bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trainees’ experience of cognitive behavioural therapy training: a mixed methods systematic review
Authors: Jenkins Hannah , Waddington Louise , Thomas Nicola , Hare Dougal Julian 
Published: February 2018

AbstractResearch in the field of cognitive behavioural therapy (CBT) has primarily focused on the acquisition and development of skills and competence. Little is known regarding the experience of training from trainees’ perspectives. This systematic review aimed to review and critique the research conducted on the experience of CBT training. Four electronic databases were searched for published studies reporting on the experience of CBT training. Thirteen articles were selected based on pre-determined inclusion and exclusion criteria and were assessed for quality using the Quality Assessment Tool for Studies with Diverse Designs (QATSDD; Sirriyeh et al., 2012). Due to the lack of consistency in the study designs and outcome measures used, a narrative synthesis of the findings was conducted. Findings were categorized within three themes for synthesis: ‘experience of benefit’, ‘internal processes of engagement’ and ‘external influences on engagement’. Overall, this review was able to draw conclusions regarding the experiences of aspects of CBT training from relatively good quality research. However, the review also highlights the lack of studies exploring specific hypotheses regarding the experience of training.
RETRACTED ARTICLE: A novel microRNA identified in hepatocellular carcinomas is responsive to LEF1 and facilitates proliferation and epithelial-mesenchymal transition via targeting of NFIX
Authors: Hu Yaqi , Guo Xu , Wang Jinxia , Liu Yankun , Gao Huijie , Fan Hongxia , Nong Xiangyang , Yang Xi , Liu Min , Li Shengping , Tang Hua 
Published: February 2018

AbstractHepatocellular carcinoma (HCC) is one of the most prevalent cancers. It has been demonstrated that various cellular microRNAs (miRNAs) play an important role in HCC development. Here, we analyzed the miRNA profile in HCC tissues by Solexa sequencing, and we identified a novel microRNA, miR-HCC1, which is upregulated in HCC tissues. Further experiments showed that miR-HCC1 promoted HCC cell proliferation in vivo and in vitro, and migration and invasion resulting from the epithelial-mesenchymal transition (EMT) process. Nuclear factor I/X (NFIX), which inhibited cell proliferation, migration and invasion in HCC cells, was identified as a direct and functional target of miR-HCC1. Furthermore, lymphoid enhancer binding factor 1 (LEF1), a transcription factor, was shown to bind the promoter of miR-HCC1 and activate its expression. Collectively, these results indicate that LEF1-upregulated miR-HCC1 functions as an oncogene through the negative regulation of NFIX expression, which links the LEF1/miR-HCC1/NFIX axis to contribute to cell proliferation, migration and invasion of HCC cells and could provide novel insights into miRNA function and hepatocarcinogenesis and potential biomarkers for HCC.
Efficacy of the highly selective focal adhesion kinase inhibitor BI 853520 in adenocarcinoma xenograft models is linked to a mesenchymal tumor phenotype
Authors: Hirt Ulrich A. , Waizenegger Irene C. , Schweifer Norbert , Haslinger Christian , Gerlach Daniel , Braunger Jürgen , Weyer-Czernilofsky Ulrike , Stadtmüller Heinz , Sapountzis Ioannis , Bader Gerd , Zoephel Andreas , Bister Bojan , Baum Anke , Quant Jens , Kraut Norbert , Garin-Chesa Pilar , Adolf Günther R. 
Published: February 2018

AbstractFocal adhesion kinase (FAK), a non-receptor tyrosine kinase, has attracted interest as a target for pharmacological intervention in malignant diseases. Here, we describe BI 853520, a novel ATP-competitive inhibitor distinguished by high potency and selectivity. In vitro, the compound inhibits FAK autophosphorylation in PC-3 prostate carcinoma cells with an IC50 of 1 nmol/L and blocks anchorage-independent proliferation of PC-3 cells with an EC50 of 3 nmol/L, whereas cells grown in conventional surface culture are 1000-fold less sensitive. In mice, the compound shows long half-life, high volume of distribution and high oral bioavailability; oral dosing of immunodeficient mice bearing subcutaneous PC-3 prostate adenocarcinoma xenografts resulted in rapid, long-lasting repression of FAK autophosphorylation in tumor tissue. Daily oral administration of BI 853520 to nude mice at doses of 50 mg/kg was well tolerated for prolonged periods of time. In a diverse panel of 16 subcutaneous adenocarcinoma xenograft models in nude mice, drug treatment resulted in a broad spectrum of outcomes, ranging from group median tumor growth inhibition values >100% and tumor regression in subsets of animals to complete lack of sensitivity. Biomarker analysis indicated that high sensitivity is linked to a mesenchymal tumor phenotype, initially defined by loss of E-cadherin expression and subsequently substantiated by gene set enrichment analysis. Further, we obtained microRNA expression profiles for 13 models and observed that hsa-miR-200c-3p expression is strongly correlated with efficacy (R2 = 0.889). BI 853520 is undergoing evaluation in early clinical trials.
PIM1 mediates epithelial-mesenchymal transition by targeting Smads and c-Myc in the nucleus and potentiates clear-cell renal-cell carcinoma oncogenesis
Authors: Zhao Bin , Liu Lei , Mao Jun , Zhang Zhiwei , Wang Qifei , Li Quanlin 
Published: February 2018

AbstractEmerging evidence has shown that the PIM serine/threonine kinase family, including PIM1, PIM2 and PIM3, is associated with tumour progression towards metastasis. PIM1, an attractive molecular target, has been identified as a potential prognostic biomarker for haematological and epithelial malignancies. However, to date, the potential regulatory roles and molecular mechanisms by which PIM1 affects the development and progression of cancers, including clear-cell renal-cell carcinoma (ccRCC), remain largely unknown. Herein, we present the first evidence that PIM1 is aberrantly overexpressed in human ccRCC tissues and cell lines and positively correlated with human ccRCC progression. In our study, depletion of PIM1 attenuated ccRCC cell proliferation, colony formation, migration, invasion and angiogenesis, suggesting that PIM1 expression may be a cancer-promoting event in ccRCC. Mechanistically, we observed that PIM1 could interact with Smad2 or Smad3 in the nucleus and subsequently phosphorylate Smad2 and Smad3 to induce the expression of transcription factors, including ZEB1, ZEB2, Snail1, Snail2 and Twist, to promote epithelial-mesenchymal transition (EMT). In addition, PIM1-mediated phosphorylation of c-Myc activates the expression of the above transcription factors to synergistically promote EMT but does not activate Smads. Collectively, our results demonstrate that aberrant expression of PIM1 contributes to ccRCC development and progression. Moreover, our data reveal a potential molecular mechanism in which PIM1 mediates crosstalk between signalling pathways, including different Smad proteins and c-Myc, which target downstream transcription factors (ZEB1, ZEB2, Snail1, Snail2 and Twist) to trigger EMT. Together, our data suggest that PIM1 may be a potential therapeutic target for ccRCC patients.
Atm reactivation reverses ataxia telangiectasia phenotypes in vivo
Authors: Di Siena Sara , Campolo Federica , Gimmelli Roberto , Di Pietro Chiara , Marazziti Daniela , Dolci Susanna , Lenzi Andrea , Nussenzweig Andre , Pellegrini Manuela 
Published: February 2018

AbstractHereditary deficiencies in DNA damage signaling are invariably associated with cancer predisposition, immunodeficiency, radiation sensitivity, gonadal abnormalities, premature aging, and tissue degeneration. ATM kinase has been established as a central player in DNA double-strand break repair and its deficiency causes ataxia telangiectasia, a rare, multi-system disease with no cure. So ATM represents a highly attractive target for the development of novel types of gene therapy or transplantation strategies. Atm tamoxifen-inducible mouse models were generated to explore whether Atm reconstitution is able to restore Atm function in an Atm-deficient background. Body weight, immunodeficiency, spermatogenesis, and radioresistance were recovered in transgenic mice within 1 month from Atm induction. Notably, life span was doubled after Atm restoration, mice were protected from thymoma and no cerebellar defects were observed. Atm signaling was functional after DNA damage in vivo and in vitro. In summary, we propose a new Atm mouse model to investigate novel therapeutic strategies for ATM activation in ataxia telangiectasia disease.
High capacity in G protein-coupled receptor signaling
Authors: Keshelava Amiran , Solis Gonzalo P. , Hersch Micha , Koval Alexey , Kryuchkov Mikhail , Bergmann Sven , Katanaev Vladimir L. 
Published: February 2018

AbstractG protein-coupled receptors (GPCRs) constitute a large family of receptors that activate intracellular signaling pathways upon detecting specific extracellular ligands. While many aspects of GPCR signaling have been uncovered through decades of studies, some fundamental properties, like its channel capacity—a measure of how much information a given transmission system can reliably transduce—are still debated. Previous studies concluded that GPCRs in individual cells could transmit around one bit of information about the concentration of the ligands, allowing only for a reliable on or off response. Using muscarinic receptor-induced calcium response measured in individual cells upon repeated stimulation, we show that GPCR signaling systems possess a significantly higher capacity. We estimate the channel capacity of this system to be above two, implying that at least four concentration levels of the agonist can be distinguished reliably. These findings shed light on the basic principles of GPCR signaling.
Spatial specificity of auxin responses coordinates wood formation
Authors: Brackmann Klaus , Qi Jiyan , Gebert Michael , Jouannet Virginie , Schlamp Theresa , Grünwald Karin , Wallner Eva-Sophie , Novikova Daria D. , Levitsky Victor G. , Agustí Javier , Sanchez Pablo , Lohmann Jan U. , Greb Thomas 
Published: February 2018

AbstractSpatial organization of signalling events of the phytohormone auxin is fundamental for maintaining a dynamic transition from plant stem cells to differentiated descendants. The cambium, the stem cell niche mediating wood formation, fundamentally depends on auxin signalling but its exact role and spatial organization is obscure. Here we show that, while auxin signalling levels increase in differentiating cambium descendants, a moderate level of signalling in cambial stem cells is essential for cambium activity. We identify the auxin-dependent transcription factor ARF5/MONOPTEROS to cell-autonomously restrict the number of stem cells by directly attenuating the activity of the stem cell-promoting WOX4 gene. In contrast, ARF3 and ARF4 function as cambium activators in a redundant fashion from outside of WOX4-expressing cells. Our results reveal an influence of auxin signalling on distinct cambium features by specific signalling components and allow the conceptual integration of plant stem cell systems with distinct anatomies.
Two distinct domains contribute to the substrate acyl chain length selectivity of plant acyl-ACP thioesterase
Authors: Jing Fuyuan , Zhao Le , Yandeau-Nelson Marna D. , Nikolau Basil J. 
Published: February 2018

AbstractThe substrate specificity of acyl-ACP thioesterase (TE) plays an essential role in controlling the fatty acid profile produced by type II fatty acid synthases. Here we identify two groups of residues that synergistically determine different substrate specificities of two acyl-ACP TEs from Cuphea viscosissima (CvFatB1 and CvFatB2). One group (V194, V217, N223, R226, R227, and I268 in CvFatB2) is critical in determining the structure and depth of a hydrophobic cavity in the N-terminal hotdog domain that binds the substrate’s acyl moiety. The other group (255-RKLSKI-260 and 285-RKLPKL-289 in CvFatB2) defines positively charged surface patches that may facilitate binding of the ACP moiety. Mutagenesis of residues within these two groups results in distinct synthetic acyl-ACP TEs that efficiently hydrolyze substrates with even shorter chains (C4- to C8-ACPs). These insights into structural determinants of acyl-ACP TE substrate specificity are useful in modifying this enzyme for tailored fatty acid production in engineered organisms.
Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity
Authors: Steinhardt James J. , Guenaga Javier , Turner Hannah L. , McKee Krisha , Louder Mark K. , O’Dell Sijy , Chiang Chi-I , Lei Lin , Galkin Andrey , Andrianov Alexander K. , A. Doria-Rose Nicole , Bailer Robert T. , Ward Andrew B. , Mascola John R. , Li Yuxing 
Published: February 2018

AbstractHIV-1 broadly neutralizing antibodies (bNAbs) are being explored as passively administered therapeutic and preventative agents. However, the extensively diversified HIV-1 envelope glycoproteins (Env) rapidly acquire mutations to evade individual bNAbs in monotherapy regimens. The use of a “single” agent to simultaneously target distinct Env epitopes is desirable to overcome viral diversity. Here, we report the use of tandem single-chain variable fragment (ScFv) domains of two bNAbs, specific for the CD4-binding site and V3 glycan patch, to form anti-HIV-1 bispecific ScFvs (Bi-ScFvs). The optimal Bi-ScFv crosslinks adjacent protomers within one HIV-1 Env spike and has greater neutralization breadth than its parental bNAbs. Furthermore, the combination of this Bi-ScFv with a third bNAb recognizing the Env membrane proximal external region (MPER) results in a trispecific bNAb, which has nearly pan-isolate neutralization breadth and high potency. Thus, multispecific antibodies combining functional moieties of bNAbs could achieve outstanding neutralization capacity with augmented avidity.
‘Cyclical Bias’ in Microbiome Research Revealed by A Portable Germ-Free Housing System Using Nested Isolation
Authors: Rodriguez-Palacios Alexander , Aladyshkina Natalia , Ezeji Jessica C. , Erkkila Hailey L. , Conger Mathew , Ward John , Webster Joshua , Cominelli Fabio 
Published: February 2018

AbstractGerm-Free (GF) research has required highly technical pressurized HEPA-ventilation anchored systems for decades. Herein, we validated a GF system that can be easily implemented and portable using Nested Isolation (NesTiso). GF-standards can be achieved housing mice in non-HEPA-static cages, which only need to be nested ‘one-cage-inside-another’ resembling ‘Russian dolls’. After 2 years of monitoring ~100,000 GF-mouse-days, NesTiso showed mice can be maintained GF for life (>1.3 years), with low animal daily-contamination-probability risk (1 every 867 days), allowing the expansion of GF research with unprecedented freedom and mobility. At the cage level, with 23,360 GF cage-days, the probability of having a cage contamination in NesTiso cages opened in biosafety hoods was statistically identical to that of opening cages inside (the ‘gold standard’) multi-cage pressurized GF isolators. When validating the benefits of using NesTiso in mouse microbiome research, our experiments unexpectedly revealed that the mouse fecal microbiota composition within the ‘bedding material’ of conventional SPF-cages suffers cyclical selection bias as moist/feces/diet/organic content (‘soiledness’) increases over time (e.g., favoring microbiome abundances ofBacillales, Burkholderiales, Pseudomonadales;and cultivableEnterococcus faecalisoverLactobacillus murinusandEscherichia coli), which in turn cyclically influences the gut microbiome dynamics of caged mice. Culture ‘co-streaking’ assays showed that cohoused mice exhibiting different fecal microbiota/hemolytic profiles in clean bedding (high-within-cage individual diversity) ‘cyclically and transiently appear identical’ (less diverse) as bedding soiledness increases, and recurs. Strategies are proposed to minimize this novel functional form of cyclical bedding-dependent microbiome selection bias.
Explaining combinatorial effects of mycotoxins Deoxynivalenol and Zearalenone in mice with urinary metabolomic profiling
Authors: Ji Jian , Zhu Pei , Blaženović Ivana , Cui Fangchao , Gholami Morteza , Sun Jiadi , Habimana Jean , Zhang Yinzhi , Sun Xiulan 
Published: February 2018

AbstractUrine metabolic profiling of mice was conducted utilizing gas chromatography-mass spectrometry (GC-MS) to investigate the combinatory effect of mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) on the metabolism of the mice. Experiments were conducted by means of five-week-old mice which were individually exposed to 2 mg/kg DON, 20 mg/kg ZEN and the mixture of DON and ZEN (2 mg/kg and 20 mg/kg, respectively). The intragastric administration was applied for three weeks and urine samples were collected for metabolic analysis. Univariate and multivariate analysis were applied to data matrix processing along with respective pathway analysis by MetaMapp and CytoScape. The results showed that the combined DON and ZEN administration resulted in lower significant changes, compared to the individual mycotoxin treated groups verified by heatmap. Metabolic pathways network mapping indicated that the combined mycotoxins treated groups showed a little effect on the metabolites in most pathways, especially in glucose metabolism and its downstream amino acid metabolism. In glucose metabolism, the content of galactose, mannitol, galactonic acid, myo-inositol, tagatose was drastically down-regulated. Furthermore, the organic acids, pyruvate, and amino acids metabolism displayed the same phenomenon. In conclusion, the combined DON/ZEN administration might lead to an “antagonistic effect” in mice metabolism.
The Spanish version of Face-Name Associative Memory Exam (S-FNAME) performance is related to amyloid burden in Subjective Cognitive Decline
Authors: Sanabria Angela , Alegret Montserrat , Rodriguez-Gomez Octavio , Valero Sergi , Sotolongo-Grau Oscar , Monté-Rubio Gemma , Abdelnour Carla , Espinosa Ana , Ortega Gemma , Perez-Cordon Alba , Gailhajanet Anna , Hernandez Isabel , Rosende-Roca Maitee , Vargas Liliana , Mauleon Ana , Sanchez Domingo , Martin Elvira , Rentz Dorene M. , Lomeña Francisco , Ruiz Agustin , Tarraga Lluis , Boada Merce ,   The FACEHBI study group, Aguilera N. , Berthier M. , Buendia M. , Bullich S. , Campos F. , Cañabate P. , Cuevas C. , de Rojas I. , Diego S. , Gil S. , Giménez J. , Gismondi R. , Gómez-Chiari M. , Guitart M. , Hernández-Olasagarre B. , Ibarria M. , Lafuente A. , Martínez J. , Moreno M. , Moreno-Grau S. , Núñez L. , Orellana A. , Páez A. , Pancho A. , Pavía J. , Pelejà E. , Pérez-Grijalba V. , Pesini P. , Preckler S. , Romero J. , Ruiz S. , Santos M. , Sarasa M. , Tejero M. A. , Torres M. , Vivas A. 
Published: February 2018

AbstractThe Face-Name Associative Memory Exam (FNAME) is a paired associative memory test created to detect memory deficits in individuals with preclinical Alzheimer’s disease (AD). Worse performance on FNAME in cognitively healthy individuals were found related to higher amyloid beta (Aβ) burden measured with Positron-Emission-Tomography using 11C-PiB (PiB-PET). We previously reported normative data of a Spanish version of FNAME (S-FNAME) in cognitively healthy Spanish-speaking subjects. The aim of the present study was to determine whether performance on S-FNAME was associated with Aβ burden in subjective cognitive decline (SCD) individuals. 200 SCD subjects received neurological and neuropsychological assessments, including the S-FNAME and the Word List task from the Wechsler-Memory-Scale-III (WMS-III). Moreover, they received an MRI and (18)F-Florbetaben Positron-Emission-Tomography (FBB-PET) to measure Aβ burden. Three cognitive factor composites were derived for the episodic memory measures (face-name [SFN-N], face-occupation [SFN-O] and WMS-III) to determine whether episodic memory performance was related to Aβ deposition. Higher global Aβ deposition was significantly related to worse performance on SFN-N but not with SFN-O or WMS-III Composite. Moreover, worse SFN-N performance was significantly related to higher Aβ deposition in bilateral Posterior Cingulate Cortex. The S-FNAME may be a promising neuropsychological tool for detecting SCD individuals with preclinical AD.
Towards in cellulo virus crystallography
Authors: Duyvesteyn Helen M. E. , Ginn Helen M. , Pietilä Maija K. , Wagner Armin , Hattne Johan , Grimes Jonathan M. , Hirvonen Elina , Evans Gwyndaf , Parsy Marie-Laure , Sauter Nicholas K. , Brewster Aaron S. , Huiskonen Juha T. , Stuart David I. , Sutton Geoff , Bamford Dennis H. 
Published: February 2018

AbstractViruses are a significant threat to both human health and the economy, and there is an urgent need for novel anti-viral drugs and vaccines. High-resolution viral structures inform our understanding of the virosphere, and inspire novel therapies. Here we present a method of obtaining such structural information that avoids potentially disruptive handling, by collecting diffraction data from intact infected cells. We identify a suitable combination of cell type and virus to accumulate particles in the cells, establish a suitable time point where most cells contain virus condensates and use electron microscopy to demonstrate that these are ordered crystalline arrays of empty capsids. We then use an X-ray free electron laser to provide extremely bright illumination of sub-micron intracellular condensates of bacteriophage phiX174 inside living Escherichia coli at room temperature. We have been able to collect low resolution diffraction data. Despite the limited resolution and completeness of these initial data, due to a far from optimal experimental setup, we have used novel methodology to determine a putative space group, unit cell dimensions, particle packing and likely maturation state of the particles.
Cognitive control over memory – individual differences in memory performance for emotional and neutral material
Authors: Wierzba M. , Riegel M. , Wypych M. , Jednoróg K. , Grabowska A. , Marchewka A. 
Published: February 2018

AbstractIt is widely accepted that people differ in memory performance. The ability to control one’s memory depends on multiple factors, including the emotional properties of the memorized material. While it was widely demonstrated that emotion can facilitate memory, it is unclear how emotion modifies our ability to suppress memory. One of the reasons for the lack of consensus among researchers is that individual differences in memory performance were largely neglected in previous studies. We used the directed forgetting paradigm in an fMRI study, in which subjects viewed neutral and emotional words, which they were instructed to remember or to forget. Subsequently, subjects’ memory of these words was tested. Finally, they assessed the words on scales of valence, arousal, sadness and fear. We found that memory performance depended on instruction as reflected in the engagement of the lateral prefrontal cortex (lateral PFC), irrespective of emotional properties of words. While the lateral PFC engagement did not differ between neutral and emotional conditions, it correlated with behavioural performance when emotional – as opposed to neutral – words were presented. A deeper understanding of the underlying brain mechanisms is likely to require a study of individual differences in cognitive abilities to suppress memory.