bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel leukemic cell lines resistant to clofarabine by mechanisms of decreased active metabolite and increased antiapoptosis
Authors: Shigemi Hiroko , Yamauchi Takahiro , Tanaka Yukie , Ueda Takanori
Published: February 2013

Clofarabine (CAFdA) is incorporated into leukemic cells by human equilibrative nucleoside transporters (hENT) 1 and 2 and human concentrative nucleoside transporter (hCNT) 3. CAFdA is then phosphorylated to the active metabolite CAFdA triphosphate (CAFdATP) by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK). Two novel CAFdA‐resistant variants were established and their mechanism of resistance was elucidated. The two variants (HL/CAFdA20, HL/CAFdA80) were 20‐fold and 80‐fold more CAFdA‐resistant than HL‐60, respectively. mRNA levels of hENT1, hENT2 and hCNT3 were 53.9, 41.8 and 17.7% in HL/CAFdA20, and 30.8, 13.9 and 7.9% in HL/CAFdA80, respectively, compared with HL‐60. Thus, the total nucleoside transport capacity of CAFdA was reduced in both variants. dCK protein levels were 1/2 in HL/CAFdA20 and 1/8 in HL/CAFdA80 of that of HL‐60. dGK protein levels were 1/2 and 1/3, respectively. CAFdATP production after 4‐h incubation with 10 μM CAFdA was 20 pmol/107cells in HL/CAFdA20 and 3 pmol/107cells in HL/CAFdA80 compared with 63 pmol/107cells in HL‐60. The decreased CAFdATP production attenuated drug incorporation into both mitochondrial and nuclear DNA. In addition, the two variants were resistant to CAFdA‐induced apoptosis due to Bcl2 overexpression and decreased Bim. A Bcl2 inhibitor, ABT737, acted synergistically with CAFdA to inhibit the growth with combination index values of 0.27 in HL/CAFdA20 and 0.23 in HL/CAFdA80, compared with 0.65 in HL‐60. Thus, the mechanism of resistance primarily included not only reduced CAFdATP production, but also increased antiapoptosis. The combination of CAFdA and ABT737 may be effective against CAFdA resistance.
Synthesis, Cytotoxicity and In Vitro Antileishmanial Activity of Naphthothiazoles
Authors: de Toledo Juliano S. , Junior Paulo E. S. , Manfrim Viviane , Pinzan Camila F. , de Araujo Alexandre S. , Cruz Angela K. , Emery Flavio S.
Published: February 2013

The leishmaniasis is a spectral disease caused by the protozoan Leishmania spp., which threatens millions of people worldwide. Current treatments exhibit high toxicity, and there is no vaccine available. The need for new lead compounds with leishmanicidal activity is urgent. Considering that many lead leishmanicidal compounds contain a quinoidal scaffold and the thiazole heterocyclic ring is found in a number of antimicrobial drugs, we proposed a hybridization approach to generate a diverse set of semi‐synthetic heterocycles with antileishmanial activity. We found that almost all synthesized compounds demonstrated potent activity against promastigotes of Leishmania (Viannia) braziliensis and reduced the survival index of Leishmania amastigotes in mammalian macrophages. Furthermore, the compounds were not cytotoxic to macrophages at fivefold higher concentrations than the EC50 for promastigotes. All molecules fulfilled Lipinski's Rule of Five, which predicts efficient orally absorption and permeation through biological membranes, the in silico pharmacokinetic profile confirmed these characteristics. The potent and selective activity of semi‐synthetic naphthothiazoles against promastigotes and amastigotes reveals that the 2‐amino‐naphthothiazole ring may represent a scaffold for the design of compounds with leishmanicidal properties and encourage the development of drug formulation and new compounds for further studies in vivo.
Long‐term outcome of antineutrophil cytoplasmic antibody‐associated small vessel vasculitis after renal transplantation
Authors: Marco Helena , Mirapeix Eduard , Arcos Emma , Comas Jordi , Ara Jordi , Gil‐Vernet Salvador , Puig Josep , Vinyas Odette , Perello Manel , Oppenheimer Federico , Poveda Rafael , Ibernón Meritxell , Díaz Montserrat , Ballarin Jose ,   Catalan Study Group of Glomerular Diseases (GLOMCAT)
Published: February 2013

The survival after renal transplantation of patients with antineutrophil cytoplasmic antibody (ANCA)‐associated to systemic vasculitis is as good as in other diseases, although most of the reports are based on small numbers of patients. Furthermore, it is not known whether comorbidities (cardiovascular [CV] disease and cancer) are more frequent than in general population. We report our experience and the analysis of the published data on this topic. The outcome after transplantation in 49 patients with ANCA‐associated small vessel vasculitis was compared with a control group. The relapse rate of vasculitis was 0.01 per patient per year. Comparison with the control patients revealed no difference in long‐term outcome, CV mortality or incidence of malignancies. In the published literature, patients with ANCA at transplantation and with Wegener's granulomatosis are at greater risk of relapse. Taking our own results together with the review of the literature, we conclude that patient and graft survival rates compare favorably with those in control group that the recurrence rate is very low and that there is no increase in the incidence of cancer or in CV mortality. Patients with ANCA at transplantation and with Wegener's granulomatosis have a higher relapse rate.
Women's Care/Career Changes as Connection and Resilience: Challenging Discourses of Breakdown and Conflict
Authors: Maher JaneMaree
Published: February 2013

In this study, 20 nursing families were interviewed with a focus on the integration of family care needs and employment. The predominantly female cohort of nurses revealed considerable career change, employment breaks and the use of part‐time and casual work options as they worked to manage and integrate family care responsibilities with employment opportunities. Here, drawing on the stories of two particular respondents, I use Trentmann's notion of ‘disruption as normal’ to explore these shifts and reformations of family and career, arguing that multiple changes and reconfigurations of routine are not necessarily signs of fraying careers or fracturing family lives, but can be understood as an adaptive and resilient response to the everyday nature of disruption and the consistency of family change.
Molecular Typing of Cyst‐Forming Nematodes Globodera pallida and G. rostochiensis, Using Real‐Time PCR and Evaluation of Five Methods for Template Preparation
Authors: Papayiannis Lambros C. , Christoforou Michalis , Markou Yiannis M. , Tsaltas Dimitris
Published: February 2013

Globodera pallida and G. rostochiensis are two cyst‐forming nematodes known to infest potato crops, causing severe economic losses worldwide. In this study, a real‐time TaqMan PCR assay was developed and optimized for the simultaneous detection of G. pallida and G. rostochiensis. The assay's analytical and diagnostic sensitivity and specificity were evaluated using reference isolates. Four different DNA extraction methods and one rapid crude template‐preparation procedure were compared in terms of extraction purity, efficiency for PCR applications, utility and cost. Extraction methods A and B included two commercially available kits that utilize silica columns and magnetic beads, respectively. Method C was based on DNA isolation using Chelex resin, and method D was a standard chemistry in‐house protocol. Procedure E included the direct use of crude mixture composed of disrupted cysts in Tris–EDTA buffer. The multiplex TaqMan PCR assay successfully discriminated the two nematode species from all reference cyst samples and its recorded diagnostic sensitivity (Dse) and specificity (Dsp) was 100%. On the contrary, in conventional (Co) PCR tests, the overall Dsp and Dse were lower and estimated at 94 and 87% for G. pallida, and 97 and 88% for G. rostochiensis, respectively. Spectrophotometric results showed that DNA extraction methods A, B and C yielded the purest DNA and gave the lowest mean Ct values as well as the most consistent results in Co PCR. Alternative crude preparation method E resulted in statistically similar and Ct values consistent with those obtained with methods A to C when tested by TaqMan PCR. The developed assay, using crude template‐preparation E, allows the simple, accurate and cost‐effective testing of a large number of cyst samples and can be applied in surveys and certification schemes.
Determination and physiological roles of the glycosylphosphatidylinositol lipid remodelling pathway in yeast
Authors: Yoko‐o Takehiko , Ichikawa Daisuke , Miyagishi Yasunori , Kato Akiko , Umemura Mariko , Takase Kumiko , Ra Moonjin , Ikeda Kazutaka , Taguchi Ryo , Jigami Yoshifumi
Published: February 2013

In the yeast Saccharomyces cerevisiae, glycosylphosphatidylinositol (GPI)‐anchored proteins play important roles in cell wall biogenesis/assembly and the formation of lipid microdomains. The lipid moieties of mature GPI‐anchored proteins in yeast typically contain either ceramide moieties or diacylglycerol. Recent studies have identified that the GPI phospholipase A2 Per1p and O‐acyltransferase Gup1p play essential roles in diacylglycerol‐type lipid remodelling of GPI‐anchored proteins, while Cwh43p is involved in the remodelling of lipid moieties to ceramide. It has been generally proposed that phosphatidylinositol with diacylglycerol containing a C26 saturated fatty acid, which is generated by the sequential activity of Per1p and Gup1p, is converted to inositolphosphorylceramide by Cwh43p. In this report, we constructed double‐mutant strains defective in lipid remodelling and investigated their growth phenotypes and the lipid moieties of GPI‐anchored proteins. Based on our analyses of single‐ and double‐mutants of proteins involved in lipid remodelling, we demonstrate that an alternative pathway, in which lyso‐phosphatidylinositol generated by Per1p is used as a substrate for Cwh43p, is involved in the remodelling of GPI lipid moieties to ceramide when the normal sequential pathway is inhibited. In addition, mass spectrometric analysis of lipid species of Flag‐tagged Gas1p revealed that Gas1p contains ceramide moieties in its GPI anchor.
Cold‐induced organelle relocation in the liverwort Marchantia polymorpha L.
Authors: OGASAWARA YUKA , ISHIZAKI KIMITSUNE , KOHCHI TAKAYUKI , KODAMA YUTAKA
Published: February 2013

Organelles change their subcellular positions in response to various environmental conditions. Recently, we reported that cold treatments alter the intracellular position of chloroplasts and nuclei (cold positioning) in the fern Adiantum capillus‐veneris; chloroplasts and nuclei localized to the periclinal cell wall relocated to anticlinal cell wall after cold treatments. To further understand organelle positioning under cold conditions, we studied cold‐induced organelle relocation in the liverwort Marchantia polymorpha L. When sporelings and gemmmalings were treated under low temperature (5 °C), chloroplast cold positioning response was successfully induced both in the sporelings and the gemmmalings of M. polymorpha. Using a genetic transformation, nuclei, mitochondria or peroxisomes were visualized with a fluorescent protein, and the transgenic gemmmalings were incubated under the cold condition. Nuclei and peroxisomes, but not mitochondria, clearly relocated from the periclinal cell wall to the anticlinal cell wall after cold treatments. Our findings suggest that several organelles concurrently change their positions in the liverwort cell to cope with cold temperature.
Induction of dyspnea evokes increased anxiety and maladaptive breathing in individuals with high anxiety sensitivity and suffocation fear
Authors: Alius Manuela G. , Pané‐Farré Christiane A. , Von Leupoldt Andreas , Hamm Alfons O.
Published: February 2013

Although respiratory symptoms are relevant for diagnosis and etiology of panic disorder, anxiety responses and breathing behavior evoked by induction of dyspnea have rarely been studied. Therefore, dyspnea sensations and affective evaluations evoked by inspiratory resistive loads of different intensities were first assessed in 23 individuals with high versus 24 participants with low anxiety sensitivity (AS). High AS participants with high fear of suffocation rated loads of the same physical intensity as more unpleasant and reported more intense feelings of dyspnea and more respiratory and panic symptoms than low AS individuals. In the second experiment assessing physiological responses to physically comparable loads, high suffocation fear participants showed an increase in minute ventilation to compensate for fear‐induced air hunger. This ventilation behavior results in increased frequency of dyspnea sensations, thus increasing fear of suffocation.
A possible role for CD8+ and non‐CD8+ cell granzyme B in early small airway wall remodelling in centrilobular emphysema
Authors: Kim Won‐Dong , Chi Hyun‐Sook , Choe Kang‐Hyeon , Oh Yeon‐Mok , Lee Sang‐Do , Kim Kyu‐Rae , Yoo Kwang‐Ha , Ngan David A. , Elliott W. Mark , Granville David J. , Sin Don D. , Hogg James C.
Published: February 2013

Background and objective

CD8+ cell infiltration and apoptosis of airway epithelial cells are increased in chronic obstructive pulmonary disease (COPD). CD8+ T cells induce apoptosis by releasing granzymes, which can also cause extracellular matrix degradation and remodelling. Granzyme B levels and T cells expressing granzyme B are increased in bronchoalveolar lavage fluid of COPD patients, which suggests that granzyme B may contribute to the pathogenesis of COPD. This study provides quantitation of granzyme B‐positive cells in relation to CD8+ cells in the small airway walls of emphysema.

Methods

Antibodies against CD8 and granzyme B were used to identify CD8+ and granzyme B+ cells. Volume fraction (Vv) of CD8+ and granzyme B+ cells were quantitated by the point counting method in the small airways of 13 non‐smoker control subjects and 46 emphysema patients (14 panlobular emphysema (PLE) and 32 centrilobular emphysema (CLE) lungs). Immunohistochemical detection of macrophage scavenger receptor was also performed in randomly selected cases.

Results

The Vv of CD8+ and granzyme B+ cells in CLE was greater than those in control and PLE (both P < 0.001) subjects. The Vv of granzyme B+ cells was greater than that of CD8+ cells (P = 0.006), and not all CD8+ cells were positive for granzyme B in CLE subjects. Monocytes expressing both granzyme B and macrophage scavenger receptor and granulocytes expressing granzyme B were identified.

Conclusions

Upregulation of granzyme B in CD8+ and non‐CD8+ cells is an early phenomenon of small airway wall remodelling in centrilobular emphysema and suggests its possible role in the pathogenesis of COPD.
Discovering Structure in Design Databases Through Functional and Surface Based Mapping
Authors: Fu Katherine , Cagan Jonathan , Kotovsky Kenneth , Wood Kristin
Published: February 2013

This work presents a methodology for discovering structure in design repository databases, toward the ultimate goal of stimulating designers through design-by-analogy. Using a Bayesian model combined with latent semantic analysis (LSA) for discovering structural form in data, an exploration of inherent structural forms, based on the content and similarity of design data, is undertaken to gain useful insights into the nature of the design space. In this work, the approach is applied to uncover structure in the U.S. patent database. More specifically, the functional content and surface content of the patents are processed and mapped separately, yielding structures that have the potential to develop a better understanding of the functional and surface similarity of patents. Structures created with this methodology yield spaces of patents that are meaningfully arranged into labeled clusters, and labeled regions, based on their functional similarity or surface content similarity. Examples show that cross-domain associations and transfer of knowledge based on functional similarity can be extracted from the function based structures, and even from the surface content based structures as well. The comparison of different structural form types is shown to yield different insights into the arrangement of the space, the interrelationships between the patents, and the information within the patents that is attended to—enabling multiple representations of the same space to be easily accessible for design inspiration purposes. In addition, the placement of a design problem in the space effectively points to the most relevant cluster of patents in the space as an effective starting point of stimulation. These results provide a basis for automated discovery of cross-domain analogy, among other implications for creating a computational design stimulation tool.
Optimization of Nonlinear Hyperelastic Coefficients for Foot Tissues Using a Magnetic Resonance Imaging Deformation Experiment
Authors: Petre Marc , Erdemir Ahmet , Panoskaltsis Vassilis P. , Spirka Thomas A. , Cavanagh Peter R.
Published: February 2013

Accurate prediction of plantar shear stress and internal stress in the soft tissue layers of the foot using finite element models would provide valuable insight into the mechanical etiology of neuropathic foot ulcers. Accurate prediction of the internal stress distribution using finite element models requires that realistic descriptions of the material properties of the soft tissues are incorporated into the model. Our investigation focused on the creation of a novel three-dimensional (3D) finite element model of the forefoot with multiple soft tissue layers (skin, fat pad, and muscle) and the development of an inverse finite element procedure that would allow for the optimization of the nonlinear elastic coefficients used to define the material properties of the skin muscle and fat pad tissue layers of the forefoot based on a Ogden hyperelastic constitutive model. Optimization was achieved by comparing deformations predicted by finite element models to those measured during an experiment in which magnetic resonance imaging (MRI) images were acquired while the plantar surface forefoot was compressed. The optimization procedure was performed for both a model incorporating all three soft tissue layers and one in which all soft tissue layers were modeled as a single layer. The results indicated that the inclusion of multiple tissue layers affected the deformation and stresses predicted by the model. Sensitivity analysis performed on the optimized coefficients indicated that small changes in the coefficient values (±10%) can have rather large impacts on the predicted nominal strain (differences up to 14%) in a given tissue layer.
Liposomal Amphotericin B Displays Rapid Dose-Dependent Activity against Candida albicans Biofilms
Authors: Ramage Gordon , Jose Anto , Sherry Leighann , Lappin David F. , Jones Brian , Williams Craig
Published: February 2013

Biofilms formed by
Candida albicans
bloodstream isolates on catheters are an important clinical problem. Devising chemotherapeutic strategies to treat these
in situ
is an attractive option. We report here that liposomal amphotericin effectively kills
C. albicans
biofilms rapidly (12 h) and effectively (>90%) in a dose-dependent manner, whereas caspofungin displays an inverse concentration-dependent effect. This study has implications for considering the effective doses of antifungal agents used for catheter lock therapy.
Bloody
coli
: a Gene Cocktail in Escherichia coli O104:H4
Authors: Baquero Fernando , Tobes Raquel
Published: February 2013

A recent study published in
mBio
[Y. H. Grad et al.,
mBio
4(1):e00452-12, 2013] indicates that a rapid introgressive evolution has occurred in
Escherichia coli
O104:H4 by sequential acquisition of foreign genetic material involving pathogenicity traits. O104 genetic promiscuity cannot be readily explained by high population sizes. However, extensive interactions leading to cumulative assemblies of pathogenicity genes might be assured by small
K
-strategist populations exploiting particular intestinal niches. Next-generation sequencing technologies will be critical to detect particular “gene cocktails” as potentially pathogenic ensembles and to predict the risk of future outbreaks.
The effects of a congested fixture period on physical performance, technical activity and injury rate during matches in a professional soccer team
Authors: Dellal Alexandre , Lago-Peñas Carlos , Rey Ezequiel , Chamari Karim , Orhant Emmanuel
Published: February 2013

Background

In modern professional soccer, the ability to recover from official match-play and intense training is often considered a determining factor in subsequent performance.

Objective

To investigate the influence of playing multiple games with a short recovery time between matches on physical activity, technical performance and injury rates.

Methods

The variation of physical (overall distance, light-intensity, low-intensity, moderate-intensity and high-intensity running) and technical performance (successful passes, balls lost, number of touches per possession and duels won) of 16 international players was examined during three different congested periods of matches (six games in 18 days) from the French League and Cup (n=12), and the UEFA Champions’ League (n=6) during the 2011–2012 season and compared with that reported in matches outside these periods. Data were collected using a computerised match analysis system (Amisco). Injury rate, time loss injuries, as well as the mechanism, circumstances and severity of the injury were also analysed.

Results

No differences were found across the six successive games in the congested period, and between no congested and the three congested periods for all the physical and technical activities. The total incidence of injury (matches and training) across the prolonged congested periods did not differ significantly to that reported in the non-congested periods. However, the injury rate during match-play was significantly higher during the congested period compared with the non-congested period (p<0.001). The injury rate during training time was significantly lower during the congested period compared with the non-congested periods (p<0.001). The mean lay-off duration for injuries was shorter during the congested periods compared with the non-congested periods (9.5±8.8 days vs 17.5±29.6 days, respectively p=0.012, effect sizes=0.5).

Conclusions

Although physical activity, technical performance and injury incidence were unaffected during a prolonged period of fixture congestion, injury rates during training and match-play and the lay-off duration were different to that reported in matches outside this period.
OBLIQUE DUAL FRAMES IN FINITE-DIMENSIONAL HILBERT SPACES
Authors: XIAO XIANG-CHUN , ZHU YU-CAN , ZENG XIAO-MING
Published: February 2013

A frame can be completed to a tight frame by adding some additional vectors. However, for the purpose of computational efficiency, we need to put restrictions to the number of added vectors. In this paper we propose a constructive method that allows to extend a given frame to an oblique dual frame pair such that the number of added vectors is in general much smaller than the number of added vectors used to extend it to a tight frame. We also present a uniqueness characterization and several equivalent characterizations for an oblique dual frame pair, it turns out that oblique dual frame pair provides more flexibilities than alternate dual frame pair.
A NEW REFINEMENT WAVELET–GALERKIN METHOD IN A SPLINE LOCAL MULTIRESOLUTION ANALYSIS SCHEME FOR BOUNDARY VALUE PROBLEMS
Authors: VAMPA VICTORIA , MARTÍN MARÍA T. , SERRANO EDUARDO
Published: February 2013

In this work, a new Wavelet–Galerkin method for boundary value problems is presented. It improves the approximation in terms of scaling functions obtained through a collocation scheme combined with variational equations. A B-spline multiresolution structure on the interval is designed in order to refine the solution recursively and efficiently using wavelets. Numerical examples are given to verify good convergence properties of the proposed method.
Ovarian regulation of neuromedin U and its local actions in the ovary, mediated through neuromedin U receptor 2
Authors: Lin Ting-Yu , Wu Fang-Ju , Lee Wei-Yu , Hsiao Chih-Lun , Luo Ching-Wei
Published: February 2013

Neuromedin U (NMU) was originally identified as an anorexigenic peptide that modulates appetite as well as energy homeostasis through the brain-gut axis. Although growing evidence has linked NMU activity with the development of female reproductive organs, no direct expression of and function for NMU in these organs has been pinpointed. Using a superovulated rat model, we found that NMU is directly expressed in the ovary, where its transcript level is tightly regulated by gonadotropins. Ovarian microdissection and immunohistochemical staining showed clearly that NMU is expressed mainly in theca/interstitial cells and to a moderate extent in granulosa cells. Primary cell studies together with reporter assays indicated the Nmu mRNA level in these cells is strongly induced via cAMP signaling, whereas this increase in expression can be reversed by the degradation message residing within its 3′-untranslated region, which recruits cis-acting mRNA degradation mechanisms, such as the gonadotropin-induced zinc finger RNA-binding protein Zfp36l1. This study also demonstrated that NMUR2, but not NMUR1, is the dominant NMU receptor in the ovary, where its expression is restricted to theca/interstitial cells. Treatment with NMU led to induction of the early response c- Fos gene, phosphorylation of extracellular signal-regulated kinase 1/2, and promotion of progesterone production in both developing and mature theca/interstitial cells. Taken as a whole, this study demonstrates that NMU and NMU receptor 2 compose a novel autocrine system in theca/interstitial cells in which the intensity of signaling is tightly controlled by gonadotropins.
How Different Methodologies of Harvesting and Analysing the Samples Affect the Test Results in Determining Joint Mediators
Authors: Yilmaz Ibrahim , Gokay Nevzat Selim , Bircan Rifat , Saracoglu Gamze V. , Dervisoglu Sergulen , Gokce Alper
Published: February 2013

Purpose. This study has researched the affect of different methodologies of harvesting and analysing the samples in determining the mediators emerging after the rat articular cartilage injury. Materials and Methods. One hundred and forty-four male wistar rats were divided into 2 groups. Synovial fluid samples were taken from all of the rats. We entered into the right knees of the rats in group I (n=36) under anaesthesia and took cartilage tissue samples from their distal femur. Samples were taken as reference values for enzyme linked immunosorbent assay (ELISA) and histopathological evaluations. We entered into the right knees of the rats in group II (n=108) and formed complete layer of cartilage injury in their medial femoral condyles. At the end of the 15th day, the rats were sacrificed after taking synovial fluid samples from their right knees creating defect in the rats in group II. The molecular markers in the synovial fluid and cartilage tissue samples which were taken from the experimental and control groups (MMP-9, MMP-13, TIMP-1, TNF-α, and NO) were analysed by direct or indirect methodologies. SPSS 18.0 Package program was used in the statistical evaluation. Students t-test where the measurement variables between the experimental and control groups were compared was applied. Receiver Operating Characteristics (ROC) curves were used in the determination of the diagnostic sufficiency from the tissue. Results. No difference was found between TIMP-1 (P=0.67) and MMP-9 (P=0.28) levels in synovial fluid and cartilage tissue. From the molecular markers, when MMP-9, MMP-13, NO, TIMP-1, TNF-α′, the area under ROC curve, and P values were examined, MMP-13 (P<0.0001, 95% CI: 0.70–0.85), NO (P<0.0001, 95% CI: 0.72–0.86), and TNF-α (P<0.0001, 95% CI: 0.91–0.98) results were found to be statistically significant. Inferences. The indirect ELISA protocol which we apply for the cartilage tissue as an alternative to synovial lavage fluid is a reliable method which can be used in the determination of articular cartilage injury markers.
Generation of Chimeric “ABS Nanohemostat” Complex and Comparing Its HistomorphologicalIn VivoEffects to the Traditional Ankaferd Hemostat in Controlled Experimental Partial Nephrectomy Model
Authors: Huri Emre , Beyazit Yavuz , Mammadov Rashad , Toksoz Sila , Tekinay Ayse B. , Guler Mustafa O. , Ustun Huseyin , Kekilli Murat , Dadali Mumtaz , Celik Tugrul , Astarci Müzeyyen , Haznedaroglu Ibrahim C.
Published: February 2013

Purpose. Using the classical Ankaferd Blood Stopper (ABS) solution to create active hemostasis during partial nephrectomy (PN) may not be so effective due to insufficient contact surface between the ABS hemostatic liquid agent and the bleeding area. In order to broaden the contact surface, we generated a chimeric hemostatic agent, ABS nanohemostat, via combining a self-assembling peptide amphiphile molecule with the traditional Ankaferd hemostat.Materials and Methods. In order to generate ABS nanohemostat, a positively charged Peptide Amphiphile (PA) molecule was synthesized by using solid phase peptide synthesis. For animal experiments, 24 Wistar rats were divided into the following 4 groups: Group 1: control; Group 2: conventional PN with only 0.5 ml Ankaferd hemostat; Group 3: conventional PN with ABS + peptide gel; Group 4: conventional PN with only 0.5 ml peptide solution.Results. Mean warm ischemia times (WITs) were232.8 ± 56.3,65.6±11.4,75.5±17.2, and58.1±17.6seconds in Group 1 to Group 4, respectively. Fibrosis was not different among the groups, while inflammation was detected to be significantly different in G3 and G4.Conclusions. ABS nanohemostat has comparable hemostatic efficacy to the traditional Ankaferd hemostat in the partial nephrectomy experimental model. Elucidation of the cellular and tissue effects of this chimeric compound may establish a catalytic spark and open new avenues for novel experimental and clinical studies in the battlefield of hemostasis.
An ICT Architecture for Managed Charging of Electric Vehicles in Smart Grid Environments
Authors: Bohn S. , Agsten M. , Waldhorst O. , Mitschele-Thiel A. , Westermann D. , Bretschneider P.
Published: February 2013

Growing shortage of fossil resources and an increasing demand of individual mobility worldwide require technology alternatives to existing mobility solutions. Electric vehicles (EVs) as one possible solution have moved into the focus of research and development. To maximize the positive environmental effect of EVs, it is proposed to charge them with respect to the availability of renewable energies. As the number of EVs will grow in the near future, their impact on the power distribution grid is no longer neglectable. Related research shows that unmanaged charging of EVs could result in overload situations or voltage instabilities. To overcome this, methods are proposed to manage the charging process holistically. Herein EVs become substantial elements of intelligent power grids (Smart Grids). As of today, research in the area of Smart Grids focuses mainly on either energy aspects or communication aspects while neglecting the interoperability of energy and communication related aspects. In this paper, an insight into Information and Communication Technology (ICT) aspects with respect to Managed Charging of EVs in Smart Grid environments will be given. Based on the use case of Managed Charging, requirements will be analyzed, results will be derived, and ICT solutions will be proposed with a set of recommendations for Smart Grid architectures.
CYP24A1 and CYP27B1 Polymorphisms Modulate Vitamin D Metabolism in Colon Cancer Cells
Authors: Jacobs Elizabeth T. , Van Pelt Chad , Forster Ryan E. , Zaidi Wasiq , Hibler Elizabeth A. , Galligan Michael A. , Haussler Mark R. , Jurutka Peter W.
Published: February 2013

Vitamin D is a well-studied agent for cancer chemoprevention and treatment. Its chief circulating metabolite, 25-hydroxyvitamin D, is converted into the active hormone 1,25-dihydroxyvitamin D (1,25D) by the cytochrome P450 enzyme CYP27B1 in kidney and other tissues. 1,25D is then deactivated by CYP24A1 and ultimately catabolized. Colorectal carcinoma cells express CYP27B1 and CYP24A1 that locally regulate 1,25D with potential implications for its impact on carcinogenesis. While 1,25D inhibits cancer growth, the effects of polymorphic variations in genes encoding proteins involved in 1,25D homeostasis are poorly understood. Using an RXR-VDR mammalian two-hybrid (M2H) biologic assay system, we measured vitamin D metabolite uptake and activation of the vitamin D receptor (VDR) pathway in colon cancer cells that expressed one of five CYP27B1 single-nucleotide polymorphisms (SNP) or four CYP24A1 SNPs. Compared with the wild-type control, four of five CYP27B1 SNPs reduced enzymatic activity, whereas one (V166L) increased activity. For CYP24A1, all tested SNPs reduced enzyme activity. Quantitative real-time PCR analyses supported the results of M2H experiments. The observed SNP-directed variation in CYP functionality indicated that vitamin D homeostasis is complex and may be influenced by genetic factors. A comprehensive understanding of 1,25D metabolism may allow for a more personalized approach toward treating vitamin D–related disorders and evaluating risk for carcinogenesis. Cancer Res; 73(8); 2563–73. ©2013 AACR.
Bexarotene Induces Cellular Senescence in MMTV-Neu Mouse Model of Mammary Carcinogenesis
Authors: Shilkaitis Anne , Bratescu Laura , Green Albert , Yamada Tohru , Christov Konstantin
Published: February 2013

Previous studies have shown that retinoids and rexinoids can prevent breast cancer in animal models and in women with increased risk of developing the disease. The cellular effects of these vitamin A analogues have been primarily associated with induction of differentiation and inhibition of proliferation. In this study, we tested the hypothesis that bexarotene (LGD1069, Targretin), a rexinoid, can not only inhibit cell proliferation but also induce cellular senescence in mammary epithelial cells, premalignant lesions, and tumors of the MMTV-Neu model of mammary carcinogenesis, which develops estrogen receptor–negative tumors. Mice with palpable mammary tumors were treated for 4 weeks with bexarotene at 80 or 40 mg/kg body weight, and senescent cells were determined by SA-β-Gal assay. Bexarotene decreased in a dose-dependent manner the multiplicity of premalignant lesions and tumors, and this was associated with inhibition of cell proliferation and induction of cellular senescence and apoptosis. By double labeling of senescent cells, first by SA-β-Gal and then by antibodies against genes related to cellular senescence, we found that p21, p16, and RARβ, but not p53, were upregulated by bexarotene in mammary tumors and in breast cancer cell lines, suggesting involvement of multiple signaling pathways in mediating the senescence program of rexinoids. These findings indicate that, in addition to cell proliferation and apoptosis, cellular senescence could be used as a potential biomarker of response in breast cancer prevention and therapy studies with rexinoids and possibly with other antitumor agents. Cancer Prev Res; 6(4); 299–308. ©2013 AACR.
Acute Single-Stage Reconstruction of Multiligament Knee Injuries Using the Ligament Advanced Reinforcement System
Authors: Tao Jie , Li Xia , Zhou Zihui , Zhu Zhenan
Published: February 2013

Objective: The purpose of the study was to report our early outcome in the management of multiligament knee injuries with the ligament advanced reinforcement system (LARS). Subjects and Methods: Between 2007 and 2010, 9 of 11 patients operated on for multiligament knee injuries were included in this study; 2 patients were excluded due to complicated neurovascular injuries, open knee dislocations and severe comorbidities. All patients were managed acutely (<3 weeks) by reconstructions of the cruciate and collateral ligaments with LARS ligament and were followed up for an average of 30 months (18-46 months). Results: The mean Lysholm score of the 9 patients at final follow-up was around 90 (range 88-94) with an average Tegner activity score of 5.5. The postoperative function of 1 case of KD-11 and 2 cases of KD-111 was rated as ‘A,' while the remaining cases were rated ‘B'. At final follow-up, minor osteoarthritic degeneration was detected in 1 case of KD-III and 2 cases of KD-IV. Superficial infection developed in 1 case, and no cases of knee synovitis and premature osteoarthritis were recorded. Conclusion: A creditable outcome at mean of 30 months' follow-up was obtained in acute single-stage reconstruction of uncomplicated multiligament knee injuries with LARS ligament.
Angiotensin-(1–7) in the Rostral Ventrolateral Medulla Modulates Enhanced Cardiac Sympathetic Afferent Reflex and Sympathetic Activation in Renovascular Hypertensive Rats
Authors: Li Peng , Sun Hai-Jian , Cui Bai-Ping , Zhou Ye-Bo , Han Ying
Published: February 2013

Enhancement of the cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic excitation in hypertension. The aim of the present study was to determine whether angiotensin (Ang)-(1–7) in the rostral ventrolateral medulla (RVLM) modulated the enhanced CSAR and sympathetic activation, and the signaling pathways that mediated these effects in the 2-kidney, 1-clip renovascular hypertension model. Cardiac sympathetic afferent reflex was evaluated using renal sympathetic nerve activity and mean arterial pressure responses to epicardial capsaicin application in anesthetized sinoaortic-denervated and cervical-vagotomized rats. RVLM microinjection of Ang-(1–7) induced greater increases in renal sympathetic nerve activity and mean arterial pressure, and greater enhancement in CSAR in 2-kidney, 1-clip rats than in sham-operated rats, which was blocked by Mas receptor antagonist A-779, adenylyl cyclase inhibitors SQ22536 and MDL-12,330A, and protein kinase A inhibitors rp-adenosine-3′,5′-cyclic monophosphorothionate and H-89. Mas receptor expression in RVLM was increased in 2-kidney, 1-clip rats. Treatment with A-779, SQ22536, MDL-12,330A, rp-adenosine-3′,5′-cyclic monophosphorothionate, or H-89 in RVLM inhibited CSAR and decreased renal sympathetic nerve activity and mean arterial pressure in 2-kidney, 1-clip rats, whereas cAMP analogue dibutyryl-cAMP had the opposite effects. Ang-(1–7) in RVLM increased, whereas A-779 decreased the cAMP level and the epicardial capsaicin application-induced increases in the cAMP level in RVLM. These results indicate that Ang-(1–7) in the RVLM enhances the CSAR and increases the sympathetic outflow and blood pressure via Mas receptor activation. The increased endogenous Ang-(1–7) and Mas receptor activity in RVLM contributes to the enhanced CSAR and sympathetic activation in renovascular hypertension, and the cAMP-protein kinase A pathway is involved in these Ang-(1–7)–mediated effects in the RVLM.
Independent Risk Factors for Intracranial Aneurysms and Their Joint Effect
Authors: Vlak Monique H.M. , Rinkel Gabriel J.E. , Greebe Paut , Algra Ale
Published: February 2013

Background and Purpose—

Three percent of the population has an unruptured intracranial aneurysm (UIA). We aimed to identify independent risk factors from lifestyle and medical history for the presence of UIAs and to investigate the combined effect of well-established risk factors.

Methods—

We studied 206 patients with an UIA who never had a subarachnoid hemorrhage and 574 controls who were randomly retrieved from general practitioner files. All participants filled in a questionnaire on potential risk factors for UIAs. With logistic regression analysis, we identified independent risk factors for UIA and assessed their combined effect.

Results—

Independent risk factors were current smoking (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.0–4.5), hypertension (OR, 2.9; 95% CI, 1.9–4.6), family history of stroke other than subarachnoid hemorrhage (OR, 1.6; 95% CI, 1.0–2.5), hypercholesterolemia (OR, 0.5; 95% CI, 0.3–0.9), and regular physical exercise (OR, 0.6; 95% CI, 0.3–0.9). The joint risk of smoking and hypertension was higher (OR, 8.3; 95% CI, 4.5–15.2) than the sum of the risks independently.

Conclusions—

Current smoking, hypertension, and family history of stroke increase the risk of UIA, with smoking and hypertension having an additive effect, whereas hypercholesterolemia and regular physical exercise decrease this risk. A healthy lifestyle probably reduces the risk of UIA and thereby possibly also that of aneurysmal subarachnoid hemorrhage. Whether smoking and hypertension increase the risk of aneurysmal subarachnoid hemorrhage only through an increased risk of aneurysm formation or also through an increased risk of rupture remains to be established.
Patient-Reported Measures Provide Unique Insights Into Motor Function After Stroke
Authors: Stewart Jill Campbell , Cramer Steven C.
Published: February 2013

Background and Purpose—

Patient-reported outcome measures have been found useful in many disciplines but have received limited evaluation after stroke. The current study investigated the relationship that patient-reported measures have with standard impairment and disability scales after stroke.

Methods—

Patients with motor deficits after stroke were scored on standard assessments including the National Institutes of Health Stroke Scale, modified Rankin Scale, and Fugl-Meyer motor scale, and on 2 patient-reported measures, the hand function domain of the Stroke Impact Scale, which documents difficulty of hand motor usage, and the amount of use portion of the Motor Activity Log, which records amount of arm motor usage.

Results—

The 43 participants had mild disability (median modified Rankin Scale=2), moderate motor deficits (Fugl-Meyer motor scale=46±22), and mild cognitive/language deficits. The 2 patient-reported outcome measures, Stroke Impact Scale and Motor Activity Log, were sensitive to the presence of arm motor deficits. Of 21 patients classified as having minimal or no impairment or disability by the National Institutes of Health Stroke Scale or modified Rankin Scale (score of 0–1), 15 (71%) reported difficulty with hand movements by the Stroke Impact Scale score or reduced arm use by the Motor Activity Log score. Furthermore, of 14 patients with a normal examination, 10 (71%) reported difficulty with hand movements or reduction in arm use.

Conclusions—

Patient-reported measures were a unique source of insight into clinical status in the current population. Motor deficits were revealed in a majority of patients classified by standard scales as having minimal or no disability, and in a majority of patients classified as having no deficits.
Nuclear and mitochondrial markers reveal the existence of several geographically concordant lineages within a Sahelian gecko species, Ptyodactylus ragazzii
Authors: Froufe Elsa , Gonçalves Duarte V. , Brito José Carlos , Harris David James
Published: February 2013

The genetic diversity within Ptyodactylus ragazzii was analysed for the first time across the Western part of its range. We have used two mitochondrial (12s rRNA and 16s rRNA) and one nuclear (Cmos) marker to compare results directly with other related Ptyodactylus species, P. oudrii and P. hasselquistii. Results show high levels of intraspecific variability, with at least three divergent mtDNA lineages that have different haplotypes for Cmos and that are geographically concordant. P. ragazzii from Mauritania is probably a distinct species and possibly other lineages too, such as those from the Aïr Mountains in Niger, although more nuclear markers are needed to confirm this. All analysed Ptyodactylus species appear to be cryptic species complexes containing multiple deeply divergent forms, highlighting the need for a careful reassessment of the taxonomy of the whole genus.
Iridescent blue and orange components contribute to the recognition of a multicomponent warning signal
Authors: Pegram Kimberly V. , Lillo Melissa J. , Rutowski Ronald L.
Published: February 2013

Warning colouration functions to deter predators from attacking unprofitable (e.g., unpalatable or toxic) prey items. While warning colours are often characterized by long-wavelength components (e.g., orange, red or yellow), many distasteful animals across the animal kingdom display orange or red colour patches adjacent to or within a field of short-wavelength colouration such as blue (e.g., strawberry poison dart frogs, pipevine swallowtail and pyjama nudibranch), which yields a multicomponent visual warning signal. Here we show that, in such signals, blue and orange patches can function as redundant signal components; avian predators trained not to attack the intact blue and orange colouration of the pipevine swallowtail (Battus philenor) recognised the butterflies as distasteful even when the blue and orange were presented individually. Our results demonstrate that blue colouration and potential multiple, unimodal, signal components should be considered in research on visual warning signals, including in well-studied animals, such as dendrobatid frogs and swallowtail butterflies.
Jesus Traditions and Masculinities in World Christianity
Authors: van Klinken Adriaan S. , Smit Peter-Ben
Published: February 2013

Abstract

This opening article offers an introduction to the theme of this special issue of Exchange: Jesus traditions and masculinities in world Christianity. Highlighting the historical trajectory of feminist theological debates on the maleness of Jesus Christ and its implications for configurations of gender (read: the position of women) in Christian traditions, the article particularly explores two recent developments: first, the critical discussion in academic, theological and ecumenical circles of men and masculinities in contemporary Christian contexts, and second, the growing body of scholarship on the masculinity (or better, masculinities) of Jesus Christ in the New Testament in relation to masculinities in the early Christian era. Building on these debates and this scholarship, the article identifies a new and critical field of inquiry that explores the complex and productive relationships between the ambiguous and unstable masculinity/ies of Jesus Christ and the multiple and changing masculinities that are found today in the local contexts of an increasingly diverse global Christianity.
Effects of the combined artesunate and mefloquine antimalarial drugs on rat embryos
Authors: Boareto A.C. , Müller J.C. , Lourenço E.L.B. , Lombardi N. , Lourenço A.C. , Rabitto I. , de Morais R.N. , Rios F.S. , Dalsenter P.R.
Published: February 2013

Artemisinins combination therapy (ACT) is the first choice therapy for falciparum malaria. Data on the safety of ACTs in pregnancy are limited and controversial and the use is not recommended on the first trimester. To evaluate the effects of isolated and combined artesunate (AS)/mefloquine (MQ) on embryo rats, pregnant rats were treated orally with AS (15 and 40 mg/kg body weight (bwt)/day), MQ (30 and 80 mg/kg bwt/day) and AS/MQ (15/30 and 40/80 mg/kg bwt/day) on days 9–11 post coitum (pc). The dams were euthanized on day 12 pc and gestational and embryos histological parameters were evaluated. Embryolethality and histopathological anomalies were significant when AS was given alone or combined with MQ. Combination of AS and MQ did not enhance their toxicity compared to their separate administrations; on the other side, there was a reduction in the toxic effects of the AS when combined with MQ. Isolated MQ did not induce developmental toxicity.
Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease
Authors: Le Huu Doanh , Matsushita Takashi , Jin Guihua , Hamaguchi Yasuhito , Hasegawa Minoru , Takehara Kazuhiko , Tedder Thomas F. , Fujimoto Manabu
Published: February 2013

Key Points

CD19-deficient donors augmented Scl-cGVHD. Donor regulatory B cells suppressed Scl-cGVHD.