bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming growth factor-β signalling controls human breast cancer metastasis in a zebrafish xenograft model
Authors: Drabsch Yvette , He Shuning , Zhang Long , Snaar-Jagalska B Ewa , ten Dijke Peter 
Published: November 2013

Abstract
Introduction
The transforming growth factor beta (TGF-β) signalling pathway is known to control human breast cancer invasion and metastasis. We demonstrate that the zebrafish xenograft assay is a robust and dependable animal model for examining the role of pharmacological modulators and genetic perturbation of TGF-β signalling in human breast tumour cells.

Methods
We injected cancer cells into the embryonic circulation (duct of cuvier) and examined their invasion and metastasis into the avascular collagenous tail. Various aspects of the TGF-β signalling pathway were blocked by chemical inhibition, small interfering RNA (siRNA), or small hairpin RNA (shRNA). Analysis was conducted using fluorescent microscopy.

Results
Breast cancer cells with different levels of malignancy, according to in vitro and in vivo mouse studies, demonstrated invasive and metastatic properties within the embryonic zebrafish model that nicely correlated with their differential tumourigenicity in mouse models. Interestingly, MCF10A M2 and M4 cells invaded into the caudal hematopoietic tissue and were visible as a cluster of cells, whereas MDA MB 231 cells invaded into the tail fin and were visible as individual cells. Pharmacological inhibition with TGF-β receptor kinase inhibitors or tumour specific Smad4 knockdown disturbed invasion and metastasis in the zebrafish xenograft model and closely mimicked the results we obtained with these cells in a mouse metastasis model. Inhibition of matrix metallo proteinases, which are induced by TGF-β in breast cancer cells, blocked invasion and metastasis of breast cancer cells.

Conclusions
The zebrafish-embryonic breast cancer xenograft model is applicable for the mechanistic understanding, screening and development of anti-TGF-β drugs for the treatment of metastatic breast cancer in a timely and cost-effective manner.
Cefepime neurotoxicity in the intensive care unit: a cause of severe, underappreciated encephalopathy
Authors: Fugate Jennifer E , Kalimullah Ejaaz A , Hocker Sara E , Clark Sarah L , Wijdicks Eelco FM , Rabinstein Alejandro A 
Published: November 2013

Abstract
Introduction
Cefepime, a broad spectrum antibiotic, is commonly prescribed in intensive care units (ICU) and may be an overlooked cause of neurologic symptoms such as encephalopathy, myoclonus, seizures, and coma. We aimed to characterize cefepime neurotoxicity in the ICU.

Methods
We performed a retrospective study of adult ICU patients treated with intravenous cefepime for at least 3 days between January 1, 2009 and December 31, 2011. The primary outcome was the development of cefepime neurotoxicity, with the likelihood of causality ascribed via a modified Delphi method.

Results
This study included 100 patients. The mean age was 65.8 years (± 12.7 years). The median daily average dose of cefepime was 2.5 (IQR 2.0 to 3.5) grams. The median treatment duration was 6 (IQR 4 to 10) days. Renal failure in any form was present in 84 patients. Chronic kidney disease affected 40 patients, and 77 had acute kidney injury. Cefepime neurotoxicity occurred in 15 patients. Of these, seven were considered definite cases, three probable, and five possible. Neurotoxic symptoms included impaired consciousness (n = 13), myoclonus (n = 11), disorientation (n = 6), and nonconvulsive status epilepticus (n = 1). The dose of cefepime was appropriately adjusted for renal clearance in 64 patients (75.3%) without cefepime neurotoxicity and four patients (28.6%) with neurotoxicity (P = 0.001). Chronic kidney disease was present in 30 patients (35.3%) without neurotoxicity and in 10 (66.7%) of those with neurotoxicity (P = 0.04).

Conclusions
Critically ill patients with chronic kidney disease are particularly susceptible to cefepime neurotoxicity. Myoclonus and impaired consciousness are the predominant clinical manifestations. Neurotoxic symptoms occur more often when the cefepime dose is not adjusted for renal function, but can still occur despite those modifications.
Initial use of one or two antibiotics for critically ill patients with community-acquired pneumonia: impact on survival and bacterial resistance
Authors: Adrie Christophe , Schwebel Carole , Garrouste-Orgeas Maïté , Vignoud Lucile , Planquette Benjamin , Azoulay Elie , Kallel Hatem , Darmon Michael , Souweine Bertrand , Dinh-Xuan Anh-Tuan , Jamali Samir , Zahar Jean-Ralph , Timsit Jean-François ,   This article was written on behalf of the Outcomerea Study Group
Published: November 2013

Abstract
Introduction
Several guidelines recommend initial empirical treatment with two antibiotics instead of one to decrease mortality in community-acquired pneumonia (CAP) requiring intensive-care-unit (ICU) admission. We compared the impact on 60-day mortality of using one or two antibiotics. We also compared the rates of nosocomial pneumonia and multidrug-resistant bacteria.

Methods
This is an observational cohort study of 956 immunocompetent patients with CAP admitted to ICUs in France and entered into a prospective database between 1997 and 2010.
Patients with chronic obstructive pulmonary disease were excluded. Multivariate analysis adjusted for disease severity, gender, and co-morbidities was used to compare the impact on 60-day mortality of receiving adequate initial antibiotics and of receiving one versus two initial antibiotics.

Results
Initial adequate antibiotic therapy was significantly associated with better survival (subdistribution hazard ratio (sHR), 0.63; 95% confidence interval (95% CI), 0.42 to 0.94; P = 0.02); this effect was strongest in patients with Streptococcus pneumonia CAP (sHR, 0.05; 95% CI, 0.005 to 0.46; p = 0.001) or septic shock (sHR: 0.62; 95% CI 0.38 to 1.00; p = 0.05). Dual therapy was associated with a higher frequency of initial adequate antibiotic therapy. However, no difference in 60-day mortality was found between monotherapy (β-lactam) and either of the two dual-therapy groups (β-lactam plus macrolide or fluoroquinolone). The rates of nosocomial pneumonia and multidrug-resistant bacteria were not significantly different across these three groups.

Conclusions
Initial adequate antibiotic therapy markedly decreased 60-day mortality. Dual therapy improved the likelihood of initial adequate therapy but did not predict decreased 60-day mortality. Dual therapy did not increase the risk of nosocomial pneumonia or multidrug-resistant bacteria.
Landmarks and ant search strategies after interrupted tandem runs
Authors: Basari Norasmah , Bruendl Aisha C. , Hemingway Charlotte E. , Roberts Nicholas W. , Sendova-Franks Ana B. , Franks Nigel R. 
Published: November 2013

Summary
During a tandem run, a single leading ant recruits a single follower to an important resource such as a new nest. Here, for the first time, we used a motorized gantry to track tandem running ants accurately in a large arena and we compared their performance in the presence of different types of landmark. We interrupted tandem runs by taking away the leader and moved a large distant landmark behind the new nest just at the time of this separation. Our aim was to determine what information followers may have obtained from the incomplete tandem run they had followed and how they behave after the tandem run had been interrupted. Our results show that former followers search by using composite random strategies with elements of sub-diffusive and diffusive movements. Furthermore, when we provided more landmarks former followers searched for longer. However, when all landmarks were removed completely from the arena, the ants' search duration lasted up to four times longer. Hence, their search strategy changes in the presence or absence of landmarks. Even after extensive search of this kind, former followers headed back to their old nest but did not return along the path of the tandem run they had followed. The combination of the position to which the large distant landmark behind the new nest was moved and the presence or absence of additional landmarks influenced the orientation of the former followers' paths back to the old nest. We also found that these ants exhibit behavioural lateralization in which they may use their right eye more than their left eye to recognize landmarks for navigation. Our results suggest that former follower ants learn landmarks during tandem running and use this information to make strategic decisions.
Interspecies variation in hypoxia tolerance, swimming performance and plasticity in cyprinids that prefer different habitats
Authors: Fu Shi-Jian , Yan Guan-Jie , Cao Zhen-Dong , Fu Cheng , Zhang An-Jie , Pang Xu 
Published: November 2013

Summary
This study quantified and compared hypoxia tolerance and swim performance among cyprinid fish species from rapid-flow, slow-flow and intermediate-flow habitats (4 species per habitat) in China. In addition, we explored effects of short-term acclimation on swim performance, maximum metabolic rate (Mo2 max) and gill remodelling to detect habitat-associated patterns of plastic response to hypoxia. Indices of hypoxia tolerance included oxygen threshold for loss of equilibrium (LOE50) and aquatic surface respiration (ASR50) and critical oxygen tension for routine metabolic rate (Pcrit). Critical swimming speed (Ucrit) and Mo2 max were measured under normoxic and hypoxic conditions after 48 hours acclimation to normoxia and hypoxia, and gill remodelling was estimated after 48 hours of hypoxia exposure. Both traditional ANCOVA and phylogenetically independent contrast (PDANOVA) analyses showed that fish species from rapid-flow habitat exhibited lower LOE50 compared to fish from intermediate and slow-flow habitats. Habitat-specific difference in Pcrit and Ucrit were detected using PDANOVA but not traditional ANCOVA analyses, with fish species from rapid-flow habitat exhibited lower Pcrit but higher Ucrit compared to fish from intermediate and slow-flow habitats. Fish species from rapid-flow habitats were also characterized by less plasticity in swim performance and gill morphology in response to hypoxia acclimation compared to species from slow-flow habitats, but a greater drop in swim performance in response to acute hypoxia exposure. The study detected a habitat-specific difference in hypoxia tolerance, swimming performance and its plasticity among fish from habitats with different flow conditions possibly due to the long-term adaptation to the habitat caused by selection stress. The phylogenetically independent contrasts were more powerful than traditional statistical analyses according to the habitat effects in both hypoxia tolerance and swimming performance in this study.
Potential for sexual conflict assessed via testosterone-mediated transcriptional changes in liver and muscle of a songbird
Authors: Peterson Mark P. , Rosvall Kimberly A. , Taylor Charlene A. , Lopez Jacqueline A. , Choi Jeong-Hyeon , Ziegenfus Charles , Tang Haixu , Colbourne John K. , Ketterson Ellen D. 
Published: November 2013

SummaryMales and females can be highly dimorphic in metabolism and physiology despite sharing nearly identical genomes, and males and females both respond phenotypically to elevated testosterone, a steroid hormone that alters gene expression. Only recently has it become possible to learn how a hormone like testosterone affects global gene expression in non-model systems, and whether it affects the same genes in males and females. To investigate the transcriptional mechanisms by which testosterone exerts its metabolic and physiological effects on the periphery, we compared gene expression by sex and in response to experimentally elevated testosterone in a well-studied bird species, the dark-eyed junco (Junco hyemalis). We identified 291 genes in the liver, and 658 in the pectoralis muscle that were differentially expressed between males and females. In addition, we identified 1,727 genes that were differentially expressed between testosterone-treated and control individuals in at least one tissue and sex. Testosterone-treatment altered the expression of only 128 genes in both males and females in the same tissue, and 847 genes were affected significantly differently by testosterone-treatment in the two sexes. These substantial differences in transcriptional response to testosterone suggest that males and females may employ different pathways when responding to elevated testosterone, despite the fact that many phenotypic effects of experimentally elevated testosterone are similar in the sexes. In contrast, of the 121 genes that were affected by testosterone-treatment in both sexes, 78% were regulated in the same direction (e.g. either higher or lower in testosterone-treated than control) in both males and females. Thus, it appears that testosterone acts through both unique and shared transcriptional pathways in males and females, suggesting multiple mechanisms by which sexual conflict can be mediated.
The involvement of the brain region containing pigment-dispersing factor-immunoreactive neurons in the photoperiodic response of the bean bugRiptortus pedestris
Authors: Ikeno Tomoko , Numata Hideharu , Goto Shin G. , Shiga Sakiko 
Published: November 2013

SummaryThe concept of insect photoperiodism based on a circadian clock has been supported by many studies demonstrating that the behavioural circadian rhythm and the photoperiodic response are driven by the same circadian clock genes. However, the neuronal mechanism of the circadian clock underlying photoperiodism has been poorly understood. To examine whether circadian rhythm and photoperiodism share a neuronal mechanism, we focused on the neurons that express neuropeptide pigment-dispersing factor (PDF) in the bean bug Riptortus pedestris. PDF has been identified as an important regulator of the insect circadian rhythm and is expressed in circadian clock neurons of various insect species. In R. pedestris, PDF immunoreactivity was detected in some clusters of cells and their fibres in the optic lobe and the protocerebrum. cDNA encoding a PDF precursor protein was highly conserved between R. pedestris and many other insects. Differences between day and night were not observed in the immunolabelling intensity in cell bodies of PDF-immunoreactive neurons and pdf mRNA expression levels in the head. Surgical removal of the region containing PDF-immunoreactive cell bodies at the medulla disrupted the photoperiodic regulation of diapause. However, gene suppression of pdf by RNA interference did not affect the photoperiodic response. These results suggest that the region containing PDF-immunoreactive somata is important for the photoperiodic response in R. pedestris, but pdf mRNA expression is probably not required for the response.
Intraspecific variation in flight metabolic rate in the bumblebeeBombus impatiens: repeatability and functional determinants in workers and drones
Authors: Darveau Charles-A. , Billardon Fannie , Bélanger Kasandra 
Published: November 2013

SummaryThe evolution of flight energetics requires that phenotypes be variable, repeatable and heritable. We studied intraspecific variation in flight energetics in order to assess the repeatability of flight metabolic rate and wingbeat frequency, as well as the functional basis of phenotypic variation in workers and drones of the bumblebee species Bombus impatiens. We showed that flight metabolic rate and wingbeat frequency were highly repeatable in workers, even when controlling for body mass variation using residual analysis. We did not detect significant repeatability in drones, but a smaller range of variation might have prevented us from finding significant values in our sample. Based on our results and previous findings, we associated the high repeatability of flight phenotypes in workers to the functional links between body mass, thorax mass, wing size, wingbeat frequency and metabolic rate. Moreover, differences between workers and drones were as predicted from these functional associations, where drones had larger wings for their size, lower wingbeat frequency and lower flight metabolic rate. We also investigated thoracic muscle metabolic phenotypes by measuring the activity of carbohydrate metabolism enzymes, and we found positive correlations between mass-independent metabolic rate and the activity of all enzymes measured, but in workers only. When comparing workers and drones that differ in flight metabolic rate, only the activity of the enzymes hexokinase and trehalase showed the predicted differences. Overall, our study indicates that there should be correlated evolution among physiological phenotypes at multiple levels of organization and morphological traits associated with flight.
Molt regulation in green and red color morphs of the crab,Carcinus maenas: gene expression of molt-inhibiting hormone signaling components
Authors: Abuhagr Ali M. , Blindert Jennifer L. , Nimitkul Sukkrit , Zander Ian A. , LaBere Stefan M. , Chang Sharon A. , MacLea Kyle S. , Chang Ernest S. , Mykles Donald L. 
Published: November 2013

SummaryIn decapod crustaceans, regulation of molting is controlled by the X-organ/sinus gland complex in the eyestalks. The complex secretes molt-inhibiting hormone (MIH), which suppresses production of ecdysteroids by the Y-organ (YO). MIH signaling involves NO and cGMP in the YO, which expresses NO synthase (NOS) and NO-sensitive guanylyl cyclase (GC-I). Molting can generally be induced by eyestalk ablation (ESA), which removes the primary source of MIH, or by multiple leg autotomy (MLA). In our work on Carcinus maenas, however, ESA has limited effects on hemolymph ecdysteroid titers and animals remain in intermolt by 7 days post-ESA, suggesting that adults are refractory to molt induction techniques. Consequently, the effects of ESA and MLA on molting and YO gene expression in C. maenas green and red color morphotypes were determined at intermediate (16 and 24 days) and long-term (~90 days) intervals. In intermediate-interval experiments, ESA of intermolt animals caused transient 2- to 4-fold increases in hemolymph ecdysteroid titers during the first 2 weeks. In intermolt animals, long-term ESA increased hemolymph ecdysteroid titers 4 to 5-fold by 28 days post treatment, but there was no late premolt peak (&gt;400 pg/μl) characteristic of late premolt animals and animals did not molt by 90 days post-ESA. There was no effect of ESA and MLA on the expression of Cm-elongation factor 2 (EF2), Cm-NOS, the beta subunit of GC-I (Cm-GC-Iβ), a membrane receptor GC (Cm-GC-II), and a soluble NO-insensitive GC (Cm-GC-III) in green morphs. Red morphs were affected by prolonged ESA and MLA treatments, as indicated by large decreases in Cm-EF2, Cm-GC-II, and Cm-GC-III mRNA levels. ESA accelerated the transition of green morphs to the red phenotype in intermolt animals, indicating that molting and integument color changes are not necessarily coupled. ESA delayed molting in premolt green morphs, whereas intact and MLA animals molted by 30 days post treatment. There were significant effects on YO gene expression in intact animals; Cm-GC-Iβ mRNA increased during premolt and Cm-GC-III mRNA decreased during premolt and increased during postmolt. Cm-MIH transcripts were detected in eyestalk ganglia, brain, and thoracic ganglion from green intermolt animals and ESA had no significant effect on Cm-MIH mRNA levels in brain and thoracic ganglion. The data suggest that MIH in the brain and thoracic ganglion prevents molt induction in green ESA animals.
Figure-ground discrimination behavior in Drosophila. I. Spatial organization of wing steering responses
Authors: Fox Jessica L. , Aptekar Jacob W. , Zolotova Nadezhda M. , Shoemaker Patrick A. , Frye Mark A. 
Published: November 2013

Summary
The behavioral algorithms and neural subsystems for visual figure-ground discrimination are not sufficiently described in any model system. The fly visual system shares structural and functional similarity with that of vertebrates, and like vertebrates, flies robustly track visual figures in the face of ground motion. This computation is crucial for animals that pursue salient objects under the high performance requirements imposed by flight behavior. Flies smoothly track small objects and use wide-field optic flow to maintain flight-stabilizing optomotor reflexes. The spatial and temporal properties of visual figure tracking and wide-field stabilization have been characterized in flies, but how the two systems interact spatially to allow flies to actively track figures against a moving ground has not. We took a systems identification approach in flying Drosophila and measured wing-steering responses to velocity impulses of figure and ground motion independently. We constructed a spatio-temporal action field (STAF) - the behavioral analog of a spatio-temporal receptive field (STRF) - revealing how the behavioral impulse responses to figure tracking and concurrent ground stabilization vary for figure motion centered at each location across the visual azimuth. The figure tracking and ground stabilization STAFs show distinct spatial tuning and temporal dynamics, confirming the independence of the two systems. When the figure tracking system is activated by a narrow vertical bar moving within the frontal field of view, ground motion is essentially ignored despite comprising over 90% of the total visual input.
Synthesis and Properties of 6-Methoxy- and 6-Dimethylamino-1-methylthio- and 1,3-Bis(methylthio)azulenes and Triflic Anhydride-Mediated Synthesis of Their Biaryl Derivatives
Authors: Shoji Taku , Maruyama Akifumi , Maruyama Mitsuhisa , Ito Shunji , Okujima Tetsuo , Higashi Junya , Toyota Kozo , Morita Noboru 
Published: November 2013

Abstract
6-Methoxy- and 6-dimethylaminoazulenes with methylthio groups at the 1- or 1,3-positions have been prepared by electrophilic substitution of the corresponding azulenes with DMSO in the presence of acid anhydride, followed by treatment with Et3N. The products, 1-methylthioazulenes, reacted with Tf2O to afford the corresponding 1,1′-biazulene derivatives in moderate yields. The redox behavior of these azulene and 1,1′-biazulene derivatives was examined by cyclic voltammetry (CV), which revealed reversible electron transfers under electrochemical oxidation conditions. 6-Dimethylamino-1,3-bis(methylthio)azulenes with a heteroaryl group at the 2-position were also prepared by the reaction of 6-dimethylamino-1,3-bis(methylthio)azulene with triflates of N-containing heterocycles, i.e., pyridine, quinoline, isoquinoline, acridine, and 1,10-phenanthroline, followed by treatment with KOH in alcohols.
Bilingualism and cross-cultural communication
Authors: Цветкова  
Published: November 2013

The author looks at the problems of bilingualism and cross-cultural communication from the angle of professional command of a foreign language which requires both a certain degree of bilingualism and a cross-cultural competence. The author provides her own definition of professional command of a foreign language, a typology of bilingualism and a conception of its development from elementary to professional.
The author also argues that there is no direct link between bilingualism and cross-cultural competence, illustrating the statement with analysis of difficulties involved in mastering a foreign culture.
The main approaches to formation of communicative competence of the municipal employee
Authors: Романенко  , Romanenko Nadezhda 
Published: November 2013

The article describes the main approaches to formation of communicative
competence of municipal employees. The author stresses that within modern education system, communicative competence is reflected in the ability to design and master new contents and technologies, capability to realize one»s professional mission and build creative interaction with the surrounding world. Efficiency of professional activity depends on optimal compliance of the subject of activity with social demands, norms, conditions.