bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Adherens Junction Protein Afadin Is an AKT Substrate that Regulates Breast Cancer Cell Migration
Authors: Elloul Sivan , Kedrin Dmitriy , Knoblauch Nicholas W. , Beck Andrew H. , Toker Alex 
Published: November 2013

Abstract
The PI3K–AKT signaling pathway regulates all phenotypes that contribute to progression of human cancers, including breast cancer. AKT mediates signal relay by phosphorylating numerous substrates, which are causally implicated in biologic responses such as cell growth, survival, metabolic reprogramming, migration, and invasion. Here a new AKT substrate is identified, the adherens junction protein Afadin, which is phosphorylated by AKT at Ser1718. Importantly, under conditions of physiologic IGF-1 signaling and oncogenic PI3K and AKT, Afadin is phosphorylated by all AKT isoforms, and this phosphorylation elicits a relocalization of Afadin from adherens junctions to the nucleus. Also, phosphorylation of Afadin increased breast cancer cell migration that was dependent on Ser1718 phosphorylation. Finally, nuclear localization of Afadin was observed in clinical breast cancer specimens, indicating that regulation of Afadin by the PI3K–AKT pathway has pathophysiologic significance.
Implications: Phosphorylation of the adhesion protein Afadin by AKT downstream of the PI3K pathway, leads to redistribution of Afadin and controls cancer cell migration. Mol Cancer Res; 12(3); 464–76. ©2013 AACR.
Mammalian Target of Rapamycin Complex 2 (mTORC2) Coordinates Pulmonary Artery Smooth Muscle Cell Metabolism, Proliferation, and Survival in Pulmonary Arterial Hypertension
Authors: Goncharov Dmitry A. , Kudryashova Tatiana V. , Ziai Houman , Ihida-Stansbury Kaori , DeLisser Horace , Krymskaya Vera P. , Tuder Rubin M. , Kawut Steven M. , Goncharova Elena A. 
Published: November 2013

Background—
Enhanced proliferation, resistance to apoptosis, and metabolic shift to glycolysis of pulmonary arterial vascular smooth muscle cells (PAVSMCs) are key pathophysiological components of pulmonary vascular remodeling in idiopathic pulmonary arterial hypertension (PAH). The role of the distinct mammalian target of rapamycin (mTOR) complexes mTORC1 (mTOR-Raptor) and mTORC2 (mTOR-Rictor) in PAVSMC proliferation and survival in PAH and their therapeutic relevance are unknown.

Methods and Results—
Immunohistochemical and immunoblot analyses revealed that mTORC1 and mTORC2 pathways are markedly upregulated in small remodeled pulmonary arteries and isolated distal PAVSMCs from subjects with idiopathic PAH that have increased ATP levels, proliferation, and survival that depend on glycolytic metabolism. Small interfering RNA– and pharmacology-based analysis showed that although both mTORC1 and mTORC2 contribute to proliferation, only mTORC2 is required for ATP generation and survival of idiopathic PAH PAVSMCs. mTORC2 downregulated the energy sensor AMP-activated protein kinase, which led to activation of mTORC1-S6 and increased proliferation, as well as a deficiency of the proapoptotic protein Bim and idiopathic PAH PAVSMC survival. NADPH oxidase 4 (Nox4) protein levels were increased in idiopathic PAH PAVSMCs, which was necessary for mTORC2 activation, proliferation, and survival. Nox4 levels and mTORC2 signaling were significantly upregulated in small pulmonary arteries from hypoxia-exposed rats at days 2 to 28 of hypoxia. Treatment with the mTOR kinase inhibitor PP242 at days 15 to 28 suppressed mTORC2 but not Nox4, induced smooth muscle–specific apoptosis in small pulmonary arteries, and reversed hypoxia-induced pulmonary vascular remodeling in rats.

Conclusions—
These data provide a novel mechanistic link of Nox4-dependent activation of mTORC2 via the energy sensor AMP-activated protein kinase to increased proliferation and survival of PAVSMCs in PAH, which suggests a new potential pathway for therapeutic interventions.
Straight Line Fitting and Predictions: On a Marginal Likelihood Approach to Linear Regression and Errors-In-Variables Models
Authors: Christiansen Bo 
Published: November 2013

AbstractEven in the simple case of univariate linear regression and prediction there are important choices to be made regarding the origins of the noise terms and regarding which of the two variables under consideration that should be treated as the independent variable. These decisions are often not easy to make but they may have a considerable impact on the results. A unified probabilistic (i.e., Bayesian with flat priors) treatment of univariate linear regression and prediction is given by taking, as starting point, the general errors-in-variables model. Other versions of linear regression can be obtained as limits of this model. The likelihood of the model parameters and predictands of the general errors-in-variables model is derived by marginalizing over the nuisance parameters. The resulting likelihood is relatively simple and easy to analyze and calculate. The well-known unidentifiability of the errors-in-variables model is manifested as the absence of a well-defined maximum in the likelihood. However, this does not mean that probabilistic inference cannot be made; the marginal likelihoods of model parameters and the predictands have, in general, well-defined maxima. A probabilistic version of classical calibration is also included and it is shown how it is related to the errors-in-variables model. The results are illustrated by an example from the coupling between the lower stratosphere and the troposphere in the Northern Hemisphere winter.
Wave Breaking in Dense Plumes
Authors: Holland Paul R. , Hewitt Richard E. , Scase Matthew M. 
Published: November 2013

AbstractSinking dense plumes are important in many oceanographic settings, notably the polar formation of deep and bottom waters. The dense water sources feeding such plumes are commonly affected by tidal modulation, leading to plume variability on short time scales. In a simple unsteady theory of one-dimensional plumes (based on conservation equations for volume, momentum, and buoyancy), this plume variability is manifested as waves that travel down the resulting current. Using numerical techniques applied to the hyperbolic conservation equations, this study investigates the novel concept that these waves may break as they travel down the plumes, triggering intense local mixing between the dense fluid and surrounding ocean. The results demonstrate that the waves break at geophysically relevant distances from the plume source. The location of wave breaking is very sensitive to plume drag from the seabed, the properties of the dense source, and the amplitude and period of the source modulation. To the extent that the simple model represents the real world, these results suggest that wave breaking originating from the tidal modulation of dense plumes could lead to a strong and previously unexplored source of local deep-ocean mixing.
Unlocking the diagnosis of depression in primary care: Which key symptoms are GPs using to determine diagnosis and severity?
Authors: Malhi Gin S , Coulston Carissa M , Fritz Kristina , Lampe Lisa , Bargh Danielle M , Ablett Michael , Lyndon Bill , Sapsford Rick , Theodoros Mike , Woolfall Derek , van der Zypp Andrea , Hopwood Malcolm , Mitchell Alex J 
Published: November 2013

Objective: Diagnosing depression in primary care settings is challenging. Patients are more likely to present with somatic symptoms, and typically with mild depression. Use of assessment scales is variable. In this context, it is uncertain how general practitioners (GPs) determine the severity of depressive illness in clinical practice. The aim of the current paper was to identify which symptoms are used by GPs when diagnosing depression and when determining severity. Method: A total of 1760 GPs participated in the RADAR Program, an educational program focusing on the diagnosis and management of clinical depression. GPs identified a maximum of four patients whom they diagnosed with depression and answered questions regarding their diagnostic decision-making process for each patient. Results: Overall, assessment of depression severity was influenced more by somatic symptoms collectively than emotional symptoms. Suicidal thoughts, risk of self-harm, lack of enjoyment and difficulty with activities were amongst the strongest predictors of a diagnosis of severe depression. Conclusions: The conclusions are threefold: (1) collectively, somatic symptoms are the most important predictors of determining depression severity in primary care; (2) GPs may equate risk of self-harm with suicidal intent; (3) educational initiatives need to focus on key depressive subtypes derived from emotional, somatic and associated symptoms.
Interval vs Massed Training: How Best Do We Teach Surgery?
Authors: Kesser Bradley W. , Hallman Matthew , Murphy Loren , Tillar Maggie , Keeley Meg , Peirce Shayn 
Published: November 2013

ObjectiveTo compare 2 different training paradigms, massed vs interval training, when novice students learn a surgical procedure, myringotomy with ventilation tube insertion, on a validated surgical simulator.Study DesignMedical students were randomized into 2 training groups: the interval group (n = 19) was trained to perform the procedure in 5 trials/d over 3 days, and the massed group (n = 21) was trained to perform the procedure in 15 trials all in 1 session. One week later, all students were tested in 5 additional final trials. Pre‐ and posttest surveys were administered.SettingAcademic medical center.Subjects and MethodsForty medical students: 19 students in the interval group were compared with 21 students in the massed group. Time to complete the procedure and number and type of error made were recorded and compared between groups. Pre‐ and poststudy surveys examined confidence levels working under a microscope and with the procedure.ResultsStudents in both groups had a significant decrease in time between practice and final trials. In the final 5 trials, there was no difference in average time to complete the procedure between the massed and interval training groups. No difference was observed in the number of errors committed per trial between initial and final trials (both groups) or between massed and interval training groups. The students’ confidence levels significantly increased across the trials, regardless of group.ConclusionSurgical training improves proficiency, but method of training had little impact on proficiency in performing a simulated surgical procedure in this setting.
Clustering of Acute and Subacute Stent Thrombosis Related to the Introduction of Generic Clopidogrel
Authors: Kovacic Jason C. , Mehran Roxana , Sweeny Joseph , Li Jennifer R. , Moreno Pedro , Baber Usman , Krishnan Prakash , Badimon Juan J. , Hulot Jean-Sebastien , Kini Annapoorna , Sharma Samin K. 
Published: November 2013

Introduction: Generic clopidogrel recently became available in the United States and was rapidly adopted as a cost-effective alternative to the brand name formulation. However, unlike other medications, subtle differences in clopidogrel bioavailability may lead to acute consequences including stent thrombosis (ST). Materials and Methods: We studied the incidence of acute and subacute ST during the initial period of generic clopidogrel use (June 18, 2012-September 6, 2012 [80 days]) at a single percutaneous coronary intervention (PCI) center. There were 4 definite ST cases within 30 days of successful PCI in patients receiving generic clopidogrel, which were compared to historic control ST cases from 80 days prior to generic clopidogrel use and for 3 years from June 18, 2009 to June 17, 2012. Results: During generic clopidogrel administration, 1054 PCIs were performed, giving a definite 30-day ST incidence of 0.38% (4 of 1054) among these patients. By comparison, there were 2 episodes of definite 30-day ST during the 80 days immediately preceding generic clopidogrel use (2 of 1114), while 3-year historic data indicated a definite 30-day ST incidence of 0.14% (20 of 14 432), representing a 2.7-fold increase in definite 30-day ST with generic clopidogrel use ( P = .076). Exclusion of 3 historic controls with a defined reason for ST (noncompliance, marked thrombocytosis) gave a 3.2-fold increase in 30-day ST with generic clopidogrel ( P = .050). An ST-predictive algorithm revealed no difference in the likelihood of ST between patients receiving generic clopidogrel and historic controls. Conclusions: We observed an unexpected >2-fold increase in ST coincident with generic clopidogrel use. Although we cannot ascribe causality, this observation warrants increased vigilance and close monitoring of patients receiving generic clopidogrel.
Parents’ views on toilet training (TT)
Authors: van Nunen Karolien , Kaerts Nore , Wyndaele Jean-Jacques , Vermandel Alexandra , Hal Guido Van 
Published: November 2013

Background: In recent years, the age at which parents start and finish toilet training (TT) their children has increased. To cope with the problems caused by this later completion, it is essential to identify the beliefs and attitudes of the parents. Methods: Two thousand questionnaires were distributed to parents of children aged 30 to 36 months, attending 50 randomly selected schools in Antwerp, Belgium. Results: Too many children are toilet trained after the minimum school age of 30 months. Most parents are not aware of the possible negative consequences this can entail. Mothers with a paid occupation think more often that children should be toilet trained before the age of 30 months, and the higher the mother’s educational level, the more likely she will send her child to school toilet trained. More of single parents think that children who are not yet toilet trained should be allowed to go to school and more often send their not fully toilet-trained children to school. Conclusion: Parents should be better informed about the possible negative consequences of a later completion of TT. Single parents, more than other parents, should be assisted in the TT process and offered more support.
Perioperative Cytokine Response to Infection Associated With Elective Arterial Surgery
Authors: Daryapeyma Alireza , Aarstad Hans Jørgen , Wahlgren Carl-Magnus , Jonung Torbjörn 
Published: November 2013

Objective: The aim was to assess the cytokine response to acute inflammation and infection in vascular surgery. Design of Study: Single-center, prospective cohort study. Methods: Blood samples from 96 consecutive patients undergoing elective vascular surgery were analyzed for C-reactive protein (CRP), total leukocyte counts (LPK), neutrophil CD64 expression, and cytokines using enzyme-linked immunosorbent assay. Results: Of the 25 investigated cytokines, 22 had lower postoperative mean values compared to preoperative values. Interleukin (IL) 6 (IL-6) was the only cytokine that increased significantly postoperatively. Combined analysis of CRP and CD64 together with IL-6 or IL-10 showed an individually unique association with postoperative infection ( P < .05). Conclusion: We have shown a positive correlation with perioperative infection for the proinflammatory cytokines and the anti-inflammatory cytokine IL-10 as well as a number of chemokines. To our knowledge, this is the first report linking IL-10 and chemokine plasma levels to perioperative infection in vascular surgery.
Platelet gene therapy corrects the hemophilic phenotype in immunocompromised hemophilia A mice transplanted with genetically manipulated human cord blood stem cells
Authors: Shi Qizhen , Kuether Erin L. , Chen Yingyu , Schroeder Jocelyn A. , Fahs Scot A. , Montgomery Robert R. 
Published: November 2013

Key PointsPlatelet-specific lentiviral gene delivery to human hematopoietic stem cells can efficiently introduce FVIII expression in human platelets. Human platelet–derived FVIII can ameliorate the hemophilic phenotype in an immunocompromised hemophilia A mouse model.
Impact of obesity-related genes in Spanish population
Authors: Martínez-García Fernando , Mansego María L , Rojo-Martínez Gemma , De Marco-Solar Griselda , Morcillo Sonsoles , Soriguer Federico , Redón Josep , Pineda Alonso Monica , Martín-Escudero Juan C , Cooper Richard S , Chaves Felipe J 
Published: November 2013

AbstractBackgroundThe objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis.ResultsPolymorphisms of theFTOwere significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2in Hortega and 2.0 kg/m2in Pizarra. Overall, the obesity predictive value was low (less than 1%).ConclusionThe risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.
Transcriptome profiling of fruit development and maturation in Chinese white pear (Pyrus bretschneideri Rehd)
Authors: Xie Min , Huang Ying , Zhang Yanping , Wang Xin , Yang Hua , Yu Oliver , Dai Wenhao , Fang Congbing 
Published: November 2013

AbstractBackgroundPear (Pyrus spp) is an important fruit species worldwide; however, its genetics and genomic information is limited. Combining the Solexa/Illumina RNA-seq high-throughput sequencing approach (RNA-seq) with Digital Gene Expression (DGE) analysis would be a powerful tool for transcriptomic study. This paper reports the transcriptome profiling analysis of Chinese white pear (P. bretschneideri) using RNA-seq and DGE to better understand the molecular mechanisms in fruit development and maturation of Chinese white pear.ResultsDe novotranscriptome assembly and gene expression analysis of Chinese white pear were performed in an unprecedented depth (5.47 gigabase pairs) using high-throughput Illumina RNA-seq combined with a tag-based Digital Gene Expression (DGE) system. Approximately, 60.77 million reads were sequenced, trimmed, and assembled into 90,227 unigenes. These unigenes comprised 17,619 contigs and 72,608 singletons with an average length of 508 bp and had an N50of 635 bp. Sequence similarity analyses against six public databases (Uniprot, NR, and COGs at NCBI, Pfam, InterPro, and KEGG) found that 61,636 unigenes can be annotated with gene descriptions, conserved protein domains, or gene ontology terms. By BLASTing all 61,636 unigenes in KEGG, a total of 31,215 unigenes were annotated into 121 known metabolic or signaling pathways in which a few primary, intermediate, and secondary metabolic pathways are directly related to pear fruit quality. DGE libraries were constructed for each of the five fruit developmental stages. Variations in gene expression among all developmental stages of pear fruit were significantly different in a large amount of unigenes.ConclusionExtensive transcriptome and DGE profiling data at five fruit developmental stages of Chinese white pear have been obtained from a deep sequencing, which provides comprehensive gene expression information at the transcriptional level. This could facilitate understanding of the molecular mechanisms in fruit development and maturation. Such a database can also be used as a public information platform for research on molecular biology and functional genomics in pear and other related species.
De novo characterization of the Anthuriumtranscriptome and analysis of its digital gene expression under cold stress
Authors: Tian Dan-Qing , Pan Xiao-Yun , Yu Yong-Ming , Wang Wei-Yong , Zhang Fei , Ge Ya-Ying , Shen Xiao-Lan , Shen Fu-Quan , Liu Xiao-Jing 
Published: November 2013

Abstract

Background

Anthurium andraeanum is one of the most popular tropical flowers. In temperate and cold zones, a much greater risk of cold stress occurs in the supply of Anthurium plants. Unlike the freeze-tolerant model plants, Anthurium plants are particularly sensitive to low temperatures. Improvement of chilling tolerance in Anthurium may significantly increase its production and extend its shelf-life. To date, no previous genomic information has been reported in Anthurium plants.

Results
Using Illumina sequencing technology, we generated over two billion base of high-quality sequence in Anthurium, and demonstrated de novo assembly and annotation of genes without prior genome information. These reads were assembled into 44,382 unigenes (mean length = 560 bp). Based on similarity search with known protein in the non-redundant (nr) protein database, 27396 unigenes (62%) were functionally annotated with a cut-off E-value of 10-5. Further, DGE tags were mapped to the assembled transcriptome for gene expression analysis under cold stress. In total, 4363 differentially expressed genes were identified. Among these genes, 292, 805 and 708 genes were up-regulated after 1-h, 5-h and 24-h cold treatment, respectively. Then we mapped these cold-induced genes to the KEGG database. Specific enrichment was observed in photosynthesis pathway, metabolic pathways and oxidative phosphorylation pathway in 1-h cold-treated plants. After a 5-h cold treatment, the metabolic pathways and oxidative phosphorylation pathway were significantly identified as the top two pathways. After 24-h cold treatment, mRNA surveillance pathway, RNA transport pathway and plant-pathogen interaction pathway were significantly enriched. Together, a total of 39 cold-inducible transcription factors were identified, including subsets of AP2/ERF, Zinc figure, NAC, MYB and bZIP family members.

Conclusion
Our study is the first to provide the transcriptome sequence resource for Anthurium plants, and demonstrate its digital gene expression profiling under cold conditions using the assembled transcriptome data for reference. These data provides a valuable resource for genetic and genomic studies under abiotic conditions for Anthurium plants.
Identification of the type II cytochrome cmaturation pathway in anammox bacteria by comparative genomics
Authors: Ferousi Christina , Speth Daan R , Reimann Joachim , Op den Camp Huub JM , Allen James WA , Keltjens Jan TM , Jetten Mike SM 
Published: November 2013

Abstract

Background
Anaerobic ammonium oxidizing (anammox) bacteria may contribute up to 50% to the global nitrogen production, and are, thus, key players of the global nitrogen cycle. The molecular mechanism of anammox was recently elucidated and is suggested to proceed through a branched respiratory chain. This chain involves an exceptionally high number of c-type cytochrome proteins which are localized within the anammoxosome, a unique subcellular organelle. During transport into the organelle the c-type cytochrome apoproteins need to be post-translationally processed so that heme groups become covalently attached to them, resulting in mature c-type cytochrome proteins.

Results
In this study, a comparative genome analysis was performed to identify the cytochrome c maturation system employed by anammox bacteria. Our results show that all available anammox genome assemblies contain a complete type II cytochrome c maturation system.

Conclusions
Our working model suggests that this machinery is localized at the anammoxosome membrane which is assumed to be the locus of anammox catabolism. These findings will stimulate further studies in dissecting the molecular and cellular basis of cytochrome c biogenesis in anammox bacteria.