis, actin depolymerization commences near the secretory organelle, not the plasma membrane, and that secretory granules use a JFC1- and GMIP-dependent molecular mechanism to traverse cortical actin.
FTEC: a coalescent simulator for modeling faster than exponential growth
Authors: Reppell Mark , Boehnke Michael , Zöllner Sebastian
Published: March 2012

Summary: Recent genetic studies as well as recorded history point to massive growth in human population sizes during the recent past. To model and understand this growth accurately we introduce FTEC, an easy-to-use coalescent simulation program capable of simulating haplotype samples drawn from a population that has undergone faster than exponential growth. Samples drawn from a population that has undergone faster than exponential growth show an excess of very rare variation and more rapid LD decay when compared with samples drawn from a population that has maintained a constant size over time.

Availability: Source code for FTEC is freely available for download from the University of Michigan Center for Statistical Genetics Wiki at http://genome.sph.umich.edu/wiki/FTEC

Contact:  mreppell@umich.edu; szoellne@umich.edu

Supplementary information:  Supplementary data are available at Bioinformatics online
High reproducible ADCC analysis revealed a competitive relation between ADCC and CDC and differences between FcγRllla polymorphism
Authors: Mishima Yuji , Terui Yasuhito , Mishima Yuko , Kuniyoshi Ryoko , Matsusaka Satoshi , Mikuniya Mariko , Kojima Kiyotsugu , Hatake Kiyohiko
Published: March 2012

The anti-CD20 chimeric monoclonal antibody rituximab mediates cytotoxicity in malignant B cells via multiple mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and direct induction of apoptosis. To optimize treatment of non-Hodgkin's lymphoma, a fuller understanding of these mechanisms and their relative contributions to clinical efficacy is required. Here, we report the characteristics of the mutual impact between ADCC and CDC, the two major effector functions through the Fc receptors. To compare ADCC induced under various conditions, we developed a highly reproducible method of estimating ADCC activity using immortalized effector cells. The set of the effector cells that we established was able to calculate net ADCC with high reproducibility by comparing the cytotoxicity of effector cells expressing exogeneous FcγRIIIa to those of mock effector cells. In addition, the different property of effector cells of two FcγRIIIa single-nucleotide polymorphisms (SNP) could be also evaluated in exactly identical background. ADCC assessment in the presence of human serum directly provided the evidence of the competitive interaction of ADCC and CDC. The inhibition of ADCC of effector cells having low affinity SNP of FcγRIIIa by active complement was more potent than those having high-affinity SNP at the rituximab-concentration comparable to the serum level obtained in patients. These findings could have a profound impact on optimization of the regimen of therapeutic antibodies and on the development of antibodies that will enhance effector function.
Transmission of Six Ampeloviruses and Two Vitiviruses to Grapevine by Phenacoccus aceris
Authors: Le Maguet J. , Beuve M. , Herrbach E. , Lemaire O.
Published: March 2012

Grapevine leafroll disease is caused by grapevine leafroll-associated viruses (GLRaVs). These viruses are common in vineyards worldwide and often associated with vitiviruses that are involved in the rugose wood complex of grapevine. Ten mealybug species are known as vectors of one or several of these grapevine viruses, including the apple mealybug Phenacoccus aceris which is widespread in Holarctic regions and able to transmit Grapevine leafroll-associated virus-1 and -3 (GLRaV-1 and -3). Our aim was to characterize the transmission features of leafroll viruses by Phenacoccus aceris in order to better understand the contribution of this mealybug to leafroll epidemics. Results showed that Phenacoccus aceris is able to transmit GLRaV-1, -3, -4, -5, -6, and -9 to grapevine but not GLRaV-7. This is the first report of GLRaV-6 transmission by a mealybug. Also, for the first time it was shown that Phenacoccus aceris could vector vitiviruses Grapevine virus A (GVA) and Grapevine virus B (GVB). First instar nymphs were the most efficient stage in transmitting GLRaV-1, -3, and GVA. This research sheds light on the transmission biology of grapevine viruses by Phenacoccus aceris and represents a step forward to leafroll disease management.
Murine cytomegalovirus infection of cultured mouse cells induces expression of miR-7a
Authors: Dittmer Alexandra , Förstemann Klaus
Published: March 2012

One goal of virus infection is to reprogramme the host cell to optimize virus replication. As part of this process, viral microRNAs (miRNAs) may compete for components of the miRNA/small interfering RNA pathway, as well as regulate cellular targets. Murine cytomegalovirus (MCMV) has been described to generate large numbers of viral miRNAs during lytic infection and was therefore used to analyse the impact of viral miRNAs on the host-cell small-RNA system, as well as to check for sorting of viral small RNAs into specific Argonaute (Ago) proteins. Deep-sequencing analysis of MCMV-infected cells revealed that viral miRNAs represented only ~13 % of all detected miRNAs. All previously described MCMV miRNAs with the exception of miR-m88-1* were confirmed, and for the MCMV miR-m01-1 hairpin, an additional miRNA, designated miR-m01-1-3p, was found. Its presence was confirmed by quantitative real-time PCR and Northern blotting. Deep sequencing after RNA-induced silencing complex (RISC) immunoprecipitation with antibodies specific for either Ago1 or Ago2 showed that all MCMV miRNAs were loaded into both RISCs. The ratio of MCMV to mouse miRNAs was not increased after immunoprecipitation of Ago proteins. Viral miRNAs therefore did not overwhelm the host miRNA processing system, nor were they incorporated preferentially into RISCs. Three mouse miRNAs were found that showed altered expression as a result of MCMV infection. Downregulation of miR-27a, as described previously, could be confirmed. In addition, miR-26a was downregulated, and upregulation of miR-7a dependent on viral protein expression could be observed.
A preliminary survey of whale shark Rhincodon typus catch and trade in China: an emerging crisis
Authors: Li W. , Wang Y. , Norman B.
Published: March 2012

This study gives an account of spatial and temporal distribution of whale shark Rhincodon typus catch events in China on the basis of historical records and information obtained from interviews with fishing industry stakeholders. A total of 186 R. typus were recorded with key harvest areas identified as in Hainan and Zhejiang, and the peak catching seasons were May to June and September to October. Aspects of the R. typus trade are discussed, including products, markets and the process. The results suggest that R. typus is increasingly becoming a targeted resource in China as a consequence of fierce competition for large shark fins and an emerging local market for consumption of all body parts. Current obstacles and potential measures for sustainable exploitation and trade of R. typus are discussed.
Generation of transgenic plantain (Musa spp.) with resistance to plant pathogenic nematodes
Authors: RODERICK HUGH , TRIPATHI LEENA , BABIRYE ANNET , WANG DONG , TRIPATHI JAINDRA , URWIN PETER E. , ATKINSON HOWARD J.
Published: March 2012

Plant parasitic nematodes impose a severe constraint on plantain and banana productivity; however, the sterile nature of many cultivars precludes conventional breeding for resistance. Transgenic plantain cv. Gonja manjaya (Musa AAB) plants, expressing a maize cystatin that inhibits nematode digestive cysteine proteinases and a synthetic peptide that disrupts nematode chemoreception, were assessed for their ability to resist nematode infection. Lines were generated that expressed each gene singly or both together in a stacked defence. Nematode challenge with a single species or a mixed population identified 10 lines with significant resistance. The best level of resistance achieved against the major pest species Radopholus similis was 84% ± 8% for the cystatin, 66% ± 14% for the peptide and 70% ± 6% for the dual defence. In the mixed population, trial resistance was also demonstrated to Helicotylenchus multicinctus. A fluorescently labelled form of the chemodisruptive peptide underwent retrograde transport along certain sensory dendrites of R. similis as required to disrupt chemoreception. The peptide was degraded after 30 min in simulated intestinal fluid or boiling water and after 1 h in nonsterile soil. In silico sequence analysis suggests that the peptide is not a mammalian antigen. This work establishes the mode of action of a novel nematode defence, develops the evidence for its safe and effective deployment against multiple nematode species and identifies transgenic plantain lines with a high level of resistance for a proposed field trial.
Defective in Vitro Colony Formation by Human Bone Marrow Preceding Overt Leukaemia
Authors: Senn J. S. , Pinkerton P. H.
Published: March 2012

Summary. Disordered haemopoiesis may precede acute leukaemia for prolonged periods. Three patients are presented in whom splenomegaly, peripheral cytopenia, hypercellular bone marrow, and reduced colony formation in marrow cell culture were present for intervals of 27, 15 and 5 mth prior to definite diagnosis of acute leukaemia. Reduced colony formation by human bone marrow does not appear to be solely related to infiltration by recognizable leukaemic cells, but may reflect a disturbance in granulopoiesis occurring prior to the development of overt leukaemia.
Some Properties of Transcobalamin III from Normal Human Serum
Authors: Bloomfield F. J. , Weir D. G. , Scott J. M.
Published: March 2012

Summary. Further investigations on the newly described normal serum binder of vitamin B12, Transcobalamin HI, indicate that it has a greater affinity for the vitamin than Transcobalamin I. Also, while its elution from DEAE‐cellulose is similar to Transcobalamin II, variations of elution conditions can cause it to elute before this latter binder.
Interrelation of Serum Vitamin B12, Total Body Vitamin B12, Peripheral Blood Morphology and the Nature of Erythropoiesis
Authors: Adams J. F. , Boddy K. , Douglas A. S.
Published: March 2012

Summary. The interrelation of serum vitamin B12 concentration, body vitamin B12, peripheral blood morphology and the nature of erythropoiesis was studied in patients with pernicious anaemia. On presentation the patients were treated with radioactive vitamin B12 and the retained radioactivity, measured by whole body monitoring, was taken as a measure of the body vitamin B12.

Post‐treatment results suggest that erythropoiesis became megaloblastic when the serum vitamin B12 was between 70 and 154 pg/ml and usually when the body vitamin B12 was between 100 and 660 μg and that the serum vitamin B12 was of more immediate importance in the nature of erythropoiesis than the body vitamin B12.

A normal peripheral blood film was no indication of the nature of erythropoiesis but an abnormal film carried a high probability of megaloblastic erythropoiesis. Abnormalities in blood films probably developed after abnormalities in marrow.

The correlation found between serum vitamin B12 and body vitamin B12 differed from that found in controls and the mean quotient of body vitamin B12 and serum vitamin B12 concentration was less than in controls showing that, in the patients studied, there was a disproportionately greater amount of vitamin B12 in serum compared to controls.

The balance of serum vitamin B12 and body vitamin B12 may involve at least two mechanisms and folate may have a role in both. One mechanism relates to the release of vitamin B12 from stores to plasma and the other to the clearance of vitamin B12 from plasma.
Small Intestinal Mucosal Abnormalities and Disaccharidase Activity in Pernicious Anaemia
Authors: Peña A. S. , Callender Sheila T. , Truelove S. C. , Whitehead R.
Published: March 2012

Summary. Patients with untreated pernicious anaemia usually show the following morphological and biochemical abnormalities in small‐intestinal biopsy specimens: (1) shortening of villi with diminished surface area; (2) megalocytic changes of the epithelial cells; (3) increased inflammatory infiltrate; (4) generalized depression of disaccharidases. These abnormalities revert to normal following treatment with injections of vitamin B12.
Cell cycle analysis in lymphoid neoplasia of childhood: differences among immunologic subtypes and similarities in the proliferation of normal and leukaemic precursor B cells
Authors: Hirt Andreas , Werren Eva‐Maria , Luethy Annette Ridolfi , Gerdes Johannes , Wagner Hans P.
Published: March 2012

Summary. Cell proliferation in untreated lymphoid malignancies of children was investigated by an in vitro assessment of the 3H‐thymidine labelling index (LI), the growth fraction (GF) with the monoclonal antibody Ki‐67, and the duration of the DNA‐synthesis phase (ts) with a double labelling technique. Mean cell cycle time (tg) was similar in lymphoid malignancies of precursor B cell and T cell origin (115 h and 102 h, respectively), while B cell neoplasias had a mean tg of only 25 h. A positive correlation between the II and the GF (r = 0·892) and a negative correlation between the LI and tg (r = −0·908) could be detected in childhood lymphoid malignancies.

The proliferation of neoplastic precursor B cells was compared with the proliferation of presumably normal terminal transferase (TdT) positive bone marrow cells that, according to the immunophenotype, correspond mainly to normal precursor B cells. Although mean ts was identical in both cell populations (18–19 h), the neoplastic cell population showed a significantly longer mean tg than the normal counterpart (115 h and 65 h, respectively). However, if malignant and normal precursor B cell populations with a similar LI were compared, the difference in tg disappeared. Therefore, a down‐regulation of leukaemic cell proliferation by an increasing cell mass is postulated for most cases of untreated precursor B cell ALL.
VAD or VMBCP in severe multiple myeloma
Authors: Monconduit M. , Menard J. F. , Michaux J. L. , Loet X. Le , Bernard J. F. , Grosbois B. , Pollet J. P. , Azais I. , Laporte J. Ph. , Doyen C. , Gramont A. De , Wetterwald M. , Duclos B. , Euller‐Ziegler L. , Peny A. M.
Published: March 2012

Summary. A randomized trial has been performed in which 91 patients with stage III myeloma and additional severe criteria were randomly allocated to either VAD or VMBCP.

No significant difference was noted between these two groups using the following criteria: response rate (VMBCP: 54%; VAD: 39%), impact on symptoms, median survival (VMBCP: 14 months, VAD: 17 months). However, toxic effects and refusal to pursue treatment were more frequent with VAD than with VMBCP (12 v 6). Therefore, in this trial, VMBCP appears to be more useful than VAD.
Combined activation of platelets by cathepsin G and platelet activating factor, two neutrophil‐derived agonists
Authors: Renesto Patricia , Kadiri Chakir , Chignard Michel
Published: March 2012

Summary. In this paper we have studied the combined effects on platelet activation, of two polymorphonuclear neutrophil (PMN)‐derived agonists, namely platelet‐activating factor (PAF) and cathepsin G (Cat.G), used at threshold concentrations. Our results showed that the order of agonist addition was a determinant factor since the addition of Cat.G prior to PAF induced a full platelet activation while the reverse combination had no effects. The successive challenge of platelets by Cat.G and then PAF induced a strong aggregation accompanied by an enhancement of α and dense granule secretion. The observed phenomenon was also dependent on the time interval between agonist addition. It was significant at 30 s (P < 0·05) and plateaued over 1–2 min. Platelet activation resulting from the combination Cat.G‐PAF can be described as a function of PAF concentrations, the synergism being significant between 10 Nm and 1 μm. The mechanism by which Cat.G primes platelets remains to be elucidated. However, some points have been examined and have led us to conclude that an increase in expression and/or affinity of PAF receptors, [Ca2+]i movements, protein kinase C activation and phospholipase A2 pathway are not involved. Whatever the biochemical mechanism underlying this synergism which involved PMN and platelets, it may constitute a link between the inflammatory and haemostatic processes in response to tissue damage.
Clinical and biological evaluation in von Willebrand's disease of a von Willebrand factor concentrate with low factor VIII activity
Authors: Goudemand J. , Mazurier C. , Marey A. , Caron C. , Coupez B. , Mizon P. , Goudemand M.
Published: March 2012

Summary. This study was carried out to assess the clinical efficacy in von Willebrand's disease (vWD) of a new, very high purity (VHP), solvent/detergent (SD)‐treated, vWF concentrate (VHP Human von Willebrand Factor Concentrate, Biotransfusion) characterized by a high specific ristocetin cofactor (vWF:RCo) activity and a low factor VIII (FVIII) coagulant activity (FVIII:C). Nine patients (four type I, one type IIA, one type IIB, one type IIC, one type III and one acquired type II) were infused on 13 occasions including a pharmacokinetic study. Satisfactory haemostasis was achieved in all cases, including the treatment of spontaneous haemorrhages and the prevention of bleeding following surgery. The bleeding time was corrected for 6–12 h in 6/9 patients and shortened in the others. Furthermore, it was shown that the plasma vWF multimeric pattern of types II and III patients was greatly improved. When measured in eight patients 1 h after infusion, the vWF: RCo recovery was 77·3 (± 10·7)% while the F VIII:C recovery was strikingly higher (876 ± 906%). This high recovery is likely related to the predominant ‘pseudo‐synthesis’ of FVIII following the restoration of normal vWF levels. Maximum levels of FVIII: C occurred 6–12 h after the first infusion and normal levels of FVIII:C were maintained throughout the treatments with a dosage of 26–39 IU/kg vWF:RCo and only 0·2–5 IU/kg FVIII:C. The half‐lives of the vWF‐related parameters determined in a type III vWD patient were 20·6 h for vWF antigen, 17·8 h for vWF:RCo, 14 h for the high molecular weight multimers of vWF, 55·3 h for FVIII: Ag and 74 h for FVIII:C. In conclusion, it does not appear necessary that vWF concentrates intended for the treatment of vWD should contain FVIII in addition to vWF to be clinically effective in most patients.
Seismic data analysis using local time‐frequency decomposition
Authors: Liu Yang , Fomel Sergey
Published: March 2012

Many natural phenomena, including geologic events and geophysical data, are fundamentally nonstationary ‐ exhibiting statistical variation that changes in space and time. Time‐frequency characterization is useful for analysing such data, seismic traces in particular.

We present a novel time‐frequency decomposition, which aims at depicting the nonstationary character of seismic data. The proposed decomposition uses a Fourier basis to match the target signal using regularized least‐squares inversion. The decomposition is invertible, which makes it suitable for analysing nonstationary data. The proposed method can provide more flexible time‐frequency representation than the classical S transform. Results of applying the method to both synthetic and field data examples demonstrate that the local time‐frequency decomposition can characterize nonstationary variation of seismic data and be used in practical applications, such as seismic ground‐roll noise attenuation and multicomponent data registration.
Differential expression of moesin in breast cancers and its implication in epithelial–mesenchymal transition
Authors: Wang Chung‐Chieh , Liau Jau‐Yu , Lu Yen‐Shen , Chen Jun‐Wei , Yao Yu‐Tung , Lien Huang‐Chun
Published: March 2012

Wang C‐C, Liau J‐Y, Lu Y‐S, Chen J‐W, Yao Y‐T & Lien H‐C  (2012) Histopathology 61, 78–87

Differential expression of moesin in breast cancers and its implication in epithelial–mesenchymal transition

Aims:  Moesin belongs to the ERM (ezrin, radixin and moesin) family. Recent in‐vitro studies have shown the possible involvement of moesin in epithelial–mesenchymal transition (EMT), but correlating in‐vivo evidence is lacking.

Methods and results:  To study the biological significance of moesin, we used immunohistochemistry to investigate the in‐situ expression profiles of moesin in 322 breast carcinomas of different subtypes, including 23 cases of metaplastic carcinoma (MCB) which is pathogenetically considered to involve EMT. Moesin was highly expressed in 95.7% of cases of MCB, and in 16% of cases of invasive ductal carcinoma (IDC), but was negative in all other subtypes of breast carcinomas. In IDCs, moesin expression correlated positively with a high histological grade (P < 0.001), basal‐like phenotype (P < 0.001) and poor overall survival (P = 0.0263). Transfection of MCF7 cells with Snail, one of the key regulators of EMT, showed up‐regulation of moesin at the transcriptional level. Finally, mRNA level of moesin correlated positively with Snail and EMT‐related genes in a microarray data set using primary breast cancer samples.

Conclusion:  These results offer biological evidence of moesin as an EMT marker, support the association between moesin, Snail and EMT and suggest a role for moesin in breast cancer prognostication.
An in vivo evaluation of the Auto Apical Reverse function of the Root ZX II
Authors: Fadel G. , Piasecki L. , Westphalen V. P. D. , Silva Neto U. X. , Fariniuk L. F. , Carneiro E.
Published: March 2012

Fadel G, Piasecki L, Westphalen VPD, Silva Neto UX, Fariniuk LF, Carneiro E. An in vivo evaluation of the Auto Apical Reverse function of the Root ZX II. International Endodontic Journal, 45, 950–954, 2012.

Aim  To evaluate in vivo the accuracy of the Root ZX II (J. Morita) apex locator in controlling the apical extent of rotary instrumentation when using the Auto Apical Reverse (AAR) set at the levels 0.5, 1.0 and 1.5.

Methodology  Thirty single‐rooted premolar teeth scheduled for extraction were divided into three groups (n = 10), according to the AAR setting 0.5, 1.0 and 1.5. The root canals were prepared using ProTaper (Dentsply Maillefer). After rotary instrumentation, the last file used (F3) was manually introduced into the extent of the root canal preparation and fixed before tooth extraction. The apical third of the root was dissected until exposure of the file. The distance from the file tip to the major apical foramen was obtained.

Results  Measurements within the range −1.0 to 0.0 mm were obtained in 30% of the teeth with AAR 0.5, 50% with AAR 1.0 and in 0% with AAR 1.5. The proportions test revealed a significant difference between the AAR settings 1.0 and 1.5 (P = 0.0188). Overinstrumentation occurred in 70% of the teeth with AAR 0.5 and in 40% with AAR 1.0. The measurements short of the acceptable range occurred in 10% of the teeth with setting AAR 1.0 and in 100% of the cases with AAR 1.5. A significant difference was found when comparing the percentage of teeth in which the file tip was short and beyond the established range between groups, except when comparing AAR 0.5 and AAR 1.0.

Conclusion  The AAR function of the Root ZX II was not an accurate method for controlling the apical extent of rotary instrumentation in vivo. The setting 0.5 presented overinstrumentation in most of the canals, the setting 1.5 was short in all cases, and the setting 1.0 provided an adequate working length in only 50% of the teeth.
Why choose a career in nursing?
Authors: Jirwe Maria , Rudman Ann
Published: March 2012

jirwe m. & rudman a. (2012) Why choose a career in nursing? Journal of Advanced Nursing68(7), 1615–1623.

Aim.  This paper examines the prevalence of various career‐choice motives given by nursing students in two national cohorts at the beginning and end of their education respectively and how these motives are interrelated and associated with perceived career‐choice stress.

Background.  Several international studies have identified various motives for choosing nursing. The degree to which motives are autonomous or controlled affects an individual’s professional development and health. Earlier research on career choice has used small non‐representative samples.

Design.  Cross‐sectional survey.

Methods.  This was a study of all Swedish undergraduate nursing students in their first (n = 1697) or last (n = 1150) year. The data for this study were collected in 2002, forming the baseline of a prospective longitudinal study where data were collected annually between 2002–2010. Data analysis included descriptive statistics, exploratory factor analysis and multiple regression analysis.

Results.  A model incorporating three factors explained 50–60% of the variance in motives for becoming a nurse. ‘Genuine interest’ was ranked highest, followed by ‘practical reasons’. Only a small group of students gave nursing as ‘default choice’. Fewer autonomous motives for choosing nursing were associated with perceived career‐choice stress.

Conclusion.  We suggest that it is imperative for nurse educators to identify students who lack autonomy. Supporting students’ autonomy is likely to improve educational outcome, enable professional socialization and decrease professional turnover. Future research on students’ motivation in relation to educational outcome and professional turnover as well as quality of patient care is needed.
A new perspective on blame culture: an experimental study
Authors: Gorini Alessandra , Miglioretti Massimo , Pravettoni Gabriella
Published: March 2012

Objectives  Recently, a range of different institutions worldwide has identified the ‘culture of blame’ and the fear of being punished as the principal reasons for the lack of medical error reporting and, consequently, of their reiteration and of the poor quality of patient care. Despite much theoretical debate, there currently exist no experimental studies that directly investigate the presence and pervasiveness of the blame and punishment culture in health care contexts. In order to document empirical evidence for this culture in medicine and nursing, we conducted an experimental study asking physicians and nurses to express their fear of blame or punishment in the context of having made an error that would cause: (i) no; (ii) mild; (iii) severe consequences; or (iv) the death of the patient.

Methods  Two hundred and forty‐nine health care providers (38 physicians, 11 medical students, 127 nurses and 73 nursing students) were included in the study. Two main data emerged: first, in general, the fear of being blamed is higher than the fear of being punished. Second, while the fear of being blamed is equally distributed among all participants, the fear of being punished varies according to the experience of subjects (it is higher in nursing students than in seniors nurses) and to their professional role (student and senior nurses are more susceptible to it than medical students and senior physicians).

Conclusion  Given the relevance of these factors in medical error reporting and the evidence that they are so deep‐seated not only in senior professionals, but also in students, we argue that an educational approach, together with an organization‐based intervention, is desirable to shape cultural attitudes of health care providers in the direction of a ‘safety culture’.
Maternal Hypothyroidism Decreases Progesterone Receptor Expression in the Cortical Subplate of Foetal Rat Brain
Authors: Jahagirdar V. , Zoeller T. R. , Tighe D. P. , Wagner C. K.
Published: March 2012

Steroid hormones exert profound effects on the development of brain areas controlling complex cognitive function in adulthood. One class, progestins, may contribute by acting on the progestin receptor (PR), which is transiently expressed in a critical layer of developing cortex: the subplate. PR expression in the subplate coincides with the establishment of ongoing cortical connectivity and may play an important organisational role. Identification of the factor(s) that regulate the precise timing of PR expression within subplate may help elucidate the function of PR. Thyroid hormone may interact with hormone response elements within the PR gene. The present study examined the effects of maternal hypothyroidism on levels of PR immunoreactivity (PR‐IR) within the foetal subplate. Pregnant rats were made hypothyroid by the administration of methimazole and potassium perchlorate in drinking water. Maternal hypothyroidism significantly decreased PR‐IR within the foetal subplate. Using the incorporation of 5‐bromo‐2′‐deoxyuridine (BrDU) during subplate cell neurogenesis (embryonic day 13.5) to determine subplate cell survival in hypothyroid animals, we found that decreases in PR‐IR cannot be attributed to significant subplate cell loss but are more likely the result of altered PR expression. Gestational thyroxine replacement to hypothyroid dams prevented the decrease in PR‐IR within the subplate. These results identify thyroid hormone as a potential factor in the regulation of PR expression in the developing brain. These results are consistent with the idea that endocrine cross‐talk between progesterone and thyroid hormone may be one mechanism by which maternal hypothyroidism alters normal cortical development.
Analysis of subtelomeric virulence gene families in Plasmodium falciparum by comparative transcriptional profiling
Authors: Witmer Kathrin , Schmid Christoph D. , Brancucci Nicolas M. B. , Luah Yen‐Hoon , Preiser Peter R. , Bozdech Zbynek , Voss Till S.
Published: March 2012

The Plasmodium falciparum genome is equipped with several subtelomeric gene families that are implicated in parasite virulence and immune evasion. Members of these families are uniformly positioned within heterochromatic domains and are thus subject to variegated expression. The best‐studied example is that of the var family encoding the major parasite virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 undergoes antigenic variation through switches in mutually exclusive var gene transcription. var promoters function as crucial regulatory elements in the underlying epigenetic control strategy. Here, we analysed promoters of upsA, upsB and upsC var, rifA1‐type rif, stevor, phist and pfmc‐2tm genes and investigated their role in endogenous gene transcription by comparative genome‐wide expression profiling of transgenic parasite lines. We find that the three major var promoter types are functionally equal and play an essential role in singular gene choice. Unlike var promoters, promoters of non‐var families are not silenced by default, and transcription of non‐var families is not subject to the same mode of mutually exclusive transcription as has been observed for var genes. Our findings identified a differential logic in the regulation of var and other subtelomeric virulence gene families, which will have important implications for our understanding and future analyses of phenotypic variation in malaria parasites.
The toxin/immunity network of Burkholderia pseudomallei contact‐dependent growth inhibition (CDI) systems
Authors: Nikolakakis Kiel , Amber Saba , Wilbur J. Scott , Diner Elie J. , Aoki Stephanie K. , Poole Stephen J. , Tuanyok Apichai , Keim Paul S. , Peacock Sharon , Hayes Christopher S. , Low David A.
Published: March 2012

Burkholderia pseudomallei is a category B pathogen and the causative agent of melioidosis – a serious infectious disease that is typically acquired directly from environmental reservoirs. Nearly all B. pseudomallei strains sequenced to date (> 85 isolates) contain gene clusters that are related to the contact‐dependent growth inhibition (CDI) systems of γ‐proteobacteria. CDI systems from Escherichia coli and Dickeya dadantii play significant roles in bacterial competition, suggesting these systems may also contribute to the competitive fitness of B. pseudomallei. Here, we identify 10 distinct CDI systems in B. pseudomallei based on polymorphisms within the cdiA‐CT/cdiI coding regions, which are predicted to encode CdiA‐CT/CdiI toxin/immunity protein pairs. Biochemical analysis of three B. pseudomallei CdiA‐CTs revealed that each protein possesses a distinct tRNase activity capable of inhibiting cell growth. These toxin activities are blocked by cognate CdiI immunity proteins, which specifically bind the CdiA‐CT and protect cells from growth inhibition. Using Burkholderia thailandensis E264 as a model, we show that a CDI system from B. pseudomallei 1026b mediates CDI and is capable of delivering CdiA‐CT toxins derived from other B. pseudomallei strains. These results demonstrate that Burkholderia species contain functional CDI systems, which may confer a competitive advantage to these bacteria.
Loss of FlhE in the flagellar Type III secretion system allows proton influx into Salmonella and Escherichia coli
Authors: Lee Jaemin , Harshey Rasika M.
Published: March 2012

flhE belongs to the flhBAE flagellar operon in Enterobacteria, whose first two members function in Type III secretion (T3S). In Salmonella enterica, absence of FlhE affects swarming, but not swimming, motility. Based on a chance observation of a ‘green’ colony phenotype of flhE mutants on pH indicator plates containing glucose, we have established that this phenotype is associated with lysis of flagellated cells in an acidic environment created by glucose metabolism. The flhE mutant phenotype of Escherichia coli is similar overall to that of S. enterica but is seen in the absence of glucose and, unlike in S. enterica, causes a substantial growth defect. flhE mutants have a lowered cytoplasmic pH in both bacteria, indicative of a proton leak. GFP reporter assays indicate that the leak is dependent on the flagellar system, is present before the T3S system switches to secretion of late substrates, and gets worse after the switch and upon filament assembly, leading to cell lysis. We show that FlhE is a periplasmic protein that co‐purifies with flagellar basal bodies. FlhE may act as a plug or a chaperone to regulate proton flow through the flagellar T3S system.
Effects of aging on cholinergic neuromuscular transmission in isolated small intestine of ad libitum fed and calorically‐restricted rats
Authors: Hoyle C. H. V. , Saffrey M. J.
Published: March 2012

Background  Age‐associated losses of enteric neurons have been described. In rat ileum, myenteric neurons lost during aging have been reported to be predominantly cholinergic, and caloric restriction (CR) has been shown to protect against these losses. Cholinergic myenteric neurons include excitatory motor neurons, so the aim of this work was to determine whether neuronal loss in ad libitum (AL)‐fed animals is reflected in dysfunctional cholinergic neuromuscular transmission, and if CR reduces any such dysfunction.

Methods  Effects of electrical field stimulation (EFS) and applied acetylcholine (ACh) were examined in the longitudinal muscle of isolated ileal segments from 6‐month‐old rats and from 13‐ and 24‐month‐old rats fed either AL or CR diets.

Key Results  Contractile responses to EFS were abolished by atropine and potentiated by the acetylcholinesterase inhibitor, eserine. Frequency‐response relationships were not significantly different amongst the three age‐groups. Sensitivity to applied ACh, however, was three‐fold lower in the oldest animals (P < 0.05). Eserine potentiated responses to ACh; there were no statistically significant differences amongst the sensitivities to ACh in its presence. No significant differences between AL‐ and CR‐fed animals were measured, although variability was less in CR‐fed than in AL‐fed groups.

Conclusions & Inferences  The cholinergic system supplying the rat ileum longitudinal muscle did not appear to be impaired in old age. Decreased sensitivity to applied ACh in old tissues may have been due to increased acetylcholinesterase activity. Caloric restriction had no significant effect on responses to EFS or applied ACh. The implications of these results are discussed.
Progressive cribriform and zosteriform hyperpigmentation: a clinicopathologic study
Authors: Cho Eujin , Cho Sang Hyun , Lee Jeong Deuk
Published: March 2012

Background  Progressive cribriform and zosteriform hyperpigmentation (PCZH) is a disorder of pigmentation. Although several cases of PCZH have been reported, no clinicopathologic studies of the condition have been published in the English‐language literature.

Objectives  The purpose of this study was to determine the clinical characteristics and histologic findings of PCZH.

Methods  Between 1999 and 2009, 30 patients were diagnosed with PCZH in our Department of Dermatology. Medical records, clinical photographs, and pathologic findings for each patient were retrospectively reviewed.

Results  The patients included 16 men and 14 women. The mean age at onset was 14.27 years. The trunk was the most common site of involvement. Microscopic examination showed an increased level of melanin pigment in the basal cell layer compared with adjacent normal skin, although no significant difference existed in the number of melanocytes. Pigmentary incontinence was observed in 13 of 30 cases.

Conclusions  There was no significant difference in prevalence, age at onset, and duration of lesions between male and female patients with PCZH. The lesions corresponded to the lines of Blaschko and were localized rather than exhibiting diffuse patterns. A common feature of the histopathologic findings was higher melanin content in the lesions than in normal skin but with no significant difference in the number of melanocytes.