bluuebunny/crossref_metadata_2025 huggingface dataset:
Anomalous Hall effects in Co2FeSi Heusler compound films and Co2FeSi-Al2O3 granular films
Authors: Qin Zhu , Liu Xin-Dian , Li Zhi-Qing
Published: April 2012

We fabricated three Co2FeSi Heusler compound films at different temperatures (room temperature, 673, and 873 K) by rf sputtering deposition method and a series of (Co2FeSi)x(Al2O3)1−x (0.4 ≲x≤1) granular films at room temperature by co-sputtering method. The structures as well as the temperature behaviors of anomalous Hall resistivities, low-field Hall sensitivities, and longitudinal resistivities of those films were investigated experimentally. We found that the Co2FeSi Heusler compound film deposited at room temperature is poorly crystallized, the film deposited at 673 K is crystallized in the disordered A2 type structure, and L21 and B2 structures are present in the film deposited at 873 K. For the Co2FeSi films deposited at 673 and 873 K, the saturated anomalous Hall resistivity ρAs scales with the longitudinal resistivity ρxx as ρAs∝ρxxn, with n much larger than 2. There is no scaling relation between ρAs and ρxx for the (Co2FeSi)x(Al2O3)1−x (0.58≤x≤1, x=1 represents the Co2FeSi film deposited at room temperature) granular films. For the granular films, as x decreases from 1 to 0.67, the magnitude of ρxx increases by a factor of ∼25, whereas the magnitude enhancement in ρAs is less than 50%, which strongly suggests that the longitudinal and anomalous Hall transports in ferromagnetic granular films are governed by different mechanisms. The low-field Hall sensitivities of (Co2FeSi)x(Al2O3)1−x films with x values of 0.6 and 0.65 are large and temperature insensitivity from 300 down to ∼75 K, which might make them be good candidate materials for low-field Hall sensors.
Two-photon excitation in an intermediate band solar cell structure
Authors: Ahsan Nazmul , Miyashita Naoya , Monirul Islam Muhammad , Man Yu Kin , Walukiewicz Wladek , Okada Yoshitaka
Published: April 2012

We present evidence for the production of photocurrent due to two-photon excitation in an intermediate band solar cell structure. The structure consists of an n-GaNAs intermediate band layer sandwiched between a p-AlGaAs emitter and an n-AlGaAs barrier layer with suitable doping level to block electron escaping from the intermediate band to the bottom n-GaAs substrate. Multi-band transitions observed in two-photon excitation experiments are explained using photo-modulated reflectance spectrum, and further support for intermediate band solar cell operation of this structure is given by current-voltage measurements.
Tunable photovoltaic effects in transparent Pb(Zr0.53,Ti0.47)O3 capacitors
Authors: Chen Bin , Zuo Zhenghu , Liu Yiwei , Zhan Qing-Feng , Xie Yali , Yang Huali , Dai Guohong , Li Zhixiang , Xu Gaojie , Li Run-Wei
Published: April 2012

We report an investigation on optical, ferroelectric, and photovoltaic properties of transparent Sn-doped In2O3 (ITO)/Pb(Zr0.53,Ti0.47)O3 (PZT)/ITO thin film capacitors. The ferroelectric PZT sandwiched structures grown on glass substrates exhibit a transmittance of 65% in the visible light range. The current-voltage characteristics show that the transparent PZT capacitors possess a significant photovoltaic response under a light illumination. Moreover, the photovoltaic response can be well tuned by an external electrical field, which can be understood by considering the tunable depolarized field in the PZT capacitors.
Monitoring single-cell bioenergetics via the coarsening of emulsion droplets
Authors: Boitard L. , Cottinet D. , Kleinschmitt C. , Bremond N. , Baudry J. , Yvert G. , Bibette J.
Published: April 2012

Microorganisms are widely used to generate valuable products, and their efficiency is a major industrial focus. Bioreactors are typically composed of billions of cells, and available measurements only reflect the overall performance of the population. However, cells do not equally contribute, and process optimization would therefore benefit from monitoring this intrapopulation diversity. Such monitoring has so far remained difficult because of the inability to probe concentration changes at the single-cell level. Here, we unlock this limitation by taking advantage of the osmotically driven water flux between a droplet containing a living cell toward surrounding empty droplets, within a concentrated inverse emulsion. With proper formulation, excreted products are far more soluble within the continuous hydrophobic phase compared to initial nutrients (carbohydrates and salts). Fast diffusion of products induces an osmotic mismatch, which further relaxes due to slower diffusion of water through hydrophobic interfaces. By measuring droplet volume variations, we can deduce the metabolic activity down to isolated single cells. As a proof of concept, we present the first direct measurement of the maintenance energy of individual yeast cells. This method does not require any added probes and can in principle apply to any osmotically sensitive bioactivity, opening new routes for screening, and sorting large libraries of microorganisms and biomolecules.
Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist
Authors: Iwaisako Keiko , Haimerl Michael , Paik Yong-Han , Taura Kojiro , Kodama Yuzo , Sirlin Claude , Yu Elizabeth , Yu Ruth T. , Downes Michael , Evans Ronald M. , Brenner David A. , Schnabl Bernd
Published: April 2012

Peroxisome proliferator-activated receptor delta (PPARδ), a member of the nuclear receptor family, is emerging as a key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle, and liver. Here we show that the PPARδ agonist KD3010, but not the well-validated GW501516, dramatically ameliorates liver injury induced by carbon tetrachloride (CCl
4
) injections. Deposition of extracellular matrix proteins was lower in the KD3010-treated group than in the vehicle- or GW501516-treated group. Interestingly, profibrogenic connective tissue growth factor was induced significantly by GW501516, but not by KD3010, following CCl
4
treatment. The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using bile duct ligation for 3 wk. Primary hepatocytes treated with KD3010 but not GW501516 were protected from starvation or CCl
4
-induced cell death, in part because of reduced reactive oxygen species production. In conclusion, our data demonstrate that an orally active PPARδ agonist has hepatoprotective and antifibrotic effects in animal models of liver fibrosis, suggesting a possible mechanistic and therapeutic approach in treating patients with chronic liver diseases.
Botany.
Authors: Bosland P. W. , Votava E. J.
Published: April 2012

This chapter focuses on the morphology, growth and development of the vegetative structures of pepper, i.e. embryos and seedlings, stems and leaves, flowers, pollen, calyx/pedicel and fruits.
Lyme disease.
Authors: Halperin J. J.
Published: April 2012

Lyme disease is a focally endemic tick-borne spirochaetal infection that causes a well-defined constellation of symptoms. Diagnosis requires a combination of appropriate epidemiologic and clinical factors; laboratory confirmation with standardized serologic testing is highly accurate except in the setting of very early disease, such as in patients with erythema migrans, but is not helpful in judging treatment response. Treatment with simple, time-limited courses of penicillins, third-generation cephalosporins and tetracyclines is highly effective.
Environmental impacts of organic agriculture in temperate regions.
Authors: Lynch D. H. , Halberg N. , Bhatta G. D.
Published: April 2012

Can organic agriculture elaborate a scientifically based, resource-efficient and agroecological approach to low-input farm management? This review examines the literature from temperate regions, with a particular emphasis on Canadian and US studies that relate to environmental and ecological impacts of organic agriculture with respect to (i) soil organic matter storage, (ii) soil quality/soil health, (iii) nutrient loading and risks of off-farm nutrient and agrochemical losses, (iv) biodiversity and (v) energy use and global warming potential. The context and implications of semi-arid conditions and low soil P levels, common to many organic farms in North America, and widespread adoption of genetically engineered crops in conventional production, is also considered. The consensus of the data available to date indicates the distinctiveness of cropping, floral and habitat diversity, soil management regime, nutrient intensity and use efficiency, and energy, and pesticide use in organic farming confer important environmental and ecological benefits. These include maintenance of soil organic matter and added return of carbon to soil, improved soil health, reduced off-farm nitrogen and phosphorus losses, enhanced vegetative and wildlife (bird) biological diversity, extended sometimes to other taxa depending on landscape context, improved support for pollinators and pollination and reduced energy use and improved energy efficiency. The continued evolution of organic agriculture to a more outcomes-based, agroecological production system will require an expanded multi-disciplinary research effort, linked ideally to support from consumers and policy-makers on the basis of renewed understanding of its potential contribution to global environmental sustainability.
EUROPEAN MARXISM AND THE QUESTION OF ANTISEMITISM
Authors: Spencer Philip
Published: April 2012

Opposition to racism and antisemitism is often assumed to be a distinguishing feature of radical left politics. Before and during the Holocaust, the most radical case of antisemitism, most Marxists were slow to recognise the threat posed to the Jews. After the event, there has been little significant rethinking. There may then be difficulties if and when antisemitism reappears. There are, however, some neglected resources within Marxism which could help shape a more effective response to a problem which continues to trouble European and other societies even after this traumatic event.
The ℎ-principle and the equations of fluid dynamics
Authors: De Lellis Camillo , Székelyhidi László
Published: April 2012

In this note we survey some recent results for the Euler equations in compressible and incompressible fluid dynamics. The main point of all these theorems is the surprising fact that a suitable variant of Gromov’s

h
h

-principle holds in several cases.
The ulnar-mammary syndrome gene,Tbx3, is a direct target of the retinoic acid signaling pathway, which regulates its expression during mouse limb development
Authors: Ballim Reyna Deeya , Mendelsohn Cathy , Papaioannou Virginia E. , Prince Sharon
Published: April 2012

TBX3, a member of the T-box transcription factor gene family, is a transcriptional repressor that is required for the development of the heart, limbs, and mammary glands. Mutations in TBX3 that result in reduced functional protein lead to ulnar-mammary syndrome, a developmental disorder characterized by limb, mammary gland, tooth, and genital abnormalities. Increased levels of TBX3 have been shown to contribute to the oncogenic process, and TBX3 is overexpressed in several cancers, including breast cancer, liver cancer, and melanoma. Despite its important role in development and postnatal life, little is known about the signaling pathways that modulate TBX3 expression. Here we show, using in vitro and in vivo assays, that retinoic acid (RA) activates endogenous TBX3 expression, which is mediated by an RA–receptor complex directly binding and activating the TBX3 promoter, and we provide evidence that this regulation may be functionally relevant in mouse embryonic limb development. Our data identify TBX3 as a direct target of the RA signaling pathway and extend our understanding of the role and regulation of TBX3 in limb development.
Plk1 regulates the kinesin-13 protein Kif2b to promote faithful chromosome segregation
Authors: Hood Emily A. , Kettenbach Arminja N. , Gerber Scott A. , Compton Duane A.
Published: April 2012

Solid tumors are frequently aneuploid, and many display high rates of ongoing chromosome missegregation in a phenomenon called chromosomal instability (CIN). The most common cause of CIN is the persistence of aberrant kinetochore-microtubule (k-MT) attachments, which manifest as lagging chromosomes in anaphase. k-MT attachment errors form during prometaphase due to stochastic interactions between kinetochores and microtubules. The kinesin-13 protein Kif2b promotes the correction of k-MT attachment errors in prometaphase, but the mechanism restricting this activity to prometaphase remains unknown. Using mass spectrometry, we identified multiple phosphorylation sites on Kif2b, some of which are acutely sensitive to inhibition of Polo-like kinase 1 (Plk1). We show that Plk1 directly phosphorylates Kif2b at threonine 125 (T125) and serine 204 (S204), and that these two sites differentially regulate Kif2b function. Phosphorylation of S204 is required for the kinetochore localization and activity of Kif2b in prometaphase, and phosphorylation of T125 is required for Kif2b activity in the correction of k-MT attachment errors. These data demonstrate that Plk1 regulates both the localization and activity of Kif2b during mitosis to promote the correction of k-MT attachment errors to ensure mitotic fidelity.
Constitutive dynein activity inshe1mutants reveals differences in microtubule attachment at the yeast spindle pole body
Authors: Bergman Zane J. , Xia Xue , Amaro I. Alexandra , Huffaker Tim C.
Published: April 2012

The organization of microtubules is determined in most cells by a microtubule-organizing center, which nucleates microtubule assembly and anchors their minus ends. In Saccharomyces cerevisiae cells lacking She1, cytoplasmic microtubules detach from the spindle pole body at high rates. Increased rates of detachment depend on dynein activity, supporting previous evidence that She1 inhibits dynein. Detachment rates are higher in G1 than in metaphase cells, and we show that this is primarily due to differences in the strengths of microtubule attachment to the spindle pole body during these stages of the cell cycle. The minus ends of detached microtubules are stabilized by the presence of γ-tubulin and Spc72, a protein that tethers the γ-tubulin complex to the spindle pole body. A Spc72–Kar1 fusion protein suppresses detachment in G1 cells, indicating that the interaction between these two proteins is critical to microtubule anchoring. Overexpression of She1 inhibits the loading of dynactin components, but not dynein, onto microtubule plus ends. In addition, She1 binds directly to microtubules in vitro, so it may compete with dynactin for access to microtubules. Overall, these results indicate that inhibition of dynein activity by She1 is important to prevent excessive detachment of cytoplasmic microtubules, particularly in G1 cells.
PSI-Search: iterative HOE-reduced profile SSEARCH searching
Authors: Li Weizhong , McWilliam Hamish , Goujon Mickael , Cowley Andrew , Lopez Rodrigo , Pearson William R.
Published: April 2012

Summary: Iterative similarity searches with PSI-BLAST position-specific score matrices (PSSMs) find many more homologs than single searches, but PSSMs can be contaminated when homologous alignments are extended into unrelated protein domains—homologous over-extension (HOE). PSI-Search combines an optimal Smith–Waterman local alignment sequence search, using SSEARCH, with the PSI-BLAST profile construction strategy. An optional sequence boundary-masking procedure, which prevents alignments from being extended after they are initially included, can reduce HOE errors in the PSSM profile. Preventing HOE improves selectivity for both PSI-BLAST and PSI-Search, but PSI-Search has ~4-fold better selectivity than PSI-BLAST and similar sensitivity at 50% and 60% family coverage. PSI-Search is also produces 2- for 4-fold fewer false-positives than JackHMMER, but is ~5% less sensitive.

Availability and implementation: PSI-Search is available from the authors as a standalone implementation written in Perl for Linux-compatible platforms. It is also available through a web interface (www.ebi.ac.uk/Tools/sss/psisearch) and SOAP and REST Web Services (www.ebi.ac.uk/Tools/webservices).

Contact:  pearson@virginia.edu; rodrigo.lopez@ebi.ac.uk
Metabolic heart failure
Authors: Korman Stanley H. , Keren Andre
Published: April 2012

Inherited metabolic disorders are an important cause of heart failure(HF), particularly because many of them are amenable to treatment.It is therefore important that metabolic disorders arerecognized and accurately diagnosed. The heart is dependent onnormal metabolic function to provide a continuous source ofenergy at rest and even more so during exertion or stress. Manydisorders of metabolism therefore affect cardiac function and mayhave devastating consequences).Cardiac failure in metabolic disorders is most commonly a consequenceof cardiomyopathy. Hypertrophic cardiomyopathy istypical of the glycogen and lysosomal storage diseases as well asthe disorders of mitochondrial energy production. Dilated cardiomyopathyis a feature of some of the organic acidurias, disordersof carnitine metabolism, and some mitochondrial disorders. Oftenthe distinction is unclear, with a transition from hypertrophic todilated cardiomyopathy as the disease progresses.Additional mechanisms leading to cardiac failure in metabolicdisorders include valvular disease, arrhythmias and conductiondisturbances, coronary artery disease, and pulmonaryhypertension.
The pathophysiology of heart failure
Authors: McDonagh Theresa A. , Dargie Henry J.
Published: April 2012

The classical definition of heart failure (HF) is fundamentally a pathophysiological one. It is the ‘inability of the heart to provide sufficient oxygen to the metabolizing tissues despite an adequate filling pressure’. Initially, the abnormalities found in the HF syndrome were described in terms of their haemodynamic effects. However, as the relationship between the pathophysiology of HF and its therapy has emerged over the last 20 years, it is now clear that the pathophysiology of HF is highly complex. It also involves neurohormonal and inflammatory adaptations which initially help the situation but chronically contribute to progression of the HF syndrome and adversely affect the structure and function of the heart itself. This chapter reviews the pathophysiology of HF by outlining what is known about its key players: haemodynamic abnormalities, ventricular remodelling, neurohormonal activation, and inflammatory responses. Although any cardiac pathology can ultimately lead to HF, most is known about the pathophysiology of HF due to myocardial failure leading to left ventricular systolic dysfunction (LVSD), which concerns most of this chapter. Much work is needed to elucidate further the pathophysiology of HF when it occurs in the presence of normal systolic function.
Cytokines and inflammatory markers
Authors: Adamopoulos Stamatis , Georgiadou Panagiota , Voudris Vassilios
Published: April 2012

The expression of classic neurohormones, such as angiotensin IIand noradrenaline, plays an important role in disease progressionin chronic heart failure (HF). This so-called neurohormonal activationseems to be involved in the cardiomyopathic process ofadverse left ventricular remodelling and dysfunction, via bothdirect and indirect effects. Therapies blocking the excessiveactivation of the renin–angiotensin system and the adrenergic systemhave become the mainstay of pharmacological treatment ofchronic HF. Another important pathway in chronic HF progression is inflamatoryactivation. Experimental studies have shown that proinflammatory cytokines may induce many aspects of the syndromeof chronic HF, such as left ventricular dysfunction, pulmonaryoedema, and the process of left ventricular remodelling, includingmyocyte hypertrophy, progressive myocyte loss through apoptosis,and endothelial dysfunction. Although the cause of the inflammationis unknown, both infectious (e.g.endotoxins) and non-infectious (e.g. oxidative stress, haemodynamic overload) events couldbe operating, including interaction with the neurohormone system. Inflammatory markers have emerged as potential indicatorsof the evolution of HF, ranging from their use for screening, diagnosis,determining prognosis, and guiding treatment. The emerging association of inflammatory mediators with thepathogenesis and progression of chronic HF has already resulted inthe development of new anti-inflammatory strategies, which might beused as adjunctive therapy in patients with chronic HF. Moreover,there is accumulating evidence that a critical network of interactionsis formed by inflammatory and the classic neurohormonal mediators,and that many of the conventional therapies for HF may, at least partially, modulate the proinflammatory cytokine milieu. However,therapies tested so far have been largely disappointing.
Mitral valve surgery in heart failure
Authors: Murday Andrew
Published: April 2012

Functional, or secondary, mitral regurgitation (MR) develops aspart of the process of remodelling which in turn occurs as a resultof left ventricular failure. Although this complication can resultwhatever the primary pathology causing the left ventricular failure,the pathophysiological process varies to a certain extent dependingon the aetiology. There is some confusion in the literature withrespect to ischaemic MR, with some authors calling all ischaemic MR functional. For the sake of clarity, this chapter deals with functionalMR resulting from left ventricular failure which for the sake of argument I will define as a left ventricular ejection fraction(LVEF) of less than 35%. Functional MR is a common consequence of left ventricularsystolic dysfunction (LVSD) and it has an important bearing onboth symptoms and outcome in patients suffering from heart failure(HF). In a study of 2057 patients with symptomatic HF andwith a LVEF of less than 40% but without structural valve disease,56.2% had some degree of MR and in 29.8% of these it was moderate or severe. Furthermore, the presence of moderate or severeMR was associated with a significantly higher mortality at 1, 3, and5 years. In a multivariate analysis, MR of any degree wasan independent predictor of death. The success of mitral valve surgery, and in particular the flourishingof mitral valve repair techniques, along with the ever-increasingburden of patients with HF, has led to the adaptationof repair techniques, originally developed to correct structuralabnormalities of the mitral valve, to attempt to halt or even reversethe remodelling process.
Detection of host immune responses in acute phase sera of spontaneous resolution versus persistent hepatitis C virus infection
Authors: Selvarajah Suganya , Keating Sheila , Heitman John , Lu Kai , Simmons Graham , Norris Philip J. , Operskalski Eva , Mosley James W. , Busch Michael P.
Published: April 2012

Prior to the identification of hepatitis C virus (HCV), transfusion-transmission was common. Viral transmission in subjects with a known date of infection allows the study of the immune responses to acute HCV infection. We analysed 39 soluble immune factors in serum samples from subjects with transfusion-transmitted HCV. Dynamic expression kinetics of interferon gamma-induced protein 10 (IP-10), tumour necrosis factor-alpha and interleukin (IL)-10 were observed during acute HCV infection. Serum IP-10 was the only analyte that was significantly elevated in HCV resolvers compared with uninfected controls. In individuals who progressed to chronic HCV elevated levels of IP-10 and IL-10 coincided with first significant alanine aminotransferase elevation and remained elevated during the first year of acute HCV infection. In addition to monitoring lack of reduction in viral load, serum levels of IP-10 and IL-10 expression during acute HCV infection may be useful biomarkers to predict the progress to chronic HCV.
Non-canonical translation in RNA viruses
Authors: Firth Andrew E. , Brierley Ian
Published: April 2012

Viral protein synthesis is completely dependent upon the translational machinery of the host cell. However, many RNA virus transcripts have marked structural differences from cellular mRNAs that preclude canonical translation initiation, such as the absence of a 5′ cap structure or the presence of highly structured 5′UTRs containing replication and/or packaging signals. Furthermore, whilst the great majority of cellular mRNAs are apparently monocistronic, RNA viruses must often express multiple proteins from their mRNAs. In addition, RNA viruses have very compact genomes and are under intense selective pressure to optimize usage of the available sequence space. Together, these features have driven the evolution of a plethora of non-canonical translational mechanisms in RNA viruses that help them to meet these challenges. Here, we review the mechanisms utilized by RNA viruses of eukaryotes, focusing on internal ribosome entry, leaky scanning, non-AUG initiation, ribosome shunting, reinitiation, ribosomal frameshifting and stop-codon readthrough. The review will highlight recently discovered examples of unusual translational strategies, besides revisiting some classical cases.
The Use of Recombinant Pseudotype Virus-Like Particles Harbouring Inserted Target Antigen to Generate Antibodies against Cellular Marker p16INK4A
Authors: Lasickienė Rita , Gedvilaite Alma , Norkiene Milda , Simanaviciene Vaida , Sezaite Indre , Dekaminaviciute Dovile , Shikova Evelina , Zvirbliene Aurelija
Published: April 2012

Protein engineering provides an opportunity to generate new immunogens with desired features. Previously, we have demonstrated that hamster polyomavirus major capsid protein VP1-derived virus-like particles (VLPs) are highly immunogenic and can be employed for the insertion of foreign epitopes at certain surface-exposed positions. In the current study, we have designed pseudotype VLPs consisting of an intact VP1 protein and VP2 protein fused with the target antigen—cellular marker p16INK4A—at its N terminus. Both proteins coexpressed in yeast were self-assembled to pseudotype VLPs harbouring the inserted antigen on the surface. The pseudotype VLPs were used for generation of antibodies against p16INK4Athat represents a potential biomarker for cells transformed by high-risk human papillomavirus (HPV). The pseudotype VLPs induced in immunized mice a strong immune response against the target antigen. The antisera raised against pseudotype VLPs showed specific immunostaining of p16INK4Aprotein in malignant cervical tissue. Spleen cells of the immunized mice were used to generate monoclonal antibodies against p16INK4Aprotein. The specificity of antibodies was proven by the immunostaining of HPV-transformed cells. In conclusion, the current study demonstrates the potential of pseudotype VLPs with inserted target antigen as a new type of immunogens to generate antibodies of high diagnostic value.
Socioeconomic Importance of the Banana Tree (Musa Spp.) in the Guinean Highland Savannah Agroforests
Authors: Mapongmetsem Pierre Marie , Nkongmeneck Bernard Aloys , Gubbuk Hamide
Published: April 2012

Home gardens are defined as less complex agroforests which look like and function as natural forest ecosystems but are integrated into agricultural management systems located around houses. Investigations were carried out in 187 households. The aim of the study was to identify the different types of banana home gardens existing in the periurban zone of Ngaoundere town. The results showed that the majority of home gardens in the area were very young (less than 15 years old) and very small in size (less than 1 ha). Eleven types of home gardens were found in the periurban area of Ngaoundere town. The different home garden types showed important variations in all their structural characteristics. Two local species of banana are cultivated in the systems,Musa sinensisandMusa paradisiaca. The total banana production is 3.57 tons per year. The total quantity of banana consumed in the periurban zone was 3.54 tons (93.5%) whereas 1.01 tons were sold in local or urban markets. The main banana producers belonged to home gardens 2, 4, 7, and 9. The quantity of banana offered to relatives was more than what the farmers received from others. Farmers, rely on agroforests because the flow of their products helps them consolidate friendship and conserve biodiversity at the same time.
Global analysis reveals multiple pathways for unique regulation of mRNA decay in induced pluripotent stem cells
Authors: Neff Ashley T. , Lee Ju Youn , Wilusz Jeffrey , Tian Bin , Wilusz Carol J.
Published: April 2012

Pluripotency is a unique state in which cells can self-renew indefinitely but also retain the ability to differentiate into other cell types upon receipt of extracellular cues. Although it is clear that stem cells have a distinct transcriptional program, little is known about how alterations in post-transcriptional mechanisms, such as mRNA turnover, contribute to the achievement and maintenance of pluripotency. Here we have assessed the rates of decay for the majority of mRNAs expressed in induced pluripotent stem (iPS) cells and the fully differentiated human foreskin fibroblasts (HFFs) they were derived from. Comparison of decay rates in the two cell types led to the discovery of three independent regulatory mechanisms that allow coordinated turnover of specific groups of mRNAs. One mechanism results in increased stability of many histone mRNAs in iPS cells. A second pathway stabilizes a large set of zinc finger protein mRNAs, potentially through reduced levels of miRNAs that target them. Finally, a group of transcripts bearing 3′ UTR C-rich sequence elements, many of which encode transcription factors, are significantly less stable in iPS cells. Intriguingly, two poly(C)-binding proteins that recognize this type of element are reciprocally expressed in iPS and HFF cells. Overall, our results highlight the importance of post-transcriptional control in pluripotent cells and identify miRNAs and RNA-binding proteins whose activity may coordinately control expression of a wide range of genes in iPS cells.
In vitro and in vivo identification of a novel cytotoxic T lymphocyte epitope from Rv3425 of Mycobacterium tuberculosis
Authors: Chen Fei , Zhai Ming‐xia , Zhu Yu‐huang , Qi Yuan‐ming , Zhai Wen‐jie , Gao Yan‐feng
Published: April 2012

The identification of novel cytotoxic T lymphocyte (CTL) epitopes is important to analysis of the involvement of CD8+ T cells in Mycobacterium tuberculosis infection as well as to the development of peptide vaccines. In this study, a novel CTL epitope from region of difference 11 encoded antigen Rv3425 was identified. Epitopes were predicted by the reversal immunology approach. Rv3425‐p118 (LIASNVAGV) was identified as having relatively strong binding affinity and stability towards the HLA‐A*0201 molecule. Peripheral blood mononuclear cells pulsed by this peptide were able to release interferon‐γ in healthy donors (HLA‐A*02+ purified protein derivative+). In cytotoxicity assays in vitro and in vivo, Rv3425‐p118 induced CTLs to specifically lyse the target cells. Therefore, this epitope could provide a subunit component for designing vaccines against Mycobacterium tuberculosis.
Dose‐dependent mesothelioma induction by intraperitoneal administration of multi‐wall carbon nanotubes in p53 heterozygous mice
Authors: Takagi Atsuya , Hirose Akihiko , Futakuchi Mitsuru , Tsuda Hiroyuki , Kanno Jun
Published: April 2012

Among various types of multi‐wall carbon nanotubes (MWCNT) are those containing fibrous particles longer than 5 μm with an aspect ratio of more than three (i.e. dimensions similar to mesotheliomagenic asbestos). A previous study showed that micrometer‐sized MWCNT (μm‐MWCNT) administered intraperitoneally at a dose of 3000 μg/mouse corresponding to 1 × 109 fibers per mouse induced mesotheliomas in p53 heterozygous mice. Here, we report a dose‐response study; three groups of p53 heterozygous mice (n = 20) were given a single intraperitoneal injection of 300 μg/mouse of μm‐MWCNT (corresponding to 1 × 108 fibers), 30 μg/mouse (1 × 107) or 3 μg/mouse (1 × 106), respectively, and observed for up to 1 year. The cumulative incidence of mesotheliomas was 19/20, 17/20 and 5/20, respectively. The severity of peritoneal adhesion and granuloma formation were dose‐dependent and minimal in the lowest dose group. However, the time of tumor onset was apparently independent of the dose. All mice in the lowest dose group that survived until the terminal kill had microscopic atypical mesothelial hyperplasia considered as a precursor lesion of mesothelioma. Right beneath was a mononuclear cell accumulation consisting of CD45‐ or CD3‐positive lymphocytes and CD45/CD3‐negative F4/80 faintly positive macrophages; some of the macrophages contained singular MWCNT in their cytoplasm. The lesions were devoid of epithelioid cell granuloma and fibrosis. These findings were in favor of the widely proposed mode of action of fiber carcinogenesis, that is, frustrated phagocytosis where the mesotheliomagenic microenvironment on the peritoneal surface is neither qualitatively altered by the density of the fibers per area nor by the formation of granulomas against agglomerates. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02318.x, 2012)
Identification of new Potato virus Y (PVY) molecular determinants for the induction of vein necrosis in tobacco
Authors: FAUREZ FLORENCE , BALDWIN THOMAS , TRIBODET MICHEL , JACQUOT EMMANUEL
Published: April 2012

Two tobacco vein necrosis (TVN) determinants, the residues K400 and E419, have been identified previously in the helper component‐protease (HC‐Pro) protein sequence of Potato virus Y (PVY). However, since their description, non‐necrotic PVY isolates with both K400 and E419 necrotic determinants have been reported in the literature. This suggests the presence in the viral genome of other, as yet uncharacterized, TVN determinant(s). The identification of PVYN pathogenicity determinants was approached through the replacement of genomic regions of the necrotic PVYN‐605 infectious clone by corresponding sequences from the non‐necrotic PVYO‐139 isolate. Series of PVYN/O chimeras and site‐directed PVY mutants were constructed to test the involvement of different parts of the PVY genome (from nucleotide 421 to nucleotide 9629) in the induction of TVN symptoms. The analysis of both the genomic characteristics and biological properties of these mutants made it possible to highlight the involvement, in addition to residues K400 and E419, of the residue N339 of the HC‐Pro protein and two regions in the cytoplasmic inclusion (CI) protein to nuclear inclusion protein a‐protease (NIa‐Pro) sequence (nucleotides 5496–5932 and 6233–6444) in the induction of vein necrosis in tobacco infected by PVY isolates.
Haematopoietic stem cell transplantation (HSCT) in severe autoimmune diseases: analysis of UK outcomes from the British Society of Blood and Marrow Transplantation (BSBMT) data registry 1997–2009
Authors: Snowden John A. , Pearce Rachel M. , Lee Julia , Kirkland Keiren , Gilleece Maria , Veys Paul , Clark Richard E. , Kazmi Majid , Abinun Mario , Jackson Graham H. , Mackinnon Stephen , Russell Nigel H. , Cook Gordon ,   on behalf of the BSBMT Clinical Trials Committee
Published: April 2012

The British Society of Blood and Marrow Transplantation Data Registry was used to analyse outcomes of haematopoietic stem cell transplantation (HSCT) in severe autoimmune diseases (SADs) from 1997 to 2009. 55 autologous and 15 allogeneic HSCT were registered (0·22% of overall UK HSCT activity). Sustained responses were observed following HSCT, although toxicity was significant. This is the first reported national analysis of long‐term outcomes of HSCT in SADs, and should be viewed in the context of translational and developmental phases of HSCT in poor prognosis and refractory SADs. Treatment of poor‐risk but reversible SADs with adequate fitness for HSCT in accordance with current guidelines is warranted.
Comparison of the diagnostic accuracy of combined elastosonography and BRAF analysis vs cytology and ultrasonography for thyroid nodule suspected of malignancy
Authors: Nacamulli Davide , Nico Lorena , Barollo Susi , Zambonin Laura , Pennelli Giammaria , Girelli Maria Elisa , Casal Ide Eric , Pelizzo Maria Rosa , Vianello Federica , Negro Isabella , Watutantrige‐Fernando Sara , Mantero Franco , Rugge Massimo , Mian Caterina
Published: April 2012

Objective

Diagnosing thyroid nodules preoperatively using traditional diagnostic tools – ultrasonography (US) and cytology – still carries a considerable degree of uncertainty, and surgery is recommended for a far from negligible number of patients simply for diagnostic purposes. Thyroid elastosonography (USE) and BRAF analysis have recently proved useful in detecting thyroid malignancies. The aim of this study is to establish whether combining USE and BRAF testing ameliorates preoperative diagnosis of thyroid nodule candidates for intervention by conventional approaches, thereby avoiding the need for diagnostic surgical procedures.

Design and Patients

We retrospectively analysed the files of 155 consecutive patients with 164 nodules, all assessed by ultrasonography, cytology, USE and BRAF testing, who underwent thyroid surgery.

Results

Of the 164 nodules, 74 (45%) were benign and 90 (55%) were malignant at final histology. Combining ultrasonography and cytology identified 21 (13%) as benign, 93 (57%) as malignant or probably malignant and 50 (30%) as ‘suspended’ (when the combined test was not able to classify the node as benign or malignant) with a 99% sensitivity, 28% specificity, 63% PPV, 95% NPV and 67% accuracy. Combining USE and BRAF testing indicated that 59 (36%) were benign, 74 (45%) were malignant and 31 (19%) were in a ‘suspended’ category, with a 95% sensitivity, 74% specificity, 82% PPV, 93% NPV and 86% accuracy.

Conclusions

In assessing thyroid nodules suspected of malignancy, the combined analysis of USE and BRAF is equally sensitive and more specific than conventional procedures, achieving more accurate preoperative diagnoses than US and cytology combined. USE and BRAF analysis for thyroid nodule evaluation might reduce the number of unnecessary surgical procedures.
Parental history of type 2 diabetes and cardiometabolic biomarkers in offspring
Authors: Abbasi Ali , Corpeleijn Eva , van der Schouw Yvonne T. , Stolk Ronald P. , Spijkerman Annemieke , van der A Daphne L. , Navis Gerjan , Bakker Stephan J. L. , Beulens Joline W. J.
Published: April 2012

Eur J Clin Invest 2012; 42 (9): 974–982

Background  Parental history of type 2 diabetes (T2D) is associated with cardiometabolic risk. We aimed to investigate the associations of parental history of T2D with cardiometabolic biomarkers and to subsequently investigate to what extent these putative associations were explained by modifiable factors.

Materials and methods  Cross‐sectionally, we analysed a random sample of 2001 participants without T2D (20–70 years) from the European Prospective Investigation into Cancer and Nutrition–Netherlands (EPIC‐NL). Plasma levels of 12 biomarkers – total, HDL and LDL‐cholesterol, triglycerides, HbA1c, gamma‐glutamyltransferase (GGT), alanine aminotransferase (ALT), asparate aminotransferase (AST), albumin, uric acid, creatinine and high‐sensitivity CRP (hs‐CRP) – were assessed according to categories of parental history of T2D.

Results  In age and sex–adjusted analyses, offspring with parental history of T2D had significantly higher ALT [β = 0·074; 95% confidence interval (95%CI), 0·023–0·126] and AST levels (β = 0·033; 95%CI, 0·001 to 0·066) and a trend towards higher HbA1c (β = 0·011; 95%CI, −0·001 to 0·024) and GGT (β = 0·049; 95%CI, −0·015 to 0·112) levels. Adjustment for diet, smoking, alcohol intake, physical activity and educational level modestly attenuated the magnitude of these associations, but they remained significant for ALT and borderline significant for AST. After further adjustment for adiposity, additional attenuation was observed, but the association remained significant for ALT. Only maternal history of T2D was associated with higher ALT levels. T2D in both parents was associated with increased levels of all liver enzymes, but the association remained significant for GGT after adjustment for adiposity. Overall, the modifiable factors explained 21·2–45·4% of these associations. The contribution of adiposity was 18·2–38·9%.

Conclusion  We conclude that parental history of T2D was associated with higher non‐fasting levels of liver enzymes in a general population without T2D. Adiposity substantially contributed to these associations. The contribution of diet and lifestyle factors was modest.
Application of stabilized Fe0 nanoparticles for remediation of Cr(VI)‐spiked soil
Authors: Reyhanitabar A. , Alidokht L. , Khataee A. R. , Oustan S.
Published: April 2012

In this study, laboratory batch experiments were conducted on a chromium (Cr)‐spiked soil to evaluate the effectiveness of synthesized starch‐stabilized iron (Fe0) nanoparticles and compared with Fe0 and Fe3O4 with different particle sizes, and also with decreasing water‐extractable Cr(VI). Comparative studies were carried out at a Cr(VI) concentration of 100 mg kg−1 and a Fe materials dosage of 1.5% w/w. Results indicated that stabilized Fe0 nanoparticles had a greater efficiency (100%) to immobilize Cr(VI). The efficiency of the iron materials that we used for immobilization of Cr(VI) was in the following order: starch‐stabilized Fe0 nanoparticles > non‐stabilized Fe0 nanoparticles > Fe3O4 nanoparticles > Fe0 micro‐particles > Fe3O4 micro‐particles. Several factors affecting the immobilization of Cr(VI) by stabilized Fe0 nanoparticles, including reaction time, initial Cr(VI) concentration in soil, Fe0 nanoparticles dosage and soil‐solution suspension pH, were investigated. The overall rate of the Cr(VI) immobilization process was quick and almost 50% of the immobilization was reached within the first 2 minutes of the reaction. Cr(VI) immobilization percentages decreased from 100 to 54% as the initial Cr(VI) concentration increased from 50 to 1650 mg kg−1. Furthermore, increasing Fe0 nanoparticles dosage from 0.5 to 3% w/w caused a 70% increase in the immobilization efficiency. The results indicated that increasing the soil suspension pH from 5 to 9, in both buffered and unbuffered conditions, did not have any significant effect on the extent of water‐extractable Cr(VI).
Metaphors used by in‐service training nurses for in‐service training nurses in Turkey
Authors: Kaya Hülya , Işik Burçin , Çalişkan Figen
Published: April 2012

kaya h., işik b. & çalişkan f. (2012) Metaphors used by in‐service training nurses for in‐service training nurses in Turkey. Journal of Advanced Nursing69(2), 404–414. doi: 10.1111/j.1365‐2648.2012.06019.x

Aim.  To report a study conducted using a qualitative and quantitative study pattern with an aim to reveal the perceptions of in‐service training nurses about in‐service training nurses via metaphors.

Background.  The in‐service training nurse assumes great responsibility in the effective and efficient implementation of the educational activities in healthcare. In line with this, determining the perceptions of the in‐service training nurses about in‐service training nurses via metaphors and taking this into consideration in professional activities are important in terms of developing, changing, or questioning the perspectives of the in‐service training nurses about their roles and developing their own training nurse identity.

Design.  This article was designed as qualitative and quantitative study pattern.

Methods.  The population of the study included 93 in‐service training nurses. Data were collected between June–September 2009. To collect data, each in‐service training nurse was asked to complete the blanks in the sentence, ‘The in‐service training nurse is like a/an.....................because..................’ The data were analysed using qualitative (content analysis) and quantitative (chi‐square) data analysis methods.

Findings.  According to the findings of the study, the in‐service training nurses identified 59 metaphors in total. The metaphors were grouped under nine conceptual categories depending on the characteristics they had in common. In cognitive image of the in‐service training nurses relating to the concept of in‐service training nurse, the outstanding conceptual category was the in‐service training nurse as a knowledge provider.

Conclusion.  The metaphors can be used as a strong research tool in understanding, revealing and explaining the cognitive images of the in‐service training nurses.
Asymmetric reproductive interference between specialist and generalist predatory ladybirds
Authors: Noriyuki Suzuki , Osawa Naoya , Nishida Takayoshi
Published: April 2012

1. Closely related species often differ greatly in the quality and breadth of resources exploited, but the actual mechanisms causing these differences are poorly understood. Because in the laboratory specialized species often survive and perform as well or better on host species that are never utilized in nature, negative ecological interactions restricting host range must exist. Here, we focused on reproductive interference, which has been theoretically predicted to drive niche separation between closely related species with overlapping mating signals.

2. We examined the interspecific sexual interactions in relation to ecological specialization and generalization in two sibling ladybird species,Harmonia yedoensisandHarmonia axyridis.Harmonia yedoensisis a specialist predator that preys only on pine aphids, which are highly elusive prey for ladybird hatchlings, whereasH. axyridisis a generalist predator with a broad prey and habitat range.

3. We experimentally showed that conspecific sperm fertilized the vast majority of eggs regardless of mating order (i.e. conspecific sperm precedence) when a female ofH. yedoensisorH. axyridismated with both a conspecific and a heterospecific male. Moreover, we demonstrated that mating opportunities ofH. yedoensisfemales strongly decreased as heterospecific density increased relative to conspecific density. In contrast, inH. axyridis, female mating success was high regardless of conspecific or heterospecific density.

4. Our results suggest that the generalistH. axyridisshould be dominant to the specialistH. yedoensisin terms of reproductive interference. Our results support the hypothesis that asymmetric reproductive interference from the dominant species may force the non‐dominant species to become a specialist predator that exclusively utilizes less preferred prey in nature.
A low prevalence of mycobacteria in freshwater fish from water reservoirs, ponds and farms
Authors: Mrlik V , Slany M , Kubecka J , Seda J , Necas A , Babak V , Slana I , Kriz P , Pavlik I
Published: April 2012

A survey of the occurrence of mycobacteria was conducted from 717 freshwater fish (25 species) in two water reservoirs, five ponds and two farms in the Czech Republic. A total of 2182 tissue samples from these fish were examined using the conventional culture method. Thirteen mycobacterial isolates were obtained from 12 (1.7%) fish belonging to nine species. Isolates were identified using sequence analysis of the 16S rRNA gene as: Mycobacterium algericum, M. fortuitum, M. gordonae, M. insubricum, M. kumamotonense, M. nonchromogenicum, two isolates of M. peregrinum, M. terrae and M. triplex. Mycobacteria were isolated more frequently from fish skin and gills than from internal organs or muscles.