bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCL1 expression predicts overall survival in patients with mantle cell lymphoma
Authors: Shin Su‐Jin , Roh Jin , Cha Hee Jeong , Choi Yoo Duk , Kim Jin‐Man , Min Soo Kee , Kim Ji Eun , Eom Dae‐Woon , Lee Hojung , Kim Hyun‐Jung , Yoon Dok Hyun , Suh Cheolwon , Huh Jooryung 
Published: February 2015

AbstractObjectivesMantle cell lymphoma (MCL) has a heterogeneous clinical course. Although most cases show a poor prognosis, a minority has an indolent course. It is difficult to identify indolent MCL cases prospectively. T‐cell leukemia/lymphoma protein 1 (TCL1) is expressed by several B‐cell lymphomas, including MCL. This study examined the expression of TCL1 and its prognostic relevance for MCL.MethodsClinical data for 162 patients with MCL were collected. Of these, 144 cases with available tissues for tissue microarray construction and immunostaining were included in the analysis. TCL1 staining was quantified using the Nuclear Quant application with Pannoramic™ Viewer v. 1.14. High TCL1 expression was defined as moderate to strong nuclear and/or cytoplasmic staining in 40% or more of the cells.ResultsHigh TCL1 expression was observed in 39 of 144 samples (27.1%). Patients with low TCL1 expression were more likely to present with blastoid/pleomorphic morphology (P = 0.010). Low TCL1 expression was associated with significantly shorter overall survival (OS, P = 0.006). Multivariate analysis identified low TCL1 expression (P = 0.003), high‐risk MIPI (P = 0.027), and anemia (P = 0.018) as adverse prognostic factors.ConclusionsOur study suggests that TCL1 expression profile may have a role in the prediction of overall outcome in patient with MCL and call for prospective studies.
Investigating the genetic basis of fever‐associated syndromic epilepsies using copy number variation analysis
Authors: Hartmann Corinna , von Spiczak Sarah , Suls Arvid , Weckhuysen Sarah , Buyse Gunnar , Vilain Catheline , Van Bogaert Patrick , De Jonghe Peter , Cook Joseph , Muhle Hiltrud , Stephani Ulrich , Helbig Ingo , Mefford Heather C. 
Published: February 2015

SummaryFever‐associated syndromic epilepsies ranging from febrile seizures plus (FS+) to Dravet syndrome have a significant genetic component. However, apart from SCN1A mutations in >80% of patients with Dravet syndrome, the genetic underpinnings of these epilepsies remain largely unknown. Therefore, we performed a genome‐wide screening for copy number variations (CNVs) in 36 patients with SCN1A‐negative fever‐associated syndromic epilepsies. Phenotypes included Dravet syndrome (n = 23; 64%), genetic epilepsy with febrile seizures plus (GEFS+) and febrile seizures plus (FS+) (n = 11; 31%) and unclassified fever‐associated epilepsies (n = 2; 6%). Array comparative genomic hybridization (CGH) was performed using Agilent 4 × 180K arrays. We identified 13 rare CNVs in 8 (22%) of 36 individuals. These included known pathogenic CNVs in 4 (11%) of 36 patients: a 1q21.1 duplication in a proband with Dravet syndrome, a 14q23.3 deletion in a proband with FS+, and two deletions at 16p11.2 and 1q44 in two individuals with fever‐associated epilepsy with concomitant autism and/or intellectual disability. In addition, a 3q13.11 duplication in a patient with FS+ and two de novo duplications at 7p14.2 and 18q12.2 in a patient with atypical Dravet syndrome were classified as likely pathogenic. Six CNVs were of unknown significance. The identified genomic aberrations overlap with known neurodevelopmental disorders, suggesting that fever‐associated epilepsy syndromes may be a recurrent clinical presentation of known microdeletion syndromes.
Drosophilablood cells and their role in immune responses
Authors: Vlisidou Isabella , Wood Will 
Published: February 2015

Drosophila melanogasterhas been extensively used to study the humoral arm of innate immunity because of the developmental and functional parallels with mammalian innate immunity. However, the fly cellular response to infection is far less understood. Investigative work onDrosophilahaemocytes, the immunosurveillance cells of the insect, has revealed that they fulfil roles similar to mammalian monocytes and macrophages. They respond to wound signals and orchestrate the coagulation response. In addition, they phagocytose and encapsulate invading pathogens, and clear up apoptotic bodies controlling inflammation. This review briefly describes theDrosophilahaematopoietic system and discusses what is currently known about the contribution of haemocytes to the immune response upon infection and wounding, during all stages of development.
Climate Trends but Little Net Water Supply Shift in One of Canada's Most Water‐Stressed Regions over the Last Century
Authors: Fleming S.W. , Barton M. 
Published: February 2015

AbstractThe southern interior ecoprovince (SIE) of British Columbia, Canada represents the northernmost extent of the great western North American deserts, it is experiencing some of the nation's fastest economic and population growth making it one of Canada's most water‐stressed regions, and it includes two headwater basins of the transboundary (Canada‐US) Columbia River. Statistical trend analyses were performed on 90‐year regional indicator time series for annual conditions in observed temperature, precipitation, and streamflow reflecting the three major SIE river basins: the Thompson, and transboundary Okanagan and Similkameen. Results suggest that regional climate has grown warmer and wetter, but with little net impact on total water supply availability. The outcome might reflect mutual cancellation of increases in precipitation inputs vs. evapotranspiration losses. Conclusions appeared largely insensitive to low‐pass data filtering, Pacific Decadal Oscillation effects, or solar output variability. Ensemble historical global climate model runs over the same time interval support this absence of appreciable trend in regionally integrated annual runoff volume, but a possible mismatch in precipitation results suggests a direction for further study. Overall, while important changes in hydrologic timing and extremes are likely occurring here, there is limited evidence for a net change in overall water supply availability over the last century.
A novel mutation in IL36RN underpins childhood pustular dermatosis
Authors: Ellingford J.M. , Black G.C.M. , Clayton T.H. , Judge M. , Griffiths C.E.M. , Warren R.B. 
Published: February 2015

AbstractBackgroundChronic pustular dermatoses are severe and debilitating autoinflammatory conditions that can have a monogenic basis. Their clinical features are, however, complex with considerable overlap. Null and missense mutations in the genes encoding interleukin (IL)‐1 family (IL‐1 and IL‐36) anti‐inflammatory receptor antagonist (Ra) cytokines can underlie the development of severe pustular dermatoses.ObjectiveWe present a clinical and genetic study of four children of Pakistani descent with similar clinical presentations and treatment course, each of whom suffers from a severe pustular dermatosis, initially described as a pustular variant of psoriasis. We use DNA sequencing to refine the diagnosis of two of the children studied.MethodsBidirectional Sanger sequencing was performed on the coding regions of the IL‐1Ra and IL‐36Ra genes (IL1RN and IL36RN, respectively), for the four affected children and their parents.ResultsWe identified a novel homozygous missense mutation in IL36RN in two siblings, and showed the molecular basis of the condition to be both distinct from psoriasis and distinct between the two families studied.ConclusionsWe describe a novel mutation which underpins the diagnosis of childhood pustular dermatosis. Molecular diagnostics can be used to aid the clinical diagnosis and potential treatment of autoinflammatory conditions.
The expression of nitrate transporter genes reveals different nitrogen statuses of dominant diatom groups in the southern East China Sea
Authors: Kang Lee‐Kuo , Gong Gwo‐Ching , Wu Yi‐Hsuan , Chang Jeng 
Published: February 2015

AbstractIn this study, the mRNA levels of the Nrt2 nitrate transporter gene were used as a molecular indicator of nitrogen status in two dominant diatom groups, Skeletonema and Chaetoceros, which inhabit the southern East China Sea (ECS). To accurately interpret the abundance of Nrt2 transcripts in situ, maximum and minimum expression levels were determined under conditions of nitrogen deprivation and ammonium addition, respectively. In August 2010, Nrt2 transcript levels in Skeletonema at the inner shelf region exhibited a mean of 111 mmole/(mole EFL); at the mid‐shelf region, the mean Nrt2 mRNA levels were 298 mmole/(mole EFL), which was very close to the maximum levels observed under nitrogen starvation. By contrast, the Nrt2 transcript levels in Chaetoceros were low at all of the shelf locations, except at one station in the mid‐shelf region. The cross‐shelf mean was 2.86 mmole/(mole EFL), which was similar to the expression levels observed in cultured Chaetoceros under conditions of sufficient ammonium. Similar expression patterns were observed in diatoms in the southern ECS in June 2011, but the Nrt2 transcript levels in Skeletonema at the inner shelf region were reduced to a mean of 28.6 mmole/(mole EFL). Regression analysis indicated that cell abundance and Nrt2 expression were closely related to the nutricline depth in the coastward half of the southern ECS for Skeletonema but not for Chaetoceros. These results indicate that the evaluated species differ in nitrogen status, which may reflect their evolutionary strategies to survive in a fluctuating marine environment.
On the complexity of triggering evolutionary radiations
Authors: Bouchenak‐Khelladi Yanis , Onstein Renske E. , Xing Yaowu , Schwery Orlando , Linder H. Peter 
Published: February 2015

SummaryRecent developments in phylogenetic methods have made it possible to reconstruct evolutionary radiations from extant taxa, but identifying the triggers of radiations is still problematic. Here, we propose a conceptual framework to explore the role of variables that may impact radiations. We classify the variables into extrinsic conditions vs intrinsic traits, whether they provide background conditions, trigger the radiation, or modulate the radiation.We used three clades representing angiosperm phylogenetic and structural diversity (Ericaceae, Fagales and Poales) as test groups. We located radiation events, selected variables potentially associated with diversification, and inferred the temporal sequences of evolution.We found 13 shifts in diversification regimes in the three clades. We classified the associated variables, and determined whether they originated before the relevant radiation (backgrounds), originated simultaneously with the radiations (triggers), or evolved later (modulators).By applying this conceptual framework, we establish that radiations require both extrinsic conditions and intrinsic traits, but that the sequence of these is not important. We also show that diversification drivers can be detected by being more variable within a radiation than conserved traits that only allow occupation of a new habitat. This framework facilitates exploration of the causative factors of evolutionary radiations.
Utilizing systems biology to unravel stomatal function and the hierarchies underpinning its control
Authors: MEDEIROS DAVID B. , DALOSO DANILO M. , FERNIE ALISDAIR R. , NIKOLOSKI ZORAN , ARAÚJO WAGNER L. 
Published: February 2015

AbstractStomata control the concomitant exchange of CO2 and transpiration in land plants. While a constant supply of CO2 is need to maintain the rate of photosynthesis, the accompanying water losses must be tightly regulated to prevent dehydration and undesired metabolic changes. The factors affecting stomatal movement are directly coupled with the cellular networks of guard cells. Although the guard cell has been used as a model for characterization of signaling pathways, several important questions about its functioning remain elusive. Current modeling approaches describe the stomatal conductance in terms of relatively few easy‐to‐measure variables being unsuitable for in silico design of genetic manipulation strategies. Here, we argue that a system biology approach, combining modeling and high‐throughput experiments, may be used to elucidate the mechanisms underlying stomata control and to determine targets for modulation of stomatal responses to environment. In support of our opinion, we review studies demonstrating how high‐throughput approaches have provided a systems‐view of guard cells. Finally, we emphasize the opportunities and challenges of genome‐scale modeling and large‐scale data integration for in silico manipulation of guard cell functions to improve crop yields, particularly under stress conditions which are of pertinence both to climate change and water use efficiency.
Obedience and Believing a Person
Authors: McMyler Benjamin 
Published: February 2015

AbstractI argue that there is a mutually illuminating parallel between the concept of obedience and the concept of believing a person. Just as both believing what a person says and believing what a person says for the reason that the person says it are insufficient for believing the person, so acting as a person demands and acting as a person demands for the reason that the person demands it are insufficient for obeying the person. Unlike the concept of believing a person, however, the concept of obedience has two distinct senses, one applying to coerced action and one applying to non‐coerced action based on authoritative directives. While the former sense of obedience has no theoretical analogue, the latter sense of obedience can be understood as the practical analogue of the theoretical case of believing a person, making room for a deep parallel between believing and acting on authority.
International Comparison of Public and Private Employees’ Work Motives, Attitudes, and Perceived Rewards
Authors: Bullock Justin B. , Stritch Justin M. , Rainey Hal G. 
Published: February 2015

AbstractThis article presents a conceptual perspective on the distinctive characteristics of public organizations and their personnel. This perspective leads to hypotheses that public organizations deliver distinctive goods and services that influence the motives and rewards for their employees. These hypotheses are tested with evidence from the International Social Survey Programme in order to compare public and private employees in 30 nations. Public employees in 28 of the 30 nations expressed higher levels of public‐service‐oriented motives. In all of the countries, public employees were more likely to say they receive rewards in the form of perceived social impact. In most of the countries, public employees placed less importance on high income as a reward and expressed higher levels of organizational commitment.Practitioner PointsThe findings presented here add to previous evidence that public employees seek and attain more altruistic and public‐service‐oriented rewards than private sector employees. In particular, we add evidence that these differences hold in many different nations and cultural contexts.Compensation and incentive system reforms in many governments have often concentrated on financial incentives and streamlining procedures for discipline and removal. Such matters are important but should not drive out concerns with showing public employees the impact of their work on the well‐being of others and on the community and society. Leaders and managers should invest in incentive systems that emphasize such motives and rewards.Leaders and managers should invest in the use of altruistic and socially beneficial motives and rewards in recruiting systems.
Porphyromonas gingivalis B cell Antigen Epitope Vaccine, pIRES‐ragB'‐mGITRL, Promoted RagB‐Specific Antibody Production and Tfh Cells Expansion
Authors: Kong F. , Zheng D. , She P. , Ni P. , Zhu H. , Xu H. , Su Z. 
Published: February 2015

AbstractThe outer membrane protein RagB is one of the major virulence factors of Porphyromonas gingivalis (P. gingivalis). To prevent periodontitis and associated systemic diseases induced by P. gingivalis, we built B cell antigen epitope vaccine characterized by pIRES‐ragB'‐mGITRL to induce a protective immune responses. The B cell antigen epitope and scrambled peptide of ragB were predicted, cloned into pIRES and constructed pIRES‐ragB', pIRES‐scrambled epitopes and pIRES‐ragB'‐mGITRL. pIRES‐ragB'‐mGITRL was transfected into COS‐7 cells. Subsequently, the 6‐week‐old female BALB/c mice were challenged by P. gingivalis following three time immunization by pIRES, pIRES‐ragB', pIRES‐scrambled epitopes and pIRES‐ragB'‐mGITRL. The levels of RagB‐specific antibody in the serum and Tfh cells in the spleen were measured by ELISA and flow cytometry, respectively. And higher levels of RagB‐specific IgG were produced in the immunized mice with pIRES‐ragB'‐mGITRL. Additionally, the number of Tfh cells was also expanded and lesions were diminished in pIRES‐ragB'‐mGITRL mice comparing with control groups. Our results clearly demonstrated that P. gingivalis B cell antigen epitope vaccine, pIRES‐ragB'‐mGITRL, could induce protective immune responses. Furthermore, our data also indicated that pIRES‐ragB'‐mGITRL was a potential therapeutic vaccine against P. gingivalis.
Negotiating Fitness, From Consumption to Virtuous Production
Authors: Neville Ross D. , Gorman Catherine , Flanagan Sheila , Dimanche Frédéric 
Published: February 2015

By shifting our attention toward everyday life, its manifold commitments and responsibilities, this paper examines the potential for “fitness” to take on an extended meaning beyond consumption activity. In the opening sections, Robert Nozick’s (1974) “Experience Machine” thought experiment is presented as an alternative analytic frame for interpreting the problem of fitness in terms of a tension between mere activity and experience. In relation to this tension, the paper presents findings from a study of experienced participants and emphasizes the possibilities of a virtuous production through fitness. In particular, we emphasize that there is much work to be done in sedimenting (and maintaining) an appropriate frame of reference for “doing fitness” and that “being someone through fitness” might operate as an indexical marker of virtue.En dirigeant notre attention vers la vie de tous les jours et ses multiples engagements et responsabilités, nous examinons dans cet article le potentiel du « fitness » d’avoir une signification étendue au-delà de l’activité de consommation. Dans les premières sections, l’expérience de pensée de la « machine à expérience » de Robert Nozick (1974) est présentée comme un cadre analytique alternatif pour l’interprétation du problème de la condition physique en termes de tension entre simple activité et expérience. En lien avec cette tension, cet article présente les résultats d’une étude de participants expérimentés et met l’accent sur les possibilités d’une production vertueuse par l’intermédiaire de la condition physique. En particulier, nous soulignons qu’il y a beaucoup de travail à faire dans la sédimentation (et le maintien) d’un cadre de référence approprié pour « faire de l’activité physique » et qu’« être quelqu’un par l’intermédiaire de la condition physique » peut agir comme indicateur de vertu.
Selective Inhibition of HDAC1 and HDAC2 as a Potential Therapeutic Option for B-ALL
Authors: Stubbs Matthew C. , Kim Wonil , Bariteau Megan , Davis Tina , Vempati Sridhar , Minehart Janna , Witkin Matthew , Qi Jun , Krivtsov Andrei V. , Bradner James E. , Kung Andrew L. , Armstrong Scott A. 
Published: February 2015

Abstract
Purpose: Histone deacetylase inhibitors (HDACi) have recently emerged as efficacious therapies that target epigenetic mechanisms in hematologic malignancies. One such hematologic malignancy, B-cell acute lymphoblastic leukemia (B-ALL), may be highly dependent on epigenetic regulation for leukemia development and maintenance, and thus sensitive to small-molecule inhibitors that target epigenetic mechanisms.
Experimental Design: A panel of B-ALL cell lines was tested for sensitivity to HDACi with varying isoform sensitivity. Isoform-specific shRNAs were used as further validation of HDACs as relevant therapeutic targets in B-ALL. Mouse xenografts of B-cell malignancy–derived cell lines and a pediatric B-ALL were used to demonstrate pharmacologic efficacy.
Results: Nonselective HDAC inhibitors were cytotoxic to a panel of B-ALL cell lines as well as to xenografted human leukemia patient samples. Assessment of isoform-specific HDACi indicated that targeting HDAC1-3 with class I HDAC-specific inhibitors was sufficient to inhibit growth of B-ALL cell lines. Furthermore, shRNA-mediated knockdown of HDAC1 or HDAC2 resulted in growth inhibition in these cells. We then assessed a compound that specifically inhibits only HDAC1 and HDAC2. This compound suppressed growth and induced apoptosis in B-ALL cell lines in vitro and in vivo, whereas it was far less effective against other B-cell–derived malignancies.
Conclusions: Here, we show that HDAC inhibitors are a potential therapeutic option for B-ALL, and that a more specific inhibitor of HDAC1 and HDAC2 could be therapeutically useful for patients with B-ALL. Clin Cancer Res; 21(10); 2348–58. ©2015 AACR.
Novel Actions of Next-Generation Taxanes Benefit Advanced Stages of Prostate Cancer
Authors: de Leeuw Renée , Berman-Booty Lisa D. , Schiewer Matthew J. , Ciment Stephen J. , Den Robert B. , Dicker Adam P. , Kelly William K. , Trabulsi Edouard J. , Lallas Costas D. , Gomella Leonard G. , Knudsen Karen E. 
Published: February 2015

Abstract
Purpose: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond.
Experimental design: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro and in xenograft tumors for cabazitaxel response.
Results: The data herein show that (i) cabazitaxel exerts stronger cytostatic and cytotoxic response compared with docetaxel, especially in CRPC; (ii) cabazitaxel induces aberrant mitosis, leading to pyknotic and multinucleated cells; (iii) taxanes do not act through the androgen receptor (AR); (iv) gene-expression profiling reveals distinct molecular actions for cabazitaxel; and (v) tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to cabazitaxel.
Conclusions: Cabazitaxel not only induces improved cytostatic and cytotoxic effects, but also affects distinct molecular pathways, compared with docetaxel, which could underlie its efficacy after docetaxel treatment has failed in patients with CRPC. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization to taxanes, which could benefit up to 50% of CRPC cases. Clin Cancer Res; 21(4); 795–807. ©2015 AACR.