bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical assessment of ATG7, LC3, and p62 in ameloblastomas
Authors: Okada Miwa , Oikawa Mariko , Miki Yasuhiro , Shimizu Yoshinaka , Echigo Seishi , Takahashi Tetsu , Kumamoto Hiroyuki 
Published: April 2014

BackgroundTo investigate the roles of autophagy in tumorigenesis, cytodifferentiation, and prognosis of odontogenic tumors, we analyzed the immunohistochemical expression of ATG7, LC3, and p62 in odontogenic tissues.MethodsTissue specimens of nine dental follicles and 69 ameloblastomas were immunohistochemically examined with antibodies against ATG7, LC3, and p62.ResultsImmunohistochemical reactivity for ATG7, LC3, and p62 was detected in many odontogenic epithelial cells and several endothelial cells and fibroblasts in dental follicles and ameloblastomas. ATG7 reactivity in ameloblatomas was significantly higher than that in dental follicles. Expression of ATG7, LC3, and p62 was found markedly in neoplastic cells near the basement membrane rather than central polyhedral cells in ameloblastomas. Reactivity for these molecules was significantly higher in unicystic ameloblastomas than in solid ameloblastomas. Granular cells in granular cell ameloblastomas showed obvious reactivity for the autophagy‐ related molecules, and LC3 reactivity in granular cell ameloblastomas was significantly higher than in other ameloblastoma variations. Recurrent ameloblastomas showed significantly lower reactivity of LC3 and p62 than primary ameloblastomas.ConclusionsExpression of ATG7, LC3, and p62 in dental follicles and ameloblastomas suggests that autophagy regulation might be affected by microenvironment alterations during tumorigenesis. The molecular machinery for autophagy is possibly involved in tissue architecture, neoplastic cell differentiation, and prognosis of the benign epithelial odontogenic tumor.
Frequent hypermethylation of WNT pathway genes in laryngeal squamous cell carcinomas
Authors: Paluszczak Jarosław , Hemmerling Dawid , Kostrzewska‐Poczekaj Magdalena , Jarmuż‐Szymczak Małgorzata , Grenman Reidar , Wierzbicka Małgorzata , Baer‐Dubowska Wanda 
Published: April 2014

BackgroundAberrations in the function of the WNT signaling pathway have been recently implicated in the pathogenesis of head and neck cancer, and the hypermethylation of several WNT cascade inhibitors were shown to be useful in disease prognosis. However, the extent of deregulation of WNT pathway by DNA hypermethylation has not been studied in detail in laryngeal cancer so far. The aim of this study was to establish the frequency of methylation of WNT pathway negative regulators in laryngeal squamous cell carcinomas and evaluate its prognostic significance.MethodsTwenty‐six laryngeal squamous cell carcinoma cell lines and samples obtained from twenty‐eight primary laryngeal carcinoma patients were analyzed. The methylation status of DKK1, LKB1, PPP2R2B, RUNX3, SFRP1, SFRP2, and WIF‐1 was assessed using the methylation‐specific polymerase chain reaction.ResultsFrequent hypermethylation of DKK1, PPP2R2B, SFRP1, SFRP2, and WIF‐1 was detected, and a high methylation index was usually observed. Half of the cell lines analyzed and seventy percent of primary laryngeal carcinoma cases were characterized by the methylation of at least four genes. The hypermethylation of PPP2R2B or WIF‐1 was associated with longer survival in laryngeal carcinoma cell lines. Moreover, the concurrent methylation of PPP2R2B and SFRP1 differentiated primary from recurrent laryngeal carcinoma cell lines.ConclusionsFrequent hypermethylation of WNT pathway negative regulators is observed in laryngeal squamous cell carcinomas. The possible prognostic significance of the methylation of DKK1, PPP2R2B, and SFRP1 needs to be evaluated in further prospective studies.
Zoledronic acid and geranylgeraniol regulate cellular behaviour and angiogenic gene expression in human gingival fibroblasts
Authors: Zafar S. , Coates D. E. , Cullinan M. P. , Drummond B. K. , Milne T. , Seymour G. J. 
Published: April 2014

The mevalonate pathway (MVP) and the anti‐angiogenic effect of bisphosphonates have been shown to play a role in the pathogenesis of bisphosphonate‐related osteonecrosis of the jaw (BRONJ). This study determined the effect of the bisphosphonate, zoledronic acid and the replenishment of the MVP by geranylgeraniol on human gingival fibroblasts. Cell viability, apoptosis, morphological analysis using transmission electron microscopy, and gene expression for vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B, epiregulin and interferon‐alpha were conducted. Results showed cellular viability was decreased in the presence of zoledronic acid and the co‐addition of zoledronic acid with geranylgeraniol restored cell viability to control levels. Caspase 3/7 was detected in zoledronic‐acid‐treated cells indicating apoptosis. Transmission electron microscopy revealed dilation of the rough endoplasmic reticulum with zoledronic acid and the appearance of multiple lipid‐like vesicles following the addition of geranylgeraniol. Zoledronic acid significantly (P < 0.05, FR > ±2) up‐regulated vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B and epiregulin at one or more time points but not interferon‐alpha. Addition of geranylgeraniol resulted in a reduction in the expression of all five genes compared with zoledronic‐acid‐treated human gingival fibroblasts. The study concluded geranylgeraniol partially reversed the effects of zoledronic acid in human gingival fibroblasts both at the cellular and genetic levels, suggesting the regulation of these genes is mediated via the mevalonate pathway.
Arecoline is cytotoxic for human endothelial cells
Authors: Ullah Mafaz , Cox Stephen , Kelly Elizabeth , Boadle Ross , Zoellner Hans 
Published: April 2014

BackgroundOral submucous fibrosis is a pre‐malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity. Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts. Endothelial cell cycle arrest is reported on exposure to arecoline, as is cytotoxicity for endothelial–lung carcinoma hybrid cells. We here describe cytotoxicity for primary human endothelial cultures from seven separate donors.Materials and methodsHuman umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by: phase‐contrast microscopy, haemocytometer counts, transmission electron microscopy, lactate dehydrogenase release and the methyl‐thiazol‐tetrazolium assay.ResultsVacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333 μg/ml or more. Ultrastructural features of cellular stress were seen after 24‐h treatment with 111 μg/ml arecoline and included reduced ribosomal studding of endoplasmic reticulum, increased autophagolysosomal structures, increased vacuolation and reduced mitochondrial cristae with slight swelling. Similar changes were seen at 4 h with arecoline at 333 μg/ml or above, but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling, while by 24 h, these cells were frankly necrotic. Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl‐thiazol‐tetrazolium assays.ConclusionsArecoline is cytotoxic via necrosis for endothelium, while biochemical assays indicate no appreciable cellular leakage before death and detachment, as well as no clear effect on mitochondrial function in viable cells. Arecoline toxicity may thus contribute to reduced vascularity in oral submucous fibrosis.
Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease
Authors: Voican Cosmin S. , Njiké‐Nakseu Micheline , Boujedidi Hédia , Barri‐Ova Nadège , Bouchet‐Delbos Laurence , Agostini Hélène , Maitre Sophie , Prévot Sophie , Cassard‐Doulcier Anne‐Marie , Naveau Sylvie , Perlemuter Gabriel 
Published: April 2014

AbstractBackground & AimsPatients with alcoholic liver disease (ALD) display inflammation of the subcutaneous adipose tissue (SAT) which correlates with liver lesions. We examined macrophage markers and polarization in the SAT of alcoholic patients and adipokine expression according to liver inflammation; we studied the consequences of alcohol withdrawal.Patients and methodsForty‐seven patients with ALD were prospectively included. SAT and blood samples were collected at inclusion and after 1 week of alcohol withdrawal. Pro‐inflammatory cytokines/chemokines, inflammasome components and products, adipokine expression levels, macrophage markers and polarization in liver and SAT samples were assessed by RT‐PCR arrays.ResultsmRNA expression level of chemokines (IL8, semaphorin 7A) correlated with hepatic steatosis in both liver and SAT. Liver expression of inflammasome components (IL1β, IL18, caspase‐1) and SAT IL6 and CCL2 correlated with liver damage. In patients with mild ALD, 1 week of alcohol withdrawal was sufficient to decrease expression level of total macrophage markers in the adipose tissue, to orient adipose tissue macrophages (ATM) towards an anti‐inflammatory M2 phenotype and to decrease the mRNA expression of cytokines/chemokines (IL18, CCL2, osteopontin, semaphorin 7A). In patients with severe ALD, 1 week of abstinence was also associated with an increase in CCL18 expression.ConclusionsIn alcoholic patients, upregulation of chemotactic factors in the liver and SAT is an early event that begins as early as the steatosis stage. The inflammasome pathway is upregulated in the liver of patients with ALD. One week of alcohol withdrawal alleviates macrophage infiltration in SAT and orients ATM towards a M2 anti‐inflammatory phenotype; this implicates alcohol in adipose tissue inflammation (ClinicalTrials.gov NCT00388323).
Cirrhosis regression in hepatitis C patients with sustained virological response after antiviral therapy: a meta‐analysis
Authors: Akhtar Ehsaan , Manne Vignan , Saab Sammy 
Published: April 2014

AbstractBackground & AimsChronic hepatitis C may be associated with cirrhosis, liver failure and hepatocellular carcinoma. Studies have demonstrated improved clinical outcome in patients who achieved a sustained viral response (SVR).MethodsA systematic literature search was performed to identify studies that assessed the association between SVR and cirrhosis regression. The main outcome studied was cirrhosis regression in patients with a SVR as compared with patients without a SVR. Six studies totalling 443 patients were included. Dichotomous outcomes were reported as risk ratios (RR) with 95% confidence intervals (CI).ResultsOf the 443 patients with cirrhosis, 137 achieved a SVR. Of these 137 patients who achieved an SVR, 73 (53%) patients had regression of cirrhosis. The risk ratio of cirrhosis regression was 2.69 [Confidence Interval (CI) 1.45–4.97, P < 0.01] in patients who achieved a SVR. The risk of cirrhosis regression was consistently in favour of patients who achieved a SVR regardless of the length of the biopsy or whether the biopsy was reviewed by a single or multiple pathologists. The risk ratio of cirrhosis regression was related to the duration of follow‐up between biopsies. The relative risk for regression of cirrhosis in studies in which the mean or median time for the follow‐up liver biopsy was greater than 36‐month was 4.33 (CI 1.1–17.0, P = 0.04) as compared to a relative risk of 1.79 (CI 1.26–2.29, P < 0.01) in studies with a mean or median time between the follow‐up biopsy of less than 36‐month.ConclusionsOur results suggest that the majority of patients with cirrhosis who achieve a SVR develop cirrhosis regression. Time between biopsies appears to be an important determinant of the likelihood of cirrhosis regression.
Molecular mechanisms controlling the phenotype and the EMT/MET dynamics of hepatocyte
Authors: Cicchini Carla , Amicone Laura , Alonzi Tonino , Marchetti Alessandra , Mancone Carmine , Tripodi Marco 
Published: April 2014

AbstractThe complex spatial and paracrine relationships between the various liver histotypes are essential for proper functioning of the hepatic parenchymal cells. Only within a correct tissue organization, in fact, they stably maintain their identity and differentiated phenotype. The loss of histotype identity, which invariably occurs in the primary hepatocytes in culture, or in vivo in particular pathological conditions (fibrosis and tumours), is mainly because of the phenomenon of epithelial‐to‐mesenchymal transition (EMT). The EMT process, that occurs in the many epithelial cells, appears to be driven by a number of general, non‐tissue‐specific, master transcriptional regulators. The reverse process, the mesenchymal‐to‐epithelial transition (MET), as yet much less characterized at a molecular level, restores specific epithelial identities, and thus must include tissue‐specific master elements. In this review, we will summarize the so far unveiled events of EMT/MET occurring in liver cells. In particular, we will focus on hepatocyte and describe the pivotal role in the control of EMT/MET dynamics exerted by a tissue‐specific molecular mini‐circuitry. Recent evidence, indeed, highlighted as two transcriptional factors, the master gene of EMT Snail, and the master gene of hepatocyte differentiation HNF4α, exhorting a direct reciprocal repression, act as pivotal elements in determining opposite cellular outcomes. The different balances between these two master regulators, further integrated by specific microRNAs, in fact, were found responsible for the EMT/METs dynamics as well as for the preservation of both hepatocyte and stem/precursor cells identity and differentiation. Overall, these findings impact the maintenance of stem cells and differentiated cells both in in vivo EMT/MET physio‐pathological processes as well as in culture.
Divergent transcriptional responses to low temperature among populations of alpine and lowland species of New Zealand stick insects (Micrarchus)
Authors: Dunning Luke T. , Dennis Alice B. , Sinclair Brent J. , Newcomb Richard D. , Buckley Thomas R. 
Published: April 2014

AbstractIn widespread and genetically structured populations, temperature variation may lead to among‐population differentiation of thermal biology. The New Zealand stick insect genus Micrarchus contains four species that inhabit different thermal environments, two of which are geographically widespread. RNA‐Seq and quantitative PCR were used to investigate the transcriptional responses to cold shock among lowland and alpine species to identify cold‐responsive transcripts that differ between the species and to determine whether there is intraspecific geographical variation in gene expression. We also used mitochondrial DNA, nuclear 28S ribosomal DNA and transcriptome‐wide SNPs to determine phylogeographic structure and the potential for differences in genetic backgrounds to contribute to variation in gene expression. RNA‐Seq identified 2160 unigenes that were differentially expressed as a result of low‐temperature exposure across three populations from two species (M. hystriculeus and M. nov. sp. 2), with a majority (68% ± 20%) being population specific. This extensive geographical variation is consistent across years and is likely a result of background genetic differences among populations caused by genetic drift and possibly local adaptation. Responses to cold shock shared among alpine M. nov. sp. 2 populations included the enrichment of cuticular structure‐associated transcripts, suggesting that cuticle modification may have accompanied colonization of low‐temperature alpine environments and the development of a more cold‐hardy phenotype.
Disseminated Scedosporium prolificans infection in an ‘extensive metaboliser’: navigating the minefield of drug interactions and pharmacogenomics
Authors: Trubiano J. A. , Paratz E. , Wolf M. , Teh B. W. , Todaro M. , Thursky K. A. , Slavin M. A. 
Published: April 2014

SummaryWe report a case of non‐fatal disseminated Scedosporium prolificans infection, including central nervous system disease and endophthalmitis, in a relapsed acute myeloid leukaemia patient with extensive CYP2C19 metabolism. Successful treatment required aggressive surgical debridement, three times daily voriconazole dosing and cimetidine CYP2C19 inhibition. In addition, the unique use of miltefosine was employed due to azole‐chemotherapeutic drug interactions. Prolonged survival following disseminated S. prolificans, adjunctive miltefosine and augmentation of voriconazole exposure with cimetidine CYP2C19 inhibition has not been reported.
Argumentativeness, Avoidance, Verbal Aggressiveness, and Verbal Benevolence as Predictors of Partner Perceptions of an Individual's Conflict Style
Authors: Guerrero Laura K. , Gross Michael A. 
Published: April 2014

AbstractThis study addressed two main questions. First, are the traits of argumentativeness, verbal aggressiveness, avoidance, and verbal benevolence reflected in conflict styles such that they are perceived by others? Second, how do these traits predict the five conflict styles in the dual concern model? These questions were tested using dyadic data from a simulated downsizing activity. Results showed that participants perceived their partners differently depending on the traits their partners endorsed. For example, people who reported being avoidant or verbally aggressive were less likely to be perceived as using the compromising style. Overall, the results suggested that the four traits investigated in this study are likely to be associated with observable behavior. Findings also demonstrated that these traits help differentiate the five conflict styles in more nuanced ways than predicted by the dual concern model. Finally, the results supported the idea that conflict styles are not only shaped by one's own traits but also by the traits of others and the interaction between two people's traits.
Identification of quantitative trait loci (QTLs) for seed protein concentration in soybean and analysis for additive effects and epistatic effects of QTLs under multiple environments
Authors: Qi Zhaoming , Hou Meng , Han Xue , Liu Chunyan , Jiang Hongwei , Xin Dawei , Hu Guohua , Chen Qingshan 
Published: April 2014

AbstractSoybean protein concentration is a key trait driver of successful soybean quality. A recombination inbred lines derived from a cross between ‘Charleston’ and ‘Dongnong594’, were planted in three environments across four years in China. Then, the genetic effects were partitioned into additive main effects, epistatic main effects and their environment interaction effects by using composite interval mapping, multiple interval mapping and composite interval mapping in a mixed linear model. Forty‐three quantitative trait loci QTLs were identified on 17 of 20 soybean chromosomes excluding Ch 7, Ch 8 and Ch 17. Two QTLs showed a good stability across multiple environments, qPRO20‐1 was detected under four environments, which explained 4.4–9.95% phenotypic variances and the allele was from ‘Charleston’ among four environments. qPRO7‐5 was detected under three environments, which explained 7.2–14.5% phenotypic variances and the allele was from ‘Dongnong 594’, three pathway genes of protein biosynthesis were detected in the interval of qPRO7‐5. The additive main‐effect QTLs contributed more phenotypic variation than the epistasis and environmental interaction. This indicated that it is feasible by marker‐assisted selection to improve soybean protein concentration.
Chilling to zero degrees disrupts pollen formation but not meiotic microtubule arrays in Triticum aestivum L.
Authors: BARTON DEBORAH A. , CANTRILL LAURENCE C. , LAW ANDREW M. K. , PHILLIPS COLLIN G. , SUTTON BRUCE G. , OVERALL ROBYN L. 
Published: April 2014

AbstractThroughout the wheat‐growing regions of Australia, chilling temperatures below 2 °C occur periodically on consecutive nights during the period of floral development in spring wheat (Triticum aestivum L.). In this study, wheat plants showed significant reductions in fertility when exposed to prolonged chilling temperatures in controlled environment experiments. Among the cultivars tested, the Australian cultivars Kite and Hartog had among the lowest levels of seed set due to chilling and their responses were investigated further. The developmental stage at exposure, the chilling temperature and length of exposure all influenced the level of sterility. The early period of booting, and specifically the +4 cm auricle distance class, was the most sensitive and corresponded to meiosis within the anthers. The response of microtubules to chilling during meiosis in Hartog was monitored, but there was little difference between chilled and control plants. Other abnormalities, such as plasmolysis and cytomixis increased in frequency, were associated with death of developing pollen cells, and could contribute to loss of fertility. The potential for an above‐zero chilling sensitivity in Australian spring wheat varieties could have implications for exploring the tolerance of wheat flower development to chilling and freezing conditions in the field.
Induced carbon reallocation and compensatory growth as root herbivore tolerance mechanisms
Authors: ROBERT CHRISTELLE A. M. , FERRIERI RICHARD A. , SCHIRMER STEFANIE , BABST BENJAMIN A. , SCHUELLER MICHAEL J. , MACHADO RICARDO A. R. , ARCE CARLA C. M. , HIBBARD BRUCE E. , GERSHENZON JONATHAN , TURLINGS TED C. J. , ERB MATTHIAS 
Published: April 2014

AbstractUpon attack by leaf herbivores, many plants reallocate photoassimilates below ground. However, little is known about how plants respond when the roots themselves come under attack. We investigated induced resource allocation in maize plants that are infested by the larvae Western corn rootworm Diabrotica virgifera virgifera. Using radioactive 11CO2, we demonstrate that root‐attacked maize plants allocate more new 11C carbon from source leaves to stems, but not to roots. Reduced meristematic activity and reduced invertase activity in attacked maize root systems are identified as possible drivers of this shoot reallocation response. The increased allocation of photoassimilates to stems is shown to be associated with a marked thickening of these tissues and increased growth of stem‐borne crown roots. A strong quantitative correlation between stem thickness and root regrowth across different watering levels suggests that retaining photoassimilates in the shoots may help root‐attacked plants to compensate for the loss of belowground tissues. Taken together, our results indicate that induced tolerance may be an important strategy of plants to withstand belowground attack. Furthermore, root herbivore‐induced carbon reallocation needs to be taken into account when studying plant‐mediated interactions between herbivores.