bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoter methylation patterns in Richter syndrome affect stem‐cell maintenance and cell cycle regulation and differ from de novo diffuse large B‐cell lymphoma
Authors: Rinaldi Andrea , Mensah Afua Adjeiwaa , Kwee Ivo , Forconi Francesco , Orlandi Ester M. , Lucioni Marco , Gattei Valter , Marasca Roberto , Berger Françoise , Cogliatti Sergio , Cavalli Franco , Zucca Emanuele , Gaidano Gianluca , Rossi Davide , Bertoni Francesco 
Published: August 2013

SummaryIn a fraction of patients, chronic lymphocytic leukaemia (CLL) can transform to Richter syndrome (RS), usually a diffuse large B–cell lymphoma (DLBCL). We studied genome‐wide promoter DNA methylation in RS and clonally related CLL‐phases of transformed patients, alongside de novo DLBCL (of non‐germinal centre B type), untransformed‐CLL and normal B‐cells. The greatest differences in global DNA methylation levels were observed between RS and DLBCL, indicating that these two diseases, although histologically similar, are epigenetically distinct. RS was more highly methylated for genes involved in cell cycle regulation. When RS was compared to the preceding CLL‐phase and with untransformed‐CLL, RS presented a higher degree of methylation for genes possessing the H3K27me3 mark and PRC2 targets, as well as for gene targets of TP53 and RB1. Comparison of the methylation levels of individual genes revealed that OSM, a stem cell regulatory gene, exhibited significantly higher methylation levels in RS compared to CLL‐phases. Its transcriptional repression by DNA methylation was confirmed by 5‐aza‐2′deoxycytidine treatment of DLBCL cells, determining an increased OSM expression.Our results showed that methylation patterns in RS are largely different from de novo DLBCL. Stem cell‐related genes and cell cycle regulation genes are targets of DNA methylation in RS.
Reversible inhibition of the glycine transporter GlyT2 circumvents acute toxicity while preserving efficacy in the treatment of pain
Authors: Mingorance‐Le Meur A , Ghisdal P , Mullier B , De Ron P , Downey P , Van Der Perren C , Declercq V , Cornelis S , Famelart M , Van Asperen J , Jnoff E , Courade J P 
Published: August 2013

Background and PurposeAvailable medications for chronic pain provide only partial relief and often cause unacceptable side effects. There is therefore a need for novel molecular targets to develop new therapeutics with improved efficacy and tolerability. Despite encouraging efficacy data in rodents with inhibitors of the neuronal glycine transporter‐2 (GlyT2), there are also some reports of toxicity and their development was discontinued.Experimental ApproachIn order to clarify the possibility of targeting GlyT2 for the treatment of pain, we have used an integrated approach comprising in vitro pharmacology, selectivity, bioavailability, in vivo efficacy and safety assessment to analyse the properties and efficacy of ALX‐1393 and Org‐25543, the two published GlyT2 inhibitors from which in vivo data are available.Key ResultsWe report that these compounds have a different set of undesirable properties that limit their usefulness as pharmacological tools. Importantly, we discover that inhibitors of GlyT2 can exert an apparent reversible or irreversible inhibition of the transporter and describe a new class of reversible GlyT2 inhibitors that preserves efficacy while avoiding acute toxicity.Conclusions and ImplicationsOur pharmacological comparison of two closely related GlyT2 inhibitors with different modes of inhibition provides important insights into their safety and efficacy profiles, uncovering that in the presence of a GlyT2 mechanism‐based toxicity, reversible inhibitors might allow a tolerable balance between efficacy and toxicity. These findings shed light into the drawbacks associated with the early GlyT2 inhibitors and describe a new mechanism that might serve as the starting point for new drug development.
Cytomegalovirus contributes partly to uraemia-associated premature immunological ageing of the T cell compartment
Authors: Meijers R W J , Litjens N H R , de Wit E A , Langerak A W , van der Spek A , Baan C C , Weimar W , Betjes M G H 
Published: August 2013

Summary
Cytomegalovirus (CMV) infection has been implicated in accelerated T cell ageing. End-stage renal disease (ESRD) patients have a severely immunologically aged T cell compartment but also a high prevalence of CMV infection. We investigated whether CMV infection contributes to T cell ageing in ESRD patients. We determined the thymic output by the T cell receptor excision circle (TREC) content and percentage of CD31+ naïve T cells. The proliferative history of the T cell compartment by determination of the relative telomere length (RTL) and the T cell differentiation status was determined by immunophenotyping. It appeared that CMV infection did not affect thymic output but reduced RTL of CD8+ T cells in ESRD patients. Moreover, increased T cell differentiation was observed with higher percentages of CD57+ and CD28null CD4+ and CD8+ memory T cells. These CD28null T cells had significantly shorter telomeres compared to CD28+ T cells. Therefore we concluded that CMV infection does not affect the decreased thymic output but increases T cell differentiation as observed in ESRD-related premature T cell ageing.
Mild iodine deficiency in women after spontaneous abortions living in an iodine‐sufficient area of Czech Republic: prevalence and impact on reproductive health
Authors: Jiskra Jan , Fait Tomáš , Bílek Radovan , Krátký Jan , Bartáková Jana , Lukáš Jindřich , Límanová Zdeňka , Telička Zdeněk , Zamrazil Václav , Potluková Eliška 
Published: August 2013

SummaryObjectiveIodine deficiency is associated with thyroid dysfunction and adverse pregnancy outcomes. The aim of our study was to investigate the status of iodine saturation in women after spontaneous abortion (SpA) residing in an iodine‐sufficient area and to evaluate their subsequent reproductive health.DesignNonrandomized prospective follow‐up study.Patients and methodsWe compared urinary iodine concentration (UIC) in 171 women 2–8 weeks (median 4) after an early SpA with age‐matched controls. Women with known thyroid diseases were excluded. We also analysed a relationship of UIC to serum thyroid‐stimulating hormone, free thyroxine, antibodies against thyroid peroxidase and thyroid ultrasound. Afterwards, we followed the women for a median of 38 months (range 12–47). We used a multivariate regression analysis to assess the influence of iodine status and other thyroid biochemical and ultrasound parameters on their subsequent reproductive health.ResultsWomen after SpA were almost twice as likely to suffer from mild iodine deficiency and had lower median UIC as compared to age‐matched controls [rate 105/181 (58·0%) vs 57/181 (31·5%), P < 0·001, medians UIC 92·00 vs 117·80 mcg/l, P < 0·001]. UIC was not influenced by the use of iodine supplements in the previous pregnancy. We did not find any association neither between UIC and thyroid dysfunction and/or thyroid antibodies, nor between UIC and rates of subsequent successful pregnancies or obstetric complications.ConclusionsMore than half of women after SpA residing in an iodine‐sufficient area are suffering from mild iodine deficiency. However, it does not seem to have a negative impact on their subsequent reproductive health.
Total‐evidence phylogenetic analysis and reclassification of the Phylinae (Insecta: Heteroptera: Miridae), with the recognition of new tribes and subtribes and a redefinition of Phylini
Authors: Menard Katrina L. , Schuh Randall T. , Woolley James B. 
Published: August 2013

AbstractThe subfamily Phylinae (Heteroptera: Miridae) is one of the largest subfamilies of plant bugs and in the most recent classification comprised six tribes: Pilophorini, Hallodapini, Auricillocorini, Phylini, Pronotocrepini, and Leucophoropterini. Phylogenetic analyses of the subfamily using dynamic homology (POY), parsimony (TNT), and model‐based (RAxML) methods are presented. A dataset comprising both morphological and molecular characters (16S, 18S, 28S, and COI–COII) was assembled for taxon samples of 164 ingroup and nine outgroup taxa. A reclassification of the subfamily based on the POY analysis is presented, recognizing nine tribes and nine subtribes. The Auricillocorini is synonymized with the Hallodapini and the Pronotocrepini with the Cremnorrhini; the Phylini was found to be polyphyletic and is redefined; the Semiini and Nasocorini are resurrected and redefined; and the Decomiini and Coatonocapsiniare presented as new tribes. The Hallodapini, rather than the Pilophorini, was found to be the sister‐group to the remaining Phylinae.
Effects of baclofen on mechanical noxious and innocuous transmission in the spinal dorsal horn of the adult rat: in vivo patch‐clamp analysis
Authors: Fukuhara Kaori , Katafuchi Toshihiko , Yoshimura Megumu 
Published: August 2013

AbstractThe effects of a GABAB agonist, baclofen, on mechanical noxious and innocuous synaptic transmission in the substantia gelatinosa (SG) were investigated in adult rats with the in vivo patch‐clamp technique. Under current‐clamp conditions, perfusion with baclofen (10 μm) on the surface of the spinal cord caused hyperpolarisation of SG neurons and a decrease in the number of action potentials elicited by pinch and touch stimuli applied to the receptive field of the ipsilateral hindlimb. The suppression of action potentials was preserved under blockade of postsynaptic G‐proteins, although baclofen‐induced hyperpolarisation was completely blocked. These findings suggest presynaptic effects of baclofen on the induced action potentials. Under voltage‐clamp conditions, application of baclofen reduced the frequency, but not the amplitude, of miniature excitatory postsynaptic currents (mEPSCs), whereas the GABAB receptor antagonist CGP55845 increased the frequency of mEPSCs without affecting the amplitude. Furthermore, application of a GABA uptake inhibitor, nipecotic acid, decreased the frequency of mEPSCs; this effect was blocked by CGP55845, but not by the GABAA antagonist bicuculline. Both the frequency and the amplitude of the pinch‐evoked barrage of excitatory postsynaptic currents (EPSCs) were suppressed by baclofen in a dose‐dependent manner. The frequency and amplitude of touch‐evoked EPSCs was also suppressed by baclofen, but the suppression was significantly smaller than that of pinch‐evoked EPSCs. We conclude that mechanical noxious transmission is presynaptically blocked through GABAB receptors in the SG, and is more effectively suppressed than innocuous transmission, which may account for a part of the mechanism of the efficient analgesic effects of baclofen.
On Kant's Idea of Humanity as an End in Itself
Authors: Nyholm Sven 
Published: August 2013

AbstractWriters like Christine Korsgaard and Allen Wood understand Kant's idea of rational nature as an end in itself as a commitment to a substantive value. This makes it hard for them to explain the supposed equivalence between the universal law and humanity formulations of the categorical imperative, since the former does not appear to assert any substantive value. Nor is it easy for defenders of value‐based readings to explain Kant's claim that the law‐giving nature of practical reason makes all beings with practical reason regard the idea of a rational nature as an end in itself. This article seeks to replace these value‐based readings with a reading of the idea of rational nature as an end that fits better with the overall argument of the Groundwork.
Mitigating unaccounted fishing mortality from gillnets and traps
Authors: Uhlmann Sebastian S , Broadhurst Matt K 
Published: August 2013

AbstractGillnets and traps often are considered to have fewer holistic environmental impacts than active fishing gears. However, in addition to the targeted catches, gillnets and traps still cause unwanted mortalities due to (i) discarding, (ii) ghost fishing of derelict gear, (iii) depredation, (iv) escaping or dropping out of gear, (v) habitat damage, and potentially (vi) avoiding gear and predation and (vii) infection of injuries sustained from most of the above. Population‐level concerns associated with such ‘unaccounted fishing mortalities’ from gillnets and traps have been sufficient to warrant numerous attempts at mitigation. In this article, we reviewed relevant research efforts, locating 130 studies in the primary literature that concomitantly quantified mortalities and their resolution through technical modifications, with the division of effort indicating ongoing concerns. Most studies (85) have focused on discard mortality, followed by ghost‐fishing (24), depredation (10) and escape (8) mortalities. The remaining components have been poorly studied (3). All problematic mortality components are affected by key biological (e.g. species), technical (e.g. fishing mechanisms) and/or environmental (e.g. temperature) factors. We propose that these key factors should be considered as part of a strategy to reduce impacts of these gears by first assessing modifications within and then beyond conventional configurations, followed by changes to operational and handling practices. Justification for this three‐tiered approach is based not only on the potential for cumulative reduction benefits, but also on the likely ease of adoption, legislation and compliance.
Simple quantitative method for estimation of herbage damage caused by sika deer (Cervus nippon)
Authors: Tsukada Hideharu , Kida Tamaki , Kitagawa Miya , Suyama Tetsuo , Shimizu Norihiro 
Published: August 2013

AbstractQuantitatively estimating herbage damage caused by wild herbivores, such as deer, provides a basis for developing countermeasures designed to prevent the damage. However, a simple and easy way to quantify deer damage has not yet been developed. In this study, we estimated herbage damage caused by sika deer (Cervus nippon) in three meadows of a dairy farm in central Japan during three cutting periods. We then compared the validity of quantitative estimation of herbage damage using three simple methods: by comparing plant height or plant length outside and inside a deer exclosure cage, and by estimating the density of sika deer populations using spotlight census surveys in the meadows. We also examined the effect of the timing of herbage damage (i.e. early, middle and late season) caused by sika deer on a total herbage yield during each cutting period. The decreased plant height outside of a deer exclosure had a significant and unbiased linear relationship with herbage damage caused by sika deer. However, the decreased plant length outside of a deer exclosure had a significant but biased linear relationship with herbage damage caused by sika deer. The required sample size for assessing the difference in plant height outside of a deer exclosure increased when the herbage damage was small. On the other hand, the mean density of sika deer did not have a linear relationship with herbage damage. The timing of herbage damage caused by sika deer did not significantly affect total herbage yield. These results show comparing plant height outside and within a deer exclosure provides a simple and inexpensive quantitative method that can be used to estimate herbage damage caused by sika deer. This simple method, however, can be reliable when the herbage damage is relatively large (e.g. >30%).
A systematic analysis of commonly used antibodies in cancer diagnostics
Authors: Gremel Gabriela , Bergman Julia , Djureinovic Dijana , Edqvist Per‐Henrik , Maindad Vikas , Bharambe Bhavana M , Khan Wasif Ali Z A , Navani Sanjay , Elebro Jacob , Jirström Karin , Hellberg Dan , Uhlén Mathias , Micke Patrick , Pontén Fredrik 
Published: August 2013

AimsImmunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence‐based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics.Methods and resultsA tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non‐localized cancer types, was analysed using immunohistochemistry with 27 well‐established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate‐specific antigen and thyroglobulin, showed a cancer type‐related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types.ConclusionsThe results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer.
Apical extrusion of bacteria when using reciprocating single‐file and rotary multifile instrumentation systems
Authors: Tinoco J. M. , De‐Deus G. , Tinoco E. M. B. , Saavedra F. , Fidel R. A. S. , Sassone L. M. 
Published: August 2013

AbstractAimTo evaluate ex vivo, apical bacterial extrusion associated with two reciprocating single‐file systems (WaveOne and Reciproc) compared with a conventional multifile rotary system (BioRace).MethodologyForty‐five human single‐rooted mandibular incisors were used. Endodontic access cavities were prepared, and root canals were contaminated with an Enterococcus faecalis suspension. Following incubation at 37 °C for thirty days, the contaminated teeth were divided into three groups of 15 specimens each (G1 – Reciproc, G2 – WaveOne and G3 – BioRace). Positive and negative controls consisted of 5 infected teeth and 3 uninfected incisors that were instrumented with one of the tested NiTi systems, respectively. Bacteria extruded from the apical foramen during instrumentation were collected into vials containing 0.9% NaCl. The microbiological samples were taken from the vials and incubated in brain heart agar medium for 24 h. The resulting bacterial titre, in colony‐forming units (CFU) per mL, was determined, and these data were analysed by Wilcoxon matched‐pairs signed rank test and Kruskal–Wallis H‐test. The level of significance was set at α = 0.05.ResultsNo significant difference was found in the number of CFU between the two reciprocating systems (P = 0.41). The conventional multifile rotary system group was associated with significantly higher CFU than both of the two reciprocating groups (P = 0.01).ConclusionsAll instrumentation systems extruded bacteria beyond the foramen. However, both reciprocating single‐file systems extruded fewer bacteria apically than the conventional multifile rotary system.
Increased cytokine/chemokines in serum from asthmatic and non‐asthmatic patients with viral respiratory infection
Authors: Giuffrida María J , Valero Nereida , Mosquera Jesús , Alvarez de Mon Melchor , Chacín Betulio , Espina Luz Marina , Gotera Jennifer , Bermudez John , Mavarez Alibeth 
Published: August 2013

BackgroundRespiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory‐infected asthmatic patients compared with non‐asthmatic patients.ObjectivesThe aim of this study was to determine changes in circulating cytokines (IL‐1β, TNF‐α, IL‐4, IL‐5) and chemokines (MCP1: monocyte chemoattractant protein‐1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non‐asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles.Patients/MethodsPatients with asthmatic (n = 34) and non‐asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above‐mentioned viruses.ResultsSimilar increased cytokine concentrations were observed in asthmatic and non‐asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus‐infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients.ConclusionsCirculating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections.
Why No Mayan Party? Indigenous Movements and National Politics in Guatemala
Authors: Pallister Kevin 
Published: August 2013

AbstractUnlike indigenous social movements in several other Latin American countries, Mayan movements in Guatemala have not formed a viable indigenous-based political party. Despite the prominence of the Mayan social movement and a relatively open institutional environment conducive to party formation, indigenous groups have foregone a national political party in favor of a more dispersed pattern of political mobilization at the local level. This article argues that the availability of avenues for political representation at the municipal level, through both traditional political parties and civic committees, and the effects of political repression and violence have reinforced the fragmentation and localism of indigenous social movements in Guatemala and prevented the emergence of a viable Mayan political party. The result has been a pattern of uneven political representation, with indigenous Guatemalans gaining representation in local government while national political institutions remain exclusionary.
Patterns of Abiotic Stress–Induced Homoeologous Gene Silencing in Hexaploid Wheat
Authors: Bottley A. 
Published: August 2013

AbstractGenes duplicated following polyploidization (termed homoeologues) are not always equally expressed. Although homoeologous silencing is an established phenomenon among polyploid species, to date, only limited evidence has been gathered which associates a phenotype with the absence of an individual homoeologous transcript. Here, we show that salinity stress can induce homoeologous silencing in hexaploid wheat and that selective expression can also occur in a tissue not directly exposed to the stress. Some of the instances of salinity stress‐induced homoeologous silencing were dependent on the severity of the stress. The responses were conserved across three diverse cultivars. It is likely that this type of response contributes significantly to the overall level of salinity resistance shown by polyploid wheat.
Gamers just want to have fun? Toward an understanding of the online game acceptance
Authors: Yoon Gunwoo , Duff Brittany R. L. , Ryu Seoungho 
Published: August 2013

AbstractThis study sought to examine the factors affecting the acceptance of an entertainment medium, particularly online games, by expanding the technology acceptance model. To measure factors affecting the acceptance of online games, we fielded a survey with 244 gamers serving as respondents. Perceived usefulness, enjoyment, and economic value were found to have a positive influence on attitude toward gaming, whereas perceived ease of use was not a significant predictor. In addition, we found that gender and game type (multiplayer or not) showed differing patterns of results. Interestingly, perceptions of mass acceptance of gaming were found to have a negative effect on attitude toward online games. Theoretical and practical implications of these findings are discussed.