bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational generation and dissection of lexical replacement humor
Authors: VALITUTTI ALESSANDRO , DOUCET ANTOINE , TOIVANEN JUKKA M. , TOIVONEN HANNU 
Published: April 2015

AbstractWe consider automated generation of humorous texts by substitution of a single word in a given short text. In this setting, several factors that potentially contribute to the funniness of texts can be integrated into a unified framework as constraints on the lexical substitution. We discuss three types of such constraints: formal constraints concerning the similarity of sounds or spellings between the original word and the substitute, semantic or connotational constraints requiring the substitute to be a taboo word, and contextual constraints concerning the position and context of the replacement. Empirical evidence from extensive user studies using real SMSs as the corpus indicates that taboo constraints are statistically very effective, and so is a constraint requiring that the substitution takes place at the end of the text even though the effect is smaller. The effects of individual constraints are largely cumulative. In addition, connotational taboo words and word position have a strong interaction.
BCL-2 is dispensable for thrombopoiesis and platelet survival
Authors: Debrincat M A , Pleines I , Lebois M , Lane R M , Holmes M L , Corbin J , Vandenberg C J , Alexander W S , Ng A P , Strasser A , Bouillet P , Sola-Visner M , Kile B T , Josefsson E C 
Published: April 2015

AbstractNavitoclax (ABT-263), an inhibitor of the pro-survival BCL-2 family proteins BCL-2, BCL-XL and BCL-W, has shown clinical efficacy in certain BCL-2-dependent haematological cancers, but causes dose-limiting thrombocytopaenia. The latter effect is caused by Navitoclax directly inducing the apoptotic death of platelets, which are dependent on BCL-XL for survival. Recently, ABT-199, a selective BCL-2 antagonist, was developed. It has shown promising anti-leukaemia activity in patients whilst sparing platelets, suggesting that the megakaryocyte lineage does not require BCL-2. In order to elucidate the role of BCL-2 in megakaryocyte and platelet survival, we generated mice with a lineage-specific deletion of Bcl2, alone or in combination with loss of Mcl1 or Bclx. Platelet production and platelet survival were analysed. Additionally, we made use of BH3 mimetics that selectively inhibit BCL-2 or BCL-XL. We show that the deletion of BCL-2, on its own or in concert with MCL-1, does not affect platelet production or platelet lifespan. Thrombocytopaenia in Bclx-deficient mice was not affected by additional genetic loss or pharmacological inhibition of BCL-2. Thus, BCL-2 is dispensable for thrombopoiesis and platelet survival in mice.
NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma
Authors: Wilson C. L. , Jurk D. , Fullard N. , Banks P. , Page A. , Luli S. , Elsharkawy A. M. , Gieling R. G. , Chakraborty J. Bagchi , Fox C. , Richardson C. , Callaghan K. , Blair G. E. , Fox N. , Lagnado A. , Passos J. F. , Moore A. J. , Smith G. R. , Tiniakos D. G. , Mann J. , Oakley F. , Mann D. A. 
Published: April 2015

AbstractHepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dimers and the co-repressor HDAC1. These anti-inflammatory proteins combine to transcriptionally repress hepatic expression of a S100A8/9, CXCL1 and CXCL2 neutrophil chemokine network. Loss of nfkb1 promotes ageing-associated chronic liver disease (CLD), characterized by steatosis, neutrophillia, fibrosis, hepatocyte telomere damage and HCC. Nfkb1S340A/S340Amice carrying a mutation designed to selectively disrupt p50:p50:HDAC1 complexes are more susceptible to HCC; by contrast, mice lacking S100A9 express reduced neutrophil chemokines and are protected from HCC. Inhibiting neutrophil accumulation in CLD or targeting their tumour-promoting activities may offer therapeutic opportunities in HCC.
Parent–offspring conflict and the genetic trade-offs shaping parental investment
Authors: Kölliker Mathias , Boos Stefan , Wong Janine W.Y. , Röllin Lilian , Stucki Dimitri , Raveh Shirley , Wu Min , Meunier Joël 
Published: April 2015

AbstractThe genetic conflict between parents and their offspring is a cornerstone of kin selection theory and the gene-centred view of evolution, but whether it actually occurs in natural systems remains an open question. Conflict operates only if parenting is driven by genetic trade-offs between offspring performance and the parent’s ability to raise additional offspring, and its expression critically depends on the shape of these trade-offs. Here we investigate the occurrence and nature of genetic conflict in an insect with maternal care, the earwigForficula auricularia. Specifically, we test for a direct response to experimental selection on female future reproduction and correlated responses in current offspring survival, developmental rate and growth. The results demonstrate genetic trade-offs that differ in shape before and after hatching. Our study not only provides direct evidence for parent–offspring conflict but also highlights that conflict is not inevitable and critically depends on the genetic trade-offs shaping parental investment.
High-resolution genetic mapping of maize pan-genome sequence anchors
Authors: Lu Fei , Romay Maria C. , Glaubitz Jeffrey C. , Bradbury Peter J. , Elshire Robert J. , Wang Tianyu , Li Yu , Li Yongxiang , Semagn Kassa , Zhang Xuecai , Hernandez Alvaro G. , Mikel Mark A. , Soifer Ilya , Barad Omer , Buckler Edward S. 
Published: April 2015

AbstractIn addition to single-nucleotide polymorphisms, structural variation is abundant in many plant genomes. The structural variation across a species can be represented by a ‘pan-genome’, which is essential to fully understand the genetic control of phenotypes. However, the pan-genome’s complexity hinders its accurate assembly via sequence alignment. Here we demonstrate an approach to facilitate pan-genome construction in maize. By performing 18 trillion association tests we map 26 million tags generated by reduced representation sequencing of 14,129 maize inbred lines. Using machine-learning models we select 4.4 million accurately mapped tags as sequence anchors, 1.1 million of which are presence/absence variations. Structural variations exhibit enriched association with phenotypic traits, indicating that it is a significant source of adaptive variation in maize. The ability to efficiently map ultrahigh-density pan-genome sequence anchors enables fine characterization of structural variation and will advance both genetic research and breeding in many crops.
A rapid ambient ionization-mass spectrometry approach to monitoring the relative abundance of isomeric glycerophospholipids
Authors: Kozlowski Rachel L. , Mitchell Todd W. , Blanksby Stephen J. 
Published: April 2015

AbstractGlycerophospholipids with two, non-equivalent fatty acyl chains can adopt one of two isomeric forms depending on the relative position of substitutions on the glycerol backbone. These so-called sn-positional isomers can have distinct biophysical and biochemical behaviors making it desirable to uniquely assign their regiochemistries. Unambiguous assignment of such similar molecular structures in complex biological extracts is a significant challenge to current analytical technologies. We have recently reported a novel mass spectrometric method that combines collision- and ozone-induced dissociation in series (CID/OzID) to yield product ions characteristic of acyl chain substitution patterns in glycerophospholipids. Here phosphatidylcholines are examined using the CID/OzID protocol combined with desorption electrospray ionization (DESI) to facilitate the rapid exploration of sample arrays comprised of a wide variety of synthetic and biological sources. Comparison of the spectra acquired from different extracts reveals that the sn-positional isomers PC 16:0/18:1 and PC 18:1/16:0 (where the 18:1 chain is present at the sn-2 and sn-1 position of the glycerol backbone, respectively) are most often found together in lipids of either natural or synthetic origin. Moreover, the proportions of the two isomers vary significantly between extracts from different organisms or even between adjacent tissues from the same organism.
Titration of biologically active amyloid–β seeds in a transgenic mouse model of Alzheimer's disease
Authors: Morales Rodrigo , Bravo-Alegria Javiera , Duran-Aniotz Claudia , Soto Claudio 
Published: April 2015

AbstractExperimental evidence in animal models suggests that misfolded Amyloid-β (Aβ) spreads in disease following a prion-like mechanism. Several properties characteristics of infectious prions have been shown for the induction of Aβ aggregates. However, a detailed titration of Aβ misfolding transmissibility and estimation of the minimum concentration of biologically active Aβ seeds able to accelerate pathological changes has not yet been performed. In this study, brain extracts from old tg2576 animals were serially diluted and intra-cerebrally injected into young subjects from the same transgenic line. Animals were sacrificed several months after treatment and brain slices were analyzed for amyloid pathology. We observed that administration of misfolded Aβ was able to significantly accelerate amyloid deposition in young mice, even when the original sample was diluted a million times. The titration curve obtained in this experiment was compared to the natural Aβ load spontaneously accumulated by these mice overtime. Our findings suggest that administration of the largest dose of Aβ seeds led to an acceleration of pathology equivalent to over a year. These results show that active Aβ seeds present in the brain can seed amyloidosis in a titratable manner, similarly as observed for infectious prions.
Enhancer of rudimentary homolog regulates DNA damage response in hepatocellular carcinoma
Authors: Weng Meng-Tzu , Tung Tzu-Hsun , Lee Jih-Hsiang , Wei Shu-Chen , Lin Hang-Li , Huang Yu-Jung , Wong Jau-Min , Luo Ji , Sheu Jin-Chuan 
Published: April 2015

AbstractWe previously demonstrated that the enhancer of rudimentary homolog (ERH) gene is required for the expression of multiple cell cycle and DNA damage response (DDR) genes. The present study investigated the role of ERH and its target DNA damage repair genes in hepatocellular carcinoma cells. We observed positive correlation between ERH and ataxia telangiectasia and Rad3 related (ATR) expression in liver tissues. Expression of ERH, ATR as well as checkpoint kinase 1 (CHK1) were higher in HCCs than in normal liver tissues. Knocking-down ERH augmented ultraviolet light induced DNA damage in HepG2 cells. ATR protein level is reduced upon ERH depletion as a result of defect in the splicing of ATR mRNA. Consequently, the ATR effector kinase Chk1 failed to be phosphorylated upon ultraviolet light or hydroxyurea treatment in ERH knocked-down HepG2 cells. Finally, we observed Chk1 inhibitor AZD7762 enhanced the effect of doxorubicin on inhibiting growth of HCC cells in vitro and in vivo. This study suggested that ERH regulates the splicing of the DNA damage response proteins ATR in HCC cells and targeting DNA damage response by Chk1 inhibitor augments chemotherapy to treat HCC cells.
Nelfinavir and Nelfinavir Analogs Block Site-2 Protease Cleavage to Inhibit Castration-Resistant Prostate Cancer
Authors: Guan Min , Su Leila , Yuan Yate-Ching , Li Haiqing , Chow Warren A. 
Published: April 2015

AbstractNelfinavir and its analogs inhibit proliferation and induce apoptosis of castration-resistant prostate cancer through inhibition of site-2 protease (S2P) activity, which leads to suppression of regulated intramembrane proteolysis. Western blotting in nelfinavir and its analog treated cells confirms accumulation of precursor SREBP-1 and ATF6. Nelfinavir and its analogs inhibit human homolog M. jannaschii S2P cleavage of an artificial protein substrate CED-9 in an in vitro proteolysis assay in a dose-dependent manner. Nelfinavir and its analogs are more potent inhibitors of S2P cleavage activity than 1,10-phenanthroline, a metalloprotease-specific inhibitor. Further, cluster analysis of gene expression from treated DU145 and PC3 cell lines demonstrate a close similarity of nelfinavir, its analogs and 1,10-phenanthroline. These results show nelfinavir and its analogs inhibit castration-resistant prostate cancer proliferation by blocking regulated intramembrane proteolysis through suppression of S2P cleavage activity. This leads to accumulation of precursor SREBP-1 and ATF6 and development of insufficient reserves of their transcriptionally-active forms. The present results validate S2P and regulated intramembrane proteolysis as novel therapeutic targets for castration-resistant prostate cancer therapeutics. A clinical trial of nelfinavir or its analogs should be developed for castration-resistant prostate cancer.
Biochemical and redox characterization of the mediator complex and its associated transcription factor GeBPL, a GLABROUS1 enhancer binding protein
Authors: Shaikhali Jehad , Davoine Céline , Brännström Kristoffer , Rouhier Nicolas , Bygdell Joakim , Björklund Stefan , Wingsle Gunnar 
Published: April 2015

The eukaryotic mediator integrates regulatory signals from promoter-bound transcription factors (TFs) and transmits them to RNA polymerase II (Pol II) machinery. Although redox signalling is important in adjusting plant metabolism and development, nothing is known about a possible redox regulation of mediator. In the present study, using pull-down and yeast two-hybrid assays, we demonstrate the association of mediator (MED) subunits MED10a, MED28 and MED32 with the GLABROUS1 (GL1) enhancer-binding protein-like (GeBPL), a plant-specific TF that binds a promoter containing cryptochrome 1 response element 2 (CryR2) element. All the corresponding recombinant proteins form various types of covalent oligomers linked by intermolecular disulfide bonds that are reduced in vitro by the thioredoxin (TRX) and/or glutathione/glutaredoxin (GRX) systems. The presence of recombinant MED10a, MED28 and MED32 subunits or changes of its redox state affect the DNA-binding capacity of GeBPL suggesting that redox-driven conformational changes might modulate its activity. Overall, these results advance our understanding of how redox signalling affects transcription and identify mediator as a novel actor in redox signalling pathways, relaying or integrating redox changes in combination with specific TFs as GeBPL.
Preterm Birth Reduces Nutrient Absorption With Limited Effect on Immune Gene Expression and Gut Colonization in Pigs
Authors: Østergaard Mette V. , Cilieborg Malene S. , Skovgaard Kerstin , Schmidt Mette , Sangild Per T. , Bering Stine B. 
Published: April 2015

ABSTRACTObjectives:The primary risk factors for necrotizing enterocolitis (NEC) are preterm birth, enteral feeding, and gut colonization. It is unclear whether feeding and colonization induce excessive expression of immune genes that lead to NEC. Using a pig model, we hypothesized that reduced gestational age would upregulate immune‐related genes and cause bacterial imbalance after birth.Methods:Preterm (85%–92% gestation, n = 53) and near‐term (95%–99% gestation, n = 69) pigs were delivered by cesarean section and euthanized at birth or after 2 days of infant formula or bovine colostrum feeding.Results:At birth, preterm delivery reduced 5 of 30 intestinal genes related to nutrient absorption and innate immunity, relative to near‐term pigs, whereas 2 genes were upregulated. Preterm birth also reduced ex vivo intestinal glucose and leucine uptake (40%–50%), but failed to increase cytokine secretions from intestinal explants relative to near‐term birth. After 2 days of formula feeding, NEC incidence was increased in preterm versus near‐term pigs (47% vs 0%–13%). A total of 6 of the 30 genes related to immunity (TLR2, IL1B, and IL8), permeability (CLDN3, and OCLN), and absorption (SGLT) decreased in preterm pigs without affecting Gram‐negative bacteria–related responses (TLR4, IKBA, NFkB1, TNFAIP3, and PAFA). Bacterial abundance tended to be higher in preterm versus near‐term pigs (P = 0.09), whereas the composition was unaffected.Conclusions:Preterm birth predisposes to NEC and reduces nutrient absorption but does not induce upregulation of immune‐related genes or cause bacterial dyscolonization in the neonatal period. Excessive inflammation and bacterial overgrowth may occur relatively late in NEC progression in preterm neonates.
Assessing the cultural intelligence and task performance equation
Authors: Jyoti Jeevan , Kour Sumeet 
Published: April 2015

Purpose– Organizations in India are multicultural in nature. In this context, cultural intelligence is a tool, which can increase an individual’s ability to interact with people outside his/her culture. The purpose of this paper is to analyze the impact of cultural intelligence on task performance as well as to investigate the mediating role of cultural adjustment between the two.Design/methodology/approach– Extensive review of literature was done to acknowledge the cultural intelligence and task performance concept. Data for the study has been collected from the 225 managers working in nationalized banks in Jammu province (J&K, India). Data collected has been validated using confirmatory factor analysis and hypotheses have been tested through structural equation modeling.Findings– The study reveals that cultural intelligence significantly contributes toward task performance. The findings further reveal full mediation of cultural adjustment between cultural intelligence and task performance.Research limitations/implications– The study has been conducted in Indian cultural context, which can be extended to other Asian countries. Further, more outcomes of cultural intelligence can be taken into consideration in future for better understanding of the concept.Practical implications– The study contributes toward cultural intelligence theory. Organization should provide cultural training to the managers before sending them to out of home state assignment, which helps to understand the culture of that state and effectively interact with people belonging to that place.Originality/value– The paper empirically identifies the relationship between cultural intelligence and task performance in Indian context. Further, this relationship has been explored by using cultural adjustment as a mediator between the two. The model developed can be used for future research keeping it as a base.
Putting the peaces together: a situated model of mediation
Authors: Coleman Peter T. , Kugler Katharina G. , Mazzaro Kyong , Gozzi Christianna , El Zokm Nora , Kressel Kenneth 
Published: April 2015

Purpose– Research on conflict mediation presents a scattered, piecemeal understanding of what determines mediators’ strategies and tactics and ultimately what constitutes successful mediation. This paper presents research on developing a unifying framework – the situated model of mediation – that identifies and integrates the most basic dimensions of mediation situations. These dimensions combine to determine differences in mediator’s strategies that in turn influence mediation processes and outcomes.Design/methodology/approach– The approach used by this paper was twofold. First, the existing empirical literature was reviewed on factors that influence mediator’s behaviors. Based on the findings of this review, a survey study was conducted with experienced mediators to determine the most fundamental dimensions of mediation situations affecting mediators’ behaviors and mediation processes and outcomes. The data were analyzed through exploratory factor analysis and regression analysis.Findings– The results of the study show that four of the most fundamental dimensions of mediation situations include: low vs high intensity of the conflict, cooperative vs competitive relationship between the parties, tight vs flexible context and overt vs covert processes and issues. Each of these factors was found to independently predict differences in mediators’ behaviors and perceptions of processes and outcomes. These dimensions are then combined to constitute the basic dimensions of the situated model of mediation.Originality/value– The situated model of mediation is both heuristic and generative, and it shows how a minimal number of factors are sufficient to capture the complexity of conflict mediation in a wide range of contexts.
Conflicts in innovation and how to approach the “last mile” of conflict management research – a literature review
Authors: Vollmer Albert 
Published: April 2015

Purpose– The purpose of this study is to present the state-of-the-art in empirical research on conflicts in innovation inorganizations and to outline strategic implications both for research and practical application with the specific focus on intervention studies.Design/methodology/approach– Literature search in the Web-of-Science identified 32 empirical publications from 1990 to July 2012. Characteristics of the studies, methodological approaches and empirical findings are summarized and discussed. Strategic implications are derived.Findings– The literature review reveals studies of the relationship between conflict and innovation on different organizational levels. Most of the studies address different aspects of conflict as antecedents of innovation, while some address conflict as an outcome of innovative behavior or structures. Almost all authors come up with theoretical and practical implications. But intervention studies which could close the gap between theory and practice, here termed the “last mile” of conflict management, are yet to be addressed.Research limitations/implications– While several implications are derived that aim at consolidating and deepening the understanding of the conflict – innovation dynamics, the major implication is to develop a knowledge-oriented research approach and to expand the scope of research to intervention studies. Constructive controversy is described as an example of this new research avenue.Practical implications– From intervention studies, researchers could gain more direct, practical insights into actual work processes. Managers could profit by incorporating first-hand knowledge augmented by researchers’ expertise.Originality/value– This article provides a systematic review of the relationship between conflict and innovation in the business context and practical implications thereof.