bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autocrine CSF-1R signaling drives mesothelioma chemoresistance via AKT activation
Authors: Cioce M , Canino C , Goparaju C , Yang H , Carbone M , Pass H I 
Published: April 2014

AbstractClinical management of malignant pleural mesothelioma (MPM) is very challenging because of the uncommon resistance of this tumor to chemotherapy. We report here increased expression of macrophage colony-stimulating-factor-1-receptor (M-CSF/CSF-1R) mRNA in mesothelioma versus normal tissue specimens and demonstrate that CSF-1R expression identifies chemoresistant cells of mesothelial nature in both primary cultures and mesothelioma cell lines. By using RNAi or ligand trapping, we demonstrate that the chemoresistance properties of those cells depend on autocrine CSF-1R signaling. At the single-cell level, the isolated CSF-1Rpos cells exhibit a complex repertoire of pluripotency, epithelial–mesenchymal transition and detoxifying factors, which define a clonogenic, chemoresistant, precursor-like cell sub-population. The simple activation of CSF-1R in untransformed mesothelial cells is sufficient to confer clonogenicity and resistance to pemetrexed, hallmarks of mesothelioma. In addition, this induced a gene expression profile highly mimicking that observed in the MPM cells endogenously expressing the receptor and the ligands, suggesting that CSF-1R expression is mainly responsible for the phenotype of the identified cell sub-populations. The survival of CSF1Rpos cells requires active AKT (v-akt murine thymoma viral oncogene homolog 1) signaling, which contributed to increased levels of nuclear, transcriptionally competent β-catenin. Inhibition of AKT reduced the transcriptional activity of β-catenin-dependent reporters and sensitized the cells to senescence-induced clonogenic death after pemetrexed treatment. This work expands what is known on the non-macrophage functions of CSF-1R and its role in solid tumors, and suggests that CSF-1R signaling may have a critical pathogenic role in a prototypical, inflammation-related cancer such as MPM and therefore may represent a promising target for therapeutic intervention.
Features of air masses associated with the deposition of Pseudomonas syringae and Botrytis cinerea by rain and snowfall
Authors: Monteil Caroline L , Bardin Marc , Morris Cindy E 
Published: April 2014

Abstract
Clarifying the role of precipitation in microbial dissemination is essential for elucidating the processes involved in disease emergence and spread. The ecology of Pseudomonas syringae and its presence throughout the water cycle makes it an excellent model to address this issue. In this study, 90 samples of freshly fallen rain and snow collected from 2005–2011 in France were analyzed for microbiological composition. The conditions favorable for dissemination of P. syringae by this precipitation were investigated by (i) estimating the physical properties and backward trajectories of the air masses associated with each precipitation event and by (ii) characterizing precipitation chemistry, and genetic and phenotypic structures of populations. A parallel study with the fungus Botrytis cinerea was also performed for comparison. Results showed that (i) the relationship of P. syringae to precipitation as a dissemination vector is not the same for snowfall and rainfall, whereas it is the same for B. cinerea and (ii) the occurrence of P. syringae in precipitation can be linked to electrical conductivity and pH of water, the trajectory of the air mass associated with the precipitation and certain physical conditions of the air mass (i.e. temperature, solar radiation exposure, distance traveled), whereas these predictions are different for B. cinerea. These results are pertinent to understanding microbial survival, emission sources and atmospheric processes and how they influence microbial dissemination.
Universal dispersion of surface plasmons in flat nanostructures
Authors: Schmidt Franz-Philipp , Ditlbacher Harald , Hohenester Ulrich , Hohenau Andreas , Hofer Ferdinand , Krenn Joachim R. 
Published: April 2014

AbstractDimensionality has a significant impact on the optical properties of solid-state nanostructures. For example, dimensionality-dependent carrier confinement in semiconductors leads to the formation of quantum wells, quantum wires and quantum dots. While semiconductor properties are governed by excitonic effects, the optical response of metal nanostructures is dominated by surface plasmons. Here we find that, in contrast to excitonic systems, the mode dispersions in plasmonic structures of different dimensionality are related by simple scaling rules. Employing electron energy loss spectroscopy, we show that the modes of silver nanodisks can be scaled to the surface and edge modes of extended silver thin films. We thereby introduce a general and intuitive ordering scheme for plasmonic excitations with edge and surface modes as the elementary building blocks.
Sampling Biases in Datasets of Historical Mean Air Temperature over Land
Authors: Wang Kaicun 
Published: April 2014

AbstractGlobal mean surface air temperature (Ta) has been reported to have risen by 0.74°C over the last 100 years. However, the definition of mean Ta is still a subject of debate. The most defensible definition might be the integral of the continuous temperature measurements over a day (Td0). However, for technological and historical reasons, mean Ta over land have been taken to be the average of the daily maximum and minimum temperature measurements (Td1). All existing principal global temperature analyses over land rely heavily on Td1. Here, I make a first quantitative assessment of the bias in the use of Td1 to estimate trends of mean Ta using hourly Ta observations at 5600 globally distributed weather stations from the 1970s to 2013. I find that the use of Td1 has a negligible impact on the global mean warming rate. However, the trend of Td1 has a substantial bias at regional and local scales, with a root mean square error of over 25% at 5° × 5° grids. Therefore, caution should be taken when using mean Ta datasets based on Td1 to examine high resolution details of warming trends.
Association between DAZL polymorphisms and susceptibility to male infertility: systematic review with meta-analysis and trial sequential analysis
Authors: Zhang Simin , Tang Qiuqin , Wu Wei , Yuan Beilei , Lu Chuncheng , Xia Yankai , Ding Hongjuan , Hu Lingqing , Chen Daozhen , Sha Jiahao , Wang Xinru 
Published: April 2014

AbstractSeveral studies have investigated the association between polymorphisms in the Deleted in AZoospermia-Like (DAZL) gene and male infertility risk, but with inconsistent results. We aimed to derive a more precise estimation of the relationship, therefore a meta-analysis was performed. A total of 13 case-control studies, including 2556 cases and 1997 controls, were selected. Two polymorphisms in DAZL were investigated, namely T12A (Thr12 → Ala) and T54A (Thr54 → Ala). Our meta-analysis showed that A > G is a risk factor for male infertility (P = 0.047, OR = 1.262, 95%CI = 1.003–1.587). However, when using trial sequential analysis (TSA) to confirm, we found that A > G risk effect turned out to be false positive. In addition, significant association was found between the T54A polymorphism and male infertility under co-dominant model (AG vs. AA: OR = 4.364, 95%CI = 2.207–8.630, P < 0.001) and dominant model (OR = 4.584, 95%CI = 2.320–9.058, P < 0.001). Stratified analysis showed that significantly strong association between T54A polymorphism and male infertility was present only in Asians, but not in Caucasians. Further studies of T12A and T54A with their biological functions are needed to understand the role of these polymorphisms in the development of male infertility.
Alternative substrates reveal catalytic cycle and key binding events in the reaction catalysed by anthranilate phosphoribosyltransferase from Mycobacterium tuberculosis
Authors: Cookson Tammie V. M. , Castell Alina , Bulloch Esther M. M. , Evans Genevieve L. , Short Francesca L. , Baker Edward N. , Lott J. Shaun , Parker Emily J. 
Published: April 2014

AnPRT (anthranilate phosphoribosyltransferase), required for the biosynthesis of tryptophan, is essential for the virulence of Mycobacterium tuberculosis (Mtb). AnPRT catalyses the Mg2+-dependent transfer of a phosphoribosyl group from PRPP (5′-phosphoribosyl-1′-pyrophosphate) to anthranilate to form PRA (5′-phosphoribosyl anthranilate). Mtb-AnPRT was shown to catalyse a sequential reaction and significant substrate inhibition by anthranilate was observed. Antimycobacterial fluoroanthranilates and methyl-substituted analogues were shown to act as alternative substrates for Mtb-AnPRT, producing the corresponding substituted PRA products. Structures of the enzyme complexed with anthranilate analogues reveal two distinct binding sites for anthranilate. One site is located over 8 Å (1 Å=0.1 nm) from PRPP at the entrance to a tunnel leading to the active site, whereas in the second, inner, site anthranilate is adjacent to PRPP, in a catalytically relevant position. Soaking the analogues for variable periods of time provides evidence for anthranilate located at transient positions during transfer from the outer site to the inner catalytic site. PRPP and Mg2+ binding have been shown to be associated with the rearrangement of two flexible loops, which is required to complete the inner anthranilate-binding site. It is proposed that anthranilate first binds to the outer site, providing an unusual mechanism for substrate capture and efficient transfer to the catalytic site following the binding of PRPP.
Cardiomyocyte apoptosis contributes to pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated mice
Authors: Nam Soon Woo , Liu Hongqun , Wong Joe Z. , Feng Annie Y. , Chu Gavin , Merchant Naeem , Lee Samuel S. 
Published: April 2014

Cirrhotic cardiomyopathy is defined as systolic and diastolic dysfunctions, electrophysiological changes and macroscopic structural changes. However, the underlying mechanisms of this syndrome remain unclear. A possible role of myocardial apoptosis in the pathogenesis has not been previously examined. We hypothesized that dysregulation of apoptotic signalling participates in cardiac dysfunction in the cirrhotic heart. Therefore, we evaluated apoptotic pathways in the hearts of mice with chronic BDL (bile duct ligation). A cirrhotic cardiomyopathy model was induced by BDL in mice. Left ventricular geometry and volumes were evaluated by MRI. Intrinsic and extrinsic apoptotic pathways were evaluated by immunohistochemical staining and Western blot analysis. Fas-mediated apoptosis was inhibited by in vivo administration of an anti-FasL (Fas ligand) monoclonal antibody, and subsequently cardiac contractility was measured in isolated cardiomyocytes. BDL-mice showed significantly more PARP [poly(ADP-ribose) polymerase] staining than sham controls (18.2±11.4 compared with 6.7±5.3; P&lt;0.05). Fas protein expression and PARP cleavage were activated, whereas FLIP (Fas-associated death domain-like interleukin 1β-converting enzyme-inhibitory protein) was decreased compared with sham controls. The Bcl-2/Bax ratio was increased in BDL-mice compared with sham controls. Anti-FasL monoclonal antibody injection in BDL-mice improved systolic and diastolic dysfunctions in cardiomyocytes, but had no effect in sham controls. A net pro-apoptotic balance exists in BDL hearts, mainly mediated by activation of the extrinsic pathway, and abrogation of apoptosis improved contractility. These results suggest that apoptosis contributes to depressed cardiac contractility in a murine model of cirrhotic cardiomyopathy.
Molecular recognition and modification of the 30S ribosome by the aminoglycoside-resistance methyltransferase NpmA
Authors: Dunkle Jack A. , Vinal Kellie , Desai Pooja M. , Zelinskaya Natalia , Savic Miloje , West Dayne M. , Conn Graeme L. , Dunham Christine M. 
Published: April 2014

Significance
Increasing global spread of antibiotic resistance among pathogenic bacteria threatens a postantibiotic era in healthcare. Detailed studies of resistance mechanisms are therefore urgently required. The ribosome is a major antibiotic target, but bacteria can acquire resistance by modification of drug-binding sites. Here, we describe, to our knowledge, the first molecular snapshot of bacterial ribosome recognition by a pathogen-derived, aminoglycoside-resistance rRNA methyltransferase. Our results support a model in which initial rigid docking on a highly conserved ribosome tertiary surface drives conformational changes in the enzyme that capture the target base within a remodeled active site. Extreme conservation of the ribosome-docking surface suggests there is no impediment to the spread of this resistance activity but also presents a target for specific inhibitor development.
Regulation of the differentiation of osteoblasts and osteoclasts by a hot-water extract of adzuki beans (Vigna angularis)
Authors: Itoh Tomohiro , Nakamura Masahiro , Nakamichi Hirohisa , Ando Masashi , Tsukamasa Yasuyuki , Furuichi Yukio 
Published: April 2014

Abstract
Osteoporosis is a global public health problem thought to be caused by an imbalance in bone metabolism. We examined in this study the 40% ethanol fraction of HP-20 resin in combination with a hot-water adzuki extract (EtEx.40) for its effect on osteoblast and osteoclast differentiation. EtEx.40-treated murine preosteoblast MC3T3-E1 cells exhibited significantly elevated alkaline phosphatase activity and mineralization. EtEx.40 facilitated osteoblast differentiation by up-regulating such osteoblast differentiation-related molecules as runt-related transcription factor 2, distal-less homeobox 5, and osterix via p38 mitogen-activated protein kinase. EtEx.40 also suppressed the formation of large tartrate-resistant acid phosphatase-positive multinucleated cells in RAW264.7 cells that had been stimulated with the receptor activator of the nuclear factor κB ligand/macrophage colony-stimulating factor. EtEx.40 significantly inhibited NF-κB activation, thus reducing the expression of such downstream molecules as c-Fos and NFATc1. Our findings suggest that EtEx.40 could be used to maintain bone mass.
Formation by yeast of 2-furanmethanethiol and ethyl 2-mercaptopropionate aroma compounds in Japanese soy sauce
Authors: Meng Qi , Hatakeyama Makoto , Sugawara Etsuko 
Published: April 2014

Abstract
Two aroma compounds of volatile thiols, 2-furanmethanethiol (2FM) and ethyl 2-mercaptopropionate (ET2MP), were formed in five types of Japanese soy sauce during fermentation by yeast. The concentrations of 2FM and ET2MP in the soy sauce samples increased during alcoholic fermentation. The concentrations of 2FM and ET2MP were higher in the soy sauce fermented by Zygosaccharomyces rouxii than in that fermented by Candida versatilis. The enantiomers of ET2MP were separated by gas chromatography in a capillary column. The average enantiomeric ratio of ET2MP in the soy sauce was approximately 1:1. 2FM was formed by yeast in a medium prepared from cysteine and furfural, and cysteine is considered the key precursor of 2FM by yeast in soy sauce.
Indicators of sailing performance in youth dinghy sailing
Authors: Callewaert Margot , Boone Jan , Celie Bert , De Clercq Dirk , Bourgois Jan G. 
Published: April 2014

AbstractThis study aimed to determine indicators of sailing performance in 2 (age) groups of youth sailors by investigating the anthropometric, physical and motor coordination differences and factors discriminating between elite and non‐elite male optimist sailors and young dynamic hikers. Anthropometric measurements from 23 optimist sailors (mean ± SD age = 12.3 ± 1.4 years) and 24 dynamic youth hikers (i.e. Laser 4.7, Laser radial and Europe sailors <18 years who have to sail the boat in a very dynamic manner, due to a high sailor to yacht weight ratio) (mean ± SD age = 16.5 ± 1.6 years) were conducted. They performed a physical fitness test battery (EUROFIT), motor coordination test battery (Körperkoordinationstest für Kinder) and the Bucket test. Both groups of sailors were divided into two subgroups (i.e. elites and non‐elites) based on sailing expertise. The significant differences, taking biological maturation into account and factors discriminating between elite and non‐elite optimist sailors and dynamic hikers were explored by means of multivariate analysis of covariance and discriminant analysis, respectively. The main results indicated that 100.0% of elite optimist sailors and 88.9% of elite dynamic hikers could be correctly classified by means of two motor coordination tests (i.e. side step and side jump) and Bucket test, respectively. As such, strength‐ and speed‐oriented motor coordination and isometric knee‐extension strength endurance can be identified as indicators of sailing performance in young optimist and dynamic youth sailors, respectively. Therefore, we emphasise the importance of motor coordination skill training in optimist sailors (<15 years) and maximum strength training later on (>15 years) in order to increase their isometric knee‐extension strength endurance.
A note on the linear systems on the projective bundles over Abelian varieties
Authors: Zhang Lei 
Published: April 2014

It is well known that for an ample line bundle

L
L

on an Abelian variety

A
A

, the linear system

|

2
L

|

|2L|

is base point free and

3
L

3L

is very ample; moreover, the map defined by the linear system

|

2
L

|

|2L|

is well understood (cf. Theorem 1.1). In this paper we generalize this classical result and give a new proof using the theory developed by Pareschi and Popa in 2011 (cf. Theorem 1.2).
Sources of Individual Differences in L2 Narrative Production: The Contribution of Input, Processing, and Output Anxiety
Authors: Trebits Anna 
Published: April 2014

Abstract
The aim of this study was to investigate the effects of cognitive task complexity and individual differences in input, processing, and output anxiety (IPOA) on L2 narrative production. The participants were enrolled in a bilingual secondary educational program. They performed two narrative tasks in speech and writing. The participants’ level of anxiety was assessed using the IPOA scale (MacIntyre and Gardner 1994). The results demonstrate that spoken and written modalities are influenced differently by anxiety with the impact of output anxiety being significantly stronger in speech than in writing. Another important finding was that input and processing anxiety had both facilitating and debilitating effects on learners’ L2 output. As regards the effect of task complexity on participants’ narratives, the findings suggest that the different stages of language production need to be taken into account when categorizing tasks on the basis of the cognitive load they impose on learners.
Pharmacy Survey on Patient Safety Culture: Benchmarking Results
Authors: Herner Sheryl J. , Rawlings Julia E. , Swartzendruber Kelly , Delate Thomas 
Published: April 2014

Objective
This study’s objective was to assess the patient safety culture in a large, integrated health delivery system’s pharmacy department to allow for benchmarking with other health systems.

Methods
This was a cross-sectional survey conducted in a pharmacy department consisting of staff members who provide dispensing, clinical, and support services within an integrated health delivery system. The U.S. Agency for Healthcare Research and Quality’s 11-composite, validated Pharmacy Survey on Patient Safety Culture questionnaire was transcribed into an online format. All departmental staff members were invited to participate in this anonymous survey. Cronbach α and overall results and contrasts between dispensing and clinical services staff and dispensing pharmacists and technicians/clerks as percentage positive scores (PPSs) are presented. Differences in contrasts were assessed with χ2 tests of association.

Results
Completed questionnaires were received from 598 (69.9%) of 855 employees. Cronbach α ranged from 0.55 to 0.90. Overall, the highest and lowest composite PPSs were for patient counseling (94.5%) and staffing and work pressure (44.7%), respectively. Compared with dispensing service, the clinical service participants had statistically higher PPSs for all composites except patient counseling, communication about mistakes, and staffing and work pressure (all P > 0.05). The technicians/clerks had a statistically higher PPS compared with the pharmacists for communication about mistakes (P = 0.007). All other composites were equivalent between groups.

Conclusions
Patient counseling consistently had the highest PPS among composites measured, but opportunities existed for improvement in all aspects measured. Future research should identify and assess interventions targeted to improving the patient safety culture in pharmacy.
Whistle‐blowing and workplace culture in older peoples' care: qualitative insights from the healthcare and social care workforce
Authors: Jones Aled , Kelly Daniel 
Published: April 2014

AbstractInquiries in the UK into mistreatment of older people by healthcare employees over the last 30 years have focused on introducing or supporting employee whistle‐blowing. Although whistle‐blowers have made an important contribution to patient safety it remains a controversial activity. The fate of whistle‐blowers is bleak, often resulting in personal and professional sacrifices. Here we draw on the views of healthcare and social care employees working with older people to explore perceptions of whistle‐blowing as well as alternative strategies that may be used to raise concerns about the mistreatment of patients by co‐workers. Whistle‐blowing was perceived as a negative term. Managers said they promoted open cultures underpinned by regular team meetings and an open‐door ethos. Others described workplace norms that were somewhat at odds with these open culture ideals. Whistle‐blowing was considered risky, and this led to staff creating informal channels through which to raise concerns. Those who witnessed wrongdoing were aware that support was available from external agencies but preferred local solutions and drew upon personal ethics rather than regulatory edicts to shape their responses. We argue that the importance of workplace relationships and informal channels for raising concerns should be better understood to help prevent the mistreatment of vulnerable groups.
Effect of production season on protein fraction content in milk of various breeds of goats in Poland
Authors: Brodziak Aneta , Król Jolanta , Barłowska Joanna , Litwińczuk Zygmunt 
Published: April 2014

Milk of various goat breeds was analysed to assess the effect of production season on content of basic chemical components, with regard to whey proteins. Milk of goats in the productive herds (white and coloured coat) contained significantly (P < 0.01) more total protein, casein, fat, dry matter and functional whey proteins. The production season significantly determined the content of total protein (P < 0.01), casein (P < 0.01) and whey proteins (P < 0.05), including α‐lactalbumin (P < 0.01) and lactoferrin (P < 0.01). A higher content of total protein and casein was found in the autumn–winter season and the content of whey proteins was higher in the spring–summer period.